FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Karnati, R
Talla, V
Peterson, K
Laurie, GW
AF Karnati, Roy
Talla, Venu
Peterson, Katherine
Laurie, Gordon W.
TI Lacritin and other autophagy associated proteins in ocular surface
health
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Review
DE Lacritin; Autophagy; Lysosomal storage disease; Eye; Dry eye; Cornea
ID PROSECRETORY MITOGEN LACRITIN; LYSOSOMAL STORAGE DISORDERS; ENZYME
REPLACEMENT THERAPY; CORNEAL EPITHELIAL-CELLS; OPEN-ANGLE GLAUCOMA; DRY
EYE PATIENTS; METACHROMATIC LEUKODYSTROPHY; CEROID-LIPOFUSCINOSIS;
DAMAGED MITOCHONDRIA; REGULATES AUTOPHAGY
AB Advantage may be taken of macroautophagy ('autophagy') to promote ocular health. Autophagy continually captures aged or damaged cellular material for lysosomal degradation and recyling. When autophagic flux is chronically elevated, or alternatively deficient, health suffers. Chronic elevation of flux and stress are the consequence of inflammatory cytokines or of dry eye tears but not normal tears in vitro. Exogenous tear protein lacritin transiently accelerates flux to restore homeostasis in vitro and corneal health in vivo, and yet the monomeric active form of lacritin appears to be selectively deficient in dry eye. Tissue transglutaminase-dependent cross-linking of monomer decreases monomer quantity and monomer affinity for coreceptor syndecan-1 thereby abrogating activity. Tissue transglutaminase is elevated in dry eye. Mutation of arylsulfatase A, arylsulfatase B, ceroid-lipofuscinosis neuronal 3, mucolipin, or Niemann-Pick disease type Cl respectively underlie several diseases of apparently insufficient autophagic flux that affect the eye, including: metachromatic leukodystrophy, mucopoly-saccharidosis type VI, juvenile-onset Batten disease, mucolipidosis IV, and Niemann-Pick type C associated with myelin sheath destruction of corneal sensory and ciliary nerves and of the optic nerve; corneal clouding, ocular hypertension, glaucoma and optic nerve atrophy; accumulation of 'ceroid-lipofuscin' in surface conjunctival cells, and in ganglion and neuronal cells; decreased visual acuity and retinal dystrophy; and neurodegeneration. For some, enzyme or gene replacement, or substrate reduction, therapy is proving to be successful. Here we discuss examples of restoring ocular surface homeostasis through alteration of autophagy, with particular attention to lacritin. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Karnati, Roy] Univ Hyderabad, Sch Life Sci, Hyderabad 500134, Andhra Pradesh, India.
[Talla, Venu] Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Peterson, Katherine] NEI, Sect Mol Struct & Funct Genom, Bethesda, MD 20892 USA.
[Laurie, Gordon W.] Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA.
RP Laurie, GW (reprint author), Univ Virginia, Dept Cell Biol, UVA Hlth Syst, POB 800732, Charlottesville, VA 22908 USA.
EM glaurie@virginia.edu
OI Talla, Venu/0000-0002-5695-7536; Laurie, Gordon/0000-0002-5311-2650
FU NIH [R01 EY024327]; [SR/FT/LS-157/2012]
FX GWL is supported by NIH R01 EY024327. RK is supported by
SR/FT/LS-157/2012. The authors acknowledge the multi-institutional
Lacritin Consortium for help with much of the lacritin work reviewed.
NR 110
TC 1
Z9 1
U1 4
U2 13
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2016
VL 144
SI SI
BP 4
EP 13
DI 10.1016/j.exer.2015.08.015
PG 10
WC Ophthalmology
SC Ophthalmology
GA DG9BI
UT WOS:000372377400002
PM 26318608
ER
PT J
AU Mumford, SL
Silver, RM
Sjaarda, LA
Wactawski-Wende, J
Townsend, JM
Lynch, AM
Galai, N
Lesher, LL
Faraggi, D
Perkins, NJ
Schliep, KC
Zarek, SM
Schisterman, EF
AF Mumford, Sunni L.
Silver, Robert M.
Sjaarda, Lindsey A.
Wactawski-Wende, Jean
Townsend, Janet M.
Lynch, Anne M.
Galai, Noya
Lesher, Laurie L.
Faraggi, David
Perkins, Neil J.
Schliep, Karen C.
Zarek, Shvetha M.
Schisterman, Enrique F.
TI Expanded findings from a randomized controlled trial of preconception
low-dose aspirin and pregnancy loss
SO HUMAN REPRODUCTION
LA English
DT Article
DE low-dose aspirin; conception; pregnancy loss; fertility; live birth
ID IN-VITRO FERTILIZATION; RECURRENT MISCARRIAGE; WOMEN; METAANALYSIS;
HEPARIN; TIME; IVF
AB What is the association between daily preconception-initiated low-dose aspirin (LDA) treatment and very early pregnancy losses or euploid (chromosomally normal) losses among women with one to two prior losses?
Daily LDA initiated preconception was not associated with the rate or type of pregnancy loss among women with a history of one to two prior pregnancy losses.
LDA is often used to treat recurrent pregnancy loss with reductions in pregnancy loss generally only observed among women with antiphospholipid antibodies, and null associations observed among women without antiphospholipid antibodies. We previously evaluated the association between LDA and pregnancy loss overall among women with one to two prior losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and found no association, though did not distinguish between potential effects at different stages of pregnancy loss, including implantation failure, or between euploid and aneuploid losses.
The EAGeR trial was a multi-site prospective block-randomized double-blind placebo-controlled trial. In total, 1228 women were randomized to daily LDA (81 mg/day) plus folic acid (400 mcg/day), or placebo plus folic acid. Participants were assigned study drug for less than or equal to six menstrual cycles or if they conceived, throughout pregnancy with study drug discontinued at 36 weeks gestation. This analysis includes additional outcome information obtained from chart abstractions after the completion of the trial, as well as testing of stored urine for measurement of hCG and detection of very early pregnancy losses, and karyotyping of the products of conception for assessment of aneuploidy of the losses.
Women aged 18-40 with a history of one to two prior losses and actively trying to conceive were randomized (n = 615 LDA and n = 613 placebo) at four clinical centers in the USA (2007-2011). Log-binomial regression was used to estimate risk ratios under the intent-to-treat approach.
Daily LDA initiated preconception was not associated with clinically recognized pregnancy losses or implantation failures among women with proved fecundity and a history of one to two prior losses. Specifically, 1088 (88.6%) women completed the trial with 797 having an hCG detected pregnancy (64.9%). Overall there were 133 clinical losses (12.7% LDA versus 11.8% placebo, P = 0.71) and 55 implantation failures (5.2% LDA versus 4.9% placebo, P = 0.89). No differences were found in rate of euploid losses (RR 1.11, 95% confidence interval: 0.99, 1.26).
Generalizability of these findings is limited to women with a history of one to two prior losses, and may further be limited to women of white race with higher socioeconomic status as given the rigors of the study protocol participants tended to be white and have higher incomes and more education. We were also missing karyotype information on approximately one-third of the clinically recognized pregnancy losses, which may limit our power to detect effects on euploid losses, though detailed sensitivity analysis showed similar results.
Our data do not support the general use of LDA to decrease pregnancy loss and further demonstrate no increased risk of loss for women on LDA treatment.
This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). The authors have no conflicts of interest.
The trial was registered at ClinicalTrials.gov #NCT00467363.
27 April 2007.
15 June 2007.
C1 [Mumford, Sunni L.; Sjaarda, Lindsey A.; Perkins, Neil J.; Schliep, Karen C.; Zarek, Shvetha M.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
[Silver, Robert M.; Lesher, Laurie L.] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Room 2B200 SOM,50 North Med Dr, Salt Lake City, UT 84132 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, 270 Farber Hall, Buffalo, NY 14214 USA.
[Townsend, Janet M.] Commonwealth Med Coll, Dept Family Community & Rural Hlth, 525 East Pine St, Scranton, PA 18509 USA.
[Lynch, Anne M.] Univ Colorado, Dept Obstet & Gynecol, 12700 East 19th Ave, Aurora, CO 80045 USA.
[Galai, Noya; Faraggi, David] Univ Haifa, Dept Stat, IL-31905 Haifa, Israel.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Sjaarda, Lindsey/0000-0003-0539-8110;
Schisterman, Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland [HHSN267200603423, HHSN267200603424,
HHSN267200603426]
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland (Contract
Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426).
NR 24
TC 2
Z9 2
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
EI 1460-2350
J9 HUM REPROD
JI Hum. Reprod.
PD MAR
PY 2016
VL 31
IS 3
BP 657
EP 665
DI 10.1093/humrep/dev329
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DG9QN
UT WOS:000372419000019
PM 26759138
ER
PT J
AU Bressler, SB
Ayala, AR
Bressler, NM
Melia, M
Qin, HJ
Ferris, FL
Flaxel, CJ
Friedman, SM
Glassman, AR
Jampol, L
Rauser, ME
AF Bressler, Susan B.
Ayala, Allison R.
Bressler, Neil M.
Melia, Michele
Qin, Haijing
Ferris, Frederick L., III
Flaxel, Christina J.
Friedman, Scott M.
Glassman, Adam R.
Jampol, Leem.
Rauser, Michael E.
CA Diabet Retinopathy Clin Res
TI Persistent Macular Thickening After Ranibizumab Treatment for Diabetic
Macular Edema With Vision Impairment
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID PLUS PROMPT LASER; DEFERRED LASER
AB IMPORTANCE The prevalence of persistent diabetic macular edema (DME) after months of anti-vascular endothelial growth factor therapy and its effect on visual acuity are unknown.
OBJECTIVE To assess subsequent outcomes of eyes with DME persisting for 24 weeks after initiating treatment with 0.5 mg of ranibizumab.
DESIGN, SETTING, AND PARTICIPANTS We performed post hoc, exploratory analyses of a randomized clinical trial from March 20, 2007, through January 29, 2014, from 117 of 296 eyes (39.5%) randomly assigned to receive ranibizumab with persistent DME (central subfield thickness >= 250 mu m on time domain optical coherence tomography) through the 24-week visit.
INTERVENTIONS Four monthly intravitreous injections of ranibizumab and then as needed per protocol.
MAIN OUTCOMES AND MEASURES Cumulative 3-year probabilities of chronic persistent DME (failure to achieve a central subfield thickness <250 mu m and at least a 10% reduction from the 24-week visit on at least 2 consecutive study visits) determined by life-table analyses, and at least 10 letter (>= 2 line) gain or loss of visual acuity among those eyes.
RESULTS The probability of chronic persistent DME among eyes with persistent DME at the 24-week visit decreased from 100% at the 32-week visit to 81.1% (99% CI, 69.6%-88.6%), 55.8% (99% CI, 42.9%-66.9%), and 40.1%(99% CI, 27.4%-52.4%) at the 1-, 2-, and 3-year visits, respectively. At 3 years, visual acuity improved in eyes with and without chronic persistent DME through the follow-up period, respectively, by a mean of 7 letters and 13 letters from baseline. Among 40 eyes with chronic persistent edema through 3 years, 17 (42.5%) (99% CI, 23.1%-63.7%) gained 10 letters or more from baseline, whereas 5 (12.5%) (99% CI, 2.8%-31.5%) lost 10 letters or more from baseline.
CONCLUSIONS AND RELEVANCE These data suggest less than half of eyes treated for DME with intravitreous ranibizumab have persistent central-involved DME through 24 weeks after initiating treatment. Among the 40% that then have chronic persistent central-involved DME through 3 years, longer-term visual acuity outcomes appear to be slightly worse than in the 60% in which DME does not persist. Nevertheless, when following the treatment protocol used in this trial among eyes with vision impairment from DME, long-term improvement in visual acuity from baseline is typical and substantial (>= 2-line) loss of visual acuity is likely uncommon through 3 years, even when central-involved DME chronically persists.
C1 [Bressler, Susan B.; Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Ayala, Allison R.; Melia, Michele; Qin, Haijing; Glassman, Adam R.] Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA.
[Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
[Flaxel, Christina J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Friedman, Scott M.] Florida Retina Consultants, Lakeland, FL USA.
[Jampol, Leem.] Northwestern Univ, Sch Med, Feinberg Sch Med, Chicago, IL USA.
[Rauser, Michael E.] Loma Linda Univ Hlth Care, Loma Linda, CA USA.
RP Ayala, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA.
EM drcrstat1@jaeb.org
FU National Eye Institute [EY14231, EY23207, EY18817]; National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, US Department of Health and Human Services
FX This study was supported through grants EY14231, EY23207, and EY18817
from the National Eye Institute and the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health, US
Department of Health and Human Services.
NR 6
TC 7
Z9 7
U1 2
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD MAR
PY 2016
VL 134
IS 3
BP 278
EP 285
DI 10.1001/jamaophthalmol.2015.5346
PG 8
WC Ophthalmology
SC Ophthalmology
GA DH1JN
UT WOS:000372540300013
PM 26746868
ER
PT J
AU Fair, C
Cuttance, J
Sharma, N
Maslow, G
Wiener, L
Betz, C
Porter, J
McLaughlin, S
Gilleland-Marchak, J
Renwick, A
Naranjo, D
Jan, S
Javalkar, K
Ferris, M
AF Fair, Cynthia
Cuttance, Jessica
Sharma, Niraj
Maslow, Gary
Wiener, Lori
Betz, Cecily
Porter, Jerlym
McLaughlin, Suzanne
Gilleland-Marchak, Jordan
Renwick, Amy
Naranjo, Diana
Jan, Sophia
Javalkar, Karina
Ferris, Maria
CA Int Interdisciplinary Hlth Care Tr
TI International and Interdisciplinary Identification of Health Care
Transition Outcomes
SO JAMA PEDIATRICS
LA English
DT Article
ID LIVER-TRANSPLANT RECIPIENTS; ADULT CARE; CHRONIC ILLNESS; SPINA-BIFIDA;
YOUNG-PEOPLE; ADOLESCENTS; ADHERENCE; YOUTH; SERVICES; DELPHI
AB IMPORTANCE There is a lack of agreement on what constitutes successful outcomes for the process of health care transition (HCT) among adolescent and young adults with special health care needs.
OBJECTIVE To present HCT outcomes identified by a Delphi process with an interdisciplinary group of participants.
DESIGN, SETTING, AND PARTICIPANTS A Delphi method involving 3 stages was deployed to refine a list of HCT outcomes. This 18-month study (from January 5, 2013, of stage 1 to July 3, 2014, of stage 3) included an initial literature search, expert interviews, and then 2 waves of a web-based survey. On this survey, 93 participants from outpatient, community-based, and primary care clinics rated the importance of the top HCT outcomes identified by the Delphi process. Analyses were performed from July 5, 2014, to December 5, 2014.
EXPOSURES Health care transition outcomes of adolescents and young adults with special health care needs.
MAIN OUTCOMES AND MEASURES Importance ratings of identified HCT outcomes rated on a Likert scale from 1 (not important) to 9 (very important).
RESULTS The 2 waves of surveys included 117 and 93 participants as the list of outcomes was refined. Transition outcomes were refined by the 3 waves of the Delphi process, with quality of life being the highest-rated outcome with broad agreement. The 10 final outcomes identified included individual outcomes (quality of life, understanding the characteristics of conditions and complications, knowledge of medication, self-management, adherence to medication, and understanding health insurance), health services outcomes (attending medical appointments, having a medical home, and avoidance of unnecessary hospitalization), and a social outcome (having a social network). Participants indicated that different outcomes were likely needed for individuals with cognitive disabilities.
CONCLUSIONS AND RELEVANCE Quality of life is an important construct relevant to HCT. Future research should identify valid measures associated with each outcome and further explore the role that quality of life plays in the HCT process. Achieving consensus is a critical step toward the development of reliable and objective comparisons of HCT outcomes across clinical conditions and care delivery locations.
C1 [Fair, Cynthia] Elon Univ, Dept Human Serv Studies, CB 2337, Elon, NC 27244 USA.
[Cuttance, Jessica; Javalkar, Karina; Ferris, Maria] Univ N Carolina, End Stage Kidney Dis Program, Chapel Hill, NC 27515 USA.
[Sharma, Niraj] Harvard Univ, Sch Med, Brigham & Womens & Boston Childrens Hosp, Med Pediat Residency Program, Boston, MA USA.
[Maslow, Gary] Duke Univ, Psychiat & Behav Sci & Pediat, Durham, NC USA.
[Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Betz, Cecily] Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90089 USA.
[Porter, Jerlym] St Jude Childrens Res Hosp, Dept Psychol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[McLaughlin, Suzanne] Brown Univ, Internal Med Pediat, Providence, RI 02912 USA.
[McLaughlin, Suzanne] Hasbro Hosp, Dept Pediat & Med, Providence, RI USA.
[Gilleland-Marchak, Jordan] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Renwick, Amy] Alfred I duPont Hosp Children, Transit Care, Nemours, Wilmington, DE USA.
[Naranjo, Diana] Stanford Univ, Dept Psychiat, Sch Med, Stanford, CA 94305 USA.
[Jan, Sophia] Childrens Hosp Philadelphia, Div Gen Pediat, Philadelphia, PA 19104 USA.
RP Fair, C (reprint author), Elon Univ, Dept Human Serv Studies, CB 2337, Elon, NC 27244 USA.
EM cfair@elon.edu
OI Iglesia, Enrique/0000-0003-4109-1001
NR 50
TC 6
Z9 6
U1 3
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD MAR
PY 2016
VL 170
IS 3
BP 205
EP 211
DI 10.1001/jamapediatrics.2015.3168
PG 7
WC Pediatrics
SC Pediatrics
GA DG8AL
UT WOS:000372304700010
PM 26619178
ER
PT J
AU Yeung, EH
Sundaram, R
Bell, EM
Druschel, C
Kus, C
Ghassabian, A
Bello, S
Xie, YL
Louis, GMB
AF Yeung, Edwina H.
Sundaram, Rajeshwari
Bell, Erin M.
Druschel, Charlotte
Kus, Christopher
Ghassabian, Akhgar
Bello, Scott
Xie, Yunlong
Louis, Germaine M. Buck
TI Examining Infertility Treatment and Early Childhood Development in the
Upstate KIDS Study
SO JAMA PEDIATRICS
LA English
DT Article
ID ASSISTED REPRODUCTIVE TECHNOLOGY; AUTISM SPECTRUM DISORDERS; IN-VITRO
FERTILIZATION; STAGES QUESTIONNAIRES; FERTILITY TREATMENT; CHILDREN
BORN; CONCURRENT VALIDITY; PRETERM INFANTS; BIRTH COHORT; AGES
AB IMPORTANCE An increasing percentage of births are conceived with assisted reproductive technology (ART) and other infertility treatment. Despite findings that such treatments may be associated with diminished gestation and birth size, scarce data exist regarding infertility treatments and children's development in the United States.
OBJECTIVE To assess the use and type of infertility treatment in relation to children's development through age 36 months.
DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study (conducted 2008-2014) that sampled based on infertility treatment and plurality. Included in the study were infants born between 2008 and 2010 in New York state (excluding New York City) whose parents completed developmental screening instruments through 36 months of age. A total of 4824 mothers (97% of 4989) completed 1 or more developmental screening instruments for 5841 children, including 1830 conceived with infertility treatment and 2074 twins.
EXPOSURES Maternal self-report of any infertility treatment was further categorized into ART and ovulation induction/intrauterine insemination. Assisted reproductive technology use was previously validated by linkage with the Society for Assisted Reproductive Technology-Clinical Outcome Reporting System.
MAIN OUTCOMES AND MEASURES Five developmental domains (fine motor, gross motor, communication, personal-social functioning, and problem-solving ability), as measured by the parental completion of the Ages and Stages Questionnaires at 4, 8, 12, 18, 24, 30, and 36 months of age. Generalized linear mixed modeling techniques estimated adjusted odds ratios (aORs) and 95% CIs for use and type of infertility treatment in relation to failing a developmental domain. Data were stratified by plurality and weighted for the sampling scheme.
RESULTS There were 1422 mothers (29.5%; mean [SD], age, 34.1 [5.2] years) who underwent infertility treatment. Infertility treatment was not associated with risk of their children failing any developmental domain (aOR, 1.33; 95% CI, 0.94-1.89). Assisted reproductive technology was associated with increased risk for failing any developmental domain but only when singletons and twins were evaluated together (aOR, 1.81; 95% CI, 1.21-2.72). Adjustment for birth weight further attenuated this estimate (aOR, 1.26; 95% CI, 0.82-1.93). After stratifying by plurality, type of treatment also was not significantly associated with failing any developmental domain for ovulation induction/intrauterine insemination (aOR, 1.00; 95% CI, 0.57-1.77 for singletons and aOR, 1.30; 95% CI, 0.76-2.21 for twins) or ART (aOR, 1.38; 95% CI, 0.78-2.43 for singletons and aOR, 1.58; 95% CI, 0.94-2.65 for twins).
CONCLUSIONS AND RELEVANCE After considering plurality, children's development through age 3 years was similar irrespective of infertility treatment or specific type. To our knowledge, these findings are among the first to focus on non-ART treatments in the United States.
C1 [Yeung, Edwina H.; Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Bell, Erin M.; Druschel, Charlotte] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY USA.
[Bell, Erin M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA.
[Druschel, Charlotte] New York State Dept Hlth, Bur Environm & Occupat Epidemiol, Ctr Environm Hlth, Albany, NY 12237 USA.
[Kus, Christopher] New York State Dept Hlth, Div Family Hlth, Albany, NY 12237 USA.
[Bello, Scott] CapitalCare Pediat Troy, Dev Pediat, Troy, NY USA.
RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
EM yeungedw@mail.nih.gov
OI Ghassabian, Akhgar/0000-0001-9551-4706; Buck Louis,
Germaine/0000-0002-1774-4490; Yeung, Edwina/0000-0002-3851-2613;
Sundaram, Rajeshwari/0000-0002-6918-5002
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [HHSN275201200005C,
HHSN267200700019C]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (contracts HHSN275201200005C and HHSN267200700019C).
NR 39
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Z9 5
U1 3
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD MAR
PY 2016
VL 170
IS 3
BP 251
EP 258
DI 10.1001/jamapediatrics.2015.4164
PG 8
WC Pediatrics
SC Pediatrics
GA DG8AL
UT WOS:000372304700016
PM 26746435
ER
PT J
AU Figueroa, JD
Prokunina-Olsson, L
Koutros, S
Garcia-Closas, M
Chanock, S
Silverman, DT
Rothman, N
AF Figueroa, Jonine D.
Prokunina-Olsson, Ludmila
Koutros, Stella
Garcia-Closas, Montserrat
Chanock, Stephen
Silverman, Debra T.
Rothman, Nathaniel
TI RE: Modification of Occupational Exposures on Bladder Cancer Risk by
Common Genetic Polymorphisms RESPONSE
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID GENOME-WIDE ASSOCIATION; METALWORKING FLUIDS; PHENOTYPES; LOCI
C1 [Figueroa, Jonine D.; Prokunina-Olsson, Ludmila; Koutros, Stella; Garcia-Closas, Montserrat; Chanock, Stephen; Silverman, Debra T.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Figueroa, Jonine D.] Univ Edinburgh, Inst Genet & Mol Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
RP Figueroa, JD (reprint author), Univ Edinburgh, Sch Med, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
EM jonine.figueroa@ed.ac.uk
NR 8
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAR
PY 2016
VL 108
IS 3
AR djv441
DI 10.1093/jnci/djv441
PG 1
WC Oncology
SC Oncology
GA DH2BP
UT WOS:000372589400026
ER
PT J
AU Freidlin, B
Korn, EL
AF Freidlin, Boris
Korn, Edward L.
TI RE: Impact of a Biomarker-Based Strategy on Oncology Drug Development: A
Meta-Analysis of Clinical Trials Leading to FDA Approval
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM freidlinb@ctep.nci.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAR
PY 2016
VL 108
IS 3
AR djv430
DI 10.1093/jnci/djv430
PG 2
WC Oncology
SC Oncology
GA DH2BP
UT WOS:000372589400022
PM 26912650
ER
PT J
AU Zeidner, JF
Karp, JE
Blackford, AL
Foster, MC
Dees, EC
Smith, G
Ivy, SP
Harris, P
AF Zeidner, Joshua F.
Karp, Judith E.
Blackford, Amanda L.
Foster, Matthew C.
Dees, E. Claire
Smith, Gary
Ivy, S. Percy
Harris, Pamela
TI Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience
From Cancer Therapy Evaluation Program of the National Cancer Institute
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID ACUTE MYELOCYTIC-LEUKEMIA; GEMTUZUMAB OZOGAMICIN; GROUP-B; INDUCTION;
REGIMENS; MELANOMA; SAFETY; AGE
AB Background: Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time.
Methods: A retrospective analysis was performed on 711 adult AML patients enrolling in 45 phase I clinical trials supported by the Cancer Therapy Evaluation Program of the National Cancer Institute from 1986 to 2009. Changes in ORR and mortality rates for patients enrolled in 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009 were estimated with multivariable logistic regression models. All statistical tests were two-sided.
Results: There was a statistically significant increase in AML patients enrolling in phase I clinical trials over time (1986 to 1990: n = 61; 2006 to 2009: n = 256; P = .03). The ORR for the entire cohort was 15.4% (1986 to 1990: 8.9%, 1991 to 1995: 21.1%; 1996 to 2000: 7.0%; 2001 to 2005: 10.0%; 2006 to 2009: 22.6%), and it statistically significantly improved over time (P < .001). There was a statistically significant improvement in ORRs with novel agents in combination vs single agents (ORR = 22.8% vs 4.7%, respectively, odds ratio = 5.95, 95% confidence interval = 3.22 to 11.9, P < .001). The 60-day mortality rate for the entire cohort was 22.6%, but it statistically significantly improved over time (P = .009).
Conclusions: There has been an encouraging increase in AML patients enrolling in phase I clinical studies over time. The improvement in ORRs appears to be partly because of the increase in combination trials and the inclusion of previously untreated poor-risk AML. Continued enrollment of AML patients in early phase clinical trials is vital for drug development and improvement in therapeutic outcomes.
C1 [Zeidner, Joshua F.; Foster, Matthew C.; Dees, E. Claire] Univ N Carolina, Lineberger Comprehens Canc Ctr, 170 Manning Dr,Phys Off Bldg,3rd Floor,CB 7305, Chapel Hill, NC 27599 USA.
[Karp, Judith E.; Blackford, Amanda L.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Smith, Gary; Ivy, S. Percy; Harris, Pamela] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Zeidner, JF (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, 170 Manning Dr,Phys Off Bldg,3rd Floor,CB 7305, Chapel Hill, NC 27599 USA.
EM joshua_zeidner@med.unc.edu
FU National Cancer Institute
FX This work was supported by the National Cancer Institute. JFZ received a
2013 Conquer Cancer Foundation Young Investigator Award, in memory of
Dr. John R. Durant, and is a 2014 to 2017 Leukemia and Lymphoma Society
Special Fellow in Clinical Research.
NR 21
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAR
PY 2016
VL 108
IS 3
AR djv335
DI 10.1093/jnci/djv335
PG 8
WC Oncology
SC Oncology
GA DH2BP
UT WOS:000372589400004
ER
PT J
AU Kim, M
Lee, M
Kim, Y
Oh, S
Lee, D
Yoon, B
AF Kim, Minhee
Lee, Minyoung
Kim, Yushin
Oh, Sejun
Lee, Dongshin
Yoon, BumChul
TI Myofascial Pain Syndrome in the Elderly and Self-Exercise: A
Single-Blind, Randomized, Controlled Trial
SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
LA English
DT Article
ID TRIGGER POINTS; NECK PAIN; MUSCULOSKELETAL PAIN; CLINICAL-TRIAL; MANUAL
THERAPY; SOFT-TISSUE; TO-TREAT; ULTRASOUND; MANAGEMENT; MUSCLE
AB Objective: This study aimed to demonstrate the effect of self-exercise with a therapeutic inflatable ball (SEIB) in elderly patients with myofascial pain syndrome.
Design: Single-blind, randomized, controlled noninferiority trial.
Setting: University campus.
Participants: Forty elderly patients with myofascial pain syndrome completed the study. They were randomly allocated to SEIB (n = 22; mean age, 70.23 +/- 6.11 years) or ultrasound (US) therapy (n = 18; mean age, 67.99 +/- 5.64 years).
Intervention: SEIB and US therapy (twice weekly for 4 consecutive weeks).
Outcome measures: Visual analog scale (VAS), pressure pain threshold (PPT), and cervical lateral flexion (CLF) were measured at baseline and at 1, 2, 3, and 4 weeks.
Results: The noninferiority test indicated that SEIB was not inferior to US for VAS, PPT, and CLF. Between-group comparisons showed no significant differences in the VAS (F = 2.579; p = 0.117), the PPT (F = 0.245; p = 0.624), and the CLF (F = 2.072; p = 0.159). In within-group comparisons, both groups presented significant differences in VAS (SEIB after 1 week and US after 1 week), PPT (SEIB after 3 weeks and US after 4 weeks), and CLF (SEIB after 4 weeks and US after 4 weeks) compared with baseline values.
Conclusions: SEIB for 4 weeks has an effect similar to that of US for desensitizing myofascial pain and increasing joint flexibility. High accessibility and low cost would make SEIB a practical self-treatment method in elderly patients with myofascial pain syndrome.
C1 [Kim, Minhee; Lee, Minyoung; Oh, Sejun; Yoon, BumChul] Korea Univ, Dept Phys Therapy, Coll Hlth Sci, Hana Hlth Sci B BLD 670,145 Anam Ro, Seoul 136701, South Korea.
[Kim, Yushin] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Dongshin] Eulji Univ, Dept Phys Therapy, Coll Hlth Sci, Gyeonggido, South Korea.
RP Yoon, B (reprint author), Korea Univ, Dept Phys Therapy, Coll Hlth Sci, Hana Hlth Sci B BLD 670,145 Anam Ro, Seoul 136701, South Korea.
EM yoonbc@korea.ac.kr
FU Korea University Institute of Health Sciences Grant [K1508331]
FX This research was supported by a Korea University Institute of Health
Sciences Grant, (K1508331). The authors would like to thank all the
participants who volunteered for this study.
NR 55
TC 2
Z9 2
U1 3
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1075-5535
EI 1557-7708
J9 J ALTERN COMPLEM MED
JI J. Altern. Complement Med.
PD MAR 1
PY 2016
VL 22
IS 3
BP 244
EP 251
DI 10.1089/acm.2015.0205
PG 8
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA DG9OG
UT WOS:000372412500010
PM 26910293
ER
PT J
AU Wallace, GL
Kenworthy, L
Pugliese, CE
Popal, HS
White, EI
Brodsky, E
Martin, A
AF Wallace, Gregory L.
Kenworthy, Lauren
Pugliese, Cara E.
Popal, Haroon S.
White, Emily I.
Brodsky, Emily
Martin, Alex
TI Real-World Executive Functions in Adults with Autism Spectrum Disorder:
Profiles of Impairment and Associations with Adaptive Functioning and
Co-morbid Anxiety and Depression
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Adult; Executive function; Adaptive functioning; Anxiety;
Depression
ID MULTIPLE CASE SERIES; ASPERGER-SYNDROME; WORKING-MEMORY; DIAGNOSTIC
INTERVIEW; SYMPTOMS; CHILDREN; CHILDHOOD; DEFICITS; ADOLESCENCE;
PERFORMANCE
AB Although executive functioning (EF) difficulties are well documented among children and adolescents with autism spectrum disorder (ASD), little is known about real-world measures of EF among adults with ASD. Therefore, this study examined parent-reported real-world EF problems among 35 adults with ASD without intellectual disability and their correlations with adaptive functioning and co-morbid anxiety and depression symptomatology. A variable EF profile was found with prominent deficits occurring in flexibility and metacognition. Flexibility problems were associated with anxiety-related symptoms while metacognition difficulties were associated with depression symptoms and impaired adaptive functioning (though the metacognition-adaptive functioning relationship was moderated by ADHD symptoms). These persistent EF problems are predictors of broader functioning and therefore remain an important treatment target among adults with ASD.
C1 [Wallace, Gregory L.; Brodsky, Emily] George Washington Univ, Dept Speech & Hearing Sci, 2115 G St NW,Room 201, Washington, DC 20052 USA.
[Wallace, Gregory L.; Popal, Haroon S.; White, Emily I.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Kenworthy, Lauren; Pugliese, Cara E.] Childrens Natl Hlth Syst, Ctr Autism Spectrum Disorders, Washington, DC USA.
RP Wallace, GL (reprint author), George Washington Univ, Dept Speech & Hearing Sci, 2115 G St NW,Room 201, Washington, DC 20052 USA.; Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
EM gwallac1@gwu.edu
OI Wallace, Gregory/0000-0003-0329-5054
FU Intramural Research Program at NIMH, NIH [1-ZIA-MH002920]; T32 Grant
[HD046388-01A2]; NIH Combined Neuroscience Institutional Review Board
[10-M-0027]
FX This work was supported by the Intramural Research Program at NIMH, NIH
under Grant Number 1-ZIA-MH002920. CEP was supported by a T32 Grant
HD046388-01A2. Ethics approval for this study was granted by the NIH
Combined Neuroscience Institutional Review Board under Protocol Number
10-M-0027. We would like to express our gratitude to the individuals and
families who volunteered their time to contribute to this research.
NR 49
TC 7
Z9 7
U1 19
U2 35
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
EI 1573-3432
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD MAR
PY 2016
VL 46
IS 3
BP 1071
EP 1083
DI 10.1007/s10803-015-2655-7
PG 13
WC Psychology, Developmental
SC Psychology
GA DG7RO
UT WOS:000372281600029
PM 26572659
ER
PT J
AU Brugnera, E
Bhandoola, A
Cibotti, R
Yu, Q
Guinter, TI
Yamashita, Y
Sharrow, SO
Singer, A
AF Brugnera, Enrico
Bhandoola, Avinash
Cibotti, Richrdo
Yu, Qing
Guinter, Terry I.
Yamashita, Yoshio
Sharrow, Susan O.
Singer, Alfred
TI Coreceptor Reversal in the Thymus: Signaled CD4(+)8(+) Thymocytes
Initially Terminate CD8 Transcription Even When Differentiating into
CD8(+) T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4/CD8 LINEAGE COMMITMENT; POSITIVE SELECTION; INTERLEUKIN-7 RECEPTOR;
GENE-EXPRESSION; IN-VITRO; LYMPHOCYTES; OVEREXPRESSION; SPECIFICITY;
MECHANISMS; PRECURSORS
AB A central paradigm of T cell development is that CD4(+)8(+) (DP) thymocytes differentiate into CD4(+) or CD8(+) T cells in response to intrathymic signals that extinguish transcription of the inappropriate corecep tor molecule. Contrary to this prevailing paradigm, we now demonstrate that signaled DP thymocytes initially terminate CD8 transcription even when differentiating into CD8(+) T cells. Remarkably, thymocytes that have selectively terminated CD8 transcription can be signaled by IL-7 to differentiate into CD8(+) T cells by silencing CD4 transcription and reinitiating CD8 transcription, events we refer to as "coreceptor reversal." These observations significantly alter our understanding of CD8 1 T cell differentiation and lead to a new perspective ("kinetic signaling") on CD4/CD8 lineage determination in the thymus. These observations also suggest a novel mechanism by which bipotential cells throughout development can determine their appropriate cell fate.
C1 [Brugnera, Enrico; Bhandoola, Avinash; Cibotti, Richrdo; Yu, Qing; Guinter, Terry I.; Sharrow, Susan O.; Singer, Alfred] NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA.
[Yamashita, Yoshio] Oklahoma Med Res Fdn, Immunobiol Program, Oklahama City, OK 73104 USA.
[Brugnera, Enrico] Univ Virgina, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
[Cibotti, Richrdo] Vaccinex LP, Rochester, NY 14620 USA.
[Yamashita, Yoshio] Saga Med Sch, Dept Oral & Maxillofacial Surg, Saga 849, Japan.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM singera@nih.gov
FU Swiss National Science Foundation
FX We would like to thank Dan Littman for generously providing 004 promoter
transgenic mice; Paul Kincade for anti-IL-7Ru antibodies; Larry Granger
and Tony Adams for expert flow cytometry; and Remy Bosselut, Carolyn
Doyle, Scot Durum, Richard Hodes, David McKean, Jennifer Punt, and Dinah
Singer for critically reading the manuscript. This work was supported in
part by a grant to E. B. from the Swiss National Science Foundation.
NR 37
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2016
VL 196
IS 5
BP 1985
EP 1997
PG 13
WC Immunology
SC Immunology
GA DG8LT
UT WOS:000372336300002
PM 26896482
ER
PT J
AU Yan, M
Wang, HS
Sun, JF
Liao, W
Li, P
Zhu, Y
Xu, CF
Joo, J
Sun, Y
Abbasi, S
Kovalchuk, A
Lv, N
Leonard, WJ
Morse, HC
AF Yan, Ming
Wang, Hongsheng
Sun, Jiafang
Liao, Wei
Li, Peng
Zhu, Yin
Xu, Chengfu
Joo, Jungsoo
Sun, Yan
Abbasi, Sadia
Kovalchuk, Alexander
Lv, Nonghua
Leonard, Warren J.
Morse, Herbert C., III
TI Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers
Protective Innate Immunity against Helicobacter pylori Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GENE; DIFFERENTIATION; MUTATION; PROGRAM; PROTEIN; MOUSE; IFIT3
AB IFN regulatory factor 8 (IRF8) is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. However, the role of IRF8 in nonhematopoietic systems remains poorly understood. In this study, we provide evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting Helicobacter pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which, in turn, promoted IFN-gamma expression by gastric epithelial cells. Mice deficient in IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-gamma. Genome-wide analyses of IFN-gamma-treated gastric epithelial cells by chromatin immunoprecipitation sequencing and RNA sequencing led to the identification of IRF8 target genes, with many belonging to the IFN-regulated gene family that was observed previously in immune cells. Our results identify the IRF8-IFN-gamma circuit as a novel gastric innate immune mechanism in the host defense against infection with H. pylori.
C1 [Yan, Ming; Xu, Chengfu; Joo, Jungsoo; Sun, Yan] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Wang, Hongsheng; Sun, Jiafang; Abbasi, Sadia; Kovalchuk, Alexander; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Liao, Wei; Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Liao, Wei; Li, Peng; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Zhu, Yin; Lv, Nonghua] Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang 330006, Peoples R China.
RP Yan, M (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.; Wang, HS; Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM yanming@mail.nih.gov; wanghongs@niaid.nih.gov; hmorse@niaid.nih.gov
FU Intramural Research Programs of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases; National
Institute of Diabetes and Digestive and Kidney Diseases; National Heart,
Lung, and Blood Institute
FX This work was supported in part by the Intramural Research Programs of
the National Institutes of Health, the National Institute of Allergy and
Infectious Diseases (to H.W., J.S., S.A., A.K., and H.C.M.), the
National Institute of Diabetes and Digestive and Kidney Diseases (to
M.Y., Y.Z., J.J., Y.S., C.X., and N.L.), and the National Heart, Lung,
and Blood Institute (to W.L., P.L., and W.J.L.).
NR 23
TC 1
Z9 1
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2016
VL 196
IS 5
BP 1999
EP 2003
DI 10.4049/jimmunol.1500766
PG 5
WC Immunology
SC Immunology
GA DG8LT
UT WOS:000372336300003
PM 26843324
ER
PT J
AU Rahman, MJ
Rahir, G
Dong, MB
Zhao, YG
Rodrigues, KB
Hotta-Iwamura, C
Chen, Y
Guerrero, A
Tarbell, KV
AF Rahman, M. Jubayer
Rahir, Gwendoline
Dong, Matthew B.
Zhao, Yongge
Rodrigues, Kameron B.
Hotta-Iwamura, Chie
Chen, Ye
Guerrero, Alan
Tarbell, Kristin V.
TI Despite Increased Type 1 IFN, Autoimmune Nonobese Diabetic Mice Display
Impaired Dendritic Cell Response to CpG and Decreased Nuclear
Localization of IFN-Activated STAT1
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; NOD MICE; INTERFERON-ALPHA; INNATE IMMUNITY; MAP
KINASE; IN-VITRO; MOUSE; DC; EXPRESSION; PATHOGENESIS
AB Innate immune signals help break self-tolerance to initiate autoimmune diseases such as type 1 diabetes, but innate contributions to subsequent regulation of disease progression are less clear. Most studies have measured in vitro innate responses of GM-CSF dendritic cells (DCs) that are functionally distinct from conventional DCs (cDCs) and do not reflect in vivo DC subsets. To determine whether autoimmune NOD mice have alterations in type 1 IFN innate responsiveness, we compared cDCs from prediabetic NOD and control C57BL/6 (B6) mice stimulated in vivo with the TLR9 ligand CpG, a strong type 1 IFN inducer. In response to CpG, NOD mice produce more type 1 IFN and express higher levels of CD40, and NOD monocyte DCs make more TNF. However, the overall CpG-induced transcriptional response is muted in NOD cDCs. Of relevance the costimulatory proteins CD80/CD86, signals needed for regulatory T cell homeostasis, are upregulated less on NOD cDCs. Interestingly, NOD Rag1(-/-) mice also display a defect in CpG-induced CD86 upregulation compared with B6 Rag1(-/-), indicating this particular innate alteration precedes adaptive autoimmunity. The impaired response in NOD DCs is likely downstream of the IFN-alpha/beta receptor because DCs from NOD and B6 mice show similar CpG-induced CD86 levels when anti-IFN-alpha/beta receptor Ab is added. IFN-alpha-induced nuclear localization of activated STAT1 is markedly reduced in NOD CD11c(+) cells, consistent with lower type 1 IFN responsiveness. In conclusion, NOD DCs display altered innate responses characterized by enhanced type 1 IFN and activation of monocyte-derived DCs but diminished cDC type 1 IFN response.
C1 [Rahman, M. Jubayer; Rahir, Gwendoline; Dong, Matthew B.; Zhao, Yongge; Rodrigues, Kameron B.; Hotta-Iwamura, Chie; Guerrero, Alan; Tarbell, Kristin V.] NIDDK, Immune Tolerance Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Ye] NHLBI, Bioinformat & Syst Biol Core, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Tarbell, KV (reprint author), NIDDK, Immune Tolerance Sect, 10 Ctr Dr,Bldg 10,5-5940, Bethesda, MD 20892 USA.
EM tarbellk@niddk.nih.gov
OI Rodrigues, Kameron/0000-0002-0270-3688; Tarbell,
Kristin/0000-0003-3738-379X; Rahman, M. Jubayer/0000-0002-4496-8385
FU intramural research programs of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart, Lung, and Blood
Institute; Janssen Research and Development
FX This work was supported by the intramural research programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
National Heart, Lung, and Blood Institute and by a collaborative
research agreement with Janssen Research and Development.
NR 59
TC 2
Z9 2
U1 1
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2016
VL 196
IS 5
BP 2031
EP 2040
DI 10.4049/jimmunol.1501239
PG 10
WC Immunology
SC Immunology
GA DG8LT
UT WOS:000372336300008
PM 26826238
ER
PT J
AU Qian, Y
Jeong, JS
Ye, J
Dang, B
Abdeladhim, M
Aoki, V
Hans-Filhio, G
Rivitti, EA
Valenzuela, JG
Diaz, LA
AF Qian, Ye
Jeong, Joseph S.
Ye, Jian
Dang, Bim
Abdeladhim, Maha
Aoki, Valeria
Hans-Filhio, Gunter
Rivitti, Evandro A.
Valenzuela, Jesus G.
Diaz, Luis A.
TI Overlapping IgG4 Responses to Self- and Environmental Antigens in
Endemic Pemphigus Foliaceus
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EXPERT PANEL WORKSHOP; FOGO-SELVAGEM; AUTOIMMUNE-DISEASES; PHAGE
DISPLAY; LUTZOMYIA-LONGIPALPIS; IGG4-RELATED DISEASE; MOLECULAR MIMICRY;
SOMATIC MUTATIONS; BLOOD-LYMPHOCYTES; PASSIVE TRANSFER
AB The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H-and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases.
C1 [Qian, Ye; Jeong, Joseph S.; Dang, Bim; Diaz, Luis A.] Univ N Carolina, Dept Dermatol, CB 7287, Chapel Hill, NC 27599 USA.
[Ye, Jian] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Abdeladhim, Maha; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Aoki, Valeria; Rivitti, Evandro A.] Univ Sao Paulo, Dept Dermatol, BR-04038 Sao Paulo, Brazil.
[Hans-Filhio, Gunter] Univ Fed Mato Grosso do Sul, Dept Dermatol, BR-79070 Campo Grande, MS, Brazil.
RP Qian, Y (reprint author), Univ N Carolina, Dept Dermatol, CB 7287, Chapel Hill, NC 27599 USA.
EM ye_qian@med.unc.edu
RI Aoki, Valeria/H-1415-2012
FU National Institutes of Health [K01-AR056378, R01 AR067315, R01-AR32599];
Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX This work was supported by National Institutes of Health Grants
K01-AR056378, R01 AR067315 (to Y.Q.), and R01-AR32599 (to L.A.D.) and
was supported in part by the Intramural Research Program of the National
Institutes of Health, National Library of Medicine.
NR 65
TC 3
Z9 3
U1 2
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2016
VL 196
IS 5
BP 2041
EP 2050
DI 10.4049/jimmunol.1502233
PG 10
WC Immunology
SC Immunology
GA DG8LT
UT WOS:000372336300009
PM 26826247
ER
PT J
AU Prescott, J
Feldmann, H
AF Prescott, Joseph
Feldmann, Heinz
TI Humanized Mice-A Neoteric Animal Disease Model for Ebola Virus?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
DE humanized mouse; animal model; Ebola virus
ID I INTERFERON RESPONSE; HEMORRHAGIC-FEVER; FILOVIRUS INFECTION; DENDRITIC
CELLS; PATHOGENESIS; MOUSE; TRANSMISSION; MEN
C1 [Prescott, Joseph; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Lab, 903 S 4th St, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU Intramural NIH HHS
NR 32
TC 0
Z9 0
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2016
VL 213
IS 5
BP 691
EP 693
DI 10.1093/infdis/jiv539
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XY
UT WOS:000372438300002
PM 26582953
ER
PT J
AU Viboud, C
Simonsen, L
Fuentes, R
Flores, J
Miller, MA
Chowell, G
AF Viboud, Cecile
Simonsen, Lone
Fuentes, Rodrigo
Flores, Jose
Miller, Mark A.
Chowell, Gerardo
TI Global Mortality Impact of the 1957-1959 Influenza Pandemic
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE mortality rates; pandemic influenza; historical studies; vital
statistics; severity; models; global disease burden; development
indicators; health indicators; pandemic planning
ID EXCESS MORTALITY; UNITED-STATES; AGE; EPIDEMIC; WAVE; INFECTION;
ENGLAND; CITY; SEX
AB Background. Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics.
Methods. We used annual rates of age-and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic.
Results. The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2-2.6 cases/10 000 population) on average during 1957-1959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1-2 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%-77% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million-1.5 million excess deaths) globally to the 1957-1959 pandemic.
Conclusions. The global mortality rate of the 1957-1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.
C1 [Viboud, Cecile; Simonsen, Lone; Miller, Mark A.; Chowell, Gerardo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC USA.
[Flores, Jose] Univ S Dakota, Dept Math Sci, Vermillion, SD 57069 USA.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Simonsen, Lone] Univ Copenhagen, Dept Publ Hlth, DK-1168 Copenhagen, Denmark.
[Fuentes, Rodrigo] Univ Chile, Minist Salud, Dept Epidemiol, Santiago, Chile.
[Flores, Jose] Univ Chile, Natl Ctr Environm, Biodivers Labs, Santiago, Chile.
RP Viboud, C (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Simonsen, Lone/0000-0003-1535-8526
FU International Influenza Unit, Office of Global Affairs, Office of the
Secretary of the Department of Health and Human Services; RAPIDD
Program, Science and Technology Directorate, Department of Homeland
Security; Lundbeck Foundation, Denmark; Marie Sklodowska-Curie Senior
Fellowship [H2020-MSCA-IF-2014, 6594]
FX This work was supported by the International Influenza Unit, Office of
Global Affairs, Office of the Secretary of the Department of Health and
Human Services; the RAPIDD Program, Science and Technology Directorate,
Department of Homeland Security (to L. S.); the Lundbeck Foundation,
Denmark (visiting scientist award to L. S.); and a Marie
Sklodowska-Curie Senior Fellowship (award H2020-MSCA-IF-2014 to L. S.;
project no. 6594).
NR 24
TC 2
Z9 2
U1 4
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2016
VL 213
IS 5
BP 738
EP 745
DI 10.1093/infdis/jiv534
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XY
UT WOS:000372438300008
PM 26908781
ER
PT J
AU Anuradha, R
Munisankar, S
Dolla, C
Kumaran, P
Nutman, TB
Babu, S
AF Anuradha, Rajamanickam
Munisankar, Saravanan
Dolla, Chandrakumar
Kumaran, Paul
Nutman, Thomas B.
Babu, Subash
TI Modulation of CD4(+) and CD8(+) T-Cell Function by Interleukin 19 and
Interleukin 24 During Filarial Infections
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE filarial infections; T cells; cytokines; IL-19; IL-24; IL-10
ID HUMAN LYMPHATIC FILARIASIS; IL-10 FAMILY; CYTOKINES; IL-20;
INFLAMMATION; EXPANSION; MEMBERS
AB Interleukin 19 (IL-19) and interleukin 24 (IL-24) are cytokines that are highly expressed in filarial infections. To study the role of IL-19 and IL-24 in regulating T-cell responses, we examined the frequency of T-helper type 1 (Th1)/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, Th22/Tc22, and Tr1 cells in 26 filariae-infected individuals stimulated with filarial antigen following IL-19 or IL-24 neutralization. IL-19 or IL-24 neutralization resulted in significantly enhanced frequencies of Th1/Tc1 and/or Th17/Tc17 cells and significantly reduced frequencies of Th2/Tc2, Tr1, and/or Th9/Tc9 cells. Thus, we demonstrate that IL-19 and IL-24 are associated with the modulation of T-cell responses in filarial infections.
C1 [Anuradha, Rajamanickam; Munisankar, Saravanan; Babu, Subash] NIRT, NIH, Int Ctr Excellence Res, Madras, Tamil Nadu, India.
[Dolla, Chandrakumar; Kumaran, Paul] NIRT, Madras, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Lab Parasit Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), NIH NIRT ICER, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 14
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2016
VL 213
IS 5
BP 811
EP 815
DI 10.1093/infdis/jiv497
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XY
UT WOS:000372438300019
PM 26486636
ER
PT J
AU Bianchi, MLE
Leoncini, E
Masciullo, M
Modoni, A
Gadalla, SM
Massa, R
Rastelli, E
Terracciano, C
Antonini, G
Bucci, E
Petrucci, A
Costanzi, S
Santoro, M
Boccia, S
Silvestri, G
AF Bianchi, Maria Laura Ester
Leoncini, Emanuele
Masciullo, Marcella
Modoni, Anna
Gadalla, Shahinaz M.
Massa, Roberto
Rastelli, Emanuele
Terracciano, Chiara
Antonini, Giovanni
Bucci, Elisabetta
Petrucci, Antonio
Costanzi, Sandro
Santoro, Massimo
Boccia, Stefania
Silvestri, Gabriella
TI Increased risk of tumor in DM1 is not related to exposure to common
lifestyle risk factors
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Myotonic dystrophy type 1; Tumor; Cancer; Thyroid disease; Risk factors
ID MYOTONIC-DYSTROPHY TYPE-1; MULTIPLE PILOMATRICOMAS; INSULIN-RECEPTOR;
CANCER
AB Recent studies documented an increased risk of neoplasm in patients with myotonic dystrophies (DM). Yet, none of these studies evaluated the contribution of common cancer risk factors in such observation. In this study, we included a cohort of patients (n = 255) with an established molecular diagnosis of DM type 1 (DM1), and who receives their treatment in one of the four centers with recognized expertise in neuromuscular disorders in Rome. We estimated the prevalence of benign and malignant tumors, and assessed if lifestyle factors and/or specific disease features would be associated to their occurrence. Overall, 59 benign tumors in 54 patients and 19 malignant tumors in 17 patients were diagnosed. The most common malignant neoplasms were cancers of the skin (31.6 %), thyroid (21.0 %), ovary (10.5 %), and breast (10.5 %). Uterine fibroid was the most common benign tumor (37.6 %) in women, while pilomatricoma was the most common in men (28.6 %). Age at enrollment (OR = 1.02, 95 % CI 1.00-1.05), and female gender (OR = 5.71, 95 % CI 2.90-11.22) were associated with tumor development in DM1 patients, while thyroid disorders was associated with malignant tumors only in women (OR = 5.12, 95 % CI 1.35-19.37). There was no association between tumor development and evaluated lifestyle factors. In conclusion, the lack of association between common cancer risk factors and tumor development in DM1 support a pathogenic link between tumors and DM1 itself, emphasizing the need for a systematic surveillance. Our observation of an association between thyroid diseases in women and cancer development needs confirmation.
C1 [Bianchi, Maria Laura Ester; Modoni, Anna; Silvestri, Gabriella] Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Largo F Vito 1, I-00168 Rome, Italy.
[Leoncini, Emanuele; Boccia, Stefania] UCSC, Sect Hyg, Inst Publ Hlth, Rome, Italy.
[Masciullo, Marcella] IRCSS Fdn Santa Lucia, Rome, Italy.
[Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Massa, Roberto; Rastelli, Emanuele; Terracciano, Chiara] Univ Roma Tor Vergata, Dept Syst Med Neurol, Rome, Italy.
[Antonini, Giovanni; Bucci, Elisabetta] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs NESMOS, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
[Petrucci, Antonio] Azienda Osped San Camillo Forlanini, Unita Operat Complessa Neurol & Neurofisiopatol, Rome, Italy.
[Costanzi, Sandro] S Camillo Forlanini Hosp, Ctr Neuromuscular & Neurol Rare Dis, Unit Med Genet, Rome, Italy.
[Santoro, Massimo] Fdn Don Carlo Gnocchi Onlus, Milan, Italy.
RP Silvestri, G (reprint author), Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Largo F Vito 1, I-00168 Rome, Italy.
EM gsilvestri@rm.unicatt.it
RI Massa, Roberto/I-7223-2012; Masciullo, Marcella/J-9144-2016; Santoro,
Massimo/P-6575-2014;
OI Massa, Roberto/0000-0001-7523-6956; Masciullo,
Marcella/0000-0003-1368-7692; Santoro, Massimo/0000-0002-3037-2775;
SILVESTRI, Gabriella/0000-0002-1950-1468
FU Fondazione Veronesi; National Cancer Institute, Bethesda, MA
FX The work of Dr. Emanuele Leoncini was supported by Fondazione Veronesi.
Dr. Shahinaz Gadalla is supported by the intramural program of the
National Cancer Institute, Bethesda, MA.
NR 30
TC 4
Z9 5
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD MAR
PY 2016
VL 263
IS 3
BP 492
EP 498
DI 10.1007/s00415-015-8006-y
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DG9WD
UT WOS:000372433600011
PM 26739382
ER
PT J
AU Bianchi, MLE
Leoncini, E
Masciullo, M
Modoni, A
Gadalla, SM
Massa, R
Botta, A
Rastelli, E
Terracciano, C
Antonini, G
Bucci, E
Petrucci, A
Costanzi, S
Santoro, M
Boccia, S
Silvestri, G
AF Bianchi, Maria Laura Ester
Leoncini, Emanuele
Masciullo, Marcella
Modoni, Anna
Gadalla, Shahinaz M.
Massa, Roberto
Botta, Annalisa
Rastelli, Emanuele
Terracciano, Chiara
Antonini, Giovanni
Bucci, Elisabetta
Petrucci, Antonio
Costanzi, Sandro
Santoro, Massimo
Boccia, Stefania
Silvestri, Gabriella
TI Increased risk of tumor in DM1 is not related to exposure to common
lifestyle risk factors (vol 263, pg 492, 2016)
SO JOURNAL OF NEUROLOGY
LA English
DT Correction
C1 [Bianchi, Maria Laura Ester; Modoni, Anna; Silvestri, Gabriella] Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Largo F Vito 1, I-00168 Rome, Italy.
[Leoncini, Emanuele; Boccia, Stefania] UCSC, Sect Hyg, Inst Publ Hlth, Rome, Italy.
[Masciullo, Marcella] IRCSS Fdn Santa Lucia, Rome, Italy.
[Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Massa, Roberto; Rastelli, Emanuele; Terracciano, Chiara] Univ Roma Tor Vergata, Dept Syst Med Neurol, Rome, Italy.
[Antonini, Giovanni; Bucci, Elisabetta] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs NESMOS, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
[Petrucci, Antonio] Azienda Osped San Camillo Forlanini, Unita Operat Complessa Neurol & Neurofisiopatol, Rome, Italy.
[Costanzi, Sandro] S Camillo Forlanini Hosp, Ctr Neuromuscular & Neurol Rare Dis, Unit Med Genet, Rome, Italy.
[Santoro, Massimo] Fdn Don Carlo Gnocchi Onlus, Milan, Italy.
[Botta, Annalisa] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy.
RP Silvestri, G (reprint author), Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Largo F Vito 1, I-00168 Rome, Italy.
EM gsilvestri@rm.unicatt.it
RI Masciullo, Marcella/J-9144-2016; Santoro, Massimo/P-6575-2014
OI Masciullo, Marcella/0000-0003-1368-7692; Santoro,
Massimo/0000-0002-3037-2775
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD MAR
PY 2016
VL 263
IS 3
BP 499
EP 499
DI 10.1007/s00415-016-8068-5
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA DG9WD
UT WOS:000372433600012
PM 26914929
ER
PT J
AU Pokrovskaya, ID
Aronova, MA
Kamykowski, JA
Prince, AA
Hoyne, JD
Calco, GN
Kuo, BC
He, Q
Leapman, RD
Storrie, B
AF Pokrovskaya, I. D.
Aronova, M. A.
Kamykowski, J. A.
Prince, A. A.
Hoyne, J. D.
Calco, G. N.
Kuo, B. C.
He, Q.
Leapman, R. D.
Storrie, B.
TI STEM tomography reveals that the canalicular system and -granules remain
separate compartments during early secretion stages in blood platelets
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE blood platelets; cytoplasmic granules; electron microscope tomography;
hemostasis; platelet activation
ID ALPHA-GRANULES; ELECTRON TOMOGRAPHY; FREEZE-SUBSTITUTION; PROTEINS;
PATHWAY; RELEASE; ULTRASTRUCTURE; ANGIOGENESIS; EXOCYTOSIS; FIXATION
AB How platelets organize their -granule cargo and use their canalicular system remains controversial. Past structural studies were limited due to small sampling volumes or decreased resolution. Our analyses revealed homogeneous granules and a closed canalicular system that opened on activation. Understanding how platelets alter their membranes during activation and secretion elucidates hemostasis.
Summary Background Platelets survey the vasculature for damage and, in response, activate and release a wide range of proteins from their -granules. Alpha-granules may be biochemically and structurally heterogeneous; however, other studies suggest that they may be more homogeneous with the observed variation reflecting granule dynamics rather than fundamental differences.
Objectives Our aim was to address how the structural organization of -granules supports their dynamics.
Methods To preserve the native state, we prepared platelets by high-pressure freezing and freeze-substitution; and to image nearly entire cells, we recorded tomographic data in the scanning transmission electron microscope (STEM).
Results and Conclusions In resting platelets, we observed a morphologically homogeneous -granule population that displayed little variation in overall matrix electron density in freeze-substituted preparations (i.e., macro-homogeneity). In resting platelets, the incidence of tubular granule extensions was low, similar to 4%, but this increased by > 10-fold during early steps in platelet secretion. Using STEM, we observed that the initially decondensing -granules and the canalicular system remained as separate membrane domains. Decondensing -granules were found to fuse heterotypically with the plasma membrane via long, tubular connections or homotypically with each other. The frequency of canalicular system fusion with the plasma membrane also increased by about three-fold. Our results validate the utility of freeze-substitution and STEM tomography for characterizing platelet granule secretion and suggest a model in which fusion of platelet -granules with the plasma membrane occurs via long tubular connections that may provide a spatially limited access route for the timed release of -granule proteins.
C1 [Pokrovskaya, I. D.; Kamykowski, J. A.; Prince, A. A.; Storrie, B.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Aronova, M. A.; Hoyne, J. D.; Calco, G. N.; Kuo, B. C.; He, Q.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Storrie, B (reprint author), Univ Arkansas Med Sci, Dept Physiol & Biophys, Slot 505,4301 W Markham St, Little Rock, AR 72205 USA.
EM storriebrian@uams.edu
FU NIH [R01 HL119393]; National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health
FX We gratefully acknowledge the technical contributions of Laura MacDonald
to this research and the constructive comments of Laura MacDonald and
Sidney W. Whiteheart of the University of Kentucky on the manuscript.
Research in the Storrie laboratory was supported by NIH grant R01
HL119393. Research in the Leapman laboratory was supported by the
intramural program of the National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health.
NR 36
TC 2
Z9 2
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD MAR
PY 2016
VL 14
IS 3
BP 572
EP 584
DI 10.1111/jth.13225
PG 13
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DH1DR
UT WOS:000372525100019
PM 26663480
ER
PT J
AU Fassiotto, M
Hamel, EO
Ku, MW
Correll, S
Grewal, D
Lavori, P
Periyakoil, VJ
Reiss, A
Sandborg, C
Walton, G
Winkleby, M
Valantine, H
AF Fassiotto, Magali
Hamel, Elizabeth Otto
Ku, Manwai
Correll, Shelley
Grewal, Daisy
Lavori, Philip
Periyakoil, V. J.
Reiss, Allan
Sandborg, Christy
Walton, Gregory
Winkleby, Marilyn
Valantine, Hannah
TI Women in Academic Medicine: Measuring Stereotype Threat Among Junior
Faculty
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID MATH PERFORMANCE; NEGATIVE STEREOTYPES; GENDER-DIFFERENCES; POSSIBLE
SELVES; IDENTITY; ADVANCEMENT; SENSITIVITY; EXPERIENCE; REJECTION;
PROGRESS
AB Background: Gender stereotypes in science impede supportive environments for women. Research suggests that women's perceptions of these environments are influenced by stereotype threat (ST): anxiety faced in situations where one may be evaluated using negative stereotypes. This study developed and tested ST metrics for first time use with junior faculty in academic medicine.
Methods: Under a 2012 National Institutes of Health Pathfinder Award, Stanford School of Medicine's Office of Diversity and Leadership, working with experienced clinicians, social scientists, and epidemiologists, developed and administered ST measures to a representative group of junior faculty.
Results: 174 School of Medicine junior faculty were recruited (62% women, 38% men; 75% assistant professors, 25% instructors; 50% white, 40% Asian, 10% underrepresented minority). Women reported greater susceptibility to ST than did men across all items including ST vulnerability (p < 0.001); rejection sensitivity (p = 0.001); gender identification (p < 0.001); perceptions of relative potential (p = 0.048); and, sense of belonging (p = 0.049). Results of career-related consequences of ST were more nuanced. Compared with men, women reported lower beliefs in advancement (p = 0.021); however, they had similar career interest and identification, felt just as connected to colleagues, and were equally likely to pursue careers outside academia (all p > 0.42).
Conclusions: Innovative ST metrics can provide a more complete picture of academic medical center environments. While junior women faculty are susceptible to ST, they may not yet experience all of its consequences in their early careers. As such, ST metrics offer a tool for evaluating institutional initiatives to increase supportive environments for women in academic medicine.
C1 [Fassiotto, Magali] Stanford Univ, Off Fac Dev & Div, Sch Med, 1265 Welch Rd,Suite X100, Stanford, CA 94305 USA.
[Lavori, Philip] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
[Periyakoil, V. J.; Winkleby, Marilyn; Valantine, Hannah] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Reiss, Allan] Stanford Univ, Dept Psychiat & Behav Med, Sch Med, Stanford, CA 94305 USA.
[Sandborg, Christy] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Hamel, Elizabeth Otto] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
[Correll, Shelley] Stanford Univ, Dept Sociol, Stanford, CA 94305 USA.
[Grewal, Daisy] Stanford Univ, Off Vice Provost Undergrad Educ, Stanford, CA 94305 USA.
[Walton, Gregory] Stanford Univ, Dept Psychol, Stanford, CA USA.
[Ku, Manwai] Apple Inc, Cupertino, CA USA.
[Valantine, Hannah] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Fassiotto, M (reprint author), Stanford Univ, Off Fac Dev & Div, Sch Med, 1265 Welch Rd,Suite X100, Stanford, CA 94305 USA.
EM magali.fassiotto@stanford.edu
FU National Institutes of Health
FX This work was funded by a National Institutes of Health Pathfinder Award
to Promote Diversity in the Scientific Workforce. Stanford University
School of Medicine's IRB reviewed and approved the study protocol,
IRB-19272.
NR 46
TC 2
Z9 2
U1 10
U2 17
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAR 1
PY 2016
VL 25
IS 3
BP 292
EP 298
DI 10.1089/jwh.2015.5380
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA DG6DU
UT WOS:000372173200014
PM 26555562
ER
PT J
AU Schwartz, SR
Kumwenda, N
Kumwenda, J
Chen, S
Mofenson, LM
Taylor, AW
Fowler, MG
Taha, TE
AF Schwartz, Sheree R.
Kumwenda, Newton
Kumwenda, Johnstone
Chen, Shu
Mofenson, Lynne M.
Taylor, Allan W.
Fowler, Mary Glenn
Taha, Taha E.
TI Maternal Highly Active Antiretroviral Therapy and Child HIV-Free
Survival in Malawi, 2004-2009
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE HIV-1; Prevention of mother-to-child transmission; Highly active
antiretroviral therapy; Child survival; Breastfeeding
ID DAR-ES-SALAAM; TRANSMISSION; WOMEN; MORTALITY; PROPHYLAXIS; PREVENTION;
TANZANIA; TRIAL; DRUGS; PREGNANCY
AB Objectives Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi. Methods The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately postpartum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status. Results Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naive with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naive mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naive mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality. Conclusions HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes.
C1 [Schwartz, Sheree R.; Kumwenda, Newton; Chen, Shu; Taha, Taha E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 North Wolfe St,E7139, Baltimore, MD 21205 USA.
[Kumwenda, Johnstone] Univ Malawi, Coll Med, Dept Med, Blantyre, Malawi.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
[Taylor, Allan W.] Ctr Dis Control & Prevent, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Div HIV AIDS Prevent, Epidemiol Branch, Atlanta, GA USA.
[Fowler, Mary Glenn] Johns Hopkins Med Sch, Dept Pathol, Baltimore, MD USA.
RP Schwartz, SR (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 North Wolfe St,E7139, Baltimore, MD 21205 USA.
EM sschwartz@jhu.edu; ttaha1@jhu.edu
FU Centers for Disease Control and Prevention [5 U50 PS022061-05,
U50/CC0222061]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health
FX This work was supported by a Cooperative Agreement (Grant number 5 U50
PS022061-05 and award # U50/CC0222061) from the Centers for Disease
Control and Prevention and the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health.
NR 24
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD MAR
PY 2016
VL 20
IS 3
BP 542
EP 549
DI 10.1007/s10995-015-1852-5
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG6BW
UT WOS:000372168200006
PM 26525557
ER
PT J
AU Huggins, CJ
Mayekar, MK
Martin, N
Saylor, KL
Gonit, M
Jailwala, P
Kasoji, M
Haines, DC
Quinones, OA
Johnson, PF
AF Huggins, Christopher J.
Mayekar, Manasi K.
Martin, Nancy
Saylor, Karen L.
Gonit, Mesfin
Jailwala, Parthav
Kasoji, Manjula
Haines, Diana C.
Quinones, Octavio A.
Johnson, Peter F.
TI C/EBP gamma Is a Critical Regulator of Cellular Stress Response Networks
through Heterodimerization with ATF4
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTIONAL
INHIBITORY PROTEIN; BRONCHIAL EPITHELIAL-CELLS; AMINO-ACID RESPONSE;
ER-STRESS; OXIDATIVE STRESS; BINDING-PROTEIN; GENE-EXPRESSION; TARGETED
DISRUPTION
AB The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBP gamma:ATF4 heterodimers, but not C/EBP beta:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBP gamma and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBP beta and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg(-/-) mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBP gamma-deficient new-borns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant N-acetylcysteine. Cebpg(-/-) mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBP gamma as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells.
C1 [Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Gonit, Mesfin; Johnson, Peter F.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Saylor, Karen L.] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Jailwala, Parthav; Kasoji, Manjula] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Haines, Diana C.] Leidos Biomed Res Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Quinones, Octavio A.] DMS Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Johnson, PF (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM johnsope@mail.nih.gov
FU HHS \ NIH \ National Cancer Institute (NCI) [HHSN261200800001E]
FX HHS vertical bar NIH vertical bar National Cancer Institute (NCI)
provided funding to Christopher J. Huggins, Manasi K. Mayekar, Nancy
Martin, Karen L. Saylor, Mesfin Gonit, Parthav Jailwala, Manjula Kasoji,
Diana C. Haines, Octavio A. Quinones, and Peter F. Johnson. HHS vertical
bar NIH vertical bar National Cancer Institute (NCI) provided funding to
Diana C. Haines under grant number contract no. HHSN261200800001E.
NR 67
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Z9 1
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2016
VL 36
IS 5
BP 693
EP 713
DI 10.1128/MCB.00911-15
PG 21
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG8IY
UT WOS:000372328600004
ER
PT J
AU He, B
Cruz-Topete, D
Oakley, RH
Xiao, X
Cidlowski, JA
AF He, Bo
Cruz-Topete, Diana
Oakley, Robert H.
Xiao, Xiao
Cidlowski, John A.
TI Human Glucocorticoid Receptor beta Regulates Gluconeogenesis and
Inflammation in Mouse Liver
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GENE-THERAPY VECTORS; ADENOASSOCIATED VIRUS; TRANSCRIPTIONAL ACTIVITY;
IMMUNE-RESPONSES; EXPRESSION; ISOFORM; MECHANISMS; DISEASE; CELLS;
INHIBITION
AB While in vitro studies have demonstrated that a glucocorticoid receptor (GR) splice isoform, beta-isoform of human GR (hGR beta), acts as a dominant-negative inhibitor of the classic hGR alpha and confers glucocorticoid resistance, the in vivo function of hGR beta is poorly understood. To this end, we created an adeno-associated virus (AAV) to express hGR beta in the mouse liver under the control of the hepatocyte-specific promoter. Genome-wide expression analysis of mouse livers showed that hGR beta significantly increased the expression of numerous genes, many of which are involved in endocrine system disorders and the inflammatory response. Physiologically, hGR beta antagonized GR alpha's function and attenuated hepatic gluconeogenesis through downregulation of phosphoenolpyruvate carboxykinase (PEPCK) in wild-type (WT) mouse liver. Interestingly, however, hGR beta did not repress PEPCK in GR liver knockout (GRLKO) mice. In contrast, hGR beta regulates the expression of STAT1 in the livers of both WT and GRLKO mice. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that hGR beta binds to the intergenic glucocorticoid response element (GRE) of the STAT1 gene. Furthermore, treatment with RU486 inhibited the upregulation of STAT1 mediated by hGR beta. Finally, our array data demonstrate that hGR beta regulates unique components of liver gene expression in vivo by both GR alpha-dependent and GR alpha-independent mechanisms.
C1 [He, Bo; Cruz-Topete, Diana; Oakley, Robert H.; Cidlowski, John A.] NIEHS, Signal Transduct Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Xiao, Xiao] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC USA.
RP Cidlowski, JA (reprint author), NIEHS, Signal Transduct Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU NIH Intramural Research Program
FX NIH Intramural Research Program provided funding to John A. Cidlowski.
NR 35
TC 1
Z9 1
U1 2
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2016
VL 36
IS 5
BP 714
EP 730
DI 10.1128/MCB.00908-15
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG8IY
UT WOS:000372328600005
PM 26711253
ER
PT J
AU Pedersen, SM
Chan, WP
Jattani, RP
Mackie, DS
Pomerantz, JL
AF Pedersen, Sarah M.
Chan, Waipan
Jattani, Rakhi P.
Mackie, deMauri S.
Pomerantz, Joel L.
TI Negative Regulation of CARD11 Signaling and Lymphoma Cell Survival by
the E3 Ubiquitin Ligase RNF181
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NF-KAPPA-B; RESPONSIVE INHIBITORY DOMAIN; COMBINED IMMUNODEFICIENCY;
INDUCED PHOSPHORYLATION; KINASE-BETA; ACTIVATION; CARMA1; MUTATIONS;
BCL10; COMPLEX
AB NF-kappa B activation downstream of antigen receptor engagement is a highly regulated event required for lymphocyte activation during the adaptive immune response. The pathway is often dysregulated in lymphoma, leading to constitutive NF-kappa B activity that supports the aberrant proliferation of transformed lymphocytes. To identify novel regulators of antigen receptor signaling to NF-kappa B, we developed bioluminescence resonance energy transfer-based interaction cloning (BRIC), a screening strategy that can detect protein-protein interactions in live mammalian cells in a high-throughput manner. Using this strategy, we identified the RING finger protein RNF181 as an interactor of CARD11, a key signaling scaffold in the antigen receptor pathway. We present evidence that RNF181 functions as an E3 ubiquitin ligase to inhibit antigen receptor signaling to NF-kappa B downstream of CARD11. The levels of the obligate signaling protein Bcl10 are reduced by RNF181 even prior to signaling, and Bcl10 can serve as a substrate for RNF181 E3 ligase activity in vitro. Furthermore, RNF181 limits the proliferation of human diffuse large B cell lymphoma cells that depend upon aberrant CARD11 signaling to NF-kappa B for growth and survival in culture. Our results define a new regulatory checkpoint that can modulate the output of CARD11 signaling to NF-kappa B in both normal and transformed lymphocytes.
C1 [Pomerantz, Joel L.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA.
[Chan, Waipan] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Pomerantz, JL (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
EM joel.pomerantz@jhmi.edu
OI Pomerantz, Joel L./0000-0002-5030-1018
FU HHS \ NIH \ National Cancer Institute (NCI) [RO1CA177600, F31CA171532];
HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [R21AI118606]
FX HHS vertical bar NIH vertical bar National Cancer Institute (NCI)
provided funding to Sarah Pedersen, Rakhi Jattani, deMauri Mackie, and
Joel Pomerantz under grant number RO1CA177600. HHS vertical bar NIH
vertical bar National Cancer Institute (NCI) provided funding to deMauri
Mackie under grant number F31CA171532. HHS vertical bar NIH vertical bar
National Institute of Allergy and Infectious Diseases (NIAID) provided
funding to Sarah Pedersen, Rakhi Jattani, deMauri Mackie, and Joel
Pomerantz under grant number R21AI118606.
NR 45
TC 3
Z9 4
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2016
VL 36
IS 5
BP 794
EP 808
DI 10.1128/MCB.00876-15
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG8IY
UT WOS:000372328600011
PM 26711259
ER
PT J
AU Ortiz, AM
Klase, ZA
DiNapoli, SR
Vujkovic-Cvijin, I
Carmack, K
Perkins, MR
Calantone, N
Vinton, CL
Riddick, NE
Gallagher, J
Klatt, NR
McCune, JM
Estes, JD
Paiardini, M
Brenchley, JM
AF Ortiz, A. M.
Klase, Z. A.
DiNapoli, S. R.
Vujkovic-Cvijin, I.
Carmack, K.
Perkins, M. R.
Calantone, N.
Vinton, C. L.
Riddick, N. E.
Gallagher, J.
Klatt, N. R.
McCune, J. M.
Estes, J. D.
Paiardini, M.
Brenchley, J. M.
TI IL-21 and probiotic therapy improve Th17 frequencies, microbial
translocation, and microbiome in ARV-treated, SIV-infected macaques
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; HIV-INFECTION; IMMUNE ACTIVATION; ANTIRETROVIRAL
THERAPY; LENTIVIRAL INFECTIONS; VIRAL REPLICATION; PIGTAIL MACAQUES;
RHESUS MACAQUES; T(H)17 CELLS; TGF-BETA
AB Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4(+) T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.
C1 [Ortiz, A. M.; Klase, Z. A.; DiNapoli, S. R.; Carmack, K.; Perkins, M. R.; Calantone, N.; Vinton, C. L.; Riddick, N. E.; Gallagher, J.; Klatt, N. R.; Brenchley, J. M.] NIAID, Program Tissue Immun & Repair, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Ortiz, A. M.; Klase, Z. A.; DiNapoli, S. R.; Carmack, K.; Perkins, M. R.; Calantone, N.; Vinton, C. L.; Riddick, N. E.; Gallagher, J.; Klatt, N. R.; Brenchley, J. M.] NIAID, Immunopathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Klase, Z. A.] Univ Sci, Dept Biol Sci, Philadelphia, PA USA.
[Vujkovic-Cvijin, I.; McCune, J. M.] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USA.
[Klatt, N. R.] Univ Washington, Dept Pharmaceut, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Estes, J. D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, FrederickNat Lab Canc Res, Frederick, MD USA.
[Paiardini, M.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Div Microbiol & Immunol,Yerkes Natl Primate Res C, Atlanta, GA 30322 USA.
RP Brenchley, JM (reprint author), NIAID, Program Tissue Immun & Repair, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Brenchley, JM (reprint author), NIAID, Immunopathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbrenchl@niaid.nih.gov
OI DiNapoli, Sarah/0000-0002-3675-9030; Vujkovic-Cvijin,
Ivan/0000-0002-8611-4900
FU Division of Intramural Research/NIAID/NIH; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX We thank F. Villinger (Emory University) for providing the IL-21; D.
Hazuda (Gilead), M. Miller (Merck), and J. Lifson (NCI) for providing
the ARVs; C. de Simon (Sigma Tau Pharmaceuticals) for providing the
VSL#3; H. Cronise, J. Swerczek, and R. Herbert for veterinary
assistance; and the NIAID LMM-Core for assessing viral loads. Funding
for this study was provided in part by the Division of Intramural
Research/NIAID/NIH. This project has been funded in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E to JDE. The content of this
publication does not necessarily reflect the views or policies of DHHS,
or does the mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 46
TC 14
Z9 14
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2016
VL 9
IS 2
BP 458
EP 467
DI 10.1038/mi.2015.75
PG 10
WC Immunology
SC Immunology
GA DG9TD
UT WOS:000372425800014
PM 26286233
ER
PT J
AU Drummond, RA
Dambuza, IM
Vautier, S
Taylor, JA
Reid, DM
Bain, CC
Underhill, DM
Masopust, D
Kaplan, DH
Brown, GD
AF Drummond, R. A.
Dambuza, I. M.
Vautier, S.
Taylor, J. A.
Reid, D. M.
Bain, C. C.
Underhill, D. M.
Masopust, D.
Kaplan, D. H.
Brown, G. D.
TI CD4(+) T-cell survival in the GI tract requires dectin-1 during fungal
infection
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID CD103(+) DENDRITIC CELLS; BETA-GLUCAN RECEPTOR; CANDIDA-ALBICANS;
HOST-DEFENSE; RECOGNITION; HOMEOSTASIS; IMMUNITY; SUBSETS; COLONIZATION;
EXPRESSION
AB Dectin-1 is an innate antifungal C-type lectin receptor necessary for protective antifungal immunity. We recently discovered that Dectin-1 is involved in controlling fungal infections of the gastrointestinal (GI) tract, but how this C-type lectin receptor mediates these activities is unknown. Here, we show that Dectin-1 is essential for driving fungal-specific CD4(+) T-cell responses in the GI tract. Loss of Dectin-1 resulted in abrogated dendritic cell responses in the mesenteric lymph nodes (mLNs) and defective T-cell co-stimulation, causing substantial increases in CD4(+) T-cell apoptosis and reductions in the cellularity of GI-associated lymphoid tissues. CD8(+) T-cell responses were unaffected by Dectin-1 deficiency. These functions of Dectin-1 have significant implications for our understanding of intestinal immunity and susceptibility to fungal infections.
C1 [Drummond, R. A.; Dambuza, I. M.; Vautier, S.; Taylor, J. A.; Reid, D. M.; Brown, G. D.] Univ Aberdeen, Inst Med Sci, Aberdeen Fungal Grp, Aberdeen, Scotland.
[Bain, C. C.] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Vet Med & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Underhill, D. M.] Cedars Sinai Med Ctr, Div Immunol, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA.
[Masopust, D.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Kaplan, D. H.] Univ Minnesota, Dept Dermatol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Drummond, R. A.; Vautier, S.] NIH, Fungal Pathogenesis Unit RAD, Lab Mucosal Immunol, Bldg 10, Bethesda, MD 20892 USA.
RP Brown, GD (reprint author), Univ Aberdeen, Inst Med Sci, Aberdeen Fungal Grp, Aberdeen, Scotland.
EM gordon.brown@abdn.ac.uk
OI Drummond, Rebecca/0000-0001-5424-7074
FU Medical Research Council; Wellcome Trust [086558, 102705, 97377];
University of Aberdeen
FX We thank the Medical Research Council, the Wellcome Trust (086558,
102705, 97377) and the University of Aberdeen for funding. We thank
Doreen Cantrell for useful comments, and acknowledge Medical Research
Facility staff for care of the animals used in this study.
NR 37
TC 2
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U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2016
VL 9
IS 2
BP 492
EP 502
DI 10.1038/mi.2015.79
PG 11
WC Immunology
SC Immunology
GA DG9TD
UT WOS:000372425800017
PM 26349660
ER
PT J
AU Turfkruyer, M
Verhasselt, V
AF Turfkruyer, M.
Verhasselt, V.
TI Response to "Disparity between vitamin A-induced Th1-dependent oral
tolerance in newborn mice and vitamin A-induced atopic sensitization in
Guinean girls"
SO MUCOSAL IMMUNOLOGY
LA English
DT Letter
C1 [Turfkruyer, M.] NIAID, Food Allergy Res Unit, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Turfkruyer, M.; Verhasselt, V.] Univ Nice Sophia Antipolis, Immune Tolerance Team TIM EA6302, F-06189 Nice, France.
[Verhasselt, V.] Worldwide Univ Network, Int Inflammat In FLAME Network, Nice, France.
RP Verhasselt, V (reprint author), Univ Nice Sophia Antipolis, Immune Tolerance Team TIM EA6302, F-06189 Nice, France.; Verhasselt, V (reprint author), Worldwide Univ Network, Int Inflammat In FLAME Network, Nice, France.
EM verhasselt@unice.fr
NR 7
TC 0
Z9 0
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2016
VL 9
IS 2
BP 565
EP 565
DI 10.1038/mi.2016.3
PG 1
WC Immunology
SC Immunology
GA DG9TD
UT WOS:000372425800024
PM 26860819
ER
PT J
AU Backonja, U
Louis, GMB
Lauver, DR
AF Backonja, Uba
Louis, Germaine M. Buck
Lauver, Diane R.
TI Overall Adiposity, Adipose Tissue Distribution, and Endometriosis A
Systematic Review
SO NURSING RESEARCH
LA English
DT Review
DE endometriosis; adiposity; body size; systematic review
ID PERITONEAL-FLUID LEPTIN; BODY-FAT DISTRIBUTION; PELVIC ENDOMETRIOSIS;
RETROGRADE MENSTRUATION; MASS INDEX; WOMEN; BIOMARKERS; METAANALYSIS;
ADIPONECTIN; OBESITY
AB Background
Endometriosis has been associated with a lean body habitus. However, we do not understand whether endometriosis is also associated with other characteristics of adiposity, including adipose tissue distribution and amount of visceral adipose tissue (VAT; adipose tissue lining inner organs). Having these understandings may provide insights on how endometriosis develops-some of the physiological actions of adipose tissue differ depending on tissue amount and location and are related to proposed mechanisms of endometriosis development.
Objectives
The aim of this study was to review the literature regarding overall adiposity, adipose tissue distribution and/or VAT, and endometriosis.
Methods
We reviewed and synthesized studies indexed in PubMed and/or Web of Science. We included studies that had one or more measures of overall adiposity, adipose tissue distribution, and/or VAT and women with and without endometriosis for comparison. We summarized the findings and commented on the methods used and potential sources of bias.
Results
Of 366 identified publications, 19 (5.2%) were eligible. Two additional publications were identified from reference lists. Current research included measures of overall adiposity (e.g., body figure drawings) or adipose tissue distribution (e.g., waist-to-hip ratio), but not VAT. The weight of evidence indicated that endometriosis was associated with low overall adiposity and with a preponderance of adipose tissue distributed below the waist (peripheral).
Discussion
Endometriosis may be associated with being lean or having peripherally distributed adipose tissue. Well-designed studies with various sampling frameworks and precise measures of adiposity and endometriosis are needed to confirm associations between adiposity measures and endometriosis and delineate potential etiological mechanisms underlying endometriosis.
C1 [Backonja, Uba] Univ Washington, Sch Med, Dept Biomed Informat & Med Educ, Box 358047, Seattle, WA 98109 USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Off Director, Rockville, MD USA.
[Lauver, Diane R.] Univ Wisconsin, Sch Nursing, Madison, WI 53706 USA.
RP Backonja, U (reprint author), Univ Washington, Sch Med, Dept Biomed Informat & Med Educ, Box 358047, Seattle, WA 98109 USA.
EM backonja@uw.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU NINR/NIH; NIH, National Library of Medicine Biomedical and Health
Informatics Training Program at the University of Washington
[T15LM007442]
FX Dr. Backonja was funded through the NINR/NIH Graduate Partnership
Program during the literature review and initial writing of the
manuscript. She is currently funded by the NIH, National Library of
Medicine Biomedical and Health Informatics Training Program at the
University of Washington (Grant No. T15LM007442).
NR 84
TC 0
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2016
VL 65
IS 2
BP 151
EP 166
DI 10.1097/NNR.0000000000000146
PG 16
WC Nursing
SC Nursing
GA DG6RZ
UT WOS:000372215100004
PM 26938364
ER
PT J
AU Nadarajah, S
Buchholz, S
Wiegand, D
Berger, A
AF Nadarajah, Sheeba
Buchholz, Susan
Wiegand, Debra
Berger, Ann
TI Barriers and Facilitators of Cardiac Recovery in Cardiac Rehabilitation
Patients
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Nadarajah, Sheeba] Bowie State Univ, Bowie, MD USA.
[Buchholz, Susan] Rush Univ, Coll Nursing, Chicago, IL USA.
[Wiegand, Debra] Univ Maryland, Bethesda, MD USA.
[Berger, Ann] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2016
VL 65
IS 2
BP E66
EP E66
PG 1
WC Nursing
SC Nursing
GA DG6SA
UT WOS:000372215200180
ER
PT J
AU Tuthill, E
Cusson, R
McGrath, J
AF Tuthill, Emily
Cusson, Regina
McGrath, Jacqueline
TI Exclusive Breastfeeding Promotion Among HIV-Infected Women in South
Africa: An IMB-Model Based Pilot Intervention
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Tuthill, Emily] NIH, Bethesda, MD USA.
[Cusson, Regina; McGrath, Jacqueline] Univ Connecticut, Storrs, CT USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2016
VL 65
IS 2
BP E67
EP E67
PG 1
WC Nursing
SC Nursing
GA DG6SA
UT WOS:000372215200183
ER
PT J
AU Weaver, KR
Melkus, GD
Henderson, WA
AF Weaver, Kristen R.
Melkus, Gail D'Eramo
Henderson, Wendy A.
TI Allostatic Load in IBS
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Weaver, Kristen R.; Henderson, Wendy A.] NINR, Bethesda, MD 20892 USA.
[Melkus, Gail D'Eramo] NYU, New York, NY 10003 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2016
VL 65
IS 2
BP E53
EP E54
PG 2
WC Nursing
SC Nursing
GA DG6SA
UT WOS:000372215200147
ER
PT J
AU Burris, AM
Ballew, BJ
Kentosh, JB
Turner, CE
Norton, SA
Giri, N
Alter, BP
Nellan, A
Gamper, C
Hartman, KR
Savage, SA
AF Burris, Ashley M.
Ballew, Bari J.
Kentosh, Joshua B.
Turner, Clesson E.
Norton, Scott A.
Giri, Neelam
Alter, Blanche P.
Nellan, Anandani
Gamper, Christopher
Hartman, Kip R.
Savage, Sharon A.
CA NCI DCEG Canc Genomics
NCI DCEG Canc Sequencing
TI Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of
Follow-Up
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome; telomere; PARN;
microcephaly; CNS calcification
ID BONE-MARROW FAILURE; POLY(A)-SPECIFIC RIBONUCLEASE PARN; TELOMERE
BIOLOGY DISORDERS; DYSKERATOSIS-CONGENITA; COMBINED IMMUNODEFICIENCY;
GERMLINE MUTATION; PROTEIN TPP1; CANCER; VARIANTS; LENGTH
AB BACKGROUND: Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. PATIENT DESCRIPTION: We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. CONCLUSIONS: This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.
C1 [Burris, Ashley M.] San Antonio Mil Med Ctr, San Antonio, TX USA.
[Ballew, Bari J.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.; NCI DCEG Canc Sequencing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kentosh, Joshua B.; Turner, Clesson E.; Hartman, Kip R.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Norton, Scott A.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[NCI DCEG Canc Genomics] NCI Frederick, Canc Genom Res Lab, Leidos Biomed Res, Rockville, MD USA.
[Nellan, Anandani; Gamper, Christopher] Johns Hopkins Univ, Dept Oncol, Div Pediat Oncol, Baltimore, MD USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E456,MSC 9772, Bethesda, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Tobias, Geoffrey/M-4135-2016
OI Tobias, Geoffrey/0000-0002-2878-8253
FU Intramural Research Program, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH
FX Intramural Research Program, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH
NR 30
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U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD MAR
PY 2016
VL 56
BP 62
EP 68
DI 10.1016/j.pediatrneurol.2015.12.005
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA DH3JN
UT WOS:000372683400014
PM 26810774
ER
PT J
AU Goey, AKL
Figg, WD
AF Goey, Andrew K. L.
Figg, William D.
TI UGT genotyping in belinostat dosing
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE Belinostat; UGT1A1; Polymorphisms; Pharmacogenomics; Pharmacokinetics;
Pharmacodynamics
ID UDP-GLUCURONOSYLTRANSFERASE 1A1; IRINOTECAN-INDUCED NEUTROPENIA;
METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; GILBERTS-SYNDROME;
PHASE-I; INDUCED HYPERBILIRUBINEMIA; GENETIC-VARIANTS; NEONATAL
HYPERBILIRUBINEMIA; UGT1A1-ASTERISK-28 GENOTYPE
AB Certain genetic polymorphisms of UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) can reduce gene expression (*28, *60, *93) or activity (*6), thereby altering the pharmacokinetics, pharmacodynamics, and the risk of toxicities of UGT1A1 substrates, of which irinotecan is a widely-described example. This review presents an overview of the clinical effects of UGT1A1 polymorphisms on the pharmacology of UGT1A1 substrates, with a special focus on the novel histone deacetylase inhibitor belinostat. Belinostat, approved for the treatment of peripheral T-cell lymphoma, is primarily glucuronidated by UGT1A1. Recent preclinical and clinical data showed that UGT1A1*28 was associated with reduced glucuronidation in human liver microsomes, while in a retrospective analysis of a Phase I trial with patients receiving belinostat UGT1A1*60 was predominantly associated with increased belinostat plasma concentrations. Furthermore, both UGT1A1*28 and *60 variants were associated with increased incidence of thrombocytopenia and neutropenia. Using population pharmacokinetic analysis a 33% dose reduction has been proposed for patients carrying UGT1A1 variant alleles. Clinical effects of this genotype-based dosing recommendation is currently prospectively being investigated. Overall, the data suggest that UGT1A1 genotyping is useful for improving belinostat therapy. Published by Elsevier Ltd.
C1 [Goey, Andrew K. L.; Figg, William D.] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, CCR, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM andrew.goey@nih.gov; figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Dr. Cindy H. Chau for critically reviewing the manuscript. This
research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organization imply endorsement by the U.S. Government.
NR 67
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U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD MAR
PY 2016
VL 105
BP 22
EP 27
DI 10.1016/j.phrs.2016.01.002
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG9CE
UT WOS:000372379600003
PM 26773202
ER
PT J
AU Reshma, RS
Sreelatha, KH
Somasundaram, V
Kumar, SS
Nadhan, R
Nair, RS
Srinivas, P
AF Reshma, R. S.
Sreelatha, K. H.
Somasundaram, Veena
Kumar, Satheesh S.
Nadhan, Revathy
Nair, Rakesh Sathish
Srinivas, Priya
TI Plumbagin, a naphthaquinone derivative induces apoptosis in BRCA 1/2
defective castrate resistant prostate cancer cells as well as prostate
cancer stem-like cells
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE Plumbagin; Prostate cancer; BRCA1/2; Cancer stem cells
ID NF-KAPPA-B; PROTHYMOSIN-ALPHA; CYCLE ARREST; IN-VIVO; GROWTH; PATHWAY;
PROGRESSION; MODULATION; EXPRESSION; OVARIAN
AB Eventhough the role of BRCA1/2 in hereditary prostatic cancer is being unleashed at a rapid rate; their optimal clinical management remains undefined. Cancer stem cells are thought to be responsible for cancer chemoresistance and relapse, thus they represent a significant concern for cancer prognosis and therapy. In this study, we have analyzed the effect of Plumbagin (PB) and structurally related naphthaquinones on BRCA1/2 silenced prostate cancer cells and the ability of PB to target stem cells. Our cell proliferation studies showed that both PC-3 and DU145 cells were more sensitive to PB, though all the compounds induced mitochondrial potential loss, DNA fragmentation and morphological changes which are indicative of apoptosis. Both BRCA1/2 siRNA transfected PC-3 and DU145 cells exhibited increased sensitivity to PB. Gene expression profiling post PB treatment in BRCA1/2 silenced cells revealed that PB has a putative role in tumor suppression in BRCA defective cancers. Using flow cytometric analysis we have proved that PB has the putative ability to directly target CSCs. Overall studies suggest that PB's antitumour mechanisms holds promise for novel therapeutic approaches against BRCA mutated cancers as well as CSCs. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Reshma, R. S.; Sreelatha, K. H.; Somasundaram, Veena; Kumar, Satheesh S.; Nadhan, Revathy; Nair, Rakesh Sathish; Srinivas, Priya] Rajiv Gandhi Ctr Biotechnol, Canc Res Program, Thiruvananthapuram, Kerala, India.
[Somasundaram, Veena] NCI, Ctr Canc Res, Bldg 567,Room 254, Frederick, MD 21702 USA.
[Nair, Rakesh Sathish] Dept Surg, 840 South Wood St, Chicago, IL 60612 USA.
[Nair, Rakesh Sathish] Univ Illinois, Sch Med, 840 South Wood St, Chicago, IL 60612 USA.
RP Srinivas, P (reprint author), Rajiv Gandhi Ctr Biotechnol, Canc Res Program, Thiruvananthapuram, Kerala, India.
EM priyasrinivas@rgcb.res.in
FU Board of Research in Nuclear Sciences (BRNS) Department of Atomic
Energy, Govt. of India [2009/37/5/BRNS/1213, 37(1)/14/16/2014]; Indian
Council of Medical Research (ICMR) [3/2/2/215/2013/NCD-III (OPA-29483),
53/20/2012]; Rajiv Gandhi Centre for Biotechnology; Kerala State Council
for Science Technology and Environment [016/SRSHS/2011/CSTE]; Council
for Scientific and Industrial Research (CSIR), Govt. of India;
University Grants Commission (UGC), Govt. of India; BRNS; ICMR
FX We thank Dr. Asoke Banerji, Professor, Amrita School of Biotechnology,
Kerala, India, for the generous gift of 1,4-NQ, This work was supported
by Board of Research in Nuclear Sciences (BRNS) Department of Atomic
Energy, Govt. of India (BRNS Project No. 2009/37/5/BRNS/1213 and
No.37(1)/14/16/2014) and Indian Council of Medical Research (ICMR) ICMR
Project No. 3/2/2/215/2013/NCD-III (OPA-29483 & No.53/20/2012). The
authors also acknowledge financial support from intramural grant, Rajiv
Gandhi Centre for Biotechnology, Kerala State Council for Science
Technology and Environment (No.016/SRSHS/2011/CSTE) to PS. R.R.S
acknowledges research fellowship from BRNS and ICMR and S.K.H
acknowledges Senior Research Fellowship from ICMR. The authors also
acknowledge the research fellowship from the Council for Scientific and
Industrial Research (CSIR), Govt. of India to V.S., R.N and R.S. and
from the University Grants Commission (UGC), Govt. of India to S.K.S.
NR 50
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U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD MAR
PY 2016
VL 105
BP 134
EP 145
DI 10.1016/j.phrs.2016.01.012
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG9CE
UT WOS:000372379600014
PM 26808083
ER
PT J
AU Bayik, D
Gursel, I
Klinman, DM
AF Bayik, Defne
Gursel, Ihsan
Klinman, Dennis M.
TI Structure, mechanism and therapeutic utility of immunosuppressive
oligonucleotides
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE CpG oligonucleotide; IRF8; IRF5; Dendritic cell; TLR9
ID STIMULATORY CPG OLIGONUCLEOTIDES; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
DENDRITIC CELL ACTIVATION; INDUCED IMMUNE ACTIVATION; TOLL-LIKE
RECEPTORS; REGULATORY T-CELLS; SUPPRESSIVE OLIGODEOXYNUCLEOTIDES;
INHIBITORY OLIGONUCLEOTIDES; BACTERIAL-DNA; IN-VITRO
AB Synthetic oligodeoxynucleotides that can down-regulate cellular elements of the immune system have been developed and are being widely studied in preclinical models. These agents vary in sequence, mechanism of action, and cellular target(s) but share the ability to suppress a plethora of inflammatory responses. This work reviews the types of immunosuppressive oligodeoxynucleotide (Sup ODN) and compares their therapeutic activity against diseases characterized by pathologic levels of immune stimulation ranging from autoimmunity to septic shock to cancer (see graphical abstract). The mechanism(s) underlying the efficacy of Sup ODN and the influence size, sequence and nucleotide backbone on function are considered. Published by Elsevier Ltd.
C1 [Bayik, Defne; Klinman, Dennis M.] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Bayik, Defne; Gursel, Ihsan] Bilkent Univ, Mol Biol & Genet Dept, Therapeut ODN Res Lab, TR-06800 Ankara, Turkey.
RP Klinman, DM (reprint author), Frederick Natl Lab Canc Res, Bldg 567 Rm 205, Frederick, MD 21702 USA.; Gursel, I (reprint author), Bilkent Univ, Fac Sci, Biotherapeut ODN Res Lab, TR-06800 Ankara, Turkey.
EM ihsangursel@bilkent.edu.tr; klinmand@mail.nih.gov
FU Intramural Research Program of National Cancer Institute of National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute of the National Institutes of Health.
NR 106
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U2 13
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD MAR
PY 2016
VL 105
BP 216
EP 225
DI 10.1016/j.phrs.2015.11.010
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG9CE
UT WOS:000372379600023
PM 26779666
ER
PT J
AU Adesanya, MR
Bailey, W
Belcher, DC
Beltran, M
Branch, T
Brand, MK
Craft, EM
Donahue, AH
Dye, BA
Thornton-Evans, G
Garcia, I
Hyman, F
Joskow, R
Lester, AM
Makrides, NS
Manski, RJ
Mehegan, M
Mouden, LD
Nelson, D
Norris, L
O'Hara, J
Cherry-Peppers, G
Ricks, TL
Rollins, R
AF Adesanya, Margo R.
Bailey, William
Belcher, Donald C.
Beltran, Marco
Branch, Tracy
Brand, Marcia K.
Craft, Edwin M.
Donahue, Agnes H.
Dye, Bruce A.
Thornton-Evans, Gina
Garcia, Isabel
Hyman, Frederick
Joskow, Renee
Lester, Arlene M.
Makrides, Nicholas S.
Manski, Richard J.
Mehegan, Marian
Mouden, Lynn Douglas
Nelson, Danielle
Norris, Laurie
O'Hara, Jessica
Cherry-Peppers, Gail
Ricks, Timothy L.
Rollins, Rochelle
CA US Dept Hlth Human Serv
TI US Department of Health and Human Services Oral Health Strategic
Framework, 2014-2017
SO PUBLIC HEALTH REPORTS
LA English
DT Editorial Material
ID DENTAL-CARE; CARIES
C1 [Adesanya, Margo R.] Natl Inst Dent & Craniofacial Res, NIH, Off Sci Policy & Anal, Rockville, MD USA.
[Bailey, William] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Belcher, Donald C.] US Coast Guard, Qual & Performance Improvement, Washington, DC USA.
[Beltran, Marco; Rollins, Rochelle] Adm Children & Families, Washington, DC USA.
[Branch, Tracy; Lester, Arlene M.] OS Off Minor Hlth, Washington, DC USA.
[Brand, Marcia K.; Joskow, Renee] Hlth Resources & Serv Adm, Rockville, MD USA.
[Craft, Edwin M.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Donahue, Agnes H.] OS Off Assistant Secretary Hlth, OASH Intergovt Affairs RHA, Washington, DC USA.
[Dye, Bruce A.] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Thornton-Evans, Gina] Ctr Dis Control & Prevent, Div Oral Hlth, Atlanta, GA USA.
[Garcia, Isabel] Natl Inst Dent & Craniofacial Res, NIH, Rockville, MD USA.
[Hyman, Frederick] US FDA, Ctr Drug Evaluat & Res, Div Dermatol & Dent Prod, Silver Spring, MD USA.
[Makrides, Nicholas S.] Fed Bur Prisons, Washington, DC USA.
[Manski, Richard J.] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Mehegan, Marian] Off Assistant Secretary Hlth, Off Womens Hlth, Washington, DC USA.
[Mouden, Lynn Douglas] Ctr Medicare & Medicaid Serv, Div Qual Evaluat & Hlth Outcomes, Children & Adults Hlth Programs Grp, Washington, DC USA.
[Nelson, Danielle] Adm Community Living, Washington, DC USA.
[Norris, Laurie] Ctr Medicare & Medicaid Serv, Oral Hlth Initiat, Div Qual Evaluat & Hlth Outcomes, Washington, DC USA.
[O'Hara, Jessica] Off Secretary, Off Assistant Secretary Planning & Evaluat, Washington, DC USA.
[Cherry-Peppers, Gail] US FDA, Ctr Tobacco Prod, Off Sci, Silver Spring, MD USA.
[Ricks, Timothy L.] Indian Hlth Serv, Nashville Area Off Publ Hlth, Nashville, TN USA.
RP Adesanya, MR (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Off Sci Policy & Anal, Rockville, MD USA.
NR 56
TC 0
Z9 0
U1 2
U2 2
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD MAR-APR
PY 2016
VL 131
IS 2
BP 242
EP 257
PG 16
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DG9HH
UT WOS:000372392900007
ER
PT J
AU Panchision, DM
AF Panchision, David M.
TI Concise Review: Progress and Challenges in Using Human Stem Cells for
Biological and Therapeutics Discovery: Neuropsychiatric Disorders
SO STEM CELLS
LA English
DT Review
DE Induced pluripotent stem cells; Induced neuronal cells; Schizophrenia;
Bipolar disorder; Autism spectrum disorders; Genetics; Drug discovery
ID FRAGILE-X-SYNDROME; AUTISM SPECTRUM DISORDERS; INNERVATING
MOTOR-NEURONS; IPSC-DERIVED NEURONS; HUMAN SOMATIC-CELLS; HUMAN
FIBROBLASTS; RETT-SYNDROME; HUMAN BRAIN; BIPOLAR DISORDER; DIRECTED
DIFFERENTIATION
AB In facing the daunting challenge of using human embryonic and induced pluripotent stem cells to study complex neural circuit disorders such as schizophrenia, mood and anxiety disorders, and autism spectrum disorders, a 2012 National Institute of Mental Health workshop produced a set of recommendations to advance basic research and engage industry in cell-based studies of neuropsychiatric disorders. This review describes progress in meeting these recommendations, including the development of novel tools, strides in recapitulating relevant cell and tissue types, insights into the genetic basis of these disorders that permit integration of risk-associated gene regulatory networks with cell/circuit phenotypes, and promising findings of patient-control differences using cell-based assays. However, numerous challenges are still being addressed, requiring further technological development, approaches to resolve disease heterogeneity, and collaborative structures for investigators of different disciplines. Additionally, since data obtained so far is on small sample sizes, replication in larger sample sets is needed. A number of individual success stories point to a path forward in developing assays to translate discovery science to therapeutics development.
C1 [Panchision, David M.] NIMH, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd,MSC 9641, Bethesda, MD 20892 USA.
RP Panchision, DM (reprint author), NIMH, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd,MSC 9641, Bethesda, MD 20892 USA.
EM panchisiond@mail.nih.gov
FU National Institute of Mental Health
FX I thank Margaret Grabb, Douglas Meinecke, and Lois Winsky at NIMH and
Kristen Fabre at NCATS for thoughtful advice and Sergiu Pasca for the
use of primary data images. Support for and clearance of this manuscript
was provided by the National Institute of Mental Health. The views
expressed do not necessarily represent the views of the NIMH, the
National Institutes of Health, the Department of Health and Human
Services, or the United States Government.
NR 149
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U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD MAR
PY 2016
VL 34
IS 3
BP 523
EP 536
DI 10.1002/stem.2295
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA DH1NU
UT WOS:000372552600001
PM 26840228
ER
PT J
AU Xie, ZH
Chan, EC
Druey, KM
AF Xie, Zhihui
Chan, Eunice C.
Druey, Kirk M.
TI R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and
Immunity
SO AAPS JOURNAL
LA English
DT Review
DE G proteins; immune system; inflammation; RGS proteins
ID T-LYMPHOCYTE MIGRATION; MULTIPLE-SCLEROSIS; COUPLED RECEPTOR;
GENE-EXPRESSION; B-LYMPHOCYTES; DIFFERENTIAL EXPRESSION; NEGATIVE
REGULATOR; CELL-ACTIVATION; DENDRITIC CELLS; DRUG DISCOVERY
AB G protein-coupled receptors (GPCRs) have important functions in both innate and adaptive immunity, with the capacity to bridge interactions between the two arms of the host responses to pathogens through direct recognition of secreted microbial products or the by-products of host cells damaged by pathogen exposure. In the mid-1990s, a large group of intracellular proteins was discovered, the regulator of G protein signaling (RGS) family, whose main, but not exclusive, function appears to be to constrain the intensity and duration of GPCR signaling. The R4/B subfamily-the focus of this review-includes RGS1-5, 8, 13, 16, 18, and 21, which are the smallest RGS proteins in size, with the exception of RGS3. Prominent roles in the trafficking of B and T lymphocytes and macrophages have been described for RGS1, RGS13, and RGS16, while RGS18 appears to control platelet and osteoclast functions. Additional G protein independent functions of RGS13 have been uncovered in gene expression in B lymphocytes and mast cell-mediated allergic reactions. In this review, we discuss potential physiological roles of this RGS protein subfamily, primarily in leukocytes having central roles in immune and inflammatory responses. We also discuss approaches to target RGS proteins therapeutically, which represents a virtually untapped strategy to combat exaggerated immune responses leading to inflammation.
C1 [Xie, Zhihui; Chan, Eunice C.; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 50 South Dr Room 4154, Bethesda, MD 20892 USA.
RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 50 South Dr Room 4154, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 117
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U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAR
PY 2016
VL 18
IS 2
BP 294
EP 304
DI 10.1208/s12248-015-9847-0
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG3NV
UT WOS:000371977400003
PM 26597290
ER
PT J
AU Diao, XX
Scheidweiler, KB
Wohlfarth, A
Pang, SK
Kronstrand, R
Huestis, MA
AF Diao, Xingxing
Scheidweiler, Karl B.
Wohlfarth, Ariane
Pang, Shaokun
Kronstrand, Robert
Huestis, Marilyn A.
TI In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids
FDU-PB-22 and FUB-PB-22
SO AAPS JOURNAL
LA English
DT Article
DE FDU-PB-22; FUB-PB-22; hepatocyte metabolism; high-resolution mass
spectrometry; synthetic cannabinoid
ID RESOLUTION MASS-SPECTROMETRY; HUMAN HEPATOCYTES; ILLEGAL PRODUCTS;
5-FLUORO ANALOG; DRUG DISCOVERY; DESIGNER DRUGS; HUMAN URINE;
IDENTIFICATION; PHARMACOLOGY; 3-N-BUTYLPHTHALIDE
AB In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 mu M FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 mu M was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after beta-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the samemetabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after beta-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.
C1 [Diao, Xingxing; Scheidweiler, Karl B.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab, IRP, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
[Wohlfarth, Ariane; Kronstrand, Robert] Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
[Wohlfarth, Ariane; Kronstrand, Robert] Linkoping Univ, Dept Drug Res, S-58185 Linkoping, Sweden.
[Pang, Shaokun] SCIEX Ltd, Redwood City, CA 94404 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Chem & Drug Metab, IRP, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health
FX This research is supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health.
FDU-PB-22 and FUB-PB-22 were generously donated by the US Drug
Enforcement Administration. Molecular Discovery kindly provided the
MetaSite software.
NR 38
TC 8
Z9 8
U1 6
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAR
PY 2016
VL 18
IS 2
BP 455
EP 464
DI 10.1208/s12248-016-9867-4
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG3NV
UT WOS:000371977400019
PM 26810398
ER
PT J
AU Dutta, N
Helton, SG
Schwandt, M
Zhu, X
Momenan, R
Lohoff, FW
AF Dutta, Nisha
Helton, Sarah G.
Schwandt, Melanie
Zhu, Xi
Momenan, Reza
Lohoff, Falk W.
TI Genetic Variation in the Vesicular Monoamine Transporter 1
(VMAT1/SLC18A1) Gene and Alcohol Withdrawal Severity
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Withdrawal; Presynaptic Monoamine Transporter; Genetics; VMAT1
ID DELIRIUM-TREMENS; POLYMORPHISMS; ASSOCIATION; DEPENDENCE; AMPHETAMINE;
SYMPTOMS; KNOCKOUT; SEIZURES; SYSTEM
AB BackgroundAlcohol withdrawal (AW) can be a serious consequence of alcohol dependence and consists of various neurochemical adaptations in the brain. One such neuroadaptation occurs in the monoamine neurotransmitter system. Recently, a functional variant in the presynaptic vesicular monoamine transporter gene (VMAT1/SLC18A1Thr136Ilers1390938) was found to significantly increase transport of monoamines into synaptic vesicles invitro. We hypothesize that the alteration of magnitude of monoamine release contributes to severity of AW symptoms.
MethodsAlcohol-dependent individuals (n=609; European American n=340; African American n=216; other n=53) were administered the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) questionnaire at the time of inpatient admission. Patients were subsequently genotyped for 12 single nucleotide polymorphism (SNP) markers in VMAT1. Association analyses were conducted on the combined sample and separated by ethnicity.
ResultsSingle marker association tests revealed a significant association between 3 VMAT1 markers and CIWA-Ar scores in the EA sample. The minor alleles of rs1390938 (A) and rs952859 (C) were significantly associated with lower CIWA-Ar scores (p=0.0006; p=0.0007), whereas the minor allele of rs3779672 (G) was significantly associated with higher scores (p=0.006). Additionally, these 3 SNPs were found in a haplotype block that was significantly associated with lower CIWA-Ar scores after haplotype analyses were run (p=0.009).
ConclusionsThis study shows that genetic variants in VMAT1, including the functional SNP rs1390938, contribute to the severity of AW in patients of European descent. Our data show for the first time a role of presynaptic neurotransmitter release in AW severity. This finding could contribute to identifying patients at risk for severe AW and shed light into the pathophysiology of AW and its treatment.
C1 [Dutta, Nisha; Helton, Sarah G.; Schwandt, Melanie; Lohoff, Falk W.] NIAAA, Sect Clin Genom & Expt Therapeut, NIH, 10 Ctr Dr,10CRC-2-2352, Bethesda, MD 20892 USA.
[Zhu, Xi; Momenan, Reza] NIAAA, Sect Brain & Electrophys & Imaging, NIH, Bethesda, MD 20892 USA.
RP Lohoff, FW (reprint author), NIAAA, Sect Clin Genom & Expt Therapeut, NIH, 10 Ctr Dr,10CRC-2-2352, Bethesda, MD 20892 USA.
EM falk.lohoff@nih.gov
RI Schwandt, Melanie/L-9866-2016; Lohoff, Falk/M-7951-2016
FU intramural research funding from National Institute on Alcohol Abuse and
Alcoholism
FX The study was supported by intramural research funding from the National
Institute on Alcohol Abuse and Alcoholism.
NR 40
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2016
VL 40
IS 3
BP 474
EP 481
DI 10.1111/acer.12991
PG 8
WC Substance Abuse
SC Substance Abuse
GA DG4EC
UT WOS:000372023000005
PM 26876819
ER
PT J
AU Yokoyama, A
Brooks, PJ
Yokoyama, T
Mizukami, T
Matsui, T
Kimura, M
Matsushita, S
Higuchi, S
Maruyama, K
AF Yokoyama, Akira
Brooks, Philip J.
Yokoyama, Tetsuji
Mizukami, Takeshi
Matsui, Toshifumi
Kimura, Mitsuru
Matsushita, Sachio
Higuchi, Susumu
Maruyama, Katsuya
TI Blood Leukocyte Counts and Genetic Polymorphisms of Alcohol
Dehydrogenase-1B and Aldehyde Dehydrogenase-2 in Japanese Alcoholic Men
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Acetaldehyde; Alcohol Dehydrogenase; Alcoholic; Aldehyde Dehydrogenase;
Leukocyte; White Blood Cell
ID FOLATE-DEFICIENCY; LIVER-DISEASE; BONE-MARROW; ACETALDEHYDE; ETHANOL;
METABOLISM; RISK; MICE; GRANULOCYTES; INFLAMMATION
AB BackgroundRoughly 40% of East Asians have inactive aldehyde dehydrogenase-2 (ALDH2) encoded by the ALDH2*2 allele, and 90% have highly active alcohol dehydrogenase-1B (ADH1B) encoded by the ADH1B*2 allele. Macrocytosis and macrocytic anemia in alcoholics have been associated with ADH1B and ALDH2gene variants which increase acetaldehyde (AcH) levels.
MethodsWe investigated the relationship between ADH1B*2, ALDH2*2, and leukocyte counts of Japanese alcoholic men (N=1,661).
ResultsAfter adjusting for age, drinking habits, smoking habits, body mass index, presence of liver cirrhosis, and serum levels of C-reactive protein, we found that total and differential leukocyte counts were lower in the presence of the ALDH2*1/*2 genotype (vs. ALDH2*1/*1 genotype). ALDH2*2/*2 carriers were not found in our study population. Leukocyte, granulocyte, and monocyte counts were also lower in the presence of ADH1B*2 (vs. ADH1B*1/*1 genotype), but the lymphocyte count was higher. The ALDH2*1/*2 genotype was associated with leukocytopenia (<4,000/l; adjusted odds ratio [95% confidence interval]=1.89 [1.27 to 2.80]), granulocytopenia (<2,000/l; 1.86 [1.22 to 2.82]), monocytopenia (<250/l; 2.22 [1.49 to 3.29]), and lymphocytopenia (<1,000/l; 1.93 [1.32 to 2.83]). In contrast, the ADH1B*2 had the opposite effect on lymphocytopenia (0.65 [0.46 to 0.93]). Considering genotype effects under conditions of immune stimulation, we observed suppressive effects of ADH1B*2 allele on leukocytosis (9,000/l; 0.69 [0.50 to 0.97]), granulocytosis (6,500/l; 0.66 [0.47 to 0.93]), and monocytosis (750/l; 0.56 [0.39 to 0.79]). The ADH1B*2 plus ALDH2*1/*2 combination had the greatest suppressive effects on the leukocyte, granulocyte, and monocyte counts.
ConclusionsThe total and differential blood leukocyte counts of Japanese alcoholics were strongly affected by their ADH1B and ALDH2 gene variants. High AcH exposure levels probably play a critical role in the suppression of blood leukocyte counts in alcoholics.
C1 [Yokoyama, Akira; Mizukami, Takeshi; Matsui, Toshifumi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya] Natl Hosp Org, Kurihama Med & Addict Ctr, Kanagawa, Japan.
[Brooks, Philip J.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Yokoyama, Tetsuji] Natl Inst Publ Hlth, Dept Hlth Promot, Saitama, Japan.
[Matsui, Toshifumi] Kyorin Univ Hosp, Dept Geriatr Med, Tokyo, Japan.
[Brooks, Philip J.] NIH, Natl Ctr Adv Translat Sci, Div Clin Innovat, Bldg 10, Bethesda, MD 20892 USA.
RP Yokoyama, A (reprint author), Natl Hosp Org, Kurihama Med & Addict Ctr, Clin Res Unit, 5-3-1 Nobi, Yokosuka, Kanagawa 2390841, Japan.
EM a_yokoyama@kurihama1.hosp.go.jp
NR 49
TC 1
Z9 1
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2016
VL 40
IS 3
BP 507
EP 517
DI 10.1111/acer.12983
PG 11
WC Substance Abuse
SC Substance Abuse
GA DG4EC
UT WOS:000372023000009
PM 26917006
ER
PT J
AU Komori, M
Lin, YC
Cortese, I
Blake, A
Ohayon, J
Cherup, J
Maric, D
Kosa, P
Wu, TX
Bielekova, B
AF Komori, Mika
Lin, Yen Chih
Cortese, Irene
Blake, Andrew
Ohayon, Joan
Cherup, Jamie
Maric, Dragan
Kosa, Peter
Wu, Tianxia
Bielekova, Bibiana
TI Insufficient disease inhibition by intrathecal rituximab in progressive
multiple sclerosis
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID CEREBROSPINAL-FLUID; PHASE-I; B-CELLS; MONOCLONAL-ANTIBODY; LYMPHOMA;
TRIAL; THERAPY; NEURODEGENERATION; INFLAMMATION; IDEC-C2B8
AB Objective: Inaccessibility of the inflammation compartmentalized to the central nervous system (CNS) may underlie the lack of efficacy of immunomodulatory treatments in progressive multiple sclerosis (MS). The double blind combination of Rituximab by IntraVenous and IntraThecAl injection versus placebo in patients with Low-Inflammatory SEcondary progressive MS (RIVITALISE; NCT01212094) trial was designed to answer: (1) Whether an induction dose of intravenous and intrathecal rituximab efficiently depletes CNS B cells? and (2) If so, whether this leads to global inhibition of CNS inflammation and slowing of CNS tissue destruction?
MethodsPatients aged 18-65years were randomly assigned to rituximab or placebo. Protocol-stipulated interim analysis quantified the efficacy of B-cell depletion.
ResultsThe efficacy on cerebrospinal fluid (CSF) biomarkers failed to reach criteria for continuation of the trial. B-cell-related CSF biomarkers (sCD21 and B-cell activating factor) changed only in the active-treatment arm. While CSF B cells were killed robustly (median -79.71%, P=0.0176), B cells in CNS tissue were depleted inadequately (similar to-10-20%, P<0.0001). Consequently, the T-cell-specific CSF biomarker sCD27 decreased slightly (-10.97%, P=0.0005), while axonal damage marker, neurofilament light chain did not change. Insufficient saturation of CD20, lack of lytic complement, and paucity of cytotoxic CD56(dim) NK cells contribute to decreased efficacy of rituximab in the CNS.
InterpretationBiomarker studies reliably quantified complementary pharmacodynamic effects of rituximab in the CNS, exposed causes for poor efficacy and determined that RIVITALISE trial would be underpowered to measure efficacy on clinical outcomes. Identified mechanisms for poor efficacy are applicable to all CNS-inflammation targeting monoclonal antibodies.
C1 [Komori, Mika; Lin, Yen Chih; Blake, Andrew; Cherup, Jamie; Kosa, Peter; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Cortese, Irene; Ohayon, Joan] NINDS, Neuroimmunol Clin, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Neurosci Program, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bielekova, Bibiana] NIH, NIH Ctr Human Immunol CHI, Bldg 10, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch NIB, NIH, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
NR 33
TC 10
Z9 10
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD MAR
PY 2016
VL 3
IS 3
BP 166
EP 179
DI 10.1002/acn3.293
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DG2WS
UT WOS:000371931900002
PM 27042677
ER
PT J
AU Postnikov, YV
Bustin, M
AF Postnikov, Yuri V.
Bustin, Michael
TI Functional interplay between histone H1 and HMG proteins in chromatin
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE Histone H1; HMG proteins; Chromatin
ID MOBILITY-GROUP PROTEINS; GROUP CHROMOSOMAL-PROTEINS; 4-WAY JUNCTION DNA;
RNA-POLYMERASE-II; LINKER HISTONES; LIVING CELLS; DYNAMIC INTERACTION;
BINDING PROTEINS; TRANSCRIPTION; NUCLEOSOMES
AB The dynamic interaction of nucleosome binding proteins with their chromatin targets is an important element in regulating the structure and function of chromatin. Histone H1 variants and High Mobility Group (HMG) proteins are ubiquitously expressed in all vertebrate cells, bind dynamically to chromatin, and are known to affect chromatin condensation and the ability of regulatory factors to access their genomic binding sites. Here, we review the studies that focus on the interactions between H1 and HMGs and highlight the functional consequences of the interplay between these architectural chromatin binding proteins. H-1 and HMG proteins are mobile molecules that bind to nucleosomes as members of a dynamic protein network. All HMGs compete with H1 for chromatin binding sites, in a dose dependent fashion, but each HMG family has specific effects on the interaction of H1 with chromatin. The interplay between H1 and HMGs affects chromatin organization and plays a role in epigenetic regulation. Published by Elsevier B.V.
C1 [Postnikov, Yuri V.; Bustin, Michael] NIH, Prot Sect, Lab Metab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
RP Postnikov, YV (reprint author), NIH, Bldg 37 Room 3122,37 Convent Dr, Bethesda, MD 20892 USA.
EM PostnikY@mail.nih.gov
RI Bustin, Michael/G-6155-2015
FU CCR, NCI, NIH [ZIA BC011154, ZIA BC004496]
FX The literature on H1 and HMGs is relatively large and we could not
acknowledge and quote all the pertinent references. We do apologize to
the authors which we did not quote. This research was supported by
project #s ZIA BC011154 and ZIA BC004496 from the Intramural Research
Programs of the CCR, NCI, NIH.
NR 82
TC 5
Z9 5
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD MAR
PY 2016
VL 1859
IS 3
SI SI
BP 462
EP 467
DI 10.1016/j.bbagrm.2015.10.006
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DG2ZS
UT WOS:000371939900006
PM 26455954
ER
PT J
AU Bat, T
Bat, BE
El-Moghraby, A
Patel, S
Feng, XM
Dunbar, CE
Sarac, E
AF Bat, Taha
Bat, Betul E.
El-Moghraby, Ahmed
Patel, Samir
Feng, Xingmin
Dunbar, Cynthia E.
Sarac, Erdal
TI Thrombopoietic status of patients on haemodialysis
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE thrombopoietin; immature platelet fraction; absolute immature platelet
number; haemodialysis; IL1A (IL1)
ID BONE-MARROW; THROMBOCYTOPENIA; MEMBRANES
AB Thrombocytopenia is a potential dialysis-related treatment complication. Developments in bio-compatible dialyser membranes have decreased the occurrence of thrombocytopenia. We investigated whether thrombopoiesis is impaired in haemodialysis patients by measuring the thrombopoietin level and absolute immature platelet number (AIPN) in the blood of patients undergoing haemodialysis. Samples were collected from the dialysis tubing pre- and post- haemodialysis in a cohort of 45 well-characterized haemodialysis patients. Thrombopoietin levels and AIPN increased following haemodialysis, despite no change in platelet count. Observed increase in release of immature platelets from the bone marrow following haemodialysis indicates possible complement activation secondary to interaction between blood constituents and the dialysis membrane.
C1 [Bat, Taha; Bat, Betul E.; El-Moghraby, Ahmed; Patel, Samir; Sarac, Erdal] Northeastern Ohio Med Univ NEOMED, Western Reserve Hlth Educ, Youngstown, OH 44504 USA.
[Feng, Xingmin; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Bat, T (reprint author), Northeastern Ohio Med Univ NEOMED, Western Reserve Hlth Educ, Internal Med, 500 Gypsy Lane, Youngstown, OH 44504 USA.
EM md.tbat@gmail.com
OI Patel, Samir/0000-0002-4471-2996
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute
FX We would like to thank Martha Pallant, of the Department of Laboratory
Medicine at Northside Medical Center for her expertise and assistance
with this study and Dr. Neal S Young, Hematology Branch, NHLBI, for
supporting these studies. This work was supported in part by the
Division of Intramural Research, National Heart, Lung, and Blood
Institute.
NR 14
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAR
PY 2016
VL 172
IS 6
BP 954
EP 957
DI 10.1111/bjh.13918
PG 4
WC Hematology
SC Hematology
GA DG7NA
UT WOS:000372269800013
PM 26887628
ER
PT J
AU Drahos, J
Schwameis, K
Orzolek, LD
Hao, HP
Birner, P
Taylor, PR
Pfeiffer, RM
Schoppmann, SF
Cook, MB
AF Drahos, Jennifer
Schwameis, Katrin
Orzolek, Linda D.
Hao, Haiping
Birner, Peter
Taylor, Phillip R.
Pfeiffer, Ruth M.
Schoppmann, Sebastian F.
Cook, Michael B.
TI MicroRNA Profiles of Barrett's Esophagus and Esophageal Adenocarcinoma:
Differences in Glandular Non-native Epithelium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HIGH-GRADE DYSPLASIA; DOWN-REGULATION;
NASOPHARYNGEAL CARCINOMA; GASTRIC-CARCINOMA; TUMOR-SUPPRESSOR;
BREAST-CANCER; EXPRESSION; TARGETS; PROGRESSION
AB Background: The tissue specificity and robustness of miRNAs may aid risk prediction in individuals diagnosed with Barrett's esophagus. As an initial step, we assessed whether miRNAs can positively distinguish esophageal adenocarcinoma from the precursor metaplasia Barrett's esophagus.
Methods: In a case-control study of 150 esophageal adenocarcinomas frequency matched to 148 Barrett's esophagus cases, we quantitated expression of 800 human miRNAs in formalin-fixed paraffin-embedded tissue RNA using Nano-String miRNA v2. We tested differences in detection by case group using the chi(2) test and differences in expression using the Wilcoxon rank-sum test. Bonferroni-corrected statistical significance threshold was set at P < 6.25E-05. Sensitivity and specificity were assessed for the most significant miRNAs using 5-fold cross-validation.
Results: We observed 46 distinct miRNAs significantly increased in esophageal adenocarcinoma compared with Barrett's esophagus, 35 of which remained when restricted to T1b and T2 malignancies. Three miRNAs (miR-663b, miR-421, and miR-502-5p) were detected in >80% esophageal adenocarcinoma, but <20% of Barrett's esophagus. Seven miRNAs (miR-4286, miR-630, miR-575, miR-494, miR-320e, miR-4488, and miR-4508) exhibited the most extreme differences in expression with > 5-fold increases. Using 5-fold cross-validation, we repeated feature (miR) selection and case-control prediction and computed performance criteria. Each of the five folds selected the same top 10 miRNAs, which, together, provided 98% sensitivity and 95% specificity.
Conclusion: This study provides evidence that tissue miRNA profiles can discriminate esophageal adenocarcinoma from Barrett's esophagus. This large analysis has identified miRNAs that merit further investigation in relation to pathogenesis and diagnosis of esophageal adenocarcinoma.
C1 [Drahos, Jennifer; Taylor, Phillip R.; Pfeiffer, Ruth M.; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, NIH, DDHS, Bethesda, MD 20892 USA.
[Schwameis, Katrin; Birner, Peter; Schoppmann, Sebastian F.] Med Univ Vienna, Upper GI Serv, CCC GET Unit, Dept Surg, Vienna, Austria.
[Orzolek, Linda D.; Hao, Haiping] Johns Hopkins Med Inst, Deep Sequencing & Microarray Core, Baltimore, MD USA.
RP Drahos, J (reprint author), NCI, 9609 Med Ctr Dr,Rm 7E 226,MSC 9774, Bethesda, MD 20892 USA.
EM jennifer.drahos@nih.gov
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU Intramural Program of NCI at NIH; Department of Health and Human
Services
FX This work was supported by the Intramural Program of the NCI at the NIH
and the Department of Health and Human Services.
NR 58
TC 1
Z9 1
U1 2
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2016
VL 25
IS 3
BP 429
EP 437
DI 10.1158/1055-9965.EPI-15-0161
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6EA
UT WOS:000372173900001
PM 26604271
ER
PT J
AU Winham, SJ
Pirie, A
Chen, YA
Larson, MC
Fogarty, ZC
Earp, MA
Anton-Culver, H
Bandera, EV
Cramer, D
Doherty, JA
Goodman, MT
Gronwald, J
Karlan, BY
Kjaer, SK
Levine, DA
Menon, U
Ness, RB
Pearce, CL
Pejovic, T
Rossing, MA
Wentzensen, N
Bean, YT
Bisogna, M
Brinton, LA
Carney, ME
Cunningham, JM
Cybulski, C
Defazio, A
Dicks, EM
Edwards, RP
Gayther, SA
Gentry-Maharaj, A
Gore, M
Iversen, ES
Jensen, A
Johnatty, SE
Lester, J
Lin, HY
Lissowska, J
Lubinski, J
Menkiszak, J
Modugno, F
Moysich, KB
Orlow, I
Pike, MC
Ramus, SJ
Song, HL
Terry, KL
Thompson, PJ
Tyrer, JP
van den Berg, DJ
Vierkant, RA
Vitonis, AF
Walsh, C
Wilkens, LR
Wu, AH
Yang, H
Ziogas, A
Berchuck, A
Chenevix-Trench, G
Schildkraut, JM
Permuth-Wey, J
Phelan, CM
Pharoah, PDP
Fridley, BL
Sellers, TA
Goode, EL
AF Winham, Stacey J.
Pirie, Ailith
Chen, Yian Ann
Larson, Melissa C.
Fogarty, Zachary C.
Earp, Madalene A.
Anton-Culver, Hoda
Bandera, Elisa V.
Cramer, Daniel
Doherty, Jennifer A.
Goodman, Marc T.
Gronwald, Jacek
Karlan, Beth Y.
Kjaer, Susanne K.
Levine, Douglas A.
Menon, Usha
Ness, Roberta B.
Pearce, Celeste L.
Pejovic, Tanja
Rossing, Mary Anne
Wentzensen, Nicolas
Bean, Yukie T.
Bisogna, Maria
Brinton, Louise A.
Carney, Michael E.
Cunningham, Julie M.
Cybulski, Cezary
Defazio, Anna
Dicks, Ed M.
Edwards, Robert P.
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Gore, Martin
Iversen, Edwin S.
Jensen, Allan
Johnatty, Sharon E.
Lester, Jenny
Lin, Hui-Yi
Lissowska, Jolanta
Lubinski, Jan
Menkiszak, Janusz
Modugno, Francesmary
Moysich, Kirsten B.
Orlow, Irene
Pike, Malcolm C.
Ramus, Susan J.
Song, Honglin
Terry, Kathryn L.
Thompson, Pamela J.
Tyrer, Jonathan P.
van den Berg, David J.
Vierkant, Robert A.
Vitonis, Allison F.
Walsh, Christine
Wilkens, Lynne R.
Wu, Anna H.
Yang, Hannah
Ziogas, Argyrios
Berchuck, Andrew
Chenevix-Trench, Georgia
Schildkraut, Joellen M.
Permuth-Wey, Jennifer
Phelan, Catherine M.
Pharoah, Paul D. P.
Fridley, Brooke L.
Sellers, Thomas A.
Goode, Ellen L.
CA Australian Ovarian Canc Study Grp
TI Investigation of Exomic Variants Associated with Overall Survival in
Ovarian Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; BREAST-CANCER; MUTATION
CARRIERS; COMMON VARIANTS; RARE VARIANTS; BRCA1; WOMEN; AUTOPHAGY;
DISEASES
AB Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).
Methods: The primary patient set (Set 1) included 14 independent-EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped).
Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (P-meta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (P-meta = 1.1E-6; P-corrected = 0.01).
Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.
C1 [Winham, Stacey J.; Larson, Melissa C.; Fogarty, Zachary C.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Pirie, Ailith] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Chen, Yian Ann; Lin, Hui-Yi; Permuth-Wey, Jennifer; Phelan, Catherine M.; Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Earp, Madalene A.; Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Harvard Univ, Sch Med, Boston, MA USA.
[Cramer, Daniel; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Lebanon, NH USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Gronwald, Jacek; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Karlan, Beth Y.; Lester, Jenny; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Kjaer, Susanne K.; Jensen, Allan] Danish Canc Soc, Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark.
[Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark.
[Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Menon, Usha; Gentry-Maharaj, Aleksandra] UCL, Inst Womens Hlth, Dept Womens Canc, Gynaecol Canc Res Ctr, London, England.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Pearce, Celeste L.; Gayther, Simon A.; Pike, Malcolm C.; Ramus, Susan J.; van den Berg, David J.; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Pejovic, Tanja; Bean, Yukie T.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Pejovic, Tanja; Bean, Yukie T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Wentzensen, Nicolas; Brinton, Louise A.; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Carney, Michael E.] Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA.
[Cybulski, Cezary] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Defazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia.
[Defazio, Anna; Chenevix-Trench, Georgia] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Sydney, NSW 2006, Australia.
[Dicks, Ed M.; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
[Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Gore, Martin] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Johnatty, Sharon E.; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Menkiszak, Janusz] Pomeranian Med Univ, Dept Surg Gynecol & Gynecol Oncol Adults & Adoles, Szczecin, Poland.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
[Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92717 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Herston, Qld, Australia.
[Chenevix-Trench, Georgia; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, 481 Little Lonsdale St, Melbourne, Vic 3000, Australia.
[Schildkraut, Joellen M.] Univ Virginia, Publ Hlth Serv, Charlottesville, VA USA.
[Fridley, Brooke L.] Univ Kansas, Ctr Canc, Kansas IDeA Network Biomed Res Excellence Bioinfo, Kansas City, KS USA.
RP Goode, EL (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA.
EM egoode@mayo.edu
RI Menkiszak, Janusz/I-4036-2014; Johnatty, Sharon/R-8890-2016; Gronwald,
Jacek/A-4576-2017;
OI Johnatty, Sharon/0000-0002-7888-1966; Gronwald,
Jacek/0000-0002-3643-2871; Ramus, Susan/0000-0003-0005-7798; Winham,
Stacey/0000-0002-8492-9102; Ewing, Ailith/0000-0002-2272-1277
FU NIH Office of Research on Women's Health (Building Interdisciplinary
Careers in Women's Health award) [K12HD065987]; Genetic Associations and
Mechanisms in Oncology (GAME-ON); NCI Cancer Post-GWAS Initiative
[U19-CA148112]; NHMRC; University of Sydney Cancer Research Fund; Cancer
Institute NSW through Sydney West Translational Cancer Research Centre;
NIH [R01 CA-149429]; Medical Research Council Studentship; Eve Appeal;
Oak Foundation; AUS: U.S. Army Medical Research and Materiel Command
[DAMD17-01-1-0729]; National Health & Medical Research Council of
Australia [199600, 400281]; Cancer Council of New South Wales; Cancer
Councils of Victoria; Cancer Councils of Queensland; Cancer Councils of
South Australia; Cancer Councils of Tasmania; Cancer Foundation of
Western Australia; HAW: NIH [R01-CA58598, N01-CN-55424, N01-PC-67001];
HOP: US Army Medical Research and Material Command [DAMD17-02-1-0669];
NCI [K07-CA080668, R01-CA95023, R01-CA126841]; NIH/National Center for
Research Resources/General Clinical Research Center [M01-RR000056]; LAX:
American Cancer Society Early Detection Professorship
[SIOP-06-258-01-COUN]; National Center for Advancing Translational
Sciences (NCATS) [UL1TR000124]; NCI, Bethesda, MD [R01-CA61107]; Danish
Cancer Society, Copenhagen, Denmark [94 222 52]; Mermaid I project; MAC
and MAY: NIH [R01-CA122443, P30-CA15083, P50-CA136393]; NCO: Department
of Defense [DAMD17-02-1-0666]; NEC: NIH [R01-CA54419, P50-CA105009];
Department of Defense [W81XWH-10-1-02802]; NJO: NCI [NIH-K07 CA095666,
NIH-K22-CA138563, P30-CA072720]; Cancer Institute of New Jersey; ORE:
OHSU Foundation; POC: Pomeranian Medical University; RMH: Cancer
Research UK; Royal Marsden Hospital; SEA: Cancer Research UK
[C490/A10119 C490/A10124]; UK National Institute for Health Research
Biomedical Research Centres at the University of Cambridge, SEARCH team,
Craig Luccarini, Caroline Baynes, Don Conroy; Eve Appeal (The Oak
Foundation); National Institute for Health Research University College
London Hospitals Biomedical Research Centre; California Cancer Research
Program [0001389V-20170, 2II0200]; [P50-CA159981]; [USC: P01-CA17054];
[P30-CA14089]; [R01-CA61132]; [N01-PC67010]; [N01-CN025403];
[R03-CA113148]; [R03-CA115195]
FX This work was supported by grants from the NIH Office of Research on
Women's Health (Building Interdisciplinary Careers in Women's Health
award K12HD065987; to S.J. Winham) and Genetic Associations and
Mechanisms in Oncology (GAME-ON), an NCI Cancer Post-GWAS Initiative
(U19-CA148112; to T.A. Sellers). G. Chenevix-Trench is supported by
Fellowships from NHMRC. A. deFazio is supported by the University of
Sydney Cancer Research Fund and the Cancer Institute NSW through the
Sydney West Translational Cancer Research Centre. C.M. Phelan is funded
in part by NIH R01 CA-149429. A. Pirie is funding in part by a Medical
Research Council Studentship. A. Gentry-Maharaj is supported by Eve
Appeal and the Oak Foundation. In addition, the individual study sites
were supported by: AUS: U.S. Army Medical Research and Materiel Command
(DAMD17-01-1-0729; to G. Chenevix-Trench), National Health & Medical
Research Council of Australia (199600 and 400281; to G.
Chenevix-Trench), Cancer Councils of New South Wales, Victoria,
Queensland, South Australia, and Tasmania, Cancer Foundation of Western
Australia. DOV: Funding for this study was provided by U19-CA148112 (to
T. Sellers); HAW: NIH (R01-CA58598, N01-CN-55424, and N01-PC-67001; to
M.T. Goodman); HOP: US Army Medical Research and Material Command
DAMD17-02-1-0669 (to F. Modugno); NCI K07-CA080668, R01-CA95023,
R01-CA126841 (to F. Modugno); P50-CA159981 (to F. Modugno); NIH/National
Center for Research Resources/General Clinical Research Center grant
M01-RR000056 (to F. Modugno); LAX: American Cancer Society Early
Detection Professorship (SIOP-06-258-01-COUN; to B.Y. Karlan) and the
National Center for Advancing Translational Sciences (NCATS), grant
UL1TR000124 (to B. Y. Karlan); MAL: funding for this study was provided
by research grant R01-CA61107 from the NCI, Bethesda, MD (to S.K. Kjaer
and A. Jensen); research grant 94 222 52 from the Danish Cancer Society,
Copenhagen, Denmark (to S.K. Kjaer and A. Jensen); and the Mermaid I
project (to S.K. Kjaer and A. Jenesn); MAC and MAY: NIH (R01-CA122443,
P30-CA15083, P50-CA136393; to E.L. Goode); NCO: Department of Defense
(DAMD17-02-1-0666; to J.M. Schildkraut); NEC: NIH R01-CA54419 and
P50-CA105009 and Department of Defense W81XWH-10-1-02802 (to K.L.
Terry); NJO: NCI (NIH-K07 CA095666, NIH-K22-CA138563, and P30-CA072720;
to E.V. Bandera) and the Cancer Institute of New Jersey (to E.V.
Bandera); ORE: OHSU Foundation (to T. Pejovic); POC: Pomeranian Medical
University (to J. Gronwald); RMH: Cancer Research UK (no grant number is
available), Royal Marsden Hospital (to P.D. Pharoah); SEA: Cancer
Research UK (C490/A10119 C490/A10124; to P.D. Pharoah); UK National
Institute for Health Research Biomedical Research Centres at the
University of Cambridge, SEARCH team, Craig Luccarini, Caroline Baynes,
Don Conroy; UKO: The UKOPS study was funded by The Eve Appeal (The Oak
Foundation) and supported by the National Institute for Health Research
University College London Hospitals Biomedical Research Centre (to U.
Menon and S.A. Gayther). USC: P01-CA17054, P30-CA14089, R01-CA61132,
N01-PC67010, N01-CN025403 (to M.C. Pike), R03-CA113148, R03-CA115195 (to
C.L. Pearce), and California Cancer Research Program (0001389V-20170,
2II0200; to A. Wu); POL: Intramural Research Program of the NCI.
NR 38
TC 1
Z9 1
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2016
VL 25
IS 3
BP 446
EP 454
DI 10.1158/1055-9965.EPI-15-0240
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6EA
UT WOS:000372173900003
PM 26747452
ER
PT J
AU Murtola, TJ
Gurel, B
Umbehr, M
Lucia, MS
Thompson, IM
Goodman, PJ
Kristal, AR
Parnes, HL
Lippman, SM
Sutcliffe, S
Peskoe, SB
Barber, JR
Drake, CG
Nelson, WG
De Marzo, AM
Platz, EA
AF Murtola, Teemu J.
Gurel, Bora
Umbehr, Martin
Lucia, M. Scott
Thompson, Ian M., Jr.
Goodman, Phyllis J.
Kristal, Alan R.
Parnes, Howard L.
Lippman, Scott M.
Sutcliffe, Siobhan
Peskoe, Sarah B.
Barber, John R.
Drake, Charles G.
Nelson, William G.
De Marzo, Angelo M.
Platz, Elizabeth A.
TI Inflammation in Benign Prostate Tissue and Prostate Cancer in the
Finasteride Arm of the Prostate Cancer Prevention Trial
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SYSTEM
AB Background: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm.
Methods: Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis.
Results: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [ OR, 0.90; 95% confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls.
Conclusion: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer.
C1 [Murtola, Teemu J.] Univ Tampere, Sch Med, Dept Urol, FIN-33101 Tampere, Finland.
[Murtola, Teemu J.] Univ Tampere, Tampere Univ Hosp, FIN-33101 Tampere, Finland.
[Murtola, Teemu J.; Umbehr, Martin; Peskoe, Sarah B.; Barber, John R.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Gurel, Bora] Kocaeli Univ, Dept Pathol, Sch Med, Kocaeli, Turkey.
[Umbehr, Martin] Univ Zurich, Univ Hosp, Dept Urol, Zurich, Switzerland.
[Lucia, M. Scott] Univ Colorado, Denver Sch Med, Dept Pathol, Aurora, CO USA.
[Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Goodman, Phyllis J.; Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Goodman, Phyllis J.; Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Parnes, Howard L.] NCI, Div Canc Prevent, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Sutcliffe, Siobhan] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA.
[Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
[Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Baltimore, MD 21205 USA.
[Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA.
[Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Platz, EA (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Room E6132,615 North Wolfe St, Baltimore, MD 21205 USA.; De Marzo, AM (reprint author), Johns Hopkins Sch Med, Dept Pathol, 1650 Orleans St, Baltimore, MD 21231 USA.
EM ademarz@jhmi.edu; eplatz1@jhu.edu
FU Public Health Service grants from NCI [P01 CA108964, P50 CA58236, U10
CA37429, UM1 CA182883]
FX This work was funded by Public Health Service grants P01 CA108964 (to
I.M. Thompson Jr; Project 4, to E.A. Platz) and P50 CA58236 (to W.G.
Nelson) from the NCI. The PCPT is funded by Public Health Service grants
U10 CA37429 (to C.D. Blanke) and UM1 CA182883 (to I.M. Thompson Jr and
C.M. Tangen) from the NCI.
NR 11
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2016
VL 25
IS 3
BP 463
EP 469
DI 10.1158/1055-9965.EPI-15-0987
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6EA
UT WOS:000372173900005
PM 26715424
ER
PT J
AU Pine, SR
Mechanic, LE
Enewold, L
Bowman, ED
Ryan, BM
Cote, ML
Wenzlaff, AS
Loffredo, CA
Olivo-Marston, S
Chaturvedi, A
Caporaso, NE
Schwartz, AG
Harris, CC
AF Pine, Sharon R.
Mechanic, Leah E.
Enewold, Lindsey
Bowman, Elise D.
Ryan, Brid M.
Cote, Michele L.
Wenzlaff, Angela S.
Loffredo, Christopher A.
Olivo-Marston, Susan
Chaturvedi, Anil
Caporaso, Neil E.
Schwartz, Ann G.
Harris, Curtis C.
TI Differential Serum Cytokine Levels and Risk of Lung Cancer Between
African and European Americans
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID C-REACTIVE PROTEIN; GENE POLYMORPHISMS; INTERLEUKIN-6; INFLAMMATION;
TRANSCRIPTION; DISPARITIES; FREQUENCIES; CLASSIFIER; EXPRESSION;
MORTALITY
AB Background: African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races.
Methods: Differences in 10 serum cytokine levels, IL1 beta, IL4, IL5, IL6, IL8, IL10, IL12, granulocyte macrophage colony-stimulating factor, IFN gamma, and TNF alpha, between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the Wayne State University Karmanos Cancer Institute case-control study.
Results: Six cytokines, IL4, IL5, IL8, IL10, IFN gamma, and TNF alpha, were significantly higher among European-American as compared with African-American controls. Elevated IL6 and IL8 levels were associated with lung cancer among both races in all three studies. Elevated IL1b, IL10, and TNFa levels were associated with lung cancer only among African Americans. The association between elevated TNFa levels and lung cancer among European Americans was significant after adjustment for additional factors.
Conclusions: Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans.
C1 [Pine, Sharon R.; Mechanic, Leah E.; Bowman, Elise D.; Ryan, Brid M.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pine, Sharon R.] Rutgers State Univ, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Mechanic, Leah E.] NCI, Epidemiol & Genom Res Program, Host Factors Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Enewold, Lindsey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Enewold, Lindsey] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Cote, Michele L.; Wenzlaff, Angela S.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Loffredo, Christopher A.] Georgetown Univ, Canc Genet & Epidemiol Program, Oncol & Biostat, Washington, DC USA.
[Olivo-Marston, Susan] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA.
[Chaturvedi, Anil] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, 37 Convent Dr,Room 3068A,MSC 4258, Bethesda, MD 20892 USA.; Pine, SR (reprint author), Rutgers State Univ, 195 Little Albany St, New Brunswick, NJ 08903 USA.
EM pinesr@cinj.rutgers.edu; curtis_harris@nih.gov
RI Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU Intramural Research Program of NIH, NCI, Center for Cancer Research;
Prevent Cancer Foundation; NIH [R01CA060691, N01-PC35145, P30CA22453,
K07CA125203]
FX This study was supported by Intramural Research Program of the NIH, NCI,
Center for Cancer Research (to C.C. Harris); Prevent Cancer Foundation
(to S.R. Pine); NIH grant R01CA060691, NIH contracts N01-PC35145 and
P30CA22453 (to A.G. Schwartz); and NIH grant K07CA125203 (to M.L. Cote).
NR 42
TC 3
Z9 3
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2016
VL 25
IS 3
BP 488
EP 497
DI 10.1158/1055-9965.EPI-15-0378
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6EA
UT WOS:000372173900008
PM 26711330
ER
PT J
AU Mathews, S
Feng, DC
Maricic, I
Ju, C
Kumar, V
Gao, B
AF Mathews, Stephanie
Feng, Dechun
Maricic, Igor
Ju, Cynthia
Kumar, Vipin
Gao, Bin
TI Invariant natural killer T cells contribute to chronic-plus-binge
ethanol-mediated liver injury by promoting hepatic neutrophil
infiltration
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Article
DE alcoholic hepatitis; CD1d; inflammation; liver
ID NECROSIS-FACTOR-ALPHA; NKT CELLS; THERAPEUTIC TARGETS; DISEASE; MICE;
PATHOGENESIS; INFLAMMATION; OSTEOPONTIN; PROGRESS; BIOLOGY
AB Neutrophil infiltration is a hallmark of alcoholic steatohepatitis; however, the underlying mechanisms remain unclear. We previously reported that chronic-plus-binge ethanol feeding synergistically induces hepatic recruitment of neutrophils, which contributes to liver injury. In this paper, we investigated the roles of invariant natural killer T (iNKT) cells in chronic-plus-binge ethanol feeding-induced hepatic neutrophil infiltration and liver injury. Wild-type and two strains of iNKT cell-deficient mice (CD1d- and J alpha 18-deficient mice) were subjected to chronic-plus-binge ethanol feeding. Liver injury and inflammation were examined. Chronic-plus-binge ethanol feeding synergistically increased the number of hepatic iNKT cells and induced their activation, compared with chronic feeding or binge alone. iNKT cell-deficient mice were protected from chronic-plus-binge ethanol-induced hepatic neutrophil infiltration and liver injury. Moreover, chronic-plus-binge ethanol feeding markedly upregulated the hepatic expression of several genes associated with inflammation and neutrophil recruitment in wild-type mice, but induction of these genes was abrogated in iNKT cell-deficient mice. Importantly, several cytokines and chemokines (e.g., MIP-2, MIP-1, IL-4, IL-6 and osteopontin) involved in neutrophil infiltration were upregulated in hepatic NKT cells isolated from chronic-plus-binge ethanol-fed mice compared to pair-fed mice. Finally, treatment with CD1d blocking antibody, which blocks iNKT cell activation, partially prevented chronic-plus-binge ethanol-induced liver injury and inflammation. Chronic-plus-binge ethanol feeding activates hepatic iNKT cells, which play a critical role in the development of early alcoholic liver injury, in part by releasing mediators that recruit neutrophils to the liver, and thus, iNKT cells represent a potential therapeutic target for the treatment of alcoholic liver disease.
C1 [Mathews, Stephanie; Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Maricic, Igor; Kumar, Vipin] Torrey Pines Inst Mol Studies, Lab Autoimmun, San Diego, CA USA.
[Ju, Cynthia] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci & Integrated Im, Anschutz Med Campus, Aurora, CO USA.
RP Gao, B (reprint author), NIAAA, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
FU intramural program of NIAAA, NIH [U01AA021723, R01 AA020864, R01
CA100660]
FX This work was supported by the intramural program of NIAAA, NIH (BG),
U01AA021723 (to CJ and BG) and R01 AA020864 & R01 CA100660 (VK).
NR 39
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U1 1
U2 1
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD MAR
PY 2016
VL 13
IS 2
BP 206
EP 216
DI 10.1038/cmi.2015.06
PG 11
WC Immunology
SC Immunology
GA DG3VC
UT WOS:000371997600008
PM 25661730
ER
PT J
AU Foppa, M
Arora, G
Gona, P
Ashrafi, A
Salton, CJ
Yeon, SB
Blease, SJ
Levy, D
O'Donnell, CJ
Manning, WJ
Chuang, ML
AF Foppa, Murilo
Arora, Garima
Gona, Philimon
Ashrafi, Arman
Salton, Carol J.
Yeon, Susan B.
Blease, Susan J.
Levy, Daniel
O'Donnell, Christopher J.
Manning, Warren J.
Chuang, Michael L.
TI Right Ventricular Volumes and Systolic Function by Cardiac Magnetic
Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally
Followed Cohort Free of Pulmonary and Cardiovascular Disease The
Framingham Heart Study
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac MRI; cardiac volume; epidemiology; right ventricle; systolic
function
ID EJECTION FRACTION; REFERENCE VALUES; BODY-SIZE; ATHEROSCLEROSIS;
DIMENSIONS; CARDIOLOGY; COMMITTEE; SURVIVAL; FAILURE; MRI
AB Background Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease.
Methods and Results The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (649 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68 +/- 6% versus 64 +/- 7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and height-indexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population.
Conclusions We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes.
C1 [Foppa, Murilo; Ashrafi, Arman; Salton, Carol J.; Manning, Warren J.; Chuang, Michael L.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, 330 Brookline Ave, Boston, MA 02215 USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
[Foppa, Murilo] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Arora, Garima; Levy, Daniel] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Gona, Philimon; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.; Chuang, Michael L.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Gona, Philimon] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
[Yeon, Susan B.] Wolters Kluwer Hlth, UpToDate, Waltham, MA USA.
[O'Donnell, Christopher J.] Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA USA.
[O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 330 Brookline Ave, Boston, MA 02215 USA.
EM wmanning@bidmc.harvard.edu
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institutes of Health [RO1 HL70279]; Ministry of
Education, Brazil (Coordination for the Improvement of Higher Education
Personnel, CAPES) [9601-11-2]
FX This study was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195) and a
grant from the National Institutes of Health (RO1 HL70279). Dr Foppa was
supported in part by the Ministry of Education, Brazil (Coordination for
the Improvement of Higher Education Personnel, CAPES No. 9601-11-2).
NR 22
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD MAR
PY 2016
VL 9
IS 3
AR e003810
DI 10.1161/CIRCIMAGING.115.003810
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DG3OZ
UT WOS:000371980700001
PM 26962126
ER
PT J
AU Iantorno, M
Hays, AG
Schar, M
Krishnaswamy, R
Soleimanifard, S
Steinberg, A
Stuber, M
Gerstenblith, G
Weiss, RG
AF Iantorno, Micaela
Hays, Allison G.
Schar, Michael
Krishnaswamy, Rupa
Soleimanifard, Sahar
Steinberg, Angela
Stuber, Matthias
Gerstenblith, Gary
Weiss, Robert G.
TI Simultaneous Noninvasive Assessment of Systemic and Coronary Endothelial
Function
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE atherosclerosis; coronary artery disease; endothelium; magnetic
resonance imaging; vasodilation
ID ARTERY-DISEASE; NITRIC-OXIDE; DEPENDENT VASODILATION; HANDGRIP EXERCISE;
VENOUS GRAFTS; ACETYLCHOLINE; DYSFUNCTION; HUMANS; ATHEROSCLEROSIS;
METAANALYSIS
AB Background Normal endothelial function is a measure of vascular health and dysfunction is a predictor of coronary events. Nitric oxide-mediated coronary artery endothelial function, as assessed by vasomotor reactivity during isometric handgrip exercise (IHE), was recently quantified noninvasively with magnetic resonance imaging (MRI). Because the internal mammary artery (IMA) is often visualized during coronary MRI, we propose the strategy of simultaneously assessing systemic and coronary endothelial function noninvasively by MRI during IHE.
Methods and Results Changes in cross-sectional area and blood flow in the right coronary artery and the IMA in 25 patients with coronary artery disease and 26 healthy subjects during IHE were assessed using 3T MRI. In 8 healthy subjects, a nitric oxide synthase inhibitor was infused to evaluate the role of nitric oxide in the IMA-IHE response. Interobserver IMA-IHE reproducibility was good for cross-sectional area (R=0.91) and blood flow (R=0.91). In healthy subjects, cross-sectional area and blood flow of the IMA increased during IHE, and these responses were significantly attenuated by monomethyl-l-arginine (P<0.01 versus placebo). In patients with coronary artery disease, the right coronary artery did not dilate with IHE, and dilation of the IMA was less than that of the healthy subjects (P=0.01). The blood flow responses of both the right coronary artery and IMA to IHE were also significantly reduced in patients with coronary artery disease.
Conclusions MRI-detected IMA responses to IHE primarily reflect nitric oxide-dependent endothelial function and are reproducible and reduced in patients with coronary artery disease. Endothelial function in both coronary and systemic (IMA) arteries can now be measured noninvasively with the same imaging technique and promises novel insights into systemic and local factors affecting vascular health.
C1 [Iantorno, Micaela; Hays, Allison G.; Krishnaswamy, Rupa; Steinberg, Angela; Gerstenblith, Gary; Weiss, Robert G.] Johns Hopkins Univ, Dept Med, Div Cardiol, Blalock 544,600N Wolfe St, Baltimore, MD 21287 USA.
[Schar, Michael; Soleimanifard, Sahar; Stuber, Matthias; Weiss, Robert G.] Johns Hopkins Univ, Div Magnet Resonance Res, Dept Radiol, Baltimore, MD 21287 USA.
[Soleimanifard, Sahar] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21287 USA.
[Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Stuber, Matthias] Univ Lausanne, CHU Vaudois, Dept Radiol, Ctr Biomed Imaging CIBM, Lausanne, Switzerland.
RP Weiss, RG (reprint author), Johns Hopkins Univ, Dept Med, Div Cardiol, Blalock 544,600N Wolfe St, Baltimore, MD 21287 USA.
EM rweiss@jhmi.edu
RI Schar, Michael/C-8087-2015
FU National Institutes of Health [HL120905, HL125059, HL61912]; American
Heart Association [11SDG5200004]; Swiss National Science Foundation
[320030-143923]; PJ Schafer Award; Clarence Doodeman Endowment of Johns
Hopkins
FX This work was supported by the National Institutes of Health (HL120905,
HL125059, HL61912), the American Heart Association (11SDG5200004), the
Swiss National Science Foundation Grant 320030-143923, the PJ Schafer
Award, and the Clarence Doodeman Endowment of Johns Hopkins.
NR 32
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD MAR
PY 2016
VL 9
IS 3
AR e003954
DI 10.1161/CIRCIMAGING.115.003954
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DG3PI
UT WOS:000371981600001
PM 26919997
ER
PT J
AU Korach, K
Arao, Y
Hamilton, KJ
Coons, L
Hewitt, SC
AF Korach, Kenneth
Arao, Y.
Hamilton, K. J.
Coons, L.
Hewitt, S. C.
TI Genetically modified mouse models to dissect the physiological roles of
ER alpha's functional domains
SO CLINICAL ENDOCRINOLOGY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the Endocrine-Society-of-Australia
CY AUG 23-26, 2015
CL Adelaide, AUSTRALIA
SP Endocrine Soc Australia
C1 [Korach, Kenneth; Arao, Y.; Hamilton, K. J.; Coons, L.; Hewitt, S. C.] NIEHS, NIH, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD MAR
PY 2016
VL 84
SU 1
SI SI
MA 60
BP 7
EP 7
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DG8CQ
UT WOS:000372310400021
ER
PT J
AU Talbot, GH
Powers, JH
Hoffmann, SC
AF Talbot, George H.
Powers, John H.
Hoffmann, Steven C.
CA Fdn Natl Inst Hlth CABP-ABSSSI & H
TI Developing Outcomes Assessments as Endpoints for Registrational Clinical
Trials of Antibacterial Drugs: 2015 Update From the Biomarkers
Consortium of the Foundation for the National Institutes of Health
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE antibacterial drug development; noninferiority trial design; early
clinical response; patient-reported outcome; PRO
ID COMMUNITY-ACQUIRED PNEUMONIA; SKIN-STRUCTURE INFECTIONS; ACUTE BACTERIAL
SKIN; TASK-FORCE
AB One important component in determining the benefits and harms of medical interventions is the use of well-defined and reliable outcome assessments as endpoints in clinical trials. Improving endpoints can better define patient benefits, allowing more accurate assessment of drug efficacy and more informed benefit-vs-risk decisions; another potential plus is facilitating efficient trial design. Since our first report in 2012, 2 Foundation for the National Institutes of Health Biomarkers ConsortiumProject Teams have continued to develop outcome assessments for potential uses as endpoints in registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. In addition, the teams have initiated similar work in the indications of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. This report provides an update on progress to date in these 4 diseases.
C1 [Talbot, George H.] Talbot Advisors LLC, POB 2121, Anna Maria, FL 34216 USA.
[Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA.
[Powers, John H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Hoffmann, Steven C.] Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA.
RP Talbot, GH (reprint author), Talbot Advisors LLC, POB 2121, Anna Maria, FL 34216 USA.
EM ghtalbot@gmail.com
OI Wunderink, Richard/0000-0002-8527-4195
FU Actelion; Basilea; Bayer; Cubist (now Merck); Medicines Company; Merck;
Nabriva; Roche; Tetraphase
FX The work of the HABP-VABP Project Team was supported by financial
contributions from Actelion, Basilea, Bayer, Cubist (now Merck), The
Medicines Company, Merck, Nabriva, Roche, and Tetraphase. Clinical trial
data were generously contributed in-kind by Antoni Torres, MD
(University of Barcelona, Spain), Pfizer Inc, Shionogi Pharmaceuticals,
and Theravance Inc. The CABP-ABSSSI Project Team members and the
sponsors that provided in-kind clinical trial data and/or generous
financial support were acknowledged in our 2012 publication.
NR 19
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U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 1
PY 2016
VL 62
IS 5
BP 603
EP 607
DI 10.1093/cid/civ927
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DF9XK
UT WOS:000371715600018
PM 26668337
ER
PT J
AU McGuire, JF
Orr, SP
Wu, MS
Lewin, AB
Small, BJ
Phares, V
Murphy, TK
Wilhelm, S
Pine, DS
Geller, D
Storch, EA
AF McGuire, Joseph F.
Orr, Scott P.
Wu, Monica S.
Lewin, Adam B.
Small, Brent J.
Phares, Vicky
Murphy, Tanya K.
Wilhelm, Sabine
Pine, Daniel S.
Geller, Daniel
Storch, Eric A.
TI FEAR CONDITIONING AND EXTINCTION IN YOUTH WITH OBSESSIVE-COMPULSIVE
DISORDER
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE fear conditioning; extinction; skin conductance; inhibitory learning;
obsessive-compulsive disorder; children
ID COGNITIVE-BEHAVIORAL THERAPY; ANXIETY DISORDERS; FUNCTIONAL IMPAIRMENT;
TREATMENT RESPONSE; BIAS MODIFICATION; CHILD VERSION; ADOLESCENTS;
PREDICTORS; ADULTS; RELIABILITY
AB BackgroundFear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy (CBT). Youth with OCD may have impairments in fear acquisition and extinction that carry treatment implications. We examined these processes using a differential conditioning procedure.
MethodsForty-one youth (19 OCD, 22 community comparisons) completed a battery of clinical interviews, rating scales, and a differential conditioning task that included habituation, acquisition, and extinction phases. Skin conductance response (SCR) served as the primary dependent measure.
ResultsDuring habituation, no difference between groups was observed. During acquisition, differential fear conditioning was observed across participants as evidenced by larger SCRs to the CS+ compared to CS-; there were no between-group differences. Across participants, the number and frequency of OCD symptoms and anxiety severity was associated with greater reactivity to stimuli during acquisition. During extinction, a three-way interaction and follow-up tests revealed that youth with OCD showed a different pattern of SCR extinction compared to the community comparison group.
ConclusionsYouth with OCD exhibit a different pattern of fear extinction relative to community comparisons. This may be attributed to impaired inhibitory learning and contingency awareness in extinction. Findings suggest the potential benefit of utilizing inhibitory-learning principles in CBT for youth with OCD, and/or augmentative retraining interventions prior to CBT to reduce threat bias and improve contingency detection.
C1 [McGuire, Joseph F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Pl,48-228B, Los Angeles, CA 90095 USA.
[Orr, Scott P.; Wilhelm, Sabine; Geller, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Wu, Monica S.; Lewin, Adam B.; Phares, Vicky; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA.
[Wu, Monica S.; Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, Dept Psychiat & Behav Neurosci, Tampa, FL USA.
[Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.] Univ S Florida, All Childrens Hosp, Johns Hopkins Med, St Petersburg, FL 33701 USA.
[Small, Brent J.] Univ S Florida, Sch Aging Studies, Tampa, FL USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Rockville, MD 20857 USA.
[Storch, Eric A.] Rogers Behav Hlth Tampa Bay, Tampa, FL USA.
[Storch, Eric A.] Univ S Florida, Dept Hlth Policy & Management, Tampa, FL USA.
RP McGuire, JF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Pl,48-228B, Los Angeles, CA 90095 USA.
EM jfmcguire@mednet.ucla.edu
FU National Institute of Mental Health (NIMH) of the National Institutes of
Health (NIH) [R01MH093381-02S1]; NIMH Intramural Research Program
FX Contract grant sponsor: Support for this article comes in part from the
National Institute of Mental Health (NIMH) of the National Institutes of
Health (NIH) as a research supplement to promote diversity in
health-related research (R01MH093381-02S1). Dr. Pine is supported by the
NIMH Intramural Research Program. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIMH or NIH.
NR 54
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U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2016
VL 33
IS 3
BP 229
EP 237
DI 10.1002/da.22468
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DG6FY
UT WOS:000372179800007
PM 26799264
ER
PT J
AU Wlodawer, A
AF Wlodawer, Alexander
TI Introducing Structural Snapshots
SO FEBS JOURNAL
LA English
DT Editorial Material
C1 [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA.
RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA.
EM wlodawer@camfebs.co.uk
NR 2
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD MAR
PY 2016
VL 283
IS 5
BP 815
EP 815
DI 10.1111/febs.13583
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DG3XX
UT WOS:000372005600004
PM 26524689
ER
PT J
AU Santesso, N
Mustafa, RA
Schunemann, HJ
Arbyn, M
Blumenthal, PD
Cain, J
Chirenje, M
Denny, L
De Vuyst, H
Eckert, LO
Forhan, SE
Franco, EL
Gage, JC
Garcia, F
Herrero, R
Jeronimo, J
Lu, ER
Luciani, S
Quek, SC
Sankaranarayanan, R
Tsu, V
Broutet, N
AF Santesso, Nancy
Mustafa, Reem A.
Schuenemann, Holger J.
Arbyn, Marc
Blumenthal, Paul D.
Cain, Joanna
Chirenje, Michael
Denny, Lynette
De Vuyst, Hugo
Eckert, Linda O'Neal
Forhan, Sara E.
Franco, Eduardo L.
Gage, Julia C.
Garcia, Francisco
Herrero, Rolando
Jeronimo, Jose
Lu, Enriquito R.
Luciani, Silvana
Quek, Swee Chong
Sankaranarayanan, Rengaswamy
Tsu, Vivien
Broutet, Nathalie
CA Guideline Support Grp
TI World Health Organization Guidelines for treatment of cervical
intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent
cervical cancer
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Editorial Material
DE Cervical cancer; Cervical intraepithelial neoplasia; Guidelines;
Recommendations; Screen; Treat
ID HUMAN-PAPILLOMAVIRUS INFECTION; WOMENS PREFERENCES; GRADE; MANAGEMENT;
INDIA
AB Background: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat pre-cancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. Methods: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. Results: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. Conclusion: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries. (C) 2015 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
C1 [Santesso, Nancy; Mustafa, Reem A.; Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Room 2C16,1280 Main St West, Hamilton, ON L8S 4K1, Canada.
[Mustafa, Reem A.] Univ Missouri, Dept Internal Med, Kansas City, MO 64110 USA.
[Mustafa, Reem A.] Univ Missouri, Dept Nephrol, Kansas City, MO 64110 USA.
[Mustafa, Reem A.] Univ Missouri, Dept Biomed & Hlth Informat, Kansas City, MO 64110 USA.
[Arbyn, Marc] Sci Inst Publ Hlth, Canc Epidemiol Unit, Brussels, Belgium.
[Blumenthal, Paul D.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Cain, Joanna] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Chirenje, Michael] Univ Zimbabwe, Harare, Zimbabwe.
[Denny, Lynette] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Denny, Lynette] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[De Vuyst, Hugo; Herrero, Rolando; Sankaranarayanan, Rengaswamy] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Eckert, Linda O'Neal] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Forhan, Sara E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Franco, Eduardo L.] McGill Univ, Montreal, PQ, Canada.
[Gage, Julia C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Garcia, Francisco] Amer Canc Soc, Tucson, AZ USA.
[Jeronimo, Jose; Tsu, Vivien] PATH, Seattle, WA USA.
[Lu, Enriquito R.] Jhpiego, Baltimore, MD USA.
[Luciani, Silvana] Canc Prevent & Control PAHO, Washington, DC USA.
[Quek, Swee Chong] KK Womens & Childrens Hosp, Singapore, Singapore.
[Broutet, Nathalie] WHO, Reprod Hlth & Res, CH-1211 Geneva, Switzerland.
RP Schunemann, HJ (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, Room 2C16,1280 Main St West, Hamilton, ON L8S 4K1, Canada.
OI Franco, Eduardo/0000-0002-4409-8084
FU World Health Organization [001]
NR 22
TC 7
Z9 8
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
EI 1879-3479
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD MAR
PY 2016
VL 132
IS 3
BP 252
EP 258
DI 10.1016/j.ijgo.2015.07.038
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DG3AO
UT WOS:000371942100002
PM 26868062
ER
PT J
AU Mitson-Salazar, A
Yin, YZ
Wansley, DL
Young, M
Bolan, H
Arceo, S
Ho, N
Koh, C
Milner, JD
Stone, KD
Wank, SA
Prussin, C
AF Mitson-Salazar, Alyssa
Yin, Yuzhi
Wansley, Daniel L.
Young, Michael
Bolan, Hyejeong
Arceo, Sarah
Ho, Nancy
Koh, Christopher
Milner, Joshua D.
Stone, Kelly D.
Wank, Stephen A.
Prussin, Calman
TI Hematopoietic prostaglandin D synthase defines a proeosinophilic
pathogenic effector human T(H)2 cell subpopulation with enhanced
function
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Atopic dermatitis; eosinophilic inflammation; eosinophilic
gastrointestinal disease; IL-5; hematopoietic prostaglandin D synthase;
chemoattractant receptor-homologous molecule expressed on T(H)2 cells;
T(H)2; CD4; CD161; CD294
ID CHEMOKINE RECEPTOR EXPRESSION; INNATE LYMPHOID-CELLS; THYMIC STROMAL
LYMPHOPOIETIN; HELPER TYPE-2 CELLS; HUMAN TH2 CELLS; CD4(+) T-CELLS;
CYTOKINE PRODUCTION; ATOPIC-DERMATITIS; UP-REGULATION; CUTTING EDGE
AB Background: IL-5 1 pathogenic effector T(H)2 (peT(H)2) cells are a T(H)2 cell subpopulation with enhanced proinflammatory function that has largely been characterized in murine models of allergic inflammation.
Objective: We sought to identify phenotype markers for human peT(H)2 cells and characterize their function in patients with allergic eosinophilic inflammatory diseases.
Methods: Patients with eosinophilic gastrointestinal disease (EGID), patients with atopic dermatitis (AD), and nonatopic healthy control (NA) subjects were enrolled. peT(H)2 and conventional T(H)2 (cT(H)2) cell phenotype, function, and cytokine production were analyzed by using flow cytometry. Confirmatory gene expression was measured by using quantitative RT-PCR. Prostaglandin D-2 levels were measured with ELISA. Gut T(H)2 cells were obtained by means of esophagogastroduodenoscopy.
Results: peT(H)2 cells were identified as chemoattractant receptor-homologous molecule expressed onT(H)2 cells-positive (CRT(H)2(+)), hematopoietic prostaglandin D synthase-positive CD161 hi CD4 T cells. peT(H)2 cells expressed significantly greater IL-5 and IL-13 than did hematopoietic prostaglandin D synthase-negative and CD161 2 cT(H)2 cells. peT(H)2 cells were highly correlated with blood eosinophilia (r = 0.78-0.98) and were present in 30- to 40-fold greater numbers in subjects with EGID and those with AD versus NA subjects. Relative to cT(H)2 cells, peT(H)2 cells preferentially expressed receptors for thymic stromal lymphopoietin, IL-25, and IL-33 and demonstrated greater responsiveness to these innate pro-T(H)2 cytokines. peT(H)2 but not cT(H)2 cells produced prostaglandin D-2. In patients with EGID and those with AD, peT(H)2 cells expressed gut-and skin-homing receptors, respectively. There were significantly greater numbers of peT(H)2 cells in gut tissue from patients with EGID versus NA subjects.
Conclusion: peT(H)2 cells are the primary functional proinflammatory human T(H)2 cell subpopulation underlying allergic eosinophilic inflammation. The unambiguous phenotypic identification of human peT(H)2 cells provides a powerful tool to track these cells in future pathogenesis studies and clinical trials.
C1 [Mitson-Salazar, Alyssa; Yin, Yuzhi; Wansley, Daniel L.; Bolan, Hyejeong; Arceo, Sarah; Milner, Joshua D.; Stone, Kelly D.; Prussin, Calman] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Young, Michael] Frederick Natl Lab Canc Res, Clin Res Directorate CMRP, Leidos Biomed Res, Frederick, MD USA.
[Ho, Nancy; Koh, Christopher; Wank, Stephen A.] NIDDK, Gastroenterol Sect, NIH, Frederick, MD USA.
RP Prussin, C (reprint author), 10 Ctr Dr,MSC 181, Bethesda, MD 20892 USA.
EM calmanp@gmail.com
FU National Institute of Allergy and Infectious Diseases, Division of
Intramural Research, National Institutes of Health [1ZIAAI000993]
FX Supported by the National Institute of Allergy and Infectious Diseases,
Division of Intramural Research, National Institutes of Health, project
1ZIAAI000993.
NR 51
TC 6
Z9 6
U1 2
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2016
VL 137
IS 3
BP 907
EP +
DI 10.1016/j.jaci.2015.08.007
PG 21
WC Allergy; Immunology
SC Allergy; Immunology
GA DG2LB
UT WOS:000371897500035
PM 26431580
ER
PT J
AU Ku, CL
Lin, CH
Chang, SW
Chu, CC
Chan, JFW
Kong, XF
Lee, CH
Rosen, EA
Ding, JY
Lee, WI
Bustamante, J
Witte, T
Shih, HP
Kuo, CY
Chetchotisakd, P
Kiertiburanakul, S
Suputtamongkol, Y
Yuen, KY
Casanova, JL
Holland, SM
Doffinger, R
Browne, SK
Chi, CY
AF Ku, Cheng-Lung
Lin, Chia-Hao
Chang, Su-Wei
Chu, Chen-Chung
Chan, Jasper F. W.
Kong, Xiao-Fei
Lee, Chen-Hsiang
Rosen, Emily A.
Ding, Jing-Ya
Lee, Wen-I.
Bustamante, Jacinta
Witte, Torsten
Shih, Han-Po
Kuo, Chen-Yen
Chetchotisakd, Ploenchan
Kiertiburanakul, Sasisopin
Suputtamongkol, Yupin
Yuen, Kwok-Yung
Casanova, Jean-Laurent
Holland, Steven M.
Doffinger, Rainer
Browne, Sarah K.
Chi, Chih-Yu
TI Anti-IFN-gamma autoantibodies are strongly associated with
HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID NONTUBERCULOUS MYCOBACTERIAL INFECTIONS
C1 [Ku, Cheng-Lung; Lin, Chia-Hao; Ding, Jing-Ya; Shih, Han-Po; Kuo, Chen-Yen] Chang Gung Univ, Grad Inst Clin Med Sci, Lab Human Immunol & Infect Dis, Taoyuan, Taiwan.
[Ku, Cheng-Lung; Chi, Chih-Yu] China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan.
[Ku, Cheng-Lung] Chang Gung Mem Hosp, Chang Gung Immunol Consortium, Taoyuan, Taiwan.
[Ku, Cheng-Lung] Chang Gung Univ, Taoyuan, Taiwan.
[Chang, Su-Wei] Chang Gung Univ, Clin Informat & Med Stat Res Ctr, Taoyuan, Taiwan.
[Chan, Jasper F. W.; Yuen, Kwok-Yung] Univ Hong Kong, Queen Mary Hosp, Carol Yu Ctr Infect, Key Lab Emerging Infect Dis,Dept Microbiol, Hong Kong, Hong Kong, Peoples R China.
[Kong, Xiao-Fei; Bustamante, Jacinta; Casanova, Jean-Laurent] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
[Lee, Chen-Hsiang] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Infect Dis, Kaohsiung, Taiwan.
[Lee, Chen-Hsiang] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Rosen, Emily A.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lee, Wen-I.] Chang Gung Mem Hosp, Div Allergy Immunol & Rheumatol, Dept Pediat, Taoyuan, Taiwan.
[Bustamante, Jacinta; Casanova, Jean-Laurent] INSERM, U1163, Lab Human Genet Infect Dis, Necker Branch, Paris, France.
[Bustamante, Jacinta; Casanova, Jean-Laurent] Paris Descartes Univ, Imagine Inst, Paris, France.
[Witte, Torsten] Med Sch Hanover, Clin Immunol & Rheumatol, Hannover, NH, Germany.
[Kuo, Chen-Yen] Chang Gung Mem Hosp Linkou, Dept Pediat, Taoyuan, Taiwan.
[Chetchotisakd, Ploenchan] Khon Kaen Univ, Srinagarind Hosp, Khon Kaen, Thailand.
[Kiertiburanakul, Sasisopin] Ramathibodi Hosp, Fac Med, Bangkok, Thailand.
[Suputtamongkol, Yupin] Mahidol Univ, Fac Med, Siriraj Hosp, Div Infect Dis & Trop Med,Dept Med, Bangkok 10700, Thailand.
[Casanova, Jean-Laurent] Howard Hughes Med Inst, New York, NY USA.
[Casanova, Jean-Laurent] Necker Hosp Sick Children, AP HP, Pediat Immunohematol Unit, Paris, France.
[Doffinger, Rainer] Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge, England.
[Doffinger, Rainer] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England.
[Chi, Chih-Yu] China Med Univ Hosp, Dept Internal Med, Div Infect Dis, Taichung, Taiwan.
[Chu, Chen-Chung] Mackay Mem Hosp, Dept Med Res, Immunogenet Lab, Taipei, Taiwan.
RP Ku, CL (reprint author), Chang Gung Univ, Grad Inst Clin Med Sci, Lab Human Immunol & Infect Dis, Taoyuan, Taiwan.; Ku, CL (reprint author), China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan.; Ku, CL (reprint author), Chang Gung Mem Hosp, Chang Gung Immunol Consortium, Taoyuan, Taiwan.; Ku, CL (reprint author), Chang Gung Univ, Taoyuan, Taiwan.
EM clku@mail.cgu.edu.tw
NR 9
TC 4
Z9 4
U1 2
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2016
VL 137
IS 3
BP 945
EP 948
DI 10.1016/j.jaci.2015.09.018
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA DG2LB
UT WOS:000371897500045
PM 26522403
ER
PT J
AU Dassanayake, RP
Orru, CD
Hughson, AG
Caughey, B
Graca, T
Zhuang, DY
Madsen-Bouterse, SA
Knowles, DP
Schneider, DA
AF Dassanayake, Rohana P.
Orru, Christina D.
Hughson, Andrew G.
Caughey, Byron
Graca, Telmo
Zhuang, Dongyue
Madsen-Bouterse, Sally A.
Knowles, Donald P.
Schneider, David A.
TI Sensitive and specific detection of classical scrapie prions in the
brains of goats by real-time quaking-induced conversion
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID EXPERIMENTALLY CHALLENGED GOATS; CREUTZFELDT-JAKOB-DISEASE; NATURAL
SCRAPIE; IMMUNOHISTOCHEMICAL DETECTION; SEEDED CONVERSION; CAPRINE
SCRAPIE; LYMPHOID-TISSUE; SHEEP SCRAPIE; RECTAL MUCOSA; PROTEIN GENE
AB Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrP(Sen)) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrP(Sen) substrates (PrP genotypes A(136)R(154)Q(171) and V(136)R(154)Q(171)) provided good discrimination between scrapie-infected and normal goat brain samples at 10(-3) dilution within 15 h. Our findings indicate that RT-QuIC was at least 10 000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.
C1 [Dassanayake, Rohana P.; Graca, Telmo; Madsen-Bouterse, Sally A.; Knowles, Donald P.; Schneider, David A.] Washington State Univ, Coll Vet Med, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA.
[Orru, Christina D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Graca, Telmo] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
[Zhuang, Dongyue; Knowles, Donald P.; Schneider, David A.] ARS, Anim Dis Res Unit, USDA, Pullman, WA 99164 USA.
RP Dassanayake, RP (reprint author), Washington State Univ, Coll Vet Med, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA.
EM rohana1@vetmed.wsu.edu
FU US Department of Agriculture Agricultural Research Service [CRIS
2090-32000-030-00D]; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases
FX This study was funded by the US Department of Agriculture Agricultural
Research Service (CRIS 2090-32000-030-00D) and also in part by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases. We thank Katherine O'Rourke (Washington State
University) for critical reading of the manuscript. The authors would
also like to thank Linda Hamburg, Lori Fuller, Laetisha O'Rourke,
Deborah Wolheter, Jan Luft, Karel Emma and Desiree Lesiak for technical
assistance. Mention of trade names or commercial products in this
article is solely for the purpose of providing specific information and
does not imply recommendation or endorsement by the US Department of
Agriculture.
NR 37
TC 3
Z9 3
U1 0
U2 1
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2016
VL 97
BP 803
EP 812
DI 10.1099/jgv.0.000367
PN 3
PG 10
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA DG8KP
UT WOS:000372333000027
PM 26653410
ER
PT J
AU Qi, R
Joo, HS
Sharma-Kuinkel, B
Berlon, NR
Park, L
Fu, CL
Messina, JA
Thaden, JT
Yan, Q
Ruffin, F
Maskarinec, S
Warren, B
Chu, VH
Fortes, CQ
Giannitsioti, E
Durante-Mangoni, E
Kanafani, ZA
Otto, M
Fowler, VG
AF Qi, Robert
Joo, Hwang-Soo
Sharma-Kuinkel, Batu
Berlon, Nicholas R.
Park, Lawrence
Fu, Chih-Lung
Messina, Julia A.
Thaden, Joshua T.
Yan, Qin
Ruffin, Felicia
Maskarinec, Stacey
Warren, Bobby
Chu, Vivian H.
Fortes, Claudio Q.
Giannitsioti, Efthymia
Durante-Mangoni, Emanuele
Kanafani, Zeina A.
Otto, Michael
Fowler, Vance G., Jr.
TI Increased in vitro phenol-soluble modulin production is associated with
soft tissue infection source in clinical isolates of
methicillin-susceptible Staphylococcus aureus
SO JOURNAL OF INFECTION
LA English
DT Article
DE Phenol-soluble modulin; Methicillin-susceptible Staphylococcus aureus;
Skin and soft tissue infection; Pneumonia; Endocarditis
ID VIRULENCE DETERMINANTS; RABBIT MODEL; ENDOCARDITIS; RESISTANT; SKIN;
PATHOGENESIS; VANCOMYCIN; TELAVANCIN; DIAGNOSIS; PEPTIDES
AB Background: Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced significantly higher levels of PSM than MRSA isolates from hospital-acquired pneumonia (HAP) or infective endocarditis (IE). In this investigation, we sought to validate this finding in methicillin-susceptible S. aureus (MSSA) isolates.
Methods: MSSA isolates (n = 162) from patients with SSTI, HAP, and IE were matched 1: 1: 1 based on geographic origin of the infection to form 54 triplets (North America n = 27, Europe n = 25, Australia n = 2). All isolates underwent spa typing and were classified using eGenomics. In vitro PSM production was quantified by high-performance liquid chromatography/mass spectrometry. Fischer's Exact Test and the Kruskal-Wallis test were used for statistical analysis.
Results: Spa1 was more common in SSTI (14.81% SSTI, 3.70% HAP, 1.85% IE) (p < 0.03). Spa2 was more common in HAP (0% SSTI, 12.96% HAP, 3.70% IE) (p < 0.01). Levels of PSM alpha 1-4 all differed significantly among the three clinical groups, with SSTI isolates producing the highest levels and IE producing the lowest levels of PSMa1-4. Spa1 isolates produced significantly more delta-toxin (p < 0.03) than non-Spa1 isolates. No associations between PSM levels and clinical outcome of SSTI, HAP, or IE were identified.
Conclusion: Production of PSMa1-4 is highest in SSTI MSSA isolates, supporting the hypothesis that these peptides are important for SSTI pathogenesis. These findings are similar to those described in MRSA, and demonstrate that associations between PSM levels and type of infection are independent of the methicillin-resistance status of the isolate. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
C1 [Qi, Robert; Sharma-Kuinkel, Batu; Berlon, Nicholas R.; Park, Lawrence; Messina, Julia A.; Thaden, Joshua T.; Yan, Qin; Ruffin, Felicia; Maskarinec, Stacey; Warren, Bobby; Chu, Vivian H.; Fowler, Vance G., Jr.] Duke Univ, Div Infect Dis, Dept Med, Med Ctr, Box 102359 Med Ctr, Durham, NC 27710 USA.
[Joo, Hwang-Soo; Fu, Chih-Lung; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Messina, Julia A.; Fowler, Vance G., Jr.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[Fortes, Claudio Q.] Hosp Univ Clementino Fraga Filho UFRJ, Rio De Janeiro, Brazil.
[Giannitsioti, Efthymia] Attikon Univ, Gen Hosp, Athens, Greece.
[Durante-Mangoni, Emanuele] Univ Naples 2, Dept Cardiothorac Sci, Internal Med Sect, Monaldi Hosp, Naples, Italy.
[Durante-Mangoni, Emanuele] Univ Naples 2, Monaldi Hosp, Div Infect & Transplant Med, Naples, Italy.
[Kanafani, Zeina A.] Amer Univ Beirut, Med Ctr, Dept Internal Med, Div Infect Dis, Beirut, Lebanon.
RP Fowler, VG (reprint author), Duke Univ, Div Infect Dis, Dept Med, Med Ctr, Box 102359 Med Ctr, Durham, NC 27710 USA.
EM fowle003@mc.duke.edu
OI Qi, Robert/0000-0001-6445-7331; Otto, Michael/0000-0002-2222-4115
FU National Institute of Health [R01-AI068804, K24-AI093969]; Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases; Duke University School of Medicine Eugene A. Stead Student
Research Scholarship
FX This work was supported by the Duke University School of Medicine Eugene
A. Stead Student Research Scholarship [to RQ], grants provided by the
National Institute of Health [R01-AI068804 and K24-AI093969 to VGF], and
the Intramural Research Program of the National Institute of Allergy and
Infectious Diseases [to MO].
NR 30
TC 3
Z9 3
U1 1
U2 3
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD MAR
PY 2016
VL 72
IS 3
BP 302
EP 308
DI 10.1016/j.jinf.2015.11.002
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA DG2XW
UT WOS:000371935100004
PM 26778460
ER
PT J
AU Aberra, T
Joshi, A
Lerman, J
Rodante, J
Silverman, J
Aridi, T
Chen, M
Playford, M
Mehta, N
AF Aberra, T.
Joshi, A.
Lerman, J.
Rodante, J.
Silverman, J.
Aridi, T.
Chen, M.
Playford, M.
Mehta, N.
TI COMORBID DEPRESSION OR ANXIETY IS ASSOCIATED WITH AORTIC VASCULAR
INFLAMMATION AND CORONARY HEART DISEASE BEYOND TRADITIONAL
CARDIOVASCULAR RISK FACTORS IN PSORIASIS
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Eastern Regional Meeting of the American-Federation-for-Medical-Research
(AFMR)
CY APR 13, 2016
CL Washington, DC
SP Amer Federat Med Res
C1 [Aberra, T.; Joshi, A.; Lerman, J.; Rodante, J.; Silverman, J.; Aridi, T.; Chen, M.; Playford, M.; Mehta, N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2016
VL 64
IS 3
MA MP11
BP 809
EP 809
DI 10.1136/jim-2016-000080.23
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6GE
UT WOS:000372180700030
ER
PT J
AU Joshi, A
Shukla, P
Aberra, TM
Lerman, JB
Natarajan, B
Ng, Q
Silverman, J
Rodante, J
Mehta, NN
AF Joshi, A.
Shukla, P.
Aberra, T. M.
Lerman, J. B.
Natarajan, B.
Ng, Q.
Silverman, J.
Rodante, J.
Mehta, N. N.
TI VASCULAR INFLAMMATION AND AORTIC WALL CHARACTERISTICS MODULATE FOLLOWING
LIFESTYLE CHANGES IN PSORIASIS PATIENTS AT 1 YEAR FOLLOW UP
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Eastern Regional Meeting of the American-Federation-for-Medical-Research
(AFMR)
CY APR 13, 2016
CL Washington, DC
SP Amer Federat Med Res
C1 [Joshi, A.; Shukla, P.; Aberra, T. M.; Lerman, J. B.; Natarajan, B.; Ng, Q.; Silverman, J.; Rodante, J.; Mehta, N. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2016
VL 64
IS 3
MA 23
BP 816
EP 816
DI 10.1136/jim-2016-000080.39
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6GE
UT WOS:000372180700044
ER
PT J
AU Kabbany, MT
Joshi, AA
Ahlman, M
Rodante, J
Lerman, JB
Aberra, T
Silverman, J
Dahiya, A
Bluemke, DA
Playford, MP
Mehta, NN
AF Kabbany, M. T.
Joshi, A. A.
Ahlman, M.
Rodante, J.
Lerman, J. B.
Aberra, T.
Silverman, J.
Dahiya, A.
Bluemke, D. A.
Playford, M. P.
Mehta, N. N.
TI DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI:
FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE
INITIATIVE
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Eastern Regional Meeting of the American-Federation-for-Medical-Research
(AFMR)
CY APR 13, 2016
CL Washington, DC
SP Amer Federat Med Res
C1 [Kabbany, M. T.; Joshi, A. A.; Ahlman, M.; Rodante, J.; Lerman, J. B.; Aberra, T.; Silverman, J.; Dahiya, A.; Bluemke, D. A.; Playford, M. P.; Mehta, N. N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2016
VL 64
IS 3
MA 21
DI 10.1136/jim-2016-000080.37
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6GE
UT WOS:000372180700043
ER
PT J
AU Lerman, JB
Joshi, AA
Rodante, J
Aberra, T
Kabbany, MT
Salahuddin, TF
Ng, Q
Silverman, J
Chen, MY
Mehta, NN
AF Lerman, J. B.
Joshi, A. A.
Rodante, J.
Aberra, T.
Kabbany, M. T.
Salahuddin, T. F.
Ng, Q.
Silverman, J.
Chen, M. Y.
Mehta, N. N.
TI IMPROVEMENT IN PSORIASIS SKIN DISEASE SEVERITY IS ASSOCIATED WITH
REDUCTION OF CORONARY PLAQUE BURDEN
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Eastern Regional Meeting of the American-Federation-for-Medical-Research
(AFMR)
CY APR 13, 2016
CL Washington, DC
SP Amer Federat Med Res
C1 [Lerman, J. B.; Joshi, A. A.; Rodante, J.; Aberra, T.; Kabbany, M. T.; Salahuddin, T. F.; Ng, Q.; Silverman, J.; Chen, M. Y.; Mehta, N. N.] NHLBI, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2016
VL 64
IS 3
MA 18
DI 10.1136/jim-2016-000080.34
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6GE
UT WOS:000372180700041
ER
PT J
AU Li, LZ
Chen, KQ
Xiang, Y
Yoshimura, T
Su, SB
Zhu, JW
Bian, XW
Wang, JM
AF Li, Liangzhu
Chen, Keqiang
Xiang, Yi
Yoshimura, Teizo
Su, Shaobo
Zhu, Jianwei
Bian, Xiu-wu
Wang, Ji Ming
TI New development in studies of formyl-peptide receptors: critical roles
in host defense
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Review
DE leukocytes; trafficking; inflammation; immunity; cancer
ID N-FORMYLPEPTIDE RECEPTOR; HUMAN GLIOBLASTOMA CELLS;
LISTERIA-MONOCYTOGENES; CHEMOATTRACTANT RECEPTOR; BONE-MARROW; IN-VIVO;
NEUTROPHIL MIGRATION; MOUSE NEUTROPHILS; IMMUNE-RESPONSES; 2 FPR2
AB Formyl-peptide receptors are a family of 7 transmembrane domain, Gi-protein-coupled receptors that possess multiple functions in many pathophysiologic processes because of their expression in a variety of cell types and their capacity to interact with a variety of structurally diverse, chemotactic ligands. Accumulating evidence demonstrates that formyl-peptide receptors are critical mediators of myeloid cell trafficking in the sequential chemotaxis signal relays in microbial infection, inflammation, and immune responses. Formylpeptide receptors are also involved in the development and progression of cancer. In addition, one of the formylpeptide receptor family members, Fpr2, is expressed by normal mouse-colon epithelial cells, mediates cell responses to microbial chemotactic agonists, participates in mucosal development and repair, and protects against inflammation-associated tumorigenesis. These novel discoveries greatly expanded the current understanding of the role of formyl-peptide receptors in host defense and as potential molecular targets for the development of therapeutics.
C1 [Li, Liangzhu; Zhu, Jianwei] Shanghai Jiao Tong Univ, Sch Pharm, Minist Educ, Engn Res Ctr Cell & Therapeut Antibody, Shanghai 200030, Peoples R China.
[Li, Liangzhu; Chen, Keqiang; Yoshimura, Teizo; Wang, Ji Ming] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Chen, Keqiang; Su, Shaobo] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Shanghai 200092, Peoples R China.
[Xiang, Yi] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pulm Med, Sch Med, Shanghai 200030, Peoples R China.
[Bian, Xiu-wu; Wang, Ji Ming] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China.
[Bian, Xiu-wu; Wang, Ji Ming] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China.
[Bian, Xiu-wu] Collaborat Innovat Ctr Canc Med, 651 Dongfeng East Rd, Guangzhou, Guangdong, Peoples R China.
RP Wang, JM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.; Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China.; Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China.; Bian, XW (reprint author), Collaborat Innovat Ctr Canc Med, 651 Dongfeng East Rd, Guangzhou, Guangdong, Peoples R China.
EM bianxiuwu@263.net; wangji@mail.nih.gov
RI Bian, Xiu-wu/D-4736-2017
OI Bian, Xiu-wu/0000-0003-4383-0197
FU U.S. National Institutes of Health (NIH) National Cancer Institute (NCI)
[HHSN261200800001E]; Intramural Research Program of NCI, NIH; Starting
Foundation for New Teachers of Shanghai Jiao Tong University, Shanghai,
China [14X100040016]; National Natural Science Foundation of China
[81470073, 31170861, 81101771, 81473127, 81230062]
FX This project was funded in part with federal funds from the U.S.
National Institutes of Health (NIH) National Cancer Institute (NCI),
under Contract No. HHSN261200800001E, and also in part by the Intramural
Research Program of NCI, NIH. Additional sources of support were The
Starting Foundation for New Teachers of Shanghai Jiao Tong University,
Shanghai, China (Grant 14X100040016 to L.L.); the National Natural
Science Foundation of China (Grant 81470073 to L.L., Grant 31170861 to
S.S., Grant 81101771 to Y.X., Grant 81473127 to J.Z., and Grant 81230062
to X.B.). The authors thank Dr.J.J. Oppenheim for critically reviewing
the manuscript, Ms. C. Lamb and Ms. S. Livingstone for secretarial
assistance.
NR 117
TC 5
Z9 6
U1 1
U2 9
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2016
VL 99
IS 3
BP 425
EP 435
DI 10.1189/jlb.2RI0815-354RR
PG 11
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IO
UT WOS:000371890800005
PM 26701131
ER
PT J
AU Zhang, LJ
Bell, BA
Yu, MZ
Chan, CC
Peachey, NS
Fung, J
Zhang, XM
Caspi, RR
Lin, F
AF Zhang, Lingjun
Bell, Brent A.
Yu, Minzhong
Chan, Chi-Chao
Peachey, Neal S.
Fung, John
Zhang, Xiaoming
Caspi, Rachel R.
Lin, Feng
TI Complement anaphylatoxin receptors C3aR and C5aR are required in the
pathogenesis of experimental autoimmune uveitis
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE T cell; regulation; retinal inflammation; mouse model; innate immunity
ID OPTICAL COHERENCE TOMOGRAPHY; SCANNING LASER OPHTHALMOSCOPY; T-CELL
ALLOIMMUNITY; RETINAL DEGENERATION; DENDRITIC CELLS; INNATE IMMUNITY;
IN-VIVO; MOUSE; UVEORETINITIS; MICE
AB Recent studies have suggested that reagents inhibiting complement activation could be effective in treating T cell mediated autoimmune diseases such as autoimmune uveitis. However, the precise role of the complement anaphylatoxin receptors (C3a and C5a receptors) in the pathogenesis of autoimmune uveitis remains elusive and controversial. We induced experimental autoimmune uveitis in mice deficient or sufficient in both C3a and C5a receptors and rigorously compared their retinal phenotype using various imaging techniques, including indirect ophthalmoscopy, confocal scanning laser ophthalmoscopy, spectral domain optical coherence tomography, topical endoscopic fundus imaging, and histopathological analysis. We also assessed retinal function using electroretinography. Moreover, we performed Ag-specific T cell recall assays and T cell adoptive transfer experiments to compare pathogenic T cell activity between wild-type and knockout mice with experimental autoimmune uveitis. These experiments showed that C3a receptor/C5a receptor-deficient mice developed much less severe uveitis than did control mice using all retinal examination methods and that these mice had reduced pathogenic T cell responses. Our data demonstrate that both complement anaphylatoxin receptors are important for the development of experimental autoimmune uveitis, suggesting that targeting these receptors could be a valid approach for treating patients with autoimmune uveitis.
C1 [Zhang, Lingjun; Zhang, Xiaoming] Tianjin Med Univ, Eye Res Inst, Ctr Eye, Tianjin, Peoples R China.
[Zhang, Lingjun; Lin, Feng] Cleveland Clin, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA.
[Bell, Brent A.; Yu, Minzhong; Peachey, Neal S.] Cleveland Clin, Dept Ophthalm Res, Cole Eye Inst, Cleveland, OH 44195 USA.
[Fung, John] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44195 USA.
[Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Lin, F (reprint author), Cleveland Clin, Dept Immuno NE60, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.; Zhang, XM (reprint author), Tianjin Med Univ, Eye Res Inst, Tianjin, Peoples R China.
EM xzhang08@tmu.edu.cn; linf2@ccf.org
FU U.S. National Institutes of Health National Institute of Arthritis and
Musculoskeletal and Skin Diseases [AR061564]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK10358]; Foundation
Fighting Blindness; Research to Prevent Blindness; Wolf Family
Foundation; Llura and Gordon Gund Foundation; China National Natural
Science Foundation [8142800018]
FX This work was supported in part by U.S. National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(Grant AR061564) and National Institute of Diabetes and Digestive and
Kidney Diseases (Grant DK10358), and the Foundation Fighting Blindness,
Research to Prevent Blindness, the Wolf Family Foundation, and the Llura
and Gordon Gund Foundation. L.Z. was supported in part by China National
Natural Science Foundation Grant 8142800018. We thank Catherine Doller
from Visual Sciences Research Center at Case Western Reserve University
(EY11373) for histology and Christine Kassuba from Cleveland Clinic for
help with manuscript preparation.
NR 48
TC 1
Z9 2
U1 1
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2016
VL 99
IS 3
BP 447
EP 454
DI 10.1189/jlb.3A0415-157R
PG 8
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IO
UT WOS:000371890800007
PM 26394814
ER
PT J
AU Solaymani-Mohammadi, S
Lakhdari, O
Minev, I
Shenouda, S
Frey, BF
Billeskov, R
Singer, SM
Berzofsky, JA
Eckmann, L
Kagnoff, MF
AF Solaymani-Mohammadi, Shahram
Lakhdari, Omar
Minev, Ivelina
Shenouda, Steve
Frey, Blake F.
Billeskov, Rolf
Singer, Steven M.
Berzofsky, Jay A.
Eckmann, Lars
Kagnoff, Martin F.
TI Lack of the programmed death-1 receptor renders host susceptible to
enteric microbial infection through impairing the production of the
mucosal natural killer cell effector molecules
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE Citrobacter rodentium; granzyme B; perforin; attaching/effacing
bacteria; PD-1
ID CITROBACTER-RODENTIUM INFECTION; BACTERIAL PATHOGENS; DENDRITIC CELLS;
NK CELLS; PD-1; DEFENSE; EXPRESSION; IMMUNITY; MICE; CYTOTOXICITY
AB The programmed death-1 receptor is expressed on a wide range of immune effector cells, including T cells, natural killer T cells, dendritic cells, macrophages, and natural killer cells. In malignancies and chronic viral infections, increased expression of programmed death-1 by T cells is generally associated with a poor prognosis. However, its role in early host microbial defense at the intestinal mucosa is not well understood. We report that programmed death-1 expression is increased on conventional natural killer cells but not on CD4(+), CD8(+) or natural killer T cells, or CD11b(+) or CD11c(+) macrophages or dendritic cells after infection with the mouse pathogen Citrobacter rodentium. Mice genetically deficient in programmed death-1 or treated with anti-programmed death-1 antibody were more susceptible to acute enteric and systemic infection with Citrobacter rodentium. Wildtype but not programmed death-1-deficient mice infected with Citrobacter rodentium showed significantly increased expression of the conventional mucosal NK cell effector molecules granzyme B and perforin. In contrast, natural killer cells from programmed death-1-deficient mice had impaired expression of those mediators. Consistent with programmed death-1 being important for intracellular expression of natural killer cell effector molecules, mice depleted of natural killer cells and perforin-deficient mice manifested increased susceptibility to acute enteric infection with Citrobacter rodentium. Our findings suggest that increased programmed death-1 signaling pathway expression by conventional natural killer cells promotes host protection at the intestinal mucosa during acute infection with a bacterial gut pathogen by enhancing the expression and production of important effectors of natural killer cell function.
C1 [Solaymani-Mohammadi, Shahram; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.] Univ Calif San Diego, Lab Mucosal Immunol, La Jolla, CA 92093 USA.
[Eckmann, Lars] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Solaymani-Mohammadi, Shahram; Frey, Blake F.; Billeskov, Rolf; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41,Room D702, Bethesda, MD 20892 USA.
[Singer, Steven M.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Singer, Steven M.] Georgetown Univ, Ctr Infect Dis, Washington, DC USA.
RP Solaymani-Mohammadi, S (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 41,Room D702, Bethesda, MD 20892 USA.
EM shahram.sm@nih.gov
OI Billeskov, Rolf/0000-0003-4533-7304
FU U.S. National Institutes of Health (NIH) National Institute of Diabetes
and Digestive and Kidney Diseases [DK35108]; NIH National Institute of
Allergy and Infectious Diseases [AI 094492]; NIH National Cancer
Institute Intramural Research Program of Center for Cancer Research
[Z01-C04020]
FX This work was supported by the U.S. National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases Grant
DK35108 (M.F.K), the NIH National Institute of Allergy and Infectious
Diseases Grant AI 094492 (S.M.S), and by the NIH National Cancer
Institute Intramural Research Program of the Center for Cancer Research
(Project Z01-C04020; J.A.B). We are grateful to Dr. T. Honjo, Department
of Immunology and Genomic Medicine, Kyoto University, Japan, and Dr.
W.R. Green, the Geisel School of Medicine at Dartmouth for providing
PD-1-/- mice. We thank E. Hanson, L. Hall, K. McKinnon, and
L. Pasquet for technical assistance and C. McAllister and K. Vu for
advice during the course of these studies.
NR 37
TC 2
Z9 2
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2016
VL 99
IS 3
BP 475
EP 482
DI 10.1189/jlb.4A0115-003RR
PG 8
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IO
UT WOS:000371890800010
PM 26467188
ER
PT J
AU Li, HM
Hiroi, T
Zhang, YQ
Shi, A
Chen, GB
De, S
Metter, EJ
Wood, WH
Sharov, A
Milner, JD
Becker, KG
Zhan, M
Weng, NP
AF Li, Hoi Ming
Hiroi, Toyoko
Zhang, Yongqing
Shi, Alvin
Chen, Guobing
De, Supriyo
Metter, E. Jeffrey
Wood, William H., III
Sharov, Alexei
Milner, Joshua D.
Becker, Kevin G.
Zhan, Ming
Weng, Nan-ping
TI TCR beta repertoire of CD4(+) and CD8(+) T cells is distinct in
richness, distribution, and CDR3 amino acid composition
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE Human; TCR diversity; supervised learning; RACE; RNAseq
ID PROTEIN-SEQUENCE; CLASS-I; DIVERSITY; SELECTION; NAIVE; RECOGNITION;
REVEALS; MACHINE; NUMBER; AGE
AB The TCR repertoire serves as a reservoir of TCRs for recognizing all potential pathogens. Two major types of T cells, CD4(+) and CD8(+), that use the same genetic elements and process to generate a functional TCR differ in their recognition of peptide bound to MHC class II and I, respectively. However, it is currently unclear to what extent the TCR repertoire of CD4(+) and CD8(+) T cells is different. Here, we report a comparative analysis of the TCR beta repertoires of CD4(+) and CD8(+) T cells by use of a 59 rapid amplification of cDNA ends-PCR-sequencing method. We found that TCRb richness of CD4(+) T cells ranges from 1.2 to 9.8 x 10(4) and is approximately 5 times greater, on average, than that of CD8(+) T cells in each study subject. Furthermore, there was little overlap in TCR beta sequences between CD4(+) (0.3%) and CD8(+) (1.3%) T cells. Further analysis showed that CD4(+) and CD8(+) T cells exhibited distinct preferences for certain amino acids in the CDR3, and this was confirmed further by a support vector machine classifier, suggesting that there are distinct and discernible differences between TCRb CDR3 in CD4(+) and CD8(+) T cells. Finally, we identified 5-12% of the unique TCR beta s that share an identical CDR3 with different variable genes. Together, our findings reveal the distinct features of the TCRb repertoire between CD4(+) and CD8(+) T cells and could potentially be used to evaluate the competency of T cell immunity.
C1 [Li, Hoi Ming; Hiroi, Toyoko; Shi, Alvin; Chen, Guobing; Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Sharov, Alexei] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Zhang, Yongqing; De, Supriyo; Wood, William H., III; Becker, Kevin G.] NIA, Lab Gene Express & Genom, NIH, Baltimore, MD 21224 USA.
[Zhan, Ming] NIA, Bioinformat Units, NIH, Baltimore, MD 21224 USA.
[Metter, E. Jeffrey] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Baltimore, MD USA.
[Shi, Alvin] MIT, Computat & Syst Biol Grad Program, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM wengn@mail.nih.gov
RI Chen, Guobing/D-9572-2012
OI Chen, Guobing/0000-0002-2401-6168
FU Intramural Research Program of the U.S. National Institutes of Health
National Institute on Aging (NIA)
FX This research was supported by the Intramural Research Program of the
U.S. National Institutes of Health National Institute on Aging (NIA).
The authors thank Ranjan Sen for critically reviewing the manuscript,
Dr. Luigi Ferrucci for his support in studying the Baltimore
Longitudinal Study of Aging participants, and NIA Clinical Core Lab for
collecting blood samples.
NR 36
TC 2
Z9 2
U1 2
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2016
VL 99
IS 3
BP 505
EP 513
DI 10.1189/jlb.6A0215-071RR
PG 9
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IO
UT WOS:000371890800013
PM 26394815
ER
PT J
AU Perna, FM
Coa, K
Troiano, RP
Lawman, HG
Wang, CY
Li, Y
Moser, RP
Ciccolo, JT
Comstock, BA
Kraemer, WJ
AF Perna, Frank M.
Coa, Kisha
Troiano, Richard P.
Lawman, Hannah G.
Wang, Chia-Yih
Li, Yan
Moser, Richard P.
Ciccolo, Joseph T.
Comstock, Brett A.
Kraemer, William J.
TI MUSCULAR GRIP STRENGTH ESTIMATES OF THE US POPULATION FROM THE NATIONAL
HEALTH AND NUTRITION EXAMINATION SURVEY 2011-2012
SO JOURNAL OF STRENGTH AND CONDITIONING RESEARCH
LA English
DT Article
DE NHANES; fitness; youth; adults
ID BODY-COMPOSITION; OLDER-ADULTS; MUSCLE MASS; MUSCULOSKELETAL FITNESS;
HANDGRIP STRENGTH; MORTALITY; CHILDREN; ADOLESCENTS; RESISTANCE; WEIGHT
AB Perna, FM, Coa, K, Troiano, RP, Lawman, HG, Wang, C-Y, Li, Y, Moser, RP, Ciccolo, JT, Comstock, BA, and Kraemer, WJ. Muscular grip strength estimates of the U.S. population from the National Health and Nutrition Examination Survey 2011-12. J Strength Cond Res 30(3): 867-874, 2016The purposes of this study were to use the National Health and Nutrition Examination Study (2011-12) data to determine nationally representative combined handgrip strength ranges and percentile information by sex and age group, examine trends in strength across age by sex, and to determine the relative proportion of children and adults falling into established health benefit zones (HBZ). Results indicate that mean strength was greater among men than women and increased linearly for children and in a quadratic fashion among adults for both sexes. Grip strength peaked in the 30- to 39-year age group for both men (216.4 lbs) and women (136.5 lbs) with subsequent age groups showing gradual decline, p < 0.0001. Relative and absolute increases in grip strength were greater for men than for women, but relative decrease from peak strength was less among women than men. Although absolute strength was greater among men than women, HBZ data indicated that a higher percentage of men than women overall and at each age group fell into the needs improvement zone, with differences particularly pronounced during adolescence and older adulthood. These data provide the first nationally representative population estimates of combined handgrip strength and percentile information from childhood through senescence and suggest consideration of HBZ information in conjunction with grip strength to improve surveillance data interpretation and intervention planning.
C1 [Perna, Frank M.; Coa, Kisha; Troiano, Richard P.; Moser, Richard P.] NCI, Bethesda, MD 20892 USA.
[Lawman, Hannah G.; Wang, Chia-Yih] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Li, Yan] Univ Maryland, Silver Spring, MD USA.
[Ciccolo, Joseph T.] Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA.
[Comstock, Brett A.] Univ S Dakota, Dept Kinesiol & Sport Sci, Vermillion, SD 57069 USA.
[Kraemer, William J.] Ohio State Univ, Dept Human Sci, Columbus, OH 43210 USA.
RP Perna, FM (reprint author), NCI, Bethesda, MD 20892 USA.
EM pernafm@mail.nih.gov
NR 35
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1064-8011
EI 1533-4287
J9 J STRENGTH COND RES
JI J. Strength Cond. Res.
PD MAR
PY 2016
VL 30
IS 3
BP 867
EP 874
DI 10.1519/JSC.0000000000001104
PG 8
WC Sport Sciences
SC Sport Sciences
GA DG1MF
UT WOS:000371831500034
PM 26196662
ER
PT J
AU Tempero, M
AF Tempero, Margaret
TI Promising the Moon!
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Tempero, Margaret] UCSF Pancreas Ctr, Med, San Francisco, CA USA.
[Tempero, Margaret] ASCO, Alexandria, VA 22314 USA.
[Tempero, Margaret] AACR ASCO, Alexandria, VA 22314 USA.
[Tempero, Margaret] NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA.
[Tempero, Margaret] Mayo Clin, Pancreas SPOREs, Rochester, MN 55905 USA.
[Tempero, Margaret] UAB Minnesota, Minneapolis, MN 55401 USA.
[Tempero, Margaret] Univ Arizona, GI SPORE, Tucson, AZ 85721 USA.
[Tempero, Margaret] Lustgarten Fdn, Bethpage, NY 66873 USA.
[Tempero, Margaret] Pancreat Canc Act Network, Manhattan Beach, CA 90266 USA.
[Tempero, Margaret] V Fdn, Cary, NC 27513 USA.
[Tempero, Margaret] Alberta Canada Canc Board, Edmonton, AB, Canada.
[Tempero, Margaret] EORTC, Brussels, Belgium.
[Tempero, Margaret] US FDA, Oncol Drug Advisory Comm, Rockville, MD 20857 USA.
[Tempero, Margaret] UNMC Eppley Canc Ctr, Omaha, NE 68198 USA.
[Tempero, Margaret] UCSF, Div Med Oncol, San Francisco, CA 94143 USA.
[Tempero, Margaret] UCSF Helen Diller Family Comprehens Canc Ctr, Res Programs, San Francisco, CA 94143 USA.
RP Tempero, M (reprint author), UCSF Pancreas Ctr, Med, San Francisco, CA USA.; Tempero, M (reprint author), ASCO, Alexandria, VA 22314 USA.; Tempero, M (reprint author), AACR ASCO, Alexandria, VA 22314 USA.; Tempero, M (reprint author), NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA.; Tempero, M (reprint author), Mayo Clin, Pancreas SPOREs, Rochester, MN 55905 USA.; Tempero, M (reprint author), UAB Minnesota, Minneapolis, MN 55401 USA.; Tempero, M (reprint author), Univ Arizona, GI SPORE, Tucson, AZ 85721 USA.; Tempero, M (reprint author), Lustgarten Fdn, Bethpage, NY 66873 USA.; Tempero, M (reprint author), Pancreat Canc Act Network, Manhattan Beach, CA 90266 USA.; Tempero, M (reprint author), V Fdn, Cary, NC 27513 USA.; Tempero, M (reprint author), Alberta Canada Canc Board, Edmonton, AB, Canada.; Tempero, M (reprint author), EORTC, Brussels, Belgium.; Tempero, M (reprint author), US FDA, Oncol Drug Advisory Comm, Rockville, MD 20857 USA.; Tempero, M (reprint author), UNMC Eppley Canc Ctr, Omaha, NE 68198 USA.; Tempero, M (reprint author), UCSF, Div Med Oncol, San Francisco, CA 94143 USA.; Tempero, M (reprint author), UCSF Helen Diller Family Comprehens Canc Ctr, Res Programs, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD MAR
PY 2016
VL 14
IS 3
BP 237
EP 237
PG 1
WC Oncology
SC Oncology
GA DG3VF
UT WOS:000371997900003
PM 26957609
ER
PT J
AU Bindewald, E
Afonin, KA
Viard, M
Zakrevsky, P
Kim, T
Shapiro, BA
AF Bindewald, Eckart
Afonin, Kirin A.
Viard, Mathias
Zakrevsky, Paul
Kim, Taejin
Shapiro, Bruce A.
TI Multistrand Structure Prediction of Nucleic Acid Assemblies and Design
of RNA Switches
SO NANO LETTERS
LA English
DT Article
DE RNA switch; RNA/DNA hybrid; RNA interference; Dicer; secondary structure
ID TISSUE GROWTH-FACTOR; SECONDARY STRUCTURE PREDICTION; THERMODYNAMIC
PARAMETERS; INCLUDING PSEUDOKNOTS; SPLIT FUNCTIONALITIES;
PARTITION-FUNCTION; BREAST-CANCER; DNA HYBRIDS; IN-SILICO; CELLS
AB RNA is an attractive material for the creation of molecular logic gates that release programmed functionalities only in the presence of specific molecular interaction partners. Here we present HyperFold, a multistrand RNA/DNA structure prediction approach for predicting nucleic acid complexes that can contain pseudoknots. We show that HyperFold also performs competitively compared to other published folding algorithms. We performed a large variety of RNA/DNA hybrid reassociation experiments for different concentrations, DNA toehold lengths, and G+C content and find that the observed tendencies for reassociation correspond well to computational predictions. Importantly, we apply this method to the design and experimental verification of a two-stranded RNA molecular switch that upon binding to a single-stranded RNA toehold disease-marker trigger mRNA changes its conformation releasing an shRNA-like Dicer substrate structure. To demonstrate the concept, connective tissue growth factor (CTGF) mRNA and enhanced green fluorescent protein (eGFP) mRNA were chosen as trigger and target sequences, respectively. In vitro experiments confirm the formation of an RNA switch and demonstrate that the functional unit is being released when the trigger RNA interacts with the switch toehold. The designed RNA switch is shown to be functional in MDA-MB-231 breast cancer cells. Several other switches were also designed and tested. We conclude that this approach has considerable potential because, in principle, it allows the release of an siRNA designed against a gene that differs from the gene that is utilized as a biomarker for a disease state.
C1 [Bindewald, Eckart; Viard, Mathias] Frederick Natl Lab Canc Res, Basic Sci Program, Leidos Biomed Res, Frederick, MD 21702 USA.
[Afonin, Kirin A.; Zakrevsky, Paul; Kim, Taejin; Shapiro, Bruce A.] Natl Canc Inst, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Afonin, Kirin A.] Univ N Carolina, Dept Chem, 9201 Univ City Blvd, Charlotte, NC 28223 USA.
RP Shapiro, BA (reprint author), Natl Canc Inst, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
EM shapirbr@mail.nih.gov
FU Federal funds from Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research
FX Computational support by the NCI Advanced Biomedical Computing Center
(ABCC) as well as the NIH Helix/Biowulf facility is highly appreciated.
This work has been funded in whole or in part with Federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health, under Contract No. HHSN261200800001E. This
research was supported [in part] by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 52
TC 6
Z9 6
U1 9
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
EI 1530-6992
J9 NANO LETT
JI Nano Lett.
PD MAR
PY 2016
VL 16
IS 3
BP 1726
EP 1735
DI 10.1021/acs.nanolett.5b04651
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DG3CE
UT WOS:000371946300032
PM 26926528
ER
PT J
AU Afonin, KA
Viard, M
Tedbury, P
Bindewald, E
Parlea, L
Howington, M
Valdman, M
Johns-Boehme, A
Brainerd, C
Freed, EO
Shapiro, BA
AF Afonin, Kirill A.
Viard, Mathias
Tedbury, Philip
Bindewald, Eckart
Parlea, Lorena
Howington, Marshall
Valdman, Melissa
Johns-Boehme, Alizah
Brainerd, Cara
Freed, Eric O.
Shapiro, Bruce A.
TI The Use of Minimal RNA Toeholds to Trigger the Activation of Multiple
Functionalities
SO NANO LETTERS
LA English
DT Article
DE RNA nanotechnology; RNA nanoparticles; RNA interference; RNA-DNA hybrid
reassociation
ID IN-SILICO; SPLIT FUNCTIONALITIES; PROTEIN COMPLEXES; EMERGING FIELD; DNA
HYBRIDS; PRNA 3WJ; NANOPARTICLES; DELIVERY; NANOTECHNOLOGY; INTERFERENCE
AB Current work reports the use of single-stranded RNA toeholds of different lengths to promote the reassociation of various RNA-DNA hybrids, which results in activation of multiple split functionalities inside human cells. The process of reassociation is analyzed and followed with a novel computational multistrand secondary structure prediction algorithm and various experiments. All of our previously designed RNA/DNA nanoparticles employed single stranded DNA toeholds to initiate reassociation. The use of RNA toeholds is advantageous because of the simpler design rules, the shorter toeholds, and the smaller size of the resulting nanoparticles (by up to 120 nucleotides per particle) compared to the same hybrid nanoparticles with single-stranded DNA toeholds. Moreover, the cotranscriptional assemblies result in higher yields for hybrid nanopartides with ssRNA toeholds.
C1 [Afonin, Kirill A.; Viard, Mathias; Parlea, Lorena; Johns-Boehme, Alizah; Brainerd, Cara; Shapiro, Bruce A.] Natl Canc Inst, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Afonin, Kirill A.; Howington, Marshall; Valdman, Melissa] Univ N Carolina, Dept Chem, 9201 Univ City Blvd, Charlotte, NC 28223 USA.
[Viard, Mathias; Bindewald, Eckart] Frederick Natl Lab Canc Res, Basic Sci Program, Leidos Biomed Res, Frederick, MD 21702 USA.
[Tedbury, Philip; Freed, Eric O.] Natl Canc Inst, Ctr Canc Res, HIV Dynam & Replicat Program, Frederick, MD 21702 USA.
RP Afonin, KA; Shapiro, BA (reprint author), Natl Canc Inst, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.; Afonin, KA (reprint author), Univ N Carolina, Dept Chem, 9201 Univ City Blvd, Charlotte, NC 28223 USA.
EM kafonin@uncc.edu; shapirbr@mail.nih.gov
OI Tedbury, Philip/0000-0001-8151-4967
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; UNC Charlotte; Intramural Research
Program of National Institutes of Health, Center for Cancer Research
FX This publication was funded in part with federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under Contract HHSN261200800001E and by the start-up funds
provided by UNC Charlotte to KAA. This research was additionally
supported in part by the Intramural Research Program of the National
Institutes of Health, Center for Cancer Research. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. HIV-Ig was obtained through the NIH AIDS Reagent
Program, Division of AIDS, NIAID, NIH: Catalog #3957 HIV-IG from NABI
and NHLBI).
NR 49
TC 5
Z9 5
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
EI 1530-6992
J9 NANO LETT
JI Nano Lett.
PD MAR
PY 2016
VL 16
IS 3
BP 1746
EP 1753
DI 10.1021/acs.nanolett.5b04676
PG 8
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA DG3CE
UT WOS:000371946300035
PM 26926382
ER
PT J
AU Serr, I
Furst, RW
Achenbach, P
Scherm, MG
Gokmen, F
Haupt, F
Sedlmeier, EM
Knopff, A
Shultz, L
Willis, RA
Ziegler, AG
Daniel, C
AF Serr, Isabelle
Fuerst, Rainer W.
Achenbach, Peter
Scherm, Martin G.
Goekmen, Fuesun
Haupt, Florian
Sedlmeier, Eva-Maria
Knopff, Annette
Shultz, Leonard
Willis, Richard A.
Ziegler, Anette-Gabriele
Daniel, Carolin
TI Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction
in humanized mice
SO NATURE COMMUNICATIONS
LA English
DT Article
ID REGULATORY T-CELLS; CLASS-II MHC; IN-VIVO; NOD MICE; MICRONEEDLE
PATCHES; IMMUNE-RESPONSES; HIGH-RISK; INSULIN; ANTIGEN; TOLERANCE
AB Immune tolerance is executed partly by Foxp3(+)regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing beta-cells. The development of autoantigen-specific vaccination strategies for Foxp3(+)Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3(+)Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4(+)T cells and demonstrate efficient human insulin-specific Foxp3(+)Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2R alpha and TIGIT and can efficiently suppress effector T cells. Such Foxp3(+)Treg-induction does not trigger any effector Tcells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3(+)Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D.
C1 [Serr, Isabelle; Scherm, Martin G.; Goekmen, Fuesun; Daniel, Carolin] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Diabet Res Inst, Independent Young Investigator Grp Immune Toleran, Heidemannstr 1, D-80939 Munich, Germany.
[Serr, Isabelle; Fuerst, Rainer W.; Achenbach, Peter; Scherm, Martin G.; Goekmen, Fuesun; Haupt, Florian; Sedlmeier, Eva-Maria; Knopff, Annette; Ziegler, Anette-Gabriele; Daniel, Carolin] Deutsch Zentrum Diabet Forsch, Ingolstadter Landstr 1, D-85764 Munich, Germany.
[Fuerst, Rainer W.; Achenbach, Peter; Haupt, Florian; Sedlmeier, Eva-Maria; Knopff, Annette; Ziegler, Anette-Gabriele] Tech Univ Munich, Diabet Res Inst, Klinikum Rechts Isar, Helmholtz Diabet Ctr,Helmholtz Zentrum Munchen, Heidemannstr 1, D-80939 Munich, Germany.
[Shultz, Leonard] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
[Willis, Richard A.] NIH, Emory Vaccine Ctr, Tetramer Core Facil, 201 Dowman Dr, Atlanta, GA 30322 USA.
RP Daniel, C (reprint author), Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Diabet Res Inst, Independent Young Investigator Grp Immune Toleran, Heidemannstr 1, D-80939 Munich, Germany.; Daniel, C (reprint author), Deutsch Zentrum Diabet Forsch, Ingolstadter Landstr 1, D-85764 Munich, Germany.
EM carolin.daniel@helmholtz-muenchen.de
FU Junior Research Group at Helmholtz Zentrum Munchen; Deutsche
Forschungsgemeinschaft [CRC1054]; Juvenile Diabetes Research Foundation
[JDRF 2-SRA-2014-161-Q-R, JDRF 17-2012-16, JDRF 6-2012-20];
Kompetenznetz Diabetes mellitus (Competence Network for Diabetes
mellitus) - Federal Ministry of Education and Research [FKZ 01GI0805-07,
FKZ 01GI0805]; German Center for Diabetes Research (DZD); National
Institutes of Health [U01 DK089572]; Helmsley Charitable Trust grant
[2012PG-T1D018]
FX We thank Katharina Warncke for providing umbilical cord blood samples
from the Immune Diab Risk Study (IDR); Ruth Chmiel, Melanie Bunk and
Susanne Hummel for blood sample collection and patient follow-up; and M.
H. Tschop for critical reading of the manuscript. C.D. is supported by a
Junior Research Group at Helmholtz Zentrum Munchen. C.D. received
support through an associated membership in the CRC1054 of the Deutsche
Forschungsgemeinschaft. The work was supported by grants from the
Juvenile Diabetes Research Foundation (JDRF 2-SRA-2014-161-Q-R (C.D.,
A.-G.Z.), JDRF 17-2012-16 (A.-G.Z.), JDRF 6-2012-20 (A.-G.Z.)), the
Kompetenznetz Diabetes mellitus (Competence Network for Diabetes
mellitus), funded by the Federal Ministry of Education and Research (FKZ
01GI0805-07, FKZ 01GI0805) and the German Center for Diabetes Research
(DZD). L.S. was supported by National Institutes of Health grants U01
DK089572 and the Helmsley Charitable Trust grant 2012PG-T1D018.
NR 70
TC 7
Z9 8
U1 9
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10991
DI 10.1038/ncomms10991
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG6IY
UT WOS:000372189000001
PM 26975663
ER
PT J
AU Wang, QY
Sawyer, IA
Sung, MH
Sturgill, D
Shevtsov, SP
Pegoraro, G
Hakim, O
Baek, S
Hager, GL
Dundr, M
AF Wang, Qiuyan
Sawyer, Iain A.
Sung, Myong-Hee
Sturgill, David
Shevtsov, Sergey P.
Pegoraro, Gianluca
Hakim, Ofir
Baek, Songjoon
Hager, Gordon L.
Dundr, Miroslav
TI Cajal bodies are linked to genome conformation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RNA-POLYMERASE-II; SMALL NUCLEAR-RNA; HISTONE MESSENGER-RNAS;
GENE-EXPRESSION; COILED BODIES; HUMAN-CELLS; INTEGRATOR COMPLEX; SUMO
ISOPEPTIDASE; NONCODING RNAS; IN-VIVO
AB The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. Here we examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromosome conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear or nucleolar RNA (sn/snoRNA) loci that form intra-and inter-chromosomal clusters. In particular, we observed a number of CB-dependent gene-positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production results in increased splicing noise, even in CB-distal regions. Therefore, we conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity.
C1 [Wang, Qiuyan; Sawyer, Iain A.; Shevtsov, Sergey P.; Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.
[Wang, Qiuyan; Sawyer, Iain A.; Sung, Myong-Hee; Sturgill, David; Pegoraro, Gianluca; Hakim, Ofir; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pegoraro, Gianluca] NCI, High Throughput Imaging Facil HiTIF, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Qiuyan] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China.
[Hakim, Ofir] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel.
RP Dundr, M (reprint author), Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol, N Chicago, IL 60064 USA.; Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM hagerg@dce41.nci.nih.gov; mirek.dundr@rosalindfranklin.edu
OI Pegoraro, Gianluca/0000-0003-2843-9464
FU Intramural Research Program of NIH; NIGMS [NIH R01GM090156]
FX We are particularly grateful to T. Misteli for helpful discussions. We
thank T. Misteli and S. Oberdoerffer for critical reading of the
manuscript. Analysis of high throughput sequencing data was partly
performed on the NIH supercomputing cluster Biowulf. This research is
supported by the Intramural Research Program of NIH (M.-H.S., S.B.,
S.P.S., G.P., G.L.H.) and NIH R01GM090156 from NIGMS (M.D.).
NR 75
TC 6
Z9 6
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10966
DI 10.1038/ncomms10966
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH0GW
UT WOS:000372462100001
PM 26997247
ER
PT J
AU Abunimer, AN
Salazar, J
Noursi, DP
Abu-Asab, MS
AF Abunimer, Ayman N.
Salazar, Jose
Noursi, David P.
Abu-Asab, Mones S.
TI A Systems Biology Interpretation of Array Comparative Genomic
Hybridization (aCGH) Data through Phylogenetics
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Article
ID CGH DATA; EXPRESSION; MEDICINE; OMICS
AB Array Comparative Genomic Hybridization (aCGH) is a rapid screening technique to detect gene deletions and duplications, providing an overview of chromosomal aberrations throughout the entire genome of a tumor, without the need for cell culturing. However, the heterogeneity of aCGH data obfuscates existing methods of data analysis. Analysis of aCGH data from a systems biology perspective or in the context of total aberrations is largely absent in the published literature. We present here a novel alternative to the functional analysis of aCGH data using the phylogenetic paradigm that is well-suited to high dimensional datasets of heterogeneous nature, but has not been widely adapted to aCGH data. Maximum parsimony phylogenetic analysis sorts out genetic data through the simplest presentation of the data on a cladogram, a graphical evolutionary tree, thus providing a powerful and efficient method for aCGH data analysis. For example, the cladogram models the multiphasic changes in the cancer genome and identifies shared early mutations in the disease progression, providing a simple yet powerful means of aCGH data interpretation. As such, applying maximum parsimony phylogenetic analysis to aCGH results allows for the differentiation between drivers and passenger genes aberrations in cancer specimens. In addition to offering a novel methodology to analyze aCGH results, we present here a crucial software suite that we wrote to carry out the analysis. In a broader context, we wish to underscore that phylogenetic analysis of aCGH data is a non-parametric method that circumvents the pitfalls and frustrations of standard analytical techniques that rely on parametric statistics. Organizing the data in a cladogram as explained in this research article provides insights into the disease common aberrations, as well as the disease subtypes and their shared aberrations (the synapomorphies) of each subtype. Hence, we report the method and make the software suite publicly and freely available at http://software.phylomcs.com so that researchers can test alternative and innovative approaches to the analysis of aCGH data.
C1 [Abunimer, Ayman N.] Virginia Tech Carilion Sch Med & Res Inst, Roanoke, VA USA.
[Salazar, Jose] MIT, Elect Engn & Comp Sci Dept, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Noursi, David P.] Univ Chicago, Coll, Chicago, IL 60637 USA.
[Abu-Asab, Mones S.] NEI, NIH, Bethesda, MD 20892 USA.
RP Abu-Asab, MS (reprint author), NEI, Pathol Lab, NIH, Bldg 10,Room 2A10, Bethesda, MD 20892 USA.
EM mones@mail.nih.gov
FU National Institutes of Health
FX The authors thank Dr. Hassan Brim of Howard University College of
Medicine for the opportunity to analyze the data. The research presented
here was partially supported by the intramural program of the National
Institutes of Health.
NR 25
TC 1
Z9 1
U1 3
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
EI 1557-8100
J9 OMICS
JI OMICS
PD MAR 1
PY 2016
VL 20
IS 3
BP 169
EP 179
DI 10.1089/omi.2015.0184
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DG6HX
UT WOS:000372186000004
PM 26983023
ER
PT J
AU Mahanty, S
AF Mahanty, S.
TI Host-parasite interactions and the immunobiology of cestodes
SO PARASITE IMMUNOLOGY
LA English
DT Editorial Material
DE Cestodes; immunology; pathogenesis; cellular responses; immunodiagnosis;
vaccines; parasite molecules
ID TAENIA-SOLIUM
C1 [Mahanty, S.] NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Mahanty, S (reprint author), 4 Ctr Dr,Room 424, Bethesda, MD 20892 USA.
EM smahanty@niaid.nih.gov
OI Mahanty, Siddhartha/0000-0003-1068-0524
NR 15
TC 0
Z9 0
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0141-9838
EI 1365-3024
J9 PARASITE IMMUNOL
JI Parasite Immunol.
PD MAR
PY 2016
VL 38
IS 3
SI SI
BP 121
EP 123
DI 10.1111/pim.12309
PG 3
WC Immunology; Parasitology
SC Immunology; Parasitology
GA DG7LA
UT WOS:000372264600001
PM 26864711
ER
PT J
AU Bezrukov, SM
Nestorovich, EM
AF Bezrukov, Sergey M.
Nestorovich, Ekaterina M.
TI Inhibiting bacterial toxins by channel blockage
SO PATHOGENS AND DISEASE
LA English
DT Review
DE rational drug design; structure-based drug discovery; channel-blocking
antitoxins; single molecule/protein interaction; multivalent
interactions; physical forces of efficient blockage
ID BOTULINUM C2 TOXIN; PERFRINGENS EPSILON-TOXIN; SYMMETRICAL
TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES; ANTHRAX LETHAL
TOXIN; RESISTANT STAPHYLOCOCCUS-AUREUS; BETA-CYCLODEXTRIN DERIVATIVES;
ACTIVATED POTASSIUM CHANNELS; SMALL-MOLECULE INHIBITORS;
VOLTAGE-DEPENDENT BLOCK
AB Emergent rational drug design techniques explore individual properties of target biomolecules, small and macromolecule drug candidates, and the physical forces governing their interactions. In this minireview, we focus on the single-molecule biophysical studies of channel-forming bacterial toxins that suggest new approaches for their inhibition. We discuss several examples of blockage of bacterial pore-forming and AB-type toxins by the tailor-made compounds. In the concluding remarks, the most effective rationally designed pore-blocking antitoxins are compared with the small-molecule inhibitors of ion-selective channels of neurophysiology.
C1 [Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Nestorovich, Ekaterina M.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
RP Nestorovich, EM (reprint author), Catholic Univ Amer, Dept Biol, McCort Ward, 620 Michigan Ave N-E, Washington, DC 20064 USA.
EM nestorovich@cua.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH; NIAID of the NIH [1R15AI099897-01A1]
FX SMB research is supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. EMN research is supported by NIAID of the NIH under
award number 1R15AI099897-01A1.
NR 120
TC 1
Z9 1
U1 2
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2049-632X
J9 PATHOG DIS
JI Pathog. Dis.
PD MAR
PY 2016
VL 74
IS 2
AR UNSP ftv113
DI 10.1093/femspd/ftv113
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG2VY
UT WOS:000371929200002
ER
PT J
AU Chew, M
Xie, J
Klein, R
Klein, B
Cotch, MF
Redline, S
Wong, TY
Cheung, N
AF Chew, Merwyn
Xie, Jing
Klein, Ronald
Klein, Barbara
Cotch, Mary Frances
Redline, Susan
Wong, Tien Yin
Cheung, Ning
TI Sleep apnea and retinal signs in cardiovascular disease: the
Multi-Ethnic Study of Atherosclerosis
SO SLEEP AND BREATHING
LA English
DT Article
DE Cardiovascular disease; Retinopathy; Retinal vascular caliber; Retinal
imaging; Microcirculation; Sleep apnea
ID CORONARY-HEART-DISEASE; MICROVASCULAR ABNORMALITIES; VESSEL DIAMETERS;
RISK; ASSOCIATION; WOMEN; COMMUNITIES; ARTERIOLAR; CALIBER; MEN
AB Purpose The aim of the study was to examine the relationship between sleep apnea, retinal vascular caliber and retinopathy, and their impact on cardiovascular disease (CVD) risk.
Methods A multi-ethnic cohort of 5,803 participants was examined based on standardized grading of retinal vascular caliber and retinopathy from digital fundus photographs, self-reported physician-diagnosed sleep apnea (PDSA), and incident cardiovascular events.
Results In women, PDSA was associated with narrower arterioles (regression coefficient [beta] -5.76; 95 % confidence Interval [CI] -8.51, -3.02) after adjusting for cardio-metabolic risk factors. The incident rate ratio (IRR) of CVD was also associated with narrower arterioles (IRR for highest versus lowest tertile 1.91; 95 % CI 1.08, 3.38). In men, PDSA was not associated with arteriolar caliber. However, incident CVD was associated with narrower arterioles (IRR 1.67; 95 % CI 1.10, 2.52), wider venules (IRR 1.71; 95 % CI 1.13, 2.59) and PDSA (IRR 2.03, 95 % CI 1.17, 3.51). The IRR of CVD in men with PDSA increased minimally to 2.06 (95 % CI 1.18, 3.56) after adjustment for retinal arteriolar and venular caliber. Combining women and men, the IRR of CVD was 3.41 (95 % CI 1.79, 6.50) in those with both PDSA and narrower retinal arterioles.
Conclusions Sleep apnea was associated with narrower retinal arterioles in women but not in men. However, sleep apnea was also associated with incident CVD in men. These suggest potential gender differences in susceptibility to microvascular disease in association with sleep apnea.
C1 [Chew, Merwyn; Wong, Tien Yin; Cheung, Ning] Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
[Chew, Merwyn; Wong, Tien Yin] Natl Univ Singapore, Dept Ophthalmol, Yong Loo Lin Sch Med, Singapore 117548, Singapore.
[Xie, Jing; Wong, Tien Yin; Cheung, Ning] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Klein, Ronald; Klein, Barbara] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Chew, Merwyn; Wong, Tien Yin] Natl Univ Hlth Syst, Dept Ophthalmol, Singapore, Singapore.
RP Chew, M (reprint author), Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.; Chew, M (reprint author), Natl Univ Singapore, Dept Ophthalmol, Yong Loo Lin Sch Med, Singapore 117548, Singapore.; Chew, M (reprint author), Natl Univ Hlth Syst, Dept Ophthalmol, Singapore, Singapore.
EM merwynchew@gmail.com
OI Cotch, Mary Frances/0000-0002-2046-4350
FU National Heart, Lung and Blood Institute [NHLBI T32 HL076132]; National
Institute of Health [HL69979-03]; [N01-HC-95159]; [N01-HC-95160];
[N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164];
[N01-HC-95165]; [N01-HC-95167]
FX This research was supported by contracts, N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95167, and a grant NHLBI T32 HL076132 from the National Heart,
Lung and Blood Institute. Additional support was provided by National
Institute of Health grant HL69979-03 (Klein R, Wong TY).
NR 30
TC 1
Z9 1
U1 2
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1520-9512
EI 1522-1709
J9 SLEEP BREATH
JI Sleep Breath.
PD MAR
PY 2016
VL 20
IS 1
BP 15
EP 23
DI 10.1007/s11325-015-1177-z
PG 9
WC Clinical Neurology; Respiratory System
SC Neurosciences & Neurology; Respiratory System
GA DG5ZJ
UT WOS:000372160800003
PM 25903075
ER
PT J
AU Ritchie, DL
Gibson, SV
Abee, CR
Kreil, TR
Ironside, JW
Brown, P
AF Ritchie, Diane L.
Gibson, Susan V.
Abee, Christian R.
Kreil, Thomas R.
Ironside, James W.
Brown, Paul
TI Blood transmission studies of prion infectivity in the squirrel monkey
(Saimiri sciureus): the Baxter study
SO TRANSFUSION
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; SPONGIFORM ENCEPHALOPATHY; NERVOUS-SYSTEM;
TISSUE SAMPLES; VARIANT; PROTEIN; TRANSFUSION; ACCUMULATION; UK;
APPENDIX
AB BACKGROUNDFour secondary transmissions of variant Creutzfeldt-Jakob disease (vCJD) infectivity have been associated with the transfusion of nonleukoreduced red blood cells collected from vCJD patients during the asymptomatic phase of the disease. Establishing efficient experimental models for assessing the risk of future transmissions of vCJD infectivity via blood transfusion is of paramount importance in view of a study of archived appendix samples in which the prevalence of asymptomatic vCJD infection in the United Kingdom was estimated at approximately 1 in 2000 of the population. In this study, we investigated transmission of vCJD and sporadic CJD (sCJD) infectivity from blood using the squirrel monkey, which is highly susceptible to experimental challenge with human prion disease.
STUDY DESIGN AND METHODSWhole blood collected from vCJD- and sCJD-infected squirrel monkeys was transfused at multiple time points into recipient squirrel monkeys. Blood recipients were euthanized approximately 7 years after their first blood transfusion.
RESULTSNo clinical or pathologic signs of a prion disease were observed in either the sCJD- or the vCJD-transfused monkeys, and immunohistochemistry and biochemical investigations showed no PrPTSE in central nervous system or lymphoreticular tissues. Similarly, monkeys inoculated intracerebrally (IC) and intravenously (IV) with either buffy coat or plasma from vCJD and sCJD patients failed to develop disease. However, white blood cells from a chimpanzee-passaged strain of human Gerstmann-Straussler-Scheinker (GSS) disease transmitted autopsy-proven disease to two IC-inoculated monkeys after incubation periods of 34 and 39 months.
CONCLUSIONBlood transmits GSS but not sCJD or vCJD infectivity to IC- or IV-inoculated squirrel monkeys within a 7-year observation period.
C1 [Ritchie, Diane L.; Ironside, James W.] Univ Edinburgh, Western Gen Hosp, Natl CJD Res & Surveillance Unit, Ctr Clin Brain Sci, Edinburgh EH46 7EA, Midlothian, Scotland.
[Gibson, Susan V.] Univ S Alabama, Coll Med, Mobile, AL USA.
[Abee, Christian R.] Univ Texas MD Anderson Canc Ctr, Bastrop, TX USA.
[Kreil, Thomas R.] Baxalta, Global Pathogen Safety, Vienna, Austria.
[Kreil, Thomas R.] Baxter BioSci, Vienna, Austria.
[Brown, Paul] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Ritchie, DL (reprint author), Univ Edinburgh, Sch Clin Sci, Natl CJD Res & Surveillance Unit, Western Gen Hosp, Edinburgh EH46 7EA, Midlothian, Scotland.
EM diane.ritchie@ed.ac.uk
OI Ironside, James/0000-0001-5869-2108
FU Department of Health, England; Scottish Government
FX The NCJDRSU is supported by the Department of Health, England, and the
Scottish Government. The views expressed in this publication are those
of the authors and not necessarily those of the Department of Health.
NR 33
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2016
VL 56
IS 3
BP 712
EP 721
DI 10.1111/trf.13422
PG 10
WC Hematology
SC Hematology
GA DG7SH
UT WOS:000372283500025
PM 26594017
ER
PT J
AU Chen, Q
Srivastava, K
Ardinski, SC
Lam, K
Huvard, MJ
Schmid, P
Flegel, WA
AF Chen, Qing
Srivastava, Kshitij
Ardinski, Stefanie C.
Lam, Kevin
Huvard, Michael J.
Schmid, Pirmin
Flegel, Willy A.
TI Full-length nucleotide sequences of 30 common SLC44A2 alleles encoding
human neutrophil antigen-3
SO TRANSFUSION
LA English
DT Article
ID ACUTE LUNG INJURY; ALLOANTIGEN GENOTYPE FREQUENCIES; TRANSPORTER-LIKE
PROTEIN-2; BLOOD-DONORS; GENETIC-VARIATION; INNER-EAR; HNA-3;
ALLOANTIBODIES; POPULATIONS; ANTIBODIES
AB BACKGROUNDHuman neutrophil antigen-3a (HNA-3a) alloantibodies can cause severe transfusion-related acute lung injury. The frequencies of the single-nucleotide polymorphisms (SNPs) indicative of the two clinically relevant HNA-3a/b antigens are known in many populations. In this study, we determined the full-length nucleotide sequence of common SLC44A2 alleles encoding the choline transporter-like protein-2 that harbors HNA-3a/b antigens.
STUDY DESIGN AND METHODSA method was devised to determine the full-length coding sequence (CDS) and adjacent intron sequences from genomic DNA by eight polymerase chain reaction amplifications covering all 22 SLC44A2 exons. Samples from 200 African American, 96 Caucasian, two Hispanic, and four Asian blood donors were analyzed. We developed a decision tree to determine alleles (confirmed haplotypes) from the genotype data.
RESULTSA total of 10 SNPs were detected in the SLC44A2 CDS. The noncoding sequences harbored an additional 28 SNPs (one in the 5-untranslated region [UTR]; 23 in the introns; and four in the 3-UTR). No SNP indicative of a nonfunctional allele was detected. The nucleotide sequences for 30 SLC44A2 alleles (haplotypes) were confirmed. There may be 66 haplotypes among the 604 chromosomes screened.
CONCLUSIONSWe found 38 SNPs, including one novel SNP, in 8192 nucleotides covering the CDS of the SLC44A2 gene among 302 blood donors. Population frequencies of these SNPs were established for African Americans and Caucasians. Because alleles encoding HNA-3b are more common than non-functional SLC44A2 alleles, we confirmed our previous postulate that African American donors are less likely to form HNA-3a antibodies compared to Caucasians.
C1 [Chen, Qing; Srivastava, Kshitij; Ardinski, Stefanie C.; Lam, Kevin; Huvard, Michael J.; Schmid, Pirmin; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Qing] Jiangsu Prov Blood Ctr, Nanjing, Jiangsu, Peoples R China.
RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM waf@nih.gov
FU grant "Jiangsu Health International Exchange Program"; Jiangsu Province
Medical Elite Program [RC2011088]; National Natural Science Foundation
of China [81101734]; NIH Clinical Center
FX QC was supported by a grant "Jiangsu Health International Exchange
Program," by Grant RC2011088 from the Jiangsu Province Medical Elite
Program and by Grant 81101734 from the National Natural Science
Foundation of China. Part of the study was performed at NIH in 2012 by
QC as Visiting Senior Research Scientist, by SA in partial fulfillment
of her study of molecular medicine (University of Ulm), and by KL as
part of his Summer Internship program. This research was supported by
the Intramural Research Program of the NIH Clinical Center.
NR 43
TC 3
Z9 3
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2016
VL 56
IS 3
BP 729
EP 736
DI 10.1111/trf.13300
PG 8
WC Hematology
SC Hematology
GA DG7SH
UT WOS:000372283500027
PM 26437811
ER
PT J
AU Chen, Q
Srivastava, K
Liu, Z
Xiao, JY
Huang, CY
Sun, J
Li, M
Flegel, WA
AF Chen, Qing
Srivastava, Kshitij
Liu, Zhong
Xiao, Jianyu
Huang, Chengyin
Sun, Jun
Li, Min
Flegel, Willy Albert
TI Genotype frequency of human neutrophil antigen-3 polymorphisms in the
Yi, Han, and Tibetan populations of China
SO TRANSFUSION
LA English
DT Article
ID ACUTE LUNG INJURY; BLOOD-DONORS; GENE-FREQUENCIES; ALLOANTIGENS;
ALLOANTIBODIES; HNA-3; TRALI; 5B
AB BACKGROUNDHuman neutrophil antigen-3 (HNA-3) alloantibodies can cause fatal transfusion-related acute lung injury (TRALI). Most frequencies of SLC44A2 alleles encoding the HNA-3a/b antigens have been established in Han individuals by polymerase chain reaction with sequence-specific priming (PCR-SSP). We sequenced SLC44A2 gene fragments and determined allele frequencies in three ethnicities of China.
STUDY DESIGN AND METHODSGenomic DNA was extracted from 448 samples of 100 blood donors of Yi ethnicity in Xichang, Liangshan; 248 Han in Nanjing, Jiangsu; and 100 Tibetan in Lhasa, Tibet. A PCR-SSP was applied to determine the phase of two single-nucleotide polymorphisms (SNPs); SLC44A2 haplotypes were constructed.
RESULTSIn the 567 nucleotides of the SLC44A2 gene covered by our sequencing approach in Han individuals, we detected the known 331-44G>A (rs12972963) and 461G>A (rs2288904) polymorphisms. In the 243 nucleotides sequenced in Yi and Tibetan populations, we detected the known 461G>A and 503-15T>C (rs1560711) polymorphisms. A PCR-SSP for the common HNA-3a/b SNP was 100% concordant. The frequencies of the HNA-3a allele were 0.58, 0.66, and 0.69 in Yi, Han (Nanjing), and Tibetan, respectively (0.42, 0.34, and 0.31 for HNA-3b).
CONCLUSIONSThe Yi population of China had the highest frequency of blood donors at risk of harboring anti-HNA-3a compared to any population studied so far. We confirmed that the underlying SLC44A2*2 allele is more common in China than in any European or African populations.
C1 [Chen, Qing; Xiao, Jianyu; Huang, Chengyin; Sun, Jun] Jiangsu Prov Blood Ctr, Nanjing, Jiangsu, Peoples R China.
[Chen, Qing] Soochow Univ, Suzhou, Jiangsu, Peoples R China.
[Liu, Zhong] Chinese Acad Med Sci, Inst Blood Transfus, Chengdu, Sichuan, Peoples R China.
[Liu, Zhong] Peking Union Med Coll, Chengdu, Sichuan, Peoples R China.
[Li, Min] Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.
[Li, Min] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.
[Li, Min] Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China.
[Srivastava, Kshitij; Flegel, Willy Albert] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM waf@nih.gov
FU Jiangsu Province Social Development Program [BE2015717]; Jiangsu
Province Medical Elite Program [RC2011088]; Jiangsu Health International
Exchange Program; National Natural Science Foundation of China
[81101734]; NIH Clinical Center
FX This research was supported by the Jiangsu Province Social Development
Program (BE2015717), Jiangsu Province Medical Elite Program (RC2011088),
the Jiangsu Health International Exchange Program, the National Natural
Science Foundation of China (81101734), and the Intramural Research
Program of the NIH Clinical Center.
NR 35
TC 1
Z9 1
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2016
VL 56
IS 3
BP 737
EP 742
DI 10.1111/trf.13413
PG 6
WC Hematology
SC Hematology
GA DG7SH
UT WOS:000372283500028
PM 26593331
ER
PT J
AU Hurwitz, JL
Penkert, RR
Xu, BS
Fan, YP
Partridge, JF
Maul, RW
Gearhart, PJ
AF Hurwitz, Julia L.
Penkert, Rhiannon R.
Xu, Beisi
Fan, Yiping
Partridge, Janet F.
Maul, Robert W.
Gearhart, Patricia J.
TI Hotspots for Vitamin-Steroid-Thyroid Hormone Response Elements Within
Switch Regions of Immunoglobulin Heavy Chain Loci Predict a Direct
Influence of Vitamins and Hormones on B Cell Class Switch Recombination
SO VIRAL IMMUNOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; RETINOID-X-RECEPTOR; A-DEFICIENT MICE; SOMATIC
HYPERMUTATION; RESPIRATORY-TRACT; NUCLEAR RECEPTORS; VIRUS-VACCINE; IGA
RESPONSE; ACID; DNA
AB Vitamin A deficiencies are common throughout the world and have a significant negative influence on immune protection against viral infections. Mouse models demonstrate that the production of IgA, a first line of defense against viruses at mucosal sites, is inhibited in the context of vitamin A deficiency. In vitro, the addition of vitamin A to activated B cells can enhance IgA expression, but downregulate IgE. Previous reports have demonstrated that vitamin A modifies cytokine patterns, and in so doing may influence antibody isotype expression by an indirect mechanism. However, we have now discovered hundreds of potential response elements among S, S, and S switch sites within immunoglobulin heavy chain loci. These hotspots appear in both mouse and human loci and include targets for vitamin receptors and related proteins (e.g., estrogen receptors) in the nuclear receptor superfamily. Full response elements with direct repeats are relatively infrequent or absent in S regions although half-sites are present. Based on these results, we pose a hypothesis that nuclear receptors have a direct effect on the immunoglobulin heavy chain class switch recombination event. We propose that vitamin A may alter S site accessibility to activation-induced deaminase and nonhomologous end-joining machinery, thereby influencing the isotype switch, antibody production, and protection against viral infections at mucosal sites.
C1 [Hurwitz, Julia L.; Penkert, Rhiannon R.] St Jude Childrens Res Hosp, Dept Infect Dis, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
[Xu, Beisi; Fan, Yiping] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
[Partridge, Janet F.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Hurwitz, Julia L.] Univ Tennessee, Hlth Sci Ctr, Dept Microbiol Immunol & Biochem, Memphis, TN USA.
[Maul, Robert W.; Gearhart, Patricia J.] NIA, NIH, Baltimore, MD 21224 USA.
RP Hurwitz, JL (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM julia.hurwitz@stjude.org
RI Xu, Beisi/C-8560-2009
OI Xu, Beisi/0000-0003-0099-858X
FU NIH NIAID [R01 AI088729]; NCI [P30 CA21765]; American Lebanese Syrian
Associated Charities (ALSAC); Intramural Research Program of the NIH,
National Institute on Aging
FX The research was funded in part by NIH NIAID R01 AI088729, NCI P30
CA21765, the American Lebanese Syrian Associated Charities (ALSAC), and
the Intramural Research Program of the NIH, National Institute on Aging.
NR 45
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Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0882-8245
EI 1557-8976
J9 VIRAL IMMUNOL
JI Viral Immunol.
PD MAR 1
PY 2016
VL 29
IS 2
BP 132
EP 136
DI 10.1089/vim.2015.0104
PG 5
WC Immunology; Virology
SC Immunology; Virology
GA DG2AM
UT WOS:000371868600008
PM 26741514
ER
PT J
AU Kerridge, BT
Saha, TD
Hasin, DS
AF Kerridge, Bradley T.
Saha, Tulshi D.
Hasin, Deborah S.
TI Armed Conflict, Substance Use and HIV: A Global Analysis
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV; Substance use; Conflict; Partial least squares structural equation
modeling; Terrorism; Refugees; Disasters
ID SUB-SAHARAN AFRICA; PUBLIC-HEALTH; ALCOHOL-USE; COMPLEX EMERGENCIES;
WAR; PREVENTION; HIV/AIDS; SETTINGS; PEOPLE; COMBAT
AB Armed conflict is frequently assumed to be a contributor to the global HIV epidemic, but existing evidence is sparse. We examined the relationship between armed conflict between 2002 and 2008 and HIV disability life years (DALYs) in 2010 among WHO Member States. Using partial least squares analysis we also examined moderation of the armed conflict-HIV link by two susceptibility constructs (background risk, substance use) and one vulnerability mediator (numbers of refugees, people on ART, and total HIV spending). Background risk directly impacted HIV DALYs (p < 0.05), substance use moderated the conflict-HIV relationship (p < 0.01). The vulnerability construct mediated the conflict-HIV association (p < 0.01). Findings underscore the need to align HIV prevention/intervention efforts with pre-existing HIV burden and reduce the impact of natural disasters on the populace in conflict-affected states. Integration of substance prevention/harm reduction programs within national HIV responses, attention to most-at-risk populations and increased surveillance/treatment of drug resistant HIV and TB is warranted.
C1 [Kerridge, Bradley T.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Saha, Tulshi D.] NIAAA, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3077, Rockville, MD 20852 USA.
[Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, Mailman Sch Publ Hlth,New York State Psychiat Ins, New York, NY 10032 USA.
RP Kerridge, BT (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
EM bradleykerridge@gmail.com
OI Kerridge, Bradley/0000-0003-0459-9439
FU National Institute on Drug Abuse, National Institutes of Health
[5F32DA0364431]; National Institute on Alcohol Abuse and Alcoholism
[K05AA014223]; New York State Psychiatric Institute
FX This research was supported by the National Institute on Drug Abuse,
National Institutes of Health (5F32DA0364431: Dr. Kerridge), the
National Institute on Alcohol Abuse and Alcoholism (K05AA014223: Dr.
Hasin), and the New York State Psychiatric Institute (Dr. Hasin).
NR 76
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Z9 0
U1 1
U2 12
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD MAR
PY 2016
VL 20
IS 3
BP 473
EP 483
DI 10.1007/s10461-015-1161-4
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DF8JA
UT WOS:000371602700001
PM 26286341
ER
PT J
AU Rentsch, C
Tate, JP
Akgun, KM
Crystal, S
Wang, KH
Greysen, SR
Wang, EA
Bryant, KJ
Fiellin, DA
Justice, AC
Rimland, D
AF Rentsch, Christopher
Tate, Janet P.
Akguen, Kathleen M.
Crystal, Stephen
Wang, Karen H.
Greysen, S. Ryan
Wang, Emily A.
Bryant, Kendall J.
Fiellin, David A.
Justice, Amy C.
Rimland, David
TI Alcohol-Related Diagnoses and All-Cause Hospitalization Among
HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United
States Veterans from 1997 to 2011
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Inpatient care; HIV; Substance abuse; Clinical epidemiology; Aging
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE UTILIZATION; ANTIRETROVIRAL
THERAPY; SERVICES UTILIZATION; USE DISORDERS; COHORT; RISK;
METAANALYSIS; INDIVIDUALS; ADULTS
AB Individuals with HIV infection are living substantially longer on antiretroviral therapy, but hospitalization rates continue to be relatively high. We do not know how overall or diagnosis-specific hospitalization rates compare between HIV-infected and uninfected individuals or what conditions may drive hospitalization trends. Hospitalization rates among United States Veterans were calculated and stratified by HIV serostatus and principal diagnosis disease category. Because alcohol-related diagnoses (ARD) appeared to have a disproportional effect, we further stratified our calculations by ARD history. A multivariable Cox proportional hazards model was fitted to assess the relative risk of hospitalization controlling for demographic and other comorbidity variables. From 1997 to 2011, 46,428 HIV-infected and 93,997 uninfected patients were followed for 1,497,536 person-years. Overall hospitalization rates decreased among HIV-infected and uninfected patients. However, cardiovascular and renal insufficiency admissions increased for all groups while gastrointestinal and liver, endocrine, neurologic, and non-AIDS cancer admissions increased among those with an alcohol-related diagnosis. After multivariable adjustment, HIV-infected individuals with an ARD had the highest risk of hospitalization (hazard ratio 3.24, 95 % CI 3.00, 3.49) compared to those free of HIV infection and without an ARD. Still, HIV alone also conferred increased risk (HR 2.08, 95 % CI 2.04, 2.13). While decreasing overall, risk of all-cause hospitalization remains higher among HIV-infected than uninfected individuals and is strongly influenced by the presence of an ARD.
C1 [Rentsch, Christopher; Rimland, David] Atlanta VA Med Ctr, Infect Dis, Decatur, GA USA.
[Rentsch, Christopher; Tate, Janet P.; Akguen, Kathleen M.; Wang, Karen H.; Justice, Amy C.] VA Connecticut Healthcare Syst, Res, West Haven, CT USA.
[Rentsch, Christopher; Tate, Janet P.; Akguen, Kathleen M.; Wang, Karen H.; Wang, Emily A.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Crystal, Stephen] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA.
[Greysen, S. Ryan] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA.
[Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
RP Rentsch, C (reprint author), VA Connecticut Healthcare Syst, Res, West Haven, CT USA.
EM christopher.rentsch@va.gov
OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502
FU National Institutes of Health: AHRQ [R01-HS018372]; NIAAA [U24-AA020794,
U01-AA020790, U01-AA020795, U01-AA020799, U24-AA022001, U24 AA022007,
U10 AA013566-completed]; NHLBI [R01-HL095136, R01-HL090342]; NIAID
[U01-A1069918]; NIMH [P30-MH062294]; NIDA [R01DA035616]; NCI [R01
CA173754]; Veterans Health Administration Office of Research and
Development [VA REA 08-266, V1CDA2012-20]; Office of Academic
Affiliations; Department of Veterans Affairs, Veterans Health
Administration; Office of Research and Development
FX This work was supported by the National Institutes of Health: AHRQ
[R01-HS018372], NIAAA [U24-AA020794, U01-AA020790, U01-AA020795,
U01-AA020799, U24-AA022001, U24 AA022007, U10 AA013566-completed], NHLBI
[R01-HL095136; R01-HL090342], NIAID [U01-A1069918], NIMH [P30-MH062294],
NIDA [R01DA035616], NCI [R01 CA173754] and the Veterans Health
Administration Office of Research and Development [VA REA 08-266, VA IRR
Merit Award, VISN 1 Career Development Award [V1CDA2012-20]] and Office
of Academic Affiliations [Medical Informatics Fellowship]. This material
is based upon work supported by the Department of Veterans Affairs,
Veterans Health Administration, and Office of Research and Development.
We must disclaim that the views expressed in this article are those of
the authors and do not necessarily reflect the position or policy of the
Department of Veterans Affairs.
NR 51
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Z9 5
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD MAR
PY 2016
VL 20
IS 3
BP 555
EP 564
DI 10.1007/s10461-015-1025-y
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DF8JA
UT WOS:000371602700007
PM 25711299
ER
PT J
AU Rentsch, C
Tate, JP
Akgun, KM
Crystal, S
Wang, KH
Greysen, SR
Wang, EA
Bryant, KJ
Fiellin, DA
Justice, AC
Rimland, D
AF Rentsch, Christopher
Tate, Janet P.
Akgun, Kathleen M.
Crystal, Stephen
Wang, Karen H.
Greysen, S. Ryan
Wang, Emily A.
Bryant, Kendall J.
Fiellin, David A.
Justice, Amy C.
Rimland, David
TI Alcohol-Related Diagnoses and All-Cause Hospitalization Among
HIV-Infected and Uninfected Patients: A Longitudinal Analysis of United
States Veterans from 1997 to 2011 (vol 20, pg 555, 2016)
SO AIDS AND BEHAVIOR
LA English
DT Correction
C1 [Rentsch, Christopher; Rimland, David] Atlanta VA Med Ctr, Infect Dis, Decatur, GA USA.
[Rentsch, Christopher; Tate, Janet P.; Akgun, Kathleen M.; Wang, Karen H.; Justice, Amy C.] VA Connecticut Healthcare Syst, Res, West Haven, CT USA.
[Rentsch, Christopher; Tate, Janet P.; Akgun, Kathleen M.; Wang, Karen H.; Wang, Emily A.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Crystal, Stephen] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA.
[Greysen, S. Ryan] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA.
[Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
RP Rentsch, C (reprint author), Atlanta VA Med Ctr, Infect Dis, Decatur, GA USA.; Rentsch, C (reprint author), VA Connecticut Healthcare Syst, Res, West Haven, CT USA.; Rentsch, C (reprint author), Yale Univ, Sch Med, New Haven, CT USA.
EM christopher.rentsch@va.gov
FU AHRQ HHS [R01 HS018372]; NCI NIH HHS [R01 CA173754]; NHLBI NIH HHS [R01
HL095136, R01 HL090342]; NIAAA NIH HHS [U24 AA022007, U24 AA022001, U01
AA020790, U01 AA020795, U01 AA020799, U10 AA013566, U01 AA013566, U13
AA022864, U24 AA020794]; NIDA NIH HHS [R01 DA035616]; NIMH NIH HHS [P30
MH062294]
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD MAR
PY 2016
VL 20
IS 3
BP 565
EP 565
DI 10.1007/s10461-015-1072-4
PG 1
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DF8JA
UT WOS:000371602700008
PM 25972072
ER
PT J
AU Braithwaite, RS
Fang, YX
Tate, J
Mentor, SM
Bryant, KJ
Fiellin, DA
Justice, AC
AF Braithwaite, R. Scott
Fang, Yixin
Tate, Janet
Mentor, Sherry M.
Bryant, Kendall J.
Fiellin, David A.
Justice, Amy C.
TI Do Alcohol Misuse, Smoking, and Depression Vary Concordantly or
Sequentially? A Longitudinal Study of HIV-Infected and Matched
Uninfected Veterans in Care
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Alcohol use; Aging; Temporal analysis; Depression; HIV; Smoking;
Veterans
ID NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; MENTAL-DISORDERS; AGING
COHORT; HEALTH; ASSOCIATION; CONSUMPTION; DRINKING; ABUSE; RATES
AB We analyzed temporal patterns of alcohol misuse, smoking, and depression among veterans in care to determine whether these conditions vary concordantly or sequentially. Using the Veterans Aging Cohort Study, harmful alcohol use (AUDIT-C a parts per thousand yen 4), current smoking, and depression (PHQ-9 a parts per thousand yen 8), were measured. In regression analyses, predictors included each outcome condition at baseline, the other two conditions in the same survey, the other two conditions in the immediately preceding survey, number of years since enrollment, and HIV status. We found that current smoking and depression were more common among HIV infected individuals. Harmful alcohol use was more common among uninfected individuals. Temporal analyses suggested a concurrent pattern: each condition was associated with the other two conditions (p < 0.03, OR 1.12-1.66) as well as with the prior presence of the same condition (p < 0.0001; OR 6.38-22.02). Smoking was associated with prior depression after controlling for current depression (OR 1.16; p = 0.003). In conclusion, alcohol misuse, smoking, and depression were temporally concordant and persistent, raising the question of whether they constitute a common syndrome in HIV infected patients and others with chronic diseases.
C1 [Braithwaite, R. Scott; Fang, Yixin; Mentor, Sherry M.] NYU, Dept Populat Hlth, Sch Med, 227 East 30th St,Floor 6 Room 615, New York, NY 10016 USA.
[Tate, Janet; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA.
RP Braithwaite, RS (reprint author), NYU, Dept Populat Hlth, Sch Med, 227 East 30th St,Floor 6 Room 615, New York, NY 10016 USA.
EM Scott.Braithwaite@nyumc.org
OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502;
Fang, Yixin/0000-0003-0104-9140
FU National Institute on Alcohol Abuse and Alcoholism of the National
Institutes of Health [U24AA022007]
FX Research reported in this publication was supported by the National
Institute on Alcohol Abuse and Alcoholism of the National Institutes of
Health under Award Number U24AA022007. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 25
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD MAR
PY 2016
VL 20
IS 3
BP 566
EP 572
DI 10.1007/s10461-015-1117-8
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DF8JA
UT WOS:000371602700009
PM 26187007
ER
PT J
AU Zhu, YY
Olsen, SF
Mendola, P
Yeung, EH
Vaag, A
Bowers, K
Liu, AY
Bao, W
Li, SS
Madsen, C
Grunnet, LG
Granstrom, C
Hansen, S
Martin, K
Chavarro, JE
Hu, FB
Langhoff-Roos, J
Damm, P
Zhang, CL
AF Zhu, Yeyi
Olsen, Sjurdur F.
Mendola, Pauline
Yeung, Edwina H.
Vaag, Allan
Bowers, Katherine
Liu, Aiyi
Bao, Wei
Li, Shanshan
Madsen, Camilla
Grunnet, Louise G.
Granstrom, Charlotta
Hansen, Susanne
Martin, Kelly
Chavarro, Jorge E.
Hu, Frank B.
Langhoff-Roos, Jens
Damm, Peter
Zhang, Cuilin
TI Growth and obesity through the first 7 y of life in association with
levels of maternal glycemia during pregnancy: a prospective cohort study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE childhood obesity; fasting plasma glucose; gestational diabetes;
intrauterine exposure; macrosomia; prepregnancy obesity
ID GESTATIONAL DIABETES-MELLITUS; CHILDHOOD OBESITY; GLUCOSE-TOLERANCE;
OUTCOME HAPO; HYPERGLYCEMIA; CHILDREN; MOTHERS; OVERWEIGHT; WOMEN; RISK
AB Background: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications.
Objective: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status.
Design: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors.
Results: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (beta = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase),. At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (beta = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo.
Conclusion: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI.
C1 [Zhu, Yeyi; Mendola, Pauline; Yeung, Edwina H.; Bowers, Katherine; Liu, Aiyi; Bao, Wei; Li, Shanshan; Martin, Kelly; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Olsen, Sjurdur F.; Granstrom, Charlotta; Hansen, Susanne] Staten Serum Inst, Dept Epidemiol Res, Ctr Fetal Programming, Copenhagen, Denmark.
[Vaag, Allan; Madsen, Camilla; Grunnet, Louise G.] Univ Copenhagen Hosp, Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark.
[Langhoff-Roos, Jens] Univ Copenhagen Hosp, Rigshosp, Dept Obstet, DK-2100 Copenhagen, Denmark.
[Chavarro, Jorge E.; Hu, Frank B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chavarro, Jorge E.; Hu, Frank B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Damm, Peter] Univ Copenhagen, Rigshosp, Inst Clin Med, Dept Obstet,Fac Hlth & Med Sci,Ctr Pregnant Women, DK-2100 Copenhagen, Denmark.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
EM zhangcu@mail.nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Yeung, Edwina/0000-0002-3851-2613;
Liu, Aiyi/0000-0002-6618-5082
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH
[HHSN275201000020C]; Danish Research Council [09-067124, 09-075611]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
(HHSN275201000020C). The Danish National Birth Cohort is supported by
grants 09-067124 (Center for Fetal Programming) and 09-075611 from the
Danish Research Council.
NR 41
TC 2
Z9 2
U1 1
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2016
VL 103
IS 3
BP 794
EP 800
DI 10.3945/ajcn.115.121780
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DF8ZO
UT WOS:000371650200016
PM 26817507
ER
PT J
AU Mumford, SL
Chavarro, JE
Zhang, CL
Perkins, NJ
Sjaarda, LA
Pollack, AZ
Schliep, KC
Michels, KA
Zarek, SM
Plowden, TC
Radin, RG
Messer, LC
Frankel, RA
Wactawski-Wende, J
AF Mumford, Sunni L.
Chavarro, Jorge E.
Zhang, Cuilin
Perkins, Neil J.
Sjaarda, Lindsey A.
Pollack, Anna Z.
Schliep, Karen C.
Michels, Kara A.
Zarek, Shvetha M.
Plowden, Torie C.
Radin, Rose G.
Messer, Lynne C.
Frankel, Robyn A.
Wactawski-Wende, Jean
TI Dietary fat intake and reproductive hormone concentrations and ovulation
in regularly menstruating women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE dietary fats; estradiol; menstrual cycle; ovulation; testosterone
ID HIGH-FIBER DIET; SERUM ESTROGEN CONCENTRATIONS; FOOD FREQUENCY
QUESTIONNAIRE; POLYCYSTIC-OVARY-SYNDROME; PREMENOPAUSAL WOMEN; FERTILITY
MONITOR; PHYSICAL-ACTIVITY; BREAST-CANCER; ACID; CYCLE
AB Background: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis.
Objective: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the Bio-Cycle Study.
Design: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race.
Results: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. Conclusions: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation.
C1 [Mumford, Sunni L.; Zhang, Cuilin; Perkins, Neil J.; Sjaarda, Lindsey A.; Schliep, Karen C.; Michels, Kara A.; Zarek, Shvetha M.; Plowden, Torie C.; Radin, Rose G.; Frankel, Robyn A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Zarek, Shvetha M.; Plowden, Torie C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Pollack, Anna Z.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
[Messer, Lynne C.] Portland State Univ, Sch Community Hlth, Portland, OR 97207 USA.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD USA.
EM mumfords@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Sjaarda, Lindsey/0000-0003-0539-8110
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH [HHSN275200403394C,
HHSN275201100002I, HHSN27500001]; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), NIH [P30-DK46200]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
(contracts HHSN275200403394C and HHSN275201100002I and Task 1
HHSN27500001); JEC was supported by the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK), NIH, grant P30-DK46200.
NR 47
TC 1
Z9 1
U1 2
U2 9
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2016
VL 103
IS 3
BP 868
EP 877
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DF8ZO
UT WOS:000371650200024
PM 26843151
ER
PT J
AU Agarwal, SK
Wruck, L
Quibrera, M
Matsushita, K
Loehr, LR
Chang, PP
Rosamond, WD
Wright, J
Heiss, G
Coresh, J
AF Agarwal, Sunil K.
Wruck, Lisa
Quibrera, Miguel
Matsushita, Kunihiro
Loehr, Laura R.
Chang, Patricia P.
Rosamond, Wayne D.
Wright, Jacqueline
Heiss, Gerardo
Coresh, Josef
TI Temporal Trends in Hospitalization for Acute Decompensated Heart Failure
in the United States, 1998-2011
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE acute decompensated heart failure; adjudicated heart failure; community
surveillance; hospitalizations; International Classification of Diseases
codes; national inpatient sample; secular trends; United States
ID ATHEROSCLEROSIS RISK; CLASSIFICATION; COMMUNITIES; VALIDATION; UPDATE;
RATES
AB Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005-2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged a parts per thousand yen55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998-2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005-2011, numbers of ADHF hospitalizations were stable (-0.5%/year; 95% CI: -1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by -1.5%/year (95% CI: -2.2, -0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005.
C1 [Agarwal, Sunil K.; Matsushita, Kunihiro; Coresh, Josef] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Agarwal, Sunil K.; Matsushita, Kunihiro; Coresh, Josef] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Wruck, Lisa; Quibrera, Miguel] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Loehr, Laura R.; Rosamond, Wayne D.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Sch Global Publ Hlth, Chapel Hill, NC USA.
[Loehr, Laura R.; Chang, Patricia P.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Wright, Jacqueline] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Agarwal, SK (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 2020 E Monument St,Room B-321, Baltimore, MD 21287 USA.
EM sunilagarwal1@gmail.com
FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
T32HL007024]
FX The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. S. K. A. was
supported by Cardiovascular Epidemiology Training Grant T32HL007024 from
the National Heart, Lung, and Blood Institute ( Principal Investigator:
Prof. Josef Coresh).
NR 20
TC 3
Z9 4
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2016
VL 183
IS 5
BP 462
EP 470
DI 10.1093/aje/kwv455
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DF9NU
UT WOS:000371688800022
PM 26895710
ER
PT J
AU Chen, SF
Huang, JF
Zhao, Q
Chen, J
Jaquish, CE
He, J
Lu, XF
Yang, XL
Gu, CC
Hixson, JE
Liu, FC
Rice, TK
Cao, J
Chen, JC
Gu, DF
AF Chen, Shufeng
Huang, Jianfeng
Zhao, Qi
Chen, Jing
Jaquish, Cashell E.
He, Jiang
Lu, Xiangfeng
Yang, Xueli
Gu, Charles C.
Hixson, James E.
Liu, Fangchao
Rice, Treva K.
Cao, Jie
Chen, Jichun
Gu, Dongfeng
TI Associations Between Genetic Variants of the Natriuretic Peptide System
and Blood Pressure Response to Dietary Sodium Intervention: The GenSalt
Study
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure response; dietary intervention; genetic association;
natriuretic peptide
ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; COMMON VARIANTS;
INCIDENT HYPERTENSION; ISCHEMIC-STROKE; URINARY SODIUM; SALT INTAKE;
RECEPTOR; CHINESE; RISK
AB BACKGROUND
The aim of this study was to comprehensively test the association of genetic variants in the natriuretic peptide (NP) system with blood pressure (BP) response to dietary sodium intervention in a Chinese population.
METHODS
We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the associations of 48 single-nucleotide polymorphisms (SNPs) in 6 genes of NP system with BP response to dietary sodium intervention.
RESULTS
SNP rs5063 in the NPPA gene and SNP rs2077386 in the NPPC gene exhibited significant associations with BP response to low-sodium dietary intervention under recessive genetic model. For rs5063, absolute mean arterial pressure responses (95% confidence interval) to the low-sodium intervention were 1.31 (-1.08, 3.70) mm Hg for TT genotype and -3.74 (-4.01, -3.46) mm Hg for CC or TC genotype, respectively (P = 4.1 x 10(-5)). Individuals with at least one copy of the C allele of rs2077386 had significantly reduction in systolic BP during the low-sodium intervention compared to those with genotype GG with responses of -5.48 (-5.83, -5.14) vs. -2.76 (-3.52, -2.00) mm Hg, respectively (P = 1.9 x 10(-13)).
CONCLUSIONS
These novel findings suggested that genetic variants of NP system may contribute to the variation of BP response to sodium intervention in Chinese population. Certainly, replication of these results in other populations and further functional studies are warranted to clarify their role in the regulation of BP and hypertension.
C1 [Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Yang, Xueli; Liu, Fangchao; Cao, Jie; Chen, Jichun; Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.
[Chen, Shufeng; Huang, Jianfeng; Lu, Xiangfeng; Yang, Xueli; Liu, Fangchao; Cao, Jie; Chen, Jichun; Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Zhao, Qi; Chen, Jing; He, Jiang] Tulane Univ, Sch Publ Hlth, Dept Epidemiol, New Orleans, LA USA.
[Jaquish, Cashell E.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gu, Charles C.; Rice, Treva K.] Washington Univ, Sch Med, St Louis, MO USA.
[Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
RP Chen, SF (reprint author), Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.; Chen, SF (reprint author), Peking Union Med Coll, Beijing 100021, Peoples R China.
EM shufengchen2001@163.com
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD, USA [U01HL072507, R01HL087263, R01HL090682];
High-Tech Research and Development Program of China (863 Plan) from the
Ministry of Science and Technology of China [2012AA02A516]; Beijing
Natural Science Foundation, China [7132205]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by a cooperative agreement project grant (U01HL072507,
R01HL087263, and R01HL090682) from the National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, MD, USA. This study
is also funded by a research grant (2012AA02A516) from the High-Tech
Research and Development Program of China (863 Plan) from the Ministry
of Science and Technology of China. S.C. is a scholar supported by
Beijing Natural Science Foundation (7132205), China.
NR 40
TC 0
Z9 0
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD MAR
PY 2016
VL 29
IS 3
BP 397
EP 404
DI 10.1093/ajh/hpv129
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DF9OD
UT WOS:000371689800016
PM 26224401
ER
PT J
AU Traboulsee, A
Simon, JH
Stone, L
Fisher, E
Jones, DE
Malhotra, A
Newsome, SD
Oh, J
Reich, DS
Richert, N
Rammohan, K
Khan, O
Radue, EW
Ford, C
Halper, J
Li, D
AF Traboulsee, A.
Simon, J. H.
Stone, L.
Fisher, E.
Jones, D. E.
Malhotra, A.
Newsome, S. D.
Oh, J.
Reich, D. S.
Richert, N.
Rammohan, K.
Khan, O.
Radue, E. -W.
Ford, C.
Halper, J.
Li, D.
TI Revised Recommendations of the Consortium of MS Centers Task Force for a
Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and
Follow-Up of Multiple Sclerosis
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SPINAL-CORD LESIONS;
MCDONALD CRITERIA; INTERFERON-BETA; TRIAL; ABNORMALITIES; DISABILITY;
ATROPHY; RISK; LOAD
AB This is a comprehensive group of guidelines for imaging patients with demyelinating disease, from an international group of neurologists and radiologists. Suggestions for MR imaging protocols are given for the brain, for surveillance imaging for progressive multifocal leukoencephalopathy, for spinal cord imaging, and for the orbit. Recommendations are also given for what type of material should be included in the report.
SUMMARY: An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.
C1 [Traboulsee, A.] Univ British Columbia, Dept Med Neurol, Vancouver, BC V5Z 1M9, Canada.
[Simon, J. H.] Portland VA Res Fdn, Portland, OR USA.
[Simon, J. H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Stone, L.] Cleveland Clin, Mellen Ctr MS Treatment & Res, Cleveland, OH 44106 USA.
[Fisher, E.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44106 USA.
[Jones, D. E.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Malhotra, A.] Yale Univ, Dept Radiol & Biomed Imaging, New Haven, CT USA.
[Newsome, S. D.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
[Oh, J.] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada.
[Reich, D. S.] NINDS, Translat Neuroradiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Richert, N.] Biogen Idec Inc, Cambridge, MA USA.
[Rammohan, K.] Univ Miami, Multiple Sclerosis Ctr, Miami, FL USA.
[Khan, O.] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
[Radue, E. -W.] Univ Basel Hosp, Dept Radiol, CH-4031 Basel, Switzerland.
[Ford, C.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Halper, J.] Consortium Multiple Sclerosis Ctr, Hackensack, NJ USA.
[Li, D.] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada.
RP Traboulsee, A (reprint author), Univ British Columbia, Dept Med Neurol, UBC Hosp, 2211 Wesbrook Mall,Room s199, Vancouver, BC V6T 2B5, Canada.
EM t.traboulsee@ubc.ca
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Consortium of Multiple Sclerosis Centers
FX Organizational support and funding for the meetings were provided by the
Consortium of Multiple Sclerosis Centers (www.mscare.org).
NR 46
TC 15
Z9 15
U1 3
U2 8
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD MAR
PY 2016
VL 37
IS 3
BP 394
EP 401
DI 10.3174/ajnr.A4539
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DF8TG
UT WOS:000371631500008
PM 26564433
ER
PT J
AU Feldblum, JT
Wroblewski, EE
Rudicell, RS
Li, YY
Hahn, BH
Pusey, AE
Gilby, IC
AF Feldblum, Joseph T.
Wroblewski, Emily E.
Rudicell, Rebecca S.
Li, Yingying
Hahn, Beatrice H.
Pusey, Anne E.
Gilby, Ian C.
TI Alternative reproductive tactics among male chimpanzees in Gombe
National Park, Tanzania
SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the
American-Association-of-Physical-Anthropologists
CY APR 13-16, 2016
CL Atlanta, GA
SP Amer Assoc Phys Anthropologists
C1 [Feldblum, Joseph T.; Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27706 USA.
[Wroblewski, Emily E.] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA.
[Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD USA.
[Rudicell, Rebecca S.] Sanofi, Rockville, MD USA.
[Li, Yingying; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Li, Yingying; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Gilby, Ian C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-9483
EI 1096-8644
J9 AM J PHYS ANTHROPOL
JI Am. J. Phys. Anthropol.
PD MAR
PY 2016
VL 159
SU 62
BP 142
EP 142
PG 1
WC Anthropology; Evolutionary Biology
SC Anthropology; Evolutionary Biology
GA DF3OW
UT WOS:000371255201136
ER
PT J
AU Sherry, S
Xiao, CL
Slotta, D
Rodarmer, K
Feolo, M
Kimelman, M
Godynskiy, G
O'Sullivan, C
Yaschenko, E
AF Sherry, Stephen
Xiao, Chunlin
Slotta, Douglas
Rodarmer, Kurt
Feolo, Mike
Kimelman, Michael
Godynskiy, Georgiy
O'Sullivan, Chris
Yaschenko, Eugene
TI Simplified access to human genomic evidence for clinical variants with
new NCBI services
SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the
American-Association-of-Physical-Anthropologists
CY APR 13-16, 2016
CL Atlanta, GA
SP Amer Assoc Phys Anthropologists
C1 [Sherry, Stephen; Xiao, Chunlin; Slotta, Douglas; Rodarmer, Kurt; Feolo, Mike; Kimelman, Michael; Godynskiy, Georgiy; O'Sullivan, Chris; Yaschenko, Eugene] NIH, NCBI, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-9483
EI 1096-8644
J9 AM J PHYS ANTHROPOL
JI Am. J. Phys. Anthropol.
PD MAR
PY 2016
VL 159
SU 62
BP 289
EP 290
PG 2
WC Anthropology; Evolutionary Biology
SC Anthropology; Evolutionary Biology
GA DF3OW
UT WOS:000371255202220
ER
PT J
AU Berg, CD
AF Berg, Christine D.
TI Just Say No! Smoking Abstinence Works
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID LUNG; MORTALITY
C1 [Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA.
[Berg, Christine D.] NCI, Div Canc Epidemiol & Prevent, Bethesda, MD 20892 USA.
RP Berg, CD (reprint author), Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA.; Berg, CD (reprint author), NCI, Div Canc Epidemiol & Prevent, Bethesda, MD 20892 USA.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 1
PY 2016
VL 193
IS 5
BP 476
EP 477
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DG0KI
UT WOS:000371753300004
PM 26930428
ER
PT J
AU Du Toit, J
Miller, F
AF Du Toit, Jessica
Miller, Franklin
TI THE ETHICS OF CONTINUED LIFE-SUSTAINING TREATMENT FOR THOSE DIAGNOSED AS
BRAIN-DEAD
SO BIOETHICS
LA English
DT Article
DE brain death; life-sustaining treatment; Jahi McMath; futility; scarce
resource allocation
ID RATIONALE
AB Given the long-standing controversy about whether the brain-dead should be considered alive in an irreversible coma or dead despite displaying apparent signs of life, the ethical and policy issues posed when family members insist on continued treatment are not as simple as commentators have claimed. In this article, we consider the kind of policy that should be adopted to manage a family's insistence that their brain-dead loved one continues to receive supportive care. We argue that while it would be ethically inappropriate to continue to devote scarce acute care resources to such patients in a hospital setting, it may not be ethically inappropriate for patients to receive these resources in certain other settings. Thus, if a family insists on continuing to care for their brain-dead loved at their home, we should not, from a policy perspective, interfere with the family's wishes. We also argue that healthcare professionals should make some effort to facilitate the transfer of brain-dead patients to these other settings when families insist on continued treatment despite being informed about the lack of any potential for recovery of consciousness. Our arguments are strengthened by the fact that patients in a persistent vegetative state, who, when correctly diagnosed, also have no potential for recovery of consciousness, are routinely transferred from hospitals to nursing homes or long-term care facilities where they continue to be ventilated, tube fed and to receive other supportive care. We also briefly explore the question of who should be responsible for the costs of such treatment at the long-term care facility.
C1 [Du Toit, Jessica; Miller, Franklin] NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
[Miller, Franklin] Weill Cornell Med Coll, Med Eth Med, New York, NY 10065 USA.
RP Miller, F (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.; Miller, F (reprint author), Weill Cornell Med Coll, Med Eth Med, New York, NY 10065 USA.
EM fmiller@cc.nih.gov
NR 22
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
EI 1467-8519
J9 BIOETHICS
JI Bioethics
PD MAR
PY 2016
VL 30
IS 3
BP 151
EP 158
DI 10.1111/bioe.12178
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA DF6SS
UT WOS:000371487500003
PM 26183857
ER
PT J
AU Blehm, BH
Devine, A
Staunton, JR
Tanner, K
AF Blehm, Benjamin H.
Devine, Alexus
Staunton, Jack R.
Tanner, Kandice
TI In vivo tissue has non-linear rheological behavior distinct from 3D
biomimetic hydrogels, as determined by AMOTIV microscopy
SO BIOMATERIALS
LA English
DT Article
DE Microrheology; Optical traps; Biomaterials; Tissue mechanics; Hydrogels;
Zebrafish
ID 3-DIMENSIONAL CULTURE MODELS; SINGLE KINESIN MOLECULES;
MECHANICAL-PROPERTIES; BASEMENT-MEMBRANE; OPTICAL TWEEZERS; FORCE
MICROSCOPY; CELL; MICRORHEOLOGY; CANCER; ZEBRAFISH
AB Variation in matrix elasticity has been shown to determine cell fate in both differentiation and development of malignant phenotype. The tissue microenvironment provides complex biochemical and biophysical signals in part due to the architectural heterogeneities found in extracellular matrices (ECMs). Three dimensional cell cultures can partially mimic in vivo tissue architecture, but to truly understand the role of viscoelasticity on cell fate, we must first determine in vivo tissue mechanical properties to improve in vitro models. We employed Active Microrheology by Optical Trapping In Vivo (AMOTIV), using in situ calibration to measure in vivo zebrafish tissue mechanics. Previously used trap calibration methods overestimate complex moduli by 2-20 fold compared to AMOTIV. Applying differential microscale stresses and strains showed that hyaluronic acid (HA) gels display semi-flexible polymer behavior, while laminin-rich ECM hydrogels display flexible polymer behavior. In contrast, zebrafish tissues displayed different moduli at different stresses, with higher power law exponents at lower stresses, indicating that living tissue has greater stress dependence than the 3D hydrogels examined. To our knowledge, this work is the first vertebrate tissue rheological characterization performed in vivo. Our fundamental observations are important for the development and refinement of in vitro platforms. Published by Elsevier Ltd.
C1 [Blehm, Benjamin H.; Devine, Alexus; Staunton, Jack R.; Tanner, Kandice] NIH, Cell Biol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
RP Tanner, K (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2132, Bethesda, MD 20892 USA.
EM kandice.tanner@nih.gov
FU Intramural Research Program of the National Institutes of Health, the
National Cancer Institute
FX This effort was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute. We thank
Benjamin Feldman of the National Institute of Child Health and Human
Development and Eric Glasgow of Georgetown University, for helpful
discussions and assistance with zebrafish husbandry. We also thank
George Leiman for critical reading of this manuscript. We thank Ross
Lake for help with histology. We also thank Daniel Blair, and Xinran
Zhang of Georgetown University for assistance with bulk rheometry.
NR 61
TC 2
Z9 2
U1 9
U2 28
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD MAR
PY 2016
VL 83
BP 66
EP 78
DI 10.1016/j.biomaterials.2015.12.019
PG 13
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA DF9AD
UT WOS:000371651700006
PM 26773661
ER
PT J
AU Tao, Y
Gao, H
Ackerman, B
Guo, W
Saffen, D
Shugart, YY
AF Tao, Yu
Gao, Hui
Ackerman, Benjamin
Guo, Wei
Saffen, David
Shugart, Yin Yao
TI Evidence for contribution of common genetic variants within chromosome
8p21.2-8p21.1 to restricted and repetitive behaviors in autism spectrum
disorders
SO BMC GENOMICS
LA English
DT Article
DE Restricted and Repetitive Behaviors (RRB); Genome-Wide Association
Study; Autism Spectrum Disorders (ASD); Autism Diagnostic
Interview-Revised (ADI-R)
ID GENOME-WIDE LINKAGE; PERVASIVE DEVELOPMENTAL DISORDERS; DIAGNOSTIC
INTERVIEW; ASSOCIATION; RISK; SCHIZOPHRENIA; EXPRESSION; LOCI; SCAN;
IDENTIFICATION
AB Background: Restricted and Repetitive Behaviors (RRB), one of the core symptom categories for Autism Spectrum Disorders (ASD), comprises heterogeneous groups of behaviors. Previous research indicates that there are two or more factors (subcategories) within the RRB domain. In an effort to identify common variants associated with RRB, we have carried out a genome-wide association study (GWAS) using the Autism Genetic Resource Exchange (AGRE) dataset (n = 1,335, all ASD probands of European ancestry) for each identified RRB subcategory, while allowing for comparisons of associated single nucleotide polymorphisms (SNPs) with associated SNPs in the same set of probands analyzed using all the RRB subcategories as phenotypes in a multivariate linear mixed model. The top ranked SNPs were then explored in an independent dataset.
Results: Using principal component analysis of item scores obtained from Autism Diagnostic Interview-Revised (ADI-R), two distinct subcategories within Restricted and Repetitive Behaviors were identified: Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS). Quantitative RSM and IS scores were subsequently used as phenotypes in a GWAS using the AGRE ASD cohort. Although no associated SNPs with genome-wide significance (P < 5.0E-08) were detected when RSM or IS were analyzed independently, three SNPs approached genome-wide significance when RSM and IS were considered together using multivariate association analysis. These included the top IS-associated SNP, rs62503729 (P-value = 6.48E-08), which is located within chromosome 8p21.2-8p21.1, a locus previously linked to schizophrenia. Notably, all of the most significantly associated SNPs are located in close proximity to STMN4 and PTK2B, genes previously shown to function in neuron development. In addition, several of the top-ranked SNPs showed correlations with STMN4 mRNA expression in adult CEU (Caucasian and European descent) human prefrontal cortex. However, the association signals within chromosome 8p21.2-8p21.1 failed to replicate in an independent sample of 2,588 ASD probands; the insufficient sample size and between-study heterogeneity are possible explanations for the non-replication.
Conclusions: Our analysis indicates that RRB in ASD can be represented by two distinct subcategories: RSM and IS. Subsequent univariate and multivariate genome-wide association studies of these RRB subcategories enabled the detection of associated SNPs at 8p21.2-8p21.1. Although these results did not replicate in an independent ASD dataset, genomic features of this region and pathway analysis suggest that common variants in 8p21.2-8p21.1 may contribute to RRB, particularly IS. Together, these observations warrant future studies to elucidate the possible contributions of common variants in 8p21.2-8p21.1 to the etiology of RSM and IS in ASD.
C1 [Ackerman, Benjamin; Guo, Wei; Shugart, Yin Yao] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Tao, Yu; Gao, Hui; Saffen, David] Fudan Univ, Sch Basic Med Sci, Dept Cellular & Genet Med, 130Dongan Rd, Shanghai 200032, Peoples R China.
[Ackerman, Benjamin] Johns Hopkins Univ, Baltimore, MD USA.
RP Shugart, YY (reprint author), NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM kay1yao@mail.nih.gov
FU Intramural Research Program, National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH) [MH002930-05]; National
Basic Research 973 Program of China [2010CB529601]
FX We are grateful to the families at the participating SFARI Simplex
Collection (SSC) sites and to the principal investigators (A. Beaudet,
R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D.
Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim,
J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W.
Stone, J. Sutcliffe, C. Walsh, E. Wijsman). We appreciate obtaining
access to phenotypic data on SFARI Base. Approved researchers can obtain
the SSC population dataset described in this study
(https://ordering.base.sfari.org/browsecollection/archive[sfaricollectio
nv91]/ui:view()) by applying at https://base.sfari.org. The authors
gratefully acknowledge the support of the Intramural Research Program,
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH, grant number MH002930-05) and the National Basic Research
973 Program of China (2010CB529601).
NR 83
TC 1
Z9 1
U1 2
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAR 1
PY 2016
VL 17
AR 163
DI 10.1186/s12864-016-2475-y
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DF8GF
UT WOS:000371594700003
PM 26931105
ER
PT J
AU Duzel, E
van Praag, H
Sendtner, M
AF Duzel, Emrah
van Praag, Henriette
Sendtner, Michael
TI Can physical exercise in old age improve memory and hippocampal
function?
SO BRAIN
LA English
DT Article
DE hippocampus; exercise; cerebral blood flow; Alzheimer's disease; memory
ID GROWTH-FACTOR-I; ADULT DENTATE GYRUS; SPORADIC ALZHEIMERS-DISEASE;
RANDOMIZED-CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; MEDIAL
TEMPORAL-LOBE; A-BETA OLIGOMERS; BODY-MASS INDEX; PATTERN SEPARATION;
AEROBIC EXERCISE
AB Physical activity can offer protection against cognitive decline and neurodegenerative diseases, but whether it slows the trajectory of normal ageing or boosts plasticity above and beyond preservation of function is unclear. Duzel et al. examine the evidence that exercise improves hippocampal plasticity in ageing and discuss avenues for future research.Physical activity can offer protection against cognitive decline and neurodegenerative diseases, but whether it slows the trajectory of normal ageing or boosts plasticity above and beyond preservation of function is unclear. Duzel et al. examine the evidence that exercise improves hippocampal plasticity in ageing and discuss avenues for future research.Physical exercise can convey a protective effect against cognitive decline in ageing and Alzheimer's disease. While the long-term health-promoting and protective effects of exercise are encouraging, it's potential to induce neuronal and vascular plasticity in the ageing brain is still poorly understood. It remains unclear whether exercise slows the trajectory of normal ageing by modifying vascular and metabolic risk factors and/or consistently boosts brain function by inducing structural and neurochemical changes in the hippocampus and related medial temporal lobe circuitry-brain areas that are important for learning and memory. Hence, it remains to be established to what extent exercise interventions in old age can improve brain plasticity above and beyond preservation of function. Existing data suggest that exercise trials aiming for improvement and preservation may require different outcome measures and that the balance between the two may depend on exercise intensity and duration, the presence of preclinical Alzheimer's disease pathology, vascular and metabolic risk factors and genetic variability.
C1 [Duzel, Emrah] Univ Magdeburg, Inst Cognit Neurol & Dementia Res, Leipziger Str 44, D-39120 Magdeburg, Germany.
[Duzel, Emrah] German Ctr Neurodegenerat Dis DZNE, Magdeburg Site,Leipziger Str 44, D-39120 Magdeburg, Germany.
[Duzel, Emrah] UCL, Inst Cognit Neurosci, 17 Queen Sq, London, England.
[van Praag, Henriette] NIA, Neuroplast & Behav Unit, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Sendtner, Michael] Univ Wurzburg, Inst Clin Neurobiol, Versbacher Str 5, D-97078 Wurzburg, Germany.
RP Duzel, E (reprint author), German Ctr Neurodegenerat Dis DZNE, Magdeburg Site,Leipziger Str 44, D-39120 Magdeburg, Germany.
EM emrah.duezel@dzne.de
RI van Praag, Henriette/F-3939-2015; Sendtner, Michael/J-1542-2012
OI van Praag, Henriette/0000-0002-5727-434X; Sendtner,
Michael/0000-0002-4737-2974
FU National Institute on Aging, Intramural Research Program (DFG) [TRR58,
A09]; BMBF through the EnergI consortium; Deutsche
Forschungs-Gemeinschaft [SFB 779 TP A7]
FX This work was supported in part by the National Institute on Aging,
Intramural Research Program (DFG, TRR58, A09) and the BMBF through the
EnergI consortium and the Deutsche Forschungs-Gemeinschaft (SFB 779 TP
A7).
NR 146
TC 8
Z9 8
U1 14
U2 48
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD MAR 1
PY 2016
VL 139
BP 662
EP 673
DI 10.1093/brain/awv407
PN 3
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9PX
UT WOS:000371694600013
PM 26912638
ER
PT J
AU Wang, X
Zhang, Y
Peng, Y
Hutchinson, MR
Rice, KC
Yin, H
Watkins, LR
AF Wang, X.
Zhang, Y.
Peng, Y.
Hutchinson, M. R.
Rice, K. C.
Yin, H.
Watkins, L. R.
TI Pharmacological characterization of the opioid inactive isomers
(+)-naltrexone and (+)-naloxone as antagonists of toll-like receptor 4
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
ID NEUROPATHIC PAIN; NITRIC-OXIDE; BINDING-SITE; SPINAL-CORD; ACTIVATION;
NALOXONE; CELLS; TLR4; TRIF; LIPOPOLYSACCHARIDE
AB Background and PurposeThe toll-like receptor TLR4 is involved in neuropathic pain and in drug reward and reinforcement. The opioid inactive isomers (+)-naltrexone and (+)-naloxone act as TLR4 antagonists, reversing neuropathic pain and reducing opioid and cocaine reward and reinforcement. However, how these agents modulate TLR4 signalling is not clear. Here, we have elucidated the molecular mechanism of (+)-naltrexone and (+)-naloxone on TLR4 signalling.
Experimental ApproachBV-2 mouse microglial cell line, primary rat microglia and primary rat peritoneal macrophages were treated with LPS and TLR4 signalling inhibitors. Effects were measured using Western blotting, luciferase reporter assays, fluorescence microscopy and ELISA
Key Results(+)-Naltrexone and (+)-naloxone were equi-potent inhibitors of the LPS-induced TLR4 downstream signalling and induction of the pro-inflammatory factors NO and TNF-. Similarly, (+)-naltrexone or (+)-naloxone inhibited production of reactive oxygen species and increased microglial phagocytosis, induced by LPS. However, (+)-naltrexone and (+)-naloxone did not directly inhibit the increased production of IL-1, induced by LPS. The drug interaction of (+)-naloxone and (+)-naltrexone was additive. (+)-Naltrexone or (+)-naloxone inhibited LPS-induced activation of IFN regulatory factor 3 and production of IFN-. However, they did not inhibit TLR4 signalling via the activation of either NF-B, p38 or JNK in these cellular models.
Conclusions and Implications(+)-Naltrexone and (+)-naloxone were TRIF-IFN regulatory factor 3 axis-biased TLR4 antagonists. They blocked TLR4 downstream signalling leading to NO, TNF- and reactive oxygen species. This pattern may explain, at least in part, the in vivo therapeutic effects of (+)-naltrexone and (+)-naloxone.
C1 [Wang, X.] Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China.
[Wang, X.] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China.
[Zhang, Y.; Watkins, L. R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Zhang, Y.; Watkins, L. R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
[Peng, Y.; Yin, H.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
[Peng, Y.; Yin, H.] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
[Hutchinson, M. R.] Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA 5005, Australia.
[Rice, K. C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, K. C.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Wang, X (reprint author), Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China.
EM xiaohui.wang@ciac.ac.cn
OI Hutchinson, Mark/0000-0003-2154-5950; YIN, HANG/0000-0002-9762-4818
FU National Institutes of Health [R01DE021966, R01GM101279, R01GM103843];
Australian Research Council Research Fellowship [DP110100297]; National
Natural Science Foundation of China [21543013]; Open Funding of State
Key Laboratory of Natural Medicines, China Pharmaceutical University
[SKLNMKF201502]; intramural research programs of the National Institute
on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; 100
Talents Program of Chinese Academy of Sciences
FX We thank the National Institutes of Health (R01DE021966 to L. R. W.;
R01GM101279 and R01GM103843 to H. Y.) for financial support. M. R. H. is
the recipient of an Australian Research Council Research Fellowship
(DP110100297). X. W. was supported by the starting-up funding for the
candidate of 100 Talents Program of Chinese Academy of Sciences,
National Natural Science Foundation of China (no. 21543013) and the Open
Funding of State Key Laboratory of Natural Medicines, China
Pharmaceutical University (SKLNMKF201502). Some part of this work was
supported by the intramural research programs of the National Institute
on Drug Abuse and the National Institute on Alcohol Abuse and
Alcoholism.
NR 58
TC 7
Z9 8
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD MAR
PY 2016
VL 173
IS 5
BP 856
EP 869
DI 10.1111/bph.13394
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DF9JM
UT WOS:000371677000006
PM 26603732
ER
PT J
AU Kang, XZ
Liu, HL
Onaitis, MW
Liu, ZS
Owzar, K
Han, YH
Su, L
Wei, YY
Hung, RJ
Brhane, Y
McLaughlin, J
Brennan, P
Bickeboller, H
Rosenberger, A
Houlston, RS
Caporaso, N
Landi, MT
Heinrich, J
Risch, A
Wu, XF
Ye, YQ
Christiani, DC
Amos, CI
Wei, QY
AF Kang, Xiaozheng
Liu, Hongliang
Onaitis, Mark W.
Liu, Zhensheng
Owzar, Kouros
Han, Younghun
Su, Li
Wei, Yongyue
Hung, Rayjean J.
Brhane, Yonathan
McLaughlin, John
Brennan, Paul
Bickeboeller, Heike
Rosenberger, Albert
Houlston, Richard S.
Caporaso, Neil
Landi, Maria Teresa
Heinrich, Joachim
Risch, Angela
Wu, Xifeng
Ye, Yuanqing
Christiani, David C.
Amos, Christopher I.
Wei, Qingyi
CA Transdisciplinary Res Canc Lung
TI Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a
meta-analysis of 14 463 cases and 44 188 controls
SO CARCINOGENESIS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; DISEASE; AMPLIFICATION;
ABNORMALITIES; VITILIGO; VARIANTS; CELLS; VISUALIZATION; INSTABILITY
AB After combining the summary results of SNPs in 106 centrosomal genes from eight published lung cancer GWASs, we found that two potential functional SNPs (rs151606 and rs12212247) in FGFR1OP were significantly associated with lung cancer risk.Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12 160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26 380 controls). A total of 44 significant SNPs with false discovery rate (FDR) a parts per thousand currency sign 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P (combined) = 8.032x10(-6)) was with rs151606 within FGFR1OP. The rs151606 T > G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T > C (P (combined) = 9.589x10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P (trend) = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis.
C1 [Kang, Xiaozheng; Liu, Hongliang; Onaitis, Mark W.; Liu, Zhensheng; Owzar, Kouros; Wei, Qingyi] Duke Univ, Med Ctr, Duke Canc Inst, 905 S LaSalle St, Durham, NC 27710 USA.
[Kang, Xiaozheng; Onaitis, Mark W.] Duke Univ, Med Ctr, Div Cardiovasc & Thorac Surg, Dept Surg, 905 S LaSalle St, Durham, NC 27710 USA.
[Kang, Xiaozheng] Peking Univ, Canc Hosp & Inst, Minist Educ,Dept Thorac Surg 1, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China.
[Liu, Hongliang; Liu, Zhensheng; Wei, Qingyi] Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA.
[Owzar, Kouros] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Han, Younghun; Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Community & Family Med, Hanover, NH 03755 USA.
[Su, Li; Wei, Yongyue; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Su, Li; Wei, Yongyue; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
[Hung, Rayjean J.; Brhane, Yonathan] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[McLaughlin, John] Publ Hlth Ontario, Toronto, ON M5T 3L9, Canada.
[Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, D-37073 Gottingen, Germany.
[Houlston, Richard S.] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
[Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Heinrich, Joachim] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
[Risch, Angela] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria.
[Wu, Xifeng; Ye, Yuanqing] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Wei, QY (reprint author), Duke Univ, Med Ctr, Duke Canc Inst, 905 S LaSalle St, Durham, NC 27710 USA.; Wei, QY (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA.
EM qingyi.wei@duke.edu
RI Hung, Rayjean/A-7439-2013; Risch, Angela/H-2669-2013;
OI Risch, Angela/0000-0002-8026-5505; Houlston, Richard/0000-0002-5268-0242
FU Duke Cancer Institute as part of the P30 Cancer Center Support Grant
[NIH CA014236]; Duke Cancer Institute, Duke University Medical Center
FX As Duke Cancer Institute members, Q.W., M.W.O., and K.O. acknowledge
support from the Duke Cancer Institute as part of the P30 Cancer Center
Support Grant (NIH CA014236). Q.W. was also supported by a start-up fund
from Duke Cancer Institute, Duke University Medical Center.
NR 61
TC 1
Z9 1
U1 3
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAR
PY 2016
VL 37
IS 3
BP 280
EP 289
DI 10.1093/carcin/bgw014
PG 10
WC Oncology
SC Oncology
GA DF9QP
UT WOS:000371696400006
PM 26905588
ER
PT J
AU Ma, JF
Yang, F
Mahida, SN
Zhao, L
Chen, XM
Zhang, ML
Sun, ZJ
Yao, Y
Zhang, YX
Zheng, GY
Dong, J
Feng, MJ
Zhang, R
Sun, J
Li, S
Wang, QS
Cao, HQ
Benjamin, EJ
Ellinor, PT
Li, YG
Tian, XL
AF Ma, Ji-Fang
Yang, Fan
Mahida, Saagar N.
Zhao, Ling
Chen, Xiaomin
Zhang, Micheal L.
Sun, Zhijun
Yao, Yan
Zhang, Yi-Xin
Zheng, Gu-Yan
Dong, Jie
Feng, Ming-Jun
Zhang, Rui
Sun, Jian
Li, Shuo
Wang, Qun-Shan
Cao, Huiqing
Benjamin, Emelia J.
Ellinor, Patrick T.
Li, Yi-Gang
Tian, Xiao-Li
TI TBX5 mutations contribute to early-onset atrial fibrillation in Chinese
and Caucasians
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Atrial fibrillation; TBX5; ANP; Connexin; Mutation
ID HOLT-ORAM-SYNDROME; CARDIAC CONDUCTION SYSTEM; TRANSCRIPTION FACTOR
TBX5; NATRIURETIC-PEPTIDE; COMMON VARIANTS; RISK-FACTORS; PR INTERVAL;
CONNEXIN40; GENE; POLYMORPHISMS
AB Atrial fibrillation (AF) is a common arrhythmia with an important heritable aspect. The genetic factors underlying AF have not been fully elucidated.
We screened six candidate genes (CAV1, KCNJ2, KCNQ1, NKX2.5, PITX2, and TBX5) for novel mutations in 139 patients of Chinese descent with early-onset AF and 576 controls. Four missense TBX5 mutations, p.R355C, p.Q376R, p.A428S, and p.S372L, were identified in evolutionarily conserved regions. We did not find any mutations in CAV1, KCNJ2, KCNQ1, NKX2.5, and PITX2. These mutations increased the expression of atrial natriuretic peptide (ANP) and connexin-40 (CX40) in the primarily cultured rat atrial myocytes but did not alter the expression of cardiac structural genes, atrial myosin heavy chain-alpha (MHC-alpha) and myosin light chain-2 alpha (MLC-2 alpha). Overexpression of p.R355C developed an atrial arrhythmia suggestive of paroxysmal AF in the zebrafish model. To replicate our findings, we screened TBX5 in 527 early-onset AF cases from the Massachusetts General Hospital AF study. A novel TBX5 deletion (Delta Asp118, p.D118del) was identified, while no TBX5 mutations were identified in 1176 control subjects.
Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40.
C1 [Ma, Ji-Fang; Zhang, Rui; Sun, Jian; Li, Shuo; Wang, Qun-Shan; Li, Yi-Gang] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Cardiol, Shanghai 200092, Peoples R China.
[Yang, Fan; Zhao, Ling; Zhang, Yi-Xin; Zheng, Gu-Yan; Dong, Jie; Cao, Huiqing; Tian, Xiao-Li] Peking Univ, Dept Human Populat Genet, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.
[Yang, Fan; Zhao, Ling; Zhang, Yi-Xin; Zheng, Gu-Yan; Dong, Jie; Cao, Huiqing; Tian, Xiao-Li] Peking Univ, Beijing Key Lab Cardiometabol Mol Med, IMM, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.
[Mahida, Saagar N.; Zhang, Micheal L.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Chen, Xiaomin; Feng, Ming-Jun] Ningbo Univ, Ningbo Hosp 1, Key Lab, 59 Liuting St, Ningbo 315010, Peoples R China.
[Chen, Xiaomin; Feng, Ming-Jun] Ningbo Univ, Ningbo Hosp 1, Ctr Cardiovasc, 59 Liuting St, Ningbo 315010, Peoples R China.
[Sun, Zhijun] Peoples Liberat Army Gen Hosp, Cardiovasc Dept, 28 Fuxing Rd, Beijing 100853, Peoples R China.
[Yao, Yan] Capital Med Univ, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02215 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Li, YG (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Cardiol, Shanghai 200092, Peoples R China.; Tian, XL (reprint author), Peking Univ, Dept Human Populat Genet, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.; Tian, XL (reprint author), Peking Univ, Beijing Key Lab Cardiometabol Mol Med, IMM, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.
EM drliyigang@outlook.com; tianxiaoli@pku.edu.cn
FU National Basic Research Program of China (973 program) [2013CB530700,
2007CB512100]; National Science Foundation of China [31221002, 81070154,
81270258]; Shanghai Excellent Academic Leaders Project [10xd1402800];
National Institutes of Health [1RO1HL104156, 1K24HL105780,
1RO1HL092577]; American Heart Association [13EIA14220013]
FX This study was supported by grants from the National Basic Research
Program of China (973 program) (2013CB530700 and 2007CB512100 to
X.L.T.), the National Science Foundation of China (31221002 to X.L.T.,
no. 81070154 and No. 81270258 to Y.G.L.), the Shanghai Excellent
Academic Leaders Project (grant number 10xd1402800 to Y.G.L.), the
National Institutes of Health to P.T.E. (1RO1HL104156 and 1K24HL105780
to P.T.E., 1RO1HL092577 to P.T.E. and E.J.B.), and the American Heart
Association (13EIA14220013 to P.T.E.).
NR 50
TC 4
Z9 4
U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 1
PY 2016
VL 109
IS 3
BP 442
EP 450
DI 10.1093/cvr/cvw003
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DF7ER
UT WOS:000371521100013
PM 26762269
ER
PT J
AU Chertow, DS
Palmore, TN
Masur, H
AF Chertow, Daniel S.
Palmore, Tara N.
Masur, Henry
TI Critical Care Medicine After the 2014-2015 Ebola Outbreak: Are We Ready
If It Happens Again? Foreword
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID INFECTION-CONTROL; VIRUS DISEASE; MERS; MANAGEMENT; SARS
C1 [Chertow, Daniel S.; Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIH, Hosp Epidemiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Chertow, DS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 16
TC 0
Z9 0
U1 4
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2016
VL 44
IS 3
BP 457
EP 459
DI 10.1097/CCM.0000000000001590
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA DF7HM
UT WOS:000371528700001
PM 26901541
ER
PT J
AU Zhu, ZQ
Liu, W
Gotlieb, V
AF Zhu, Ziqiang
Liu, Wei
Gotlieb, Vladimir
TI The rapidly evolving therapies for advanced melanoma-Towards
immunotherapy, molecular targeted therapy, and beyond
SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
LA English
DT Review
DE Advanced melanoma; Immunotherapy; Targeted therapy
ID CHIMERIC ANTIGEN RECEPTOR; BRAF-MUTANT MELANOMA; PHASE-III TRIAL;
METASTATIC MALIGNANT-MELANOMA; IPILIMUMAB PLUS DACARBAZINE; ADOPTIVE
CELL TRANSFER; OPEN-LABEL; MEK INHIBITION; T-CELLS; CANCER-IMMUNOTHERAPY
AB The incidence of melanoma in both males and females continues to rise during the past 40 years despite the stable or declining trends for most cancer types. Due to the tremendous advance in immunobiology and molecular biology, breakthroughs in both immunotherapies and molecular targeted therapies have recently revolutionized the standard of care for patients with advanced melanoma. In 2011, US Food and Drug Administration (FDA) approved ipilimumab, an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody for metastatic melanoma therapy. Since then, novel drugs including antibodies to programmed cell death 1 (PD-1) such as pembrolizumab and nivolumab (both approved in 2014), selective BRAF inhibitors such as vemurafenib (approved in 2011), dabrafenib (approved in 2013); and MEK inhibitor trametinib (approved in 2013), have greatly extended the potential of immunotherapy and molecular targeted therapy for advanced melanoma. All of which have been demonstrated a significant increase in overall survival rate, and long-term benefits in multiple large clinical trials. Several new agents and novel therapies are currently under phase III clinical trials with the hope of being approved in the near future. We already entered a golden era in oncology that are providing significant survival improvement. In the meantime, new challenges for clinicians also started to emerge. In this review, we presented the existing evidence for the newest treatments for advanced melanoma, including CTLA-4, PD-1/PD-L1 checkpoint inhibitors and BRAF, MEK inhibitors. We also discussed the strengths, limitations and challenges of using these novel therapies, and potential solutions as well as highlighted the areas requiring further research. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Zhu, Ziqiang] Brookdale Univ Hosp & Med Ctr, Dept Internal Med, One Brookdale Plaza, Brooklyn, NY 11212 USA.
[Liu, Wei] NCI, Metab & Canc Susceptibil Sect, NIH, Frederick, MD 21702 USA.
[Gotlieb, Vladimir] Brookdale Univ Hosp & Med Ctr, Div Hematol Oncol, One Brookdale Plaza, Brooklyn, NY 11212 USA.
RP Zhu, ZQ (reprint author), Brookdale Univ Hosp & Med Ctr, Dept Internal Med, One Brookdale Plaza, Brooklyn, NY 11212 USA.
EM zhuz2013@gmail.com
NR 124
TC 10
Z9 10
U1 4
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1040-8428
EI 1879-0461
J9 CRIT REV ONCOL HEMAT
JI Crit. Rev. Oncol./Hematol.
PD MAR
PY 2016
VL 99
BP 91
EP 99
DI 10.1016/j.critrevonc.2015.12.002
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA DG2YW
UT WOS:000371937700008
PM 26708040
ER
PT J
AU Frankl, JA
Thearle, MS
Desmarais, C
Bogardus, C
Krakoff, J
AF Frankl, Joseph A.
Thearle, Marie S.
Desmarais, Cindy
Bogardus, Clifton
Krakoff, Jonathan
TI T-cell receptor repertoire variation may be associated with type 2
diabetes mellitus in humans
SO DIABETES-METABOLISM RESEARCH AND REVIEWS
LA English
DT Article
DE autoimmunity; human; Pima Indians; survival analysis; T-cell receptor;
type 2 diabetes mellitus
ID PIMA-INDIANS; INSULIN-RESISTANCE; BETA-CHAINS; OBESITY; DIVERSITY;
IDENTIFICATION; PATHOGENESIS; INDIVIDUALS; ANTIBODIES; SECRETION
AB BackgroundRecent work in Pima Indians, a population with high rates of obesity and type 2 diabetes mellitus (T2DM), demonstrated that human leukocyte antigen haplotype DRB1*02 carriers have an increased acute insulin response and decreased risk for the development of T2DM, implicating loss of self-tolerance in the pathogenesis of T2DM. Advances in genomic sequencing have made T-cell receptor repertoire analysis a practical mode of investigation.
MethodsHigh-throughput sequencing of T-cell receptor complementarity-determining region 3 was carried out in male Pima Indians with normal glucose regulation (n=11; age=318years; %fat=30.28.7%) and the protective DRB1*02 haplotype versus those with T2DM without DRB1*02 (n=7; age=34 +/- 8years; %fat=31.2 +/- 4.7%). Findings were partially replicated in another cohort by assessing the predictive ability of T-cell receptor variation on risk of T2DM in Pima Indian men (n=27; age=28.9 +/- 7.1years; %fat=28.8 +/- 7.1%) and women (n=20; age=29 +/- 7.0years; %fat=37.1 +/- 6.8%) with baseline normal glucose regulation but without the protective haplotype who were invited to follow-up examinations as frequently as every 2years where diabetes status was assessed by a 75-g oral glucose tolerance test. Of these subjects, 13 developed diabetes.
ResultsT-cell receptor complementarity-determining region 3 length was shorter in those with T2DM, and a one-nucleotide decrease in complementarity-determining region 3 length was associated with a nearly threefold increase in risk for future diabetes. The frequency of one variable gene, TRBV7-8, was higher in those with T2DM. A 1% increase in TRBV7-8 frequency was associated with a greater than threefold increase in diabetes risk.
ConclusionsThese results indicate that T-cell autoimmunity may be an important component in progression to T2DM in Pima Indians. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Frankl, Joseph A.; Thearle, Marie S.; Bogardus, Clifton; Krakoff, Jonathan] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA.
[Desmarais, Cindy] Adapt Biotechnol, Seattle, WA USA.
RP Krakoff, J (reprint author), Phoenix Indian Med Ctr, 5th Floor,4212 N 16th St, Phoenix, AZ 85016 USA.
EM jkrakoff@mail.nih.gov
OI Frankl, Joseph/0000-0002-0156-3150
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 40
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1520-7560
J9 DIABETES-METAB RES
JI Diabetes-Metab. Res. Rev.
PD MAR
PY 2016
VL 32
IS 3
BP 297
EP 307
DI 10.1002/dmrr.2720
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DG1LK
UT WOS:000371829400008
PM 26408818
ER
PT J
AU Gadalla, SM
Pfeiffer, RM
Kristinsson, SY
Bjorkholm, M
Landgren, O
Greene, MH
AF Gadalla, S. M.
Pfeiffer, R. M.
Kristinsson, S. Y.
Bjorkholm, M.
Landgren, O.
Greene, M. H.
TI Brain tumors in patients with myotonic dystrophy: a population-based
study
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE brain; cancer; incidence; mortality; myotonic dystrophy; neoplasms
ID NERVOUS-SYSTEM TUMORS; WHITE-MATTER; CTG REPEAT; MUSCULAR-DYSTROPHY;
MALIGNANT-MELANOMA; DYSPLASTIC NEVI; CANCER-RISK; TYPE-1; EXPANSION;
GENE
AB Background and purposePatients with myotonic dystrophy (DM) are at high risk of brain cancer. This study describes the spectrum of brain neoplasms in DM patients.
MethodsData from 1119 DM patients identified from the National Swedish Patient Register between 1987 and 2007 were linked to the National Cancer and the Cause of Death Registers. Standardized incidence ratios (SIRs) and cumulative incidence to quantify the relative and absolute risks of brain neoplasms were calculated and the Kaplan-Meier estimator was used for survival analysis. Patient follow-up started at birth or the age at the start of Swedish cancer registration (1 January 1958) and ended at the age of brain neoplasm diagnosis, death or on 31 December 2007.
ResultsTwenty patients developed brain neoplasm during follow-up {median age 53, range 2-76 years, accounting for a five-fold excess risk of brain tumors during the patient lifetime [SIR = 5.4, 95% confidence interval (CI) 3.4-8.1, P = 1 x 10(-5)]}. Astrocytoma was the most common histological subtype (n = 16, 80%), and almost all cases (n = 19) developed after age 20. No statistically significant differences in gender-specific risks (SIR in men 6.3 and in women 3.8, P-heterogeneity 0.46) were observed. After accounting for competing mortality related to DM, the cumulative incidence of brain neoplasms reached 2.9% (95% CI 1.8%-4.7%) by age 70. Five-year survival after brain tumor diagnosis was 52% (95%CI 29%-75%) overall (number at risk 8) and 34% (95% CI 26%-47%) for malignant neoplasms (number at risk 5).
ConclusionDespite the high relative risk of DM-related brain tumors, the absolute risk is modest. Nonetheless, careful evaluation of DM patients with new central nervous system symptoms is warranted.
C1 [Gadalla, S. M.; Greene, M. H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Pfeiffer, R. M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden.
[Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Inst, Stockholm, Sweden.
[Kristinsson, S. Y.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Kristinsson, S. Y.] Landspitali Natl Univ Hosp, Dept Hematol, Reykjavik, Iceland.
[Landgren, O.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
RP Gadalla, SM (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM gadallas@mail.nih.gov
FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet
Foundations; National Cancer Institute, USA [N02CP31003-3]
FX This work was supported by the Swedish Cancer Society, Stockholm County
Council, the Karolinska Institutet Foundations, and the Intramural
Research Program of the National Cancer Institute, USA (contract
N02CP31003-3).
NR 36
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAR
PY 2016
VL 23
IS 3
BP 542
EP 547
DI 10.1111/ene.12886
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF5XV
UT WOS:000371427200021
PM 26508558
ER
PT J
AU Liberini, CG
Boyle, CN
Cifani, C
Venniro, M
Hope, BT
Lutz, TA
AF Liberini, Claudia G.
Boyle, Christina N.
Cifani, Carlo
Venniro, Marco
Hope, Bruce T.
Lutz, Thomas A.
TI Amylin receptor components and the leptin receptor are co-expressed in
single rat area postrema neurons
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE calcitonin receptor; laser capture microdissection; receptor
activity-modifying protein 1; receptor activity-modifying protein 2;
receptor activity-modifying protein 3
ID ACTIVITY-MODIFYING PROTEINS; VITRO AUTORADIOGRAPHIC LOCALIZATION;
VENTRAL TEGMENTAL AREA; GENE-RELATED PEPTIDE; DIET-INDUCED OBESITY;
CALCITONIN-RECEPTOR; FOOD-INTAKE; CIRCUMVENTRICULAR ORGANS; ENERGY
HOMEOSTASIS; BRAIN
AB Amylin is a pancreatic -cell hormone that acts as a satiating signal to inhibit food intake by binding to amylin receptors (AMYs) and activating a specific neuronal population in the area postrema (AP). AMYs are heterodimers that include a calcitonin receptor (CTR) subunit [CTR isoform a or b (CTRa or CTRb)] and a member of the receptor activity-modifying proteins (RAMPs). Here, we used single-cell quantitative polymerase chain reaction to assess co-expression of AMY subunits in AP neurons from rats that were injected with amylin or vehicle. Because amylin interacts synergistically with the adipokine leptin to reduce body weight, we also assessed the co-expression of AMY and the leptin receptor isoform b (LepRb) in amylin-activated AP neurons. Single cells were collected from Wistar rats and from transgenic Fos-GFP rats that express green fluorescent protein (GFP) under the control of the Fos promoter. We found that the mRNAs of CTRa, RAMP1, RAMP2 and RAMP3 were all co-expressed in single AP neurons. Moreover, most of the CTRa+ cells co-expressed more than one of the RAMPs. Amylin down-regulated RAMP1 and RAMP3 but not CTR mRNAs in AMY+ neurons, suggesting a possible negative feedback mechanism of amylin at its own primary receptors. Interestingly, amylin up-regulated RAMP2 mRNA. We also found that a high percentage of single cells that co-expressed all components of a functional AMY expressed LepRb mRNA. Thus, single AP cells expressed both AMY and LepRb, which formed a population of first-order neurons that presumably can be directly activated by amylin and, at least in part, also by leptin.
C1 [Liberini, Claudia G.; Boyle, Christina N.; Lutz, Thomas A.] Univ Zurich UZH, Vetsuisse Fac, Inst Vet Physiol, Winterthurerstr 260, CH-8057 Zurich, Switzerland.
[Liberini, Claudia G.; Lutz, Thomas A.] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland.
[Liberini, Claudia G.] Univ Zurich, Vetsuisse Fac, Zurich Ctr Clin Studies, Zurich, Switzerland.
[Cifani, Carlo] Univ Camerino, Pharmacol Unit, Sch Pharm, I-62032 Camerino, Italy.
[Cifani, Carlo; Venniro, Marco; Hope, Bruce T.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Boyle, CN (reprint author), Univ Zurich UZH, Vetsuisse Fac, Inst Vet Physiol, Winterthurerstr 260, CH-8057 Zurich, Switzerland.
EM boyle@vetphys.uzh.ch
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
FU Swiss National Science Foundation; Center for Integrative Human
Physiology of the University of Zurich; Italian Ministry of University;
[FIRB-RBFR12DELS]
FX This work was supported by the Swiss National Science Foundation and the
Center for Integrative Human Physiology of the University of Zurich. The
laboratory stay of C.C. in NIDA/NIH was supported by Italian Ministry of
University and Research Grant FIRB-RBFR12DELS to C.C. The authors
gratefully acknowledge the Center for Clinical Studies, the Center for
Microscopy and Image Analysis (University of Zurich, Zurich,
Switzerland) and Dr Savina Adamo for technical support.
NR 45
TC 2
Z9 2
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAR
PY 2016
VL 43
IS 5
BP 653
EP 661
DI 10.1111/ejn.13163
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DG2PN
UT WOS:000371909800006
PM 26750109
ER
PT J
AU Chuang, K
Nguyen, E
Sergeev, Y
Badea, TC
AF Chuang, Katherine
Nguyen, Eileen
Sergeev, Yuri
Badea, Tudor C.
TI Novel Heterotypic Rox Sites for Combinatorial Dre Recombination
Strategies
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE site specific recombination; Cre recombination; Dre recombinase; gene
targeting
ID CRE-MEDIATED RECOMBINATION; LOXP SPACER REGION; DNA RECOMBINATION;
MAMMALIAN-CELLS; VECTORS; SYSTEM; MULTIPLE; BACTERIOPHAGE-P1;
SPECIFICITY; EXPRESSION
AB Site-specific recombinases (SSRs) such as Cre are widely used in gene targeting and genetic approaches for cell labeling and manipulation. They mediate DNA strand exchange between two DNA molecules at dedicated recognition sites. Precise understanding of the Cre recombination mechanism, including the role of individual base pairs in its loxP target site, guided the generation of mutant lox sites that specifically recombine with themselves but not with the wild type loxP. This has led to the development of a variety of combinatorial Cre-dependent genetic strategies, such as multicolor reporters, irreversible inversions, or recombination-mediated cassette exchange. Dre, a Cre-related phage integrase that recognizes roxP sites, does not cross-react with the Cre-loxP system, but has similar recombination efficiency. We have previously described intersectional genetic strategies combining Dre and Cre. We now report a mutagenesis screen aimed at identifying roxP base pairs critical for self-recognition. We describe several rox variant sites that are incompatible with roxP, but are able to efficiently recombine with themselves in either purified systems or bacterial and eukaryotic tissue culture systems. These newly identified rox sites are not recognized by Cre, thus enabling potential combinatorial strategies involving Cre, Dre, and target loci including multiple loxP and roxP variants.
C1 [Chuang, Katherine; Nguyen, Eileen; Sergeev, Yuri; Badea, Tudor C.] NEI, Retinal Circuits Dev & Genet Unit, NIH, Bethesda, MD 20892 USA.
RP Badea, TC (reprint author), N NRL DIR NEI, Retinal Circuits Dev & Genet Unit, NIH, Bldg 6,Room 331B,6 Ctr Dr, Bethesda, MD 20892 USA.
EM badeatc@mail.nih.gov
FU National Eye Institute (National Institutes of Health, Bethesda)
FX The authors acknowledge Michael Cashel for helpful discussions and
suggestions, and providing the pGB2 vector; Beverly Wu for constructing
and testing the pAAVPTPY vector; and Edward Giniger, Harold Burgess,
Kathryn Tabor, and Chi-Hon Lee for critical reading of the manuscript
and insightful comments. Funding provided to T.B. and Y.S. by intramural
funds of the National Eye Institute (National Institutes of Health,
Bethesda).
NR 39
TC 0
Z9 0
U1 1
U2 2
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAR 1
PY 2016
VL 6
IS 3
BP 559
EP 571
DI 10.1534/g3.115.025841
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA DG1MA
UT WOS:000371831000007
ER
PT J
AU Miller, JG
Liu, Y
Williams, CW
Smith, HE
O'Connell, KF
AF Miller, Jacqueline G.
Liu, Yan
Williams, Christopher W.
Smith, Harold E.
O'Connell, Kevin F.
TI The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication
in Caenorhabditis elegans
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE centriole duplication; C. elegans; transcriptional regulation; E2F/DP1;
SAS-6
ID PLK4-RELATED KINASE ZYG-1; C-ELEGANS; CENTROSOME DUPLICATION;
HUMAN-CELLS; PROTEIN SPD-2; LIN-35 RB; PLK4; RECRUITMENT; BIOGENESIS;
CEP152
AB Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole. Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.
C1 [Miller, Jacqueline G.; Liu, Yan; Williams, Christopher W.; O'Connell, Kevin F.] NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr,Room 2A07, Bethesda, MD 20892 USA.
[Smith, Harold E.] NIDDK, Genom Core, NIH, Bethesda, MD 20892 USA.
RP O'Connell, KF (reprint author), NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr,Room 2A07, Bethesda, MD 20892 USA.
EM kevino@mail.nih.gov
FU National Institutes of Health Office of Research Infrastructure Programs
[P40 OD010440]; National Institutes of Health; National Institute of
Diabetes and Digestive and Kidney Diseases
FX We thank Valerie Reinke for generously providing the
DPL-1-GFP-expressing C. elegans strain and Andy Golden for some of the
CRISPR reagents. We also thank Geraldine Seydoux and Alex Paix for
sharing protocols for CRISPR technology. Some strains were provided by
the Caenorhabditis Genetics Center, which is funded by the National
Institutes of Health Office of Research Infrastructure Programs (P40
OD010440). This work was supported by the Intramural Research Program of
the National Institutes of Health and the National Institute of Diabetes
and Digestive and Kidney Diseases.
NR 83
TC 1
Z9 1
U1 0
U2 1
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAR 1
PY 2016
VL 6
IS 3
BP 709
EP 720
DI 10.1534/g3.115.025577
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DG1MA
UT WOS:000371831000020
PM 26772748
ER
PT J
AU Petersen, T
Townsend, K
Gordon, LA
Sidharthan, S
Silk, R
Nelson, A
Gross, C
Calderon, M
Proschan, M
Osinusi, A
Polis, MA
Masur, H
Kottilil, S
Kohli, A
AF Petersen, Tess
Townsend, Kerry
Gordon, Lori A.
Sidharthan, Sreetha
Silk, Rachel
Nelson, Amy
Gross, Chloe
Calderon, Monica
Proschan, Michael
Osinusi, Anu
Polis, Michael A.
Masur, Henry
Kottilil, Shyam
Kohli, Anita
TI High adherence to all-oral directly acting antiviral HCV therapy among
an inner-city patient population in a phase 2a study
SO HEPATOLOGY INTERNATIONAL
LA English
DT Article
DE HCV; DAA; Adherence; MEMS
ID HEPATITIS-C VIRUS; GENOTYPE 1; TREATMENT-NAIVE; LEDIPASVIR; SOFOSBUVIR;
RIBAVIRIN; COMBINATION; MEDICATION; INFECTION; CIRRHOSIS
AB As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described.
Medication adherence was measured in 60 HCV, genotype-1, treatment-na < ve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report.
Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report.
Adherence to short courses of DAA therapy with 1-3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.
C1 [Petersen, Tess; Sidharthan, Sreetha; Silk, Rachel; Masur, Henry; Kohli, Anita] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Townsend, Kerry; Osinusi, Anu; Polis, Michael A.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gordon, Lori A.] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
[Gordon, Lori A.] Xavier Univ Louisiana, New Orleans, LA USA.
[Silk, Rachel; Nelson, Amy; Gross, Chloe; Osinusi, Anu; Kottilil, Shyam] Univ Maryland, Inst Human Virol, Div Infect Dis, Baltimore, MD 21201 USA.
[Gross, Chloe; Calderon, Monica; Kohli, Anita] SAIC Frederick Inc, Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program,Frederick Natl Lab Ca, Frederick, MD USA.
[Calderon, Monica] US FDA, Silver Spring, MD USA.
[Proschan, Michael] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Osinusi, Anu] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
[Kohli, Anita] Creighton Univ, St Josephs Hosp, Div Hepatol, Phoenix, AZ USA.
[Kohli, Anita] Creighton Univ, Med Ctr, Sch Med, Phoenix, AZ USA.
[Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, N222,725 West Lombard St,Room S222, Baltimore, MD 21201 USA.
RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.; Kottilil, S (reprint author), Univ Maryland, Inst Human Virol, Div Infect Dis, Baltimore, MD 21201 USA.; Kottilil, S (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, N222,725 West Lombard St,Room S222, Baltimore, MD 21201 USA.
EM SKottilil@ihv.umaryland.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases; NIH; Gilead Sciences
FX The project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. ClinicalTrials.gov no. NCT01805882. The
research was supported in part by the National Institute of Allergy and
Infectious Diseases. Study medications were provided by Gilead Sciences,
Inc., and the study was partially funded by a Collaborate Research and
Development Agreement between NIH and Gilead Sciences. The study
involves human subjects, and all subjects signed informed consent
approved by the NIAID IRB. We would like to acknowledge the
contributions of Colleen Kotb, NP, Colleen Hadigan, MD, and Senora
Mitchell for their clinic support.
NR 31
TC 5
Z9 5
U1 3
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1936-0533
EI 1936-0541
J9 HEPATOL INT
JI Hepatol. Int.
PD MAR
PY 2016
VL 10
IS 2
BP 310
EP 319
DI 10.1007/s12072-015-9680-7
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DG0YM
UT WOS:000371792100010
PM 26612014
ER
PT J
AU Joyce, E
Chung, C
Badloe, S
Odutayo, K
Desai, A
Givertz, MM
Nohria, A
Lakdawala, NK
Stewart, GC
Young, M
Weintraub, J
Stevenson, LW
Lewis, EF
AF Joyce, Emer
Chung, Christine
Badloe, Sabrina
Odutayo, Kayode
Desai, Akshay
Givertz, Michael M.
Nohria, Anju
Lakdawala, Neal K.
Stewart, Garrick C.
Young, Michelle
Weintraub, Joanne
Stevenson, Lynne W.
Lewis, Eldrin F.
TI Variable Contribution of Heart Failure to Quality of Life in Ambulatory
Heart Failure With Reduced, Better, or Preserved Ejection Fraction
SO JACC-HEART FAILURE
LA English
DT Article
DE better left; heart failure; left ventricular ejection fraction; quality
of life
ID EUROPEAN ASSOCIATION; ECHOCARDIOGRAPHIC-ASSESSMENT; AMERICAN SOCIETY;
RECOMMENDATIONS; DYSFUNCTION; PREDICTOR; ADULTS
AB OBJECTIVES The relative contribution of heart failure (HF) compared with other medical and nonmedical factors on diminished quality of life (QOL) across subtypes with reduced, better, and preserved left ventricular ejection fraction (LVEF) in a large ambulatory HF population was evaluated.
BACKGROUND Dominant factors influencing limited QOL in patients with HF have not been investigated.
METHODS Before routine HF clinic visits, 726 patients with ambulatory HF (mean age 56 +/- 15 years, 37% women) completed a 1-page questionnaire that assessed QOL and relative contributions of HF compared with other medical and nonmedical factors to their QOL limitations. Visual analogue scales were used to assess overall QOL, breathing, and energy level. Results were compared across reduced (57%), preserved (16%) and better (improvement in LVEF >= 50%) (19%) subtypes.
RESULTS Just under one-half of patients (48%) rated QOL as limited dominantly by HF, 19% rated HF and medical problems as equally limiting, 18% cited medical problems as dominant, and 15% cited nonmedical factors. Patients with HF with better LVEF had the highest overall QOL score and less dyspnea burden than those with HF with preserved EF. Independent correlates of HF-dominated diminished QOL were prior cardiac surgery, worse New York Heart Association functional class, renin-angiotensin-aldosterone antagonism, use of diuretic agents;lower body mass index, lower LVEF, and tack of arthritis or history of cancer.
CONCLUSIONS Fewer than one-half of patients with ambulatory HF rated HF as the greatest limitation to their QOL, suggesting that this important outcome will be difficult to affect by HF-targeted therapies alone, particularly in those with higher LVEFs and comorbidities. Patients with HF with better LVEF represent a distinct subtype with better overall QOL. (J Am Coll Cardiol HF 2016;4:184-93) (C) 2016 by the American College of Cardiology Foundation.
C1 Brigham & Womens Hosp, Ctr Adv Heart Dis, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Joyce, Emer] NHLBI, Heart Failure Network, Bethesda, MD USA.
RP Lewis, EF (reprint author), Brigham & Womens Hosp, Ctr Adv Heart Dis, 75 Francis St, Boston, MA 02115 USA.
EM eflewis@partners.org
NR 29
TC 3
Z9 3
U1 3
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD MAR
PY 2016
VL 4
IS 3
BP 184
EP 193
DI 10.1016/j.jchf.2015.12.011
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DF9AC
UT WOS:000371651600003
PM 26874379
ER
PT J
AU Morgand, M
Bouvin-Pley, M
Plantier, JC
Moreau, A
Alessandri, E
Simon, F
Pace, CS
Pancera, M
Ho, DD
Poignard, P
Bjorkman, PJ
Mouquet, H
Nussenzweig, MC
Kwong, PD
Baty, D
Chames, P
Braibant, M
Barin, F
AF Morgand, Marion
Bouvin-Pley, Melanie
Plantier, Jean-Christophe
Moreau, Alain
Alessandri, Elodie
Simon, Francois
Pace, Craig S.
Pancera, Marie
Ho, David D.
Poignard, Pascal
Bjorkman, Pamela J.
Mouquet, Hugo
Nussenzweig, Michel C.
Kwong, Peter D.
Baty, Daniel
Chames, Patrick
Braibant, Martine
Barin, Francis
TI V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of
HIV-1
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; diversity; antibodies; epitopes; neutralization
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GROUP-O; MONOCLONAL-ANTIBODIES;
GP41-GP120 INTERFACE; DEPENDENT EPITOPE; POTENT; VACCINE; DOMAIN; GP120;
BROAD
AB Background:
Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI).
Material and Methods:
The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab).
Results:
Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04-9.39 mu g/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 mu g/mL, except 2 group O strains.
Conclusion:
The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants.
C1 [Morgand, Marion; Bouvin-Pley, Melanie; Moreau, Alain; Braibant, Martine; Barin, Francis] Univ Tours, INSERM, U966, Tours, France.
[Plantier, Jean-Christophe; Alessandri, Elodie] Univ Rouen, Rouen, France.
[Plantier, Jean-Christophe; Alessandri, Elodie] CHU Charles Nicolle, Rouen, France.
[Simon, Francois] Hop St Louis, Virol Lab, Paris, France.
[Pace, Craig S.; Ho, David D.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 1230 York Ave, New York, NY 10021 USA.
[Pancera, Marie; Kwong, Peter D.] NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Poignard, Pascal] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Bjorkman, Pamela J.] CALTECH, Pasadena, CA 91125 USA.
[Mouquet, Hugo] Inst Pasteur, Dept Immunol, Lab Humoral Response Pathogens, F-75724 Paris, France.
[Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
[Baty, Daniel; Chames, Patrick] INSERM, CRCM, U1068, F-13258 Marseille, France.
[Baty, Daniel; Chames, Patrick] Inst J Paoli I Calmettes, Marseille, France.
[Baty, Daniel; Chames, Patrick] CNRS, UMR7258, Marseille, France.
[Baty, Daniel; Chames, Patrick] AMU, UM105, Marseille, France.
[Barin, Francis] CHU Bretonneau, Ctr Natl Reference VIH, Lab Bacteriol Virol, 2 Bd Tonnelle, F-37044 Tours, France.
RP Barin, F (reprint author), CHU Bretonneau, CNR VIH, Virol Lab, 2 Bd Tonnelle, F-37044 Tours, France.
EM fbarin@med.univ-tours.fr
RI poignard, pascal/N-6678-2013; Chames, Patrick/R-1800-2016;
OI Chames, Patrick/0000-0002-6104-6286; Baty, Daniel/0000-0001-8443-4444;
PLANTIER, Jean-Christophe/0000-0001-6417-4083
FU Agence Nationale de Recherche sur le SIDA et les Hepatites (ANRS, Paris,
France); ANRS; Region Centre; Sidaction (France)
FX Supported by the Agence Nationale de Recherche sur le SIDA et les
Hepatites (ANRS, Paris, France). M. Morgand was supported by a doctoral
fellowship from the ANRS. M. Bouvin-Pley was supported by doctoral
fellowships from the Region Centre and Sidaction (France).
NR 37
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2016
VL 71
IS 3
BP 237
EP 245
DI 10.1097/QAI.0000000000000854
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DF7FB
UT WOS:000371522100001
PM 26413851
ER
PT J
AU Rutstein, SE
Pettifor, AE
Phiri, S
Kamanga, G
Hoffman, IF
Hosseinipour, MC
Rosenberg, NE
Nsona, D
Pasquale, D
Tegha, G
Powers, KA
Phiri, M
Tembo, B
Chege, W
Miller, WC
AF Rutstein, Sarah E.
Pettifor, Audrey E.
Phiri, Sam
Kamanga, Gift
Hoffman, Irving F.
Hosseinipour, Mina C.
Rosenberg, Nora E.
Nsona, Dominic
Pasquale, Dana
Tegha, Gerald
Powers, Kimberly A.
Phiri, Mcleod
Tembo, Bisweck
Chege, Wairimu
Miller, William C.
TI Incorporating Acute HIV Screening into Routine HIV Testing at Sexually
Transmitted Infection Clinics, and HIV Testing and Counseling Centers in
Lilongwe, Malawi
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV testing and counseling; AHI screening; Malawi; acute HIV infection
ID IMMUNODEFICIENCY-VIRUS-INFECTION; UNITED-STATES; SOUTH-AFRICA;
COST-EFFECTIVENESS; COASTAL KENYA; REAL-TIME; TRANSMISSION; POPULATION;
PREVENTION; MEN
AB Background and Objectives:
Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi.
Methods:
We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening.
Results:
Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)-a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL >= 10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%).
Conclusions:
The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered.
C1 [Rutstein, Sarah E.] Univ N Carolina, Dept Hlth Policy & Management, CB 7411, Chapel Hill, NC 27599 USA.
[Rutstein, Sarah E.; Hoffman, Irving F.; Hosseinipour, Mina C.; Miller, William C.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27599 USA.
[Pettifor, Audrey E.; Pasquale, Dana; Powers, Kimberly A.; Miller, William C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Phiri, Sam; Nsona, Dominic; Phiri, Mcleod; Tembo, Bisweck] Lighthouse Trust, Lilongwe, Malawi.
[Kamanga, Gift; Hosseinipour, Mina C.; Rosenberg, Nora E.; Tegha, Gerald] UNC Project, Lilongwe, Malawi.
[Chege, Wairimu] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Rutstein, SE (reprint author), Univ N Carolina, Dept Hlth Policy & Management, CB 7411, Chapel Hill, NC 27599 USA.
EM sarah_rutstein@med.unc.edu
FU NIH/NIAID [R01 AI083059]; NIH/NIMH [F30 MH098731]; NIH/NIGMS
[T32-GM008719]
FX Supported by NIH/NIAID R01 AI083059. S. E. R. was supported by NIH/NIMH
(F30 MH098731) and NIH/NIGMS (T32-GM008719).
NR 41
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2016
VL 71
IS 3
BP 272
EP 280
DI 10.1097/QAI.0000000000000853
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DF7FB
UT WOS:000371522100005
PM 26428231
ER
PT J
AU Mirembe, BG
Kelly, CW
Mgodi, N
Greenspan, S
Dai, JY
Mayo, A
Piper, J
Akello, CA
Kiweewa, FM
Magure, T
Nakabiito, C
Marrazzo, JM
AF Mirembe, Brenda G.
Kelly, Clifton W.
Mgodi, Nyaradzo
Greenspan, Susan
Dai, James Y.
Mayo, Ashley
Piper, Jeanna
Akello, Carolyne A.
Kiweewa, Flavia M.
Magure, Tsitsi
Nakabiito, Clemensia
Marrazzo, Jeanne M.
TI Bone Mineral Density Changes Among Young, Healthy African Women
Receiving Oral Tenofovir for HIV Preexposure Prophylaxis
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE tenofovir; bone density; preexposure prophylaxis; HIV prevention;
African women
ID ANTIRETROVIRAL PROPHYLAXIS; HIV-1-INFECTED PATIENTS;
ABACAVIR-LAMIVUDINE; DISOPROXIL FUMARATE; FRACTURES; EMTRICITABINE;
COMBINATION; EFAVIRENZ; INFECTION; EFFICACY
AB Background:
Limited data exist on effect of tenofovir disoproxil fumarate (TDF) when used for preexposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV-negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF compared with placebo on BMD among women enrolled in an HIV-1 PrEP trial.
Methods:
HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) by dual-energy x-ray absorptiometry at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks.
Results:
Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%-100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH.
Conclusions:
TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women.
C1 [Mirembe, Brenda G.; Akello, Carolyne A.; Kiweewa, Flavia M.; Nakabiito, Clemensia] Makerere Univ Johns Hopkins Univ Res Collaborat, Upper Mulago Hill Rd,POB 23491, Kampala, Uganda.
[Kelly, Clifton W.; Dai, James Y.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, 1124 Columbia St, Seattle, WA 98104 USA.
[Mgodi, Nyaradzo; Magure, Tsitsi] Univ Zimbabwe, Univ Calif San Francisco, Dept Obstet & Gynaecol, Harare, Zimbabwe.
[Greenspan, Susan] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Mayo, Ashley] FHI 360, Durham, NC USA.
[Piper, Jeanna] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Marrazzo, Jeanne M.] Univ Washington, Dept Med & Global Hlth, Seattle, WA 98195 USA.
RP Mirembe, BG (reprint author), Makerere Univ Johns Hopkins Univ Res Collaborat, Upper Mulago Hill Rd,POB 23491, Kampala, Uganda.
EM bgati@mujhu.org
OI Kelly, Clifton/0000-0003-0794-3901; Marrazzo, Jeanne/0000-0002-9277-7364
FU National Institute of Allergy and Infectious Diseases [UM1AI068633,
UM1AI068615, UM1AI1106707]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Maternal
Health, of the US National Institutes of Health; NIH [UM1AI069436,
UM1AI069530, P30AG024827]
FX Supported by the National Institute of Allergy and Infectious Diseases
(UM1AI068633, UM1AI068615, UM1AI1106707) with cofunding from Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the National Institute of Maternal Health, all components of the US
National Institutes of Health. Additional funding to the clinical sites
was provided by NIH grants UM1AI069436 (UZ-UCSF CTU) and UM1AI069530
(MU-JHU CTU), and P30AG024827 (Osteoporosis Research Center at the
University of Pittsburgh). Study medications were provided by Gilead
Sciences.
NR 29
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2016
VL 71
IS 3
BP 287
EP 294
DI 10.1097/QAI.0000000000000858
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DF7FB
UT WOS:000371522100007
PM 26866954
ER
PT J
AU Volkow, ND
Swanson, JM
Evins, AE
DeLisi, LE
Meier, MH
Gonzalez, R
Bloomfield, MAP
Curran, HV
Baler, R
AF Volkow, Nora D.
Swanson, James M.
Evins, A. Eden
DeLisi, Lynn E.
Meier, Madeline H.
Gonzalez, Raul
Bloomfield, Michael A. P.
Curran, H. Valerie
Baler, Ruben
TI Effects of Cannabis Use on Human Behavior, Including Cognition,
Motivation, and Psychosis: A Review
SO JAMA PSYCHIATRY
LA English
DT Review
ID HIGH-POTENCY CANNABIS; SWEDISH CONSCRIPTS; MEMORY IMPAIRMENT;
GENETIC-VARIATION; ADULT PSYCHOSIS; SEX-DIFFERENCES; SCHIZOPHRENIA;
RISK; ADOLESCENT; MARIJUANA
AB With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.
C1 [Volkow, Nora D.; Baler, Ruben] NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
[Swanson, James M.] Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA.
[Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA.
[Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA.
[DeLisi, Lynn E.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA USA.
[Meier, Madeline H.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA.
[Gonzalez, Raul] Florida Int Univ, Dept Psychol, Ctr Children & Families, Miami, FL 33199 USA.
[Bloomfield, Michael A. P.] UCL, Div Psychiat, London, England.
[Bloomfield, Michael A. P.] Hammersmith Hosp, MRC, Ctr Clin Sci, Psychiat Imaging Grp, London, England.
[Curran, H. Valerie] UCL, Clin Psychopharmacol Unit, Clin Hlth Psychol, London, England.
RP Volkow, ND (reprint author), NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Forum Pharmaceuticals from the National Institute of Drug Abuse [R01
DA030992]; Pfizer from the National Institute of Drug Abuse [R01
DA021245]; National Institutes of Health Intramural Research Program
(National Institute on Alcohol Abuse and Alcoholism)
[DE-AC02-98CH10886]; National Institute of Drug Abuse [R01 DA021576];
United Kingdom Medical Research Council; National Institute of Health
Research; British Medical Association; United Kingdom National Institute
of Health Research Biomedical Research Council; United Kingdom Medical
Research Council grant
FX This work was financed in part by support from the following: Forum
Pharmaceuticals to support grant R01 DA030992 from the National
Institute of Drug Abuse and Pfizer to support grant R01 DA021245 from
the National Institute of Drug Abuse (Dr Evins); National Institutes of
Health Intramural Research Program (National Institute on Alcohol Abuse
and Alcoholism) using the infrastructure of the Brookhaven National
Laboratory under contract DE-AC02-98CH10886 (Dr Volkow); grant R01
DA021576 from the National Institute of Drug Abuse (Dr DeLisi); United
Kingdom Medical Research Council, National Institute of Health Research,
and British Medical Association (Dr Bloomfield); and a grant from the
United Kingdom National Institute of Health Research Biomedical Research
Council to King's College London and a United Kingdom Medical Research
Council grant (Dr Curran).
NR 84
TC 32
Z9 32
U1 55
U2 120
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAR
PY 2016
VL 73
IS 3
BP 292
EP 297
DI 10.1001/jamapsychiatry.2015.3278
PG 6
WC Psychiatry
SC Psychiatry
GA DF8NC
UT WOS:000371613500017
PM 26842658
ER
PT J
AU Guardado, P
Olivera, A
Rusch, HL
Roy, M
Martin, C
Lejbman, N
Lee, H
Gill, JM
AF Guardado, Pedro
Olivera, Anlys
Rusch, Heather L.
Roy, Michael
Martin, Christiana
Lejbman, Natasha
Lee, Hwyunhwa
Gill, Jessica M.
TI Altered gene expression of the innate immune, neuroendocrine, and
nuclear factor-kappa B (NF-kappa B) systems is associated with
posttraumatic stress disorder in military personnel
SO JOURNAL OF ANXIETY DISORDERS
LA English
DT Article
DE Gene expression; Innate immune; Neuroendocrine; NF-kappa B; PTSD; Trauma
ID TRAUMATIC BRAIN-INJURY; QUALITY-OF-LIFE; COMBAT VETERANS; IMPROVED
SLEEP; ANIMAL-MODEL; PTSD RISK; DEPRESSION; SYMPTOMS; MEMORY;
INFLAMMATION
AB Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n =28) and matched controls without PTSD (n =27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of <= 1.5 relative fold change at a false discovery rate of <= 5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-kappa B systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk. (c) 2016 Published by Elsevier Ltd.
C1 [Guardado, Pedro; Olivera, Anlys; Rusch, Heather L.; Martin, Christiana; Lejbman, Natasha; Gill, Jessica M.] NINR, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rusch, Heather L.] Henry M Jackson Fdn Adv Mil Med, 6720A Rockledge Dr 100, Bethesda, MD 20817 USA.
[Roy, Michael] Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
[Lee, Hwyunhwa] Univ Nevada, Sch Nursing, 4505 South Maryland Pkwy, Las Vegas, NV 89154 USA.
RP Gill, JM (reprint author), 1 Cloister Court 256, Bethesda, MD 20892 USA.
EM gillj@mail.nih.gov
NR 65
TC 4
Z9 4
U1 5
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-6185
EI 1873-7897
J9 J ANXIETY DISORD
JI J. Anxiety Disord.
PD MAR
PY 2016
VL 38
BP 9
EP 20
DI 10.1016/j.janxdis.2015.12.004
PG 12
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DF6EQ
UT WOS:000371449100002
PM 26751122
ER
PT J
AU Wentzensen, N
Schiffman, M
Palmer, T
Arbyn, M
AF Wentzensen, Nicolas
Schiffman, Mark
Palmer, Timothy
Arbyn, Marc
TI Triage of HPV positive women in cervical cancer screening
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Review
DE HPV; Triage; Cervical cancer screening; Cytology; p16/Ki-67; Methylation
ID RANDOMIZED CONTROLLED-TRIAL; ASC-US CYTOLOGY; HUMAN-PAPILLOMAVIRUS;
INTRAEPITHELIAL NEOPLASIA; METHYLATION ANALYSIS; CLINICAL VALIDATION;
MILD DYSKARYOSIS; DNA METHYLATION; RISK; GUIDELINES
AB Despite HPV vaccines, screening will remain central for decades to control cervical cancer. Recently, HPV testing alone or with cytology was introduced as an alternative to cytology screening. However, most HPV infections are harmless and additional tests are required to identify women with progressing infections or precancer. With three options for primary screening, and without clear strategies for triage of screen-positive women, there is great confusion about the best approach. Also, increasing HPV vaccination coverage will lead to lower disease prevalence, and force new screening approaches. Currently recommended triage strategies for primary HPV screening include HPV genotyping for HPV16 and HPV18 and cytology. Other alternatives that are currently evaluated include p16/Ki-67 dual stain cytology, host methylation, and viral methylation testing. Clinical management of women with cervical cancer screening results is moving to use risk thresholds rather than individual test results. Specific risk thresholds have been defined for return to primary screening, repeat testing, referral to colposcopy, and immediate treatment. Choice of test algorithms is based on comparison of absolute risk estimates from triage tests with established clinical thresholds. Importantly, triage tests need to be evaluated together with the primary screening test and the downstream clinical management. An optimal integrated screening and triage strategy should reassure the vast majority of women that they are at very low risk of cervical cancer, send the women at highest risk to colposcopy at the right time, when disease can be colposcopically detected, and minimize the intermediate risk group that requires continued surveillance. Published by Elsevier B.V.
C1 [Wentzensen, Nicolas; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Palmer, Timothy] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Arbyn, Marc] Sci Inst Publ Hlth, Belgian Canc Ctr, Unit Canc Epidemiol, Brussels, Belgium.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
FU seventh framework program of DG Research of the European Commission,
through the COHEAHR Network [603019]; European Union; KCE-Centre
d'Expertise (Brussels, Belgium); German Guideline Program in Oncology
(German Cancer Aid project) [110163]; Intramural Research Program of the
US National Cancer Institute
FX M. Arbyn is supported by the seventh framework program of DG Research of
the European Commission, through the COHEAHR Network (grant No 603019),
the Joint Action CANCON which has received funding from the European
Union in the framework of the Health Programme (2008-13), the KCE-Centre
d'Expertise (Brussels, Belgium) and the German Guideline Program in
Oncology (German Cancer Aid project # 110163). N. Wentzensen and M.
Schiffman are supported by the Intramural Research Program of the US
National Cancer Institute. NCI has received cervical cancer screening
assays in-kind or at reduced cost from BD, Cepheid, Hologic, and Roche.
NR 68
TC 14
Z9 14
U1 7
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
EI 1873-5967
J9 J CLIN VIROL
JI J. Clin. Virol.
PD MAR
PY 2016
VL 76
SU 1
BP S49
EP S55
DI 10.1016/j.jcv.2015.11.015
PG 7
WC Virology
SC Virology
GA DG0VZ
UT WOS:000371785200007
PM 26643050
ER
PT J
AU Thurber, K
Tycko, R
AF Thurber, Kent
Tycko, Robert
TI Low-temperature dynamic nuclear polarization with helium-cooled samples
and nitrogen-driven magic-angle spinning
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Solid state NMR; Dynamic nuclear polarization; Low-temperature NMR;
Magic-angle spinning; Protein structure
ID SOLID-STATE NMR; MAGNETIC-RESONANCE; CONFORMATIONAL DISTRIBUTIONS; HIV-1
GP120; V3 LOOP; 25 K; SPECTROSCOPY; PROTEIN; TARGET; CALMODULIN
AB We describe novel instrumentation for low-temperature solid state nuclear magnetic resonance (NMR) with dynamic nuclear polarization (DNP) and magic-angle spinning (MAS), focusing on aspects of this instrumentation that have not been described in detail in previous publications. We characterize the performance of an extended interaction oscillator (EIO) microwave source, operating near 264 GHz with 1.5 W output power, which we use in conjunction with a quasi-optical microwave polarizing system and a MAS NMR probe that employs liquid helium for sample cooling and nitrogen gas for sample spinning. Enhancement factors for cross-polarized 13C NMR signals in the 100-200 range are demonstrated with DNP at 25 K. The dependences of signal amplitudes on sample temperature, as well as microwave power, polarization, and frequency, are presented. We show that sample temperatures below 30 K can be achieved with helium consumption rates below 1.3 l/h. To illustrate potential applications of this instrumentation in structural studies of biochemical systems, we compare results from low-temperature DNP experiments on a calmodulin-binding peptide in its free and bound states. Published by Elsevier Inc.
C1 [Thurber, Kent; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, a component of the National Institutes of
Health; NIH Intramural AIDS Targeted Antiviral Program
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, a
component of the National Institutes of Health, and by the NIH
Intramural AIDS Targeted Antiviral Program. We thank Nicholas Anthis and
Marius Clore for providing the unlabeled calmodulin for experiments in
Fig, 6, and Wai-Ming Yau for synthesizing the labeled M13 peptide.
NR 46
TC 2
Z9 2
U1 14
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD MAR
PY 2016
VL 264
BP 99
EP 106
DI 10.1016/j.jmr.2016.01.011
PG 8
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA DG0JJ
UT WOS:000371750800012
PM 26920835
ER
PT J
AU Tabb, DL
Wang, X
Carr, SA
Clauser, KR
Mertins, P
Chambers, MC
Holman, JD
Wang, J
Zhang, B
Zimmerman, LJ
Chen, X
Gunawardena, HP
Davies, SR
Ellis, MJC
Li, SQ
Townsend, RR
Boja, ES
Ketchum, KA
Kinsinger, CR
Mesri, M
Rodriguez, H
Liu, T
Kim, S
McDermott, JE
Payne, SH
Petyuk, VA
Rodland, KD
Smith, RD
Yang, F
Chan, DW
Zhang, B
Zhang, H
Zhang, Z
Zhou, JY
Liebler, DC
AF Tabb, David L.
Wang, Xia
Carr, Steven A.
Clauser, Karl R.
Mertins, Philipp
Chambers, Matthew C.
Holman, Jerry D.
Wang, Jing
Zhang, Bing
Zimmerman, Lisa J.
Chen, Xian
Gunawardena, Harsha P.
Davies, Sherri R.
Ellis, Matthew J. C.
Li, Shunqiang
Townsend, R. Reid
Boja, Emilsy S.
Ketchum, Karen A.
Kinsinger, Christopher R.
Mesri, Mehdi
Rodriguez, Henry
Liu, Tao
Kim, Sangtae
McDermott, Jason E.
Payne, Samuel H.
Petyuk, Vladislav A.
Rodland, Karin D.
Smith, Richard D.
Yang, Feng
Chan, Daniel W.
Zhang, Bai
Zhang, Hui
Zhang, Zhen
Zhou, Jian-Ying
Liebler, Daniel C.
TI Reproducibility of Differential Proteomic Technologies in CPTAC
Fractionated Xenografts
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE Differential proteomics; label-free; iTRAQ quality control; xenografts;
technology assessment; CPTAC
ID SPECTROMETRY-BASED PROTEOMICS; ABSOLUTE QUANTITATION ITRAQ; RELATIVE
PROTEIN ABUNDANCE; TANDEM MASS-SPECTROMETRY; DATABASE SEARCH TOOL;
SHOTGUN PROTEOMICS; LABEL-FREE; PEPTIDE IDENTIFICATION; ISOBARIC TAGS;
CANCER
AB The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilar workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation (source code is available from http://homepages.uc.edu/ similar to wang2x7/Research.htm). From these assessments, we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61 to 93% of the time. When comparing across different instruments and quantitative technologies, using multiple replicates, differential genes were reproduced by other data sets from 67 to 99% of the time. Projecting gene differences to biological pathways and networks increased the degree of similarity. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation.
C1 [Tabb, David L.; Chambers, Matthew C.; Holman, Jerry D.; Wang, Jing; Zhang, Bing] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA.
[Zimmerman, Lisa J.; Liebler, Daniel C.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
[Wang, Xia] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA.
[Carr, Steven A.; Clauser, Karl R.; Mertins, Philipp] Broad Inst MIT & Harvard, Prote Platform, Cambridge, MA 02142 USA.
[Chen, Xian; Gunawardena, Harsha P.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Davies, Sherri R.; Ellis, Matthew J. C.; Li, Shunqiang; Townsend, R. Reid] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Boja, Emilsy S.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.
[Ketchum, Karen A.] Enterprise Sci & Comp Inc, Rockville, MD 20850 USA.
[Liu, Tao; Kim, Sangtae; McDermott, Jason E.; Payne, Samuel H.; Petyuk, Vladislav A.; Rodland, Karin D.; Smith, Richard D.; Yang, Feng] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
[Chan, Daniel W.; Zhang, Bai; Zhang, Hui; Zhang, Zhen; Zhou, Jian-Ying] Johns Hopkins Univ, JHMI, Baltimore, MD 21231 USA.
[Chan, Daniel W.; Zhang, Bai; Zhang, Hui; Zhang, Zhen; Zhou, Jian-Ying] Johns Hopkins Univ, Div Clin Chem, Baltimore, MD 21231 USA.
[Ellis, Matthew J. C.] Baylor Coll Med, Smith Breast Ctr, Houston, TX 77030 USA.
RP Tabb, DL (reprint author), Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA.
EM dtabb@sun.ac.za
RI Smith, Richard/J-3664-2012;
OI Smith, Richard/0000-0002-2381-2349; Payne, Samuel/0000-0002-8351-1994
FU Washington University in St. Louis [U24-CA-160035]; Vanderbilt
University [U24-CA-159988]; Broad Institute [U24-CA-160034]; Pacific
Northwest National Lab [U24-CA-160019]; Johns Hopkins University
[U24-CA-160036]; CTSA [UL1 RR024992]; Leidos Biomedical Research
[13XS029]; [BCTR0707808]; [KG090422]; [HHSN261201100106C]
FX CPTAC includes support from U24-CA-160035 (Washington University in St.
Louis), U24-CA-159988 (Vanderbilt University), U24-CA-160034 (Broad
Institute), U24-CA-160019 (Pacific Northwest National Lab), and
U24-CA-160036 (Johns Hopkins University). The PDX models were developed
through grants to Matthew J. Ellis by Susan G. Komen for the Cure (grant
nos. BCTR0707808 and KG090422). The HAMLET Core that provided the
xenograft tumors was supported by CTSA grant UL1 RR024992. Public
dissemination of underlying raw data at the CPTAC Public Portal was made
possible through contract HHSN261201100106C to ESAC, Inc. Biological
network analysis was enabled through Leidos Biomedical Research contract
13XS029.
NR 59
TC 6
Z9 6
U1 3
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2016
VL 15
IS 3
BP 691
EP 706
DI 10.1021/acs.jproteome.5b00859
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DG0KQ
UT WOS:000371754100003
PM 26653538
ER
PT J
AU Rudnick, PA
Markey, SP
Roth, J
Mirokhin, Y
Yan, XJ
Tchekhovskoi, DV
Edwards, NJ
Thangudu, RR
Ketchum, KA
Kinsinger, CR
Mesri, M
Rodriguez, H
Stein, SE
AF Rudnick, Paul A.
Markey, Sanford P.
Roth, Jeri
Mirokhin, Yuri
Yan, Xinjian
Tchekhovskoi, Dmitrii V.
Edwards, Nathan J.
Thangudu, Ratna R.
Ketchum, Karen A.
Kinsinger, Christopher R.
Mesri, Mehdi
Rodriguez, Henry
Stein, Stephen E.
TI A Description of the Clinical Proteomic Tumor Analysis Consortium
(CPTAC) Common Data Analysis Pipeline
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE proteomics data resource; bioinformatics; cancer; CPTAC; data analysis
pipeline
ID PEPTIDE IDENTIFICATION; MASS-SPECTROMETRY; SEARCH; CANCER
AB The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has produced large proteomics data sets from the mass spectrometric interrogation of tumor samples previously analyzed by The Cancer Genome Atlas (TCGA) program. The availability of the genomic and proteomic data is enabling proteogenomic study for both reference (i.e., contained in major sequence databases) and nonreference markers of cancer. The CPTAC laboratories have focused on colon, breast, and ovarian tissues in the first round of analyses; spectra from these data sets were produced from 2D liquid chromatography tandem mass spectrometry analyses and represent deep coverage. To reduce the variability introduced by disparate data analysis platforms (e.g., software packages, versions, parameters, sequence databases, etc.), the CPTAC Common Data Analysis Platform (CDAP) was created. The CDAP produces both peptide-spectrum-match (PSM) reports and gene-level reports. The pipeline processes raw mass spectrometry data according to the following: (1) peak-picking and quantitative data extraction, (2) database searching, (3) gene based protein parsimony, and (4) false-discovery rate-based filtering. The pipeline also produces localization scores for the phosphopeptide enrichment studies using the PhosphoRS program. Quantitative information for each of the data sets is specific to the sample processing, with PSM and protein reports containing the spectrum-level or gene-level ("rolled-up") precursor peak areas and spectral counts for label-free or reporter ion log-ratios for 4plex iTRAQ The reports are available in simple tab delimited formats and, for the PSM-reports, in mzIdentML. The goal of the CDAP is to provide standard, uniform reports for all of the CPTAC data to enable comparisons between different samples and cancer types as well as across the major omics fields.
C1 [Rudnick, Paul A.] Spectragen Informat, Bainbridge Isl, WA 98110 USA.
[Rudnick, Paul A.; Markey, Sanford P.; Roth, Jeri; Mirokhin, Yuri; Yan, Xinjian; Tchekhovskoi, Dmitrii V.; Stein, Stephen E.] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
[Edwards, Nathan J.] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA.
[Thangudu, Ratna R.; Ketchum, Karen A.] ESAC Inc, Rockville, MD 20850 USA.
[Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.
RP Rudnick, PA (reprint author), Spectragen Informat, Bainbridge Isl, WA 98110 USA.; Rudnick, PA (reprint author), NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
EM paul.rudnick@spectragen-informatics.com
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The authors thank all of the contributing CPTAC laboratories for their
work generating these large datasets and for valuable feedback during
the design and testing phases of the pipeline. In particular, the
authors would like to thank Karl Clauser and Philip Mertins (Broad
Institute); Sam Payne, Matt Monroe, and Tao Liu (PNNL); David Fenyo
(NYU); Rob Slebos, Bing Zhang, and David Tabb (Vanderbilt University
Medical Center); Bai Zhang (JHU); and Alexey Nesvizhskii (UMich). We are
also grateful to Nuno Bandeira and June Snedecor for their help with
assessing phosphosite assignment algorithms. NCI CPTAC 2 NIST/NCI IAA
ACO13004 ("Proteomics Measurement Quality Assurance Program"). This
project has been funded in whole or in part with Federal funds from
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views of policies of the Department of Health
and Human Services; in addition, mention of trade names, commercial
products, or organizations does not imply endorsement by the U.S.
Government. Certain commercial instruments are identified in this
document. Such identification does not imply recommendation or
endorsement by the National Institute of Standards and Technology; in
addition, it does not imply that the products identified are necessarily
the best available for the purpose.
NR 17
TC 1
Z9 1
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2016
VL 15
IS 3
BP 1023
EP 1032
DI 10.1021/acs.jproteome.5b01091
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DG0KQ
UT WOS:000371754100035
PM 26860878
ER
PT J
AU Ruggles, KV
Tang, ZJ
Wang, XY
Grover, H
Askenazi, M
Teubl, J
Cao, S
McLellan, MD
Clauser, KR
Tabb, DL
Mertins, P
Slebos, R
Erdmann-Gilmore, P
Li, SQ
Gunawardena, HP
Xie, L
Liu, T
Zhou, JY
Sun, SS
Hoadley, KA
Perou, CM
Chen, X
Davies, SR
Maher, CA
Kinsinger, CR
Rodland, KD
Zhang, H
Zhang, Z
Ding, L
Townsend, RR
Rodriguez, H
Chan, D
Smith, RD
Liebler, DC
Carr, SA
Payne, S
Ellis, MJ
Fenyo, D
AF Ruggles, Kelly V.
Tang, Zuojian
Wang, Xuya
Grover, Himanshu
Askenazi, Manor
Teubl, Jennifer
Cao, Song
McLellan, Michael D.
Clauser, Karl R.
Tabb, David L.
Mertins, Philipp
Slebos, Robbert
Erdmann-Gilmore, Petra
Li, Shunqiang
Gunawardena, Harsha P.
Xie, Ling
Liu, Tao
Zhou, Jian-Ying
Sun, Shisheng
Hoadley, Katherine A.
Perou, Charles M.
Chen, Xian
Davies, Sherri R.
Maher, Christopher A.
Kinsinger, Christopher R.
Rodland, Karen D.
Zhang, Hui
Zhang, Zhen
Ding, Li
Townsend, R. Reid
Rodriguez, Henry
Chan, Daniel
Smith, Richard D.
Liebler, Daniel C.
Carr, Steven A.
Payne, Samuel
Ellis, Matthew J.
Fenyo, David
TI An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic
Mutations and Novel Splicing Events in Cancer
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID RNA-SEQ DATA; MASS-SPECTROMETRY DATA; PROTEIN IDENTIFICATION;
BREAST-CANCER; GENOME; DISCOVERY; DATABASES; VARIANTS; TRANSCRIPTOME;
VALIDATION
AB Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (<0.1%). Peptides mapping to DNA-detected SNVs without a detectable mRNA transcript were also observed, suggesting that transcriptome coverage was incomplete (approximate to 80%). In contrast to germline variants, somatic variants were less likely to be detected at the peptide level in the basal-like tumor than in the luminal tumor, raising the possibility of differential translation or protein degradation effects. In conclusion, this large-scale proteogenomic integration allowed us to determine the degree to which mutations are translated and identify gaps in sequence coverage, thereby benchmarking current technology and progress toward whole cancer proteome and transcriptome analysis.
C1 [Ruggles, Kelly V.; Tang, Zuojian; Wang, Xuya; Grover, Himanshu; Teubl, Jennifer; Fenyo, David] NYU, Sch Med, 227 East 30th St, New York, NY 10016 USA.
[Askenazi, Manor] Biomed Hosting LLC, Arlington, MA USA.
[Cao, Song; McLellan, Michael D.; Erdmann-Gilmore, Petra; Li, Shunqiang; Davies, Sherri R.; Maher, Christopher A.; Ding, Li; Townsend, R. Reid; Ellis, Matthew J.] Washington Univ, 660 South Euclid Ave, St Louis, MO 63110 USA.
[Clauser, Karl R.; Mertins, Philipp; Carr, Steven A.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Tabb, David L.; Slebos, Robbert; Liebler, Daniel C.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Gunawardena, Harsha P.; Xie, Ling; Hoadley, Katherine A.; Perou, Charles M.; Chen, Xian] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Liu, Tao; Rodland, Karen D.; Smith, Richard D.; Payne, Samuel] Pacific NW Natl Lab, 902 Battelle Blvd, Richland, WA 99354 USA.
[Zhou, Jian-Ying; Sun, Shisheng; Zhang, Hui; Zhang, Zhen; Chan, Daniel] Johns Hopkins Univ, Baltimore, MD USA.
[Kinsinger, Christopher R.; Rodriguez, Henry] NCI, Off Canc Clin Proteom Res, Bethesda, MD 20892 USA.
RP Fenyo, D (reprint author), NYU, Sch Med, 227 East 30th St, New York, NY 10016 USA.; Ellis, MJ (reprint author), Washington Univ, 660 South Euclid Ave, St Louis, MO 63110 USA.; Payne, S (reprint author), Pacific NW Natl Lab, 902 Battelle Blvd, Richland, WA 99354 USA.
EM Samuel.Payne@pnnl.gov; mellis@dom.wustl.edu; david@fenyolab.org
RI Smith, Richard/J-3664-2012;
OI Smith, Richard/0000-0002-2381-2349; Perou, Charles/0000-0001-9827-2247;
Fenyo, David/0000-0001-5049-3825; Ruggles, Kelly/0000-0002-0152-0863
FU National Cancer Institute (NCI) CPTAC award [U24CA159988, U24CA160019,
U24CA160034, U24CA160035, U24CA160036]; CPTAC contract from Leidos
Biomedical Research, Inc. [13XS068]
FX This work was supported by National Cancer Institute (NCI) CPTAC awards
U24CA159988, U24CA160019, U24CA160034, U24CA160035, U24CA160036 and by
CPTAC contract 13XS068 from Leidos Biomedical Research, Inc. This work
has utilized computing resources at the High Performance Computing
Facility of the Center for Health Informatics and Bioinformatics at the
NYU Langone Medical Center. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 31
TC 11
Z9 12
U1 2
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD MAR
PY 2016
VL 15
IS 3
SI SI
BP 1060
EP 1071
DI 10.1074/mcp.M115.056226
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DG2KB
UT WOS:000371894700024
PM 26631509
ER
PT J
AU Berndt, SI
Camp, NJ
Skibola, CF
Vijai, J
Wang, ZM
Gu, J
Nieters, A
Kelly, RS
Smedby, KE
Monnereau, A
Cozen, W
Cox, A
Wang, SS
Lan, Q
Teras, LR
Machado, M
Yeager, M
Brooks-Wilson, AR
Hartge, P
Purdue, MP
Birmann, BM
Vajdic, CM
Cocco, P
Zhang, YW
Giles, GG
Zeleniuch-Jacquotte, A
Lawrence, C
Montalvan, R
Burdett, L
Hutchinson, A
Ye, YQ
Call, TG
Shanafelt, TD
Novak, AJ
Kay, NE
Liebow, M
Cunningham, JM
Allmer, C
Hjalgrim, H
Adami, HO
Melbye, M
Glimelius, B
Chang, ET
Glenn, M
Curtin, K
Cannon-Albright, LA
Diver, WR
Link, BK
Weiner, GJ
Conde, L
Bracci, PM
Riby, J
Arnett, DK
Zhi, DG
Leach, JM
Holly, EA
Jackson, RD
Tinker, LF
Benavente, Y
Sala, N
Casabonne, D
Becker, N
Boffetta, P
Brennan, P
Foretova, L
Maynadie, M
McKay, J
Staines, A
Chaffee, KG
Achenbach, SJ
Vachon, CM
Goldin, LR
Strom, SS
Leis, JF
Weinberg, JB
Caporaso, NE
Norman, AD
De Roos, AJ
Morton, LM
Severson, RK
Riboli, E
Vineis, P
Kaaks, R
Masala, G
Weiderpass, E
Chirlaque, MD
Vermeulen, RCH
Travis, RC
Southey, MC
Milne, RL
Albanese, D
Virtamo, J
Weinstein, S
Clavel, J
Zheng, TZ
Holford, TR
Villano, DJ
Maria, A
Spinelli, JJ
Gascoyne, RD
Connors, JM
Bertrand, KA
Giovannucci, E
Kraft, P
Kricker, A
Turner, J
Ennas, MG
Ferri, GM
Miligi, L
Liang, LM
Ma, BS
Huang, JY
Crouch, S
Park, JH
Chatterjee, N
North, KE
Snowden, JA
Wright, J
Fraumeni, JF
Offit, K
Wu, XF
de Sanjose, S
Cerhan, JR
Chanock, SJ
Rothman, N
Slager, SL
AF Berndt, Sonja I.
Camp, Nicola J.
Skibola, Christine F.
Vijai, Joseph
Wang, Zhaoming
Gu, Jian
Nieters, Alexandra
Kelly, Rachel S.
Smedby, Karin E.
Monnereau, Alain
Cozen, Wendy
Cox, Angela
Wang, Sophia S.
Lan, Qing
Teras, Lauren R.
Machado, Moara
Yeager, Meredith
Brooks-Wilson, Angela R.
Hartge, Patricia
Purdue, Mark P.
Birmann, Brenda M.
Vajdic, Claire M.
Cocco, Pierluigi
Zhang, Yawei
Giles, Graham G.
Zeleniuch-Jacquotte, Anne
Lawrence, Charles
Montalvan, Rebecca
Burdett, Laurie
Hutchinson, Amy
Ye, Yuanqing
Call, Timothy G.
Shanafelt, Tait D.
Novak, Anne J.
Kay, Neil E.
Liebow, Mark
Cunningham, Julie M.
Allmer, Cristine
Hjalgrim, Henrik
Adami, Hans-Olov
Melbye, Mads
Glimelius, Bengt
Chang, Ellen T.
Glenn, Martha
Curtin, Karen
Cannon-Albright, Lisa A.
Diver, W. Ryan
Link, Brian K.
Weiner, George J.
Conde, Lucia
Bracci, Paige M.
Riby, Jacques
Arnett, Donna K.
Zhi, Degui
Leach, Justin M.
Holly, Elizabeth A.
Jackson, Rebecca D.
Tinker, Lesley F.
Benavente, Yolanda
Sala, Nuria
Casabonne, Delphine
Becker, Nikolaus
Boffetta, Paolo
Brennan, Paul
Foretova, Lenka
Maynadie, Marc
McKay, James
Staines, Anthony
Chaffee, Kari G.
Achenbach, Sara J.
Vachon, Celine M.
Goldin, Lynn R.
Strom, Sara S.
Leis, Jose F.
Weinberg, J. Brice
Caporaso, Neil E.
Norman, Aaron D.
De Roos, Anneclaire J.
Morton, Lindsay M.
Severson, Richard K.
Riboli, Elio
Vineis, Paolo
Kaaks, Rudolph
Masala, Giovanna
Weiderpass, Elisabete
Chirlaque, Maria-Dolores
Vermeulen, Roel C. H.
Travis, Ruth C.
Southey, Melissa C.
Milne, Roger L.
Albanese, Demetrius
Virtamo, Jarmo
Weinstein, Stephanie
Clavel, Jacqueline
Zheng, Tongzhang
Holford, Theodore R.
Villano, Danylo J.
Maria, Ann
Spinelli, John J.
Gascoyne, Randy D.
Connors, Joseph M.
Bertrand, Kimberly A.
Giovannucci, Edward
Kraft, Peter
Kricker, Anne
Turner, Jenny
Ennas, Maria Grazia
Ferri, Giovanni M.
Miligi, Lucia
Liang, Liming
Ma, Baoshan
Huang, Jinyan
Crouch, Simon
Park, Ju-Hyun
Chatterjee, Nilanjan
North, Kari E.
Snowden, John A.
Wright, Josh
Fraumeni, Joseph F.
Offit, Kenneth
Wu, Xifeng
de Sanjose, Silvia
Cerhan, James R.
Chanock, Stephen J.
Rothman, Nathaniel
Slager, Susan L.
TI Meta-analysis of genome-wide association studies discovers multiple loci
for chronic lymphocytic leukemia
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TRANSCRIPTION FACTOR EOMESODERMIN; FAS GENE-MUTATIONS; SUSCEPTIBILITY
LOCI; FOLLICULAR LYMPHOMA; RISK; VARIANTS; EXPRESSION; BANK1;
PRIORITIZATION; CLASSIFICATION
AB Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
C1 [Berndt, Sonja I.; Lan, Qing; Machado, Moara; Hartge, Patricia; Goldin, Lynn R.; Caporaso, Neil E.; Morton, Lindsay M.; Albanese, Demetrius; Weinstein, Stephanie; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Camp, Nicola J.] Huntsman Canc Inst, Dept Internal Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA.
[Camp, Nicola J.] Univ Utah, Sch Med, Salt Lake City, UT 84112 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques; Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques; Arnett, Donna K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35233 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Vijai, Joseph; Villano, Danylo J.; Maria, Ann; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Wang, Zhaoming; Yeager, Meredith; Burdett, Laurie; Hutchinson, Amy] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA.
[Gu, Jian; Ye, Yuanqing; Strom, Sara S.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Baden Wurttembe, Germany.
[Kelly, Rachel S.; Adami, Hans-Olov; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Liang, Liming; Ma, Baoshan; Huang, Jinyan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.
[Smedby, Karin E.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden.
[Monnereau, Alain; Clavel, Jacqueline] Sorbonne Paris Cite CRESS, INSERM, Ctr Res Epidemiol & Stat, Epidemiol Childhood & Adolescent Canc Grp, F-94807 Paris, France.
[Monnereau, Alain; Clavel, Jacqueline] Univ Paris 05, F-75270 Paris, France.
[Monnereau, Alain] Inst Bergonie, Registre Hemopathies Malignes Gironde, F-33076 Bordeaux, France.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Cox, Angela; Snowden, John A.; Wright, Josh] Univ Sheffield, Dept Oncol, Sheffield S10 1NS, S Yorkshire, England.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Duarte, CA 91030 USA.
[Teras, Lauren R.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Machado, Moara] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, BR-31270901 Belo Horizonte, MG, Brazil.
[Brooks-Wilson, Angela R.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Purdue, Mark P.] Ontario Hlth Study, Toronto, ON M5G 0A3, Canada.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Vajdic, Claire M.] Univ New S Wales, Ctr Big Data Res Hlth, Sydney, NSW 2052, Australia.
[Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, I-09042 Cagliari, Italy.
[Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Langone Med Ctr, Perlmutter Canc Ctr, New York, NY 10016 USA.
[Lawrence, Charles; Montalvan, Rebecca] WESTAT Corp, Rockville, MD 20850 USA.
[Call, Timothy G.; Kay, Neil E.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Shanafelt, Tait D.; Novak, Anne J.; Liebow, Mark] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Allmer, Cristine; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Norman, Aaron D.; Cerhan, James R.; Slager, Susan L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Hjalgrim, Henrik; Melbye, Mads] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Adami, Hans-Olov; Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Melbye, Mads] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Glimelius, Bengt] Uppsala Univ, Dept Immunol Genet & Pathol, S-75105 Uppsala, Sweden.
[Chang, Ellen T.] Exponent Inc, Ctr Epidemiol & Computat Biol, Hlth Sci, Menlo Pk, CA 94025 USA.
[Chang, Ellen T.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA.
[Glenn, Martha] Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Curtin, Karen; Cannon-Albright, Lisa A.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA.
[Cannon-Albright, Lisa A.] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA.
[Link, Brian K.; Weiner, George J.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Zhi, Degui; Leach, Justin M.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35233 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Tinker, Lesley F.; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA.
[Benavente, Yolanda; de Sanjose, Silvia] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona 08908, Spain.
[Benavente, Yolanda; Chirlaque, Maria-Dolores; de Sanjose, Silvia] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08036, Spain.
[Sala, Nuria] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona 08908, Spain.
[Sala, Nuria] Catalan Inst Oncol IDIBELL, Translat Res Lab, Barcelona 08908, Spain.
[Casabonne, Delphine] Inst Catala Oncol, IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona 08908, Spain.
[Casabonne, Delphine] CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain.
[Becker, Nikolaus; Kaaks, Rudolph] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Baden Wurttembe, Germany.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Brennan, Paul; McKay, James] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.
[Foretova, Lenka] MF MU, Brno 65653, Czech Republic.
[Maynadie, Marc] Univ Burgundy, Registre Hemopathies Malignes Cote dOr, EA 4184, F-21070 Dijon, France.
[Maynadie, Marc] Dijon Univ Hosp, F-21070 Dijon, France.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[Leis, Jose F.] Mayo Clin, Div Hematol Oncol, Phoenix, AZ 85054 USA.
[Weinberg, J. Brice] Duke Univ, Dept Med, Durham, NC 27710 USA.
[Weinberg, J. Brice] VA Med Ctr, Durham, NC 27710 USA.
[De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London W2 1PG, England.
[Vineis, Paolo] Human Genet Fdn, I-10126 Turin, Italy.
[Masala, Giovanna] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, I-50139 Florence, Italy.
[Weiderpass, Elisabete] Arctic Univ Norway, Univ Tromso, Dept Community Med, Fac Hlth Sci, N-9037 Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, N-0304 Oslo, Norway.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Genet Epidemiol Grp, FI-00250 Helsinki, Finland.
[Chirlaque, Maria-Dolores] Murcia Reg Hlth Author, Dept Epidemiol, E-30008 Murcia, Spain.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
[Vermeulen, Roel C. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Chron Dis Prevent Unit, FI-00271 Helsinki, Finland.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Dept Stat, New Haven, CT 06520 USA.
[Spinelli, John J.] BC Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
[Gascoyne, Randy D.; Connors, Joseph M.] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada.
[Gascoyne, Randy D.] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 1Z3, Canada.
[Connors, Joseph M.] Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kraft, Peter; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Turner, Jenny] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, N Ryde, NSW 2113, Australia.
[Ennas, Maria Grazia] Univ Cagliari, Dept Biomed Sci, I-09042 Cagliari, Italy.
[Ferri, Giovanni M.] Univ Bari, Interdisciplinary Dept Med, I-70124 Bari, Italy.
[Miligi, Lucia] Canc Prevent & Res Inst ISPO, Environm & Occupat Epidemiol Unit, I-50139 Florence, Italy.
[Ma, Baoshan] Dalian Maritime Univ, Coll Informat Sci & Technol, Dalian 116026, Liaoning Provin, Peoples R China.
[Crouch, Simon] Univ York, Dept Hlth Sci, York Y010 5DD, N Yorkshire, England.
[Park, Ju-Hyun] Dongguk Univ, Dept Stat, Seoul 100715, South Korea.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Snowden, John A.; Wright, Josh] Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Dept Haematol, Sheffield S10 2TN, S Yorkshire, England.
RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM berndts@mail.nih.gov
RI Brooks-Wilson, Angela/E-9399-2012; de Sanjose Llongueras,
Silvia/H-6339-2014; Weiderpass, Elisabete/M-4029-2016; Clavel,
Jacqueline/Q-2750-2016; Vermeulen, Roel/F-8037-2011;
OI Giles, Graham/0000-0003-4946-9099; Brooks-Wilson,
Angela/0000-0003-1009-6408; Weiderpass, Elisabete/0000-0003-2237-0128;
Clavel, Jacqueline/0000-0002-3616-7676; Vermeulen,
Roel/0000-0003-4082-8163; Sala, Nuria/0000-0003-3585-7613; albright,
lisa/0000-0003-2602-3668; Joseph, Vijai/0000-0002-7933-151X; Masala,
Giovanna/0000-0002-5758-9069; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303
FU intramural programme of the Division of Cancer Epidemiology and
Genetics; National Cancer Institute [30 CA086862, P30 CA15083, P30
CA015083]; US National Institutes of Health; Intramural Research Program
of the NIH; Department of Health and Human Services [N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C]; Canadian Institutes for
Health Research (CIHR); Michael Smith Foundation for Health Research;
American Cancer Society; NCI; Division of Cancer Epidemiology and
Genetics; Centers for Disease Control and Prevention National Program of
Cancer Registries; National Cancer Institute Surveillance Epidemiology
and End Results program; Leukaemia AMP; Lymphoma Research; Association
pour la Recherche contre le Cancer (ARC); Institut National du Cancer
(INCa); Fondation de France; Fondation contre la Leucemie; Agence
nationale de securite sanitaire de l'alimentation, de l'environnement et
du travail (ANSES); Coordinated Action [006438, SP23-CT-2005-006438];
HuGeF (Human Genetics Foundation), Torino, Italy; European Commission
[QLK4-CT-2000-00422, FOOD-CT-2006-023103]; Spanish Ministry of Health
[CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10, RTIC
RD06/0020/0095]; Marato de TV3 Foundation [051210]; Agencia de Gestiod'
AjutsUniversitarisi de Recerca-Generalitat de Catalunya [2014SRG756];
NIH [NO1-CO-12400, CA118444, CA148690, CA92153, K08CA134919, CA167552,
CA149445, CA098122, CA098566, K07 CA115687, R01 CA92153, CA186107,
CA87969, CA49449, 5R01 CA69669-02, CA1046282, CA154643,
HHSN261201000026C]; Compagnia di San Paolo-Programma Oncologia; Federal
Office for Radiation Protection [StSch4261, StSch4420]; Jose Carreras
Leukemia Foundation [DJCLS-R12/23]; German Federal Ministry for
Education and Research [BMBF-01-EO-1303]; Health Research Board,
Ireland; MH CZ-DRO (MMCI) [00209805]; RECAMO [CZ.1.05/2.1.00/03.0101];
Fondation de France and Association de Recherche Contre le Cancer;
National Cancer Institute and Veterans Affairs Research Service;
Leukemia AMP; Lymphoma Society Career Development Award; Bernstein
Family Fund for Leukemia and Lymphoma Research; National Center for
Advancing Translational Science [UL1 TR000135]; NCI Specialized Programs
of Research Excellence (SPORE) in Human Cancer [P50 CA97274]; Henry J.
Predolin Foundation; Italian Association for Cancer Research (AIRC)
[11855]; Fondazione Banco di Sardegna; Regione Autonoma della Sardegna
(LR7) [CRP-59812/2012]; VicHealth and Cancer Council Victoria;
Australian NHMRC [209057, 251553, 504711]; infrastructure provided by
Cancer Council Victoria; Instituto de Salud Carlos III (ISCIII-Spanish
Government) [CIBERESP, PI11/01810, PI14/01219, RCESP C03/09]; Agencia de
Gestiod' AjutsUniversitarisi de Recerca (AGAUR)-Generalitat de Catalunya
(Catalonian Government) [2014SGR756]; Center for Translational and
Public Health Genomics; MSKCC-Geoffrey Beene Cancer Research Grant,
Lymphoma Foundation [LF5541]; Barbara K. Lipman Lymphoma Research Fund
[74419]; Robert and Kate Niehaus Clinical Cancer Genetics Research
Initiative [57470]; ENCODE; NCI-SEER-Intramural Research Program of the
National Cancer Institute; Public Health Service [N01-PC-65064,
N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]; Australian
National Health and Medical Research Council [ID990920]; Cancer Council
NSW; University of Sydney Faculty of Medicine; NYU-WHS-National Cancer
Institute [R01 CA098661, P30 CA016087]; National Institute of
Environmental Health Sciences [ES000260]; Intramural Research Program of
the National Cancer Institute; Division of Cancer Prevention; DHHS;
SCALE-Swedish Cancer Society [2009/659]; Stockholm County Council
[20110209]; Strategic Research Program in Epidemiology at Karolinska
Institute; Swedish Cancer Society grant [02 6661]; California Department
of Health Services, statewide cancer reporting program mandated by
California Health and Safety Code Section [103885]; National Cancer
Institute's Surveillance, Epidemiology, and End Results Program
[HHSN261201000140C]; Cancer Prevention Institute of California
[HHSN261201000035C]; University of Southern California
[HHSN261201000034C]; Public Health Institute; Centers for Disease
Control and Prevention's National Program of Cancer Registries [1U58
DP000807-01]; UTAH/Sheffield-NIH [CA134674]; Utah Population Database
(UPDB); Utah Cancer Registry (UCR); Huntsman Cancer Institute (HCI); HCI
Cancer Center Support grant [P30 CA42014]; National Cancer Institute
SEER Program; Utah State Department of Health; University of Utah;
Yorkshire Cancer Research; US Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; YALE-National
Cancer Institute [CA62006, CA165923]; NSFC-the National Natural Science
Foundation of China [61471078]; National Heart, Lung, and Blood
Institute; Canadian Cancer Society; Cancer Research UK; Cancer Research
Ireland, Czech Republic; Sheffield Experimental Cancer Medicine Centre
FX We thank I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, D. Connley,
H. Cramp, R. Cutting, C. Dalley, H. Dykes, A. Gabbas, P. Gaddam, P. Hui,
L. Irish, L. Jacobus, S. Kaul, L. Klareskog, A. Lai, J. Lunde, M.
McAdams, L. Padyukov, D. Parisi, V. Rajamanickam, T. Rattle, L. Rigacci,
R. Sargent, G. Specchia, M. Stagner, P. Taylor, C. Tornow, J. WiIliams
and G. Wood. The overall GWAS project was supported by the intramural
programme of the Division of Cancer Epidemiology and Genetics, National
Cancer Institute, US National Institutes of Health. ATBC-This research
was supported in part by the Intramural Research Program of the NIH and
the National Cancer Institute. In addition, this research was supported
by US Public Health Service contracts N01-CN-45165, N01-RC-45035,
N01-RC-37004 and HHSN261201000006C from the National Cancer Institute,
Department of Health and Human Services. BC-This reasearch was supported
by Canadian Institutes for Health Research (CIHR), Canadian Cancer
Society and Michael Smith Foundation for Health Research. CPS-II-The
Cancer Prevention Study-II (CPS-II) Nutrition Cohort is supported by the
American Cancer Society. Genotyping for all CPS-II samples were
supported by the Intramural Research Program of the NIH, NCI, Division
of Cancer Epidemiology and Genetics. We acknowledge the contribution to
this study from Central Cancer Registries supported by the Centers for
Disease Control and Prevention National Program of Cancer Registries,
and cancer registries supported by the National Cancer Institute
Surveillance Epidemiology and End Results program. ELCCS-This study was
supported by Leukaemia & Lymphoma Research. ENGELA-This research was
supported by Association pour la Recherche contre le Cancer (ARC),
Institut National du Cancer (INCa), Fondation de France, Fondation
contre la Leucemie, Agence nationale de securite sanitaire de
l'alimentation, de l'environnement et du travail (ANSES). EPIC-This
study was supported by Coordinated Action (contract no. 006438,
SP23-CT-2005-006438); HuGeF (Human Genetics Foundation), Torino, Italy,
and Cancer Research UK. EpiLymph-This study was supported by European
Commission (grant references QLK4-CT-2000-00422 and
FOOD-CT-2006-023103), the Spanish Ministry of Health (grant references
CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10 and RTIC
RD06/0020/0095), the Marato de TV3 Foundation (grant reference 051210),
the Agencia de Gestiod' AjutsUniversitarisi de Recerca-Generalitat de
Catalunya (grant reference 2014SRG756) who had no role in the data
collection, analysis or interpretation of the results, the NIH (contract
NO1-CO-12400), the Compagnia di San Paolo-Programma Oncologia, the
Federal Office for Radiation Protection grants StSch4261 and StSch4420,
the Jose Carreras Leukemia Foundation grant DJCLS-R12/23, the German
Federal Ministry for Education and Research (BMBF-01-EO-1303), the
Health Research Board, Ireland and Cancer Research Ireland, Czech
Republic supported by MH CZ-DRO (MMCI, 00209805) and RECAMO,
CZ.1.05/2.1.00/03.0101, and Fondation de France and Association de
Recherche Contre le Cancer. GEC/Mayo GWAS-This reaearch was supported by
NIH (grant numbers CA118444, CA148690 and CA92153), Intramural Research
Program of the NIH, National Cancer Institute and Veterans Affairs
Research Service. Data collection for Duke University was supported by a
Leukemia & Lymphoma Society Career Development Award, the Bernstein
Family Fund for Leukemia and Lymphoma Research, the NIH (K08CA134919)
and National Center for Advancing Translational Science (UL1 TR000135).;
r HPFS-HPFS was supported in part by NIH grants CA167552, CA149445,
CA098122, CA098566 and K07 CA115687. We thank the participants and staff
of the Health Professionals Follow-up Study for their valuable
contributions as well as the following state cancer registries for their
help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME,
MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA,
WA, WY. We assume full responsibility for analyses and interpretation of
these data. Iowa-Mayo SPORE-This was supported by NCI Specialized
Programs of Research Excellence (SPORE) in Human Cancer (P50 CA97274),
National Cancer Institute (30 CA086862 and P30 CA15083) and Henry J.
Predolin Foundation. Italian GxE-This was supported by Italian
Association for Cancer Research (AIRC, Investigator Grant 11855, P. C.),
Fondazione Banco di Sardegna 2010-2012 and Regione Autonoma della
Sardegna (LR7 CRP-59812/2012, M.G.E.). Mayo Clinic Case-Control-It was
supported by NIH (R01 CA92153) and National Cancer Institute (P30
CA015083). MCCS-The Melbourne Collaborative Cohort Study (MCCS)
recruitment was funded by VicHealth and Cancer Council Victoria. The
MCCS was further supported by Australian NHMRC grants 209057, 251553 and
504711, and also by infrastructure provided by Cancer Council Victoria.
Cases and their vital status were ascertained through the Victorian
Cancer Registry (VCR). MCC-Spain-This study is funded by The Instituto
de Salud Carlos III (ISCIII-Spanish Government, PI11/01810, PI14/01219,
RCESP C03/09 and CIBERESP) and the Agencia de Gestiod'
AjutsUniversitarisi de Recerca (AGAUR)-Generalitat de Catalunya
(Catalonian Government, 2014SGR756). Nadia Garcia and Marleny Vergara
(ICO-IDIBELL) provided technical support for this study. MD Anderson
provided Institutional support to the Center for Translational and
Public Health Genomics. MSKCC-Geoffrey Beene Cancer Research Grant,
Lymphoma Foundation (LF5541); Barbara K. Lipman Lymphoma Research Fund
(74419); Robert and Kate Niehaus Clinical Cancer Genetics Research
Initiative (57470); U01 HG007033; ENCODE and U01 HG007033.
NCI-SEER-Intramural Research Program of the National Cancer Institute,
NIH, and Public Health Service (N01-PC-65064, N01-PC-67008,
N01-PC-67009, N01-PC-67010 and N02-PC-71105). NHS-The NHS was supported
in part by NIH grants CA186107, CA87969, CA49449, CA149445, CA098122,
CA098566 and K07 CA115687. We thank the participants and staff of the
Nurses' Health Study for their valuable contributions as well as the
following state cancer registries for their help: AL, AZ, AR, CA, CO,
CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY,
NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full
responsibility for analyses and interpretation of these data. NSW-NSW
was supported by grants from the Australian National Health and Medical
Research Council (ID990920), the Cancer Council NSW and the University
of Sydney Faculty of Medicine. NYU-WHS-National Cancer Institute (R01
CA098661, P30 CA016087) and National Institute of Environmental Health
Sciences (ES000260). PLCO-This research was supported by the Intramural
Research Program of the National Cancer Institute and by contracts from
the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.
SCALE-Swedish Cancer Society (2009/659). Stockholm County Council
(20110209) and the Strategic Research Program in Epidemiology at
Karolinska Institute. Swedish Cancer Society grant (02 6661). NIH (5R01
CA69669-02), Plan Denmark.; r UCSF2-The UCSF studies were supported by
the NCI, NIH (CA1046282 and CA154643). The collection of cancer
incidence data used in this study was supported by the California
Department of Health Services as part of the statewide cancer reporting
program mandated by California Health and Safety Code Section 103885;
the National Cancer Institute's Surveillance, Epidemiology, and End
Results Program under contract HHSN261201000140C awarded to the Cancer
Prevention Institute of California, contract HHSN261201000035C awarded
to the University of Southern California and contract HHSN261201000034C
awarded to the Public Health Institute; and the Centers for Disease
Control and Prevention's National Program of Cancer Registries, under
agreement no. 1U58 DP000807-01 awarded to the Public Health Institute.
UTAH/Sheffield-NIH CA134674. Partial support for data collection at the
Utah site was made possible by the Utah Population Database (UPDB) and
the Utah Cancer Registry (UCR). Partial support for all data sets within
the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI
Cancer Center Support grant, P30 CA42014. The UCR is supported in part
by NIH contract HHSN261201000026C from the National Cancer Institute
SEER Program with additional support from the Utah State Department of
Health and the University of Utah. Partial support for data collection
in Sheffield, UK was made possible by funds from Yorkshire Cancer
Research and the Sheffield Experimental Cancer Medicine Centre. We thank
the NCRI Haemato-oncology Clinical Studies Group, colleagues in the
North Trent Cancer Network the North Trent Haemato-oncology Database.
WHI-The investigators of WHI are as follows: Program Office (National
Heart, Lung, and Blood Institute, Bethesda, MD, USA) Jacques Rossouw,
Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford and Nancy Geller;
Clinical Coordinating Center (Fred Hutchinson Cancer Research Center,
Seattle, WA, USA) Garnet Anderson, Ross Prentice, Andrea LaCroix and
Charles Kooperberg; Investigators and Academic Centers (Brigham and
Women's Hospital, Harvard Medical School, Boston, MA, USA) JoAnn E.
Manson; (MedStar Health Research Institute/Howard University,
Washington, DC, USA) Barbara V. Howard; (Stanford Prevention Research
Center, Stanford, CA, USA) Marcia L. Stefanick; (The Ohio State
University, Columbus, OH, USA) Rebecca Jackson; (University of Arizona,
Tucson/Phoenix, AZ, USA) Cynthia A. Thomson; (University at Buffalo,
Buffalo, NY, USA) Jean Wactawski-Wende; (University of Florida,
Gainesville/Jacksonville, FL, USA) Marian Limacher; (University of Iowa,
Iowa City/Davenport, IA, USA) Robert Wallace; (University of Pittsburgh,
Pittsburgh, PA, USA) Lewis Kuller; (Wake Forest University School of
Medicine, Winston-Salem, NC, USA) Sally Shumaker; and Women's Health
Initiative Memory Study (Wake Forest University School of Medicine,
Winston-Salem, NC, USA) Sally Shumaker. The WHI program is funded by the
National Heart, Lung, and Blood Institute, NIH, US Department of Health
and Human Services by contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and
HHSN271201100004C. YALE-National Cancer Institute (CA62006 and
CA165923). Other support includes: NSFC-the National Natural Science
Foundation of China (no. 61471078).
NR 48
TC 7
Z9 7
U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10933
DI 10.1038/ncomms10933
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG0CH
UT WOS:000371729200001
PM 26956414
ER
PT J
AU Ebrahim, S
Avenarius, MR
Grati, M
Krey, JF
Windsor, AM
Sousa, AD
Ballesteros, A
Cui, RJ
Millis, BA
Salles, FT
Baird, MA
Davidson, MW
Jones, SM
Choi, D
Dong, LJ
Raval, MH
Yengo, CM
Barr-Gillespie, PG
Kachar, B
AF Ebrahim, Seham
Avenarius, Matthew R.
Grati, M'hamed
Krey, Jocelyn F.
Windsor, Alanna M.
Sousa, Aurea D.
Ballesteros, Angela
Cui, Runjia
Millis, Bryan A.
Salles, Felipe T.
Baird, Michelle A.
Davidson, Michael W.
Jones, Sherri M.
Choi, Dongseok
Dong, Lijin
Raval, Manmeet H.
Yengo, Christopher M.
Barr-Gillespie, Peter G.
Kachar, Bechara
TI Stereocilia-staircase spacing is influenced by myosin III motors and
their cargos espin-1 and espin-like
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACTIN-BUNDLING PROTEINS; HAIR-CELL STEREOCILIA; HEARING-LOSS; MOLECULAR
ARCHITECTURE; LENGTH REGULATION; BIRD COCHLEA; INNER-EAR; IN-VIVO;
FILAMENTS; MODEL
AB Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell.
C1 [Ebrahim, Seham; Grati, M'hamed; Windsor, Alanna M.; Sousa, Aurea D.; Ballesteros, Angela; Cui, Runjia; Millis, Bryan A.; Salles, Felipe T.; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Avenarius, Matthew R.; Krey, Jocelyn F.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.
[Avenarius, Matthew R.; Krey, Jocelyn F.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
[Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA.
[Jones, Sherri M.] Univ Nebraska, Dept Special Educ & Commun Disorders, Lincoln, NE 68583 USA.
[Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
[Dong, Lijin] NEI, Genet Engn Core, NIH, Bethesda, MD 20892 USA.
[Raval, Manmeet H.; Yengo, Christopher M.] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA.
RP Kachar, B (reprint author), NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.; Barr-Gillespie, PG (reprint author), Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.; Barr-Gillespie, PG (reprint author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
EM gillespp@ohsu.edu; kacharb@nidcd.nih.gov
FU University of Virginia W.M. Keck Biomedical Mass Spectrometry Lab; OHSU
Proteomics Shared Resource; NIH [P30 EY010572, P30 CA069533, S10
OD012246, R01 DC002368, R01 DC011034, P30 DC005983]; NIH/NIDCD/IRP;
[R01 EY018141]
FX We thank David Kohrman for genetics advice and Rachel Dumont for
assistance with SEM. We received support from the following core
facilities: mass spectrometry from the University of Virginia W.M. Keck
Biomedical Mass Spectrometry Lab and the OHSU Proteomics Shared Resource
(partial support from NIH core grants P30 EY010572 and P30 CA069533;
Orbitrap Fusion S10 OD012246); CRISPR-mediated mouse knockouts from OHSU
Transgenic Mouse Model Shared Resource; and confocal microscopy from the
OHSU Advanced Light Microscopy Core @ The Jungers Center. P.G.B.-G. was
supported by NIH grants R01 DC002368, R01 DC011034 and P30 DC005983;
C.M.Y. by R01 EY018141, and B.K. by NIH/NIDCD/IRP.
NR 61
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U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10833
DI 10.1038/ncomms10833
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9SC
UT WOS:000371700400001
PM 26926603
ER
PT J
AU Gomez-Rodriguez, J
Meylan, F
Handon, R
Hayes, ET
Anderson, SM
Kirby, MR
Siegel, RM
Schwartzberg, PL
AF Gomez-Rodriguez, Julio
Meylan, Francoise
Handon, Robin
Hayes, Erika T.
Anderson, Stacie M.
Kirby, Martha R.
Siegel, Richard M.
Schwartzberg, Pamela L.
TI Itk is required for Th9 differentiation via TCR-mediated induction of
IL-2 and IRF4
SO NATURE COMMUNICATIONS
LA English
DT Article
ID T-CELL-RECEPTOR; ALLERGIC AIRWAY INFLAMMATION; TEC FAMILY KINASES; LUNG
INFLAMMATION; TGF-BETA; NFATC TRANSLOCATION; MICE LACKING; T(H)9 CELLS;
IFN-GAMMA; EXPRESSION
AB Th9 cells produce interleukin (IL)-9, a cytokine implicated in allergic asthma and autoimmunity. Here we show that Itk, a mediator of T cell receptor signalling required for Th2 immune responses and the development of asthma, is a positive regulator of Th9 differentiation. In a model of allergic lung disease, Itk-deficient mice show reduced pulmonary inflammation and IL-9 production by T cells and innate lymphoid type 2 cells (ILC2), despite normal early induction of ILC2s. In vitro, Itk(-/-) CD4(+) T cells do not produce IL-9 and have reduced levels of IRF4 (Interferon Regulator Factor 4), a critical transcription factor for effector T cell function. Both IL-9 and IRF4 expression are rescued by either IL-2 or constitutively active STAT5, but not NFATc1. STAT5 binds the Irf4 promoter, demonstrating one mechanism by which IL-2 rescues weakly activated T cells. Itk inhibition also reduces IL-9 expression by human T cells, implicating ITK as a key regulator of Th9 induction.
C1 [Gomez-Rodriguez, Julio; Handon, Robin; Anderson, Stacie M.; Kirby, Martha R.; Schwartzberg, Pamela L.] NHGRI, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
[Meylan, Francoise; Hayes, Erika T.; Siegel, Richard M.] NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Gomez-Rodriguez, J (reprint author), NHGRI, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM jrgomez@mail.nih.gov; pams@mail.nih.gov
FU intramural program of NHGRI; intramural program of NIAMS
FX We thank J. Reilley and N. Richoz for technical assistance, J. Fekecs
for help with graphics and J. Zhu for reading the manuscript. This work
was supported by the intramural programs of NHGRI and NIAMS.
NR 70
TC 7
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U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10857
DI 10.1038/ncomms10857
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9WF
UT WOS:000371712200001
PM 26936133
ER
PT J
AU Grabundzija, I
Messing, SA
Thomas, J
Cosby, RL
Bilic, I
Miskey, C
Gogol-Doring, A
Kapitonov, V
Diem, T
Dalda, A
Jurka, J
Pritham, EJ
Dyda, F
Izsvak, Z
Ivics, Z
AF Grabundzija, Ivana
Messing, Simon A.
Thomas, Jainy
Cosby, Rachel L.
Bilic, Ilija
Miskey, Csaba
Gogol-Doering, Andreas
Kapitonov, Vladimir
Diem, Tanja
Dalda, Anna
Jurka, Jerzy
Pritham, Ellen J.
Dyda, Fred
Izsvak, Zsuzsanna
Ivics, Zoltan
TI A Helitron transposon reconstructed from bats reveals a novel mechanism
of genome shuffling in eukaryotes
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ROLLING-CIRCLE TRANSPOSONS; SUPERCOILING IN-VIVO; SINGLE-STRANDED-DNA;
MAIZE GENOME; GENE; REPLICATION; EVOLUTION; ELEMENTS; TRANSCRIPTION;
FAMILY
AB Helitron transposons capture and mobilize gene fragments in eukaryotes, but experimental evidence for their transposition is lacking in the absence of an isolated active element. Here we reconstruct Helraiser, an ancient element from the bat genome, and use this transposon as an experimental tool to unravel the mechanism of Helitron transposition. A hairpin close to the 3'-end of the transposon functions as a transposition terminator. However, the 3'-end can be bypassed by the transposase, resulting in transduction of flanking sequences to new genomic locations. Helraiser transposition generates covalently closed circular intermediates, suggestive of a replicative transposition mechanism, which provides a powerful means to disseminate captured transcriptional regulatory signals across the genome. Indeed, we document the generation of novel transcripts by Helitron promoter capture both experimentally and by transcriptome analysis in bats. Our results provide mechanistic insight into Helitron transposition, and its impact on diversification of gene function by genome shuffling.
C1 [Grabundzija, Ivana; Bilic, Ilija; Dalda, Anna; Izsvak, Zsuzsanna] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
[Grabundzija, Ivana; Messing, Simon A.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Thomas, Jainy; Cosby, Rachel L.; Pritham, Ellen J.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Miskey, Csaba; Diem, Tanja; Ivics, Zoltan] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
[Gogol-Doering, Andreas] German Ctr Integrat Biodivers Res iDiv, D-04103 Halle Jena Leipzig, Germany.
[Gogol-Doering, Andreas] Univ Halle Wittenberg, Inst Comp Sci, D-06099 Halle, Germany.
[Kapitonov, Vladimir; Jurka, Jerzy] Genet Informat Res Inst, Los Altos, CA 94022 USA.
RP Ivics, Z (reprint author), Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
EM zoltan.ivics@pei.de
OI Izsvak, Zsuzsanna/0000-0002-2053-2384
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Dieseases, NIH, Bethesda MD, USA
FX We are grateful to T. Rasko and A. Szvetnik for their technical
assistance in some of the experiments, A. Hickman for invaluable advice
and help in writing the manuscript, and C. Feschotte and L. Hurst for
critically reading the manuscript. This research was partially funded by
the Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Dieseases, NIH, Bethesda MD, USA.
NR 51
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U1 5
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10716
DI 10.1038/ncomms10716
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9UY
UT WOS:000371708600001
PM 26931494
ER
PT J
AU Gu, XL
Mao, X
Lussier, MP
Hutchison, MA
Zhou, L
Hamra, FK
Roche, KW
Lu, W
AF Gu, Xinglong
Mao, Xia
Lussier, Marc P.
Hutchison, Mary Anne
Zhou, Liang
Hamra, F. Kent
Roche, Katherine W.
Lu, Wei
TI GSG1L suppresses AMPA receptor-mediated synaptic transmission and
uniquely modulates AMPA receptor kinetics in hippocampal neurons
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TRANSMEMBRANE AUXILIARY SUBUNITS; CALCIUM-PERMEABLE AMPARS; LONG-TERM
POTENTIATION; 2 DISTINCT MECHANISMS; GLUTAMATE RECEPTORS; CORNICHON
PROTEINS; TOPOLOGY PREDICTION; STEM-CELLS; TRAFFICKING; PLASTICITY
AB Regulation of AMPA receptor (AMPAR)-mediated synaptic transmission is a key mechanism for synaptic plasticity. In the brain, AMPARs assemble with a number of auxiliary subunits, including TARPs, CNIHs and CKAMP44, which are important for AMPAR forward trafficking to synapses. Here we report that the membrane protein GSG1L negatively regulates AMPAR-mediated synaptic transmission. Overexpression of GSG1L strongly suppresses, and GSG1L knockout (KO) enhances, AMPAR-mediated synaptic transmission. GSG1L-dependent regulation of AMPAR synaptic transmission relies on the first extracellular loop domain and its carboxyl-terminus. GSG1L also speeds up AMPAR deactivation and desensitization in hippocampal CA1 neurons, in contrast to the effects of TARPs and CNIHs. Furthermore, GSG1L association with AMPARs inhibits CNIH2-induced slowing of the receptors in heterologous cells. Finally, GSG1L KO rats have deficits in LTP and show behavioural abnormalities in object recognition tests. These data demonstrate that GSG1L represents a new class of auxiliary subunit with distinct functional properties for AMPARs.
C1 [Gu, Xinglong; Mao, Xia; Hutchison, Mary Anne; Zhou, Liang; Lu, Wei] NINDS, Synapse & Neural Circuit Res Unit, NIH, 35 Convent Dr,3C1000, Bethesda, MD 20892 USA.
[Lussier, Marc P.; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, 35 Convent Dr,32C903, Bethesda, MD 20892 USA.
[Hamra, F. Kent] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA.
[Lussier, Marc P.] Univ Quebec, Dept Chim, Montreal, PQ H3C 3P8, Canada.
RP Lu, W (reprint author), NINDS, Synapse & Neural Circuit Res Unit, NIH, 35 Convent Dr,3C1000, Bethesda, MD 20892 USA.
EM luw4@mail.nih.gov
RI gu, xinglong/A-3054-2011;
OI gu, xinglong/0000-0002-0437-5606; Roche, Katherine/0000-0001-7282-6539
FU NINDS Intramural Research Program; National Center for Research
Resources [R24RR03232601]; [R24OD011108]
FX We thank Dr Tianyi Wang at the University of Pittsburgh for the Claudin1
plasmid. We also appreciate Dr Bernd Fakler at the University of
Freiburg, Germany for sharing the GSG1L data from his lab with us. We
are grateful to Drs Jeffrey Diamond and Mark Mayer for critical comments
on the manuscript. This work was supported by the NINDS Intramural
Research Program (W.L. and K.W.R.). Gsg1l mutant rats were produced by
the NIH Mutant Rat Resource at UT Southwestern Medical Center in Dallas
under grants from the National Center for Research Resources,
R24RR03232601 and the Office of the Director, R24OD011108 to F.K.H.
NR 70
TC 2
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U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10873
DI 10.1038/ncomms10873
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9VL
UT WOS:000371710000001
PM 26932439
ER
PT J
AU Lee, S
Chang, J
Blackstone, C
AF Lee, Seongju
Chang, Jaerak
Blackstone, Craig
TI FAM21 directs SNX27-retromer cargoes to the plasma membrane by
preventing transport to the Golgi apparatus
SO NATURE COMMUNICATIONS
LA English
DT Article
ID HEREDITARY SPASTIC PARAPLEGIA; WASH COMPLEX; RETROGRADE TRANSPORT;
ARP2/3 ACTIVATOR; PARKINSON DISEASE; RETROMER COMPLEX; PROTEIN;
ENDOSOME; GENE; TRAFFICKING
AB The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27-retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27-retromer-WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi.
C1 [Lee, Seongju; Chang, Jaerak; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Chang, Jaerak] Ajou Univ, Sch Med, Dept Biomed Sci, Suwon 443380, South Korea.
[Chang, Jaerak] Ajou Univ, Sch Med, Dept Brain Sci, Suwon 443380, South Korea.
[Chang, Jaerak] Ajou Univ, Sch Med, Grad Program Neurosci, Suwon 443380, South Korea.
RP Blackstone, C (reprint author), NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health. Ethan Tyler (NIH Medical Arts Branch) provided
artistic assistance.
NR 54
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U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10939
DI 10.1038/ncomms10939
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG0CK
UT WOS:000371729500001
PM 26956659
ER
PT J
AU Meyer, PA
Socias, S
Key, J
Ransey, E
Tjon, EC
Buschiazzo, A
Lei, M
Botka, C
Withrow, J
Neau, D
Rajashankar, K
Anderson, KS
Baxter, RH
Blacklow, SC
Boggon, TJ
Bonvin, AMJJ
Borek, D
Brett, TJ
Caflisch, A
Chang, CI
Chazin, WJ
Corbett, KD
Cosgrove, MS
Crosson, S
Dhe-Paganon, S
Di Cera, E
Drennan, CL
Eck, MJ
Eichman, BF
Fan, QR
Ferre-D'Amare, AR
Fromme, JC
Garcia, KC
Gaudet, R
Gong, P
Harrison, SC
Heldwein, EE
Jia, ZC
Keenan, RJ
Kruse, AC
Kvansakul, M
McLellan, JS
Modis, Y
Nam, Y
Otwinowski, Z
Pai, EF
Pereira, PJB
Petosa, C
Raman, S
Rapoport, TA
Roll-Mecak, A
Rosen, MK
Rudenko, G
Schlessinger, J
Schwartz, TU
Shamoo, Y
Sondermann, H
Tao, YZJ
Tolia, NH
Tsodikov, OV
Westover, KD
Wu, H
Foster, I
Fraser, JS
Maia, FRNC
Gonen, T
Kirchhausen, T
Diederichs, K
Crosas, M
Sliz, P
AF Meyer, Peter A.
Socias, Stephanie
Key, Jason
Ransey, Elizabeth
Tjon, Emily C.
Buschiazzo, Alejandro
Lei, Ming
Botka, Chris
Withrow, James
Neau, David
Rajashankar, Kanagalaghatta
Anderson, Karen S.
Baxter, Richard H.
Blacklow, Stephen C.
Boggon, Titus J.
Bonvin, Alexandre M. J. J.
Borek, Dominika
Brett, Tom J.
Caflisch, Amedeo
Chang, Chung-I
Chazin, Walter J.
Corbett, Kevin D.
Cosgrove, Michael S.
Crosson, Sean
Dhe-Paganon, Sirano
Di Cera, Enrico
Drennan, Catherine L.
Eck, Michael J.
Eichman, Brandt F.
Fan, Qing R.
Ferre-D'Amare, Adrian R.
Fromme, J. Christopher
Garcia, K. Christopher
Gaudet, Rachelle
Gong, Peng
Harrison, Stephen C.
Heldwein, Ekaterina E.
Jia, Zongchao
Keenan, Robert J.
Kruse, Andrew C.
Kvansakul, Marc
McLellan, Jason S.
Modis, Yorgo
Nam, Yunsun
Otwinowski, Zbyszek
Pai, Emil F.
Barbosa Pereira, Pedro Jose
Petosa, Carlo
Raman, S.
Rapoport, Tom A.
Roll-Mecak, Antonina
Rosen, Michael K.
Rudenko, Gabby
Schlessinger, Joseph
Schwartz, Thomas U.
Shamoo, Yousif
Sondermann, Holger
Tao, Yizhi J.
Tolia, Niraj H.
Tsodikov, Oleg V.
Westover, Kenneth D.
Wu, Hao
Foster, Ian
Fraser, James S.
Maia, Filipe R. N. C.
Gonen, Tamir
Kirchhausen, Tom
Diederichs, Kay
Crosas, Merce
Sliz, Piotr
TI Data publication with the structural biology data grid supports live
analysis
SO NATURE COMMUNICATIONS
LA English
DT Article
ID X-RAY SCATTERING; PROTEIN DATA-BANK; MACROMOLECULAR CRYSTALLOGRAPHY;
STRUCTURE MODELS; DATA QUALITY; SYNCHROTRON; SOFTWARE; SCIENCE;
EXPERIENCES; RESOLUTION
AB Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
C1 [Meyer, Peter A.; Socias, Stephanie; Key, Jason; Ransey, Elizabeth; Tjon, Emily C.; Blacklow, Stephen C.; Eck, Michael J.; Harrison, Stephen C.; Kruse, Andrew C.; Wu, Hao; Sliz, Piotr] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Buschiazzo, Alejandro] Inst Pasteur Montevideo, Lab Mol & Struct Microbiol, Montevideo 11400, Uruguay.
[Buschiazzo, Alejandro] Inst Pasteur, Dept Biol Struct & Chem, F-75015 Paris, France.
[Lei, Ming] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Botka, Chris] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Withrow, James; Neau, David; Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, NE CAT, Bldg 436E,9700S Cass Ave, Argonne, IL 60439 USA.
[Withrow, James; Neau, David; Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Bldg 436E,9700S Cass Ave, Argonne, IL 60439 USA.
[Anderson, Karen S.; Boggon, Titus J.] Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
[Anderson, Karen S.; Baxter, Richard H.; Boggon, Titus J.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA.
[Baxter, Richard H.] Yale Univ, Dept Chem, 225 Prospect St, New Haven, CT 06520 USA.
[Bonvin, Alexandre M. J. J.] Univ Utrecht, Bijvoet Ctr, Fac Sci, NL-3584 CH Utrecht, Netherlands.
[Borek, Dominika; Otwinowski, Zbyszek] Univ Texas SW Med Ctr Dallas, Dept Biophys & Biochem, Dallas, TX 75390 USA.
[Brett, Tom J.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Caflisch, Amedeo] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
[Chang, Chung-I] Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan.
[Chazin, Walter J.] Vanderbilt Univ, Dept Biochem, Struct Biol Ctr, Nashville, TN 37232 USA.
[Chazin, Walter J.] Vanderbilt Univ, Dept Chem, Struct Biol Ctr, Nashville, TN 37232 USA.
[Corbett, Kevin D.] Ludwig Inst Canc Res, San Diego Branch, La Jolla, CA 92093 USA.
[Corbett, Kevin D.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Cosgrove, Michael S.] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA.
[Crosson, Sean; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
[Dhe-Paganon, Sirano; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Di Cera, Enrico] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA.
[Drennan, Catherine L.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Drennan, Catherine L.] MIT, Dept Biol, Cambridge, MA 02139 USA.
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Eichman, Brandt F.] Vanderbilt Univ, Dept Biol, Nashville, TN 37235 USA.
[Eichman, Brandt F.] Vanderbilt Univ, Struct Biol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Fan, Qing R.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
[Fan, Qing R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Ferre-D'Amare, Adrian R.] NHLBI, Lab RNA Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Fromme, J. Christopher] Cornell Univ, Dept Mol Biol & Genet, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
[Garcia, K. Christopher] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
[Garcia, K. Christopher] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
[Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
[Gaudet, Rachelle] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Gong, Peng] Chinese Acad Sci, Key Lab Special Pathogens & Biosafety, Wuhan Inst Virol, Wuhan 430071, Peoples R China.
[Harrison, Stephen C.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Harrison, Stephen C.] Harvard Univ, Mol Med Lab, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Heldwein, Ekaterina E.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
[Jia, Zongchao] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7M 3G5, Canada.
[Kvansakul, Marc] La Trobe Univ, Dept Biochem & Genet, Melbourne, Vic, Australia.
[McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
[Modis, Yorgo] Univ Cambridge, Dept Med, MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
[Nam, Yunsun] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Pai, Emil F.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
[Pai, Emil F.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada.
[Pai, Emil F.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Pai, Emil F.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2M9, Canada.
[Barbosa Pereira, Pedro Jose] Univ Porto, Inst Biol Mol & Celular, P-4150 Oporto, Portugal.
[Barbosa Pereira, Pedro Jose] Univ Porto, Inst Invest & Inovacao Saude, P-4150 Oporto, Portugal.
[Petosa, Carlo] Univ Grenoble Alpes, CNRS, CFA, Inst Biol Struct, F-38027 Grenoble, France.
[Raman, S.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Roll-Mecak, Antonina] Natl Inst Neurol Disorders & Stroke, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA.
[Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
[Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[Rudenko, Gabby] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA.
[Schlessinger, Joseph] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Schwartz, Thomas U.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Shamoo, Yousif; Tao, Yizhi J.] Rice Univ, Dept Biosci, Houston, TX 77005 USA.
[Sondermann, Holger] Cornell Univ, Dept Mol Med, Coll Vet Med, Ithaca, NY 14853 USA.
[Tolia, Niraj H.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Tsodikov, Oleg V.] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA.
[Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Westover, Kenneth D.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
[Wu, Hao; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Foster, Ian] Argonne Natl Lab, Math & Comp Sci Div, 9700 S Cass Ave, Argonne, IL 60439 USA.
[Foster, Ian] Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA.
[Fraser, James S.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
[Maia, Filipe R. N. C.] Uppsala Univ, Lab Mol Biophys, Dept Cell & Mol Biol, Husargatan 3,Box 596, SE-75124 Uppsala, Sweden.
[Maia, Filipe R. N. C.] Lawrence Berkeley Natl Lab, NERSC, Berkeley, CA 94720 USA.
[Gonen, Tamir] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
[Kirchhausen, Tom] Boston Childrens Hosp, Dept Pediat, Boston, MA 02115 USA.
[Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Diederichs, Kay] Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
[Crosas, Merce] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
RP Sliz, P (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM sliz@hkl.hms.harvard.edu
RI Bonvin, Alexandre/A-5420-2009; Borek, Dominika/D-2943-2011; Pereira,
Pedro/F-8972-2011;
OI Bonvin, Alexandre/0000-0001-7369-1322; Gaudet,
Rachelle/0000-0002-9177-054X; Borek, Dominika/0000-0002-4321-6253;
Pereira, Pedro/0000-0003-0969-5438; Corbett, Kevin/0000-0001-5854-2388;
Modis, Yorgo/0000-0002-6084-0429; Fraser, James/0000-0002-5080-2859;
Pai, Emil/0000-0002-1162-7242; Kvansakul, Marc/0000-0003-2639-2498
FU Leona M. and Harry B. Helmsley Charitable Trust [2016PG-BRI002]; NSF
[1448069]; NIH [P41 GM103403, 1S10RR028832, 1U54EB020406-01]; DOE
[DE-AC02-06CH11357]; NIST [60NANB15D077]
FX Development of the Structural Biology Data Grid is funded by The Leona
M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC.
Development of citation workflows is supported NSF 1448069 (to PS). DAA
is being developed as a pilot project of the National Data Service, with
additional funds to support storage and technology development,
including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE
DE-AC02-06CH11357; NIH 1U54EB020406-01, Big Data for Discovery Science
Center; and NIST 60NANB15D077 (Globus Project). AB acknowledges Ariel
Chaparro for assistance with the DAA setup (Inst Pasteur Montevideo).
Collections of pilot data sets were supported by various grants (see
Supplementary Table 1).
NR 52
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U1 3
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10882
DI 10.1038/ncomms10882
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9YS
UT WOS:000371719200001
PM 26947396
ER
PT J
AU Kaufman, AR
Koblitz, AR
Persoskie, A
Ferrer, RA
Klein, WMP
Dwyer, LA
Park, ER
AF Kaufman, Annette R.
Koblitz, Amber R.
Persoskie, Alexander
Ferrer, Rebecca A.
Klein, William M. P.
Dwyer, Laura A.
Park, Elyse R.
TI Factor Structure and Stability of Smoking-Related Health Beliefs in the
National Lung Screening Trial
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID CANCER-RISK PERCEPTIONS; QUIT SMOKING; SMOKERS; SUSCEPTIBILITY;
INTENTIONS; BEHAVIOR; WOMEN; WORRY; PARTICIPANTS; ASSOCIATION
AB Absolute and comparative risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy are important theoretical determinants of tobacco use, but no measures have been validated to ensure the discriminant validity as well as test-retest reliability of these measures in the tobacco context. The purpose of the current study is to examine the reliability and factor structure of a measure assessing smoking-related health cognitions and emotions in a national sample of current and former heavy smokers in the National Lung Screening Trial.
A sub-study of the National Lung Screening Trial assessed current and former smokers' (age 55-74; N = 4379) self-reported health cognitions and emotions at trial enrollment and at 12-month follow-up. Items were derived from the Health Belief Model and Self-Regulation Model.
An exploratory factor analysis of baseline responses revealed a five-factor structure for former smokers (risk perceptions, worry, perceived severity, perceived benefits, and self-efficacy) and a six-factor structure for current smokers, such that absolute risk and comparative risk perceptions emerged as separate factors. A confirmatory factor analysis of 12-month follow-up responses revealed a good fit for the five latent constructs for former smokers and six latent constructs for current smokers. Longitudinal stability of these constructs was also demonstrated.
This is the first study to examine tobacco-related health cognition and emotional constructs over time in current and former heavy smokers undergoing lung screening. This study found that the theoretical constructs were stable across time and that the factor structure differed based on smoking status (current vs. former).
C1 [Kaufman, Annette R.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Koblitz, Amber R.; Persoskie, Alexander; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Dwyer, Laura A.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Park, Elyse R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Kaufman, AR (reprint author), Natl Canc Inst, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,3-E-546, Rockville, MD 20850 USA.
EM kaufmana@mail.nih.gov
FU American Cancer Society Mentored Research Scholar Award
[MRSG-005-05-CPPB]; National Cancer Institute [U01 CA079778, U01
CA080098]
FX This work was funded by an American Cancer Society Mentored Research
Scholar Award (MRSG-005-05-CPPB) to ERP, and the American College of
Radiology Imaging Network (ACRIN) received funding from the National
Cancer Institute through the grants U01 CA079778 and U01 CA080098.
NR 50
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U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD MAR
PY 2016
VL 18
IS 3
BP 321
EP 329
DI 10.1093/ntr/ntv091
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA DF8HP
UT WOS:000371598600013
PM 25964503
ER
PT J
AU Browning, B
Page, KE
Kuhn, RL
DiLiberto, MA
Deschenes, J
Taillie, E
Tomanio, E
Holubkov, R
Dean, JM
Moler, FW
Meert, K
Pemberton, VL
AF Browning, Brittan
Page, Kent E.
Kuhn, Renee L.
DiLiberto, Mary Ann
Deschenes, Jendar
Taillie, Eileen
Tomanio, Elyse
Holubkov, Richard
Dean, J. Michael
Moler, Frank W.
Meert, Kathleen
Pemberton, Victoria L.
TI Nurses' Attitudes Toward Clinical Research: Experience of the
Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE heart arrest; perceptions; research; pediatrics; nurses
ID RANDOMIZED CONTROLLED-TRIALS; CARE; CHILDREN; INFANTS; PARENTS;
ENCEPHALOPATHY; PHYSICIANS
AB Objectives:
To understand factors affecting nurses' attitudes toward the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials and association with approach/consent rates.
Design:
Cross-sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials.
Setting:
Study was conducted at 16 of 38 self-selected study sites.
Subjects:
Pediatric and cardiac intensive care nurses.
Measurements and Main Results:
The primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement "I am happy to take care of a Therapeutic Hypothermia after Pediatric Cardiac Arrest patient". Associations between perceptions and study approach/consent rates were also explored. Of 2,241 nurses invited, 1,387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p < 0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of Therapeutic Hypothermia After Pediatric Cardiac Arrest compared with those who had not (79% vs 54%; p < 0.001). Of the 754 nurses who cared for a Therapeutic Hypothermia After Pediatric Cardiac Arrest patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r = 0.54; p = 0.04), ICU support (r = 0.61; p = 0.02), and the importance of conducting the trial in children (r = 0.61; p = 0.01).
Conclusions:
The majority of nurses had positive perceptions of the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials. Institutional, colleague, and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses believed hypothermia was beneficial had lower consent rates, suggesting that educating nurses on study rationale and equipoise may enhance study participation.
C1 [Browning, Brittan] Univ Utah, Salt Lake City, UT USA.
[Page, Kent E.; Kuhn, Renee L.; Holubkov, Richard; Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[DiLiberto, Mary Ann] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
[Deschenes, Jendar] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA.
[Taillie, Eileen] Univ Rochester, Med Ctr, Golisano Childrens Hosp, Dept Pediat, Rochester, NY 14642 USA.
[Tomanio, Elyse] Childrens Natl Med Ctr, Dept Crit Care, Washington, DC 20010 USA.
[Moler, Frank W.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Meert, Kathleen] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Pemberton, Victoria L.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Browning, B (reprint author), Univ Utah, Salt Lake City, UT USA.
EM Brittan.browning@hsc.utah.edu
FU National Institutes of Health (NIH); NIH; NHLBI; Pfizer; St. Jude
Medical Inc.; Fibrocell Inc; NIH/NHLBI
FX Dr. Browning received support for article research from the National
Institutes of Health (NIH). Dr. Page received support for article
research from the NIH. Dr. Kuhn received support for article research
from the NIH. Her institution received financial support from the NHLBI.
Dr. Tallie received support for article research from the NIH. Dr.
Holubkov received financial support from Pfizer (consulting fees for
DSMB membership), St. Jude Medical Inc. (biostatistical consulting), and
Fibrocell Inc (DSMB member). He disclosed that he is also a
biostatistical consultant for Physicians' Committee for Responsible
Medicine, a nonprofit in Washington, D.C. He received support for
article research from the NIH. His institution received financial
support from the NIH/NHLBI (this grant gave salary support to Dr.
Holubkov as well as general support to the Coordinating Center). Dr.
Dean received support for article research from the NIH. His institution
received financial support from the NHLBI. Dr. Moler received support
for article research from the NIH. His institution received financial
support from the NIH/NHLBI (U01 awards to University of Michigan and
University of Utah). Dr. Meert received support for article research
from the NIH. Her institution received financial support from the NIH.
Dr. Pemberton received support for article research from the Government.
The remaining authors have disclosed that they do not have any potential
conflicts of interest.
NR 24
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U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD MAR
PY 2016
VL 17
IS 3
BP e121
EP e129
DI 10.1097/PCC.0000000000000609
PG 9
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA DG0ID
UT WOS:000371747600004
PM 26669643
ER
PT J
AU Bishop, SL
Thurm, A
Farmer, C
Lord, C
AF Bishop, Somer L.
Thurm, Audrey
Farmer, Cristan
Lord, Catherine
TI Autism Spectrum Disorder, Intellectual Disability, and Delayed Walking
SO PEDIATRICS
LA English
DT Article
ID MOTOR DEVELOPMENT; DIAGNOSTIC INTERVIEW; MENTAL-RETARDATION; CHILDREN;
INDIVIDUALS; INFANTS; AGE; POPULATION; PHENOTYPES; RISK
AB OBJECTIVE: Delayed onset of independent walking is common in intellectual disability (ID). However, in children with autism spectrum disorders (ASD), delayed walking has not been reported as frequently, despite the high rate of concurrent ID in ASD. This study directly examined the relationship between delayed walking and severity of ID in children with ASD versus other non-ASD diagnoses.
METHOD Participants were 1185 individuals (ASD, n = 903; non-ASD, n = 282) who received an assessment at age 4 to 12 years (6.89 +/- 2.25) that yielded an estimate of nonverbal IQ (NVIQ) and retrospectively reported age of walking from the Autism Diagnostic Interview-Revised. The relationship between diagnostic group and delayed walking (defined as occurring at >= 16 months) as a function of NVIQ was explored using the Cox proportional hazards model.
RESULTS: Children with ASD were less likely to exhibit delayed walking than those with non-ASD diagnoses, and this difference was larger at lower levels of NVIQ (P =.002). For example, rates of delayed walking for ASD and non-ASD were 13% and 19%, respectively, in those with NVIQ > 85 but 31% and 60% in children with NVIQ < 70.
CONCLUSIONS: Although lower IQ scores were associated with increased rates of late walking in both ASD and non-ASD groups, children with low IQ were more likely to show delayed walking in the absence of ASD. This raises the possibility of separate etiological pathways to ID in children with and without ASD.
C1 [Bishop, Somer L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Thurm, Audrey; Farmer, Cristan] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
[Lord, Catherine] Weill Cornell Med Coll, New York, NY USA.
RP Bishop, SL (reprint author), 401 Parnassus Ave, San Francisco, CA 94143 USA.
EM somer.bishop@ucsf.edu
FU Health Resources and Services Administration (HRSA) [R40MC28145];
National Institute of Child Health and Human Development (NICHD)
[R01HD065277]; National Institute of Mental Health [R01MH081873-01A1,
R01-MH066496]; NICHD [U19-HD 35482]
FX This project was supported by grants from the Health Resources and
Services Administration (HRSA; R40MC28145) and National Institute of
Child Health and Human Development (NICHD; R01HD065277) to Dr Bishop and
the National Institute of Mental Health (R01MH081873-01A1 and
R01-MH066496) and NICHD (U19-HD 35482) to Dr Lord.
NR 42
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Z9 1
U1 2
U2 7
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2016
VL 137
IS 3
AR e20152959
DI 10.1542/peds.2015-2959
PG 8
WC Pediatrics
SC Pediatrics
GA DF5MK
UT WOS:000371395800038
PM 26908679
ER
PT J
AU Reigstad, MM
Larsen, IK
Myklebust, TA
Robsahm, TE
Oldereid, NB
Brinton, LA
Storeng, R
AF Reigstad, Marte Myhre
Larsen, Inger Kristin
Myklebust, Tor Age
Robsahm, Trude Eid
Oldereid, Nan Birgitte
Brinton, Louise A.
Storeng, Ritsa
TI Risk of Cancer in Children Conceived by Assisted Reproductive Technology
SO PEDIATRICS
LA English
DT Article
ID IN-VITRO FERTILIZATION; POPULATION-BASED COHORT; CHILDHOOD-CANCER;
INFERTILITY TREATMENT; ACUTE-LEUKEMIA; FERTILITY PROBLEMS; NATIONWIDE
COHORT; ONCOLOGY GROUP; BIRTH-DEFECTS; PARENTAL AGE
AB BACKGROUND AND OBJECTIVE: An increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without.
METHODS: The Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types.
RESULTS: The study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90-1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02-2.73). Elevated risk of Hodgkin's lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12-11.72), although this was based on small numbers.
CONCLUSIONS: This population-based cohort study found elevated risks of leukemia and Hodgkin's lymphoma in children conceived by ART.
C1 [Reigstad, Marte Myhre; Storeng, Ritsa] Natl Hosp Norway, Oslo Univ Hosp, Norwegian Natl Advisory Unit Womens Hlth, POB 4950 Nydalen, N-0424 Oslo, Norway.
[Oldereid, Nan Birgitte] Natl Hosp Norway, Oslo Univ Hosp, Dept Gynecol, Sect Reprod Med, N-0424 Oslo, Norway.
[Reigstad, Marte Myhre; Larsen, Inger Kristin; Myklebust, Tor Age; Robsahm, Trude Eid] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
[Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA.
RP Reigstad, MM (reprint author), Natl Hosp Norway, Oslo Univ Hosp, Norwegian Natl Advisory Unit Womens Hlth, POB 4950 Nydalen, N-0424 Oslo, Norway.
EM martereigstad@gmail.com
FU Intramural NIH HHS [Z01 CP010128-12]
NR 63
TC 3
Z9 3
U1 3
U2 8
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2016
VL 137
IS 3
AR e20152061
DI 10.1542/peds.2015-2061
PG 12
WC Pediatrics
SC Pediatrics
GA DF5MK
UT WOS:000371395800020
PM 26908669
ER
PT J
AU Nakato, G
Hase, K
Sato, T
Kimura, S
Sakakibara, S
Sugiyama, M
Obata, Y
Hanazato, M
Iwanaga, T
Ohno, H
AF Nakato, Gaku
Hase, Koji
Sato, Takao
Kimura, Shunsuke
Sakakibara, Sayuri
Sugiyama, Machiko
Obata, Yuuki
Hanazato, Misaho
Iwanaga, Toshihiko
Ohno, Hiroshi
TI Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis
by Promoting M-Cell Maturation
SO PLOS ONE
LA English
DT Article
ID FOLLICLE-ASSOCIATED EPITHELIUM; INTESTINAL M-CELLS; PEYERS-PATCHES;
SPI-B; DIFFERENTIATION; DICER; EXPRESSION; RECEPTOR; PROTEIN; ABSENCE
AB cells in the follicle-associated epithelium (FAE) of Peyer's patches (PPs) serve as a main portal for external antigens and function as a sentinel in mucosal immune responses. The scarcity of these cells has hampered identification of M cell-specific molecules. Recent efforts have begun to provide insight into antigen transcytosis and differentiation of M cells; however, the molecular mechanisms underlying these processes are not fully elucidated. Small non-coding RNAs including microRNA (miRNA) have been reported to regulate gene expression and control various biological processes such as cellular differentiation and function. To evaluate the expression of miRNAs in FAE, including M cells, we previously performed microarray analysis comparing intestinal villous epithelium (VE) and PP FAE. Here we confirmed FAE specific miRNA expression levels by quantitative PCR. To gain insight into miRNA function, we generated mice with intestinal epithelial cell-specific deletion of Dicer1 (Dicer(Delta IEC)) and analyzed intestinal phenotypes, including M-cell differentiation, morphology and function. Dicer(Delta IEC) mice had a marked decrease in M cells compared to control floxed Dicer mice, suggesting an essential role of miRNAs in maturation of these cells. Furthermore, transmission electron microscopic analysis revealed that depletion of miRNA caused the loss of endosomal structures in M cells. In addition, antigen uptake by M cells was impaired in Dicer(Delta IEC) mice. These results suggest that miRNAs play a significant role in M cell differentiation and help secure mucosal immune homeostasis.
C1 [Nakato, Gaku; Hase, Koji; Sato, Takao; Sakakibara, Sayuri; Obata, Yuuki; Hanazato, Misaho; Ohno, Hiroshi] RIKEN Ctr Integrat Med Sci IMS RCAI, RCAI, Lab Intestinal Ecosyst, Yokohama, Kanagawa, Japan.
[Nakato, Gaku; Sato, Takao; Sugiyama, Machiko; Hanazato, Misaho; Ohno, Hiroshi] Yokohama City Univ, Grad Sch Med Life Sci, Immunobiol Lab, Yokohama, Kanagawa, Japan.
[Hase, Koji] Univ Tokyo, Inst Med Sci, Int Res & Dev Ctr Mucosal Vaccines, Div Mucosal Barriol, Tokyo, Japan.
[Hase, Koji] Japan Sci & Technol Agcy, PRESTO, Tokyo, Japan.
[Iwanaga, Toshihiko] Hokkaido Univ, Grad Sch Med, Lab Histol & Cytol, Sapporo, Hokkaido 060, Japan.
[Obata, Yuuki] Chiba Univ, Grad Sch Med & Pharmaceut Sci, Chiba, Japan.
[Nakato, Gaku] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hase, Koji] Keio Univ, Div Biochem, Fac Pharm, Tokyo, Japan.
RP Ohno, H (reprint author), RIKEN Ctr Integrat Med Sci IMS RCAI, RCAI, Lab Intestinal Ecosyst, Yokohama, Kanagawa, Japan.; Ohno, H (reprint author), Yokohama City Univ, Grad Sch Med Life Sci, Immunobiol Lab, Yokohama, Kanagawa, Japan.
EM hiroshi.ohno@riken.jp
RI Kimura, Shunsuke/D-7093-2012;
OI Kimura, Shunsuke/0000-0001-9408-2884; Obata, Yuuki/0000-0001-5461-3521
FU Japan Society for the Promotion of Science [22890238, 24790485,
22689017, 24249029]; Ministry of Education, Culture, Sports, Science and
Technology of Japan, AMED-CREST, AMED [19041072]; Japan Agency for
Medical Research and Development, Advanced Research and Development
Programs for Medical Innovation [15gm0710009h0002]; Japan Science
Society [22-453]; Sumitomo Foundation [100737]; Uehara Memorial
Foundation [201120109]; Takeda Science Foundation
FX The work was supported by the following: From The Japan Society for the
Promotion of Science, Grant-in-Aid for Research Activity Start-up (G.N.)
(Grant number: 22890238), Grants-in-Aid for Young Scientists (B) (G.N.)
(Grant number: 24790485), Grants-in-Aid for Young Scientists (A) (K.H.)
(Grant number: 22689017), Grants-in-Aid for Scientific Research (A)
(H.O.) (Grant number: 24249029); From The Ministry of Education,
Culture, Sports, Science and Technology of Japan, AMED-CREST, AMED,
Grant-in-Aid For Scientific Research on Priority Areas (K.H. and H.O.)
(Grant number: 19041072); From The Japan Agency for Medical Research and
Development, Advanced Research and Development Programs for Medical
Innovation (H.O.) (Grant number: 15gm0710009h0002); Sasakawa Scientific
Research Grant from the Japan Science Society (G.N.) (Grant
number:22-453); The Sumitomo Foundation (K.H.) (Grant number:100737);
The Uehara Memorial Foundation (K.H.) (Grant number:201120109); and
Takeda Science Foundation (H.O.) (http://www.takeda-sci.or.jp/).
NR 32
TC 4
Z9 4
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 1
PY 2016
VL 11
IS 3
AR e0150379
DI 10.1371/journal.pone.0150379
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF5ZW
UT WOS:000371434500137
PM 26930511
ER
PT J
AU Ramena, G
Yin, YF
Yu, Y
Walla, V
Elble, RC
AF Ramena, Grace
Yin, Yufang
Yu, Yang
Walla, Vijay
Elble, Randolph C.
TI CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell
Differentiation
SO PLOS ONE
LA English
DT Article
ID ACTIVATED CHLORIDE CHANNEL; TO-MESENCHYMAL TRANSITION; BREAST-CANCER
CELLS; BETA-CATENIN; E-CADHERIN; ADHESION MOLECULE; GENE-EXPRESSION;
IMMUNOGLOBULIN SUPERFAMILY; SIGNALING CASCADES; TIGHT JUNCTION
AB CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized human mammary epithelial cells (HMEC) caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The primary sequence of the CLCA2 TMS was found to be conserved in CLCA2 orthologs throughout mammals, suggesting that its interaction with EVA1 co-evolved with the mammary gland. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines.
C1 [Ramena, Grace; Yu, Yang] So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL 62794 USA.
[Yin, Yufang; Elble, Randolph C.] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA.
[Elble, Randolph C.] So Illinois Univ, Sch Med, Simmons Canc Inst, Springfield, IL 62794 USA.
[Walla, Vijay] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Elble, RC (reprint author), So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA.; Elble, RC (reprint author), So Illinois Univ, Sch Med, Simmons Canc Inst, Springfield, IL 62794 USA.
EM relble2@siumed.edu
FU National Cancer Institute [1R15CA151094-01]
FX This work was supported by National Cancer Institute 1R15CA151094-01 to
RCE. http://www.cancer.gov/. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 4
Z9 4
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 1
PY 2016
VL 11
IS 3
AR e0147489
DI 10.1371/journal.pone.0147489
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF5ZW
UT WOS:000371434500004
PM 26930581
ER
PT J
AU Mullins, N
Power, RA
Fisher, HL
Hanscombe, KB
Euesden, J
Iniesta, R
Levinson, DF
Weissman, MM
Potash, JB
Shi, J
Uher, R
Cohen-Woods, S
Rivera, M
Jones, L
Jones, I
Craddock, N
Owen, MJ
Korszun, A
Craig, IW
Farmer, AE
McGuffin, P
Breen, G
Lewis, CM
AF Mullins, N.
Power, R. A.
Fisher, H. L.
Hanscombe, K. B.
Euesden, J.
Iniesta, R.
Levinson, D. F.
Weissman, M. M.
Potash, J. B.
Shi, J.
Uher, R.
Cohen-Woods, S.
Rivera, M.
Jones, L.
Jones, I.
Craddock, N.
Owen, M. J.
Korszun, A.
Craig, I. W.
Farmer, A. E.
McGuffin, P.
Breen, G.
Lewis, C. M.
TI Polygenic interactions with environmental adversity in the aetiology of
major depressive disorder
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Depression; genetics; gene-environment interactions; polygenic risk
scoring
ID STRESSFUL LIFE EVENTS; GENOME-WIDE ASSOCIATION; TRANSPORTER GENE 5-HTT;
CONTROL-STUDY BACCS; CHILDHOOD MALTREATMENT; THREATENING EXPERIENCES;
MENTAL-DISORDERS; METAANALYSIS; RISK; HERITABILITY
AB Background. Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
Method. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
Results. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 x 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 x 10(-4) and p = 5.12 x 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
Conclusions. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.
C1 [Mullins, N.; Power, R. A.; Fisher, H. L.; Euesden, J.; Iniesta, R.; Uher, R.; Rivera, M.; Craig, I. W.; Farmer, A. E.; McGuffin, P.; Breen, G.; Lewis, C. M.] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, 16 De Crespigny Pk, London SE5 8AF, England.
[Hanscombe, K. B.; Lewis, C. M.] Kings Coll London, Sch Med, Guys Hosp, Div Genet & Mol Med, London SE5 8AF, England.
[Levinson, D. F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Weissman, M. M.] Columbia Univ, Dept Psychiat, New York, NY USA.
[Weissman, M. M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Potash, J. B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Shi, J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Uher, R.] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
[Cohen-Woods, S.] Univ Adelaide, Sch Med, Discipline Psychiat, Adelaide, SA, Australia.
[Rivera, M.] Univ Granada, CIBERSAM, Granada, Spain.
[Rivera, M.] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Granada, Spain.
[Jones, L.] Univ Birmingham, Dept Psychiat, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Jones, I.; Craddock, N.; Owen, M. J.] Cardiff Univ, Neurosci & Mental Hlth Res Inst, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Korszun, A.] Queen Mary Univ London, Barts & London Med Sch, London, England.
[Breen, G.] South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London, England.
[Breen, G.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England.
RP Mullins, N (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, 16 De Crespigny Pk, London SE5 8AF, England.
EM Niamh.mullins@kcl.ac.uk
RI Lewis, Cathryn/A-5225-2010; Iniesta, Raquel/E-6127-2017;
OI Lewis, Cathryn/0000-0002-8249-8476; Fisher, Helen/0000-0003-4174-2126;
Cohen-Woods, Sarah/0000-0003-2199-6129
FU UK Medical Research Council [G0701420]; GlaxoSmithKline [G0701420];
National Institute for Health Research (NIHR) Biomedical Research Centre
for Mental Health at South London; Maudsley NHS Foundation Trust;
Institute of Psychiatry, Psychology and Neuroscience, King's College
London; European Commission Framework 6 grant (EC)
[LSHB-CT-2003-503428]; National Institute of Mental Health (NIMH)
[MH061686, MH059542, MH075131, MH059552, MH059541, MH060912]; NIMH
[5RC2MH089916]; European Community [286213]; MQ Fellows Award [MQ14F40];
Canada Research Chairs programme
FX The RADIANT studies were funded by a joint grant from the UK Medical
Research Council, GlaxoSmithKline (G0701420) and by the National
Institute for Health Research (NIHR) Biomedical Research Centre for
Mental Health at South London and Maudsley NHS Foundation Trust and
Institute of Psychiatry, Psychology and Neuroscience, King's College
London. The GENDEP study was funded by a European Commission Framework 6
grant (EC contract ref.: LSHB-CT-2003-503428). The GenRED project was
supported by National Institute of Mental Health (NIMH) R01 grants
MH061686 (D.F.L.), MH059542 (WH Coryell), MH075131 (WB Lawson), MH059552
(J.B.P.), MH059541 (WA Scheftner) and MH060912 (M.M.W.). We acknowledge
the contributions of Dr George S. Zubenko and Dr Wendy N. Zubenko,
Department of Psychiatry, University of Pittsburgh School of Medicine to
the GenRED 1 project. The DGN study was supported by the NIMH (grant
5RC2MH089916). N.M. and C.M.L. have received funding from the European
Community's Seventh Framework Programme under the Marie Curie
Industry-Academia Partnership and Pathways (grant 286213). H.L.F. is
supported by an MQ Fellows Award (MQ14F40). R.U. is supported by the
Canada Research Chairs programme (http://www.chairs-chaires.gc.ca/).
NR 53
TC 4
Z9 5
U1 5
U2 17
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD MAR
PY 2016
VL 46
IS 4
BP 759
EP 770
DI 10.1017/S0033291715002172
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DF8PX
UT WOS:000371621500007
PM 26526099
ER
PT J
AU Yao, L
Yip, AL
Shrader, JA
Mesdaghinia, S
Volochayev, R
Jansen, AV
Miller, FW
Rider, LG
AF Yao, Lawrence
Yip, Adrienne L.
Shrader, Joseph A.
Mesdaghinia, Sepehr
Volochayev, Rita
Jansen, Anna V.
Miller, Frederick W.
Rider, Lisa G.
TI Magnetic resonance measurement of muscle T2, fat-corrected T2 and fat
fraction in the assessment of idiopathic inflammatory myopathies
SO RHEUMATOLOGY
LA English
DT Article
DE MRI; T2; fat fraction; juvenile dermatomyositis; dermatomyositis;
polymyositis; idiopathic inflammatory myopathies; muscle; myositis
ID JUVENILE DERMATOMYOSITIS; DISEASE-ACTIVITY; INTERNATIONAL CONSENSUS;
PEDIATRIC RHEUMATOLOGY; CLINICAL-ASSESSMENTS; RELAXATION-TIMES; ADULT;
POLYMYOSITIS; MRI; RESPONSIVENESS
AB Objective. This study examines the utility of MRI, including T2 maps and T2 maps corrected for muscle fat content, in evaluating patients with idiopathic inflammatory myopathy.
Methods. A total of 44 patients with idiopathic inflammatory myopathy, 18 of whom were evaluated after treatment with rituximab, underwent MRI of the thighs and detailed clinical assessment. T2, fat fraction (FF) and fat corrected T2 (fc-T2) maps were generated from standardized MRI scans, and compared with semi-quantitative scoring of short tau inversion recovery (STIR) and T1-weighted sequences, as well as various myositis disease metrics, including the Physician Global Activity, the modified Childhood Myositis Assessment Scale and the muscle domain of the Myositis Disease Activity Assessment Tool-muscle (MDAAT-muscle).
Results. Mean T2 and mean fc-T2 correlated similarly with STIR scores (Spearman r(s)=0.64 and 0.64, P < 0.01), while mean FF correlated with T1 damage scores (r(s)=0.69, P < 0.001). Baseline T2, fc-T2 and STIR scores correlated significantly with the Physician Global Activity, modified Childhood Myositis Assessment Scale and MDAAT-muscle (r(s) range = 0.41-0.74, P < 0.01). The response of MRI measures to rituximab was variable, and did not significantly agree with a standardized clinical definition of improvement. Standardized response means for the MRI measures were similar.
Conclusion. Muscle T2, fc-T2 and FF measurements exhibit content validity with reference to semi-quantitative scoring of STIR and T1 MRI, and also exhibit construct validity with reference to several myositis activity and damage measures. T2 was as responsive as fc-T2 and STIR scoring, although progression of muscle damage was negligible during the study.
C1 [Yao, Lawrence] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD USA.
[Yip, Adrienne L.; Mesdaghinia, Sepehr; Volochayev, Rita; Jansen, Anna V.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Clin Res Branch, NIH, Bethesda, MD 20892 USA.
[Shrader, Joseph A.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA.
RP Rider, LG (reprint author), NIEHS, NIH, MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of National Institute of Environmental
Health Sciences, National Institutes of Health
FX This study was supported in part by the Intramural Research Program of
the National Institute of Environmental Health Sciences, National
Institutes of Health.
NR 34
TC 6
Z9 6
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD MAR
PY 2016
VL 55
IS 3
BP 441
EP 449
DI 10.1093/rheumatology/kev344
PG 9
WC Rheumatology
SC Rheumatology
GA DF7SL
UT WOS:000371557800009
PM 26412808
ER
PT J
AU Wu, UI
Holland, SM
AF Wu, Un-In
Holland, Steven M.
TI A genetic perspective on granulomatous diseases with an emphasis on
mycobacterial infections
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Review
DE Tuberculosis; Nontuberculous; Mycobacteria; IFN-gamma; IL-12
ID INTERFERON-GAMMA-RECEPTOR; B ESSENTIAL MODULATOR; BACILLE
CALMETTE-GUERIN; INHERITED INTERLEUKIN-12 DEFICIENCY; CHRONIC
MUCOCUTANEOUS CANDIDIASIS; HUMAN STAT1 DEFICIENCY; IFN-GAMMA;
NONTUBERCULOUS MYCOBACTERIA; MENDELIAN SUSCEPTIBILITY;
AUTOSOMAL-DOMINANT
AB Identification of the genetic factors predisposing to mycobacterial infections has been a subject of intense research activities. Current knowledge of the genetic and immunological basis of susceptibility to mycobacteria largely comes from natural human and experimental models of Bacille Calmette Gu,rin (BCG) and nontuberculous mycobacterial infections. These observations support the central role of the IL-12/IFN-gamma pathway in controlling mycobacterial infection. In this review, we discuss the knowledge that associates both simple and complex inheritance with susceptibility to mycobacterial diseases. We place a special emphasis on monogenic disorders, since these clearly pinpoint pathways and can adduce mechanism. We also describe the clinical, immunological, and pathological features that may steer clinical investigation in the appropriate directions.
C1 [Wu, Un-In] Natl Taiwan Univ Hosp, Div Infect Dis, Taipei, Taiwan.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA.
RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA.
EM uninwu@gmail.com; smh@nih.gov
OI WU, UN-IN/0000-0001-8182-6071
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, US National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health.
NR 117
TC 1
Z9 1
U1 2
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
EI 1863-2300
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD MAR
PY 2016
VL 38
IS 2
BP 199
EP 212
DI 10.1007/s00281-015-0552-y
PG 14
WC Immunology; Pathology
SC Immunology; Pathology
GA DF8UI
UT WOS:000371634900006
PM 26733044
ER
PT J
AU Mott, M
Janis, S
Koroshetz, WJ
AF Mott, Meghan
Janis, Scott
Koroshetz, Walter J.
TI StrokeNet Takes Off National Institute of Neurological Disorders and
Stroke Organizational Update
SO STROKE
LA English
DT Editorial Material
DE clinical trial; image-guided intervention; National Institute of
Neurological Disorders and Stroke; thrombectomy; reperfusion injury
C1 [Mott, Meghan; Janis, Scott; Koroshetz, Walter J.] NINDS, NIH, Bldg 31,Room 8A52,31 Ctr Dr,MSC 2540, Bethesda, MD 20892 USA.
RP Koroshetz, WJ (reprint author), NINDS, NIH, Bldg 31,Room 8A52,31 Ctr Dr,MSC 2540, Bethesda, MD 20892 USA.
EM koroshetzw@mail.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD MAR
PY 2016
VL 47
IS 3
BP E51
EP E52
DI 10.1161/STROKEAHA.115.012063
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DF6VU
UT WOS:000371496400003
PM 26814236
ER
PT J
AU Lee, M
Huang, RL
Tong, WD
AF Lee, Mikyung
Huang, Ruili
Tong, Weida
TI Discovery of Transcriptional Targets Regulated by Nuclear Receptors
Using a Probabilistic Graphical Model
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE nuclear receptor; transcriptional regulation; Tox21; toxicogenomics
project; author-topic model; integrative analysis
ID BREAST-CANCER; RETINOIC ACID; PPAR-GAMMA; X RECEPTOR; EXPRESSION;
APOPTOSIS; CELLS; PROMOTER; COMPLEX; BINDING
AB Nuclear receptors (NRs) are ligand-activated transcriptional regulators that play vital roles in key biological processes such as growth, differentiation, metabolism, reproduction, and morphogenesis. Disruption of NRs can result in adverse health effects such as NR-mediated endocrine disruption. A comprehensive understanding of core transcriptional targets regulated by NRs helps to elucidate their key biological processes in both toxicological and therapeutic aspects. In this study, we applied a probabilistic graphical model to identify the transcriptional targets of NRs and the biological processes they govern. The Tox21 program profiled a collection of approximate 10 000 environmental chemicals and drugs against a panel of human NRs in a quantitative high-throughput screening format for their NR disruption potential. The Japanese Toxicogenomics Project, one of the most comprehensive efforts in the field of toxicogenomics, generated large-scale gene expression profiles on the effect of 131 compounds (in its first phase of study) at various doses, and different durations, and their combinations. We applied author-topic model to these 2 toxicological datasets, which consists of 11 NRs run in either agonist and/or antagonist mode (18 assays total) and 203 in vitro human gene expression profiles connected by 52 shared drugs. As a result, a set of clusters (topics), which consists of a set of NRs and their associated target genes were determined. Various transcriptional targets of the NRs were identified by assays run in either agonist or antagonist mode. Our results were validated by functional analysis and compared with TRANSFAC data. In summary, our approach resulted in effective identification of associated/affected NRs and their target genes, providing biologically meaningful hypothesis embedded in their relationships.
C1 [Lee, Mikyung; Huang, Ruili] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Weida.tong@fda.hhs.gov
FU U.S. Food and Drug Administration; National Center for Advancing
Translational Sciences, National Institutes of Health
FX This work was supported by the U.S. Food and Drug Administration and the
National Center for Advancing Translational Sciences, National
Institutes of Health. We would also like to thank Dr. Rajarshi Guha for
helpful discussion. The views expressed in this article are those of the
authors and do not necessarily reflect the statements, opinions, views,
conclusions, or policies of the National Center for Advancing
Translational Sciences, National Institutes of Health, U.S. Food and
Drug Administration, or the United States government. Mention of trade
names or commercial products does not constitute endorsement or
recommendation for use.
NR 26
TC 0
Z9 0
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAR
PY 2016
VL 150
IS 1
BP 64
EP 73
DI 10.1093/toxsci/kfv261
PG 10
WC Toxicology
SC Toxicology
GA DF8NS
UT WOS:000371615300007
PM 26643261
ER
PT J
AU Lau, WW
Tsang, JS
AF Lau, William W.
Tsang, John S.
TI Humoral Fingerprinting of Immune Responses: 'Super-Resolution',
High-Dimensional Serology
SO TRENDS IN IMMUNOLOGY
LA English
DT Editorial Material
ID BIOLOGY
C1 [Lau, William W.] NIH, Off Intramural Res, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
[Tsang, John S.] NIAID, Syst Genom & BioInformat Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Tsang, JS (reprint author), NIAID, Syst Genom & BioInformat Unit, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM john.tsang@nlh.gov
FU Intramural NIH HHS [Z99 AI999999, ZIA AI001152-05]
NR 9
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
EI 1471-4981
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD MAR
PY 2016
VL 37
IS 3
BP 167
EP 169
DI 10.1016/j.it.2016.01.003
PG 3
WC Immunology
SC Immunology
GA DG1OW
UT WOS:000371838400001
PM 26830541
ER
PT J
AU Wilson, MM
Bernstein, HD
AF Wilson, Marlena M.
Bernstein, Harris D.
TI Surface-Exposed Lipoproteins: An Emerging Secretion Phenomenon in
Gram-Negative Bacteria
SO TRENDS IN MICROBIOLOGY
LA English
DT Review
ID OUTER-MEMBRANE PROTEINS; COLI CELL WALL; BORRELIA-BURGDORFERI;
ESCHERICHIA-COLI; NEISSERIA-MENINGITIDIS; BINDING-PROTEIN;
MUREIN-LIPOPROTEIN; HAEMOPHILUS-INFLUENZAE; KLEBSIELLA-PNEUMONIAE;
FUNCTIONAL-CHARACTERIZATION
AB Bacterial lipoproteins are hydrophilic proteins that are anchored to a cell membrane by N-terminally linked fatty acids. It is widely believed that nearly all lipoproteins produced by Gram-negative bacteria are either retained in the inner membrane (IM) or transferred to the inner leaflet of the outer membrane (OM). Lipoproteins that are exposed on the cell surface have also been reported but are generally considered to be rare. Results from a variety of recent studies, however, now suggest that the prevalence of surface-exposed lipoproteins has been underestimated. In this review we describe the evidence that the surface exposure of lipoproteins in Gram-negative bacteria is a widespread phenomenon and discuss possible mechanisms by which these proteins might be transported across the OM.
C1 [Wilson, Marlena M.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX We thank Jessica Pierce for helpful comments on the manuscript. Research
conducted in the authors' laboratory is supported by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 86
TC 2
Z9 2
U1 3
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0966-842X
EI 1878-4380
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD MAR
PY 2016
VL 24
IS 3
BP 198
EP 208
DI 10.1016/j.tim.2015.11.006
PG 11
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA DF7PT
UT WOS:000371550800009
PM 26711681
ER
PT J
AU Yu, SJ
Wu, KJ
Bae, EK
Hsu, MJ
Richie, CT
Harvey, BK
Wang, Y
AF Yu, Seong-Jin
Wu, Kou-Jen
Bae, Eun K.
Hsu, Man-Jung
Richie, Christopher T.
Harvey, Brandon K.
Wang, Yun
TI Methamphetamine induces a rapid increase of intracellular Ca++ levels in
neurons overexpressing GCaMP5
SO ADDICTION BIOLOGY
LA English
DT Article
DE Calcium; glutamate; magnesium; methamphetamine
ID GATED CALCIUM-CHANNEL; DOPAMINE RELEASE; NUCLEUS-ACCUMBENS;
GENE-EXPRESSION; IN-VIVO; NOREPINEPHRINE TRANSPORTER; STRIATAL NEURONS;
NEURAL ACTIVITY; LIMBIC SYSTEM; PC12 CELLS
AB In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca++ (Ca(++)i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca++ probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca++ to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++)i, which was blocked by MK801, suggesting that Meth enhanced Ca(++)i through Glu receptor in neurons. The Meth-mediated Ca++ signal was also blocked by Mg++, low Ca++ or the L-type Ca++ channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca++ influx but partially reduced the peak of Ca(++)i. These data suggest that Meth enhanced Ca++ influx through membrane Ca++ channels, which then triggered the release of Ca++ from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca++ in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca(++)i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca(++)i, modulation of Ca(++)i may be useful to reduce Meth-related reactions.
C1 [Yu, Seong-Jin; Wu, Kou-Jen; Bae, Eun K.; Hsu, Man-Jung; Wang, Yun] Natl Hlth Res Inst, Ctr Neuropsychiat Res, 35 Keyan Rd, Zhunan, Taiwan.
[Richie, Christopher T.; Harvey, Brandon K.] NIDA, NIH, Baltimore, MD USA.
RP Yu, SJ; Wang, Y (reprint author), Natl Hlth Res Inst, Ctr Neuropsychiat Res, 35 Keyan Rd, Zhunan, Taiwan.
EM b7508@nhri.org.tw; ywang@nhri.org.tw
FU National Health Research Institutes, Taiwan
FX The authors thank Doug Howard and Lowella Fortuno for their technical
assistance (vector production and in vitro testing, respectively). This
study was supported by the National Health Research Institutes, Taiwan.
NR 50
TC 3
Z9 3
U1 4
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
EI 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2016
VL 21
IS 2
BP 255
EP 266
DI 10.1111/adb.12193
PG 12
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA DF2CW
UT WOS:000371148700004
PM 25377775
ER
PT J
AU Anizan, S
Concheiro, M
Lehner, KR
Bukhari, MO
Suzuki, M
Rice, KC
Baumann, MH
Huestis, MA
AF Anizan, Sebastien
Concheiro, Marta
Lehner, Kurt R.
Bukhari, Mohammad O.
Suzuki, Masaki
Rice, Kenner C.
Baumann, Michael H.
Huestis, Marilyn A.
TI Linear pharmacokinetics of 3,4-methylenedioxypyrovalerone (MDPV) and its
metabolites in the rat: relationship to pharmacodynamic effects
SO ADDICTION BIOLOGY
LA English
DT Article
DE bath salts; designer drugs; MDPV; metabolites; PK/PD; synthetic
cathinones
ID BATH SALTS; LOCOMOTOR-ACTIVITY; DESIGNER CATHINONES; MASS-SPECTROMETRY;
IN-VITRO; DRUG; STIMULANT; PHARMACOLOGY; CONSTITUENT; DOPAMINE
AB 3,4-Methylenedioxypyrovalerone (MDPV) is a commonly abused synthetic cathinone in the United States and is associated with dangerous side effects. MDPV is a dopamine transporter blocker that is 10-fold more potent than cocaine as a locomotor stimulant in rats. Previous in vitro and in vivo metabolism studies identified 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) as the two primary MDPV metabolites. This study examined MDPV pharmacokinetics and metabolism, along with associated pharmacodynamic effects in rats receiving 0.5, 1.0 and 2.0mg/kg subcutaneous (s.c.) MDPV. Blood was collected by an indwelling jugular catheter before dosing and at 10, 20, 30, 60, 120, 240 and 480 minutes thereafter. Plasma specimens were analyzed by liquid chromatography coupled to high-resolution tandem mass spectrometry. Maximum concentrations (C-max) and area-under-the-curve (AUC) for MDPV and two metabolites increased proportionally with administered dose, showing linear pharmacokinetics. MDPV exhibited the highest C-max at all doses (74.2-271.3g/l) and 4-OH-3-MeOH-PV the highest AUC (11366-47724 minutes per g/l), being the predominant metabolite. MDPV time to C-max (T-max) was 12.9-18.6 minutes, while 3,4-catechol-PV and 4-OH-3-MeO-PV peaked later with T-max 188.6-240 minutes after s.c. dosing. Horizontal locomotor activity (HLA) and stereotypy correlated positively with plasma MDPV concentrations, while HLA correlated negatively with MDPV metabolites. These results suggest that the parent compound mediates motor stimulation after systemic MDPV administration, but additionally, metabolites may be inhibitory, may not be active or may not pass the blood brain barrier.
C1 [Anizan, Sebastien; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
[Lehner, Kurt R.; Bukhari, Mohammad O.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIAAA, NIH, Baltimore, MD USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA);
National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), and the National Institute on
Alcohol Abuse and Alcoholism (NIAAA) and by the National Institutes of
Health (NIH).
NR 36
TC 6
Z9 6
U1 4
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
EI 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2016
VL 21
IS 2
BP 339
EP 347
DI 10.1111/adb.12201
PG 9
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA DF2CW
UT WOS:000371148700011
PM 25475011
ER
PT J
AU Hutsell, BA
Cheng, KJ
Rice, KC
Negus, SS
Banks, ML
AF Hutsell, Blake A.
Cheng, Kejun
Rice, Kenner C.
Negus, Sidney Stevens
Banks, Matthew L.
TI Effects of the kappa opioid receptor antagonist nor-binaltorphimine
(nor-BNI) on cocaine versus food choice and extended-access cocaine
intake in rhesus monkeys
SO ADDICTION BIOLOGY
LA English
DT Article
DE Addiction; choice; cocaine; kappa opioid receptor; nor-binaltorphimine;
rhesus monkey
ID BASAL EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; ENVIRONMENTAL
MANIPULATIONS; ALTERNATIVE REINFORCER; MESSENGER-RNA; AGONIST; RATS;
NEUROCHEMISTRY; HUMANS; PHENDIMETRAZINE
AB The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse-related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self-administration under a novel procedure that featured two daily components: (1) a 2-hour choice' component (9:00-11:00 am) when monkeys could choose between food pellets and cocaine injections (0-0.1mg/kg per injection, intravenous) and (2) a 20-hour extended-access' component (noon to 8:00 am) when cocaine (0.1mg/kg per injection) was available under a fixed-ratio schedule to promote high daily cocaine intakes. Rhesus monkeys (n=4) were given 14 days of exposure to the choice+extended-access procedure then treated with nor-BNI (3.2 or 10.0mg/kg, intramuscular), and cocaine choice and extended-access cocaine intake were evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained both a dose-dependent increase in cocaine choice during choice components and a high level of cocaine intake during extended-access components. Neither 3.2 nor 10mg/kg nor-BNI significantly altered cocaine choice or extended-access cocaine intake. In two additional monkeys, nor-BNI also had no effect on cocaine choice or extended-access cocaine intake when it was administered at the beginning of exposure to the extended-access components. Overall, these results do not support a major role for the dynorphin/KOR system in modulating cocaine self-administration under these conditions in non-human primates nor do they support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy for cocaine addiction.
C1 [Hutsell, Blake A.; Negus, Sidney Stevens; Banks, Matthew L.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 North 12th St,POB 980613, Richmond, VA 23298 USA.
[Negus, Sidney Stevens; Banks, Matthew L.] Virginia Commonwealth Univ, Inst Drug & Alcohol Abuse Studies, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Chem Biol Branch, NIH, Bethesda, MD USA.
[Cheng, Kejun] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Banks, ML (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 North 12th St,POB 980613, Richmond, VA 23298 USA.
EM mbanks7@vcu.edu
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU National Institute on Drug Abuse of the National Institutes of Health
[R01 DA026946, T32 DA007027]
FX Research reported in this publication was supported by the National
Institute on Drug Abuse of the National Institutes of Health under award
numbers R01 DA026946 and T32 DA007027. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health and the Food and
Drug Administration. We thank Jennifer Gough and Crystal Reyns for
technical assistance and Kevin Costa for writing the original computer
program version.
NR 60
TC 2
Z9 2
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
EI 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2016
VL 21
IS 2
BP 360
EP 373
DI 10.1111/adb.12206
PG 14
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA DF2CW
UT WOS:000371148700013
PM 25581305
ER
PT J
AU Colton, B
McConeghy, KW
Schreckenberger, PC
Danziger, LH
AF Colton, Benjamin
McConeghy, Kevin W.
Schreckenberger, Paul C.
Danziger, Larry H.
TI IV minocycline revisited for infections caused by multidrug-resistant
organisms
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
ID GRAM-NEGATIVE BACILLI; IN-VITRO ACTIVITIES; ACINETOBACTER-BAUMANNII;
INTRAVENOUS MINOCYCLINE; CARBAPENEM-RESISTANCE; STAPHYLOCOCCUS-AUREUS;
ESCHERICHIA-COLI; RENAL-FAILURE; RIBOSOMAL-RNA; TIGECYCLINE
AB Purpose. The evidence supporting the potential use of i.v. minocycline for serious infections caused by multidrug-resistant organisms (MDROs) is summarized.
Summary. Minocycline achieves good tissue penetration and excellent oral absorption. Minocycline achieves serum concentrations comparable to other tetracyclines, with peak serum concentrations ranging from 3 to 8.75 mg/L following i.v. administration of 200 mg. Minocycline retains antimicrobial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus as well as many gram-negative pathogens, such as Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Stenotrophomonas maltophilia. Minocycline has been used to treat respiratory infections caused by Acinetobacter baumannii and bloodstream infections. The majority of these gram-negative infections were treated with combination therapy, with results similar to those seen with first-line agents. The ability to switch from parenteral to oral therapy and its favorable tissue penetration make minocycline an attractive option for severe respiratory or skin and skin structure infections. For A. baumannii infections, minocycline is the second most active agent in vitro and may be the only therapeutic option in certain cases. The overall clinical experience with minocycline supports its use to treat A. baumannii infections alone or in combination with other agents. Minocycline could be used to treat other MDRO gram negative infections but only as an agent of last resort due to the limited data available.
Conclusion. The available pharmacokinetic and clinical data support the use of i.v. minocycline for the treatment of MDRO infections, including infections due to S. aureus coagulase-negative and gram-negative pathogens.
C1 [Colton, Benjamin] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[McConeghy, Kevin W.] Vet Affairs Med Ctr, Providence, RI USA.
[Schreckenberger, Paul C.] Loyola Univ, Sch Med, Chicago, IL 60611 USA.
[Danziger, Larry H.] Univ Illinois, Coll Pharm, Chicago, IL USA.
RP Danziger, LH (reprint author), Univ Illinois, Coll Pharm, Chicago, IL USA.
EM danziger@uic.edu
NR 46
TC 3
Z9 3
U1 0
U2 5
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
EI 1535-2900
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD MAR 1
PY 2016
VL 73
IS 5
BP 279
EP 285
DI 10.2146/ajhp150290
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DF5FB
UT WOS:000371376100009
PM 26896499
ER
PT J
AU You, LH
Zheng, BJ
Wang, SM
Ci, YZ
Yu, P
Shi, ZH
Fan, YM
Wang, LP
Chang, SY
Rouault, TA
Anderson, GJ
Wang, FD
Duan, XL
Chang, YZ
AF You, Lin-Hao
Zheng, Bing-Jie
Wang, Shu-Min
Ci, Yun-Zhe
Yu, Peng
Shi, Zhen-Hua
Fan, Yu-Mei
Wang, Li-Peng
Chang, Shi-Yang
Rouault, Tracey A.
Anderson, Gregory J.
Wang, Fudi
Duan, Xiang-Lin
Chang, Yan-Zhong
TI ASTROCYTE HEPCIDIN REGULATE IRON TRAFFIC ACROSS THE BRAIN ENDOTHELIUM
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [You, Lin-Hao; Zheng, Bing-Jie; Wang, Shu-Min; Ci, Yun-Zhe; Yu, Peng; Shi, Zhen-Hua; Fan, Yu-Mei; Wang, Li-Peng; Chang, Shi-Yang; Duan, Xiang-Lin; Chang, Yan-Zhong] Hebei Normal Univ, Shijiazhuang, Hebei, Peoples R China.
[Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Anderson, Gregory J.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Wang, Fudi] Zhejiang Univ, Hangzhou, Zhejiang, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2016
VL 91
IS 3
MA 65
BP E265
EP E265
PG 1
WC Hematology
SC Hematology
GA DF2HI
UT WOS:000371162800246
ER
PT J
AU Safaeian, M
Robbins, HA
Berndt, SI
Lynch, CF
Fraumeni, JF
Engels, EA
AF Safaeian, M.
Robbins, H. A.
Berndt, S. I.
Lynch, C. F.
Fraumeni, J. F., Jr.
Engels, E. A.
TI Risk of Colorectal Cancer After Solid Organ Transplantation in the
United States
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Scope: health services and outcomes research; translational research;
science; Discipline: organ transplantation in general; Focus: cancer;
malignancy; neoplasia: risk factors; epidemiology
ID PRIMARY SCLEROSING CHOLANGITIS; INFLAMMATORY-BOWEL-DISEASE;
LIVER-TRANSPLANTATION; KIDNEY-TRANSPLANTATION; RECIPIENTS; POPULATION;
COHORT; METAANALYSIS; NATIONWIDE; NEOPLASIA
AB Solid organ transplant recipients have increased colorectal cancer (CRC) risk. We assessed CRC risk among transplant recipients and identified factors contributing to this association. The US transplant registry was linked to 15 population-based cancer registries (1987-2010). We compared CRC risk in recipients to the general population by using standardized incidence ratios (SIRs) and identified CRC risk factors by using Poisson regression. Based on 790 cases of CRC among 224 098 transplant recipients, the recipients had elevated CRC risk (SIR 1.12, 95% confidence interval [CI] 1.04 to 1.20). The increase was driven by an excess of proximal colon cancer (SIR 1.69, 95% CI 1.53 to 1.87), while distal colon cancer was not increased (SIR 0.93, 95% CI 0.80 to 1.07), and rectal cancer was reduced (SIR 0.64, 95% CI 0.54 to 0.76). In multivariate analyses, CRC was increased markedly in lung recipients with cystic fibrosis (incidence rate ratio [IRR] 12.3, 95% CI 6.94 to 21.9, vs. kidney recipients). Liver recipients with primary sclerosing cholangitis and inflammatory bowel disease also had elevated CRC risk (IRR 5.32, 95% CI 3.73 to 7.58). Maintenance therapy with cyclosporine and azathioprine was associated with proximal colon cancer (IRR 1.53, 95% CI 1.05 to 2.23). Incidence was not elevated in a subgroup of kidney recipients treated with tacrolimus and mycophenolate mofetil, pointing to the relevance of the identified risk factors. Transplant recipients have increased proximal colon cancer risk, likely related to underlying medical conditions (cystic fibrosis and primary sclerosing cholangitis) and specific immunosuppressive regimens.
C1 [Safaeian, M.; Robbins, H. A.; Berndt, S. I.; Fraumeni, J. F., Jr.; Engels, E. A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lynch, C. F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Robbins, H. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM safaeianm@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA086862, T32
CA009314]
NR 35
TC 5
Z9 5
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAR
PY 2016
VL 16
IS 3
BP 960
EP 967
DI 10.1111/ajt.13549
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DF3JQ
UT WOS:000371240500028
PM 26731613
ER
PT J
AU Medina, SH
Miller, SE
Keim, AI
Gorka, AP
Schnermann, MJ
Schneider, JP
AF Medina, Scott H.
Miller, Stephen E.
Keim, Allison I.
Gorka, Alexander P.
Schnermann, Martin J.
Schneider, Joel P.
TI An Intrinsically Disordered Peptide Facilitates Non-Endosomal Cell Entry
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE cell-penetrating peptides; drug delivery; gene expression; live-cell
microscopy; translocation
ID BETA-HAIRPIN PEPTIDES; PENETRATING PEPTIDES; SECONDARY STRUCTURE;
LIPID-BILAYER; MEMBRANE; DEFENSINS; MECHANISM; DELIVERY; BINDING
AB Many cell-penetrating peptides (CPPs) fold at cell surfaces, adopting - or -structure that enable their intracellular transport. However, the same structural folds that facilitate cellular entry can also elicit potent membrane-lytic activity, limiting their use in delivery applications. Further, a distinct CPP can enter cells through many mechanisms, often leading to endosomal entrapment. Herein, we describe an intrinsically disordered peptide (CLIP6) that exclusively employs non-endosomal mechanisms to cross cellular membranes, while being remarkably biocompatible and serum-stable. We show that a single anionic glutamate residue is responsible for maintaining the disordered bioactive state of the peptide, defines its mechanism of cellular entry, and is central to its biocompatibility. CLIP6 can deliver membrane-impermeable cargo directly to the cytoplasm of cells, suggesting its broad utility for delivery of drug candidates limited by poor cell permeability and endosomal degradation.
C1 [Medina, Scott H.; Miller, Stephen E.; Keim, Allison I.; Gorka, Alexander P.; Schnermann, Martin J.; Schneider, Joel P.] NCI, Biol Chem Lab, Natl Inst Hlth Ft Detrick, 376 Boyle St, Frederick, MD 21702 USA.
RP Schneider, JP (reprint author), NCI, Biol Chem Lab, Natl Inst Hlth Ft Detrick, 376 Boyle St, Frederick, MD 21702 USA.
EM Joel.Schneider@nih.gov
FU National Cancer Institute, National Institutes of Health
FX We thank Drs. Susan Mackem and Jianjian Zhu, who established the MEF
transgenic cell line. Research funding was provided by the Intramural
Research Program of the National Cancer Institute, National Institutes
of Health.
NR 25
TC 4
Z9 4
U1 10
U2 31
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD MAR 1
PY 2016
VL 55
IS 10
BP 3369
EP 3372
DI 10.1002/anie.201510518
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DF5UO
UT WOS:000371418200025
PM 26835878
ER
PT J
AU Teterina, NL
Maximova, OA
Kenney, H
Liu, GP
Pletnev, AG
AF Teterina, Natalya L.
Maximova, Olga A.
Kenney, Heather
Liu, Guangping
Pletnev, Alexander G.
TI MicroRNA-based control of tick-borne flavivirus neuropathogenesis:
Challenges and perspectives
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Flavivirus; microRNAs; Neuropathogenesis
ID WEST NILE VIRUS; CENTRAL-NERVOUS-SYSTEM; 3' NONCODING REGION; STRAIN
TP21 E5; ENCEPHALITIS-VIRUS; LANGAT VIRUS; IMMUNODEFICIENT MICE; VACCINE
CANDIDATE; DENGUE TYPE-4; NEUROINVASIVENESS
AB In recent years, microRNA-targeting has become an effective strategy for selective control of tissue tropism and pathogenicity of both DNA and RNA viruses. Previously, we reported the successful application of this strategy to control the neurovirulent phenotype of a model chimeric tick-borne encephalitis/dengue type 4 virus (TBEV/DEN4), containing the structural protein genes of a highly virulent TBEV in the genetic backbone of non-neuroinvasive DEN4 virus. In the present study, we investigated the suitability of this approach for the attenuation of the more neurovirulent chimeric virus (TBEV/LGTV), which is based on the genetic backbone of the naturally attenuated member of the TBEV serocomplex, a Langat virus (LGTV). Unlike the TBEV/DEN4, the TBEV/LGTV virus retained the ability of its parental viruses to spread from the peripheral site of inoculation to the CNS. We evaluated ten potential sites in the 3'NCR of the TBEV/LGTV genome for placement of microRNA (miRNA) targets and found that the TBEV/LGTV genome is more restrictive for such genetic manipulations compared to TBEV/DEN4. In addition, unlike TBEV/DEN4 virus, the introduction of multiple miRNA targets into either the 3'NCR or ORF of the TBEV/LGTV genome had only a modest effect on virus attenuation in the developing CNS of highly permissive newborn mice. However, simultaneous miRNA-targeting in the ORF and 3'NCR had synergistic effect on control and silencing of virus replication in the brain and completely abolished the virus neurotropism. Furthermore, neuroinvasiveness of miRNA-targeted TBEV/LGTV viruses in very sensitive immunodeficient SCID mice was significantly limited. Immunocompetent animals immunized with such viruses were completely protected against challenge with the neurovirulent LGTV parent. These findings support the rationale of the miRNA-targeting approach to develop live attenuated virus vaccines against various neurotropic viruses. Published by Elsevier B.V.
C1 [Teterina, Natalya L.; Maximova, Olga A.; Kenney, Heather; Liu, Guangping; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Pletnev, AG (reprint author), NIAID, NIH, Bldg 33,Room 3W10A,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM apletnev@niaid.nih.gov
FU Division of Intramural Research Program of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX We would like to thank Dr. E. Ehrenfeld for critical reading of the
manuscript, Dr. K. Shen (BCBB, NIAID, NIH) for help with statistical
analysis, and Dr. A. Engle for help in constructing the TBEV/LGTV
viruses. This work was supported by the Division of Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 42
TC 1
Z9 1
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
EI 1872-9096
J9 ANTIVIR RES
JI Antiviral Res.
PD MAR
PY 2016
VL 127
BP 57
EP 67
DI 10.1016/j.antiviral.2016.01.003
PG 11
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA DF5CC
UT WOS:000371368400007
PM 26794396
ER
PT J
AU Canna, SW
Nigrovic, PA
AF Canna, Scott W.
Nigrovic, Peter A.
TI 21st Century Storm Chasers: Defining Macrophage Activation Syndrome
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Editorial Material
ID JUVENILE IDIOPATHIC ARTHRITIS; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS;
GUIDELINES; MUTATION; AUTOINFLAMMATION
C1 [Canna, Scott W.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Nigrovic, Peter A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Nigrovic, Peter A.] Boston Childrens Hosp, Boston, MA USA.
RP Canna, SW (reprint author), NIAMSD, Autoinflammatory Pathogenesis Unit, NIH, 10 Ctr Dr,Bldg 10,Room 13c103,MSC 1930, Bethesda, MD 20892 USA.; Nigrovic, PA (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith Bldg,Room 516b,One Jimmy Fund Way, Boston, MA 02115 USA.
EM scott.canna@nih.gov; pnigrovic@partners.org
FU Intramural NIH HHS; NIAMS NIH HHS [AR-065538, AR-061602]
NR 15
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAR
PY 2016
VL 68
IS 3
BP 557
EP 560
DI 10.1002/art.39329
PG 4
WC Rheumatology
SC Rheumatology
GA DF3ON
UT WOS:000371254300001
PM 26314501
ER
PT J
AU Habers, GEA
Huber, AM
Mamyrova, G
Targoff, IN
O'Hanlon, TP
Adams, S
Pandey, JP
Boonacker, C
van Brussel, M
Miller, FW
van Royen-Kerkhof, A
Rider, LG
AF Habers, G. Esther A.
Huber, Adam M.
Mamyrova, Gulnara
Targoff, Ira N.
O'Hanlon, Terrance P.
Adams, Sharon
Pandey, Janardan P.
Boonacker, Chantal
van Brussel, Marco
Miller, Frederick W.
van Royen-Kerkhof, Annet
Rider, Lisa G.
CA Childhood Myositis Heterogeneity S
TI Association of Myositis Autoantibodies, Clinical Features, and
Environmental Exposures at Illness Onset With Disease Course in Juvenile
Myositis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; PROGNOSTIC-FACTORS; GENE
POLYMORPHISMS; SYMPTOM ONSET; DERMATOMYOSITIS; PHENOTYPES; CHILDREN;
DURATION; POLYMYOSITIS; MULTICENTER
AB Objective. To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).
Methods. Univariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms.
Results. Multivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis-specific autoantibodies (multinomial odds ratio [OR] 4.2 and 2.8, respectively), myositis-associated autoantibodies (multinomial OR 4.8 and 3.5), and a documented infection within 6 months of illness onset (multinomial OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to a polycyclic course. Furthermore, severe illness onset was associated with a chronic course compared to monocyclic or polycyclic courses (multinomial OR 2.1 and 2.6, respectively), while anti-p155/140 autoantibodies were associated with chronic or polycyclic courses compared to a monocyclic course (multinomial OR 3.9 and 2.3, respectively). Additional univariable associations of a chronic course compared to a monocyclic course included photosensitivity, V-sign or shawl sign rashes, and cuticular overgrowth (OR 2.2-3.2). The mean ultraviolet index and highest ultraviolet index in the month before diagnosis were associated with a chronic course compared to a polycyclic course in boys (OR 1.5 and 1.3), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2).
Conclusion. Our findings indicate that myositis autoantibodies, in particular anti-p155/140, and a number of early clinical features and environmental exposures are associated with a chronic course in patients with juvenile IIM. These findings suggest that early factors, which are associated with poorer outcomes in juvenile IIM, can be identified.
C1 [Habers, G. Esther A.; Boonacker, Chantal; van Brussel, Marco; van Royen-Kerkhof, Annet] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada.
[Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada.
[Mamyrova, Gulnara] George Washington Univ, Sch Med, Washington, DC USA.
[Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, VAMC, Oklahoma City, OK USA.
[Targoff, Ira N.] Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[O'Hanlon, Terrance P.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
[Adams, Sharon] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Pandey, Janardan P.] Med Univ S Carolina, Charleston, SC USA.
RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, Clin Res Branch, Clin Res Ctr, Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH; Cure JM Foundation
FX Supported in part by the Intramural Research Program of the National
Institute of Environmental Health Sciences, NIH. Dr. Mamyrova's work was
supported by the Cure JM Foundation.
NR 29
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAR
PY 2016
VL 68
IS 3
BP 761
EP 768
DI 10.1002/art.39466
PG 8
WC Rheumatology
SC Rheumatology
GA DF3ON
UT WOS:000371254300026
PM 26474155
ER
PT J
AU Heitkemper, MM
Han, CJ
Jarrett, ME
Gu, HW
Djukovic, D
Shulman, RJ
Raftery, D
Henderson, WA
Cain, KC
AF Heitkemper, Margaret M.
Han, Claire Jungyoun
Jarrett, Monica E.
Gu, Haiwei
Djukovic, Danijel
Shulman, Robert J.
Raftery, Daniel
Henderson, Wendy A.
Cain, Kevin C.
TI Serum Tryptophan Metabolite Levels During Sleep in Patients With and
Without Irritable Bowel Syndrome (IBS)
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE metabolomics; irritable bowel syndrome; sleep; tryptophan; melatonin
ID KYNURENINE PATHWAY; MELATONIN; SEVERITY; SYMPTOMS; DISORDER; WOMEN
AB Poor sleep and stress are more frequently reported by women with irritable bowel syndrome (IBS) than by healthy control (HC) women. The pathophysiology linking poor sleep and stress to gastrointestinal symptoms remains poorly understood. We used a metabolomic approach to determine whether tryptophan (TRP) metabolites differ between women with and without IBS and whether the levels are associated with sleep indices and serum cortisol levels. This study sample included 38 women with IBS and 21 HCs. The women were studied in a sleep laboratory for three consecutive nights. On the third night of the study, a social stressor was introduced, then blood samples were drawn every 20 min and sleep indices were measured. Metabolites were determined by targeted liquid chromatography tandem mass spectrometry in a sample collected 1 hr after the onset of sleep. The ratios of each metabolite to TRP were used for analyses. Correlations were controlled for age and oral contraceptive use. Melatonin/TRP levels were lower (p = .005) in the IBS-diarrhea group versus the IBS-constipation and HC groups, and kynurenine/TRP ratios tended to be lower (p = .067) in the total IBS and IBS-diarrhea groups compared to HCs. Associations within the HC group included melatonin/TRP with polysomnography-sleep efficiency (r = .61, p = .006) and weaker positive correlations with the other ratios for either sleep efficiency or percentage time in rapid eye movement sleep (r > .40, p = .025-.091). This study suggests that reductions in early nighttime melatonin/TRP levels may be related to altered sleep quality in IBS, particularly those with diarrhea.
C1 [Heitkemper, Margaret M.; Han, Claire Jungyoun; Jarrett, Monica E.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Box 357266, Seattle, WA 98195 USA.
[Gu, Haiwei; Djukovic, Danijel; Raftery, Daniel] Univ Washington, Northwest Metabol Res Ctr, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Shulman, Robert J.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Raftery, Daniel] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Henderson, Wendy A.] NINR, Digest Disorders Unit,Biobehav Branch, Div Intramural Res, NIH,DHHS, Bethesda, MD 20892 USA.
[Cain, Kevin C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Cain, Kevin C.] Univ Washington, Off Nursing Res, Seattle, WA 98195 USA.
RP Heitkemper, MM (reprint author), Univ Washington, Dept Biobehav Nursing & Hlth Syst, Box 357266, Seattle, WA 98195 USA.
EM heit@u.washington.edu
OI Henderson, Wendy/0000-0003-3924-7118
FU NINR, NIH [NR04101]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
project was supported by the NINR, NIH (NR04101).
NR 18
TC 2
Z9 2
U1 3
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
EI 1552-4175
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD MAR
PY 2016
VL 18
IS 2
BP 193
EP 198
DI 10.1177/1099800415594251
PG 6
WC Nursing
SC Nursing
GA DF4HM
UT WOS:000371308600009
PM 26156003
ER
PT J
AU Giovinazzo, H
Kumar, P
Sheikh, A
Brooks, KM
Ivanovic, M
Walsh, M
Caron, WP
Kowalsky, RJ
Song, G
Whitlow, A
Clarke-Pearson, DL
Brewster, WR
Van Le, L
Zamboni, BA
Bae-Jump, V
Gehrig, PA
Zamboni, WC
AF Giovinazzo, Hugh
Kumar, Parag
Sheikh, Arif
Brooks, Kristina M.
Ivanovic, Marija
Walsh, Mark
Caron, Whitney P.
Kowalsky, Richard J.
Song, Gina
Whitlow, Ann
Clarke-Pearson, Daniel L.
Brewster, Wendy R.
Van Le, Linda
Zamboni, Beth A.
Bae-Jump, Victoria
Gehrig, Paola A.
Zamboni, William C.
TI Technetium Tc 99m sulfur colloid phenotypic probe for the
pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin
in women with ovarian cancer
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Pharmacokinetics; Pharmacodynamics; Liposomes; TSC; PEGylated liposomal
doxorubicin; Phenotypic probe; Ovarian cancer
ID STERICALLY STABILIZED LIPOSOMES; RETICULOENDOTHELIAL SYSTEM; ADVANCED
MALIGNANCIES; TUMOR DISPOSITION; CKD-602 S-CKD602; SOLID TUMORS;
STEALTH; ANTHRACYCLINES; CISPLATIN; PLATINUM
AB Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer.
TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30-40 mg/m(2) IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling.
There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R (2) = 0.61, p = 0.02), particularly in patients receiving PLD alone (R (2) = 0.81, p = 0.04). There was a positive relationship (rho = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands.
TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development.
C1 [Giovinazzo, Hugh; Kumar, Parag; Walsh, Mark; Caron, Whitney P.; Song, Gina; Zamboni, William C.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, 120 Mason Farm Rd,Suite 1013,CB 7361, Chapel Hill, NC 27599 USA.
[Giovinazzo, Hugh] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, 725 N Wolfe St, Baltimore, MD 21205 USA.
[Kumar, Parag; Brooks, Kristina M.] NIH, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, 10 Ctr Dr Bldg 10,1C-240G, Bethesda, MD 20892 USA.
[Sheikh, Arif; Ivanovic, Marija; Kowalsky, Richard J.; Whitlow, Ann; Clarke-Pearson, Daniel L.; Brewster, Wendy R.; Van Le, Linda; Bae-Jump, Victoria; Gehrig, Paola A.] Univ N Carolina, Sch Med, 321 S Columbia St, Chapel Hill, NC 27599 USA.
[Clarke-Pearson, Daniel L.; Brewster, Wendy R.; Van Le, Linda; Bae-Jump, Victoria; Gehrig, Paola A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 103B Phys Off Bldg CB 7572, Chapel Hill, NC 27599 USA.
[Clarke-Pearson, Daniel L.; Brewster, Wendy R.; Van Le, Linda; Bae-Jump, Victoria; Gehrig, Paola A.; Zamboni, William C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, 101 Manning Dr, Chapel Hill, NC 27514 USA.
[Zamboni, Beth A.] Carlow Univ, Dept Math, Pittsburgh, PA USA.
[Zamboni, William C.] Univ N Carolina, Inst Pharmacogenom & Individualized Therapy, 120 Mason Farm Rd, Chapel Hill, NC 27599 USA.
[Zamboni, William C.] Carolina Ctr Canc Nanotechnol Excellence, 1079 Genet Med Bldg, Chapel Hill, NC 27599 USA.
[Zamboni, William C.] North Carolina Biomed Innovat Network, 013 Genet Med Bldg CB 7361, Chapel Hill, NC 27599 USA.
RP Zamboni, WC (reprint author), Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, 120 Mason Farm Rd,Suite 1013,CB 7361, Chapel Hill, NC 27599 USA.; Zamboni, WC (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, 101 Manning Dr, Chapel Hill, NC 27514 USA.; Zamboni, WC (reprint author), Univ N Carolina, Inst Pharmacogenom & Individualized Therapy, 120 Mason Farm Rd, Chapel Hill, NC 27599 USA.; Zamboni, WC (reprint author), Carolina Ctr Canc Nanotechnol Excellence, 1079 Genet Med Bldg, Chapel Hill, NC 27599 USA.; Zamboni, WC (reprint author), North Carolina Biomed Innovat Network, 013 Genet Med Bldg CB 7361, Chapel Hill, NC 27599 USA.
EM zamboni@email.unc.edu
OI Brooks, Kristina/0000-0002-3832-8699
FU Lineberger Comprehensive Cancer Center; UNC University Cancer Research
Fund (UCRF); Carolina Center of Cancer Nanotechnology Excellence
(C-CCNE) Pilot grant (NIH/NCI) [CA119343]
FX This study was funded by the Lineberger Comprehensive Cancer Center, UNC
University Cancer Research Fund (UCRF) and the Carolina Center of Cancer
Nanotechnology Excellence (C-CCNE) Pilot grant (NIH/NCI CA119343). The
investigators would like to thank the faculty and staff of the UNC
School of Medicine, Divisions of Gynecologic Oncology and Nuclear
Medicine; UNC North Carolina Translational and Clinical Sciences
Institute, Clinical and Translational Research Center; UNC Eshelman
School of Pharmacy, Translational Oncology and Nanoparticle Drug
Development Initiative Lab; the CCNE; and the patients, families, and
friends who made this work possible.
NR 38
TC 2
Z9 3
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD MAR
PY 2016
VL 77
IS 3
BP 565
EP 573
DI 10.1007/s00280-015-2945-y
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA DF3LQ
UT WOS:000371246100012
PM 26822231
ER
PT J
AU Ruan, XB
Li, P
Cangelosi, A
Yang, L
Cao, HM
AF Ruan, Xiangbo
Li, Ping
Cangelosi, Andrew
Yang, Ling
Cao, Haiming
TI A Long Non-coding RNA, IncLGR, Regulates Hepatic Glucokinase Expression
and Glycogen Storage during Fasting
SO CELL REPORTS
LA English
DT Article
ID GENE-EXPRESSION; TRANSCRIPTION; METABOLISM; ROLES
AB Glucose levels in mammals are tightly controlled through multiple mechanisms to meet systemic energy demands. Downregulation of hepatic glucokinase (GCK) during fasting facilitates the transition of the liver from a glucose-consuming to a gluconeogenic organ. Here, we report the transcriptional regulation of hepatic GCK by a long non-coding RNA (lncRNA) named liver GCK repressor (lncLGR). lncLGR is induced by fasting, and physiological overexpression of lncLGR to mimic fasting levels effectively suppresses GCK expression and reduces hepatic glycogen content in mice. Consistently, lncLGR knockdown enhances GCK expression and glycogen storage in fasted mice. Mechanistically, lncLGR specifically binds to heterogenous nuclear ribonucleoprotein L (hnRNPL), which is further confirmed to be a transcriptional repressor of GCK in vivo. Finally, we demonstrate that lncLGR facilitates the recruitment of hnRNPL to the GCK promoter and suppresses GCK transcription. Our data establish a lncRNA-mediated mechanism that regulates hepatic GCK expression and glycogen deposition in a physiological context.
C1 [Ruan, Xiangbo; Li, Ping; Cangelosi, Andrew; Yang, Ling; Cao, Haiming] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Cao, HM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM haiming.cao@nih.gov
RI Yang, Ling/F-4404-2016; Cao, Haiming/P-4634-2016; Ruan,
Xiangbo/P-9265-2016
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute, NIH [HL006103, HL006159]
FX This work was supported by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute, NIH (HL006103 and HL006159).
We thank Yong Chen and Marjan Gucek from NHLBI Proteomics Core for their
help with mass spectrometry analysis.
NR 16
TC 3
Z9 5
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAR 1
PY 2016
VL 14
IS 8
BP 1867
EP 1875
DI 10.1016/j.celrep.2016.01.062
PG 9
WC Cell Biology
SC Cell Biology
GA DF3BC
UT WOS:000371217700007
PM 26904944
ER
PT J
AU Wu, JQ
Keng, VW
Patmore, DM
Kendall, JJ
Patel, AV
Jousma, E
Jessen, WJ
Choi, K
Tschida, BR
Silverstein, KAT
Fan, DH
Schwartz, EB
Fuchs, JR
Zou, YS
Kim, MO
Dombi, E
Levy, DE
Huang, G
Cancelas, JA
Stemmer-Rachamimov, AO
Spinner, RJ
Largaespada, DA
Ratner, N
AF Wu, Jianqiang
Keng, Vincent W.
Patmore, Deanna M.
Kendall, Jed J.
Patel, Ami V.
Jousma, Edwin
Jessen, Walter J.
Choi, Kwangmin
Tschida, Barbara R.
Silverstein, Kevin A. T.
Fan, Danhua
Schwartz, Eric B.
Fuchs, James R.
Zou, Yuanshu
Kim, Mi-Ok
Dombi, Eva
Levy, David E.
Huang, Gang
Cancelas, Jose A.
Stemmer-Rachamimov, Anat O.
Spinner, Robert J.
Largaespada, David A.
Ratner, Nancy
TI Insertional Mutagenesis Identifies a STAT3/Arid1b/beta-catenin Pathway
Driving Neurofibroma Initiation
SO CELL REPORTS
LA English
DT Article
ID NERVE SHEATH TUMORS; NATURAL ANTISENSE TRANSCRIPTS; PANCREATIC-CANCER;
BETA-CATENIN; CELLS; NF1; PROGRESSION; GENE; ACTIVATION; TYPE-1
AB To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/beta-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and beta-catenin activity. beta-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and beta-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3 beta and the SWI/SNF gene Arid1b to increase beta-catenin. Knockdown of Arid1b or Gsk3 beta in Stat3(fl/fl); Nf1(fl/fl); DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/beta-catenin pathway inhibitors in neurofibroma therapeutic trials.
C1 [Wu, Jianqiang; Patmore, Deanna M.; Kendall, Jed J.; Patel, Ami V.; Jousma, Edwin; Jessen, Walter J.; Choi, Kwangmin; Huang, Gang; Cancelas, Jose A.; Ratner, Nancy] Univ Cincinnati, Cincinnati Childrens Hosp, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Zou, Yuanshu; Kim, Mi-Ok] Univ Cincinnati, Cincinnati Childrens Hosp, Cincinnati Childrens Hosp Res Fdn, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA.
[Keng, Vincent W.; Tschida, Barbara R.; Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Keng, Vincent W.; Largaespada, David A.] Univ Minnesota, Dept Pediat Cell Biol & Dev, Minneapolis, MN 55455 USA.
[Keng, Vincent W.; Tschida, Barbara R.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA.
[Silverstein, Kevin A. T.; Fan, Danhua] Univ Minnesota, Biostat & Informat, Minneapolis, MN 55455 USA.
[Schwartz, Eric B.; Fuchs, James R.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
[Dombi, Eva] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Levy, David E.] NYU, Sch Med, Dept Pathol, 550 First Ave, New York, NY 10016 USA.
[Levy, David E.] NYU, Sch Med, Inst Canc, 550 First Ave, New York, NY 10016 USA.
[Cancelas, Jose A.] Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA.
[Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Spinner, Robert J.] Mayo Clin, Dept Neurol Surg, Rochester, MN 55905 USA.
[Keng, Vincent W.] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China.
RP Ratner, N (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp, Canc & Blood Dis Inst, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
EM nancy.ratner@cchmc.org
OI Keng, Vincent/0000-0003-3473-0653; Levy, David/0000-0002-7320-7788
FU NIH [R01 NS28840, P50 NS057531]; DAMD New Investigator Award
[W81XWH-11-1-0259]; Ohio State University Comprehensive Cancer Center
Pelotonia Idea Grant; American Cancer Society [IRG-67-00344]
FX We thank the Minnesota Supercomputing Institute for computational
resources for sequence analysis, Dr. Ari Melnick (Weil Cornell Medical
School) for assistance in design of histone modification analysis, and
Ms. Huiqing Li for animal husbandry. This work was supported by NIH R01
NS28840 (N.R.), NIH P50 NS057531 (N.R. and D.A.L.), a DAMD New
Investigator Award (W81XWH-11-1-0259), an Ohio State University
Comprehensive Cancer Center Pelotonia Idea Grant (J.W.), and the
American Cancer Society (IRG-67-003-44) (J.R.F.). The CHTN provided some
benign neurofibromas used in this study.
NR 40
TC 4
Z9 4
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAR 1
PY 2016
VL 14
IS 8
BP 1979
EP 1990
DI 10.1016/j.celrep.2016.01.074
PG 12
WC Cell Biology
SC Cell Biology
GA DF3BC
UT WOS:000371217700017
PM 26904939
ER
PT J
AU Papadakis, GZ
Millo, C
Bagci, U
Sadowski, SM
Stratakis, CA
AF Papadakis, Georgios Z.
Millo, Corina
Bagci, Ulas
Sadowski, Samira M.
Stratakis, Constantine A.
TI Schmorl Nodes Can Cause Increased 68Ga DOTATATE Activity on PET/CT,
Mimicking Metastasis in Patients With Neuroendocrine Malignancy
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE neuroendocrine tumor; Ga-68 DOTATATE PET/CT; Schmorl node; inflammation
ID GA-68-DOTATATE PET/CT; SOMATOSTATIN; MACROPHAGES; EXPRESSION
AB Schmorl node (SN) is the herniation of the nucleus pulposus through the cartilaginous and bony endplate into the adjacent vertebral body. It is documented that SNs produce areas of moderately increased F-18-FDG uptake. We present a case of a patient with history of neuroendocrine tumor, who underwent Ga-68 DOTATATE PET/CT for follow-up, showing increased focal vertebral uptake suggestive of bone metastasis. CT revealed typical findings of an SN. The presented case indicates that SNs should be considered when encountering focally increased skeletal uptake in Ga-68 DOTATATE PET/CT studies, which can mimic metastasis in patients with history of neuroendocrine tumors.
C1 [Papadakis, Georgios Z.] NIH, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Millo, Corina] NIH, Div Nucl Med, RAD&IS Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Bagci, Ulas] Univ Cent Florida, Ctr Comp Vis Res, Dept Comp Sci & Elect, Orlando, FL 32816 USA.
[Sadowski, Samira M.] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
OI Bagci, Ulas/0000-0001-7379-6829
FU Intramural NIH HHS [ZIA HD008920-01]
NR 15
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD MAR
PY 2016
VL 41
IS 3
BP 249
EP 250
DI 10.1097/RLU.0000000000001065
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DE2UI
UT WOS:000370482300024
PM 26562580
ER
PT J
AU Manjula, A
Pushpanathan, M
Sathyavathi, S
Gunasekaran, P
Rajendhran, J
AF Manjula, Arumugam
Pushpanathan, Muthuirulan
Sathyavathi, Sundararaju
Gunasekaran, Paramasamy
Rajendhran, Jeyaprakash
TI Comparative Analysis of Microbial Diversity in Termite Gut and Termite
Nest Using Ion Sequencing
SO CURRENT MICROBIOLOGY
LA English
DT Article
ID SOIL-FEEDING TERMITE; BACTERIAL COMMUNITY STRUCTURE; PHYLOGENETIC
DIVERSITY; MOUNDS; LIGNOCELLULOSE; METHANOGENS; STABILITY; SYMBIONTS;
DIGESTION; GENOME
AB Termite gut and termite nest possess complex microbial communities. However, only limited information is available on the comparative investigation of termite gut and nest-associated microbial communities. In the present study, we examined and compared the bacterial diversity of termite gut and their respective nest by high-throughput sequencing of V3 hypervariable region of 16S rDNA. A total of 14 barcoded libraries were generated from seven termite gut samples and their respective nest samples, and sequenced using Ion Torrent platform. The sequences of each group were pooled, which yielded 170,644 and 132,000 reads from termite gut and termite nest samples, respectively. Phylogenetic analysis revealed significant differences in the bacterial diversity and community structure between termite gut and termite nest samples. Phyla Verrucomicrobia and Acidobacteria were observed only in termite gut, whereas Synergistetes and Chlorobi were observed only in termite nest samples. These variations in microbial structure and composition could be attributed with the differences in physiological conditions prevailing in the termite gut (anoxic and alkaline) and termite nest (oxic, slightly acidic and rich in organic matter) environment. Overall, this study unmasked the complexity of bacterial population in the respective niche. Interestingly, majority of the sequence reads could be classified only up to the domain level indicating the presence of a huge number of uncultivable or unidentified novel bacterial species in both termite gut and nest samples. Whole metagenome sequencing and assessing the metabolic potential of these samples will be useful for biotechnological applications.
C1 [Manjula, Arumugam; Sathyavathi, Sundararaju; Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash] Madurai Kamaraj Univ, Ctr Excellence Genom Sci, Sch Biol Sci, Dept Genet, Madurai 625021, Tamil Nadu, India.
[Pushpanathan, Muthuirulan] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Rajendhran, J (reprint author), Madurai Kamaraj Univ, Ctr Excellence Genom Sci, Sch Biol Sci, Dept Genet, Madurai 625021, Tamil Nadu, India.
EM jrajendhran@gmail.com
OI Pushpanathan, Muthuirulan/0000-0001-6240-3073
FU CSIR-SRF (Council of Scientific and Industrial Research-Senior Research
Fellowship) New Delhi
FX The authors would like to thank CSIR-SRF (Council of Scientific and
Industrial Research-Senior Research Fellowship) New Delhi for providing
financial support. We would also extend our thanks to central facilities
UGC-CAS, UGC-NRCBS, DBT-IPLS and DST-PURSE programs at School of
Biological Sciences, Madurai Kamaraj University.
NR 37
TC 1
Z9 1
U1 7
U2 24
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0343-8651
EI 1432-0991
J9 CURR MICROBIOL
JI Curr. Microbiol.
PD MAR
PY 2016
VL 72
IS 3
BP 267
EP 275
DI 10.1007/s00284-015-0947-y
PG 9
WC Microbiology
SC Microbiology
GA DF3NM
UT WOS:000371251200005
PM 26613615
ER
PT J
AU Hung, IH
Schoenwolf, GC
Lewandoski, M
Ornitz, DM
AF Hung, Irene H.
Schoenwolf, Gary C.
Lewandoski, Mark
Ornitz, David M.
TI A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and
redundant roles in skeletal development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE FGF; Chondrogenesis; Growth plate; Mouse
ID GROWTH-FACTOR RECEPTOR-3; HYPERTROPHIC CHONDROCYTE DIFFERENTIATION;
INDIAN-HEDGEHOG; BONE-GROWTH; MESSENGER-RNA; OSTEOBLAST DIFFERENTIATION;
ENDOCHONDRAL OSSIFICATION; CBFA1-DEFICIENT MICE; DEVELOPMENT SUGGESTS;
TARGETED DISRUPTION
AB Fibroblast growth factor (FGF) signaling is a critical regulator of skeletal development. Fgf9 and Fgf18 are the only FGF ligands with identified functions in embryonic bone growth. Mice lacking Fgf9 or Fgf18 have distinct skeletal phenotypes; however, the extent of overlapping or redundant functions for these ligands and the stage-specific contributions of FGF signaling to chondrogenesis and osteogenesis are not known. To identify separate versus shared roles for FGF9 and FGF18, we generated a combined series of Fgf9 and Fgf18 null alleles. Analysis of embryos lacking alleles of Fgf9 and Fgf18 shows that both encoded ligands function redundantly to control all stages of skeletogenesis; however, they have variable potencies along the proximodistal limb axis, suggesting gradients of activity during formation of the appendicular skeleton. Congenital absence of both Fe and Fgf18 results in a striking osteochondrodysplasia and revealed functions for FGF signaling in early proximal limb chondrogenesis. Additional defects were also noted in craniofacial bones, vertebrae, and ribs. Loss of alleles of Fgf9 and Fgf18 also affect the expression of genes encoding other key intrinsic skeletal regulators, including IHH, PTHLH (PTHrP), and RUNX2, revealing potential direct, indirect, and compensatory mechanisms to coordinate chondrogenesis and osteogenesis. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Hung, Irene H.; Schoenwolf, Gary C.] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA.
[Hung, Irene H.; Lewandoski, Mark] NCI, Canc & Dev Biol Lab, 1050 Boyles St,Bldg 539,Rm 135, Frederick, MD 21701 USA.
[Hung, Irene H.; Ornitz, David M.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Ornitz, David M.] Washington Univ, Sch Med, Rm 3902 South Bldg,Campus Box 8103, St Louis, MO 63110 USA.
RP Hung, IH (reprint author), NCI, Canc & Dev Biol Lab, 1050 Boyles St,Bldg 539,Rm 135, Frederick, MD 21701 USA.
EM irene.hung@hsc.utah.edu; dornitz@wustl.edu
FU NIH Grants [CHRCDA K12HD0410, K08HD058219, DC011819, HD049808];
University of Utah Department of Pediatrics Seed Funding; Primary
Children's Foundation Grants; Children's Health Research Center Funding;
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Washington
University Musculoskeletal Research Center [NIH P30 AR057235]
FX We thank L. Li, H.H. Shi, J. Hunter, E. Truffer, and A. Ferris for
technical help. IHH was supported by NIH Grants CHRCDA K12HD0410 and
K08HD058219, University of Utah Department of Pediatrics Seed Funding,
Primary Children's Foundation Grants, Children's Health Research Center
Funding. GCS was supported by NIH Grant DC011819. ML was supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. DMO was supported
by NIH Grant HD049808, Washington University Musculoskeletal Research
Center NIH P30 AR057235.
NR 82
TC 4
Z9 4
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD MAR 1
PY 2016
VL 411
IS 1
BP 72
EP 84
DI 10.1016/j.ydbio.2016.01.008
PG 13
WC Developmental Biology
SC Developmental Biology
GA DF6CY
UT WOS:000371444600007
PM 26794256
ER
PT J
AU Martina, JA
Diab, HI
Brady, OA
Puertollano, R
AF Martina, Jose A.
Diab, Heba I.
Brady, Owen A.
Puertollano, Rosa
TI TFEB and TFE3 are novel components of the integrated stress response
SO EMBO JOURNAL
LA English
DT Article
DE ATF4; ER stress; PERK; TFE3; TFEB
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION
FACTOR TFE3; RENAL-CELL CARCINOMA; LYSOSOMAL BIOGENESIS; RAG GTPASES; ER
STRESS; TRANSLATIONAL CONTROL; AUTOPHAGY; METABOLISM
AB To reestablish homeostasis and mitigate stress, cells must activate a series of adaptive intracellular signaling pathways. The participation of the transcription factors TFEB and TFE3 in cellular adaptation to starvation is well established. Here, we show that TFEB and TFE3 also play an important role in the cellular response to ER stress. Treatment with ER stressors causes translocation of TFEB and TFE3 to the nucleus in a process that is dependent on PERK and calcineurin but not on mTORC1. Activated TFEB and TFE3 enhance cellular response to stress by inducing direct transcriptional upregulation of ATF4 and other UPR genes. Under conditions of prolonged ER stress, TFEB and TFE3 contribute to cell death, thus revealing an unexpected role for these proteins in controlling cell fate. This work evidences a broader role of TFEB and TFE3 in the cellular response to stress than previously anticipated and reveals an integrated cooperation between different cellular stress pathways.
C1 [Martina, Jose A.; Diab, Heba I.; Brady, Owen A.; Puertollano, Rosa] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
RI di Ronza, Alberto/H-7674-2016
OI di Ronza, Alberto/0000-0002-9813-5143
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute (NHLBI)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood Institute
(NHLBI). We thank Dr. Philip McCoy and Dr. Pradeep Dagur (Flow Cytometry
Core, NHLBI) for their assistance in the Annexin V apoptosis analysis.
We also thank Dr. Gustavo Gutierrez and Dr. Hossein Zare (NIAMS) for
their assistance in the analysis of the ChIP-seq data and Dr. Douglas
Forrest (NIDDK) for assistance with the GloMax 96 Microplate
Luminometer.
NR 45
TC 10
Z9 10
U1 4
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD MAR 1
PY 2016
VL 35
IS 5
BP 479
EP 495
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DF6CH
UT WOS:000371442300003
PM 26813791
ER
PT J
AU Falcone, EL
Petts, JR
Fasano, MB
Ford, B
Nauseef, WM
Neves, JF
Simoes, MJ
Tierce, ML
de la Morena, MT
Greenberg, DE
Zerbe, CS
Zelazny, AM
Holland, SM
AF Falcone, E. Liana
Petts, Jennifer R.
Fasano, Mary Beth
Ford, Bradley
Nauseef, William M.
Neves, Joao Farela
Simoes, Maria Joao
Tierce, Millard L.
de la Morena, M. Teresa
Greenberg, David E.
Zerbe, Christa S.
Zelazny, Adrian M.
Holland, Steven M.
TI Methylotroph Infections and Chronic Granulomatous Disease
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID PATHOGEN GRANULIBACTER-BETHESDENSIS; BACTERIAL PATHOGEN; PATIENT
AB Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.
C1 [Falcone, E. Liana; Zerbe, Christa S.; Zelazny, Adrian M.; Holland, Steven M.] NIH, Rm B3-4141,9000 Rockville Pike Blvd 10-CRC, Bethesda, MD 20892 USA.
[Petts, Jennifer R.; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Nauseef, William M.] Vet Adm Med Ctr, Iowa City, IA USA.
[Neves, Joao Farela] Ctr Hosp Lisboa Cent, Lisbon, Portugal.
[Simoes, Maria Joao] Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
[Tierce, Millard L.] Detroit Med Ctr, Detroit, MI USA.
[de la Morena, M. Teresa; Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Falcone, EL (reprint author), NIH, LCID NIAID, Rm B3-4141,9000 Rockville Pike Blvd 10-CRC, Bethesda, MD 20892 USA.
EM emilia.falcone@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland,
USA [ZO1-AI-00646-06]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland, USA (grant no. ZO1-AI-00646-06).
NR 14
TC 0
Z9 0
U1 1
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD MAR
PY 2016
VL 22
IS 3
BP 404
EP 409
DI 10.3201/eid2203.151265
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DF2RS
UT WOS:000371192100006
PM 26886412
ER
PT J
AU Wei, BN
Aiwis, KU
Li, Z
Wang, LQ
Valentin-Blasini, L
Sosnoff, CS
Xia, Y
Conway, KP
Blount, BC
AF Wei, Binnian
Aiwis, K. Udeni
Li, Zheng
Wang, Lanqing
Valentin-Blasini, Liza
Sosnoff, Connie S.
Xia, Yang
Conway, Kevin P.
Blount, Benjamin C.
TI Urinary concentrations of PAH and VOC metabolites in marijuana users
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE Cannabis smoke; Biomonitoring; PAHs; VOCs; Secondhand smoke;
Environmental tobacco smoke (ETS)
ID TANDEM MASS-SPECTROMETRY; POLYCYCLIC AROMATIC-HYDROCARBONS; PRENATAL
CANNABIS EXPOSURE; TOBACCO-SMOKE; US POPULATION; SIDESTREAM MARIJUANA;
ION CHROMATOGRAPHY; SECONDHAND SMOKE; CIGARETTE-SMOKE; LUNG-CANCER
AB Background: Marijuana is seeing increased therapeutic use, and is the world's third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns.
Objectives: To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure.
Methods: Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (>= 18 years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders.
Results: Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p < 0.05). Urinary thiocyanate (p < 0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p < 0.001) and acrylamide (p < 0.001), were significantly higher in recent marijuana users than in nonusers.
Conclusions: We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. Published by Elsevier Ltd.
C1 [Wei, Binnian; Aiwis, K. Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S.; Xia, Yang; Blount, Benjamin C.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Conway, Kevin P.] NIH, Div Epidemiol Serv & Prevent Res, Bethesda, MD USA.
RP Wei, BN (reprint author), Ctr Dis Control & Prevent, Div Sci Lab, 4770 Buford Hwy,NE Rd,Mail Stop F44, Atlanta, GA 30341 USA.
EM bwei@cdc.gov
OI Conway, Kevin/0000-0002-7638-339X; Wei, Binnian/0000-0003-0465-9964
FU Intramural CDC HHS [CC999999]
NR 53
TC 2
Z9 2
U1 9
U2 43
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD MAR
PY 2016
VL 88
BP 1
EP 8
DI 10.1016/j.envint.2015.12.003
PG 8
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DF4YU
UT WOS:000371359300001
PM 26690539
ER
PT J
AU Jukic, AM
Calafat, AM
McConnaughey, DR
Longnecker, MP
Hoppin, JA
Weinberg, CR
Wilcox, AJ
Baird, DD
AF Jukic, Anne Marie
Calafat, Antonia M.
McConnaughey, D. Robert
Longnecker, Matthew P.
Hoppin, Jane A.
Weinberg, Clarice R.
Wilcox, Allen J.
Baird, Donna D.
TI Urinary Concentrations of Phthalate Metabolites and Bisphenol A and
Associations with Follicular-Phase Length, Luteal-Phase Length,
Fecundability, and Early Pregnancy Loss
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID OXIDATIVE STRESS; INTRAUTERINE IMPLANTATION; PRENATAL EXPOSURE;
FERTILIZED OVA; IN-VITRO; WOMEN; CONCEPTION; PROGESTERONE; PROBABILITY;
VARIABILITY
AB BACKGROUND: Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss.
OBJECTIVES: We investigated these chemicals in relation to follicular-and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy.
METHODS: Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular-and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss.
RESULTS: Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02), p = 0.001].
CONCLUSIONS: BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5oxohexyl) phthalate] and SDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies.
C1 [Jukic, Anne Marie; Longnecker, Matthew P.; Hoppin, Jane A.; Wilcox, Allen J.; Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, DHHS, POB 12233, Durham, NC 27709 USA.
[Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA.
[McConnaughey, D. Robert] Westat Corp, Durham, NC USA.
[Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, DHHS, POB 12233, Durham, NC 27709 USA.
[Jukic, Anne Marie] Yale Ctr Perinatal Pediat & Environm Epidemiol, One Church St,6th Floor, New Haven, CT 06510 USA.
RP Jukic, AM (reprint author), NIEHS, Epidemiol Branch, POB 12233, Durham, NC 27709 USA.
EM jukica@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Longnecker,
Matthew/0000-0001-6073-5322; Wilcox, Allen/0000-0002-3376-1311
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01ES049003-23]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (grant Z01ES049003-23).
NR 53
TC 8
Z9 8
U1 6
U2 25
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP 321
EP 328
DI 10.1289/ehp.1408164
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500018
PM 26161573
ER
PT J
AU Rodriguez, KF
Ungewitter, EK
Crespo-Mejias, Y
Liu, C
Nicol, B
Kissling, GE
Yao, HHC
AF Rodriguez, Karina F.
Ungewitter, Erica K.
Crespo-Mejias, Yasmin
Liu, Chang
Nicol, Barbara
Kissling, Grace E.
Yao, Humphrey Hung-Chang
TI Effects of in Utero Exposure to Arsenic during the Second Half of
Gestation on Reproductive End Points and Metabolic Parameters in Female
CD-1 Mice
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID GENE-EXPRESSION CHANGES; HIGH-FAT DIET; DRINKING-WATER;
CARDIOVASCULAR-DISEASE; LUTEINIZING-HORMONE; OXIDATIVE STRESS; DNA
METHYLATION; MOUSE STRAINS; LUNG; CARCINOGENESIS
AB BACKGROUND: Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear.
OBJECTIVES: We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood.
METHODS: Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood.
RESULTS: Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance.
CONCLUSION: Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice.
C1 [Rodriguez, Karina F.; Ungewitter, Erica K.; Crespo-Mejias, Yasmin; Liu, Chang; Nicol, Barbara; Yao, Humphrey Hung-Chang] NIEHS, Reprod Dev Biol Grp, Reprod & Dev Biol Lab, NIH,Dept Hlth & Human Serv, 111 TW Alexander Dr,C4-10, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, Natl Toxicol Program, NIH,Dept Hlth & Human Serv, 111 TW Alexander Dr,C4-10, Res Triangle Pk, NC 27709 USA.
RP Yao, HHC (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,C4-10, Res Triangle Pk, NC 27709 USA.
EM humphrey.yao@nih.gov
RI Yao, Humphrey Hung-Chang/B-4795-2010;
OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469; Liu,
Chang/0000-0002-8723-7363; Nicol, Barbara/0000-0002-3434-0658
FU NIH/NIEHS [ES102965]
FX This research was supported by the Intramural Research Program
(ES102965) of the NIH/NIEHS.
NR 58
TC 1
Z9 1
U1 3
U2 14
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP 336
EP 343
DI 10.1289/ehp.1509703
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500020
PM 26295903
ER
PT J
AU Wells, EM
Herbstman, JB
Lin, YH
Jarrett, J
Verdon, CP
Ward, C
Caldwell, KL
Hibbeln, JR
Witter, FR
Halden, RU
Goldman, LR
AF Wells, Ellen M.
Herbstman, Julie B.
Lin, Yu Hong
Jarrett, Jeffery
Verdon, Carl P.
Ward, Cynthia
Caldwell, Kathleen L.
Hibbeln, Joseph R.
Witter, Frank R.
Halden, Rolf U.
Goldman, Lynn R.
TI Cord Blood Methylmercury and Fetal Growth Outcomes in Baltimore
Newborns: Potential Confounding and Effect Modification by Omega-3 Fatty
Acids, Selenium, and Sex
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID MERCURY EXPOSURE; BIRTH-WEIGHT; POLYCHLORINATED-BIPHENYLS; PROSPECTIVE
COHORT; FISHING COMMUNITY; INORGANIC MERCURY; GESTATIONAL-AGE; MATERNAL
BLOOD; FATTY-ACIDS; RISK-FACTOR
AB BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions.
OBJECTIVE: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex.
METHODS: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg).
RESULTS: Geometric mean cord blood MeHg was 0.94 mu g/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, beta ln(MeHg) = -0.045 (g/cm(3)) x 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg x sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg x n-3 HUFAs interaction with birth length [among low n-3 HUFAs, beta ln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, beta ln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, beta ln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, beta ln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, beta ln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm(3)) x 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005).
CONCLUSION: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies.
C1 [Wells, Ellen M.] Purdue Univ, Sch Hlth Sci, Hampton Hall Civil Engn 1269,550 Stadium Mall Dr, W Lafayette, IN 47907 USA.
[Herbstman, Julie B.] Columbia Univ, Columbia Ctr Childrens Environm Hlth, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
[Lin, Yu Hong; Hibbeln, Joseph R.] NIAAA, Lab Membrane Biochem & Biophys, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Jarrett, Jeffery; Verdon, Carl P.; Ward, Cynthia; Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA.
[Witter, Frank R.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Halden, Rolf U.] Arizona State Univ, Ctr Environm Secur, Biodesign Inst, Global Secur Initiat, Tempe, AZ USA.
[Goldman, Lynn R.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC USA.
RP Wells, EM (reprint author), Purdue Univ, Sch Hlth Sci, Hampton Hall Civil Engn 1269,550 Stadium Mall Dr, W Lafayette, IN 47907 USA.
EM wells54@purdue.edu
OI Jarrett, Jeffery/0000-0001-5755-3552; Wells, Ellen/0000-0002-7293-1395
FU Maryland Department of Health and Mental Hygiene Cigarette Restitution
Program (Baltimore, MD); National Institute of Environmental Health
Sciences/National Institutes of Health (NIH) (Bethesda, MD)
[1R01ES015445]; U.S. Environmental Protection Agency (EPA) STAR
Fellowship Program (Washington, DC)
FX This study was funded by the Maryland Department of Health and Mental
Hygiene Cigarette Restitution Program (Baltimore, MD), the National
Institute of Environmental Health Sciences/National Institutes of Health
(NIH) grant 1R01ES015445 (Bethesda, MD) (R.U.H.), and the U.S.
Environmental Protection Agency (EPA) STAR Fellowship Program
(Washington, DC) (E.M.W.).
NR 55
TC 2
Z9 2
U1 6
U2 20
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP 373
EP 379
DI 10.1289/ehp.1408596
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500025
PM 26115160
ER
PT J
AU Rodriguez, KF
Ungewitter, EK
Crespo-Mejias, Y
Liu, C
Nicol, B
Kissling, GE
Yao, HHC
AF Rodriguez, Karina F.
Ungewitter, Erica K.
Crespo-Mejias, Yasmin
Liu, Chang
Nicol, Barbara
Kissling, Grace E.
Yao, Humphrey Hung-Chang
TI Response to "Comment on 'Effects of in Utero Exposure to Arsenic during
the Second Half of Gestation on Reproductive End Points and Metabolic
Parameters in Female CD-1 Mice'"
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
ID ADULTHOOD; PULMONARY; INDUCTION; TUMORS; WATER
C1 [Rodriguez, Karina F.; Ungewitter, Erica K.; Crespo-Mejias, Yasmin; Liu, Chang; Nicol, Barbara; Kissling, Grace E.; Yao, Humphrey Hung-Chang] US Dept HHS, NIEHS, NIH, Res Triangle Pk, NC USA.
RP Yao, HHC (reprint author), NIEHS, 111 TW Alexander Dr,Mail Drop C4-10, Res Triangle Pk, NC 27709 USA.
EM humphrey.yao@nih.gov
OI Liu, Chang/0000-0002-8723-7363; Yao, Humphrey
Hung-Chang/0000-0003-2944-8469
NR 9
TC 0
Z9 0
U1 1
U2 4
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP A46
EP A47
DI 10.1289/ehp.1511181
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500004
PM 26930461
ER
PT J
AU Suk, WA
Ahanchian, H
Asante, KA
Carpenter, DO
Diaz-Barriga, F
Ha, EH
Huo, X
King, M
Ruchirawat, M
da Silva, ER
Sly, L
Sly, PD
Stein, RT
van den Berg, M
Zar, H
Landrigan, PJ
AF Suk, William A.
Ahanchian, Hamid
Asante, Kwadwo Ansong
Carpenter, David O.
Diaz-Barriga, Fernando
Ha, Eun-Hee
Huo, Xia
King, Malcolm
Ruchirawat, Mathuros
da Silva, Emerson R.
Sly, Leith
Sly, Peter D.
Stein, Renato T.
van den Berg, Martin
Zar, Heather
Landrigan, Philip J.
TI Environmental Pollution: An Under-recognized Threat to Children's
Health, Especially in Low- and Middle-Income Countries
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID PERSISTENT ORGANIC POLLUTANTS; BISPHENOL-A CONCENTRATION; GLOBAL BURDEN;
CHILDHOOD BEHAVIOR; LATIN-AMERICA; POLYCHLORINATED-BIPHENYLS; SYSTEMATIC
ANALYSIS; HAVEN HYPOTHESIS; AIR-POLLUTION; KUZNETS CURVE
AB Exposures to environmental pollutants during windows of developmental vulnerability in early life can cause disease and death in infancy and childhood as well as chronic, non-communicable diseases that may manifest at any point across the life span. Patterns of pollution and pollution-related disease change as countries move through economic development. Environmental pollution is now recognized as a major cause of morbidity and mortality in low-and middle-income countries (LMICs). According to the World Health Organization, pollution is responsible for 8.9 million deaths around the world each year; of these, 94% (8.4 million) are in LMICs. Toxic chemical pollution is growing into a major threat to children's health in LMICs. The disease and disability caused by environmental pollution have great economic costs, and these costs can undercut trajectories of national development. To combat pollution, improved programs of public health and environmental protection are needed in countries at every level of development. Pollution control strategies and technologies that have been developed in high-income countries must now be transferred to LMICs to assist these emerging economies to avoid the mistakes of the past. A new international clearinghouse is needed to define and track the health effects of pollution, quantify the economic costs of these effects, and direct much needed attention to environmental pollution as a risk factor for disease.
C1 [Suk, William A.] NIEHS, Hazardous Subst Res Branch, Superfund Res Program, NIH,Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
[Ahanchian, Hamid] Mashhad Univ Med Sci, Ghaem Hosp, Dept Allergy & Clin Immunol, Mashhad, Iran.
[Asante, Kwadwo Ansong] CSIR, Water Res Inst, Accra, Ghana.
[Carpenter, David O.] SUNY Albany, Inst Hlth & Environm, Rensselaer, NY USA.
[Diaz-Barriga, Fernando] Univ Autonoma San Luis Potosi, San Luis Potosi, Mexico.
[Ha, Eun-Hee] Ewha Womans Univ, Sch Med, Dept Prevent Med, Seoul, South Korea.
[Huo, Xia] Shantou Univ, Coll Med, Shantou, Peoples R China.
[King, Malcolm] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC, Canada.
[Ruchirawat, Mathuros] Chulabhorn Res Inst, Bangkok, Thailand.
[da Silva, Emerson R.] Univ Caxias Do Sul, Sch Med, Dept Pediat, Caxias Do Sul, Brazil.
[Sly, Leith; Sly, Peter D.] Univ Queensland, Queensland Childrens Med Res Inst, Childrens Hlth & Environm Program, Brisbane, Qld, Australia.
[Sly, Peter D.] Pontificia Univ Catolica Rio Grande Do Sul, Biomed Res Inst, Ctr Infant, Porto Alegre, RS, Brazil.
[van den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Zar, Heather] Univ Cape Town, MRC Unit Child & Adolescent Hlth, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa.
[Landrigan, Philip J.] Icahn Sch Med Mt Sinai, Arnhold Global Hlth Inst, New York, NY 10029 USA.
RP Suk, WA (reprint author), NIEHS, Superfund Res Program, Div Extramural Res & Training, NIH,Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM suk@niehs.nih.gov
NR 77
TC 3
Z9 3
U1 14
U2 46
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP A41
EP A45
DI 10.1289/ehp.1510517
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500002
PM 26930243
ER
PT J
AU Weis, CP
AF Weis, Christopher P.
TI The Value of Alternatives Assessment
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Weis, Christopher P.] NIEHS, NIH, US Dept HHS, Bethesda, MD USA.
RP Weis, CP (reprint author), NIEHS, NIH, US Dept HHS, Bethesda, MD USA.
EM christopher.weis@nih.gov
NR 4
TC 0
Z9 0
U1 6
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2016
VL 124
IS 3
BP A40
EP A40
DI 10.1289/ehp.1611248
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DF6CJ
UT WOS:000371442500001
PM 26930551
ER
PT J
AU Shimony, MK
Schliep, KC
Schisterman, EF
Ahrens, KA
Sjaarda, LA
Rotman, Y
Perkins, NJ
Pollack, AZ
Wactawski-Wende, J
Mumford, SL
AF Shimony, Maya K.
Schliep, Karen C.
Schisterman, Enrique F.
Ahrens, Katherine A.
Sjaarda, Lindsey A.
Rotman, Yaron
Perkins, Neil J.
Pollack, Anna Z.
Wactawski-Wende, Jean
Mumford, Sunni L.
TI The relationship between sugar-sweetened beverages and liver enzymes
among healthy premenopausal women: a prospective cohort study
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE Liver enzymes; Menstrual cycle; Fructose; Dietary sucrose;
Sugar-sweetened beverages
ID FRUCTOSE CONSUMPTION; METABOLIC SYNDROME; NUTRIENT DATABASE; DIETARY
FRUCTOSE; MENSTRUAL-CYCLE; DISEASE; BIOCYCLE; PLASMA; ADULTS; FAT
AB To prospectively assess the association between sugar-sweetened beverages (SSB), added sugar, and total fructose and serum concentrations of liver enzymes among healthy, reproductive-age women.
A prospective cohort of 259 premenopausal women (average age 27.3 +/- A 8.2 years; BMI 24.1 +/- A kg/m(2)) were followed up for up to two menstrual cycles, providing up to eight fasting blood specimens/cycle and four 24-h dietary recalls/cycle. Women with a history of chronic disease were excluded. Alanine and aspartate aminotransferases (ALT and AST, respectively) were measured in serum samples. Linear mixed models estimated associations between average SSB, added sugar, and total fructose intake and log-transformed liver enzymes adjusting for age, race, body mass index, total energy and alcohol intake, and Mediterranean diet score.
For every 1 cup/day increase in SSB consumption and 10 g/day increase in added sugar and total fructose, log ALT increased by 0.079 U/L (95 % CI 0.022, 0.137), 0.012 U/L (95 % CI 0.002, 0.022), and 0.031 (0.012, 0.050), respectively, and log AST increased by 0.029 U/L (-0.011, 0.069), 0.007 U/L (0.000, 0.014), and 0.017 U/L (0.004, 0.030), respectively. Women who consumed a parts per thousand yen1.50 cups/day (12 oz can) SSB versus less had 0.127 U/L (95 % CI 0.001, 0.254) higher ALT [percent change 13.5 % (95 % CI 0.1, 28.9)] and 0.102 (95 % CI 0.015, 0.190) higher AST [percent change 10.8 % (95 % CI 1.5, 20.9)].
Sugar-sweetened beverages were associated with higher serum ALT and AST concentrations among healthy premenopausal women, indicating that habitual consumption of even moderate SSB may elicit hepatic lipogenesis.
C1 [Shimony, Maya K.; Schliep, Karen C.; Schisterman, Enrique F.; Ahrens, Katherine A.; Sjaarda, Lindsey A.; Perkins, Neil J.; Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
[Shimony, Maya K.] George Washington Univ, Sch Publ Hlth, Milken Inst, Dept Epidemiol & Biostat, Washington, DC USA.
[Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Rockville, MD USA.
[Pollack, Anna Z.] George Mason Univ, Coll Hlth & Human Serv, Dept Global & Community Hlth, Fairfax, VA 22030 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Pollack, Anna/0000-0002-4313-3298;
Sjaarda, Lindsey/0000-0003-0539-8110; Schisterman,
Enrique/0000-0003-3757-641X
NR 31
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
EI 1436-6215
J9 EUR J NUTR
JI Eur. J. Nutr.
PD MAR
PY 2016
VL 55
IS 2
BP 569
EP 576
DI 10.1007/s00394-015-0876-3
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DF3RD
UT WOS:000371262400013
PM 25801628
ER
PT J
AU Park, KS
Pfeifer, K
AF Park, Ki-Sun
Pfeifer, Karl
TI Making choices-how stochastic decisions determine disease progression
SO GENES & DEVELOPMENT
LA English
DT Editorial Material
DE gene expression; imprinting; single cell
AB In this issue of Genes & Development, Ginart and colleagues (pp. 567-578) study a mouse model for Russell-Silver syndrome (RSS) and show that similar cells within one individual can display distinct gene expression patterns because of epigenetic marks that are established stochastically during early development. Their results provide an excellent explanation for phenotypes seen in RSS and other imprinting disorders and especially help us understand how patients with similar or even identical genetic mutations can display distinct disease profiles.
C1 [Park, Ki-Sun; Pfeifer, Karl] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20814 USA.
RP Pfeifer, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20814 USA.
EM pfeiferk@mail.nih.gov
OI Pfeifer, Karl/0000-0002-0254-682X
FU Intramural NIH HHS
NR 4
TC 0
Z9 0
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD MAR 1
PY 2016
VL 30
IS 5
BP 485
EP 486
DI 10.1101/gad.278952.116
PG 2
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DF4BU
UT WOS:000371293100001
PM 26944674
ER
PT J
AU Benyoucef, A
Palii, CG
Wang, CC
Porter, CJ
Chu, A
Dai, FT
Tremblay, V
Rakopoulos, P
Singh, K
Huang, SM
Pflumio, F
Hebert, J
Couture, JF
Perkins, TJ
Ge, K
Dilworth, FJ
Brand, M
AF Benyoucef, Aissa
Palii, Carmen G.
Wang, Chaochen
Porter, Christopher J.
Chu, Alphonse
Dai, Fengtao
Tremblay, Veronique
Rakopoulos, Patricia
Singh, Kulwant
Huang, Suming
Pflumio, Francoise
Hebert, Josee
Couture, Jean-Francois
Perkins, Theodore J.
Ge, Kai
Dilworth, F. Jeffrey
Brand, Marjorie
TI UTX inhibition as selective epigenetic therapy against TAL1-driven
T-cell acute lymphoblastic leukemia
SO GENES & DEVELOPMENT
LA English
DT Article
DE UTX; TAL1; histone demethylation; leukemia; histone demethylase
inhibitor; epigenetics
ID H3K27ME3 DEMETHYLASE UTX; METHYLTRANSFERASE COMPLEX; GENE-EXPRESSION;
STEM-CELLS; CANCER; TARGET; JMJD3; PROLIFERATION; HEMATOPOIESIS;
CHROMATIN
AB T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A. Specifically, we identify UTX as a coactivator of TAL1 and show that it acts as a major regulator of the TAL1 leukemic gene expression program. Furthermore, we demonstrate that UTX, previously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for leukemia maintenance in TAL1-positive (but not TAL1-negative) T-ALL. Exploiting this subtype-specific epigenetic vulnerability, we propose a novel therapeutic approach based on UTX inhibition through in vivo administration of an H3K27 demethylase inhibitor that efficiently kills TAL1-positive primary human leukemia. These findings provide the first opportunity to develop personalized epigenetic therapy for T-ALL patients.
C1 [Benyoucef, Aissa; Palii, Carmen G.; Chu, Alphonse; Dai, Fengtao; Rakopoulos, Patricia; Singh, Kulwant; Perkins, Theodore J.; Dilworth, F. Jeffrey; Brand, Marjorie] Ottawa Gen Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada.
[Benyoucef, Aissa; Dilworth, F. Jeffrey; Brand, Marjorie] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L6, Canada.
[Benyoucef, Aissa; Palii, Carmen G.; Tremblay, Veronique; Singh, Kulwant; Couture, Jean-Francois; Dilworth, F. Jeffrey; Brand, Marjorie] Ottawa Inst Syst Biol, Ottawa, ON K1H 8L6, Canada.
[Wang, Chaochen; Ge, Kai] NIDDK, NIH, Bethesda, MD 20892 USA.
[Porter, Christopher J.; Perkins, Theodore J.] Ottawa Hosp, Res Inst, Sprott Ctr Stem Cell Res, Ottawa Bioinformat Core Facil, Ottawa, ON K1H 8L6, Canada.
[Tremblay, Veronique; Couture, Jean-Francois; Perkins, Theodore J.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada.
[Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Pflumio, Francoise] Commissariat Energie Atom & Energies Alternat Dir, Inst Rech Radiobiol Cellulaire & Mol IRCM, Stem Cells & Radiat Dept SCSR, Lab Hematopoiet Stem Cells & Leukemia LSHL,U967, F-92265 Paris, France.
[Pflumio, Francoise] INSERM, U967, F-92265 Paris, France.
[Pflumio, Francoise] Univ Paris 11, Univ Paris Diderot, Sorbonne Paris Cite, UMR 967, F-92265 Paris, France.
[Hebert, Josee] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Hebert, Josee] Maisonneuve Rosemont Hosp, Montreal, PQ H1T 2M4, Canada.
RP Brand, M (reprint author), Ottawa Gen Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada.; Brand, M (reprint author), Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L6, Canada.; Brand, M (reprint author), Ottawa Inst Syst Biol, Ottawa, ON K1H 8L6, Canada.
EM mbrand@ohri.ca
RI Pflumio, Francoise/E-2074-2017;
OI Porter, Christopher/0000-0001-8636-4515; Ge, Kai/0000-0002-7442-5138;
Perkins, Theodore J./0000-0002-6622-8003
FU Canadian Institutes of Health Research [MOP-82813, MOP-77778];
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health (USA);
Cancer Research Network of Fonds de la Recherche du Quebec en Sante
(FRSQ); Government of Ontario Ministry of Research and Innovation (MRI)
grant
FX We thank Achim Leutz (Max-Delbruck-Center for Molecular Medicine,
Germany) for the pcDNA3 plasmid expressing human TAL1, Paul A. Khavari
(Stanford University, USA) for JMJD3 plasmids, and Cheryl Arrowsmith
(Structural Genomics Consortium; http://www.thesgc.org) for initially
providing GSK-J4. We also thank Lawrence Puente (Ottawa Hospital
Research Institute Proteomics Facility; http://www.ohri.ca/proteomics)
and Gareth Palidwor (Ottawa Bioinformatics Core Facility;
http://www.ohri.ca/bioinformatics) for MS and bioinformatic analyses.
High-throughput DNA sequencing was performed at the Molecular Biology
and Functional Genomics Core Facility of the Institut de Recherche
Clinique de Montreal (IRCM, Canada). This project was funded with grants
from the Canadian Institutes of Health Research (MOP-82813 to M.B., and
MOP-77778 to F.J.D.). C.W. and K.G. were supported by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health (USA). The Quebec
Leukemia Cell Bank (http://www.bclq.org) is supported by a grant from
the Cancer Research Network of Fonds de la Recherche du Quebec en Sante
(FRSQ). The Ottawa Bioinformatics Core Facility is supported in part by
a Government of Ontario Ministry of Research and Innovation (MRI) grant.
NR 54
TC 12
Z9 12
U1 2
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD MAR 1
PY 2016
VL 30
IS 5
BP 508
EP 521
DI 10.1101/gad.276790.115
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DF4BU
UT WOS:000371293100005
PM 26944678
ER
PT J
AU Hosseini-Vasoukolaei, N
Mahmoudi, AR
Khamesipour, A
Yaghoobi-Ershadi, MR
Kamhawi, S
Valenzuela, JG
Arandian, MH
Mirhendi, H
Emami, S
Saeidi, Z
Idali, F
Jafari, R
Jeddi-Tehrani, M
Akhavan, AA
AF Hosseini-Vasoukolaei, Nasibeh
Mahmoudi, Ahmad-Reza
Khamesipour, Ali
Yaghoobi-Ershadi, Mohammad Reza
Kamhawi, Shaden
Valenzuela, Jesus G.
Arandian, Mohammad Hossein
Mirhendi, Hossein
Emami, Shaghayegh
Saeidi, Zahra
Idali, Farah
Jafari, Reza
Jeddi-Tehrani, Mahmood
Akhavan, Amir Ahmad
TI Seasonal and Physiological Variations of Phlebotomus papatasi Salivary
Gland Antigens in Central Iran
SO JOURNAL OF ARTHROPOD-BORNE DISEASES
LA English
DT Article
DE Antibody response; Phlebotomus papatasi; Rhombomys opimus; Salivary
gland antigens; Iran
ID ZOONOTIC CUTANEOUS LEISHMANIASIS; SAND FLIES DIPTERA; ANTIBODY-RESPONSE;
PSYCHODIDAE; FLY; FOCUS; PROTECTION; SANDFLIES; PROTEINS; POPULATION
AB Background: Sand fly saliva helps parasite establishment and induce immune responses in vertebrate hosts. In the current study, we investigated the modulation of Phlebotomus papatasi salivary gland antigen expression by seasonal and biological factors.
Methods: Sand flies were grouped according to physiological stages such as unfed, fed, semi-gravid, gravid, parous, nulliparous, infected or non-infected with Leishmania major and based on the season in which they were collected. Salivary gland antigens (SGAs) were analyzed using SDS-PAGE and the antibody response against SGAs in Rhombomys opimus was determined by ELISA and Western blot.
Results: The highest protein content was found in the salivary glands of unfed sand flies. The saliva content was higher in parous compared to nulliparous, in summer compared to spring, and in Leishmania-infected compared to non-infected flies. The salivary gland lysate (SGL) electrophoretic pattern variations were observed among sand flies with various physiological stages particularly from 4-9 protein bands of 14-70 kDa. The SGL of unfed and gravid flies had extra protein bands compared to fed and semi-gravid sand flies. There was missing protein bands in SGL of parous compared to nulliparous; and in summer compared to spring collected flies. Rhombomys opimus serum reacted strongly with an antigenic band of around 28 kDa in the SGL of all sand fly groups.
Conclusion: Certain biological and environmental characteristics of wild populations of vector sand flies affect the protein content and antigenicity of saliva. This might have an important implication in the design of vector-based vaccines.
C1 [Hosseini-Vasoukolaei, Nasibeh; Yaghoobi-Ershadi, Mohammad Reza; Saeidi, Zahra; Akhavan, Amir Ahmad] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.
[Mahmoudi, Ahmad-Reza; Emami, Shaghayegh; Jeddi-Tehrani, Mahmood] ACECR, Avicenna Res Inst, Monoclonal Antibody Res Ctr, Tehran, Iran.
[Khamesipour, Ali] Univ Tehran Med Sci, Ctr Res & Training Skin Dis & Leprosy, Tehran, Iran.
[Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Arandian, Mohammad Hossein; Jafari, Reza] Tehran Univ Med SciencesEsfahan, Natl Inst Hlth Res, Esfahan Hlth Res Stn, Tehran, Iran.
[Mirhendi, Hossein] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Parasitol & Mycol, Tehran, Iran.
[Idali, Farah] ACECR, Avicenna Res Inst, Reprod Immunol Res Ctr, Tehran, Iran.
RP Akhavan, AA (reprint author), Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.; Jeddi-Tehrani, M (reprint author), ACECR, Avicenna Res Inst, Monoclonal Antibody Res Ctr, Tehran, Iran.
EM mahjed@avicenna.ac.ir; aaakhavan@tums.ac.ir
FU Research deputy of Tehran University of Medical Sciences
[18511/16.5.2012]; Avicenna Research Institute [910206018]
FX This research was supported by Research deputy of Tehran University of
Medical Sciences, Project No. 18511/16.5.2012 and Avicenna Research
Institute Project No. 910206018. We are very grateful to Dr Shabani for
his valuable comment and Ms Babaei, Ms Balaei, Mr Hadavi for their
technical assistance, from Avicenna Research Institute, ACECR. We also
thank Ms. Shareghi, Esfahan Health Research Station, National Institute
of Health Research, TUMS, for her assistance in the project. We are
grateful to Ms. Ahmadi and Ms. Bolandian, School of Public Health, TUMS,
for their assistance in sand fly rearing. The authors declare that there
is no conflict of interests.
NR 33
TC 1
Z9 1
U1 0
U2 1
PU IRANIAN SCIENTIFIC SOCIETY MEDICAL ENTOMOLOGY
PI TEHRAN
PA SCHOOL PUBLIC HEALTH & INST HEALTH RESEARCH, TEHRAN UNIV MEDICAL
SCIENCES, P O BOX 6446-14155, TEHRAN, 00000, IRAN
SN 2322-1984
EI 2322-2271
J9 J ARTHROPOD-BORNE DI
JI J. Arthropod.-Borne Dis.
PD MAR
PY 2016
VL 10
IS 1
BP 39
EP 49
PG 11
WC Public, Environmental & Occupational Health; Parasitology
SC Public, Environmental & Occupational Health; Parasitology
GA DF2AZ
UT WOS:000371142900004
PM 27047970
ER
PT J
AU Wilson, BAP
Alam, MS
Guszczynski, T
Jakob, M
Shenoy, SR
Mitchell, CA
Goncharova, EI
Evans, JR
Wipf, P
Liu, G
Ashwell, JD
O'Keefe, BR
AF Wilson, Brice A. P.
Alam, Muhammad S.
Guszczynski, Tad
Jakob, Michal
Shenoy, Shilpa R.
Mitchell, Carter A.
Goncharova, Ekaterina I.
Evans, Jason R.
Wipf, Peter
Liu, Gang
Ashwell, Jonathan D.
O'Keefe, Barry R.
TI Discovery and Characterization of a Biologically Active
Non-ATP-Competitive p38 MAP Kinase Inhibitor
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE high throughput; p38; non-ATP competitive; enzyme kinetics
ID SELECTIVE INHIBITOR; IN-VIVO; SUBSTRATE; P38-ALPHA; INFLAMMATION;
ACTIVATION; MECHANISMS; POTENT; ASSAYS
AB Mitogen-activated protein kinase (MAPK) p38 is part of a broad and ubiquitously expressed family of MAPKs whose activity is responsible for mediating an intracellular response to extracellular stimuli through a phosphorylation cascade. p38 is central to this signaling node and is activated by upstream kinases while being responsible for activating downstream kinases and transcription factors via phosphorylation. Dysregulated p38 activity is associated with numerous autoimmune disorders and has been implicated in the progression of several types of cancer. A number of p38 inhibitors have been tested in clinical trials, with none receiving regulatory approval. One characteristic shared by all of the compounds that failed clinical trials is that they are all adenosine triphosphate (ATP)-competitive p38 inhibitors. Seeing this lack of mechanistic diversity as an opportunity, we screened 32,000 substances in search of novel p38 inhibitors. Among the inhibitors discovered is a compound that is both non-ATP competitive and biologically active in cell-based models for p38 activity. This is the first reported discovery of a non-ATP-competitive p38 inhibitor that is active in cells and, as such, may enable new pharmacophore designs for both therapeutic and basic research to better understand and exploit non-ATP-competitive inhibitors of p38 activity.
C1 [Wilson, Brice A. P.; Guszczynski, Tad; Shenoy, Shilpa R.; Mitchell, Carter A.; Goncharova, Ekaterina I.; O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick Natl Lab Canc Res,NIH, Bldg 562,Rm 201, Frederick, MD 21702 USA.
[Alam, Muhammad S.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jakob, Michal] Wroclaw Univ Technol, Fac Chem, Dept Biochem, PL-50370 Wroclaw, Poland.
[Shenoy, Shilpa R.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Goncharova, Ekaterina I.; Evans, Jason R.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
[Liu, Gang] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China.
[Liu, Gang] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Peking Union Med Coll, Beijing 100084, Peoples R China.
[Liu, Gang] Tsinghua Univ, Sch Med, Dept Pharmacol & Pharmaceut Sci, Beijing 100084, Peoples R China.
[O'Keefe, Barry R.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bldg 562,Rm 201, Frederick, MD 21702 USA.
RP O'Keefe, BR (reprint author), NCI, Bldg 562,Rm 201, Frederick, MD 21702 USA.
EM okeefeba@mail.nih.gov
FU National Institutes of Health (NIH) Intramural AIDS Targeted Antiviral
Program; National Cancer Institute, NIH [HHSN26120080001E]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported in part by funds from the National Institutes of Health (NIH)
Intramural AIDS Targeted Antiviral Program (B.R.O. and M.J.). This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, NIH, under contract HHSN26120080001E
(S.R.S.). This project has also been supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government.
NR 35
TC 0
Z9 0
U1 1
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD MAR
PY 2016
VL 21
IS 3
BP 277
EP 289
DI 10.1177/1087057115615518
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA DF4PH
UT WOS:000371331100006
PM 26538432
ER
PT J
AU Ishikawa, M
Williams, GL
Ikeuchi, T
Sakai, K
Fukumoto, S
Yamada, Y
AF Ishikawa, Masaki
Williams, Geneva L.
Ikeuchi, Tomoko
Sakai, Kiyoshi
Fukumoto, Satoshi
Yamada, Yoshihiko
TI Pannexin 3 and connexin 43 modulate skeletal development through their
distinct functions and expression patterns
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Pannexin 3; Connexin 43; Skeletal formation; Ossification; Chondrocyte;
Osteoblast
ID CELL-CELL COMMUNICATION; OSTEOBLAST DIFFERENTIATION; GAP-JUNCTION;
BONE-FORMATION; GROWTH-PLATE; WNT; MICE; CARTILAGE; PROTEINS; PERLECAN
AB Pannexin 3 (Panx3) and connexin 43 (Cx43; also known as GJA1) are two major gap junction proteins expressed in osteoblasts. Here, we studied their functional relationships in skeletal formation by generating Panx3(-/-) and Panx3(-/-); Cx43(-/-) mice and comparing their skeletal phenotypes with Cx43(-/-) mice. Panx3(-/-) mice displayed defects in endochondral and intramembranous ossification, resulting in severe dwarfism and reduced bone density. The skeletal abnormalities of Panx3(-/-); Cx43(-/-) mice were similar to those in Panx3(-/-) mice. The gross appearance of newborn Cx43(-/-) skeletons showed no obvious abnormalities, except for less mineralization of the skull. In Panx3(-/-) mice, proliferation of chondrocytes and osteoblasts increased and differentiation of these cells was inhibited. Panx3 promoted expression of osteogenic proteins such as ALP and Ocn (also known as ALPL and BGLAP, respectively), as well as Cx43, by regulating Osx (also known as SP7) expression. Panx3 was induced in the early differentiation stage and reduced during the maturation stage of osteoblasts, when Cx43 expression increased in order to promote mineralization. Furthermore, only Panx3 functioned as an endoplasmic reticulum (ER) Ca2+ channel to promote differentiation, and it could rescue mineralization defects in Cx43(-/-) calvarial cells. Our findings reveal that Panx3 and Cx43 have distinct functions in skeletal formation.
C1 [Ishikawa, Masaki; Williams, Geneva L.; Ikeuchi, Tomoko; Sakai, Kiyoshi; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20814 USA.
[Ishikawa, Masaki] Tohoku Univ, Grad Sch Dent, Operat Dent, Sendai, Miyagi 9808575, Japan.
[Williams, Geneva L.] Washington Univ, Div Biol & Biomed Sci, St Louis, MO 63110 USA.
[Sakai, Kiyoshi] Nagoya Univ, Grad Sch Med, Dept Oral & Maxillofacial Surg, Nagoya, Aichi 4668550, Japan.
[Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Pediat Dent, Sendai, Miyagi 9808576, Japan.
RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20814 USA.
EM yoshi.yamada@nih.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, USA [DE000483-24, DE000483-25, DE000483-26];
Ministry of Education, Science, and Culture of Japan [26670880]; NEXT
program [LS010]; Research Fellowship of the Japan Society for the
Promotion of Science for Young Scientists
FX This work was supported in part by the Intramural Research Program of
the National Institute of Dental and Craniofacial Research, USA [grant
number DE000483-24, -25, and-26 to Y.Y.]; Grants-in-Aid from the
Ministry of Education, Science, and Culture of Japan [grant number
26670880 to S.F.]; and the NEXT program [grant number LS010 to S.F.].
M.I. and T.I. were supported in part by the Research Fellowship of the
Japan Society for the Promotion of Science for Young Scientists.
Deposited in PMC for release after 12 months.
NR 39
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Z9 2
U1 1
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 1
PY 2016
VL 129
IS 5
BP 1018
EP 1030
DI 10.1242/jcs.176883
PG 13
WC Cell Biology
SC Cell Biology
GA DF6AE
UT WOS:000371435700014
PM 26759176
ER
PT J
AU Schoenmakers, E
Carlson, B
Agostini, M
Moran, C
Rajanayagam, O
Bochukova, E
Tobe, R
Peat, R
Gevers, E
Muntoni, F
Guicheney, P
Schoenmakers, N
Farooqi, S
Lyons, G
Hatfield, D
Chatterjee, K
AF Schoenmakers, Erik
Carlson, Bradley
Agostini, Maura
Moran, Carla
Rajanayagam, Odelia
Bochukova, Elena
Tobe, Ryuta
Peat, Rachel
Gevers, Evelien
Muntoni, Francesco
Guicheney, Pascale
Schoenmakers, Nadia
Farooqi, Sadaf
Lyons, Greta
Hatfield, Dolph
Chatterjee, Krishna
TI Mutation in human selenocysteine transfer RNA selectively disrupts
selenoprotein synthesis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID METHYLATION
AB Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA (tRNAE([ser]sec)). Here, we have identified a human tRNAE([Ser]Sec) mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2'-0-methylribosylation at uridine 34 in mutant tRNA([ser]sec). Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA([ser]sec). This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.
C1 [Schoenmakers, Erik; Agostini, Maura; Moran, Carla; Rajanayagam, Odelia; Bochukova, Elena; Schoenmakers, Nadia; Farooqi, Sadaf; Lyons, Greta; Chatterjee, Krishna] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Cambridge CB2 0QQ, England.
[Carlson, Bradley; Tobe, Ryuta; Hatfield, Dolph] NIH, Mol Biol Selenium Sect, Mouse Canc Genet Program, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Peat, Rachel; Guicheney, Pascale] Univ Paris 06, Sorbonne Univ, Inst Cardiometab & Nutr ICAN, INSERM,UMR S1166, Paris, France.
[Gevers, Evelien] Royal London Hosp, Dept Paediat Endocrinol, London E1 1BB, England.
[Muntoni, Francesco] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
RP Chatterjee, K (reprint author), Univ Cambridge, Inst Metab Sci, Metab Res Labs, Addenbrookes Hosp, Level 4,Box 289, Cambridge CB2 0QQ, England.
EM kkc1@medschl.cam.ac.uk
OI Farooqi, Sadaf/0000-0001-7609-3504; Bochukova, Elena/0000-0003-0275-1548
FU Wellcome Trust [100585/Z/12/Z, 095564/Z/11/Z]; NIH Research Biomedical
Research Centre Cambridge; Intramural Research Program of the Center for
Cancer Research, National Cancer Institute, NIH
FX Our research is supported by funding from the Wellcome Trust
(100585/Z/12/Z to N. Schoenmakers, 095564/Z/11/Z to K. Chatterjee), the
NIH Research Biomedical Research Centre Cambridge (to C. Moran, N.
Schoenmakers, and K. Chatterjee) or Great Ormond Street (to F. Muntoni)
and the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, NIH (to D.L. Hatfield).
NR 11
TC 2
Z9 2
U1 1
U2 5
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2016
VL 126
IS 3
BP 992
EP 996
DI 10.1172/JCI84747
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DF2SI
UT WOS:000371193700019
PM 26854926
ER
PT J
AU Yu, HY
Artomov, M
Brahler, S
Stander, MC
Shamsan, G
Sampson, MG
White, JM
Kretzler, M
Miner, JH
Jain, S
Winkler, CA
Mitra, RD
Kopp, JB
Daly, MJ
Shaw, AS
AF Yu, Haiyang
Artomov, Mykyta
Braehler, Sebastian
Stander, M. Christine
Shamsan, Ghaidan
Sampson, Matthew G.
White, J. Michael
Kretzler, Matthias
Miner, Jeffrey H.
Jain, Sanjay
Winkler, Cheryl A.
Mitra, Robi D.
Kopp, Jeffrey B.
Daly, Mark J.
Shaw, Andrey S.
TI A role for genetic susceptibility in sporadic focal segmental
glomerulosclerosis (Retracted Article. See vol 126, pg 1603, 2016)
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article; Retracted Publication
ID RESISTANT NEPHROTIC SYNDROME; HIV-ASSOCIATED NEPHROPATHY; EMBRYONIC
STEM-CELLS; PODOCYTE INJURY; CD2-ASSOCIATED PROTEIN;
GLOMERULAR-DISEASES; AFRICAN-AMERICANS; RNA INTERFERENCE; RENAL-DISEASE;
MUTATIONS
AB Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein 1:1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes.
C1 [Yu, Haiyang; Braehler, Sebastian; Stander, M. Christine; Shamsan, Ghaidan; White, J. Michael; Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Artomov, Mykyta; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Artomov, Mykyta; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA.
[Artomov, Mykyta; Daly, Mark J.] Broad Inst, Cambridge, MA USA.
[Artomov, Mykyta] Harvard Univ, Dept Chem, 12 Oxford St, Cambridge, MA 02138 USA.
[Sampson, Matthew G.] Univ Michigan, Pediat Nephrol, Ann Arbor, MI 48109 USA.
[Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA.
[Miner, Jeffrey H.; Jain, Sanjay] Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USA.
[Winkler, Cheryl A.] NCI, Mol Genet Epidemiol Studies Sect, Frederick, MD 21701 USA.
[Mitra, Robi D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH, Bethesda, MD USA.
[Shaw, Andrey S.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
RP Shaw, AS (reprint author), Genentech Inc, One DNA Way,Mail Stop 93B, San Francisco, CA 94080 USA.; Daly, MJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Analyt & Translat Genet Unit, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA.
EM mjdaly@atgu.mgh.harvard.edu; shawa6@gene.com
FU NIDDK; HHMI; Intramural Research Programs of the NIDDK; NCI; Deutsche
Forschungsgemeinschaft (DFG)
FX This project was supported by grants from the NIDDK (to A.S. Shaw, J.H.
Miner, M. Kretzler, and M.G. Sampson); the HHMI (to A.S. Shaw); and the
Intramural Research Programs of the NIDDK (to J.B. Kopp), NCI (to C.A.
Winkler), and the Deutsche Forschungsgemeinschaft (DFG) (to S. Brahler).
We thank V. Vasioukhin for sharing Dlg5+/- mice,
overexpression and RNAi lentiviral plasmids, and histology stainings of
Dlg5-/- kidney. We also thank C. Der for sharing the Arhgefl7
cDNA construct. We also thank R. Kopan and members of the Shaw
laboratory for critical discussions.
NR 60
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Z9 4
U1 1
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2016
VL 126
IS 3
BP 1067
EP 1078
DI 10.1172/JCI82592
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DF2SI
UT WOS:000371193700025
PM 26901816
ER
PT J
AU Masujin, K
Orru, CD
Miyazawa, K
Groveman, BR
Raymond, LD
Hughson, AG
Caughey, B
AF Masujin, Kentaro
Orru, Christina D.
Miyazawa, Kohtaro
Groveman, Bradley R.
Raymond, Lynne D.
Hughson, Andrew G.
Caughey, Byron
TI Detection of Atypical H-Type Bovine Spongiform Encephalopathy and
Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced
Conversion
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; CEREBROSPINAL-FLUID; TRANSGENIC MICE;
BIOCHEMICAL-CHARACTERIZATION; MAMMALIAN PRIONS; IN-VITRO; PROTEIN;
TRANSMISSION; CATTLE; PRPSC
AB Prion diseases of cattle include the classical bovine spongiform encephalopathy (C-BSE) and the atypical H-type BSE (H-BSE) and L-type BSE (L-BSE) strains. Although the C-and L-BSE strains can be detected and discriminated by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays, no such test has yet been described for the detection of H-BSE or the discrimination of each of the major bovine prion strains. Here, we demonstrate an RT-QuIC assay for H-BSE that can detect as little as 10(-9) dilutions of brain tissue and neat cerebrospinal fluid samples from clinically affected cattle. Moreover, comparisons of the reactivities with different recombinant prion protein substrates and/or immunoblot band profiles of proteinase K-treated RT-QuIC reaction products indicated that H-, L-, and C-BSE have distinctive prion seeding activities and can be discriminated by RT-QuIC on this basis.
C1 [Masujin, Kentaro; Orru, Christina D.; Groveman, Bradley R.; Raymond, Lynne D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Masujin, Kentaro; Miyazawa, Kohtaro] Natl Agr & Food Res Org, Natl Inst Anim Hlth, Influenza & Prion Dis Res Ctr, Tsukuba, Ibaraki, Japan.
RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM bcaughey@nih.gov
FU NARO; Alliance Biosecure Foundation under the aegis of the Fondation
pour la Recherche Medicale [FABS 201401]; Intramural Research Program of
the National Institute of Allergy and Infectious Diseases (DIR, NIAID);
Intramural Research Program of the NIAID
FX A research fellowship from NARO provided funding to Kentaro Masujin.
Alliance Biosecure Foundation under the aegis of the Fondation pour la
Recherche Medicale provided funding to Byron Caughey. The Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases (DIR, NIAID) provided funding to Byron Caughey.; This work was
supported in part by the Intramural Research Program of the NIAID, by
the Alliance Biosecure Foundation under the aegis of the Fondation pour
la Recherche Medicale (FABS 201401), and by a research fellowship from
NARO to K. Masujin.
NR 63
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Z9 7
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2016
VL 54
IS 3
BP 676
EP 686
DI 10.1128/JCM.02731-15
PG 11
WC Microbiology
SC Microbiology
GA DF2EC
UT WOS:000371152200026
PM 26739160
ER
PT J
AU Davids, M
Kane, MS
He, M
Wolfe, LA
Li, XL
Raihan, MA
Chao, KR
Bone, WP
Boerkoel, CF
Gahl, WA
Toro, C
AF Davids, Mariska
Kane, Megan S.
He, Miao
Wolfe, Lynne A.
Li, Xueli
Raihan, Mohd A.
Chao, Katherine R.
Bone, William P.
Boerkoel, Cornelius F.
Gahl, William A.
Toro, Camilo
TI Disruption of Golgi morphology and altered protein glycosylation in
PLA2G6-associated neurodegeneration
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
DE Molecular genetics; Cell biology; Neuromuscular disease
ID INDEPENDENT PHOSPHOLIPASE A(2); P388D(1) MACROPHAGES; PHENOTYPIC
SPECTRUM; MASS-SPECTROMETRY; ALZHEIMER-DISEASE; ACID RELEASE; BRAIN
IRON; CELL-DEATH; O-GLCNAC; PLA2G6
AB Background Mutations in PLA2G6, which encodes the calcium-independent phospholipase A2 group VI, cause neurodegeneration and diffuse cortical Lewy body formation by a yet undefined mechanism. We assessed whether altered protein glycosylation due to abnormal Golgi morphology might be a factor in the pathology of this disease.
Methods Three patients presented with PLA2G6-associated neurodegeneration (PLAN); two had infantile neuroaxonal dystrophy (INAD) and one had adult-onset dystonia-parkinsonism. We analysed protein N-linked and O-linked glycosylation in cerebrospinal fluid, plasma, urine, and cultured skin fibroblasts using high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionisation - time of flight/mass spectrometry (MALDI-TOF/MS). We also assessed sialylation and Golgi morphology in cultured fibroblasts by immunofluorescence and performed rescue experiments using a lentiviral vector.
Results The patients with INAD had PLA2G6 mutations NM_003560.2: c.[950G>T];[426-1077dup] and c.[1799G>A];[2221C>T] and the patient with dystonia-parkinsonism had PLA2G6 mutations NM_003560.2: c.[609G>A];[2222G>A]. All three patients had altered Golgi morphology and abnormalities of protein O-linked glycosylation and sialylation in cultured fibroblasts that were rescued by lentiviral overexpression of wild type PLA2G6.
Conclusions Our findings add altered Golgi morphology, O-linked glycosylation and sialylation defects to the phenotypical spectrum of PLAN; these pathways are essential for correct processing and distribution of proteins. Lewy body and Tau pathology, two neuropathological features of PLAN, could emerge from these defects. Therefore, Golgi morphology, O-linked glycosylation and sialylation may play a role in the pathogenesis of PLAN and perhaps other neurodegenerative disorders.
C1 [Davids, Mariska; Kane, Megan S.; Wolfe, Lynne A.; Chao, Katherine R.; Bone, William P.; Boerkoel, Cornelius F.; Gahl, William A.; Toro, Camilo] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Davids, Mariska; Kane, Megan S.; Wolfe, Lynne A.; Chao, Katherine R.; Bone, William P.; Boerkoel, Cornelius F.; Gahl, William A.; Toro, Camilo] NIH, Off Clin Director, NHGRI, Bldg 10, Bethesda, MD 20892 USA.
[He, Miao; Li, Xueli; Raihan, Mohd A.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
[He, Miao; Li, Xueli; Raihan, Mohd A.] Childrens Hosp Philadelphia, Michael J Palmieri Metab Lab, Philadelphia, PA 19104 USA.
RP Davids, M (reprint author), NIH, UDP Translat Lab, 5625 Fishers Lane Room 4N-15, Rockville, MD 20852 USA.
EM mariska.davids@nih.gov
FU National Human Genome Research Institute; NIH Office of the Director of
the National Institutes of Health, Bethesda, Maryland, USA
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute and the Common Fund of the NIH
Office of the Director of the National Institutes of Health, Bethesda,
Maryland, USA.
NR 55
TC 1
Z9 2
U1 3
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD MAR
PY 2016
VL 53
IS 3
BP 180
EP 189
DI 10.1136/jmedgenet-2015-103338
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DF4OT
UT WOS:000371329600005
PM 26668131
ER
PT J
AU Odia, Y
Iwamoto, FM
Moustakas, A
Fraum, TJ
Salgado, CA
Li, AG
Kreisl, TN
Sul, J
Butman, JA
Fine, HA
AF Odia, Yazmin
Iwamoto, Fabio M.
Moustakas, Argirios
Fraum, Tyler J.
Salgado, Carlos A.
Li, Aiguo
Kreisl, Teri N.
Sul, Joohee
Butman, John A.
Fine, Howard A.
TI A phase II trial of enzastaurin (LY317615) in combination with
bevacizumab in adults with recurrent malignant gliomas
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Enzastaurin; Bevacizumab; Trial; Glioma; Glioblastoma
ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; RECURSIVE PARTITIONING
ANALYSIS; SINGLE-AGENT BEVACIZUMAB; CENTRAL-NERVOUS-SYSTEM;
GLIOBLASTOMA-MULTIFORME; CELL-GROWTH; IN-VIVO; SELECTIVE INHIBITOR;
ANAPLASTIC GLIOMA
AB We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10 mg/kg intravenously biweekly. Clinical evaluations were repeated every 4 weeks. Magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4 months, respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 (22 %) had partial or complete response and 20/37 (54 %) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7-9/24 (29.2-37.5 %). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.
C1 [Odia, Yazmin; Iwamoto, Fabio M.; Kreisl, Teri N.] Columbia Univ Coll Phys & Surg, Neurooncol Div, Neurol Inst New York, 710 West 168th St,9th Floor,NI 9-017, New York, NY 10032 USA.
[Moustakas, Argirios] Univ Vermont, Med Ctr, 89 South Williams St, Burlington, VT 05401 USA.
[Fraum, Tyler J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA.
[Salgado, Carlos A.] Univ Maryland, Sch Med, 655 West Baltimore St, Baltimore, MD 21201 USA.
[Li, Aiguo] NCI, Ctr Canc Res, Bldg 37,Room 1142, Bethesda, MD USA.
[Sul, Joohee] Fed Drug Adm, 10903 New Hampshire Ave,Bldg WO22 Rm 2331, Silver Spring, MD 20993 USA.
[Butman, John A.] NIH, Ctr Clin, Dept Radiol, Bldg 10,Clinical Ctr 10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA.
[Fine, Howard A.] New York Presbyterian Hospital, Weill Cornell Med Ctr, Brain Tumor Ctr, Div Neurooncol, 1305 York Ave,9th Floor, New York, NY 10021 USA.
RP Odia, Y (reprint author), Columbia Univ Coll Phys & Surg, Neurooncol Div, Neurol Inst New York, 710 West 168th St,9th Floor,NI 9-017, New York, NY 10032 USA.
EM yo2240@cumc.columbia.edu
FU National Cancer Institute Intramural Research Program
FX National Cancer Institute Intramural Research Program.
NR 43
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD MAR
PY 2016
VL 127
IS 1
BP 127
EP 135
DI 10.1007/s11060-015-2020-x
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DF6HF
UT WOS:000371455800014
PM 26643807
ER
PT J
AU Szatmari, P
Chawarska, K
Dawson, G
Georgiades, S
Landa, R
Lord, C
Messinger, DS
Thurm, A
Halladay, A
AF Szatmari, Peter
Chawarska, Katarzyna
Dawson, Geraldine
Georgiades, Stelios
Landa, Rebecca
Lord, Catherine
Messinger, Daniel S.
Thurm, Audrey
Halladay, Alycia
TI Prospective Longitudinal Studies of Infant Siblings of Children With
Autism: Lessons Learned and Future Directions
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Review
DE autism; longitudinal; sibling; development; opportunities
ID SPECTRUM DISORDER; RESEARCH CONSORTIUM; HIGH-RISK; MODIFIED CHECKLIST;
DIAGNOSTIC STABILITY; 6-MONTH-OLD INFANTS; CLINICAL-DIAGNOSIS; TODDLERS;
IDENTIFICATION; INTERVENTION
AB Objective: The objectives of this review are to highlight the impact of the first decade of high-risk (HR) infant sibling work in autism spectrum disorder (ASD) and to identify potential areas of translational focus for the next decade of research.
Method: A group of clinicians and researchers in ASD working both inside and outside of the HR design met on a regular basis to review the infant sibling research, and came to an agreement on areas that had changed clinical practice and areas that had the potential to change practice with further research. The group then outlined several methodological and translational challenges that must be addressed in the next decade of research if the field is to reach its potential.
Results: The review concluded that the HR design has yielded an understanding that ASD often, but not alway, begins to emerge between 6 and 18 months, with early signs affecting social communication. Research using the HR design has also allowed a better understanding of the sibling recurrence risk (between 10% and 20%). Emerging areas of interest include the developmental trajectories of social communications skills in the early years, the expression of a milder phenotype in siblings not affected with ASD, and the possibility that early intervention with infant siblings may improve outcomes for those with ASD. Important challenges for the future include linking screening to intervention, collecting large sample sizes while ensuring cross-site reliability, and building in capacity for replication.
Conclusion: Although there are significant methodological and translational challenges for high-risk infant sibling research, the potential of this design to improve long-term outcomes of all children with ASD is substantial.
C1 [Szatmari, Peter] Univ Toronto, Hosp Sick Children, Child & Youth Mental Hlth Collaborat, Toronto, ON M6J 1H4, Canada.
[Szatmari, Peter] Univ Toronto, Ctr Addict & Mental Hlth, 1001 Queen St West, Toronto, ON M6J 1H4, Canada.
[Szatmari, Peter] Univ Toronto, Div Child & Youth Mental Hlth, Toronto, ON M6J 1H4, Canada.
[Chawarska, Katarzyna] Yale Univ, Sch Med, Yale Child Study Ctr, Toddler Dev Disabil Clin, New Haven, CT USA.
[Dawson, Geraldine] Duke Univ, Sch Med, Duke Inst Brain Sci, Durham, NC USA.
[Georgiades, Stelios] McMaster Univ, Offord Ctr Child Studies, Hamilton, ON, Canada.
[Landa, Rebecca] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA.
[Lord, Catherine] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
[Lord, Catherine] Columbia Univ, Teachers Coll, New York, NY 10027 USA.
[Messinger, Daniel S.] Univ Miami, Coral Gables, FL 33124 USA.
[Thurm, Audrey] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Halladay, Alycia] Autism Sci Fdn, New York, NY USA.
[Halladay, Alycia] Rutgers State Univ, New Brunswick, NJ 08903 USA.
RP Szatmari, P (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, 1001 Queen St West, Toronto, ON M6J 1H4, Canada.
EM peter.szatmari@utoronto.ca
FU Autism Science Foundation
FX The authors would like to thank the Baby Sibs Research Consortium for
their thoughtful feedback on this paper, Autism Speaks for their
longstanding support of the High Risk Baby Siblings Research Consortium
(BSRC) activities, and the Autism Science Foundation for their support
of multiple high-risk infant projects.
NR 78
TC 4
Z9 4
U1 11
U2 37
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAR
PY 2016
VL 55
IS 3
BP 179
EP 187
DI 10.1016/j.jaac.2015.12.014
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DF2RT
UT WOS:000371192200007
PM 26903251
ER
PT J
AU Dunleavy, K
AF Dunleavy, Kieron
TI Immunomodulatory agents in mantle cell lymphoma
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID SURVIVAL; THERAPY; MCL
C1 [Dunleavy, Kieron] Natl Canc Inst, Lymphoid Malignancies Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), Natl Canc Inst, Lymphoid Malignancies Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2016
VL 17
IS 3
BP 262
EP 263
DI 10.1016/S1470-2045(16)00027-9
PG 3
WC Oncology
SC Oncology
GA DF3HN
UT WOS:000371234900025
PM 26899779
ER
PT J
AU Li, SZ
An, L
Yu, S
Araneta, MF
Johnson, CS
Wang, SM
Shen, J
AF Li, Shizhe
An, Li
Yu, Shao
Araneta, Maria Ferraris
Johnson, Christopher S.
Wang, Shumin
Shen, Jun
TI C-13 MRS of human brain at 7 Tesla using [2-C-13]glucose infusion and
low power broadband stochastic proton decoupling
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE C-13 MRS; human brain; stochastic decoupling; 7 T
ID MAGNETIC-RESONANCE-SPECTROSCOPY; ENERGY-METABOLISM; NMR-SPECTROSCOPY;
COIL; SENSITIVITY
AB PurposeCarbon-13 (C-13) MR spectroscopy (MRS) of the human brain at 7 Tesla (T) may pose patient safety issues due to high radiofrequency (RF) power deposition for proton decoupling. The purpose of present work is to study the feasibility of in vivo C-13 MRS of human brain at 7 T using broadband low RF power proton decoupling.
MethodsCarboxylic/amide C-13 MRS of human brain by broadband stochastic proton decoupling was demonstrated on a 7 T scanner. RF safety was evaluated using the finite-difference time-domain method. C-13 signal enhancement by nuclear Overhauser effect (NOE) and proton decoupling was evaluated in both phantoms and in vivo.
ResultsAt 7 T, the peak amplitude of carboxylic/amide C-13 signals was increased by a factor of greater than 4 due to the combined effects of NOE and proton decoupling. The 7 T C-13 MRS technique used decoupling power and average transmit power of less than 35 watts (W) and 3.6 W, respectively.
ConclusionIn vivo C-13 MRS studies of human brain can be performed at 7 T, well below the RF safety threshold, by detecting carboxylic/amide carbons with broadband stochastic proton decoupling. Magn Reson Med 75:954-961, 2016. (c) 2015 Wiley Periodicals, Inc.
C1 [Li, Shizhe; Shen, Jun] NIMH, Magnet Resonance Spect Core Facil, NIH, Bethesda, MD 20892 USA.
[An, Li; Araneta, Maria Ferraris; Johnson, Christopher S.; Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Yu, Shao; Wang, Shumin] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
[IRP-NIMH-NIH]
FX Grant sponsor: Intramural Research Program of the National Institute of
Mental Health, National Institutes of Health; Grant number:
IRP-NIMH-NIH.
NR 27
TC 2
Z9 2
U1 4
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2016
VL 75
IS 3
BP 954
EP 961
DI 10.1002/mrm.25721
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DE4IZ
UT WOS:000370593700004
PM 25917936
ER
PT J
AU Pegoraro, G
Misteli, T
AF Pegoraro, Gianluca
Misteli, Tom
TI High-throughput Imaging as a versatile and unbiased discovery tool
SO METHODS
LA English
DT Editorial Material
C1 [Pegoraro, Gianluca; Misteli, Tom] NCI, 41 Lib Dr,Bldg 41, Bethesda, MD 20892 USA.
RP Pegoraro, G; Misteli, T (reprint author), NCI, 41 Lib Dr,Bldg 41, Bethesda, MD 20892 USA.
EM gianluca.pegoraro@nih.gov; mistelit@mail.nih.gov
OI Pegoraro, Gianluca/0000-0003-2843-9464
NR 14
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 1
PY 2016
VL 96
BP 1
EP 2
DI 10.1016/j.ymeth.2016.01.003
PG 2
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF6CX
UT WOS:000371444500001
PM 26774352
ER
PT J
AU Kubben, N
Brimacombe, KR
Donegan, M
Li, ZY
Misteli, T
AF Kubben, Nard
Brimacombe, Kyle R.
Donegan, Megan
Li, Zhuyin
Misteli, Tom
TI A high-content imaging-based screening pipeline for the systematic
identification of anti-progeroid compounds
SO METHODS
LA English
DT Article
DE HGPS; Progerin; Retinoids; FDA-approved compounds; High-throughput
screening; High-content imaging
ID DNA-DAMAGE RESPONSES; DEFECTIVE MATURATION; DISEASE PHENOTYPES;
PRELAMIN-A; LAMIN B1; FARNESYLTRANSFERASE INHIBITOR; AMPK ACTIVATION;
NUCLEAR LAMINA; MOUSE MODEL; LIFE-SPAN
AB Hutchinson-Gilford Progeria Syndrome (HGPS) is an early onset lethal premature aging disorder caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A. The presence of progerin causes extensive morphological, epigenetic and DNA damage related nuclear defects that ultimately disrupt tissue and organismal functions. Hypothesis-driven approaches focused on HGPS affected pathways have been used in attempts to identify druggable targets with anti-progeroid effects. Here, we report an unbiased discovery approach to HGPS by implementation of a high-throughput, high-content imaging based screening method that enables systematic identification of small molecules that prevent the formation of multiple progerin-induced aging defects. Screening a library of 2816 FDA approved drugs, we identified retinoids as a novel class of compounds that reverses aging defects in HGPS patient skin fibroblasts. These findings establish a novel approach to anti-progeroid drug discovery. (C) 2016 Published by Elsevier Inc.
C1 [Kubben, Nard; Donegan, Megan; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Brimacombe, Kyle R.; Li, Zhuyin] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Li, Zhuyin] Bristol Meyers Squibb, Lead Discovery & Optimizat, 5 Res Pkwy, Wallingford, CT 06492 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research; grant for the Progeria Research
Foundation
FX We thank members of the Misteli lab for providing helpful feedback and
experimental suggestions. This research was supported by the Intramural
Research Program of the National Institutes of Health (NIH), NCI, Center
for Cancer Research and by a grant for the Progeria Research Foundation.
NR 54
TC 7
Z9 7
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 1
PY 2016
VL 96
BP 46
EP 58
DI 10.1016/j.ymeth.2015.08.024
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF6CX
UT WOS:000371444500008
PM 26341717
ER
PT J
AU Day, CR
Chen, HM
Coulon, A
Meier, JL
Larson, DR
AF Day, Christopher R.
Chen, Huimin
Coulon, Antoine
Meier, Jordan L.
Larson, Daniel R.
TI High-throughput single-molecule screen for small-molecule perturbation
of splicing and transcription kinetics
SO METHODS
LA English
DT Article
DE Transcription; Splicing; Small-molecule; RNA; Fluorescence; Fluctuation;
Single-molecule
ID BET BROMODOMAIN INHIBITION; PRE-MESSENGER-RNA; GENE-EXPRESSION;
TOPOISOMERASE-I; ELONGATION; IDENTIFICATION; REVEALS; CELLS; YEAST; TIME
AB In eukaryotes, mRNA synthesis is catalyzed by RNA polymerase II and involves several distinct steps, including transcript initiation, elongation, cleavage, and transcript release. Splicing of RNA can occur during (co-transcriptional) or after (post-transcriptional) RNA synthesis. Thus, RNA synthesis and processing occurs through the concerted activity of dozens of enzymes, each of which is potentially susceptible to perturbation by small molecules. However, there are few, if any, high-throughput screening strategies for identifying drugs which perturb a specific step in RNA synthesis and processing. Here we have developed a high-throughput fluorescence microscopy approach in single cells to screen for inhibitors of specific enzymatic steps in RNA synthesis and processing. By utilizing the high affinity interaction between bacteriophage capsid proteins (MS2, PP7) and RNA stem loops, we are able to fluorescently label the intron and exon of a beta-globin reporter gene in human cells. This approach allows one to measure the kinetics of transcription, splicing and release in both fixed and living cells using a tractable, genetically encoded assay in a stable cell line. We tested this reagent in a targeted screen of molecules that target chromatin readers and writers and identified three compounds that slow transcription elongation without changing transcription initiation. Published by Elsevier Inc.
C1 [Day, Christopher R.; Chen, Huimin; Larson, Daniel R.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Coulon, Antoine] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Meier, Jordan L.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Larson, DR (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM dan.larson@nih.gov
RI Meier, Jordan/N-2608-2014; Coulon, Antoine/A-9006-2012; Larson,
Daniel/B-9829-2008
OI Larson, Daniel/0000-0001-9253-3055
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Institute of Diabetes and Digestive
and Kidney Diseases
FX High-throughput imaging was conducted in collaboration with the HiTIF
core at NCI, with critical support from Gianluca Pegoraro and Laurent
Ozbun. Murali Palangat and Ty Voss provided critical technical support,
and Richard Day provided valuable feedback on the manuscript.
Herboxidiene was a kind gift from Melissa Jurica, University of
California at Santa Cruz. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research, and the National Institute of Diabetes and Digestive
and Kidney Diseases.
NR 39
TC 2
Z9 2
U1 4
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 1
PY 2016
VL 96
BP 59
EP 68
DI 10.1016/j.ymeth.2015.11.025
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF6CX
UT WOS:000371444500009
PM 26655523
ER
PT J
AU Lasota, J
Felisiak-Golabek, A
Wasag, B
Kowalik, A
Zieba, S
ChIopek, M
Wang, ZF
Coates, T
Kopczynski, J
Gozdz, S
Sarlomo-Rikala, M
Miettinen, M
AF Lasota, Jerzy
Felisiak-Golabek, Anna
Wasag, Bartosz
Kowalik, Artur
Zieba, Sebastian
ChIopek, Malgorzata
Wang, Zeng-Feng
Coates, Tiffany
Kopczynski, Janusz
Gozdz, Stanislaw
Sarlomo-Rikala, Maarit
Miettinen, Markku
TI Frequency and clinicopathologic profile of PIK3CA mutant GISTs:
molecular genetic study of 529 cases
SO MODERN PATHOLOGY
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; SIGNALING PATHWAY; BREAST-CANCER;
MUTATIONS; KIT; IMATINIB; RESISTANCE; INHIBITOR; PDGFRA; HETEROGENEITY
AB Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors usually driven by the mutational activation of receptor tyrosine kinases, KIT, or PDGFRA. Oncogenic activation of phosphatidylinositide-3-kinase (P13K), a downstream effector in the KIT signaling pathway, has been identified in different types of cancer, with the P13K 110 alpha subunit encoded by PIK3CA being a common mutational target. In this study, the mutational hotspot in the PIK3CA kinase domain encoded by exon 20 was evaluated in 529 imatinib-naive GISTs using PCR amplification and Sanger sequencing. Eight mutations (two co-existing in one tumor) were identified. Subsequently, The cobas PIK3CA Mutation Test was employed to evaluate mutational hotspots in exons 1, 4, 7, and 9 in 119 PIK3CA exon 20-wild type tumors. In two cases, mutations in exons 1 and 9 were identified. In one GIST, previously undetected by Sanger sequencing, the exon 20 mutation was discovered. Altogether, eight primary and two metastatic GISTs carried PIK3CA mutations. The size of primary PIK3CA-mutant GISTs was >= 14 cm (mean size 17 cm), and mitotic activity varied from 0 to 72 per 50HPF (mean 5/50HPF). Follow-up data showed short survival in 6 of 7 studied cases. Detection of PIK3CA mutations in large or metastatic KIT-mutant GISTs may suggest that PIK3CA-mutant clones have a proliferative advantage during disease progression. Tyrosine kinase inhibitors have been successfully used in GIST treatment. However, resistance frequently develops due to secondary KIT mutations or activation of downstream to KIT signaling pathways, such as the PI3K/AKT/mTOR pathway. PIK3CA mutations similar to the ones detected in GISTs have been shown to cause such activation. Therefore, genotyping of PIK3CA in GISTs might help to pinpoint primary and metastatic tumors with the potential to develop resistance to tyrosine kinase inhibitors and guide therapy with PI3K inhibitors.
C1 [Lasota, Jerzy; Felisiak-Golabek, Anna; Wang, Zeng-Feng; Coates, Tiffany; Miettinen, Markku] NCI, Pathol Lab, 10 Ctr Dr,Room B1B47, Bethesda, MD 20892 USA.
[Wasag, Bartosz] Med Univ Gdansk, Dept Biol & Genet, Gdansk, Poland.
[Kowalik, Artur; Zieba, Sebastian; ChIopek, Malgorzata] Holycross Canc Ctr, Dept Mol Diagnost, Kielce, Poland.
[Kopczynski, Janusz] Holycross Canc Ctr, Dept Surg Pathol, Kielce, Poland.
[Gozdz, Stanislaw] Holycross Canc Ctr, Dept Clin Oncol, Kielce, Poland.
[Gozdz, Stanislaw] Jan Kochanowski Univ Humanities & Sci, Fac Hlth Sci, Kielce, Poland.
[Sarlomo-Rikala, Maarit] Univ Helsinki, HUSLab, Helsinki, Finland.
RP Lasota, J (reprint author), NCI, Pathol Lab, 10 Ctr Dr,Room B1B47, Bethesda, MD 20892 USA.
EM jerzy.lasota@nih.gov
RI Kielce, SCO/O-6702-2016; Gozdz, Stanislaw/D-3300-2013;
OI Miettinen, Markku/0000-0002-3282-8107
NR 26
TC 3
Z9 3
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD MAR
PY 2016
VL 29
IS 3
BP 275
EP 282
DI 10.1038/modpathol.2015.160
PG 8
WC Pathology
SC Pathology
GA DF2TM
UT WOS:000371196800007
PM 26796526
ER
PT J
AU Wang, YX
AF Wang, Yun-Xing
TI RNA CONFORMATION Lightening up invisible states
SO NATURE CHEMICAL BIOLOGY
LA English
DT News Item
ID X-RAY-SCATTERING; ENSEMBLE; DYNAMICS; PROTEIN
C1 [Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21701 USA.
RP Wang, YX (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21701 USA.
EM wangyunx@mail.nih.gov
NR 10
TC 0
Z9 0
U1 4
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD MAR
PY 2016
VL 12
IS 3
BP 126
EP 127
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF5FK
UT WOS:000371377000001
PM 26881762
ER
PT J
AU Stuckey, JI
Dickson, BM
Cheng, N
Liu, YL
Norris, JL
Cholensky, SH
Tempel, W
Qin, S
Huber, KG
Sagum, C
Black, K
Li, FL
Huang, XP
Roth, BL
Baughman, BM
Senisterra, G
Pattenden, SG
Vedadi, M
Browne, PJ
Bedford, MT
Min, JR
Arrowsmith, CH
James, LI
Frye, SV
AF Stuckey, Jacob I.
Dickson, Bradley M.
Cheng, Nancy
Liu, Yanli
Norris, Jacqueline L.
Cholensky, Stephanie H.
Tempel, Wolfram
Qin, Su
Huber, Katherine G.
Sagum, Cari
Black, Karynne
Li, Fengling
Huang, Xi-Ping
Roth, Bryan L.
Baughman, Brandi M.
Senisterra, Guillermo
Pattenden, Samantha G.
Vedadi, Masoud
Browne, Peter J.
Bedford, Mark T.
Min, Jinrong
Arrowsmith, Cheryl H.
James, Lindsey I.
Frye, Stephen V.
TI A cellular chemical probe targeting the chromodomains of Polycomb
repressive complex 1
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID CHROMOBOX PROTEIN CBX7; ONCOGENIC ROLE; CELLS; METHYLATION; CANCER;
METHYLTRANSFERASES; DIFFERENTIATION; DEMETHYLATION; SPECIFICITY;
INHIBITION
AB We report the design and characterization of UNC3866, a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. Polycomb CBX proteins regulate gene expression by targeting Polycomb repressive complex 1 (PRC1) to sites of H3K27me3 via their chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K-d of similar to 100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains while being highly selective over >250 other protein targets. X-ray crystallography revealed that UNC3866's interactions with the CBX chromodomains closely mimic those of the methylated H3 tail. UNC4195, a biotinylated derivative of UNC3866, was used to demonstrate that UNC3866 engages intact PRC1 and that EED incorporation into PRC1 is isoform dependent in PC3 prostate cancer cells. Finally, UNC3866 inhibits PC3 cell proliferation, consistent with the known ability of CBX7 overexpression to confer a growth advantage, whereas UNC4219, a methylated negative control compound, has negligible effects.
C1 [Stuckey, Jacob I.; Dickson, Bradley M.; Cheng, Nancy; Norris, Jacqueline L.; Cholensky, Stephanie H.; Huber, Katherine G.; Baughman, Brandi M.; Pattenden, Samantha G.; James, Lindsey I.; Frye, Stephen V.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC USA.
[Liu, Yanli; Tempel, Wolfram; Qin, Su; Li, Fengling; Senisterra, Guillermo; Vedadi, Masoud; Browne, Peter J.; Min, Jinrong; Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
[Sagum, Cari; Black, Karynne; Bedford, Mark T.] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
RP James, LI; Frye, SV (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC USA.
EM ingerman@email.unc.edu; svfrye@email.unc.edu
FU National Institute of General Medical Sciences, US National Institutes
of Health (NIH) [R01GM100919]; US Department of Energy (DOE) Office of
Science User Facility; Carolina Partnership; University Cancer Research
Fund; University of North Carolina at Chapel Hill; Welch Foundation
[G-1847]; AbbVie [1097737]; Boehringer Ingelheim; Canada Foundation for
Innovation (CFI); Canadian Institutes of Health Research (CIHR); Genome
Canada; Ontario Genomics Institute Grant [OGI-055]; GlaxoSmithKline;
Janssen; Lilly Canada; Novartis Research Foundation; Ontario Ministry of
Economic Development and Innovation; Pfizer; Takeda; Wellcome Trust
[092809/Z/10/Z]; Cancer Prevention Research Institute of Texas
[RP130432]; Centre for Environmental and Molecular Carcinogenesis at the
MD Anderson Cancer Center
FX We thank K. Pearce (UNC Chapel Hill) for useful discussions and careful
reading of the manuscript, O. Fedorov (SGC Oxford) for support with the
bromodomain selectivity screening, A. Tumber (SGC Oxford) for support
with the lysine demethylase selectivity screening and J.R. Walker for
the review of the crystal structures. We thank G. Wang (UNC) for
providing PHF1, PHF19, PHF23 and JARID1A protein constructs. We thank
the labs of T. Magnuson (UNC) and D. Margolis (UNC) for providing EED
and BMI-1 antibodies, respectively. We also thank N. Sciaky (UNC) for
help with cell counting using the high content imaging microscope.
Results shown in this report are derived from work performed at Argonne
National Laboratory, Structural Biology Center at the Advanced Photon
Source, a US Department of Energy (DOE) Office of Science User Facility
operated for the DOE Office of Science by Argonne National Laboratory
under contract no. DE-AC02-06CH11357. The research described here was
supported by the National Institute of General Medical Sciences, US
National Institutes of Health (NIH, grant R01GM100919), the Carolina
Partnership and the University Cancer Research Fund, University of North
Carolina at Chapel Hill, and the Welch Foundation (G-1847). The SGC is a
registered charity (no. 1097737) that receives funds from AbbVie,
Boehringer Ingelheim, the Canada Foundation for Innovation (CFI), the
Canadian Institutes of Health Research (CIHR), Genome Canada, Ontario
Genomics Institute Grant OGI-055, GlaxoSmithKline, Janssen, Lilly
Canada, the Novartis Research Foundation, the Ontario Ministry of
Economic Development and Innovation, Pfizer, Takeda and Wellcome Trust
Grant 092809/Z/10/Z. M.T.B. directs the Protein Array Core, which is
supported by the Cancer Prevention Research Institute of Texas
(RP130432) and by the Centre for Environmental and Molecular
Carcinogenesis at the MD Anderson Cancer Center.
NR 50
TC 17
Z9 17
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD MAR
PY 2016
VL 12
IS 3
BP 180
EP 187
DI 10.1038/NGHEMBIO.2007
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF5FK
UT WOS:000371377000011
PM 26807715
ER
PT J
AU Klepac, K
Kilic, A
Gnad, T
Brown, LM
Herrmann, B
Wilderman, A
Balkow, A
Glode, A
Simon, K
Lidell, ME
Betz, MJ
Enerback, S
Wess, J
Freichel, M
Bluher, M
Konig, G
Kostenis, E
Insel, PA
Pfeifer, A
AF Klepac, Katarina
Kilic, Ana
Gnad, Thorsten
Brown, Loren M.
Herrmann, Beate
Wilderman, Andrea
Balkow, Aileen
Gloede, Anja
Simon, Katharina
Lidell, Martin E.
Betz, Matthias J.
Enerback, Sven
Wess, Juergen
Freichel, Marc
Blueher, Matthias
Koenig, Gabi
Kostenis, Evi
Insel, Paul A.
Pfeifer, Alexander
TI The G(q) signalling pathway inhibits brown and beige adipose tissue
SO NATURE COMMUNICATIONS
LA English
DT Article
ID COUPLED RECEPTOR EXPRESSION; LIPOPROTEIN-LIPASE GENE; ADIPOCYTES; FAT;
ENDOTHELIN-1; OBESITY; DIFFERENTIATION; PROGENITORS; ACTIVATION; CELLS
AB Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the G(q) family, and inhibition of G(q) signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of G(q) signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of G(q) signalling in brown adipocytes. Expression of a constitutively active G(q) protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of G(q) in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that G(q) signalling regulates brown/beige adipocytes and inhibition of G(q) signalling may be a novel therapeutic approach to combat obesity.
C1 [Klepac, Katarina; Kilic, Ana; Gnad, Thorsten; Brown, Loren M.; Herrmann, Beate; Balkow, Aileen; Gloede, Anja; Pfeifer, Alexander] Univ Bonn, Univ Hosp Bonn, Inst Pharmacol & Toxicol, D-53127 Bonn, Germany.
[Klepac, Katarina; Kilic, Ana; Herrmann, Beate; Simon, Katharina; Kostenis, Evi; Pfeifer, Alexander] Univ Bonn, Res Training Grp 1873, D-53127 Bonn, Germany.
[Brown, Loren M.; Wilderman, Andrea; Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Simon, Katharina; Koenig, Gabi; Kostenis, Evi] Univ Bonn, Inst Pharmaceut Biol, D-53115 Bonn, Germany.
[Lidell, Martin E.; Betz, Matthias J.; Enerback, Sven] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med & Clin Genet, SE-40530 Gothenburg, Sweden.
[Wess, Juergen] NIDDK, Mol Signalling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
[Freichel, Marc] Heidelberg Univ, Inst Pharmacol, D-69120 Heidelberg, Germany.
[Blueher, Matthias] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
[Insel, Paul A.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Pfeifer, Alexander] Univ Bonn, PharmaCtr, D-53127 Bonn, Germany.
RP Pfeifer, A (reprint author), Univ Bonn, Univ Hosp Bonn, Inst Pharmacol & Toxicol, D-53127 Bonn, Germany.; Pfeifer, A (reprint author), Univ Bonn, Res Training Grp 1873, D-53127 Bonn, Germany.; Pfeifer, A (reprint author), Univ Bonn, PharmaCtr, D-53127 Bonn, Germany.
EM alexander.pfeifer@uni-bonn.de
FU DFG [FOR2372, GRK1873]
FX We thank S. Kipschull and P. Zehner for expert technical assistance and
Jennifer Naumann for assistance with culturing and differentiation of
human cells. We thank C. Dani (University of Nice Sophia Antipolis) for
providing hMADS, S. Gutkind and B. Roth for providing GqQL and Dq
constructs, respectively. We thank the DFG for financial support
(especially the FOR2372 and GRK1873).
NR 45
TC 3
Z9 4
U1 8
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2016
VL 7
AR 10895
DI 10.1038/ncomms10895
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG0CB
UT WOS:000371728500001
PM 26955961
ER
PT J
AU Casellas, R
Basu, U
Yewdell, WT
Chaudhuri, J
Robbiani, D
Di Noia, JM
AF Casellas, Rafael
Basu, Uttiya
Yewdell, William T.
Chaudhuri, Jayanta
Robbiani, DavideF.
Di Noia, Javier M.
TI Mutations, kataegis and translocations in B cells: understanding AID
promiscuous activity
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION;
ACTIVATION-INDUCED DEAMINASE; RNA-POLYMERASE-II; DOUBLE-STRAND BREAKS;
ANTIBODY DIVERSIFICATION ENZYME; 5 NONCODING REGION; PROTEIN-KINASE-A;
NF-KAPPA-B; SOMATIC HYPERMUTATION
AB As B cells engage in the immune response, they express activation-induced cytidine deaminase (AID) to initiate the hypermutation and recombination of immunoglobulin genes, which are crucial processes for the efficient recognition and disposal of pathogens. However, AID must be tightly controlled in B cells to minimize off-target mutations, which can drive chromosomal translocations and the development of B cell malignancies, such as lymphomas. Recent genomic and biochemical analyses have begun to unravel the mechanisms of how AID-mediated deamination is targeted outside immunoglobulin genes. Here, we discuss the transcriptional and topological features that are emerging as key drivers of AID promiscuous activity.
C1 [Casellas, Rafael] NIAMSD, Genom & Immun, NCI, NIH, Bethesda, MD 20892 USA.
[Basu, Uttiya] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Yewdell, William T.; Chaudhuri, Jayanta] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
[Yewdell, William T.] Weill Cornell Grad Sch Med Sci, Immunol & Microbial Pathogenesis Program, New York, NY 10065 USA.
[Robbiani, DavideF.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Di Noia, Javier M.] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.
[Di Noia, Javier M.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
RP Casellas, R (reprint author), NIAMSD, Genom & Immun, NCI, NIH, Bethesda, MD 20892 USA.; Di Noia, JM (reprint author), Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.; Di Noia, JM (reprint author), Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
EM rafael.casellas@nih.gov; Javier.Di.Noia@ircm.qc.ca
RI Di Noia, Javier/D-2285-2012
OI Di Noia, Javier/0000-0003-2896-0321
FU NCI NIH HHS [P30 CA008748, T32 CA009149]; NIAID NIH HHS [R21 AI112602]
NR 135
TC 5
Z9 5
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD MAR
PY 2016
VL 16
IS 3
BP 164
EP 176
DI 10.1038/nri.2016.2
PG 13
WC Immunology
SC Immunology
GA DF5LU
UT WOS:000371394100009
PM 26898111
ER
PT J
AU Mulligan, C
Fenollar-Ferrer, C
Fitzgerald, GA
Vergara-Jaque, A
Kaufmann, D
Li, Y
Forrest, LR
Mindell, JA
AF Mulligan, Christopher
Fenollar-Ferrer, Cristina
Fitzgerald, Gabriel A.
Vergara-Jaque, Ariela
Kaufmann, Desiree
Li, Yan
Forrest, Lucy R.
Mindell, Joseph A.
TI The bacterial dicarboxylate transporter VcINDY uses a two-domain
elevator-type mechanism
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MEMBRANE-TRANSPORT; ALTERNATING
ACCESS; CRYSTAL-STRUCTURE; NEUROTRANSMITTER TRANSPORTERS;
CONFORMATIONAL-CHANGES; VIBRIO-CHOLERAE; SLC13 FAMILY; SUPERFAMILY;
TOPOLOGY
AB Secondary transporters use alternating-access mechanisms to couple uphill substrate movement to downhill ion flux. Most known transporters use a 'rocking bundle' motion, wherein the protein moves around an immobile substrate-binding site. However, the glutamate-transporter homolog Glt(ph) translocates its substrate-binding site vertically across the membrane, through an 'elevator' mechanism. Here, we used the 'repeat swap' approach to computationally predict the outward-facing state of the Na+/succinate transporter VcINDY, from Vibrio cholerae. Our model predicts a substantial elevator-like movement of VcINDY's substrate-binding site, with a vertical translation of similar to 15 angstrom and a rotation of similar to 43 degrees. Our observation that multiple disulfide cross-links completely inhibit transport provides experimental confirmation of the model and demonstrates that such movement is essential. In contrast, cross-links across the VcINDY dimer interface preserve transport, thus revealing an absence of large-scale coupling between protomers.
C1 [Mulligan, Christopher; Fitzgerald, Gabriel A.; Mindell, Joseph A.] NINDS, Membrane Transport Biophys Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Fenollar-Ferrer, Cristina; Vergara-Jaque, Ariela; Forrest, Lucy R.] NINDS, Computat Struct Biol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Fenollar-Ferrer, Cristina; Kaufmann, Desiree] Max Planck Inst Biophys, Frankfurt, Germany.
[Li, Yan] NINDS, Prot Peptide Sequencing Facil, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Fitzgerald, Gabriel A.; Kaufmann, Desiree] Weill Cornell Med Coll, Dept Physiol, New York, NY USA.
RP Mindell, JA (reprint author), NINDS, Membrane Transport Biophys Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Forrest, LR (reprint author), NINDS, Computat Struct Biol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM lucy.forrest@nih.gov; mindellj@ninds.nih.gov
FU L'Oreal Chile-United Nations Educational, Scientific and Cultural
Organization (UNESCO) Women in Science Fellowship; L'Oreal-UNESCO Rising
Talent Award; Division of Intramural Research of the US National
Institutes of Health, National Institute of Neurological Disorders and
Stroke
FX We thank A. Banerjee for helpful discussions and M. Maduke, J.
Faraldo-Gomez, G. Rudnick and M. Mayer for critical review of the
manuscript. A.V.-J. is supported as a recipient of the L'Oreal
Chile-United Nations Educational, Scientific and Cultural Organization
(UNESCO) Women in Science Fellowship and the L'Oreal-UNESCO Rising
Talent Award. This work was supported by the Division of Intramural
Research of the US National Institutes of Health, National Institute of
Neurological Disorders and Stroke.
NR 42
TC 8
Z9 8
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAR
PY 2016
VL 23
IS 3
BP 256
EP 263
DI 10.1038/nsmb.3166
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DF6FY
UT WOS:000371452500013
PM 26828963
ER
PT J
AU Cortese, I
Ohayon, J
Fenton, K
Lee, CC
Raffeld, M
Cowen, EW
DiGiovanna, JJ
Bielekova, B
AF Cortese, Irene
Ohayon, Joan
Fenton, Kaylan
Lee, Chyi-Chia
Raffeld, Mark
Cowen, Edward W.
DiGiovanna, John J.
Bielekova, Bibiana
TI Cutaneous adverse events in multiple sclerosis patients treated with
daclizumab
SO NEUROLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; INNATE LYMPHOID-CELLS; REGULATORY T-CELLS;
PITYRIASIS-ROSEA; ANTIBODY DACLIZUMAB; NONINFECTIOUS UVEITIS; IMATINIB
MESYLATE; DOUBLE-BLIND; SKIN; DISEASE
AB Objective:To analyze the spectrum and mechanisms of cutaneous adverse events (AEs) in patients with multiple sclerosis treated with daclizumab high-yield process (DAC-HYP).Methods:A total of 31 participants in an institutional review board-approved open-label phase I study of DAC-HYP (NCT01143441) were prospectively evaluated over 42 months for development of cutaneous AEs. Participants provided written informed consent. Fifteen participants were naive to anti-CD25 therapy (cohort B), while 16 had received daclizumab (Zenapax; Hoffmann-La Roche) IV for 4-9 years (mean 5.8 years) prior to enrollment (cohort A). Immunohistochemistry was performed on pretreatment and posttreatment skin biopsies of normal-appearing skin (cohort B only) and on lesional biopsies in participants presenting with rash (both cohorts).Results:Cutaneous AEs occurred in 77% of patients, the majority presenting with patches of eczema requiring no treatment. Moderate to severe rash developed in 6 participants (19%) and required discontinuation of DAC-HYP in 4 (13%). More severe rashes presented psoriasiform phenotype, but lesional biopsies lacked features of either psoriasis or drug hypersensitivity eruptions. Instead, irrespective of clinical severity, lesional biopsies showed nonspecific features of eczematous dermatitis, but with prominent CD56+ lymphocytic infiltrates. Pretreatment and posttreatment biopsies of normal-appearing skin demonstrated no histopathologic changes.Conclusions:Observed cutaneous AEs are likely related to the immunomodulatory effects DAC-HYP exerts on innate lymphoid cells, including natural killer cells. Vigilance and timely management of skin reactions may prevent treatment discontinuation in participants with severe rash.
C1 [Cortese, Irene; Ohayon, Joan] NINDS, Neuroimmunol Clin, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia; Raffeld, Mark] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Cowen, Edward W.; DiGiovanna, John J.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Fenton, Kaylan] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM bibi.bielekova@nih.gov
FU National Institute of Neurological Disorders and Stroke (NINDS), NIH;
NINDS; Abbvie/Biogen-Idec
FX This study was funded by the intramural research program of the National
Institute of Neurological Disorders and Stroke (NINDS), NIH, and by a
Collaborative Research Agreement (CRADA) between NINDS and
Abbvie/Biogen-Idec.
NR 33
TC 8
Z9 8
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 1
PY 2016
VL 86
IS 9
BP 847
EP 855
DI 10.1212/WNL.0000000000002417
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DF4TG
UT WOS:000371343100007
PM 26843560
ER
PT J
AU Lagemaat, MW
van de Bank, BL
Sati, P
Li, SZ
Maas, MC
Scheenen, TWJ
AF Lagemaat, Miriam W.
van de Bank, Bart L.
Sati, Pascal
Li, Shizhe
Maas, Marnix C.
Scheenen, Tom W. J.
TI Repeatability of P-31 MRSI in the human brain at 7T with and without the
nuclear Overhauser effect
SO NMR IN BIOMEDICINE
LA English
DT Article
DE repeatability; reproducibility; 7T; ultrahigh field; MRS
ID MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO; RELAXATION-TIMES; HUMAN
PROSTATE; MUSCLE; REPRODUCIBILITY; ENHANCEMENTS; METABOLITES; DISEASE;
TUMORS
AB An often-employed strategy to enhance signals in P-31 MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the P-31 data, because variation is reported in NOE enhancements. This would negate the signal-to-noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of P-31 MRS measurements. To verify this hypothesis, a repeatability study of native and NOE-enhanced P-31 MRSI was performed in the brains of seven healthy volunteers at 7T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoVrepeat) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE-enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoVrepeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between-voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoVrepeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE-enhanced P-31 MRSI. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Lagemaat, Miriam W.; van de Bank, Bart L.; Maas, Marnix C.; Scheenen, Tom W. J.] Radboud Univ Nijmegen, Med Ctr, Dept Radiol & Nucl Med, Nijmegen, Netherlands.
[Sati, Pascal; Scheenen, Tom W. J.] NINDS, Lab Funct & Mol Imaging, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Li, Shizhe] NIMH, MRS Core Facil, NIH, Bethesda, MD 20892 USA.
[Scheenen, Tom W. J.] Univ Duisburg Essen, Erwin L Hahn Inst Magnet Resonance Imaging, Essen, Germany.
RP Lagemaat, MW (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Radiol & Nucl Med, Post 766,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM miriamlagemaat@gmail.com
RI Scheenen, Tom/I-5921-2013
FU European Research Council under the European Community [243115];
National Institute of Mental Health (NIMH); National Institute of
Neurological Disorders and Stroke (NINDS), National Institutes of Health
(NIH)
FX This work was supported by grant number 243115 from the European
Research Council under the European Community's Seventh Framework
Programme (FP7/2007-2013). This work was partially supported by the
intramural research programs of the National Institute of Mental Health
(NIMH) and National Institute of Neurological Disorders and Stroke
(NINDS), National Institutes of Health (NIH).
NR 35
TC 1
Z9 1
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD MAR
PY 2016
VL 29
IS 3
BP 256
EP 263
DI 10.1002/nbm.3455
PG 8
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA DF5XK
UT WOS:000371426000006
PM 26647020
ER
PT J
AU Liu, HS
Shen, H
Luo, Y
Hoffer, BJ
Wang, Y
Yang, Y
AF Liu, H. -S.
Shen, H.
Luo, Y.
Hoffer, B. J.
Wang, Y.
Yang, Y.
TI Post-treatment with cocaine- and amphetamine-regulated transcript
enhances infarct resolution, reinnervation, and angiogenesis in stroke
rats - an MRI study
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRI; susceptibility-weighted imaging; fractional anisotropy; cocaine-
and amphetamine-regulated transcript
ID TRANSIENT FOCAL ISCHEMIA; EMBOLIC STROKE; CART PEPTIDE; BRAIN; RECOVERY;
NEUROGENESIS; ACTIVATION; EXPRESSION; THERAPY; CELLS
AB Recent studies have shown that post-treatment with cocaine- and amphetamine-regulated transcript (CART) has neuroregenerative effects in animal models of stroke. The purpose of this study was to characterize CART-mediated neuronal and vascular repairments using non-invasive MRI techniques. Adult male rats were subjected to a 90 min middle cerebral artery occlusion (MCAo). Animals were separated into two groups with similar infarction sizes, measured by T-2-weighted MRI on Day 2 after MCAo, and were treated with CART or vehicle intranasally from Day 3 to Day 12. Diffusion tensor imaging was used to examine changes in plasticity of white matter elements. Susceptibility-weighted imaging (SWI) was used to measure angiogenesis. Post-treatment with CART significantly increased fractional anisotropy (FA) in lesioned cortex on Days 10 and 25 post stroke. A significant correlation between the behavioral recovery in body asymmetry and the change in FA was shown, suggesting that behavioral recovery was associated with reinnervation to the lesioned hemisphere. CART also increased the intensity of SWI and the immunoreactivity of the vascular marker alpha-smooth muscle actin in lesioned cortex. Together, our data support a non-invasive treatment strategy for stroke through angiogenesis and reinnervation by CART. Copyright (c) 2016 John Wiley & Sons, Ltd.
C1 [Liu, H. -S.; Yang, Y.] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
[Wang, Y.] Natl Hlth Res Inst, Ctr Neuropsychiat Res, 35 Keyan Rd, Zhunan 35053, Miaoli County, Taiwan.
[Liu, H. -S.] Taipei Med Univ, Coll Med, Grad Inst Clin Med, Taipei, Taiwan.
[Liu, H. -S.] Taipei Med Univ Hosp, Dept Med Imaging, Taipei, Taiwan.
[Shen, H.] NIDA, Synapt Plast Sect, Cellular Neurobiol Res Branch, NIH, Baltimore, MD USA.
[Luo, Y.; Hoffer, B. J.] Case Western Reserve Univ, Dept Neurol Surg, Cleveland, OH 44106 USA.
[Hoffer, B. J.] NIDA, Biomed Res Ctr, NIH, Baltimore, MD USA.
[Liu, H. -S.] Taipei Med Univ Hosp, Radiogenom Res Ctr, Taipei, Taiwan.
[Liu, H. -S.] Translat Imaging Res Ctr, Taipei, Taiwan.
RP Yang, Y (reprint author), NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.; Wang, Y (reprint author), Natl Hlth Res Inst, Ctr Neuropsychiat Res, 35 Keyan Rd, Zhunan 35053, Miaoli County, Taiwan.
EM ywang@nhri.org.tw; yihongyang@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse.
NR 41
TC 0
Z9 0
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD MAR
PY 2016
VL 29
IS 3
BP 361
EP 370
DI 10.1002/nbm.3461
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA DF5XK
UT WOS:000371426000016
PM 26915794
ER
PT J
AU Yang, BY
Yang, HP
Ward, KK
Sahasrabuddhe, VV
McGlynn, KA
AF Yang, Baiyu
Yang, Hannah P.
Ward, Kristy K.
Sahasrabuddhe, Vikrant V.
McGlynn, Katherine A.
TI Bariatric Surgery and Liver Cancer in a Consortium of Academic Medical
Centers
SO OBESITY SURGERY
LA English
DT Article
DE Bariatric surgery; Liver cancer; Administrative records; Obesity;
Diabetes
ID OBESE-PATIENTS; METAANALYSIS; MORTALITY; OUTCOMES
AB Obesity is implicated as an important factor in the rising incidence of liver cancer in the USA. Bariatric surgery is increasingly used for treating morbid obesity and comorbidities. Using administrative data from UHC, a consortium of academic medical centers in the USA, we compared the prevalence of liver cancer among admissions with and without a history of bariatric surgery within a 3-year period. Admissions with a history of bariatric surgery had a 61 % lower prevalence of liver cancer compared to those without a history of bariatric surgery (prevalence ratio 0.39, 95 % confidence interval 0.35-0.44), and these inverse associations persisted within strata of sex, race, and ethnicity. This hospital administrative record-based analysis suggests that bariatric surgery could play a role in liver cancer prevention.
C1 [Yang, Baiyu; Yang, Hannah P.; Sahasrabuddhe, Vikrant V.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sahasrabuddhe, Vikrant V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Ward, Kristy K.] Univ Florida, Coll Med, Div Gynecol Oncol, Jacksonville, FL 32209 USA.
RP Yang, BY (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM baiyu.yang@nih.gov; yanghan@mail.nih.gov; kristy.kay.ward@gmail.com;
vikrant.sahasrabuddhe@nih.gov; mcglynnk@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
EI 1708-0428
J9 OBES SURG
JI Obes. Surg.
PD MAR
PY 2016
VL 26
IS 3
BP 696
EP 700
DI 10.1007/s11695-016-2051-1
PG 5
WC Surgery
SC Surgery
GA DF3PV
UT WOS:000371258100037
PM 26757918
ER
PT J
AU Higgins, RD
Saade, G
Polin, RA
Grobman, WA
Buhimschi, IA
Watterberg, K
Silver, RM
Raju, TNK
AF Higgins, Rosemary D.
Saade, George
Polin, Richard A.
Grobman, William A.
Buhimschi, Irina A.
Watterberg, Kristi
Silver, Robert M.
Raju, Tonse N. K.
CA Chorioamnionitis Workshop Particip
TI Evaluation and Management of Women and Newborns With a Maternal
Diagnosis of Chorioamnionitis Summary of a Workshop
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID C-REACTIVE PROTEIN; IMMEDIATE POSTNATAL-PERIOD; EPIDURAL-RELATED FEVER;
ONSET NEONATAL SEPSIS; CLINICAL CHORIOAMNIONITIS; INTRAAMNIOTIC
INFECTION; INTERLEUKIN-6; LABOR; RISK; PROCALCITONIN
AB In January 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited an expert panel to a workshop to address numerous knowledge gaps and to provide evidence-based guidelines for the diagnosis and management of pregnant women with what had been commonly called chorioamnionitis and the neonates born to these women. The panel noted that the term chorioamnionitis has been used to label a heterogeneous array of conditions characterized by infection and inflammation or both with a consequent great variation in clinical practice for mothers and their newborns. Therefore, the panel proposed to replace the term chorioamnionitis with a more general, descriptive term: "intrauterine inflammation or infection or both," abbreviated as "Triple I." The panel proposed a classification for Triple I and recommended approaches to evaluation and management of pregnant women and their newborns with a diagnosis of Triple I. It is particularly important to recognize that an isolated maternal fever is not synonymous with chorioamnionitis. A research agenda was proposed to further refine the definition and management of this complex group of conditions. This article provides a summary of the workshop presentations and discussions.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
Columbia Univ, Dept Pediat, New York, NY 10027 USA.
Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Ctr Perinatal Res,Res Inst, Columbus, OH 43210 USA.
Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA.
Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT USA.
RP Higgins, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM higginsr@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 47
TC 10
Z9 10
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAR
PY 2016
VL 127
IS 3
BP 426
EP 436
DI 10.1097/AOG.0000000000001246
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DE6DE
UT WOS:000370723000002
PM 26855098
ER
PT J
AU Hobday, T
Yin, J
Pettinger, A
Strosberg, J
Reidy-Lagunes, D
Chen, H
Erlichman, C
AF Hobday, Timothy
Yin, Jun
Pettinger, Adam
Strosberg, Jonathan
Reidy-Lagunes, Diane
Chen, Helen
Erlichman, Charles
TI Multicenter Prospective Phase II Trial of Bevacizumab (bev) for
Progressive Pancreatic Neuroendocrine Tumor (PNET)
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Hobday, Timothy; Yin, Jun; Pettinger, Adam; Erlichman, Charles] Mayo Clin, Coll Med, Mayo Phase Consortium P2C 2, Rochester, MN USA.
[Strosberg, Jonathan] Univ S Florida, H Lee Moffitt Canc Ctr, Southeast P2C, Tampa, FL 33682 USA.
[Reidy-Lagunes, Diane] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Chen, Helen] Natl Canc Inst, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD MAR
PY 2016
VL 45
IS 3
BP 477
EP 477
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DE9KQ
UT WOS:000370956600055
ER
PT J
AU Danziger-Isakov, L
Frazier, TW
Worley, S
Williams, N
Shellmer, D
Dharnidharka, VR
Gupta, NA
Ikle, D
Sweet, SC
AF Danziger-Isakov, Lara
Frazier, Thomas W.
Worley, Sarah
Williams, Nikki
Shellmer, Diana
Dharnidharka, Vikas R.
Gupta, Nitika A.
Ikle, David
Sweet, Stuart C.
CA CTOTC-05 Consortium
TI Perceived barriers to medication adherence in pediatric and adolescent
solid organ transplantation
SO PEDIATRIC TRANSPLANTATION
LA English
DT Article
DE adherence; pediatric; solid-organ transplant
ID RECIPIENTS; NONADHERENCE; OUTCOMES; METAANALYSIS; REGIMEN; RISK
AB Comparisons of perceived barriers to adherence in pediatric and adolescent SOT have not been systematically conducted despite association between medication non-adherence and poor outcome. Fifteen centers in CTOT-C enrolled patients in a cross-sectional study. Subjects' guardians completed the PMBS and subjects over eight completed the Adolescent Scale (AMBS). Association of three identified PMBS factors and subject age was assessed. Secondary analyses assessed associations between PMBS, AMBS, and patient demographics. Three hundred sixty-eight subjects or their guardians completed PMBS or AMBS. A total of 107 subjects were 6-11 yr; 261 were 12. Unadjusted and propensity-adjusted analyses indicated higher perceived barriers in guardians of adolescents as compared to guardians of pre-adolescents medication scheduling and frustration domains regardless of organ (p < 0.05). PMBS and AMBS comparisons revealed that guardians reported fewer ingestion issues than patients (p = 0.018), and differences appeared more pronounced within younger responders for scheduling (p = 0.025) and frustration (p = 0.019). Screening revealed guardians of older patients report increased perceived barriers to adherence independent of socioeconomic status. Guardians of adolescents reported fewer perceived barriers to ingestion/side effects than patients themselves, particularly in pre-adolescents (8-11 yr). Brief screening measures to assess perceived barriers should be further studied in adherence improvement programs.
C1 [Danziger-Isakov, Lara] Cincinnati Childrens Hosp Med Ctr, MLC 7017,3333 Burnet Ave, Cincinnati, OH 45229 USA.
[Frazier, Thomas W.; Worley, Sarah] Cleveland Clin Childrens, Cleveland, OH USA.
[Williams, Nikki] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Shellmer, Diana] Univ Pittsburgh, Childrens Hosp Pittsburgh, UPMC, Pittsburgh, PA 15213 USA.
[Dharnidharka, Vikas R.; Sweet, Stuart C.] Washington Univ, Sch Med, St Louis Childrens Hosp, St Louis, MO USA.
[Gupta, Nitika A.] Emory Univ, Sch Med, Atlanta, GA USA.
[Ikle, David] Rho, Chapel Hill, NC USA.
RP Danziger-Isakov, L (reprint author), Cincinnati Childrens Hosp Med Ctr, MLC 7017,3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM Lara.Danziger-Isakov@cchmc.org
FU National Institutes of Health U01 grant [U01 AI077810]
FX This research was performed as a project of the CTOT-C, a collaborative
clinical research project headquartered at the National Institute of
Allergy and Infectious Diseases. The study was supported by a supplement
to National Institutes of Health U01 grant (U01 AI077810) awarded to S.
Sweet. We acknowledge feedback from Nancy Bridges at NIAID on the study
design and interpretation of results.
NR 22
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1397-3142
EI 1399-3046
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD MAR
PY 2016
VL 20
IS 2
BP 307
EP 315
DI 10.1111/petr.12648
PG 9
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA DF5ZM
UT WOS:000371433100018
PM 26670870
ER
PT J
AU Kendall, GM
Wakeford, R
Athanson, M
Vincent, TJ
Carter, EJ
McColl, NP
Little, MP
AF Kendall, G. M.
Wakeford, R.
Athanson, M.
Vincent, T. J.
Carter, E. J.
McColl, N. P.
Little, M. P.
TI Levels of naturally occurring gamma radiation measured in British homes
and their prediction in particular residences
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Article
DE Gamma radiation; Natural background radiation; Childhood cancer;
Leukaemia
ID KINGDOM CHILDHOOD-CANCER; IONIZING-RADIATION; BACKGROUND-RADIATION;
DOMESTIC SOURCES; GREAT-BRITAIN; LEUKEMIA; EXPOSURE; RISK; UNCERTAINTY;
LIKELIHOOD
AB Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Mat,rn correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Mat,rn model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Mat,rn model.
C1 [Kendall, G. M.] Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
[Wakeford, R.] Univ Manchester, Inst Populat Hlth, Ctr Environm & Occupat Hlth, Ellen Wilkinson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England.
[Athanson, M.] Univ Oxford, Bodleian Lib, Broad St, Oxford OX1 3BG, England.
[Vincent, T. J.] Univ Oxford, Childhood Canc Res Grp, New Richards Bldg,Old Rd, Oxford, England.
[Carter, E. J.] Univ Worcester, Earth Heritage Trust, Geol Records Ctr, Worcester WR2 6AJ, England.
[McColl, N. P.] Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Didcot OX11 0RQ, Oxon, England.
[Little, M. P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA.
RP Kendall, GM (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
EM Gerald.Kendall@ceu.ox.ac.uk
OI Kendall, Gerry/0000-0002-9195-754X; Wakeford,
Richard/0000-0002-2934-0987
FU Children with Cancer (UK); National Institutes of Health, the National
Cancer Institute, Division of Cancer Epidemiology and Genetics;
Department of Health; Scottish Government
FX We are very grateful to Jill Simpson of the University of York and to
the other UKCCS investigators for making available the indoor gamma-ray
measurements made for the United Kingdom Childhood Cancer Study and for
advice on the interpretation of the data. We are also very grateful to J
D Appleton for advice on geological matters generally and in particular
for suggesting geological classification schemes. We are grateful to
Phil Gilvin, Luke Hager and Rick Tanner at Public Health England (PHE)
for advice on the dosimetry of the National Survey and the UKCCS and to
Simon Bouffler and other colleagues at PHE for allowing the use of the
National Survey data and for advice on its interpretation. They also
made helpful comments on the draft. Helpful comments were also made by
the two referees and by Bernd Grosche, Michael Murphy and Graham Smith.
This work was supported by Children with Cancer (UK) and by the
Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
Much of the work by two of the authors (GMK and TJV) was undertaken at
the Childhood Cancer Research Group, whose loss is much regretted. The
research work of CCRG was supported by the Department of Health for
England and Wales, Scottish Government and Children with Cancer (UK).
NR 49
TC 2
Z9 2
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
EI 1432-2099
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD MAR
PY 2016
VL 55
IS 1
BP 103
EP 124
DI 10.1007/s00411-016-0635-8
PG 22
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA DF4IY
UT WOS:000371312400014
PM 26880257
ER
PT J
AU Javaheri, S
Sharma, RK
Wang, R
Weng, J
Rosen, BD
Bluemke, DA
Lima, JAC
Redline, S
AF Javaheri, Sogol
Sharma, Ravi K.
Wang, Rui
Weng, Jia
Rosen, Boaz D.
Bluemke, David A.
Lima, Joao A. C.
Redline, Susan
TI Association between Obstructive Sleep Apnea and Left Ventricular
Structure by Age and Gender: the Multi-Ethnic Study of Atherosclerosis
SO SLEEP
LA English
DT Article
DE obstructive sleep apnea; left ventricular mass; cardiac magnetic
resonance imaging; left ventricular mass/volume ratio
ID POSITIVE AIRWAY PRESSURE; HEART-FAILURE; DIASTOLIC FUNCTION;
CARDIOVASCULAR EVENTS; SYSTOLIC FUNCTION; BLOOD-PRESSURE; MASS;
PREVALENCE; HYPERTENSION; HYPERTROPHY
AB Study Objectives: The presence and severity of obstructive sleep apnea (OSA) are associated with impaired left ventricular (LV) structure and function. Our goal was to quantify the associations between LV systolic function and mass with severity of OSA in an ethnically diverse cohort, assessing variations by age and sex.
Methods: We conducted a cross-sectional analysis of data from 1,412 racially/ethnically diverse participants across 6 US communities from the Multi-Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging from 2010-2012. We evaluated the association between the obstructive apnea-hypopnea index (AHI) by clinical category (< 5, 5-15, 15-30, 30-50, > 50) and secondary measures of sleep apnea with the outcomes left ventricular (LV) mass adjusted for height, LV mass/volume ratio, and LV ejection fraction.
Results: After adjusting for potential confounders and mediators, LV mass was significantly increased with increasing AHI category for subjects age 65 y or younger (beta = 1.84 +/- 0.47 g/m, P = 0.0001). The association between the AHI and LV mass appeared stronger in whites and Chinese compared to blacks and Hispanics, although interaction terms were not statistically significant. Additionally, while both LV mass and LV mass/volume ratio were significantly associated with hypoxia, ejection fraction was not associated with any OSA severity index. Comparable associations were observed in men and women.
Conclusions: Independent of confounders, higher levels of AHI are significantly associated with increased LV mass in both men and women younger than 65 y from a community-based cohort.
C1 [Javaheri, Sogol; Wang, Rui; Weng, Jia; Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Sleep & Circadian Disorders,Med Sch, Boston, MA 02115 USA.
[Javaheri, Sogol; Wang, Rui; Weng, Jia; Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Div Sleep & Circadian Disorders,Med Sch, Boston, MA 02115 USA.
[Javaheri, Sogol; Wang, Rui; Weng, Jia; Redline, Susan] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Sharma, Ravi K.; Rosen, Boaz D.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA.
[Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Javaheri, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 221 Longwood Ave,BLI-225, Boston, MA 02115 USA.
EM sjavaheri@partners.org
OI Bluemke, David/0000-0002-8323-8086
FU NIH [5T32HL007901, 1R01HL083075, R01HL098433, R01 HL098433-02S1,
1U34HL105277-01, 1R01HL110068-01A1, 1R01HL113338-01]; Jazz
Pharmaceuticals
FX This was not an industry supported study. Funding was provided by NIH
5T32HL007901, 1R01HL083075, R01HL098433, R01 HL098433-02S1,
1U34HL105277-01, 1R01HL110068-01A1, and 1R01HL113338-01. Dr. Redline has
received research support from Jazz Pharmaceuticals. The other authors
have indicated no financial conflicts of interest.
NR 39
TC 0
Z9 0
U1 0
U2 1
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD MAR 1
PY 2016
VL 39
IS 3
BP 523
EP 529
AR PII sp-00337-15
DI 10.5665/sleep.5518
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF1RB
UT WOS:000371115800006
PM 26888453
ER
PT J
AU Johnson, RF
Bagci, U
Keith, L
Tang, XC
Mollura, DJ
Zeitlin, L
Qin, J
Huzella, L
Bartos, CJ
Bohorova, N
Bohorov, O
Goodman, C
Kim, DH
Paulty, MH
Velasco, J
Whaley, KJ
Johnson, JC
Pettitt, J
Ork, BL
Solomon, J
Oberlander, N
Zhu, Q
Sun, JS
Holbrook, MR
Olinger, GG
Baric, RS
Hensley, LE
Jahrling, PB
Marasco, WA
AF Johnson, Reed F.
Bagci, Ulas
Keith, Lauren
Tang, Xianchun
Mollura, Daniel J.
Zeitlin, Larry
Qin, Jing
Huzella, Louis
Bartos, Christopher J.
Bohorova, Natasha
Bohorov, Ognian
Goodman, Charles
Kim, Do H.
Paulty, Michael H.
Velasco, Jesus
Whaley, Kevin J.
Johnson, Joshua C.
Pettitt, James
Ork, Britini L.
Solomon, Jeffrey
Oberlander, Nicholas
Zhu, Quan
Sun, Jiusong
Holbrook, Michael R.
Olinger, Gene G.
Baric, Ralph S.
Hensley, Lisa E.
Jahrling, Peter B.
Marasco, Wayne A.
TI 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology
in rhesus monkeys following intratracheal inoculation of MERS-CoV
Jordan-n3/2012
SO VIROLOGY
LA English
DT Article
DE MERS-CoV; Antibody therapy; Animal model, MERS; Respiratory syndrome;
Human monoclonal antibody therapy
ID EAST RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS INFECTION; MOUSE MODEL;
NEUTRALIZING ANTIBODIES; DROMEDARY CAMELS; SAUDI-ARABIA; VIRUS; TRACT;
GENERATION; IDENTIFICATION
AB Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5 x 10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. Published by Elsevier Inc.
C1 [Johnson, Reed F.; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
[Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Ctr Clin, Bethesda, MD 20892 USA.
[Keith, Lauren; Huzella, Louis; Bartos, Christopher J.; Johnson, Joshua C.; Pettitt, James; Ork, Britini L.; Oberlander, Nicholas; Holbrook, Michael R.; Olinger, Gene G.; Hensley, Lisa E.; Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
[Tang, Xianchun; Zhu, Quan; Sun, Jiusong; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Zeitlin, Larry; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Paulty, Michael H.; Velasco, Jesus; Whaley, Kevin J.] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.
[Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Bagci, Ulas] Univ Cent Florida, CRCV, Dept Elect Elect & Comp Sci, Orlando, FL 32816 USA.
[Solomon, Jeffrey] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Johnson, RF (reprint author), NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
EM johnsonreed@mail.nih.gov
OI Bagci, Ulas/0000-0001-7379-6829
FU NIAID Division of Intramural Research; Battelle Memorial Institute; US
National Institute of Allergy and Infectious Diseases (NIAID)
[HHSN272200700016I]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; NIAID [R01AI085524]; Defense Advanced
Research Projects Agency [W911NF-10-0226]
FX This work was supported by the NIAID Division of Intramural Research. We
are grateful to Marisa St Claire, Russell Byrum, Dan Ragland, and the
entire EVPS and IRF team for their contributions to these studies. We
thank Jiro Wada for his contribution to the preparation of figures. The
content of this publication does not necessarily reflect the views or
policies of the US Department of Health and Human Services (DHHS) or of
the institutions and companies affiliated with the authors. This work
was funded in part through Battelle Memorial Institute's prime contract
with the US National Institute of Allergy and Infectious Diseases
(NIAID) under Contract no. HHSN272200700016I. B.L.O., M.R.H., J.C.J.
performed this work as employees of Battelle Memorial Institute.
Subcontractors to Battelle Memorial Institute who performed this work
are: E.P. an employee of Tunnell Government Services, Inc; N.O., S.Y.
and L.H. are employees of Charles River Laboratories, S.M. an employee
of MRI Global, CB an employee of MedRelief. J.S. is an employee with
Lei-dos. His part in the project has been funded in whole or in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. W.A.M. and
R.S.B. were supported by Grant R01AI085524 from NIAID. W.A.M also
received support from Defense Advanced Research Projects Agency Grant
W911NF-10-0226. The authors thank Drs. Yuri Gleba and Victor Klimyuk
(Icon Genetics) for access to the magnICON expression technology and Dr.
Herta Steinkellner (BOKU) for access to the N. benthamiana seed.
NR 36
TC 8
Z9 8
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR
PY 2016
VL 490
BP 49
EP 58
DI 10.1016/j.virol.2016.01.004
PG 10
WC Virology
SC Virology
GA DF6DF
UT WOS:000371445400006
PM 26828465
ER
PT J
AU Patel, D
Gara, SK
Ellis, RJ
Boufraqech, M
Nilubol, N
Millo, C
Stratakis, CA
Kebebew, E
AF Patel, Dhaval
Gara, Sudheer Kumar
Ellis, Ryan J.
Boufraqech, Myriem
Nilubol, Naris
Millo, Corina
Stratakis, Constantine A.
Kebebew, Electron
TI FDG PET/CT Scan and Functional Adrenal Tumors: A Pilot Study for
Lateralization
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; PRIMARY ALDOSTERONISM; CUSHINGS-SYNDROME;
HEXOKINASE-II; MANAGEMENT; DIAGNOSIS; INCIDENTALOMAS; EXPRESSION;
CHALLENGE
AB Background Patients with Cushing's Syndrome (CS) and Conn's Syndrome with bilateral adrenal masses pose a dilemma. Uptake of 18F-FDG by hyperfunctioning adrenal glands has not been previously reported and may help lateralize. The aim was to determine if 18F-FDG PET/CT scan could identify hyperfunctioning adrenal masses and determine a biological basis for uptake.
Methods Patients with nonfunctional adenomas (n = 9), CS (n = 11), and Conn's syndrome (n = 4) underwent an 18F-FDG PET/CT scan with a volume of interest circumscribing each mass to obtain a maximal standardized uptake value (SUVmax). Thirty-two adrenal masses were analyzed. Genome-wide expression data from an independent cohort were analyzed in nonfunctioning adenomas (n = 20), Conn's syndrome (n = 29), and CS (n = 24) focusing on GLUT genes. For genes differentially expressed, immunohistochemistry was performed on tissue samples.
Results Cortisol-secreting masses (n = 16) had a higher average SUVmax of 5.9 compared to nonfunctioning masses (n = 11, average SUVmax 4.2) and aldosterone-hypersecreting masses (n = 5, average SUVmax 3.2) (p = 0.007). SUVmax cut-off of 5.33 had 50.0 % sensitivity and 81.8 % specificity in localizing a cortisol-secreting mass. GLUT3 expression was 2.19-fold higher in patients with CS compared to patients with nonfunctioning adenomas (p = 0.003) and 2.16-fold higher in patients with CS compared to Conn's syndrome (p = 0.006). GLUT3 immunohistochemistry showed 2.2-fold higher staining in CS tumor samples compared to nonfunctioning adenomas.
Conclusions Differential 18F-FDG PET/CT uptake was observed in patients with nonfunctioning, aldosterone-hypersecreting, and cortisol-secreting masses. GLUT3 overexpression in cortisol-secreting tumor likely accounts for the differential uptake. Future larger cohort studies will need to be conducted to determine if 18F-FDG PET/CT uptake can lateralize cortisol-secreting adrenal masses in patients with bilateral adrenal masses.
C1 [Patel, Dhaval; Gara, Sudheer Kumar; Boufraqech, Myriem; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, Clin Res Ctr, NIH, Bldg 10-CRC,Room 3-5840, Bethesda, MD 20892 USA.
[Ellis, Ryan J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Millo, Corina] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Clin Res Ctr, NIH, Bldg 10-CRC,Room 3-5840, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Gara, Sudheer Kumar/E-8084-2016; Boufraqech, Myriem/E-4823-2016;
OI Patel, Dhaval/0000-0002-5744-568X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the intramural research program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 22
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
EI 1432-2323
J9 WORLD J SURG
JI World J.Surg.
PD MAR
PY 2016
VL 40
IS 3
BP 683
EP 689
DI 10.1007/s00268-015-3242-y
PG 7
WC Surgery
SC Surgery
GA DF4GH
UT WOS:000371305500030
PM 26324161
ER
PT J
AU Nilubol, N
Patel, D
Kebebew, E
AF Nilubol, Naris
Patel, Dhaval
Kebebew, Electron
TI Does Lymphadenectomy Improve Survival in Patients with Adrenocortical
Carcinoma? A Population-Based Study
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID ADRENAL-CORTICAL CARCINOMA; LYMPH-NODE DISSECTION; SURGICAL-MANAGEMENT;
DISEASE; IMPACT; CANCER; UPDATE; TABLES
AB Background A recent study suggested a survival benefit in patients with adrenocortical carcinoma (ACC) who had undergone lymphadenectomy. The objective of this study was to study the effect of lymphadenectomy on the survival rates of patients with ACC.
Methods Data from adult patients with histology-proven ACC from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 Registries (1973-2011) were analyzed to assess the impact of lymphadenectomy (>= 4 lymph nodes removed) on disease-specific survival (DSS).
Results Of 1525 patients with ACC, 45 % were male. 36, 20, and 44 % of patients presented with localized, regional, and distant metastatic diseases, respectively. 8 % of patients (n = 67/802) underwent lymphadenectomy. We observed a higher rate of lymphadenectomy performed in patients with regional disease [locally advanced tumors (stage T3 and T4) and/or lymph node metastasis] and distant metastasis than in those with localized tumors (12.4 % and 12.0 vs. 5.1, respectively, p < 0.01) and in patients with primary tumor sizes >10 cm (12.4 vs. 4.2 %, p < 0.01). Lymph node metastasis was present in 12.8 % (19.2 % in locally advanced ACC). A lymphadenectomy was not associated with improved DSS on univariate analysis (p = 0.30), regardless of tumor size or staging. Independent prognostic factors included: ages >= 60 years (p < 0.01, HR 1.70), lymph node metastasis (p < 0.01, HR 1.7), distant metastasis (p < 0.01, HR 5.6), complete resection of tumor (p < 0.01, HR 0.47), and debulking surgery (p < 0.01, HR 0.49).
Conclusion A lymphadenectomy is not commonly performed in patients with ACC in the U.S. Although we found no survival benefit in this cohort with a low rate of lymphadenectomy, a lymphadenectomy may be considered in patients with locally advanced tumors (T3 and T4) due to a higher rate of lymph node metastasis.
C1 [Nilubol, Naris; Patel, Dhaval; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Rm 3-5840, Bethesda, MD 20892 USA.
RP Nilubol, N (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Rm 3-5840, Bethesda, MD 20892 USA.
EM niluboln@mail.nih.gov
OI Patel, Dhaval/0000-0002-5744-568X
NR 28
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
EI 1432-2323
J9 WORLD J SURG
JI World J.Surg.
PD MAR
PY 2016
VL 40
IS 3
BP 697
EP 705
DI 10.1007/s00268-015-3283-2
PG 9
WC Surgery
SC Surgery
GA DF4GH
UT WOS:000371305500032
PM 26510563
ER
PT J
AU Tryggvason, G
Jonasson, F
Cotch, MF
Li, CM
Hoffman, HJ
Themann, CL
Eiriksdottir, G
Sverrisdottir, JE
Harris, TB
Launer, LJ
Gudnason, V
Petersen, H
AF Tryggvason, Geir
Jonasson, Fridbert
Cotch, Mary Frances
Li, Chuan-Ming
Hoffman, Howard J.
Themann, Christa L.
Eiriksdottir, Gudny
Sverrisdottir, Johanna Eyrun
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Petersen, Hannes
TI Hearing in older adults with exfoliation syndrome/exfoliation glaucoma
or primary open-angle glaucoma
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE adjustment for age and sex; exfoliation glaucoma; hearing; primary
open-angle glaucoma
ID PSEUDOEXFOLIATION SYNDROME; REYKJAVIK EYE; POPULATION; PREVALENCE;
SUSCEPTIBILITY; ASSOCIATION; VARIANTS; RISK
AB Purpose: To determine whether adults, aged 66-96 years, with exfoliation syndrome (XFS)/exfoliation glaucoma (XFG), or primary open-angle glaucoma (POAG) have poorer hearing than controls of similar age.
Methods: Case (XFS/XFG and POAG) and control status was diagnosed in the Reykjavik Glaucoma Studies (RGS) using slit-lamp examination, visual field testing and optic disc photographs; the RGS data were merged with the Age, Gene/Environment Susceptibility-Reykjavik Study that collected hearing data using air-conduction, pure-tone thresholds obtained at 0.5, 1, 2, 3, 4, 6 and 8 kHz categorized by better ear and worse ear, based on pure-tone averages (PTAs) calculated separately for low and middle frequencies (PTA(512) - mean of thresholds at 0.5, 1 and 2 kHz) and high frequencies (PTA(3468) - mean of thresholds at 3, 4, 6 and 8 kHz). Multivariable linear regression was used to test for differences in PTAs between cases and controls.
Results: Themeanage for 158XFS/XFGcases (30.4% male) was 77.4 years, 95POAG cases (35.8% male) was 77.9 years, and 123 controls (46.3% male) was 76.8 years. Using multivariable linear regression analysis, there were no consistent, statistically significant differences in PTAs between the two case groups and controls in either the low-or high-frequency range, evenwhenstratifiedbyagegroup.
Conclusion: Among the older individuals examined in this study hearing loss is highly prevalent and strongly associated with male gender and increasing age. As we did not find consistent statistically significant difference in hearing between cases and controls the diagnosis of XFS/XFGorPOAG does not as such routinely call for audiological evaluation.
C1 [Tryggvason, Geir] Oslo Univ Hosp, Dept Otolaryngol Head & Neck Surg, Oslo, Norway.
[Jonasson, Fridbert] Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
[Jonasson, Fridbert; Gudnason, Vilmundur; Petersen, Hannes] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Li, Chuan-Ming; Hoffman, Howard J.] NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Themann, Christa L.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent CDC, Cincinnati, OH 45226 USA.
[Eiriksdottir, Gudny; Sverrisdottir, Johanna Eyrun; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Populat Sci, NIH, Bethesda, MD 20892 USA.
[Petersen, Hannes] Landspitali Univ Hosp, Dept Otolaryngol Head & Neck Surg, Reykjavik, Iceland.
RP Jonasson, F (reprint author), Landspitali Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.; Petersen, H (reprint author), Landspitali Univ Hosp, Dept Otolaryngol, Reykjavik, Iceland.
EM fridbert@landspitali.is; hpet@hi.is
FU National Institutes of Health NIA Intramural Research Program
[N01-AG-1-2100]; National Eye Institute [ZIAEY000401]; National
Institute on Deafness and Other Communication Disorders (NIDCD),
Division of Scientific Programs [IAA Y2-DC1004-02]; Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament);
University of Iceland Research Fund; Helga Jonsdottir and Sigurlidi
Kristjansson Research Fund
FX This study has been funded by contract N01-AG-1-2100 from the National
Institutes of Health NIA Intramural Research Program, an Intramural
Research Program Award (ZIAEY000401) from the National Eye Institute, an
award from the National Institute on Deafness and Other Communication
Disorders (NIDCD), Division of Scientific Programs (IAA Y2-DC1004-02),
Hjartavernd (the Icelandic Heart Association), the Althingi (the
Icelandic Parliament), the University of Iceland Research Fund, and the
Helga Jonsdottir and Sigurlidi Kristjansson Research Fund. We thank Ms.
May Chiu, NIDCD, NIH, for classifying the AGES-R tympanograms based on
the Liden-Jerger method. The researchers are indebted to the
participants for their willingness to participate in the studies.
NR 34
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-375X
EI 1755-3768
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD MAR
PY 2016
VL 94
IS 2
BP 140
EP 146
DI 10.1111/aos.12914
PG 7
WC Ophthalmology
SC Ophthalmology
GA DE9KR
UT WOS:000370956800024
PM 26547142
ER
PT J
AU Lee, J
Romero, R
Lee, KA
Kim, EN
Korzeniewski, SJ
Chaemsaithong, P
Yoon, BH
AF Lee, JoonHo
Romero, Roberto
Lee, Kyung A.
Kim, Eun Na
Korzeniewski, Steven J.
Chaemsaithong, Piya
Yoon, Bo Hyun
TI Meconium aspiration syndrome: a role for fetal systemic inflammation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE amniocentesis; fetal inflammatory response syndrome; funisitis;
intraamniotic inflammation; matrix metalloproteinase-8; meconium-stained
amniotic fluid; pregnancy
ID STAINED AMNIOTIC-FLUID; ACID-BASE STATUS; DELIVERY ROOM MANAGEMENT;
INDUCED LUNG INJURY; PASSAGE IN-UTERO; INTRAAMNIOTIC INFLAMMATION;
PRETERM LABOR; MICROBIAL INVASION; UMBILICAL-CORD; RISK-FACTORS
AB BACKGROUND: Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately 1 of every 7 pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intraamniotic inflammation/infection than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF.
OBJECTIVE: We sought to investigate whether intraamniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS.
STUDY DESIGN: A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n = 1281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age >= 38 weeks). Intraamniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 was > 23 ng/mL. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord.
RESULTS: The prevalence of MSAF was 9.2% (118/1281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each P >.1). Mothers whose newborns developed MAS had a higher median of AF matrix metalloproteinase-8 (456.8 vs 157.2 ng/mL, P <.05). Newborns exposed to intraamniotic inflammation had a higher rate of MAS than those who were not exposed to intraamniotic inflammation [13.0% (10/77) vs 0% (0/32), P = .03], as did those exposed to funisitis [31.3% (5/16) vs 7.3% (6/82); relative risk, 4.3; 95% confidence interval, 1.5-12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intraamniotic inflammation and funisitis than in those without intraamniotic inflammation and funisitis [28.6% (4/14) vs 0% (0/28), P = .009], while the rate of MAS did not show a significant difference between patients with intraamniotic inflammation alone (without funisitis) and those without intraamniotic inflammation and funisitis [10.9% (5/46) vs 0% (0/28)].
CONCLUSION: The combination of intraamniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models and therapeutic interventions for this disorder.
C1 [Lee, JoonHo; Lee, Kyung A.; Kim, Eun Na; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto; Korzeniewski, Steven J.; Chaemsaithong, Piya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.
[Romero, Roberto; Korzeniewski, Steven J.; Chaemsaithong, Piya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto; Korzeniewski, Steven J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Korzeniewski, Steven J.; Chaemsaithong, Piya] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.; Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.; Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Detroit, MI USA.; Romero, R (reprint author), Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.; Romero, R (reprint author), Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.; Romero, R (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
EM romeror@mail.nih.gov; yoonbh@snu.ac.kr
FU Seoul National University Hospital, Republic of Korea [03-2011-0200];
Korean Health Technology R&D Project through the Korea Health Industry
Development Institute (KHIDI) - Ministry of Health & Welfare, Republic
of Korea [HI12C0768]; Perinatology Research Branch, Division of
Intramural Research, of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development/National Institutes of Health/US
Department of Health and Human Services
FX Supported by Grant No. 03-2011-0200 from Seoul National University
Hospital, Republic of Korea, and a grant from the Korean Health
Technology R&D Project through the Korea Health Industry Development
Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic
of Korea (Grant No. HI12C0768). This work was also supported, in part,
by the Perinatology Research Branch, Division of Intramural Research, of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development/National Institutes of Health/US Department of Health and
Human Services.
NR 134
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2016
VL 214
IS 3
AR 366. e1-e9
DI 10.1016/j.ajog.2015.10.009
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DF0JC
UT WOS:000371024100022
PM 26484777
ER
PT J
AU Manuck, TA
Esplin, MS
Biggio, J
Bukowski, R
Parry, S
Zhang, HP
Huang, H
Varner, MW
Andrews, W
Saade, G
Sadovsky, Y
Reddy, UM
Ilekis, J
AF Manuck, Tracy A.
Esplin, M. Sean
Biggio, Joseph
Bukowski, Radek
Parry, Samuel
Zhang, Heping
Huang, Hao
Varner, Michael W.
Andrews, William
Saade, George
Sadovsky, Yoel
Reddy, Uma M.
Ilekis, John
CA Eunice Kennedy Shriver Natl Inst
TI Predictors of response to 17-alpha hydroxyprogesterone caproate for
prevention of recurrent spontaneous preterm birth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE decidual hemorrhage; progesterone; recurrent preterm birth; spontaneous
preterm labor
ID GESTATIONAL-AGE; RISK-FACTORS; DELIVERY; PREMATURITY; PREGNANCY;
INFANTS; COHORT; RATES; WOMEN
AB BACKGROUND: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response.
OBJECTIVE: We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder."
STUDY DESIGN: This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with >= 1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproateetreated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended >= 3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression.
RESULTS: One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort.
CONCLUSION: Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.
C1 [Manuck, Tracy A.; Esplin, M. Sean; Varner, Michael W.] Univ Utah, Sch Med, Div Maternal Fetal Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Manuck, Tracy A.; Esplin, M. Sean; Varner, Michael W.] Intermt Healthcare Dept Maternal Fetal Med, Salt Lake City, UT USA.
[Biggio, Joseph; Andrews, William] Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35294 USA.
[Biggio, Joseph; Andrews, William] Univ Alabama Birmingham, Ctr Womens Reprod, Birmingham, AL USA.
[Bukowski, Radek; Saade, George] Univ Texas Med Branch, Div Maternal Fetal Med, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Parry, Samuel] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Zhang, Heping; Huang, Hao] Yale Univ, Sch Publ Hlth, Collaborat Ctr Stat Sci, New Haven, CT USA.
[Sadovsky, Yoel] Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Pittsburgh, PA USA.
[Reddy, Uma M.; Ilekis, John] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Dev Biol & Perinatal Med, Pregnancy & Perinatol Branch, Bethesda, MD USA.
RP Manuck, TA (reprint author), Univ Utah, Sch Med, Div Maternal Fetal Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.; Manuck, TA (reprint author), Intermt Healthcare Dept Maternal Fetal Med, Salt Lake City, UT USA.
EM tmanuck@med.unc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Genomic and Proteomic Network for Preterm Birth Research
[U01-HD-050062, U01-HD-050078, U01-HD-050080, U01-HD-050088,
U01-HD-050094]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development [5K23HD067224]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development Genomic and Proteomic Network for Preterm
Birth Research (U01-HD-050062; U01-HD-050078; U01-HD-050080;
U01-HD-050088; U01-HD-050094; all authors) and by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
5K23HD067224 (T.A.M.).
NR 21
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U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2016
VL 214
IS 3
AR 376.e1-e8
DI 10.1016/j.ajog.2015.12.010
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DF0JC
UT WOS:000371024100028
PM 26692181
ER
PT J
AU Baseler, LJ
Falzarano, D
Scott, DP
Rosenke, R
Thomas, T
Munster, VJ
Feldmann, H
de Wit, E
AF Baseler, Laura J.
Falzarano, Darryl
Scott, Dana P.
Rosenke, Rebecca
Thomas, Tina
Munster, Vincent J.
Feldmann, Heinz
de Wit, Emmie
TI An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus
Replication Contributes to Viral Pathogenicity
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HEALTH-CARE FACILITIES; MERS-COV; RHESUS MACAQUES; SAUDI-ARABIA;
VIRUS-REPLICATION; INFECTION; TRACT; PNEUMONIA; INDUCTION; OUTCOMES
AB Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially Lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher Levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV infected humans, which will aid in investigating MERS-CoV disease pathogenesis.
C1 [Baseler, Laura J.; Falzarano, Darryl; Thomas, Tina; Munster, Vincent J.; Feldmann, Heinz; de Wit, Emmie] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Scott, Dana P.; Rosenke, Rebecca] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Baseler, Laura J.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
RP de Wit, E (reprint author), NIAID, Rocky Mt Labs, 903 S Fourth St, Hamilton, MT 59840 USA.
EM emmie.dewit@nih.gov
OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU National Institute of Allergy and Infectious Diseases, NIH Intramural
Research Program
FX Supported by the National Institute of Allergy and Infectious Diseases,
NIH Intramural Research Program.
NR 28
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2016
VL 186
IS 3
BP 630
EP 638
DI 10.1016/j.ajpath.2015.10.025
PG 9
WC Pathology
SC Pathology
GA DE9WY
UT WOS:000370991800017
PM 26724387
ER
PT J
AU Zhou, WX
Chung, YJ
Castellar, ERP
Zheng, Y
Chung, HJ
Bandle, R
Liu, JH
Tessarollo, L
Batchelor, E
Aplan, PD
Levens, D
AF Zhou, Weixin
Chung, Yang Jo
Castellar, Edgardo R. Parrilla
Zheng, Ying
Chung, Hye-Jung
Bandle, Russell
Liu, Juhong
Tessarollo, Lino
Batchelor, Eric
Aplan, Peter D.
Levens, David
TI Far Upstream Element Binding Protein Plays a Crucial Role in Embryonic
Development, Hematopoiesis, and Stabilizing Myc Expression Levels
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID SINGLE-STRANDED-DNA; CELL SELF-RENEWAL; C-MYC; STEM-CELLS;
HEPATOCELLULAR-CARCINOMA; BONE-MARROW; NONCANCEROUS TISSUE;
GENE-EXPRESSION; FETAL LIVER; IN-VIVO
AB The transcription factor far upstream element binding protein (FBP) binds and activates the MYC promoter when far upstream element is via TFIIH helicase activity early in the transcription cycle. The fundamental biology and pathology of FBP are complex. In some tumors FBP seems pro-oncogenic, whereas in others it is a tumor suppressor. We generated an FBP knockout (Fubp1(-/-)) mouse to study FBP deficiency. FBP is embryo lethal from embryonic day 10.5 to birth. A spectrum of pathology is associated with FBP loss; besides cerebral hyperplasia and pulmonary hypoplasia, pate livers, hypoplastic spleen, thymus, and bone marrow, cardiac hypertrophy, placental distress, and small size were all indicative of anemia. Immunophenotyping of hematopoietic cells in wild-type versus knockout livers revealed irregular trilineage anemia, with deficits in colony formation. Despite normal numbers of hematopoietic stem cells, transplantation of Fubp1(-/-) hematopoietic stem cells into irradiated mice entirely failed to reconstitute hematopoiesis. In competitive transplantation assays against wild-type donor bone marrow, Fubp1(-/-) hematopoietic stem cells functioned only sporadically at a low level. Although cultures of wild-type mouse embryo fibroblasts set Myc Levels precisely, Myc levels of mouse varied wildly between fibroblasts harvested from different Fubp1(-/-) embryos, suggesting that FBP contributes to Myc set point fixation. FBP helps to hold multiple physiologic processes to close tolerances, at least in part by constraining Myc expression.
C1 [Zhou, Weixin; Castellar, Edgardo R. Parrilla; Zheng, Ying; Chung, Hye-Jung; Bandle, Russell; Liu, Juhong; Batchelor, Eric; Levens, David] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Chung, Yang Jo; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Tessarollo, Lino] NCI, Mouse Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Levens, D (reprint author), Pathol Lab, Gene Regulat Sect, 10 Ctr Dr,Bldg 10,Room 2N106, Bethesda, MD 20892 USA.
EM levens@helix.nih.gov
RI Aplan, Peter/K-9064-2016
FU NTH Intramural Research Program, Center for Cancer Research of the
National Cancer Institute
FX Supported by the NTH Intramural Research Program, Center for Cancer
Research of the National Cancer Institute.
NR 59
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2016
VL 186
IS 3
BP 701
EP 715
DI 10.1016/j.ajpath.2015.10.028
PG 15
WC Pathology
SC Pathology
GA DE9WY
UT WOS:000370991800024
PM 26774856
ER
PT J
AU Hancock, CN
Liu, W
Alvord, WG
Phang, JM
AF Hancock, Chad N.
Liu, Wei
Alvord, W. Gregory
Phang, James M.
TI Co-regulation of mitochondrial respiration by proline
dehydrogenase/oxidase and succinate
SO AMINO ACIDS
LA English
DT Article
DE Respiration; Reactive oxygen species; Redox; Energetics; Signaling
ID RENAL-CELL CARCINOMA; COMPLEX-II; UBIQUINONE OXIDOREDUCTASE; QUINONE
OXIDOREDUCTASES; OXIDASE; PARAGANGLIOMA; MUTATIONS; APOPTOSIS; GENE;
SDHB
AB Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain (ETC), we investigated whether there was a direct relationship between PRODH/POX and regulation of the ETC. We found that PRODH/POX binds directly to CoQ1 and that CoQ1-dependent PRODH/POX activity required functional Complex III and Complex IV. PRODH/POX supported respiration in living cells during nutrient stress; however, expression of PRODH/POX resulted in an overall decrease in respiratory fitness. Effects on respiratory fitness were inhibited by DHP and NAC, indicating that these effects were mediated by PRODH/POX-dependent reactive oxygen species (ROS) generation. PRODH/POX expression resulted in a dose-dependent down-regulation of Complexes I-IV of the ETC, and this effect was also mitigated by the addition of DHP and NAC. We found that succinate was an uncompetitive inhibitor of PRODH/POX activity, inhibited ROS generation by PRODH/POX, and alleviated PRODH/POX effects on respiratory fitness. The findings demonstrate novel cross-talk between proline and succinate respiration in vivo and provide mechanistic insights into observations from previous animal studies. Our results suggest a potential regulatory loop between PRODH/POX and succinate in regulation of mitochondrial respiration.
C1 [Hancock, Chad N.; Liu, Wei; Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.
[Alvord, W. Gregory] NCI, Data Management Serv, Frederick, MD 21702 USA.
RP Hancock, CN; Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.
EM chad.hancock@nih.gov; phangj@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX We thank Allen R. Kane of Scientific Publications, Graphics & Media at
NCI-Frederick for his assistance with figure compilation and design.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 56
TC 3
Z9 3
U1 2
U2 9
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD MAR
PY 2016
VL 48
IS 3
BP 859
EP 872
DI 10.1007/s00726-015-2134-7
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DE7LJ
UT WOS:000370817900019
PM 26660760
ER
PT J
AU Baden, LR
Karita, E
Mutua, G
Bekker, LG
Gray, G
Page-Shipp, L
Walsh, SR
Nyombayire, J
Anzala, O
Roux, S
Laher, F
Innes, C
Seaman, MS
Cohen, YZ
Peter, L
Frahm, N
McElrath, MJ
Hayes, P
Swann, E
Grunenberg, N
Grazia-Pau, M
Weijtens, M
Sadoff, J
Dally, L
Lombardo, A
Gilmour, J
Cox, J
Dolin, R
Fast, P
Barouch, DH
Laufer, DS
AF Baden, Lindsey R.
Karita, Etienne
Mutua, Gaudensia
Bekker, Linda-Gail
Gray, Glenda
Page-Shipp, Liesl
Walsh, Stephen R.
Nyombayire, Julien
Anzala, Omu
Roux, Surita
Laher, Fatima
Innes, Craig
Seaman, Michael S.
Cohen, Yehuda Z.
Peter, Lauren
Frahm, Nicole
McElrath, M. Juliana
Hayes, Peter
Swann, Edith
Grunenberg, Nicole
Grazia-Pau, Maria
Weijtens, Mo
Sadoff, Jerry
Dally, Len
Lombardo, Angela
Gilmour, Jill
Cox, Josephine
Dolin, Raphael
Fast, Patricia
Barouch, Dan H.
Laufer, Dagna S.
CA B003-IPCAVD004-HVTN091 Study Grp
TI Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms
for HIV-1 Prevention
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID PHASE-I TRIAL; HEALTHY-ADULTS; IMMUNE-RESPONSES; ENV VACCINE; IPCAVD
001; NYVAC-C; ADENOVIRUS; INFECTION; TYPE-5; STEP
AB Background: A prophylactic HIV-1 vaccine is a global health priority.
Objective: To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149)
Setting: United States, East Africa, and South Africa. Patients: Healthy adults without HIV infection.
Intervention: 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 x 10(10) viral particles) in homologous and heterologous combinations.
Measurements: Safety and immunogenicity and the effect of baseline vector immunity.
Results: 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.
Limitations: Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.
Conclusion: Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.
Primary Funding Source: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Karita, Etienne; Nyombayire, Julien] Projet San Francisco, KK19Av 57,POB 780, Kigali, Rwanda.
Kenya AIDS Vaccine Initiat, Nairobi, Kenya.
Univ Nairobi, Nairobi, Kenya.
Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Page-Shipp, Liesl; Innes, Craig] Aurum Inst Hlth Res, 2nd Floor,Room 201 Jade Sq, Klerksdorp, South Africa.
Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Frahm, Nicole; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,POBox 19024, Seattle, WA 98104 USA.
HIV Vaccine Trials Network, Seattle, WA USA.
Int AIDS Vaccine Initiat Human Immunol Lab, London, England.
[Swann, Edith] NIAID, 5601 Fishers Lane,Room 9C46, Bethesda, MD 20852 USA.
[Grazia-Pau, Maria; Sadoff, Jerry] Janssen Pharmaceut Infect Dis & Vaccines, Crucell NV,POB 2048, NL-2301 CA Leiden, Netherlands.
[Dally, Len] EMMES Corp, 401 North Washington St,Suite 700, Rockville, MD USA.
[Lombardo, Angela; Cox, Josephine; Fast, Patricia; Laufer, Dagna S.] Int AIDS Vaccine Initiat, 125 Broad St,9th Floor, New York, NY 10004 USA.
Global BioSolut, Craigieburn, Vic, Australia.
[Baden, Lindsey R.; Walsh, Stephen R.] Brigham & Womens Hosp, Div Infect Dis, PBB A4,15 Francis St, Boston, MA 02115 USA.
[Mutua, Gaudensia; Anzala, Omu] Univ Nairobi, Inst Clin Res, Kenya AIDS Vaccine Initiat, POB 19676-00202 KNH, Nairobi, Kenya.
[Bekker, Linda-Gail; Roux, Surita] Desmond Tutu HIV Ctr, POB 13801, ZA-7705 Cape Town, South Africa.
[Seaman, Michael S.; Peter, Lauren; Dolin, Raphael; Barouch, Dan H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Cohen, Yehuda Z.] Rockefeller Univ, 1230 York Ave,Box 95, New York, NY 10065 USA.
[Hayes, Peter; Gilmour, Jill] Chelsea & Westminster Hosp, Int AIDS Vaccine Initiat Human Immunol Lab, 2nd Floor,369 Fulham Rd, London SW10 9NH, England.
RP Baden, LR (reprint author), Brigham & Womens Hosp, Div Infect Dis, PBB A4,15 Francis St, Boston, MA 02115 USA.
EM lbaden@partners.org; ldally@emmes.com; dlaufer@iavi.org
FU International AIDS Vaccine Initiative; National Institutes of Health;
Ragon Institute; Crucell Holland
FX International AIDS Vaccine Initiative, National Institutes of Health,
Ragon Institute, Crucell Holland.
NR 23
TC 2
Z9 2
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 1
PY 2016
VL 164
IS 5
BP 313
EP +
DI 10.7326/M15-0880
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA DF3CC
UT WOS:000371220300002
PM 26833336
ER
PT J
AU Kuhn, JH
Lauck, M
Bailey, AL
Shchetinin, AM
Vishnevskaya, TV
Bao, YM
Ng, TFF
LeBreton, M
Schneider, BS
Gillis, A
Tamoufe, U
Diffo, JL
Takuo, JM
Kondov, NO
Coffey, LL
Wolfe, ND
Delwart, E
Clawson, AN
Postnikova, E
Bollinger, L
Lackemeyer, MG
Radoshitzky, SR
Palacios, G
Wada, J
Shevtsova, ZV
Jahrling, PB
Lapin, BA
Deriabin, PG
Dunowska, M
Alkhovsky, SV
Rogers, J
Friedrich, TC
O'Connor, DH
Goldberg, TL
AF Kuhn, Jens H.
Lauck, Michael
Bailey, Adam L.
Shchetinin, Alexey M.
Vishnevskaya, Tatyana V.
Bao, Yiming
Ng, Terry Fei Fan
LeBreton, Matthew
Schneider, Bradley S.
Gillis, Amethyst
Tamoufe, Ubald
Diffo, Joseph Le Doux
Takuo, Jean Michel
Kondov, Nikola O.
Coffey, Lark L.
Wolfe, Nathan D.
Delwart, Eric
Clawson, Anna N.
Postnikova, Elena
Bollinger, Laura
Lackemeyer, Matthew G.
Radoshitzky, Sheli R.
Palacios, Gustavo
Wada, Jiro
Shevtsova, Zinaida V.
Jahrling, Peter B.
Lapin, Boris A.
Deriabin, Petr G.
Dunowska, Magdalena
Alkhovsky, Sergey V.
Rogers, Jeffrey
Friedrich, Thomas C.
O'Connor, David H.
Goldberg, Tony L.
TI Reorganization and expansion of the nidoviral family Arteriviridae
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID SIMIAN HEMORRHAGIC-FEVER; EQUINE ARTERITIS VIRUS; RESPIRATORY SYNDROME
VIRUS; SUBGENOMIC MESSENGER-RNAS; ISOLATE ATCC VR-2332; INTERNATIONAL
COMMITTEE; STANDARDIZED NOMENCLATURE; TAXONOMIC PROPOSALS; RATIFICATION
VOTE; SPECIES LEVEL
AB The family Arteriviridae presently includes a single genus Arterivirus. This genus includes four species as the taxonomic homes for equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), porcine respiratory and reproductive syndrome virus (PRRSV), and simian hemorrhagic fever virus (SHFV), respectively. A revision of this classification is urgently needed to accommodate the recent description of eleven highly divergent simian arteriviruses in diverse African nonhuman primates, one novel arterivirus in an African forest giant pouched rat, and a novel arterivirus in common brushtails in New Zealand. In addition, the current arterivirus nomenclature is not in accordance with the most recent version of the International Code of Virus Classification and Nomenclature. Here we outline an updated, amended, and improved arterivirus taxonomy based on current data. Taxon-specific sequence cut-offs are established relying on a newly established open reading frame 1b phylogeny and pairwise sequence comparison (PASC) of coding-complete arterivirus genomes. As a result, the current genus Arterivirus is replaced by five genera: Equartevirus (for EAV), Rodartevirus (LDV + PRRSV), Simartevirus (SHFV + simian arteriviruses), Nesartevirus (for the arterivirus from forest giant pouched rats), and Dipartevirus (common brushtail arterivirus). The current species Porcine reproductive and respiratory syndrome virus is divided into two species to accommodate the clear divergence of the European and American "types" of PRRSV, both of which now receive virus status. The current species Simian hemorrhagic fever virus is divided into nine species to accommodate the twelve known simian arteriviruses. Non-Latinized binomial species names are introduced to replace all current species names to clearly differentiate them from virus names, which remain largely unchanged.
C1 [Kuhn, Jens H.; Clawson, Anna N.; Postnikova, Elena; Bollinger, Laura; Lackemeyer, Matthew G.; Wada, Jiro; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
[Friedrich, Thomas C.; Goldberg, Tony L.] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Shchetinin, Alexey M.; Vishnevskaya, Tatyana V.; Deriabin, Petr G.; Alkhovsky, Sergey V.] Minist Hlth Russian Federat, DI Ivanovskii Virol Inst, Fed Res Ctr Epidemiol & Microbiol, Moscow, Russia.
[Bao, Yiming] NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Ng, Terry Fei Fan; Kondov, Nikola O.; Delwart, Eric] Blood Syst Res Inst, San Francisco, CA USA.
[LeBreton, Matthew] Mosaic, Yaounde, Cameroon.
[LeBreton, Matthew; Schneider, Bradley S.; Gillis, Amethyst; Wolfe, Nathan D.] Metabiota, San Francisco, CA USA.
[Tamoufe, Ubald; Diffo, Joseph Le Doux; Takuo, Jean Michel] Global Viral Cameroon, Yaounde, Cameroon.
[Radoshitzky, Sheli R.; Palacios, Gustavo] US Army, Med Res Inst Infect Dis, Frederick, MD USA.
[Shevtsova, Zinaida V.] Sci Res Inst Expt Pathol & Therapy, Sukhumi, Autonomous Repu, Rep of Georgia.
[Lapin, Boris A.] Russian Acad Med Sci, Sci Res Inst Med Primatol, Soci, Russia.
[Dunowska, Magdalena] Massey Univ, Inst Vet Anim & Biomed Sci, Palmerston North, New Zealand.
[Rogers, Jeffrey] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Lauck, Michael; Bailey, Adam L.; Friedrich, Thomas C.; O'Connor, David H.; Goldberg, Tony L.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Coffey, Lark L.] Univ Calif Davis, Ctr Vectorborne Dis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA 95616 USA.
[O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.; Goldberg, TL (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.; Goldberg, TL (reprint author), Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
EM kuhnjens@mail.nih.gov; tgoldberg@vetmed.wisc.edu
RI Palacios, Gustavo/I-7773-2015;
OI Palacios, Gustavo/0000-0001-5062-1938; Shchetinin,
Alexey/0000-0003-1842-3899; Schneider, Bradley S/0000-0001-7642-0018;
Vishnevskaya, Tatyana/0000-0002-6963-8681; Kuhn, Jens
H./0000-0002-7800-6045; Lauck, Michael/0000-0003-2813-3705
FU Battelle Memorial Institute's prime [HHSN272200700016I]; National
Institutes of Health (NIH) as part of the joint NIH-NSF Ecology of
Infectious Disease program [TW009237, R01 AI077376]; Office of Research
Infrastructure Programs (ORIP) [P51OD011106]; Intramural Research
Program of the National Institutes of Health; National Library of
Medicine
FX This work was funded in part through Battelle Memorial Institute's prime
contract with the US National Institute of Allergy and Infectious
Diseases (NIAID) under Contract No. HHSN272200700016I. Battelle
employees involved in this work are: L.B. and J.W. Subcontractors to
Battelle Memorial Institute who performed this work are: J.H.K and E.P.,
employees of Tunnell Government Services, Inc.; A.N.C. the owner of
Logos Consulting, Inc.; and M.G.L., an employee of Lovelace Respiratory
Research Institute. This work was also funded in part through National
Institutes of Health (NIH) grant TW009237 as part of the joint NIH-NSF
Ecology of Infectious Disease program, grant R01 AI077376, and by the
Office of Research Infrastructure Programs (ORIP) grant P51OD011106.
This research was also supported in part by the Intramural Research
Program of the National Institutes of Health, National Library of
Medicine (Y.B.), and benefited from contributions from the PREDICT
project of the United States Agency for International Development
(USAID) Emerging Pandemic Threats Program. We thank the Cameroon
government for their support during the implementation of this project.
NR 59
TC 6
Z9 6
U1 3
U2 6
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD MAR
PY 2016
VL 161
IS 3
BP 755
EP 768
DI 10.1007/s00705-015-2672-z
PG 14
WC Virology
SC Virology
GA DF0SR
UT WOS:000371049800034
PM 26608064
ER
PT J
AU Stowkowy, J
Liu, L
Cadenhead, KS
Cannon, TD
Cornblatt, BA
McGlashan, TH
Perkins, DO
Seidman, LJ
Tsuang, MT
Walker, EF
Woods, SW
Bearden, CE
Mathalon, DH
Heinssen, R
Addington, J
AF Stowkowy, Jacqueline
Liu, Lu
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
McGlashan, Thomas H.
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
Bearden, Carrie E.
Mathalon, Daniel H.
Heinssen, Robert
Addington, Jean
TI Core Schemas in Youth at Clinical High Risk for Psychosis
SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY
LA English
DT Article
DE Clinical high risk; psychosis; schemas; beliefs; NAPLS
ID CALGARY DEPRESSION SCALE; SCHIZOPHRENIA
AB Background: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. Aims: To investigate schemas over time in a large sample of CHR individuals and healthy controls. Method: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. Results: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. Conclusions: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.
C1 [Stowkowy, Jacqueline; Liu, Lu; Addington, Jean] Univ Calgary, Calgary, AB T2N 4Z6, Canada.
[Cadenhead, Kristin S.; Tsuang, Ming T.] UCSD, La Jolla, CA USA.
[Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, New Haven, CT USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Long Isl City, NY USA.
[Perkins, Diana O.] Univ N Carolina, Chapel Hill, NC USA.
[Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Mathalon, Daniel H.] UCSF, San Francisco, CA USA.
[Heinssen, Robert] NIMH, Bethesda, MD 20892 USA.
RP Stowkowy, J (reprint author), Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada.
EM stowkowy@ucalgary.ca
FU National Institute of Mental Health [U01MH081984, U01 MH081928, P50
MH080272, SCDMH82101008006, R01 MH60720, U01MH082022, K24 MH76191,
U01MH081902, P50 MH066286, U01MH082004, U01MH081988, UO1 MH081857-05]
FX This study was supported by the National Institute of Mental Health
(grant U01MH081984 to Dr Addington; grants U01 MH081928; P50 MH080272;
Commonwealth of Massachusetts SCDMH82101008006 to Dr Seidman; grants R01
MH60720, U01MH082022 and K24 MH76191 to Dr Cadenhead; grant U01MH081902
to Dr Cannon; P50 MH066286 (Prodromal Core) to Dr Bearden; grant
U01MH082004to Dr Perkins; grant U01MH081988 to Dr Walker; grant
U01MH082022 to Dr Woods; and UO1 MH081857-05 grant to Dr Cornblatt. The
NIMH had no further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication.
NR 15
TC 0
Z9 0
U1 1
U2 6
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1352-4658
EI 1469-1833
J9 BEHAV COGN PSYCHOTH
JI Behav. Cognit. Psychther.
PD MAR
PY 2016
VL 44
IS 2
BP 203
EP 213
DI 10.1017/S1352465815000144
PG 11
WC Psychology, Clinical
SC Psychology
GA DE8AA
UT WOS:000370857000007
PM 25896713
ER
PT J
AU Hsieh, MM
AF Hsieh, Matthew M.
TI A Standard Nonmyeloablative Transplantation Regimen for Adults with
Sickle Cell Disease: Are We There Yet?
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Editorial Material
C1 [Hsieh, Matthew M.] NHLBI, Mol & Clin Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10-9N112, Bethesda, MD 20892 USA.
RP Hsieh, MM (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10-9N112, Bethesda, MD 20892 USA.
EM matthewhs@nhlbi.nih.gov
OI Hsieh, Matthew/0000-0002-3706-6615
FU Intramural NIH HHS
NR 7
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
BP 397
EP 398
DI 10.1016/j.bbmt.2015.12.002
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TS
UT WOS:000370910200001
PM 26685772
ER
PT J
AU Anthias, C
Shaw, BE
Kiefer, DM
Liesveld, JL
Yared, J
Kamble, RT
D'Souza, A
Hematti, P
Seftel, MD
Norkin, M
DeFilipp, Z
Kasow, KA
Abidi, MH
Savani, BN
Shah, NN
Anderlini, P
Diaz, MA
Malone, AK
Halter, JP
Lazarus, HM
Logan, BR
Switzer, GE
Pulsipher, MA
Confer, DL
O'Donnell, PV
AF Anthias, Chloe
Shaw, Bronwen E.
Kiefer, Deidre M.
Liesveld, Jane L.
Yared, Jean
Kamble, Rammurti T.
D'Souza, Anita
Hematti, Peiman
Seftel, Matthew D.
Norkin, Maxim
DeFilipp, Zachariah
Kasow, Kimberly A.
Abidi, Muneer H.
Savani, Bipin N.
Shah, Nirali N.
Anderlini, Paolo
Diaz, Miguel A.
Malone, Adriana K.
Halter, Joerg P.
Lazarus, Hillard M.
Logan, Brent R.
Switzer, Galen E.
Pulsipher, Michael A.
Confer, Dennis L.
O'Donnell, Paul V.
TI Significant Improvements in the Practice Patterns of Adult Related Donor
Care in US Transplantation Centers
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Related donor; Accreditation; Hematopoietic cell donation
ID STEM-CELL DONATION; CONSENSUS STATEMENT; WORLDWIDE NETWORK; PBSC DONORS;
BLOOD; COLLECTION; EVENTS; ISSUES; LIVER; BM
AB Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% of US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation standards resulting from the CIBMTR study would have significantly impacted practice. Accordingly, we conducted a follow-up survey of US transplantation centers to assess practice changes since 2007, and to investigate additional areas where RD care was predicted to differ from UD care. A total of 73 centers (53%), performing 79% of RD transplantations in the United States, responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P < .0001). This study identifies several areas where RD management does not meet international donor care standards, however. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are made. (C) 2016 American Society for Blood and Marrow Transplantation.
C1 [Anthias, Chloe] Anthony Nolan Res Inst, 2 Heathgate Pl,75-87 Agincourt Rd, London NW3 2NU, England.
[Shaw, Bronwen E.; D'Souza, Anita; Logan, Brent R.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Kiefer, Deidre M.] Be The Match, Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Liesveld, Jane L.] Univ Rochester, Med Ctr, Strong Mem Hosp, Dept Med, Rochester, NY 14642 USA.
[Yared, Jean] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Dept Med, Baltimore, MD 21201 USA.
[Kamble, Rammurti T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Hematti, Peiman] Univ Wisconsin Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA.
[Seftel, Matthew D.] Univ Manitoba, CancerCare Manitoba, Dept Med Oncol & Haematol, Winnipeg, MB, Canada.
[Norkin, Maxim] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA.
[DeFilipp, Zachariah] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Kasow, Kimberly A.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA.
[Abidi, Muneer H.] Michigan State Univ, Dept Oncol, Spectrum Hlth, Grand Rapids, MI USA.
[Savani, Bipin N.] Vanderbilt Univ Sch Med, Div Hematol Oncol, Nashville, TN USA.
[Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Diaz, Miguel A.] Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain.
[Malone, Adriana K.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
[Halter, Joerg P.] Univ Basel Hosp, Dept Hematol, Basel, Switzerland.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA.
[Logan, Brent R.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
[Switzer, Galen E.] Univ Pittsburgh, VA Med Healthcare Syst, Pittsburgh, PA USA.
[Pulsipher, Michael A.] USC Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA.
[Confer, Dennis L.] Be The Match, Natl Marrow Donor Program, Minneapolis, MN USA.
[O'Donnell, Paul V.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
RP Anthias, C (reprint author), Anthony Nolan Res Inst, 2 Heathgate Pl,75-87 Agincourt Rd, London NW3 2NU, England.
EM chloe.anthias@anthonynolan.org
OI Abidi, Muneer/0000-0002-9936-6031; Yared, Jean/0000-0002-5346-6299
FU Public Health Service from the National Cancer Institute (NCI)
[U24-CA076518]; Public Health Service from National Heart, Lung and
Blood Institute (NHLBI) [U24-CA076518]; Public Health Service from
National Institute of Allergy and Infectious Diseases (NIAID)
[U24-CA076518]; NHLBI [5U10HL069294]; NCI [5U10HL069294]; Health
Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C];
Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium
Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the
Match Foundation; Blue Cross and Blue Shield Association; Celgene
Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center;
Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture
Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation;
GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute;
HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's
Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH;
Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda
Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow
Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.;
Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin
Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau
Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A
Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish
Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience,
Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah;
Wellpoint, Inc.
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA076518 from the National Cancer Institute (NCI), the
National Heart, Lung and Blood Institute (NHLBI) and the National
Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract
HHSH250201200016C with Health Resources and Services Administration
(HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the
Office of Naval Research; and grants from *Actinium Pharmaceuticals;
Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the
Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue
Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.;
Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America,
Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium
SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell
Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff
Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma
Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.;
Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi
Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum
Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi
US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St.
Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.;
Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix
Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.;
University of Minnesota; University of Utah; and *Wellpoint, Inc. The
views expressed in this article do not reflect the official policy or
position of the National Institute of Health, the Department of the
Navy, the Department of Defense, Health Resources and Services
Administration (HRSA) or any other agency of the U.S. Government.
NR 26
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
BP 520
EP 527
DI 10.1016/j.bbmt.2015.11.008
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TS
UT WOS:000370910200020
PM 26597080
ER
PT J
AU Anandi, P
Chinian, F
Cantilena, CR
Dunavin, N
Hensel, N
Draper, D
Koklanaris, E
Maxwell, S
Superata, J
Muranski, P
Battiwalla, M
Paczesny, S
Barrett, AJ
Ito, S
AF Anandi, Prathima
Chinian, Fariba
Cantilena, Caroline R.
Dunavin, Neil
Hensel, Nancy
Draper, Debbie
Koklanaris, Eleftheria
Maxwell, Sandra
Superata, Jeanine
Muranski, Pawel
Battiwalla, Minoo
Paczesny, Sophie
Barrett, A. John
Ito, Sawa
TI Improved Reproducibility of Gvhd Biomarker Assay Application of
Multiplex Microfluidic Channel System
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Anandi, Prathima; Chinian, Fariba; Cantilena, Caroline R.; Dunavin, Neil; Hensel, Nancy; Draper, Debbie; Koklanaris, Eleftheria; Maxwell, Sandra; Superata, Jeanine; Muranski, Pawel; Battiwalla, Minoo; Barrett, A. John; Ito, Sawa] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Paczesny, Sophie] Indiana Univ, Sch Med, Indianapolis, IN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 582
BP S388
EP S388
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300583
ER
PT J
AU Aydin, S
Freeman, AF
Su, H
Hickstein, D
Pai, SY
Geha, R
Chatila, T
Arnaout, RK
Al-Mousa, H
Al-Dhekri, H
Renner, ED
Belohradsky, BH
Notheis, G
Aydin, R
Gaspar, BH
Al-Herz, W
Gennery, A
Slatter, M
Metin, A
Isik, P
Azik, F
Ikinciogullari, A
Haskologlu, S
Dogu, F
Kumar, A
Ifversen, M
Schuster, F
Woessmann, W
Bredius, R
Barlogis, V
Kainulainen, L
Picard, C
Neven, B
Shereck, E
Schulz, A
Dueckers, G
Van Montfrans, J
Matthes-Martin, S
Keles, S
Ochs, H
Albert, MH
AF Aydin, Susanne
Freeman, Alexandra F.
Su, Helen
Hickstein, Dennis
Pai, Sung-Yun
Geha, Raif
Chatila, Talal
Arnaout, Rand K.
Al-Mousa, Hamoud
Al-Dhekri, Hasan
Renner, Ellen D.
Belohradsky, Bernd H.
Notheis, Gundula
Aydin, Roland
Gaspar, Bobby H.
Al-Herz, Waleed
Gennery, Andrew
Slatter, Mary
Metin, Ayse
Isik, Pamir
Azik, Fatih
Ikinciogullari, Aydan
Haskologlu, Sule
Dogu, Figen
Kumar, Ashish
Ifversen, Marianne
Schuster, Friedhelm
Woessmann, Wilhelm
Bredius, Robbert
Barlogis, Vincent
Kainulainen, Leena
Picard, Capucine
Neven, Benedicte
Shereck, Evan
Schulz, Ansgar
Dueckers, Gregor
Van Montfrans, Joris
Matthes-Martin, Susanne
Keles, Sevgi
Ochs, Hans
Albert, Michael H.
TI HSCT for DOCK8 Deficiency - an International Study on 74 Patients
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Aydin, Susanne; Renner, Ellen D.; Belohradsky, Bernd H.; Notheis, Gundula] Dr von Hauner Univ Childrens Hosp, Munich, Germany.
[Freeman, Alexandra F.; Su, Helen] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hickstein, Dennis] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Pai, Sung-Yun] Boston Childrens Hosp, Hematol Oncol, Boston, MA USA.
[Geha, Raif; Chatila, Talal] Boston Childrens Hosp, Div Immunol, Boston, MA USA.
[Arnaout, Rand K.] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Pediat Allergy & Immunol, Riyadh 11211, Saudi Arabia.
[Al-Mousa, Hamoud] King Faisal Specialist Hosp & Res Ctr, Pediat, Riyadh 11211, Saudi Arabia.
[Al-Dhekri, Hasan] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Pediat Allergy & Immunol, Riyadh 11211, Saudi Arabia.
[Aydin, Roland] Tech Univ Munich, D-80290 Munich, Germany.
[Gaspar, Bobby H.] UCL, Inst Child Hlth, London, England.
[Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait.
[Gennery, Andrew] Newcastle Univ, Paediat Immunol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Slatter, Mary] Great North Childrens Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
[Metin, Ayse] SB Ankara Diskapi Childrens Hosp, Pediat Immunol Unit, Ankara, Turkey.
[Isik, Pamir; Azik, Fatih] Ankara Childrens Hematol & Oncol Educ & Res Hosp, Clin Pediat Hematol, Ankara, Turkey.
[Ikinciogullari, Aydan] Ankara Univ, Sch Med, Dept Pediat Immunol & Allergy, TR-06100 Ankara, Turkey.
[Ikinciogullari, Aydan] Ankara Univ, Sch Med, BMT Unit, TR-06100 Ankara, Turkey.
[Kumar, Ashish] Cincinnati Childrens Hosp Med Ctr, Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Ifversen, Marianne] Copenhagen Univ Hosp, Rigshosp, Paediat Clin 2, Copenhagen, Denmark.
[Schuster, Friedhelm] Univ Munich, Kinderklin, Abt Hamatol Onkol, D-80539 Munich, Germany.
[Woessmann, Wilhelm] Univ Giessen, Dept Pediat Hematol & Oncol, D-35390 Giessen, Germany.
[Bredius, Robbert] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Barlogis, Vincent] Aix Marseille Univ, La Timone Hosp, APHM, Dept Paediat Haematol Oncol, Marseille, France.
[Kainulainen, Leena] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland.
[Picard, Capucine] Necker Enfant Malad Hosp, AP HP, Pediat Hematol Immunol Unit, Paris, France.
[Picard, Capucine] Paris Descartes Univ, Sorbonne Paris Cite, Lab Human Genet Infect Dis, Necker Branch,INSERM,UMR1163,Imagine Inst, Paris, France.
[Neven, Benedicte] Hop Univ Necker Enfants Malad, Paris, France.
[Shereck, Evan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Schulz, Ansgar] Univ Ulm Klinikum, Klin Kinder, Ulm, Germany.
[Dueckers, Gregor] HELIOS Childrens Hosp Krefeld, Krefeld, Germany.
[Van Montfrans, Joris] UMCU, Pediat Immunol, Utrecht, Netherlands.
[Matthes-Martin, Susanne] St Anna Childrens Hosp, BMT Unit, A-1090 Vienna, Austria.
[Keles, Sevgi] Konya Necmettin Erbakan Univ, Konya, Turkey.
[Ochs, Hans] Univ Washington, Pediat, Seattle, WA 98195 USA.
[Ochs, Hans] Seattle Childrens, Seattle, WA USA.
[Albert, Michael H.] Dr von Hauner Univ Childrens Hosp, Pediat Hematol Oncol, Munich, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 108
BP S103
EP S104
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300113
ER
PT J
AU Buxbaum, NP
Carpenter, A
Castro, E
Eckhaus, M
Bosselut, R
Gress, R
AF Buxbaum, Nataliya Prokopenko
Carpenter, Andrea
Castro, Ehydel
Eckhaus, Michael
Bosselut, Remy
Gress, Ronald
TI Pathogenic T Cells Target the Intraepithelial Lymphocyte Layer of Small
Intestine in Cgvhd
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Buxbaum, Nataliya Prokopenko; Castro, Ehydel; Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Carpenter, Andrea; Bosselut, Remy] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Eckhaus, Michael] NCI, Diagnost & Res Serv Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 587
BP S390
EP S391
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300588
ER
PT J
AU Cantilena, CR
Dunavin, N
Chinian, F
Anandi, P
Hensel, N
Draper, D
Koklanaris, E
Maxwell, S
Superata, J
Muranski, P
Ito, S
Paczesny, S
Barrett, AJ
Battiwalla, M
AF Cantilena, Caroline R.
Dunavin, Neil
Chinian, Fariba
Anandi, Prathima
Hensel, Nancy
Draper, Debbie
Koklanaris, Eleftheria
Maxwell, Sandra
Superata, Jeanine
Muranski, Pawel
Ito, Sawa
Paczesny, Sophie
Barrett, A. John
Battiwalla, Minoo
TI ST2 is Associated with GVHD in Ex Vivo Graft Manipulation Strategies for
Allogeneic Peripheral Blood Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Cantilena, Caroline R.; Dunavin, Neil; Chinian, Fariba; Anandi, Prathima; Hensel, Nancy; Draper, Debbie; Koklanaris, Eleftheria; Maxwell, Sandra; Superata, Jeanine; Muranski, Pawel; Ito, Sawa; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Paczesny, Sophie] Indiana Univ, Sch Med, Indianapolis, IN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 572
BP S380
EP S381
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300573
ER
PT J
AU Carpenter, PA
Logan, BR
Lee, SJ
Weisdorf, DJ
Johnston, L
Costa, LJ
Kitko, CL
Bolanos-Meade, J
Alousi, AM
Horowitz, MM
Abhyankar, S
Waller, EK
Mendizabal, A
Wang, YL
Lazaryan, A
Carter, SL
Nemecek, ER
Pavletic, SZ
Cutler, CS
Arora, M
AF Carpenter, Paul A.
Logan, Brent R.
Lee, Stephanie J.
Weisdorf, Daniel J.
Johnston, Laura
Costa, Luciano J.
Kitko, Carrie L.
Bolanos-Meade, Javier
Alousi, Amin M.
Horowitz, Mary M.
Abhyankar, Sunil
Waller, Edmund K.
Mendizabal, Adam
Wang, Yanli
Lazaryan, Aleksandr
Carter, Shelly L.
Nemecek, Eneida R.
Pavletic, Steven Z.
Cutler, Corey S.
Arora, Mukta
CA BMT CTN
TI Prednisone (PDN)/Sirolimus (SRL) Compared to PDN/SRL/Calcineurin
Inhibitor (CNI) as Treatment for Chronic Graft-Versus-Host-Disease
(cGVHD): A Randomized Phase II Study from the Blood and Marrow
Transplant Clinical Trials Network
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Carpenter, Paul A.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Div Hematol Oncol & Transplantat, Med, Minneapolis, MN USA.
[Johnston, Laura] Stanford Univ, Med Ctr, Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Costa, Luciano J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Kitko, Carrie L.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Bolanos-Meade, Javier] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Alousi, Amin M.] UT MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX USA.
[Horowitz, Mary M.] CIBMTR, Dept Med, Milwaukee, WI USA.
[Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Abhyankar, Sunil] Univ Kansas, Med Ctr, Blood & Marrow Transplant, Westwood, KS USA.
[Waller, Edmund K.] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA.
[Mendizabal, Adam; Wang, Yanli; Carter, Shelly L.] EMMES Corp, Rockville, MD USA.
[Lazaryan, Aleksandr; Arora, Mukta] Univ Minnesota, Hematol Oncol & Transplantat, Minneapolis, MN USA.
[Nemecek, Eneida R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Cutler, Corey S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA.
[BMT CTN] BMT CTN, Milwaukee, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 42
BP S50
EP S52
PG 3
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300047
ER
PT J
AU Curtis, LM
Pirsl, F
Hsu, J
Steinberg, SM
Mitchell, SA
Masuch, L
Im, A
Baruffaldi, JL
Mays, J
Halverson, D
Fowler, D
Gress, R
Pavletic, SZ
AF Curtis, Lauren M.
Pirsl, Filip
Hsu, Jennifer
Steinberg, Seth M.
Mitchell, Sandra A.
Masuch, Licia
Im, Annie
Baruffaldi, Judy L.
Mays, Jacqueline
Halverson, David
Fowler, Daniel
Gress, Ronald
Pavletic, Steven Z.
TI Predictors for Permanent Discontinuation of Systemic Immunosuppression
in Patients with Moderate to Severe Chronic Graft-Versus-Host-Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Curtis, Lauren M.; Pirsl, Filip; Hsu, Jennifer; Masuch, Licia; Baruffaldi, Judy L.; Halverson, David; Fowler, Daniel; Gress, Ronald; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Im, Annie] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Mays, Jacqueline] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 41
BP S49
EP S50
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300046
ER
PT J
AU Duncan, C
Brazauskas, R
Huang, JX
Shaw, BE
Majhail, NS
Savani, BN
Flowers, MED
Battiwalla, M
Beebe, K
Dietz, AC
Dvorak, CC
Giller, R
Jacobsohn, DA
Kletzel, M
Martin, PJ
Nemecek, ER
Talano, JAM
Pulsipher, MA
Baker, KS
AF Duncan, Christine
Brazauskas, Ruta
Huang, Jiaxing
Shaw, Bronwen E.
Majhail, Navneet S.
Savani, Bipin N.
Flowers, Mary E. D.
Battiwalla, Minoo
Beebe, Kristen
Dietz, Andrew C.
Dvorak, Christopher C.
Giller, Roger
Jacobsohn, David A.
Kletzel, Morris
Martin, Paul J.
Nemecek, Eneida R.
Talano, Julie-An M.
Pulsipher, Michael A.
Baker, K. Scott
TI Late Cardiovascular Morbidity Following Pediatric Allogeneic
Hematopoietic Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Duncan, Christine] Boston Childrens Hosp, Dept Pediat Oncol, Boston, MA USA.
[Duncan, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
[Huang, Jiaxing] Med Coll Wisconsin, CIBMTR, Dept Med, Milwaukee, WI 53226 USA.
[Shaw, Bronwen E.] CIBMTR, Dept Med, Milwaukee, WI USA.
[Shaw, Bronwen E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Majhail, Navneet S.] Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
[Flowers, Mary E. D.; Martin, Paul J.; Baker, K. Scott] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Beebe, Kristen] Mayo Clin Arizonia, Phoenix, AZ USA.
[Beebe, Kristen] Phoenix Childrens Hosp, Phoenix, AZ USA.
[Dietz, Andrew C.] Childrens Hosp Los Angeles, Pediat Heme Onc BMT, Los Angeles, CA 90027 USA.
[Dvorak, Christopher C.] Univ Calif San Francisco, Dept Pediat, Med Ctr, San Francisco, CA USA.
[Giller, Roger] Childrens Hosp Colorado, Dept Pediat, Sect Hematol Oncol & BMT, Aurora, CO USA.
[Jacobsohn, David A.] Childrens Natl Hlth Syst, Div Blood & Marrow Transplantat, Ctr Canc & Blood Disorders, Washington, DC USA.
[Kletzel, Morris] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Div Hematol Oncol & Stem Cell Transplantat, Chicago, IL 60611 USA.
[Nemecek, Eneida R.] Doernbecher Childrens Hosp, Dept Pediat, Pediat Blood & Marrow Transplant Program, Portland, OR USA.
[Nemecek, Eneida R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Talano, Julie-An M.] Med Coll Wisconsin, Pediat Hematol Oncol & BMT, Milwaukee, WI 53226 USA.
[Pulsipher, Michael A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
RI Huang, Jiaxing/B-7521-2009
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 55
BP S60
EP S60
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300060
ER
PT J
AU Fitzhugh, C
Hsieh, M
Taylor, T
Coles, W
Luznik, L
Powell, J
Tisdale, JF
AF Fitzhugh, Courtney
Hsieh, Matthew
Taylor, Tiffani
Coles, Wynona
Luznik, Leo
Powell, Jonathan
Tisdale, John F.
TI Post-Transplant Cyclophosphamide Improves Engraftment in Patients with
Sickle Cell Disease (SCD) and Severe Organ Damage who Undergo
Haploidentical Peripheral Blood Stem Cell Transplantation (PBSCT)
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Fitzhugh, Courtney] NHLBI, Sickle Cell Branch, Mol & Clin Hematol Branch, NIDDK,NIH, Bethesda, MD 20892 USA.
[Hsieh, Matthew; Taylor, Tiffani; Coles, Wynona; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, Bethesda, MD 20892 USA.
[Luznik, Leo] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Powell, Jonathan] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 472
BP S319
EP S319
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300473
ER
PT J
AU Fowler, D
Hakim, FT
Fellowes, V
Khuu, H
Stroncek, DE
Schuver, BB
Carpenter, A
Cotton, S
Carroll, E
Ghosh, M
Ali, SA
Halverson, D
Hardy, N
Pavletic, SZ
Bishop, MR
Gress, R
Korngold, R
Pecora, A
Donato, ML
Rowley, S
Vesole, DH
Siegel, D
Sportes, C
AF Fowler, Daniel
Hakim, Fran T.
Fellowes, Vicki
Khuu, Hanh
Stroncek, David E.
Schuver, Bazetta Blacklock
Carpenter, Ashley
Cotton, Stephanie
Carroll, Ellen
Ghosh, Monalisa
Ali, Syed Abbas
Halverson, David
Hardy, Nancy
Pavletic, Steven Z.
Bishop, Michael R.
Gress, Ronald
Korngold, Robert
Pecora, Andrew
Donato, Michele L.
Rowley, Scott
Vesole, David H.
Siegel, David
Sportes, Claude
TI Autologous Rapamycin-Resistant T Cell Therapy of Multiple Myeloma
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Fowler, Daniel; Hakim, Fran T.; Schuver, Bazetta Blacklock; Carroll, Ellen; Ghosh, Monalisa; Ali, Syed Abbas; Halverson, David; Pavletic, Steven Z.; Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Fellowes, Vicki] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Khuu, Hanh; Stroncek, David E.] NIH, Dept Transfus Med, Bldg 10, Bethesda, MD 20892 USA.
[Carpenter, Ashley] NCI, Bethesda, MD 20892 USA.
[Cotton, Stephanie] NCI, ETIB, Bethesda, MD 20892 USA.
[Hardy, Nancy] NCI, Expt Transplantat & Immunol, Bethesda, MD 20892 USA.
[Bishop, Michael R.] Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Korngold, Robert] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Pecora, Andrew; Donato, Michele L.; Rowley, Scott] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Vesole, David H.] Hackensack UMC, Myeloma Div, John Theurer Canc Ctr, Hackenscak, NJ USA.
[Siegel, David] Hackensack Univ, John Theurer Canc Ctr, Hackensack, NJ USA.
[Sportes, Claude] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 63
BP S65
EP S66
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300068
ER
PT J
AU Ghosh, M
Schuver, BB
Carroll, E
Khuu, H
Stroncek, DF
Pavletic, SZ
Gress, R
Halverson, D
Fowler, D
AF Ghosh, Monalisa
Schuver, Bazetta Blacklock
Carroll, Ellen
Khuu, Hanh
Stroncek, David F.
Pavletic, Steven Z.
Gress, Ronald
Halverson, David
Fowler, Daniel
TI DLI Therapy Using T-Rapa Cells: Graft-Versus-Lymphoma and GvHD Effects
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Ghosh, Monalisa; Schuver, Bazetta Blacklock; Carroll, Ellen; Pavletic, Steven Z.; Gress, Ronald; Halverson, David; Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Khuu, Hanh; Stroncek, David F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 594
BP S395
EP S396
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300595
ER
PT J
AU Graupner, S
Spellman, A
Jacobson, S
Bryan, L
Sportes, C
Pantin, J
Mian, MAH
AF Graupner, Scott
Spellman, Alison
Jacobson, Stephanie
Bryan, Locke
Sportes, Claude
Pantin, Jeremy
Mian, M. Anwarul Huq
TI Impact of Socio-Economic Disparities and Distance to Bone Marrow
Transplant Center on Transplantation Outcomes
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Graupner, Scott] Georgia Regents Univ, Internal Med, Augusta, GA USA.
[Spellman, Alison] Georgia Regents Univ, Heme Onc, Augusta, GA USA.
[Jacobson, Stephanie; Bryan, Locke] Georgia Regents Univ, BMT, Augusta, GA USA.
[Sportes, Claude] NCI, Bethesda, MD 20892 USA.
[Pantin, Jeremy; Mian, M. Anwarul Huq] Georgia Regents Med Ctr, Augusta, GA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 252
BP S187
EP S187
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300257
ER
PT J
AU Halverson, D
Rowley, S
Bishop, MR
Hansen, B
Cotton, S
Schuver, BB
Steinberg, SM
Hakim, FT
Gea-Banacloche, J
Hardy, N
Sportes, C
Pavletic, SZ
Khuu, H
Stroncek, DE
Levine, BL
June, CH
Donato, ML
Goy, A
Pecora, A
Gress, R
Fowler, D
AF Halverson, David
Rowley, Scott
Bishop, Michael R.
Hansen, Brenna
Cotton, Stephanie
Schuver, Bazetta Blacklock
Steinberg, Seth M.
Hakim, Fran T.
Gea-Banacloche, Juan
Hardy, Nancy
Sportes, Claude
Pavletic, Steven Z.
Khuu, Hanh
Stroncek, David E.
Levine, Bruce L.
June, Carl H.
Donato, Michele L.
Goy, Andre
Pecora, Andrew
Gress, Ronald
Fowler, Daniel
TI Preemptive T-Rapa Cell DLI after Low Intensity Allogeneic HCT May Allow
for Improved Overall Survival in High Risk Lymphoid Malignancies
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Halverson, David; Schuver, Bazetta Blacklock; Hakim, Fran T.; Pavletic, Steven Z.; Gress, Ronald; Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Rowley, Scott; Donato, Michele L.; Goy, Andre; Pecora, Andrew] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Bishop, Michael R.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Hansen, Brenna; Cotton, Stephanie; Gea-Banacloche, Juan] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hardy, Nancy] Greenebaum Canc Ctr, Med Oncol, Baltimore, MD USA.
[Sportes, Claude] Georgia Regents Univ, Ctr Canc, Augusta, GA USA.
[Khuu, Hanh; Stroncek, David E.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Levine, Bruce L.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[June, Carl H.] Univ Penn, Abramson Canc Ctr, Ctr Cellular Immunotherapies, Translat Res Programs, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 167
BP S139
EP S140
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300172
ER
PT J
AU Heimall, J
Logan, BR
Cowan, MJ
Notarangelo, LD
Puck, J
Fleisher, T
Griffith, LM
Kohn, DB
Pulsipher, MA
Shearer, W
Hanson, IC
Kapoor, N
O'Reilly, RJ
Boyer, M
Pai, SY
Parikh, S
Goldman, F
Burroughs, L
Marsh, RA
Kletzel, M
Thakar, M
Connelly, JA
Cuvellier, G
Loechelt, B
Shereck, E
Knudsen, A
Sullivan, K
DeSantes, K
Gillio, AP
Haddad, E
Petrovic, A
Quigg, TC
Smith, AR
Stenger, E
Dvorak, CC
Buckley, RH
AF Heimall, Jennifer
Logan, Brent R.
Cowan, Morton J.
Notarangelo, Luigi D.
Puck, Jennifer
Fleisher, Thomas
Griffith, Linda M.
Kohn, Donald B.
Pulsipher, Michael A.
Shearer, William
Hanson, Imelda C.
Kapoor, Neena
O'Reilly, Richard J.
Boyer, Michael
Pai, Sung-Yun
Parikh, Suhag
Goldman, Frederick
Burroughs, Lauri
Marsh, Rebecca A.
Kletzel, Morris
Thakar, Monica
Connelly, James A.
Cuvellier, Geoff
Loechelt, Brett
Shereck, Evan
Knudsen, Alan
Sullivan, Kathleen
DeSantes, Kenneth
Gillio, Alfred P.
Haddad, Elie
Petrovic, Aleksandra
Quigg, Troy C.
Smith, Angela R.
Stenger, Elizabeth
Dvorak, Christopher C.
Buckley, Rebecca H.
TI Poor T Cell Reconstitution at 100 Days after T Cell-Replete
Hematopoietic Cell Transplantation (HCT) for SCID Is Associated with
Later Risk of Death or Need for 2nd Transplant in the 6901 Prospective
Study of the Pidtc
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Heimall, Jennifer] Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Cowan, Morton J.; Puck, Jennifer; Dvorak, Christopher C.] UCSF Benioff Childrens Hosp, Pediat Allergy Immunol & Blood & Marrow Transplan, San Francisco, CA USA.
[Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Primary Immunodeficiencies, Boston, MA USA.
[Fleisher, Thomas] NIH, Host Def Lab, Bldg 10, Bethesda, MD 20892 USA.
[Griffith, Linda M.] NIAID, DAIT, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Hematol Oncol, Los Angeles, CA USA.
[Pulsipher, Michael A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Shearer, William; Hanson, Imelda C.] Texas Childrens Hosp, Baylor Coll Med, Immunol Allergy & Rheumatol, Houston, TX 77030 USA.
[Kapoor, Neena] Childrens Hosp Los Angeles, Blood & Marrow Transplant Program, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90027 USA.
[O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA.
[Boyer, Michael] Univ Utah, Hematol BMT, Park City, UT USA.
[Pai, Sung-Yun] Boston Childrens Hosp, Hematol Oncol, Boston, MA USA.
[Parikh, Suhag] Duke Univ, Med Ctr, Pediat Blood & Marrow Transplantat, Durham, NC USA.
[Goldman, Frederick] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Burroughs, Lauri] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Marsh, Rebecca A.] Cincinnati Childrens Hosp Med Ctr, Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Kletzel, Morris] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Thakar, Monica] Med Coll Wisconsin, Pediat Hematol Oncol BMT, Milwaukee, WI 53226 USA.
[Connelly, James A.] Univ Michigan, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA.
[Cuvellier, Geoff] CC Manitoba, Winnipeg, MB, Canada.
[Loechelt, Brett] Childrens Natl Med Ctr, Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Shereck, Evan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Knudsen, Alan] St Louis Univ, St Louis, MO 63103 USA.
[Sullivan, Kathleen] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[DeSantes, Kenneth] Univ Wisconsin, Dept Pediat, Div Hematol Oncol & Bone Marrow, Amer Family Childrens Hosp, Madison, WI USA.
[Gillio, Alfred P.] Hackensack Univ, Med Ctr, Inst Pediat Canc & Blood Disorders, Hackensack, NJ USA.
[Haddad, Elie] Ste Justine Hosp, Paediat Immunol, Montreal, PQ, Canada.
[Petrovic, Aleksandra] All Childrens Hosp Johns Hopkins Med, Blood & Marrow Transplant, St Petersburg, FL USA.
[Quigg, Troy C.] Riley Hosp Children, Pediat Hematol Oncol HSCT, Indianapolis, IN USA.
[Smith, Angela R.] Univ Minnesota, Dept Pediat, Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
[Stenger, Elizabeth] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA.
[Buckley, Rebecca H.] Duke Univ, Med Ctr, Durham, NC USA.
RI Notarangelo, Luigi/F-9718-2016
OI Notarangelo, Luigi/0000-0002-8335-0262
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 106
BP S101
EP S102
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300111
ER
PT J
AU Jacobson, S
Clemmons, AB
Shah, A
Albrecht, B
Sportes, C
Biyan, L
Pantin, J
AF Jacobson, Stephanie
Clemmons, Amber Bradley
Shah, Arpita
Albrecht, Benjamin
Sportes, Claude
Biyan, Locke
Pantin, Jeremy
TI Impact of Fluoroquinolone Prophylaxis on Survival Outcomes after
Hematopoietic Stem Cell Transplantation: A Single-Center Experience
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Jacobson, Stephanie; Shah, Arpita; Biyan, Locke] Georgia Regents Univ, BMT, Augusta, GA USA.
[Clemmons, Amber Bradley; Pantin, Jeremy] Georgia Regents Med Ctr, Augusta, GA USA.
[Clemmons, Amber Bradley; Albrecht, Benjamin] Univ Georgia, Coll Pharm, Augusta, GA USA.
[Sportes, Claude] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 216
BP S167
EP S168
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300221
ER
PT J
AU Jaglowski, S
Waller, EK
Kindwall-Keller, TL
McCarty, JM
Dugan, M
Yellin, M
Davis, T
Devine, SM
AF Jaglowski, Samantha
Waller, Edmund K.
Kindwall-Keller, Tamila L.
McCarty, John Michael
Dugan, Michael
Yellin, Michael
Davis, Thomas
Devine, Steven M.
TI Preliminary Safety and Efficacy Data Using CDX-301 (Flt3 ligand) As a
Sole Agent to Mobilize Hematopoietic Cells Prior to HLA-Matched Sibling
Donor Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Jaglowski, Samantha] Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA.
[Waller, Edmund K.] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Div BMT, Atlanta, GA 30322 USA.
[Kindwall-Keller, Tamila L.] Univ Virginia, Sch Med, Hematol Oncol, Charlottesville, VA 22908 USA.
[McCarty, John Michael] VCU Massey Canc Ctr, Richmond, VA USA.
[Dugan, Michael] Indinana Blood & Marrow Transplantat, Beech Grove, IN USA.
[Yellin, Michael] Celldex Therapeut Inc, Needham, MA USA.
[Davis, Thomas] NIH, Rockville, MD USA.
[Devine, Steven M.] Ohio State Med Ctr, James Canc Ctr, Div Hematol, Columbus, OH USA.
RI Jaglowski, Samantha/E-3304-2011
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 479
BP S324
EP S325
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300480
ER
PT J
AU Kang, EM
Parta, M
Hilligoss, D
Marquesen, M
Kelly, C
Kwatemaa, A
Malech, HL
AF Kang, Elizabeth M.
Parta, Mark
Hilligoss, Dianne
Marquesen, Martha
Kelly, Corin
Kwatemaa, Akua
Malech, Harry L.
TI Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for High Risk
Chronic Granulomatous Disease (CGD) Patients
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Kang, Elizabeth M.; Hilligoss, Dianne; Marquesen, Martha; Kelly, Corin; Kwatemaa, Akua; Malech, Harry L.] NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Parta, Mark] Leidos Biomedical Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 482
BP S327
EP S328
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300483
ER
PT J
AU Lad, DP
Zypchen, L
Ryan, F
Elwood, K
Holland, S
Hickstein, D
Nantel, SH
AF Lad, Deepesh P.
Zypchen, Leslie
Ryan, Frank
Elwood, Kevin
Holland, Steven
Hickstein, Dennis
Nantel, Stephen H.
TI Successful Allogeneic Hematopoietic Cell Transplantation Using
Flu-Bu-ATG Conditioning for "Mono-MAC Syndrome" [GATA2 Deficiency]
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Lad, Deepesh P.; Nantel, Stephen H.] BC Canc Agcy, Leukemia Bone Marrow Transplant Program British C, Vancouver, BC, Canada.
[Zypchen, Leslie] BC Canc Agcy, Div Hematol, Vancouver, BC, Canada.
[Ryan, Frank] Vancouver Gen Hosp, Div Resp Med, Vancouver, BC, Canada.
[Elwood, Kevin] BC Ctr Dis Control Soc, TB Control, Vancouver, BC, Canada.
[Holland, Steven] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hickstein, Dennis] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 493
BP S333
EP S333
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300494
ER
PT J
AU Martin, S
Abel, CB
Wolters, PL
Toledo-Tamula, MA
Fitzhugh, C
Hsieh, M
Tisdale, JF
AF Martin, Staci
Abel, Cristina B.
Wolters, Pamela L.
Toledo-Tamula, Mary Anne
Fitzhugh, Courtney
Hsieh, Matthew
Tisdale, John F.
TI Neurocognitive Functioning in Adults Who Underwent Nonmyeloablative
HLA-Matched Sibling Hematopoietic Stem Cell Transplant (SCT) for Sickle
Cell Disease (SCD)
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Martin, Staci; Abel, Cristina B.; Wolters, Pamela L.] NCI, Hlth Psychol & Neurobehav Res Grp, Bethesda, MD 20892 USA.
[Toledo-Tamula, Mary Anne] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA.
[Fitzhugh, Courtney] NHLBI, Sickle Cell Branch, Mol & Clin Hematol Branch, NIDDK,NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hsieh, Matthew; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 258
BP S190
EP S190
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300263
ER
PT J
AU Maxwell, S
Millan, N
Nottidge, J
Draper, D
Koklanaris, E
Superata, J
Battiwalla, M
Barrett, AJ
Wolff, EF
Ito, S
AF Maxwell, Sandra
Millan, Nicole
Nottidge, Jacqueline
Draper, Debbie
Koklanaris, Eleftheria
Superata, Jeanine
Battiwalla, Minoo
Barrett, A. John
Wolff, Erin F.
Ito, Sawa
TI Fertility Preservation Prior to Myeloablative Allogeneic Peripheral
Blood Stem Cell Transplant in Clinical Trials for Hematological
Malignancies - Practical Challenges in Transplant Coordination
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Maxwell, Sandra; Draper, Debbie; Koklanaris, Eleftheria; Superata, Jeanine; Battiwalla, Minoo; Barrett, A. John; Ito, Sawa] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Millan, Nicole; Nottidge, Jacqueline; Wolff, Erin F.] NICHHD, Reprod Endocrinol & Gynecol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 124
BP S113
EP S114
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300129
ER
PT J
AU Mays, JW
Weller, ML
Bassim, CW
Dhamala, S
Curtis, LM
Rose, JJ
Pavletic, SZ
Hakim, FT
AF Mays, Jacqueline W.
Weller, Melodie L.
Bassim, Carol W.
Dhamala, Susan
Curtis, Lauren M.
Rose, Jeremy J.
Pavletic, Steven Z.
Hakim, Fran T.
TI Th17 Recruitment and Interferon Pathway Activation in Oral Chronic
Graft-Versus-Host Disease Tissues
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Mays, Jacqueline W.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Weller, Melodie L.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Bassim, Carol W.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Dhamala, Susan; Curtis, Lauren M.; Rose, Jeremy J.; Pavletic, Steven Z.; Hakim, Fran T.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 94
BP S90
EP S91
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300099
ER
PT J
AU Moffet, JR
Mahadeo, KM
Fitzgerald, J
Gertz, S
Hall, M
Loomis, AL
McArthur, J
Nitu, M
Tamburro, R
Duncan, C
Rowan, C
AF Moffet, Jerelyn R.
Mahadeo, Kris Michael
Fitzgerald, Julie
Gertz, Shira
Hall, Mark
Loomis, Ashley Loomis
McArthur, Jennifer
Nitu, Mara
Tamburro, Robert
Duncan, Christine
Rowan, Courtney
TI The Impact of Neutrophil Engraftment on the Survival of Intubated
Pediatric HCT Patients: A Pediatric Acute Lung Injury and Sepsis Network
Study
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Moffet, Jerelyn R.] Duke Univ, Med Ctr, Pediat BMT Program, Durham, NC USA.
[Mahadeo, Kris Michael] Childrens Hosp Montefiore, Pediat Hematol Oncol & Blood & Marrow Cell Transp, Bronx, NY USA.
[Fitzgerald, Julie] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Gertz, Shira] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Hall, Mark] Nationwide Childrens Hosp, Intens Care Unit, Columbus, OH USA.
[Loomis, Ashley Loomis] Univ Minnesota, Pediat Crit Care, Minneapolis, MN USA.
[McArthur, Jennifer] Med Coll Wisconsin, Pediat Crit Care, Milwaukee, WI 53226 USA.
[Nitu, Mara; Rowan, Courtney] Indiana Univ, Indianapolis, IN 46204 USA.
[Tamburro, Robert] NIH, Rockville, MD USA.
[Duncan, Christine] Boston Childrens Hosp, Dept Pediat Oncol, Boston, MA USA.
[Rowan, Courtney] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 56
BP S60
EP S61
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300061
ER
PT J
AU Muffly, L
Pasquini, MC
Martens, M
Brazauskas, R
Zhu, XC
Adekola, K
Aljurf, MD
Artz, AS
Bajel, A
Ballen, KK
Battiwalla, M
Beitinjaneh, A
Cahn, JY
Carabasi, M
Chen, YB
Chhabra, S
Ciurea, SO
Copelan, EA
D'Souza, A
Edwards, J
Freytes, CO
Fung, HC
Gale, RP
Giralt, SA
Hashmi, SK
Hematti, P
Hildebrandt, GC
Ho, VT
Jakubowski, AA
Lazarus, HM
McCarthy, PL
Olin, RL
Olsson, R
Rezvani, A
Rizzieri, DA
Seftel, M
Seo, S
Sorror, ML
Szer, J
Wood, WA
AF Muffly, Lori
Pasquini, Marcelo C.
Martens, Michael
Brazauskas, Ruta
Zhu, Xiaochun
Adekola, Kehinde
Aljurf, Mahmoud D.
Artz, Andrew S.
Bajel, Ashish
Ballen, Karen K.
Battiwalla, Minoo
Beitinjaneh, Amer
Cahn, Jean-Yves
Carabasi, Matthew
Chen, Yi-Bin
Chhabra, Saurabh
Ciurea, Stefan O.
Copelan, Edward A.
D'Souza, Anita
Edwards, John
Freytes, Cesar O.
Fung, Henry C.
Gale, Robert Peter
Giralt, Sergio A.
Hashmi, Shahrukh K.
Hematti, Peiman
Hildebrandt, Gerhard C.
Ho, Vincent T.
Jakubowski, Ann A.
Lazarus, Hillard M.
McCarthy, Philip L.
Olin, Rebecca L.
Olsson, Richard
Rezvani, Andrew
Rizzieri, David A.
Seftel, Matthew
Seo, Sachiko
Sorror, Mohamed L.
Szer, Jeffrey
Wood, William A.
TI Increasing Use of Allogeneic Hematopoietic Cell Transplantation (HCT) in
Patients Age 70 Years and Older: A CIBMTR Study of Trends and Outcomes
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Muffly, Lori] Stanford Univ, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Pasquini, Marcelo C.; Zhu, Xiaochun; D'Souza, Anita] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.
[Martens, Michael] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA.
[Adekola, Kehinde] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia.
[Artz, Andrew S.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Bajel, Ashish; Szer, Jeffrey] Royal Melbourne Hosp, Clin Haematol & Bone Marrow Transplant Serv, Parkville, Vic 3050, Australia.
[Ballen, Karen K.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Beitinjaneh, Amer] Univ Virginia, Sch Med, Hematol Oncol, Charlottesville, VA 22908 USA.
[Cahn, Jean-Yves] Univ Hosp, Dept Hematol, Grenoble, France.
[Carabasi, Matthew] Thomas Jefferson Univ, Med Oncol, Philadelphia, PA 19107 USA.
[Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA.
[Chhabra, Saurabh] Med Univ S Carolina, Blood & Marrow Transplant Program, Charleston, SC 29425 USA.
[Ciurea, Stefan O.] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Copelan, Edward A.] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA.
[Edwards, John] Indiana Blood & Marrow Transplantat, Indianapolis, IN USA.
[Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Fung, Henry C.] Temple Univ Hosp & Med Sch, Fox Chase Canc Ctr, Dept Hematol & Oncol, Philadelphia, PA 19140 USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England.
[Giralt, Sergio A.; Jakubowski, Ann A.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA.
[Hashmi, Shahrukh K.] Mayo Clin, Div Hematol, Rochester, MN USA.
[Hematti, Peiman] Univ Wisconsin Hosp & Clin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA.
[Hildebrandt, Gerhard C.] Univ Kentucky, Chandler Med Ctr, Hematol & Blood & Marrow Transplant, Lexington, KY USA.
[Ho, Vincent T.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Adult Hematol Malignancies & Stem Cell Transplant, Cleveland, OH USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Olin, Rebecca L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Olsson, Richard] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
[Rezvani, Andrew] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Rizzieri, David A.] Duke Univ, Med Ctr, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA.
[Seftel, Matthew] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada.
[Seo, Sachiko; Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Wood, William A.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 67
BP S68
EP S69
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300072
ER
PT J
AU Pulsipher, MA
Logan, BR
Kiefer, DM
Chitphakdithai, P
Switzer, GE
Riches, ML
Rizzo, JD
Anderlini, P
Leitman, SF
Varni, JW
Kobusingye, H
Besser, RM
Shaw, BE
O'Donnell, PV
Miller, JP
Drexler, RJ
King, RJ
Horowitz, MM
Confer, DL
AF Pulsipher, Michael A.
Logan, Brent R.
Kiefer, Deidre M.
Chitphakdithai, Pintip
Switzer, Galen E.
Riches, Marcie L.
Rizzo, J. Douglas
Anderlini, Paolo
Leitman, Susan F.
Varni, James W.
Kobusingye, Hati
Besser, RaeAnne M.
Shaw, Bronwen E.
O'Donnell, Paul V.
Miller, John P.
Drexler, Rebecca J.
King, Roberta J.
Horowitz, Mary M.
Confer, Dennis L.
TI Pain, Donation-Related Symptoms and the Trajectory of Recovery in
Children after Bone Marrow (BM) Donation Are Influenced By Age (Pre vs.
Post-Puberty) and Sex: Primary Analysis of the Pediatric Toxicity Cohort
of the Related Donor Safety Study (RDSafe)
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Pulsipher, Michael A.] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90027 USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Logan, Brent R.] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.
[Kiefer, Deidre M.; Chitphakdithai, Pintip; Kobusingye, Hati; Besser, RaeAnne M.; Drexler, Rebecca J.; King, Roberta J.] Be The Match, CIBMTR, Natl Marrow Donor Program, Minneapolis, MN USA.
[Switzer, Galen E.] Univ Pittsburgh, Med Psychiat & Clin & Translat Sci, Pittsburgh, PA USA.
[Riches, Marcie L.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA.
[Rizzo, J. Douglas; Shaw, Bronwen E.; Horowitz, Mary M.] CIBMTR, Dept Med, Milwaukee, WI USA.
[Rizzo, J. Douglas; Shaw, Bronwen E.; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Leitman, Susan F.] NHLBI, Dept Transfus Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Varni, James W.] Texas A&M Univ, College Stn, TX USA.
[O'Donnell, Paul V.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Miller, John P.] Dept Donor Med Serv, Natl Marrow Donor Program, Minneapolis, MN USA.
[Confer, Dennis L.] CIBMTR, Minneapolis, MN USA.
[Confer, Dennis L.] Be The Match, Natl Marrow Donor Program, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 97
BP S93
EP S94
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300102
ER
PT J
AU Schoemans, HM
Goris, K
Van Durm, R
Vanhoof, J
Greinix, DWPH
Pavletic, SZ
Lee, SJ
Maertens, JA
De Geest, S
Dobbels, F
Duarte, RF
AF Schoemans, Helene M.
Goris, Kathy
Van Durm, Raf
Vanhoof, Jasper
Greinix, Daniel Wolff Prof Hildegard
Pavletic, Steven Z.
Lee, Stephanie J.
Maertens, Johan A.
De Geest, Sabina
Dobbels, Fabienne
Duarte, Rafael F.
TI The 'EBMT GVHD App' Improves the Accuracy of Graft-Versus-Host-Disease
Assessment According to NIH Criteria Compared to Standard Practice
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Schoemans, Helene M.; Goris, Kathy; Maertens, Johan A.] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Hematol, Leuven, Belgium.
[Van Durm, Raf] Katholieke Univ Leuven, Univ Hosp Leuven, IT Dept, Leuven, Belgium.
[Vanhoof, Jasper; De Geest, Sabina; Dobbels, Fabienne] Katholieke Univ Leuven, Acad Ctr Nursing & Midwifery, Leuven, Belgium.
[Greinix, Daniel Wolff Prof Hildegard] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany.
[Greinix, Daniel Wolff Prof Hildegard] Med Univ Graz, Div Hematol, Vienna, Austria.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[De Geest, Sabina; Dobbels, Fabienne] Univ Basel, Inst Nursing Sci, Basel, Switzerland.
[Duarte, Rafael F.] Hosp Llobregat, ICO Hosp Duran I Reynals, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 412
BP S284
EP S284
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300414
ER
PT J
AU Shanis, D
Scrivani, C
Bevans, M
Yang, L
Grants, C
Welshans, K
Stratton, P
AF Shanis, Dana
Scrivani, Claire
Bevans, Margaret
Yang, Li
Grants, Caitlin
Welshans, Katelyn
Stratton, Pamela
TI Impairment in Sexual Function Persists in Clinically-Stable Female
Survivors of Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Shanis, Dana] NICHD, NIH, Bethesda, MD USA.
[Scrivani, Claire] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
[Scrivani, Claire] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Bevans, Margaret; Yang, Li] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Grants, Caitlin] Howard Community Coll, Columbia, MD USA.
[Welshans, Katelyn] Commonwealth Med Coll, Scranton, PA USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 86
BP S85
EP S85
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300091
ER
PT J
AU Shanis, D
Anandi, P
Grant, C
Bachi, A
Vyas, N
Pophali, PA
Koklanaris, E
Ito, S
Savani, BN
Barrett, AJ
Battiwalla, M
Stratton, P
AF Shanis, Dana
Anandi, Prathima
Grant, Caitlin
Bachi, Averyl
Vyas, Nina
Pophali, Priyanka A.
Koklanaris, Eleftheria
Ito, Sawa
Savani, Bipin N.
Barrett, A. John
Battiwalla, Minoo
Stratton, Pamela
TI Risk Factors for Human Papilloma Virus Reactivation in the Genital Tract
of Female Stem Cell Transplant Survivors
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Shanis, Dana] NICHD, NIH, Bethesda, MD USA.
[Anandi, Prathima; Pophali, Priyanka A.; Koklanaris, Eleftheria; Ito, Sawa; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Grant, Caitlin] Howard Community Coll, Columbia, MD USA.
[Bachi, Averyl] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Vyas, Nina] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
RI Pophali, Priyanka/P-8646-2016
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 9
BP S26
EP S26
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300014
ER
PT J
AU Sharma, KR
Choi, U
Thompson, RD
Rodman, LE
Malech, HL
Kang, EM
AF Sharma, Karlie Roxanne
Choi, Uimook
Thompson, Robert D.
Rodman, Larry E.
Malech, Harry L.
Kang, Elizabeth M.
TI A Novel Method for Screening Adenosine Receptor Specific Agonists for
Use in Autoimmune Diseases
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Sharma, Karlie Roxanne; Choi, Uimook; Malech, Harry L.; Kang, Elizabeth M.] NIAID, Lab Host Def, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Thompson, Robert D.; Rodman, Larry E.] Lewis & Clark Pharmaceut INC, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 623
BP S413
EP S414
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300623
ER
PT J
AU Sharma, KR
Bryant, S
Koontz, SM
Malech, HL
Kang, EM
AF Sharma, Karlie Roxanne
Bryant, Sarah
Koontz, Sherry M.
Malech, Harry L.
Kang, Elizabeth M.
TI Loss of Expression of the Autoimmune Regulator Protein Contributes to
Autoimmune Phenotypes in GvHD and Colitis
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Sharma, Karlie Roxanne; Koontz, Sherry M.; Malech, Harry L.; Kang, Elizabeth M.] NIAID, Lab Host Defenses, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Bryant, Sarah] Providence Coll, Providence, RI 02918 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 136
BP S120
EP S120
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300141
ER
PT J
AU Soni, S
Tisdale, JF
Hsieh, M
Kanter, J
Leboulch, P
Cavazzana, M
AF Soni, Sandeep
Tisdale, John F.
Hsieh, Matthew
Kanter, Julie
Leboulch, Philippe
Cavazzana, Marina
TI Outcomes of Gene Therapy for Severe Sickle Cell Disease (SCD) via
Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex
Vivo with a Lentiviral beta(AT87Q_Globin) Vector
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Soni, Sandeep] Bluebird Biotech Inc, Hematol BMT, Cambridge, MA USA.
[Tisdale, John F.; Hsieh, Matthew] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA.
[Kanter, Julie] Med Univ S Carolina, Pediat Hematol Oncol, Charleston, SC 29425 USA.
[Leboulch, Philippe] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Leboulch, Philippe] Harvard Univ, Sch Med, Boston, MA USA.
[Leboulch, Philippe] Univ Paris Sud, IMETi, CEA, Fontenay Aux Roses, France.
[Leboulch, Philippe] Univ Paris Sud, CEA, INSERM, UMR 962, Fontenay Aux Roses, France.
[Cavazzana, Marina] Hosp Necker Enfants Malad, Paris, France.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 60
BP S63
EP S63
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300065
ER
PT J
AU Vrooman, L
Millard, H
Brazauskas, R
Majhail, NS
Battiwallas, M
Flowers, MED
Savani, BN
Akpek, G
Aljurf, MD
Bajwa, R
Baker, KS
Beitinjaneh, A
Bitan, M
Buchbinder, D
Dandoy, CE
Gale, RP
Hayashi, RJ
Hematti, P
Kamble, RT
Kasow, KA
Kletzel, M
Lazarus, HM
Malone, AK
O'Brien, T
Olsson, R
Reddy, V
Willert, JR
Ringden, O
Schears, RM
Seo, S
Steinberg, A
Yu, LC
Shaw, BE
Duncan, C
AF Vrooman, Lynda
Millard, Heather
Brazauskas, Ruta
Majhail, Navneet S.
Battiwallas, Minoo
Flowers, Mary E. D.
Savani, Bipin N.
Akpek, Goerguen
Aljurf, Mahmoud D.
Bajwa, Rajinder
Baker, K. Scott
Beitinjaneh, Amer
Bitan, Menachem
Buchbinder, David
Dandoy, Christopher E.
Gale, Robert Peter
Hayashi, Robert J.
Hematti, Peiman
Kamble, Rammurti T.
Kasow, Kimberly A.
Kletzel, Morris
Lazarus, Hillard M.
Malone, Adriana K.
O'Brien, Tracey
Olsson, Richard
Reddy, Vijay
Willert, Jennifer Reikes
Ringden, Olle
Schears, Raquel M.
Seo, Sachiko
Steinberg, Amir
Yu, Lolie C.
Shaw, Bronwen E.
Duncan, Christine
TI Survival and Late Effects of Children Undergoing Myeloablative
Allogeneic HCT at Less Than Three Years of Age: A Report from the Center
for International Blood and Marrow Transplant Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Vrooman, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Millard, Heather] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA.
[Majhail, Navneet S.] Cleveland Clin, Blood & Marrow Transplant Program, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Battiwallas, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Flowers, Mary E. D.; Baker, K. Scott] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
[Akpek, Goerguen] Banner MD Anderson Canc Ctr, Gilbert, AZ USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia.
[Bajwa, Rajinder] Nationwide Childrens, Bone Marrow Transplantat, Columbus, OH USA.
[Beitinjaneh, Amer] Univ Virginia, Sch Med, Hematol Oncol, Charlottesville, VA 22908 USA.
[Bitan, Menachem] Tel Aviv Sourasky Med Ctr, Pediat Hematol Oncol & BMT, Tel Aviv, Israel.
[Buchbinder, David] Childrens Hosp Orange Cty, Div Pediat Hematol, Orange, CA 92668 USA.
[Dandoy, Christopher E.] Cincinnati Childrens Hosp Med Ctr, Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England.
[Hayashi, Robert J.] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA.
[Hematti, Peiman] Univ Wisconsin Hosp & Clin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA.
[Kamble, Rammurti T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Kasow, Kimberly A.] Univ N Carolina, Div Hematol Oncol, Dept Pediat, Chapel Hill, NC USA.
[Kletzel, Morris] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Div Hematol Oncol & Stem Cell Transplantat, Chicago, IL 60611 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Adult Hematol Malignancies & Stem Cell Transplant, Cleveland, OH USA.
[Malone, Adriana K.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[O'Brien, Tracey] Sydney Childrens Hosp, Kids Canc Ctr, Blood & Marrow Transplant Program, Sydney, NSW, Australia.
[Olsson, Richard] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden.
[Olsson, Richard; Ringden, Olle] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden.
[Reddy, Vijay] Univ Cent Florida, Dept Internal Med, Gainesville, FL USA.
[Willert, Jennifer Reikes] Univ Calif San Diego, Rady Childrens Hosp, Pediat Hematol Oncol BMT, San Diego, CA USA.
[Ringden, Olle] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Schears, Raquel M.] Mayo Clin, Rochester, MN USA.
[Seo, Sachiko] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Steinberg, Amir] Mt Sinai Hosp, Dept Hematol Oncol, New York, NY 10029 USA.
[Yu, Lolie C.] Louisiana State Univ, Med Ctr, Childrens Hosp, Div Hematol Oncol, New Orleans, LA USA.
[Yu, Lolie C.] Louisiana State Univ, Med Ctr, Childrens Hosp, Ctr Canc & Blood Disorders,HSCT, New Orleans, LA USA.
[Shaw, Bronwen E.] CIBMTR, Dept Med, Milwaukee, WI USA.
[Shaw, Bronwen E.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Duncan, Christine] Boston Childrens Hosp, Dept Pediat Oncol, Boston, MA USA.
[Duncan, Christine] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 12
BP S28
EP S29
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300017
ER
PT J
AU Williams, KM
Hakim, FT
Rosenberg, A
Kleiner, D
Mitchell, SA
Tamm, M
Avila, D
Lee, SJ
Halter, J
Prince, SS
Bubendorf, L
Bollard, CM
Pavletic, SZ
Gress, R
AF Williams, Kirsten M.
Hakim, Fran T.
Rosenberg, Avi
Kleiner, David
Mitchell, Sandra A.
Tamm, Michael
Avila, Daniele
Lee, Stephanie J.
Halter, Joerg
Prince, Spasenija Savic
Bubendorf, Lukas
Bollard, Catherine M.
Pavletic, Steven Z.
Gress, Ronald
TI Plasma Osteopontin Is a Biomarlcer Specifically Associated with
Bronchiolitis Obliterans Syndrome after HCT
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Williams, Kirsten M.] Childrens Natl Med Ctr, BMT, Washington, DC 20010 USA.
[Hakim, Fran T.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Avi] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Kleiner, David] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Tamm, Michael; Bubendorf, Lukas] Univ Spital Basel, Basel, Switzerland.
[Avila, Daniele] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Clin Res Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Halter, Joerg] Univ Basel Hosp, CH-4031 Basel, Switzerland.
[Prince, Spasenija Savic] Univ Spital Basel, Pathol, Basel, Switzerland.
[Bollard, Catherine M.] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
[Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 630
BP S417
EP S418
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300630
ER
PT J
AU Williams, KM
Holter-Chakrabarty, JL
Lindenberg, L
Adler, S
Chai, A
Kurdziel, K
Lin, F
Blacklock-Schuver, BAJ
Avila, D
Kanakry, CG
Vesely, SK
Havlicek, JP
Duong, NQT
Nguyen, CT
Selby, G
Bollard, CM
Choyke, P
Gress, R
AF Williams, Kirsten M.
Holter-Chakrabarty, Jennifer L.
Lindenberg, Liza
Adler, Steve
Chai, Amy
Kurdziel, Karen
Lin, Frank
Blacklock-Schuver, Bazetta A. J.
Avila, Daniele
Kanakry, Christopher G.
Vesely, Sara K.
Havlicek, Joseph P.
Duong, Ngoc Quyen T.
Nguyen, Chuong T.
Selby, George
Bollard, Catherine M.
Choyke, Peter
Gress, Ronald
TI Novel PET Imaging with Fluorothymidine (FLT) Predicts Relapse
Quantitatively at Day 28 Post Transplantation in Patients with Acute
Leukemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 18-22, 2016
CL Honolulu, HI
SP Ctr Int Blood & Marrow Transplant Res, Amer Soc Blood & Marrow Transplantat
C1 [Williams, Kirsten M.] Childrens Natl Med Ctr, BMT, Washington, DC 20010 USA.
[Holter-Chakrabarty, Jennifer L.] Univ Oklahoma, Oklahoma City, OK USA.
[Lindenberg, Liza; Adler, Steve; Kurdziel, Karen; Choyke, Peter] NIH, Mol Imaging Branch, Bldg 10, Bethesda, MD 20892 USA.
[Chai, Amy; Blacklock-Schuver, Bazetta A. J.; Avila, Daniele] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Lin, Frank] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
[Kanakry, Christopher G.] NCI, ETIB, Bethesda, MD 20892 USA.
[Vesely, Sara K.; Duong, Ngoc Quyen T.] Univ Oklahoma, Hlth Sci Ctr, Stephenson Canc Ctr, Oklahoma City, OK USA.
[Havlicek, Joseph P.; Nguyen, Chuong T.] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA.
[Selby, George] Univ Oklahoma, Med Ctr, Norman, OK 73019 USA.
[Bollard, Catherine M.] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
[Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD MAR
PY 2016
VL 22
IS 3
SU 1
MA 295
BP S213
EP S214
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DE8TT
UT WOS:000370910300300
ER
PT J
AU Tyc, KM
Herwald, SE
Hogan, JA
Pierce, JV
Klipp, E
Kumamoto, CA
AF Tyc, Katarzyna M.
Herwald, Sanna E.
Hogan, Jennifer A.
Pierce, Jessica V.
Klipp, Edda
Kumamoto, Carol A.
TI The game theory of Candida albicans colonization dynamics reveals host
status-responsive gene expression
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
DE Candida albicans; Colonization; Fungal pathogen; Microbiota; Efg1p;
Evolutionary game theory; Mathematical modeling
ID PROTECTIVE TH1 RESPONSES; BALB-C MICE; SYSTEMIC CANDIDIASIS;
GASTROINTESTINAL COLONIZATION; INTRAGASTRIC COLONIZATION;
TRANSCRIPTIONAL RESPONSE; INTESTINAL COLONIZATION; HYPHAL DEVELOPMENT;
ENDOGENOUS ORIGIN; BIOFILM FORMATION
AB Background: The fungal pathogen Candida albicans colonizes the gastrointestinal (GI) tract of mammalian hosts as a benign commensal. However, in an immunocompromised host, the fungus is capable of causing life-threatening infection. We previously showed that the major transcription factor Efg1p is differentially expressed in GI-colonizing C. albicans cells dependent on the host immune status. To understand the mechanisms that underlie this host-dependent differential gene expression, we utilized mathematical modeling to dissect host-pathogen interactions. Specifically, we used principles of evolutionary game theory to study the mechanism that governs dynamics of EFG1 expression during C. albicans colonization.
Results: Mathematical modeling predicted that down-regulation of EFG1 expression within individual fungal cells occurred at different average rates in different hosts. Rather than using relatively transient signaling pathways to adapt to a new environment, we demonstrate that C. albicans overcomes the host defense strategy by modulating the activity of diverse fungal histone modifying enzymes that control EFG1 expression.
Conclusion: Based on our modeling and experimental results we conclude that C. albicans cells sense the local environment of the GI tract and respond to differences by altering EFG1 expression to establish optimal survival strategies. We show that the overall process is governed via modulation of epigenetic regulators of chromatin structure.
C1 [Tyc, Katarzyna M.; Klipp, Edda] Humboldt Univ, Theoret Biophys, Invalidenstr 42, D-10115 Berlin, Germany.
[Herwald, Sanna E.; Hogan, Jennifer A.; Pierce, Jessica V.; Kumamoto, Carol A.] Tufts Univ, Sackler Sch Biomed Sci, Grad Program Mol Microbiol, Boston, MA 02111 USA.
[Herwald, Sanna E.; Hogan, Jennifer A.; Pierce, Jessica V.; Kumamoto, Carol A.] Tufts Univ, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA.
[Tyc, Katarzyna M.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA.
[Pierce, Jessica V.] NIDDK, NIH, Genet Biochem Branch, Bethesda, MD 20892 USA.
RP Klipp, E (reprint author), Humboldt Univ, Theoret Biophys, Invalidenstr 42, D-10115 Berlin, Germany.; Kumamoto, CA (reprint author), Tufts Univ, Sackler Sch Biomed Sci, Grad Program Mol Microbiol, Boston, MA 02111 USA.; Kumamoto, CA (reprint author), Tufts Univ, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA.
EM edda.klipp@rz.hu-berlin.de; carol.kumamoto@tufts.edu
FU National Institutes of Health [R01AI081794, R01AI081794-02S1]; European
Commission through European Marie Curie Initial Training Network,
FINSysB [PITN-GA-2008-214004]; NIH [T32AI07422, T32GM008448]
FX We thank Drs. Tim van Opijnen, Bree Aldridge, Kearney Gunsalus and Talya
Davis for helpful discussion and Dr. Al Brown for catalyzing our
collaboration. This research was supported by grants R01AI081794 and
R01AI081794-02S1 from the National Institutes of Health to C.A.K. and by
the European Commission through the European Marie Curie Initial
Training Network, FINSysB (PITN-GA-2008-214004) to E.K. J.V.P. was
partially supported by T32AI07422 and S.E.H. by T32GM008448 from the
NIH. K.M.T. was supported by the European Commission through the
European Marie Curie Initial Training Network, FINSysB
(PITN-GA-2008-214004).
NR 70
TC 1
Z9 1
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD MAR 1
PY 2016
VL 10
AR 20
DI 10.1186/s12918-016-0268-1
PG 13
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DE9IR
UT WOS:000370950700001
PM 26927448
ER
PT J
AU Sinder, BP
Lloyd, WR
Salemi, JD
Marini, JC
Caird, MS
Morris, MD
Kozloff, KM
AF Sinder, Benjamin P.
Lloyd, William R.
Salemi, Joseph D.
Marini, Joan C.
Caird, Michelle S.
Morris, Michael D.
Kozloff, Kenneth M.
TI Effect of anti-sclerostin therapy and osteogenesis imperfecta on
tissue-level properties in growing and adult mice while controlling for
tissue age
SO BONE
LA English
DT Article
DE Sclerostin antibody; Osteogenesis imperfecta; Raman spectroscopy;
Nanoindentation; Anabolic therapy; Bone quality
ID BONE-MINERAL DENSITY; BRTL/+ MOUSE MODEL; POSTMENOPAUSAL WOMEN;
STRENGTH; MATRIX; MASS; BLOSOZUMAB; FRACTURE; QUALITY
AB Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (01). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical 01 Gly -> Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5 weeks with Sd-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4 wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages > 3 wks) and rapidly growing Brtl/+ (at tissue ages > 4 wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Sinder, Benjamin P.; Salemi, Joseph D.; Caird, Michelle S.; Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA.
[Sinder, Benjamin P.; Salemi, Joseph D.; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[Lloyd, William R.; Morris, Michael D.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM kenkoz@umich.edu
FU NIH [R01 AR062522, R01 AR052010]
FX Mike Ominsky provided feedback on the data and reviewed the manuscript.
Bonnie Nolan, Kathy Sweet, Logan White, and Mary Eddy assisted with
animal work. John Baker assisted with histology of paraffin sections.
David Barton helped develop the custom hydrated nanoindentation testing
device. Scl-Ab was graciously provided by Amgen and UCB. Funding support
from NIH to KMK (R01 AR062522) and MDM (R01 AR052010) is gratefully
acknowledged.
NR 36
TC 8
Z9 8
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD MAR
PY 2016
VL 84
BP 222
EP 229
DI 10.1016/j.bone.2016.01.001
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DE8VK
UT WOS:000370914600026
PM 26769006
ER
PT J
AU Tully, CM
Apolo, AB
Zabor, EC
Regazzi, AM
Ostrovnaya, I
Furberg, HF
Rosenberg, JE
Bajorin, DF
AF Tully, Christopher M.
Apolo, Andrea B.
Zabor, Emily C.
Regazzi, Ashley M.
Ostrovnaya, Irina
Furberg, Helena F.
Rosenberg, Jonathan E.
Bajorin, Dean F.
TI The high incidence of vascular thromboembolic events in patients with
metastatic or unresectable urothelial cancer treated with platinum
chemotherapy agents
SO CANCER
LA English
DT Article
DE bladder cancer; carboplatin; cisplatin; thrombosis; urothelial carcinoma
ID TRANSITIONAL-CELL CARCINOMA; CISPLATIN-BASED CHEMOTHERAPY; GEMCITABINE
PLUS CISPLATIN; PHASE-II; VENOUS THROMBOEMBOLISM; BLADDER-CANCER;
RISK-FACTORS; RETROSPECTIVE ANALYSIS; ONCOLOGY-GROUP; LUNG-CANCER
AB BACKGROUNDThe current study compared the incidence of vascular thromboembolic events (VTEs) in patients with metastatic or unresectable urothelial carcinoma (UC) who were treated with gemcitabine and carboplatin (GCb); gemcitabine, carboplatin, and bevacizumab (GCbBev); or gemcitabine and cisplatin (GCis).
METHODSPatients with UC who were treated with GCbBev on protocol were analyzed prospectively and 2 contemporary control cohorts receiving GCb or GCis were evaluated retrospectively. VTE was defined as either venous or arterial (myocardial infarctions or cerebral vascular accidents) thrombosis. VTEs were considered to be related to treatment if they occurred during treatment or within 4 weeks of the completion of treatment. Associations with chemotherapy regimen were tested using either the Fisher exact test or Kruskal-Wallis test. Clinical factors associated with VTEs were analyzed using conditional logistic regression stratified by treatment regimen.
RESULTSAmong 198 patients, VTEs occurred in 13 of 51 patients treated with GCbBev (26%), 22 of 92 patients treated with GCb (24%), and 8 of 55 patients treated with GCis (15%). Patient characteristics were significantly different between the treatment cohorts in terms of age, prior cystectomy, tumor location near pelvic vessels, Khorana risk group, and receipt of antiplatelet therapy. The incidence of VTE and type of VTE (arterial vs venous) did not differ by type of chemotherapy. Prior cystectomy was associated with an increased risk of VTE (odds ratio, 2.2; 95% confidence interval, 1.0-4.9 [P=.047]).
CONCLUSIONSThe incidence of VTE in Cis-treated patients was similar to prior reports. However, the VTE rate in Cb-treated patients was>20%, a figure not previously defined in patients with UC and higher than expected. This high incidence of both Cis-related and Cb-related VTEs warrants greater awareness by treating physicians and deserves further study. (c) 2015 American Cancer Society.
C1 [Tully, Christopher M.; Regazzi, Ashley M.; Rosenberg, Jonathan E.; Bajorin, Dean F.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10065 USA.
[Tully, Christopher M.; Rosenberg, Jonathan E.; Bajorin, Dean F.] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA.
[Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Zabor, Emily C.; Ostrovnaya, Irina; Furberg, Helena F.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
RP Bajorin, DF (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10065 USA.
EM bajorind@mskcc.org
OI Regazzi, Ashley/0000-0002-6019-1852
FU Zena and Michael A. Wiener Research and Therapeutic Program in Bladder
Cancer; National Cancer Institute Cancer Center Core Grant [P30
CA008748]
FX Supported by The Zena and Michael A. Wiener Research and Therapeutic
Program in Bladder Cancer and a National Cancer Institute Cancer Center
Core Grant (P30 CA008748).
NR 44
TC 2
Z9 2
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 1
PY 2016
VL 122
IS 5
BP 712
EP 721
DI 10.1002/cncr.29801
PG 10
WC Oncology
SC Oncology
GA DF2IP
UT WOS:000371166300011
PM 26618338
ER
PT J
AU Burnside, ES
Drukker, K
Li, H
Bonaccio, E
Zuley, M
Ganott, M
Net, JM
Sutton, EJ
Brandt, KR
Whitman, GJ
Conzen, SD
Lan, L
Ji, Y
Zhu, YT
Jaffe, CC
Huang, EP
Freymann, JB
Kirby, JS
Morris, EA
Giger, ML
AF Burnside, Elizabeth S.
Drukker, Karen
Li, Hui
Bonaccio, Ermelinda
Zuley, Margarita
Ganott, Marie
Net, Jose M.
Sutton, Elizabeth J.
Brandt, Kathleen R.
Whitman, Gary J.
Conzen, Suzanne D.
Lan, Li
Ji, Yuan
Zhu, Yitan
Jaffe, Carl C.
Huang, Erich P.
Freymann, John B.
Kirby, Justin S.
Morris, Elizabeth A.
Giger, Maryellen L.
TI Using computer-extracted image phenotypes from tumors on breast magnetic
resonance imaging to predict breast cancer pathologic stage
SO CANCER
LA English
DT Article
DE breast cancer stage; magnetic resonance imaging (MRI); prognosis;
quantitative image analysis
ID ENHANCED MR-IMAGES; MAXIMUM-LIKELIHOOD-ESTIMATION; LYMPH-NODE
METASTASES; BINORMAL ROC CURVES; PROGNOSTIC MARKERS; MOLECULAR SUBTYPES;
DCE-MRI; LESIONS; CLASSIFICATION; IDENTIFICATION
AB BACKGROUNDThe objective of this study was to demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage.
METHODSThe authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy-proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n=22; stage II, n=58; stage III, n=11) and surgically verified lymph node status (negative lymph nodes, n=46;1 positive lymph node, n=44; no lymph nodes examined, n=1). Tumors were characterized according to 1) radiologist-measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave-1-out, cross-validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest.
RESULTSTumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor homogeneity significantly improved discrimination (AUC=0.62; P=.003) compared with chance.
CONCLUSIONSThe current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. (c) 2015 American Cancer Society.
C1 [Burnside, Elizabeth S.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Drukker, Karen; Li, Hui; Conzen, Suzanne D.; Lan, Li; Giger, Maryellen L.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Bonaccio, Ermelinda] Roswell Pk Canc Inst, Dept Radiol, Buffalo, NY 14263 USA.
[Zuley, Margarita; Ganott, Marie] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Net, Jose M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Sutton, Elizabeth J.] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA.
[Brandt, Kathleen R.] Mayo Clin, Dept Diagnost Radiol, Rochester, MN USA.
[Whitman, Gary J.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Imaging, Houston, TX 77030 USA.
[Ji, Yuan] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Ji, Yuan; Zhu, Yitan] NorthShore Univ HealthSyst, Program Computat Genom & Med, Evanston, IL USA.
[Jaffe, Carl C.; Huang, Erich P.; Freymann, John B.; Kirby, Justin S.] NCI, NIH, Rockville, MD USA.
RP Giger, ML (reprint author), Univ Chicago, Radiol MC 2026,5841 S Maryland Ave, Chicago, IL 60637 USA.; Morris, EA (reprint author), Mem Sloan Kettering Canc Ctr, Breast Imaging Serv, 1275 York Ave, New York, NY 10065 USA.
EM m-giger@uchicago.edu; m-giger@uchicago.edu
FU University of Chicago Dean Bridge Fund; National Institutes of Health
[R01CA165229, R01LM010921, K24CA194251, T32 EB002103]
FX This work was supported by the University of Chicago Dean Bridge Fund
and by grants from the National Institutes of Health (R01CA165229,
R01LM010921, K24CA194251, and T32 EB002103).
NR 35
TC 0
Z9 0
U1 8
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 1
PY 2016
VL 122
IS 5
BP 748
EP 757
DI 10.1002/cncr.29791
PG 10
WC Oncology
SC Oncology
GA DF2IP
UT WOS:000371166300015
PM 26619259
ER
PT J
AU Friedman, DN
Chou, JF
Oeffinger, KC
Kleinerman, RA
Ford, JS
Sklar, CA
Li, YL
McCabe, MS
Robison, LL
Marr, BP
Abramson, DH
Dunkel, IJ
AF Friedman, Danielle Novetsky
Chou, Joanne F.
Oeffinger, Kevin C.
Kleinerman, Ruth A.
Ford, Jennifer S.
Sklar, Charles A.
Li, Yuelin
McCabe, Mary S.
Robison, Leslie L.
Marr, Brian P.
Abramson, David H.
Dunkel, Ira J.
TI Chronic medical conditions in adult survivors of retinoblastoma: Results
of the Retinoblastoma Survivor Study
SO CANCER
LA English
DT Article
DE follow-up studies; questionnaires; retinoblastoma; risk; survivors
ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; HEREDITARY
RETINOBLASTOMA; 5-YEAR SURVIVORS; LATE MORTALITY; FOLLOW-UP; RISK;
RADIOTHERAPY; CHILDREN; LIFE
AB BACKGROUNDLimited data are available regarding long-term morbidity in adult survivors of retinoblastoma (Rb).
METHODSThe Retinoblastoma Survivor Study is a retrospective cohort of adult survivors of Rb diagnosed between 1932 and 1994. Participants completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study surveys. Chronic conditions were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.03). Multivariate Poisson regression was used to compare survivors of Rb with 2377 non-Rb controls, consisting of the Childhood Cancer Survivor Study sibling cohort and survivors with bilateral versus unilateral disease.
RESULTSSurvivors of Rb (53.6% with bilateral disease) and non-Rb controls had a mean age of 43.3 years (standard deviation, 11 years) and 37.6 years (SD, 8.6 years), respectively, at the time of study enrollment. At a median follow-up of 42 years (range, 15-75 years), 86.6% of survivors of Rb had at least 1 condition and 71.1% had a severe/life-threatening (grade 3-4) condition. The adjusted relative risk (RR) of a chronic condition in survivors compared with non-Rb controls was 1.4 (95% confidence interval [95% CI], 1.3-1.4; P<.01); for a grade 3 to 4 condition, the RR was 7.6 (95% CI, 6.4-8.9; P<.01). Survivors were at an excess risk regardless of laterality. After stratifying by laterality and excluding ocular conditions and second malignant neoplasms (SMNs), only those with bilateral disease were found to be at an increased risk of any nonocular, non-SMN condition (RR, 1.2; 95% CI, 1.1-1.2) and for grade 3 to 4 nonocular, non-SMN conditions (RR, 1.7; 95% CI, 1.2-2.5).
CONCLUSIONSSurvivors of Rb have an increased risk of chronic conditions compared with non-Rb controls. After excluding ocular conditions and SMNs, this excess risk was found to persist only for those with bilateral disease. (c) 2016 American Cancer Society.
C1 [Friedman, Danielle Novetsky; Oeffinger, Kevin C.; Sklar, Charles A.; Dunkel, Ira J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10065 USA.
[Chou, Joanne F.; Li, Yuelin] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY 10065 USA.
[Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Kleinerman, Ruth A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA.
[Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10065 USA.
[McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, Survivorship Ctr, Dept Med, New York, NY 10065 USA.
[Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Marr, Brian P.; Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10065 USA.
RP Friedman, DN (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10065 USA.
EM friedmad@mskcc.org
OI Friedman, Danielle Novetsky/0000-0003-4668-9176
FU New York Community Trust; Charles A. Frueauff Foundation; Perry's
Promise Fund; National Cancer Institute [U24 CA55727]; Clinical and
Translational Science Center at Weill Cornell Medical College
[KL2TR000458]; Intramural Research Program of the National Institutes of
Health; NIH/NCI Cancer Center Support Grant [P30CA008748]
FX Supported by the New York Community Trust, the Charles A. Frueauff
Foundation, the Perry's Promise Fund, National Cancer Institute grant
U24 CA55727 (Childhood Cancer Survivor Study; Dr. Armstrong, Principal
Investigator), grant KL2TR000458 of the Clinical and Translational
Science Center at Weill Cornell Medical College, the Intramural Research
Program of the National Institutes of Health, and the NIH/NCI Cancer
Center Support Grant P30CA008748.
NR 30
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 1
PY 2016
VL 122
IS 5
BP 773
EP 781
DI 10.1002/cncr.29704
PG 9
WC Oncology
SC Oncology
GA DF2IP
UT WOS:000371166300018
PM 26755259
ER
PT J
AU Seol, HS
Lee, SE
Song, JS
Rhee, JK
Singh, SR
Chang, S
Jang, SJ
AF Seol, Hyang Sook
Lee, Sang Eun
Song, Joon Seon
Rhee, Je-Keun
Singh, Shree Ram
Chang, Suhwan
Jang, Se Jin
TI Complement proteins C7 and CFH control the stemness of liver cancer
cells via LSF-1
SO CANCER LETTERS
LA English
DT Article
DE Liver tumor-initiating cell; Complement protein C7; CFH; Stemness
factor; LSF-1; HCC
ID HEPATOCELLULAR-CARCINOMA; INFLAMMATION; TUMOR; IMMUNITY; ACTIVATION;
RESPONSES; ONCOGENE; C5A
AB Tumor-initiating, cells are important for the formation and maintenance of tumor bulks in various tumors. To identify surface markers of liver tumor-initiating cells, we performed primary tumorsphere culture and analyzed the expression of cluster of differentiation (CD) antigen genes using NanoString. Interestingly, we found significant upregulation of the complement proteins (p = 1.60 x 10(-18)), including C7 and CFH. Further studies revealed that C7 and CFH are required to maintain sternness in liver cancer cells. Knockdown of C7 and CFH expression abrogated tumorsphere formation and induced differentiation, whereas overexpression stimulated sternness factor expression as well as in vivo cell growth. Mechanistically, by studying C7 and CFH-dependent LSF-1 expression and its direct role on sternness factor transcription, we found that LSF-1 is involved in this regulation. Taken together, our data demonstrate the unprecedented role of complement proteins on the maintenance of sternness in liver tumor initiating cells. Published by Elsevier Ireland Ltd.
C1 [Seol, Hyang Sook; Lee, Sang Eun; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea.
[Song, Joon Seon; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
[Rhee, Je-Keun; Chang, Suhwan] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biomed Sci, Seoul, South Korea.
[Singh, Shree Ram] NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Ctr Canc Res, Frederick, MD 21701 USA.
RP Jang, SJ (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea.; Jang, SJ (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.; Chang, S (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biomed Sci, Seoul, South Korea.
EM suhwan.chang@amc.seoul.kr; jangsejin@amc.seoul.kr
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU National Research Foundation of Korea (NRF) - Ministry of Science, ICT
and Future Planning [2015R1A1A3A04001354]; Korea Health Technology R&D
Project through the Korea Health Industry Development Institute (KHIDI)
[HI06C0868]; National R&D Program for Cancer Control - Ministry of
Health &Welfare, Republic of Korea [1320140]
FX This research was supported by Basic Science Research Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Science, ICT and Future Planning (2015R1A1A3A04001354), the Korea
Health Technology R&D Project through the Korea Health Industry
Development Institute (KHIDI) (grant number: HI06C0868), and the
National R&D Program for Cancer Control (grant number: 1320140) funded
by the Ministry of Health &Welfare, Republic of Korea.
NR 28
TC 1
Z9 1
U1 2
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD MAR 1
PY 2016
VL 372
IS 1
BP 24
EP 35
DI 10.1016/j.canlet.2015.12.005
PG 12
WC Oncology
SC Oncology
GA DE7QU
UT WOS:000370832600003
PM 26723877
ER
PT J
AU Pasqua, T
Mahata, S
Bandyopadhyay, GK
Biswas, A
Perkins, GA
Sinha-Hikim, AP
Goldstein, DS
Eiden, LE
Mahata, SK
AF Pasqua, Teresa
Mahata, Sumana
Bandyopadhyay, Gautam K.
Biswas, Angshuman
Perkins, Guy A.
Sinha-Hikim, Amiya P.
Goldstein, David S.
Eiden, Lee E.
Mahata, Sushil K.
TI Impact of Chromogranin A deficiency on catecholamine storage,
catecholamine granule morphology and chromaffin cell energy metabolism
in vivo
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE Norepinephrine; Epinephrine; Dense core vesicle; Synaptic vesicle;
Mitochondria
ID TYROSINE-HYDROXYLASE ACTIVITY; INDUCED INSULIN-RESISTANCE; TARGETED
ABLATION; NEUROTRANSMITTER RELEASE; SYNAPTIC-TRANSMISSION; SECRETORY
VESICLES; SECRETOGRANIN-III; OSMOTIC-PRESSURE; AXONAL-TRANSPORT;
ADRENAL-MEDULLA
AB Chromogranin A (CgA) is a prohormone and granulogenic factor in neuroendocrine tissues with a regulated secretory pathway. The impact of CgA depletion on secretory granule formation has been previously demonstrated in cell culture. However, studies linking the structural effects of CgA deficiency with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not previously been reported. Adrenomedullary content of the secreted adrenal catecholamines norepinephrine (NE) and epinephrine (EPI) was decreased 30-40 % in Chga-KO mice. Quantification of NE and EPI-storing dense core (DC) vesicles (DCV) revealed decreased DCV numbers in chromaffin cells in Chga-KO mice. For both cell types, the DCV diameter in Chga-KO mice was less (100-200 nm) than in WT mice (200-350 nm). The volume density of the vesicle and vesicle number was also lower in Chga-KO mice. Chga-KO mice showed an similar to 47 % increase in DCV/DC ratio, implying vesicle swelling due to increased osmotically active free catecholamines. Upon challenge with 2 U/kg insulin, there was a diminution in adrenomedullary EPI, no change in NE and a very large increase in the EPI and NE precursor dopamine (DA), consistent with increased catecholamine biosynthesis during prolonged secretion. We found dilated mitochondrial cristae, endoplasmic reticulum and Golgi complex, as well as increased synaptic mitochondria, synaptic vesicles and glycogen granules in Chga-KO mice compared to WT mice, suggesting that decreased granulogenesis and catecholamine storage in CgA-deficient mouse adrenal medulla is compensated by increased VMAT-dependent catecholamine update into storage vesicles, at the expense of enhanced energy expenditure by the chromaffin cell.
C1 [Pasqua, Teresa; Bandyopadhyay, Gautam K.; Biswas, Angshuman; Mahata, Sushil K.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Mahata, Sumana] CALTECH, Pasadena, CA 91125 USA.
[Perkins, Guy A.] Natl Ctr Microscopy & Imaging Res, San Diego, CA USA.
[Sinha-Hikim, Amiya P.] Charles R Drew Univ Med & Sci, 1621 E 120th St, Los Angeles, CA 90059 USA.
[Sinha-Hikim, Amiya P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Goldstein, David S.] NINDS, IRP, Clin Neurocardiol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Eiden, Lee E.] NIMH, IRP, Sect Mol Neurosci, Bethesda, MD 20892 USA.
[Mahata, Sushil K.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Mahata, Sushil K.] Univ Calif San Diego, Dept Med, Metab Physiol & Ultrastruct Biol Lab, 9500 Gilman Dr, La Jolla, CA 92093 USA.
RP Mahata, SK (reprint author), Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.; Mahata, SK (reprint author), VA San Diego Healthcare Syst, San Diego, CA USA.; Mahata, SK (reprint author), Univ Calif San Diego, Dept Med, Metab Physiol & Ultrastruct Biol Lab, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM smahata@ucsd.edu
FU Department of Veterans Affairs; UCSD [RO091B]
FX Transmission Electron Microscopy was conducted at the Cellular &
Molecular Medicine Electron Microscopy Core Facility at UCSD. A Research
Career Scientist Award from the Department of Veterans Affairs supports
S.K.M. Mahata's personal fund and UCSD Academic Senate Grant (RO091B)
supported this work.
NR 84
TC 5
Z9 5
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD MAR
PY 2016
VL 363
IS 3
BP 693
EP 712
DI 10.1007/s00441-015-2316-3
PG 20
WC Cell Biology
SC Cell Biology
GA DE9JZ
UT WOS:000370954400008
PM 26572539
ER
PT J
AU Pasqua, T
Mahata, S
Bandyopadhyay, GK
Biswas, A
Perkins, GA
Sinha-Hikim, AP
Goldstein, DS
Eiden, LE
Mahata, SK
AF Pasqua, Teresa
Mahata, Sumana
Bandyopadhyay, Gautam K.
Biswas, Angshuman
Perkins, Guy A.
Sinha-Hikim, Amiya P.
Goldstein, David S.
Eiden, Lee E.
Mahata, Sushil K.
TI Impact of Chromogranin A deficiency on catecholamine storage,
catecholamine granule morphology and chromaffin cell energy metabolism
in vivo (vol 363, pg 693, 2016)
SO CELL AND TISSUE RESEARCH
LA English
DT Correction
C1 [Pasqua, Teresa; Bandyopadhyay, Gautam K.; Biswas, Angshuman; Mahata, Sushil K.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Mahata, Sumana] CALTECH, Pasadena, CA 91125 USA.
[Perkins, Guy A.] Natl Ctr Microscopy & Imaging Res, San Diego, CA USA.
[Sinha-Hikim, Amiya P.] Charles R Drew Univ Med & Sci, 1621 E 120th St, Los Angeles, CA 90059 USA.
[Sinha-Hikim, Amiya P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Goldstein, David S.] NINDS, IRP, Clin Neurocardiol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Eiden, Lee E.] NIMH, IRP, Sect Mol Neurosci, Bethesda, MD 20892 USA.
[Mahata, Sushil K.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Mahata, Sushil K.] Univ Calif San Diego, Metab Physiol & Ultrastruct Biol Lab, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
RP Mahata, SK (reprint author), Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.; Mahata, SK (reprint author), VA San Diego Healthcare Syst, San Diego, CA USA.; Mahata, SK (reprint author), Univ Calif San Diego, Metab Physiol & Ultrastruct Biol Lab, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM smahata@caltech.edu; smahata@ucsd.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD MAR
PY 2016
VL 363
IS 3
BP 823
EP 823
DI 10.1007/s00441-016-2362-5
PG 1
WC Cell Biology
SC Cell Biology
GA DE9JZ
UT WOS:000370954400017
PM 26809511
ER
PT J
AU Wickner, RB
Kelly, AC
AF Wickner, Reed B.
Kelly, Amy C.
TI Prions are affected by evolution at two levels
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Amyloid; Ure2p; Sup35p; HET-s; Rnq1; Parallel in-register beta sheet
ID CHRONIC WASTING DISEASE; WHITE-TAILED DEER; HET-S PRION; BOVINE
SPONGIFORM ENCEPHALOPATHY; BETA-SHEET STRUCTURE;
CREUTZFELDT-JAKOB-DISEASE; 2-MU-M CIRCLE PLASMID; CHAIN RELEASE FACTOR;
MESSENGER-RNA DECAY; SACCHAROMYCES-CEREVISIAE
AB Prions, infectious proteins, can transmit diseases or be the basis of heritable traits (or both), mostly based on amyloid forms of the prion protein. A single protein sequence can be the basis for many prion strains/variants, with different biological properties based on different amyloid conformations, each rather stably propagating. Prions are unique in that evolution and selection work at both the level of the chromosomal gene encoding the protein, and on the prion itself selecting prion variants. Here, we summarize what is known about the evolution of prion proteins, both the genes and the prions themselves. We contrast the one known functional prion, [Het-s] of Podospora anserina, with the known disease prions, the yeast prions [PSI+] and [URE3] and the transmissible spongiform encephalopathies of mammals.
C1 [Wickner, Reed B.; Kelly, Amy C.] NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
[Kelly, Amy C.] ARS, NCAUR, USDA, 1815 N Univ St, Peoria, IL 61604 USA.
RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov; amy.kelly@ars.usda.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This work was supported in part by the Intramural Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
NR 165
TC 2
Z9 2
U1 12
U2 27
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAR
PY 2016
VL 73
IS 6
BP 1131
EP 1144
DI 10.1007/s00018-015-2109-6
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DF1DQ
UT WOS:000371079200002
PM 26713322
ER
PT J
AU Le Couteur, DG
Solon-Biet, S
Cogger, VC
Mitchell, SJ
Senior, A
de Cabo, R
Raubenheimer, D
Simpson, SJ
AF Le Couteur, David G.
Solon-Biet, Samantha
Cogger, Victoria C.
Mitchell, Sarah J.
Senior, Alistair
de Cabo, Rafael
Raubenheimer, David
Simpson, Stephen J.
TI The impact of low-protein high-carbohydrate diets on aging and lifespan
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Aging; Ageing; Caloric restriction; Geometric Framework; CPC diet;
Dietary protein; Dietary carbohydrate
ID SHORT-TERM CALORIE; MITOCHONDRIAL OXIDATIVE STRESS; SKELETAL-MUSCLE
MITOCHONDRIA; ESSENTIAL AMINO-ACIDS; TEPHRITID FRUIT-FLY; AGE-RELATED
DISEASE; DROSOPHILA-MELANOGASTER; GEOMETRIC ANALYSIS; GRADED-LEVELS;
ANASTREPHA-LUDENS
AB Most research on nutritional effects on aging has focussed on the impact of manipulating single dietary factors such as total calorie intake or each of the macronutrients individually. More recent studies using a nutritional geometric approach called the Geometric Framework have facilitated an understanding of how aging is influenced across a landscape of diets that vary orthogonally in macronutrient and total energy content. Such studies have been performed using ad libitum feeding regimes, thus taking into account compensatory feeding responses that are inevitable in a non-constrained environment. Geometric Framework studies on insects and mice have revealed that diets low in protein and high in carbohydrates generate longest lifespans in ad libitum-fed animals while low total energy intake (caloric restriction by dietary dilution) has minimal effect. These conclusions are supported indirectly by observational studies in humans and a heterogeneous group of other types of interventional studies in insects and rodents. Due to compensatory feeding for protein dilution, low-protein, high-carbohydrate diets are often associated with increased food intake and body fat, a phenomenon called protein leverage. This could potentially be mitigated by supplementing these diets with interventions that influence body weight through physical activity and ambient temperature.
C1 [Le Couteur, David G.; Solon-Biet, Samantha; Cogger, Victoria C.; Senior, Alistair; Raubenheimer, David; Simpson, Stephen J.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia.
[Le Couteur, David G.; Solon-Biet, Samantha; Cogger, Victoria C.] Concord Hosp, Ageing & Alzheimers Inst, Concord 2139, Australia.
[Le Couteur, David G.; Solon-Biet, Samantha; Cogger, Victoria C.] Concord Hosp, ANZAC Res Inst, Concord 2139, Australia.
[Mitchell, Sarah J.] Natl Inst ON Aging, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Senior, Alistair; de Cabo, Rafael] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
[Raubenheimer, David; Simpson, Stephen J.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia.
[Raubenheimer, David] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia.
RP Simpson, SJ (reprint author), Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia.; Simpson, SJ (reprint author), Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia.
EM david.lecouteur@sydney.edu.au; stephen.simpson@sydney.edu.au
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Simpson, Stephen
J./0000-0003-0256-7687; , rafael/0000-0003-2830-5693
FU Aging and Alzheimers Research Institute; NHMRC [571328, 1084267];
Intramural Program of the National Institute on Aging, NIH
FX We acknowledge funding from the Aging and Alzheimers Research Institute,
NHMRC grants #571328 and #1084267 and our co-authors in studies cited in
this review. RdC and SJM are funded by the Intramural Program of the
National Institute on Aging, NIH.
NR 128
TC 14
Z9 15
U1 39
U2 73
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAR
PY 2016
VL 73
IS 6
BP 1237
EP 1252
DI 10.1007/s00018-015-2120-y
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DF1DQ
UT WOS:000371079200009
PM 26718486
ER
PT J
AU Mason, JM
Randall, TA
Frydrychova, RC
AF Mason, James M.
Randall, Thomas A.
Frydrychova, Radmila Capkova
TI Telomerase lost?
SO CHROMOSOMA
LA English
DT Review
ID END-PROTECTION PROBLEM; SHORT TANDEM REPEATS; BOMBYX-MORI; ORTHOPTERA
TETTIGONIIDAE; REVERSE-TRANSCRIPTASE; RETROTRANSPOSON FAMILIES; TERMINAL
HETEROCHROMATIN; RHYNCHOSCIARA DIPTERA; DROSOPHILA TELOMERES; CHROMOSOME
ENDS
AB Telomerase and telomerase-generated telomeric DNA sequences are widespread throughout eukaryotes, yet they are not universal. Neither telomerase nor the simple DNA repeats associated with telomerase have been found in some plant and animal species. Telomerase was likely lost from Diptera before the divergence of Diptera and Siphonaptera, some 260 million years ago. Even so, Diptera is one of the most successful animal orders, making up 11 % of known animal species. In addition, many species of Coleoptera and Hemiptera seem to lack canonical telomeric repeats at their chromosome ends. These and other insects that appear to lack canonical terminal repeat sequences account for another 10-15 % of animal species. Conversely, the silk moth Bombyx mori maintains canonical telomeric sequences at its chromosome ends but seems to lack a functional telomerase. We speculate that a telomere-specific capping complex that recognizes the telomeric repeats and protects chromosome ends is the determining factor in maintaining canonical telomeric sequences and that telomerase is an early and efficacious mechanism for satisfying the needs of capping complex. There are alternate mechanisms for maintaining chromosome ends that do not depend on telomerase, such as recombination found in some human cancer cells and yeast mutants. These mechanisms may maintain the canonical telomeric repeats or allow the terminal sequence to evolve when specificity of the capping complex for terminal repeat sequences is weak.
C1 [Mason, James M.] NIEHS, Lab Genome Integr & Struct Biol, POB 12233, Res Triangle Pk, NC 27709 USA.
[Randall, Thomas A.] NIEHS, Integrat Bioinformat, POB 12233, Res Triangle Pk, NC 27709 USA.
[Frydrychova, Radmila Capkova] Biol Ctr AS CR, Inst Entomol, Ceske Budejovice, Czech Republic.
RP Frydrychova, RC (reprint author), Biol Ctr AS CR, Inst Entomol, Ceske Budejovice, Czech Republic.
EM Radmila.Frydrychova@hotmail.com
FU Grant Agency of the Czech Republic [14-07172S]; European Union [316304];
Grant Agency of the University of South Bohemia [052/2013/P,
038/2014/P]; NIH, National Institute of Environmental Health Sciences
FX This work was supported by Grant No. 14-07172S from the Grant Agency of
the Czech Republic (to RCF). We acknowledge the use of research
infrastructure that has received funding from the European Union Seventh
Framework Programme (FP7/2007-2013) under grant agreement No. 316304 (to
RCF). Additional support was provided from Grant no. 052/2013/P and no.
038/2014/P of the Grant Agency of the University of South Bohemia (to
RCF) and by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (to JMM and TAR).
NR 80
TC 7
Z9 7
U1 8
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-5915
EI 1432-0886
J9 CHROMOSOMA
JI Chromosoma
PD MAR
PY 2016
VL 125
IS 1
BP 65
EP 73
DI 10.1007/s00412-015-0528-7
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DE9KB
UT WOS:000370954600006
PM 26162505
ER
PT J
AU Novelle, MG
Ali, A
Dieguez, C
Bernier, M
de Cabo, R
AF Novelle, Marta G.
Ali, Ahmed
Dieguez, Carlos
Bernier, Michel
de Cabo, Rafael
TI Metformin: A Hopeful Promise in Aging Research
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; HER-2/NEU TRANSGENIC MICE; EXTENDS LIFE-SPAN;
INHIBITS HEPATIC GLUCONEOGENESIS; FEMALE SHR MICE;
CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; CALORIC RESTRICTION;
RESPIRATORY-CHAIN; C.-ELEGANS
AB Even though the inevitable process of aging by itself cannot be considered a disease, it is directly linked to life span and is the driving force behind all age-related diseases. It is an undisputable fact that age-associated diseases are among the leading causes of death in the world, primarily in industrialized countries. During the last several years, an intensive search of antiaging treatments has led to the discovery of a variety of drugs that promote health span and/or life extension. The biguanide compound metformin is widely used for treating people with type 2 diabetes and appears to show protection against cancer, inflammation, and age-related pathologies. Here, we summarize the recent developments about metformin use in translational aging research and discuss its role as a potential geroprotector.
C1 [Novelle, Marta G.; Ali, Ahmed; Bernier, Michel; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Novelle, Marta G.] Univ Santiago de Compostela, Inst Invest Sanitaria, Res Ctr Mol Med & Chron Dis CIMUS, Santiago De Compostela 15782, Spain.
[Novelle, Marta G.; Dieguez, Carlos] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela 15706, Spain.
RP de Cabo, R (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; NOVELLE, MARTA
G/0000-0003-0285-7182; , rafael/0000-0003-2830-5693
FU National Institute on Aging, National Institutes of Health
FX This work is supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. CIBER de
Fisiopatologia de la Obesidad y Nutricion is an initiative of ISCIII.
The funding agency had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 110
TC 3
Z9 3
U1 1
U2 15
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD MAR
PY 2016
VL 6
IS 3
AR a025932
DI 10.1101/cshperspect.a025932
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DF2LX
UT WOS:000371175800005
PM 26931809
ER
PT J
AU Teumer, A
Tin, A
Sorice, R
Gorski, M
Yeo, NC
Chu, AY
Li, M
Li, Y
Mijatovic, V
Ko, YA
Taliun, D
Luciani, A
Chen, MH
Yang, Q
Foster, MC
Olden, M
Hiraki, LT
Tayo, BO
Fuchsberger, C
Dieffenbach, AK
Shuldiner, AR
Smith, AV
Zappa, AM
Lupo, A
Kollerits, B
Ponte, B
Stengel, B
Kramer, BK
Paulweber, B
Mitchell, BD
Hayward, C
Helmer, C
Meisinger, C
Gieger, C
Shaffer, CM
Muller, C
Langenberg, C
Ackermann, D
Siscovick, D
Boerwinkle, E
Kronenberg, F
Ehret, GB
Homuth, G
Waeber, G
Navis, G
Gambaro, G
Malerba, G
Eiriksdottir, G
Li, G
Wichmann, HE
Grallert, H
Wallaschofski, H
Volzke, H
Brenner, H
Kramer, H
Leach, IM
Rudan, I
Hillege, HL
Beckmann, JS
Lambert, JC
Luan, JA
Zhao, JH
Chalmers, J
Coresh, J
Denny, JC
Butterbach, K
Launer, LJ
Ferrucci, L
Kedenko, L
Haun, M
Metzger, M
Woodward, M
Hoffman, MJ
Nauck, M
Waldenberger, M
Pruijm, M
Bochud, M
Rheinberger, M
Verweij, N
Wareham, NJ
Endlich, N
Soranzo, N
Polasek, O
van der Harst, P
Pramstaller, PP
Vollenweider, P
Wild, PS
Gansevoort, RT
Rettig, R
Biffar, R
Carroll, RJ
Katz, R
Loos, RJF
Hwang, SJ
Coassin, S
Bergmann, S
Rosas, SE
Stracke, S
Harris, TB
Corre, T
Zeller, T
Illig, T
Aspelund, T
Tanaka, T
Lendeckel, U
Volker, U
Gudnason, V
Chouraki, V
Koenig, W
Kutalik, Z
O'Connell, JR
Parsa, A
Heid, IM
Paterson, AD
de Boer, IH
Devuyst, O
Lazar, J
Endlich, K
Susztak, K
Tremblay, J
Hamet, P
Jacob, HJ
Boger, CA
Fox, CS
Pattaro, C
Kottgen, A
AF Teumer, Alexander
Tin, Adrienne
Sorice, Rossella
Gorski, Mathias
Yeo, Nan Cher
Chu, Audrey Y.
Li, Man
Li, Yong
Mijatovic, Vladan
Ko, Yi-An
Taliun, Daniel
Luciani, Alessandro
Chen, Ming-Huei
Yang, Qiong
Foster, Meredith C.
Olden, Matthias
Hiraki, Linda T.
Tayo, Bamidele O.
Fuchsberger, Christian
Dieffenbach, Aida Karina
Shuldiner, Alan R.
Smith, Albert V.
Zappa, Allison M.
Lupo, Antonio
Kollerits, Barbara
Ponte, Belen
Stengel, Benedicte
Kraemer, Bernhard K.
Paulweber, Bernhard
Mitchell, Braxton D.
Hayward, Caroline
Helmer, Catherine
Meisinger, Christa
Gieger, Christian
Shaffer, Christian M.
Mueller, Christian
Langenberg, Claudia
Ackermann, Daniel
Siscovick, David
Boerwinkle, Eric
Kronenberg, Florian
Ehret, Georg B.
Homuth, Georg
Waeber, Gerard
Navis, Gerjan
Gambaro, Giovanni
Malerba, Giovanni
Eiriksdottir, Gudny
Li, Guo
Wichmann, H. Erich
Grallert, Harald
Wallaschofski, Henri
Voelzke, Henry
Brenner, Herrmann
Kramer, Holly
Leach, I. Mateo
Rudan, Igor
Hillege, Hans L.
Beckmann, Jacques S.
Lambert, Jean Charles
Luan, Jian'an
Zhao, Jing Hua
Chalmers, John
Coresh, Josef
Denny, Joshua C.
Butterbach, Katja
Launer, Lenore J.
Ferrucci, Luigi
Kedenko, Lyudmyla
Haun, Margot
Metzger, Marie
Woodward, Mark
Hoffman, Matthew J.
Nauck, Matthias
Waldenberger, Melanie
Pruijm, Menno
Bochud, Murielle
Rheinberger, Myriam
Verweij, Niek
Wareham, Nicholas J.
Endlich, Nicole
Soranzo, Nicole
Polasek, Ozren
van der Harst, Pim
Pramstaller, Peter Paul
Vollenweider, Peter
Wild, Philipp S.
Gansevoort, Ron T.
Rettig, Rainer
Biffar, Reiner
Carroll, Robert J.
Katz, Ronit
Loos, Ruth J. F.
Hwang, Shih-Jen
Coassin, Stefan
Bergmann, Sven
Rosas, Sylvia E.
Stracke, Sylvia
Harris, Tamara B.
Corre, Tanguy
Zeller, Tanja
Illig, Thomas
Aspelund, Thor
Tanaka, Toshiko
Lendeckel, Uwe
Volker, Uwe
Gudnason, Vilmundur
Chouraki, Vincent
Koenig, Wolfgang
Kutalik, Zoltan
O'Connell, Jeffrey R.
Parsa, Afshin
Heid, Iris M.
Paterson, Andrew D.
de Boer, Ian H.
Devuyst, Olivier
Lazar, Jozef
Endlich, Karlhans
Susztak, Katalin
Tremblay, Johanne
Hamet, Pavel
Jacob, Howard J.
Boeger, Carsten A.
Fox, Caroline S.
Pattaro, Cristian
Koettgen, Anna
CA DCCT EDIC
TI Genome-wide Association Studies Identify Genetic Loci Associated With
Albuminuria in Diabetes
SO DIABETES
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; RISK POPULATION COHORTS; KIDNEY-DISEASE;
COLLABORATIVE METAANALYSIS; MODULATES PROTEINURIA; EXPRESSION;
HERITABILITY; MORTALITY; INSIGHTS; RAB38
AB Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 x 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 x 10(-7)) and 13% for RAB38/CTSC (P = 5.8 x 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.
C1 [Teumer, Alexander; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Teumer, Alexander; Voelzke, Henry; Nauck, Matthias; Volker, Uwe] German Ctr Cardiovascular Res DZHK, Partner Site Greifswald, Greifswald, Germany.
[Tin, Adrienne; Li, Man; Coresh, Josef; Woodward, Mark; Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Sorice, Rossella] CNR, Inst Genet & Biophys, Adriano Buzzati Traverso, Naples, Italy.
[Gorski, Mathias; Olden, Matthias; Heid, Iris M.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
[Gorski, Mathias; Boeger, Carsten A.] Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
[Yeo, Nan Cher; Hoffman, Matthew J.; Jacob, Howard J.] Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
[Chu, Audrey Y.] Brigham & Womens Hosp, Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Chu, Audrey Y.; Hwang, Shih-Jen; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Chu, Audrey Y.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Li, Yong; Koettgen, Anna] Univ Freiburg, Med Ctr, Renal Div, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Mijatovic, Vladan; Malerba, Giovanni] Univ Verona, Dept Life & Reprod Sci, I-37100 Verona, Italy.
[Ko, Yi-An; Susztak, Katalin] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Taliun, Daniel; Fuchsberger, Christian; Pramstaller, Peter Paul; Pattaro, Cristian] Univ Lubeck, Ctr Biomed, European Acad Bozen Bolzano EURAC, Bolzano, Italy.
[Luciani, Alessandro; Devuyst, Olivier] Univ Zurich, Inst Physiol, Mech Inherited Kidney Disorders Grp, Zurich, Switzerland.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Chen, Ming-Huei; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Foster, Meredith C.] Tufts Med Ctr, Boston, MA USA.
[Olden, Matthias] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
[Hiraki, Linda T.; Paterson, Andrew D.] Hosp Sick Children, Res Inst, Genet & Genome Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Tayo, Bamidele O.; Kramer, Holly] Loyola Univ Chicago, Maywood, IL USA.
[Dieffenbach, Aida Karina; Brenner, Herrmann; Butterbach, Katja] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Dieffenbach, Aida Karina] German Canc Consortium DKTK, Heidelberg, Germany.
[Shuldiner, Alan R.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Parsa, Afshin] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Smith, Albert V.; Eiriksdottir, Gudny; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Zappa, Allison M.] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA.
[Lupo, Antonio] Univ Verona, Renal Unit, Dept Med, I-37100 Verona, Italy.
[Kollerits, Barbara; Kronenberg, Florian; Haun, Margot; Coassin, Stefan] Med Univ Innsbruck, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
[Ponte, Belen] Univ Hosp Geneva, Nephrol Div, Dept Specialties Internal Med, Geneva, Switzerland.
[Stengel, Benedicte; Metzger, Marie] Ctr Rech Epidemiol & Sante Populat CESP Team 5, INSERM U 1018, Villejuif, France.
[Stengel, Benedicte; Metzger, Marie] Univ Versailles, Univ Paris Sud, Ctr Rech Epidemiol & Sante Populat CESP Team 5, UMRS 1018, St Quentin en Yvelines, France.
[Kraemer, Bernhard K.] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany.
[Paulweber, Bernhard; Kedenko, Lyudmyla] Paracelsus Med Univ, Salzburger Landesklin, Dept Internal Med 1, Salzburg, Austria.
[Hayward, Caroline] Univ Edinburgh, Human Genet Unit, Inst Genet & Mol Med, Med Res Council, Edinburgh EH8 9YL, Midlothian, Scotland.
[Helmer, Catherine] Bordeaux Univ, ISPED, INSERM U897, Bordeaux, France.
[Meisinger, Christa; Grallert, Harald; Waldenberger, Melanie; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Gieger, Christian; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Shaffer, Christian M.; Denny, Joshua C.; Carroll, Robert J.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Mueller, Christian; Zeller, Tanja] Univ Heart Ctr Hamburg, Hamburg, Germany.
[Mueller, Christian; Zeller, Tanja] German Ctr Cardiovasc Res DZHK eV, Partner Site Hamburg, Kiel, Germany.
[Langenberg, Claudia; Luan, Jian'an; Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Univ Cambridge, Sch Clin Med, Epidemiol Unit, Med Res Council, Cambridge, England.
[Ackermann, Daniel] Univ Hosp Bern, Univ Clin Nephrol Hypertens & Clin Pharmacol, Inselspital, CH-3010 Bern, Switzerland.
[Ackermann, Daniel] Univ Bern, Bern, Switzerland.
[Siscovick, David; Li, Guo] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Siscovick, David; Li, Guo] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[DCCT EDIC] Epidemiol Diabet Intervent & Complicat Res Grp, Diabet Control & Complicat Trial, Madras, Tamil Nadu, India.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Ehret, Georg B.] Univ Hosp Geneva, Dept Specialties Internal Med, Cardiol, Geneva, Switzerland.
[Homuth, Georg; Volker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
[Waeber, Gerard; Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland.
[Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Div Nephrol, Dept Internal Med & Med Specialties, Columbus Gemelli Univ, Rome, Italy.
[Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, D-80290 Munich, Germany.
[Grallert, Harald] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Grallert, Harald] German Ctr Diabet Res DZD, Neuherberg, Germany.
[Wallaschofski, Henri; Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Leach, I. Mateo; Verweij, Niek] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Hillege, Hans L.; van der Harst, Pim; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Nephrol, Groningen, Netherlands.
[Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne, Lausanne, Switzerland.
[Beckmann, Jacques S.; Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Lambert, Jean Charles; Chouraki, Vincent] Inst Pasteur, INSERM UMR 1167 Risk Factors & Mol Determinants A, F-59019 Lille, France.
[Chalmers, John; Woodward, Mark] Univ Sydney, George Inst Global Hlth, Camperdown, NSW, Australia.
[Coresh, Josef] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
RP Teumer, A (reprint author), Univ Med Greifswald, Inst Community Med, Greifswald, Germany.; Teumer, A (reprint author), German Ctr Cardiovascular Res DZHK, Partner Site Greifswald, Greifswald, Germany.
RI Brenner, Hermann/B-4627-2017; Beckmann, Jacques S /A-9772-2008;
Woodward, Mark/D-8492-2015; Kronenberg, Florian/B-1736-2008; Stengel,
Benedicte/G-5730-2015; Cossette, Suzanne/I-8008-2016; Lambert,
jean-charles/A-9553-2014; Li, Yong/A-6283-2011; Bochud,
Murielle/A-3981-2010; Waldenberger, Melanie/B-5355-2014; Colaus,
PsyColaus/K-6607-2013; Verweij, Niek/A-4499-2017; HELMER,
Catherine/I-6581-2015; Grallert, Harald/B-3424-2013; Polasek,
Ozren/B-6002-2011; Paterson, Andrew/A-4088-2011; Smith, Albert
Vernon/K-5150-2015;
OI Brenner, Hermann/0000-0002-6129-1572; Beckmann, Jacques S
/0000-0002-9741-1900; Kronenberg, Florian/0000-0003-2229-1120; Lambert,
jean-charles/0000-0003-0829-7817; Bochud, Murielle/0000-0002-5727-0218;
Waldenberger, Melanie/0000-0003-0583-5093; HELMER,
Catherine/0000-0002-5169-7421; Polasek, Ozren/0000-0002-5765-1862;
Paterson, Andrew/0000-0002-9169-118X; Verweij, Niek/0000-0002-4303-7685;
Smith, Albert Vernon/0000-0003-1942-5845; Gieger,
Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544;
Mitchell, Braxton/0000-0003-4920-4744; Li, Yong/0000-0003-2651-8791
FU National Foundation for Alzheimer's disease and related disorders;
Institut Pasteur de Lille; Centre National de Genotypage; Fondation pour
la Recherche Medicale; Caisse Nationale Maladie des Travailleurs
Salaries; Direction Generale de la Sante; MGEN; Institut de la
Longevite; Agence Francaise de Securite Sanitaire des Produits de Sante;
Aquitaine and Bourgogne Regional Councils; Fondation de France; French
Ministry of Research/INSERM "Cohortes et collections de donnees
biologiques" programme; Eisai; Prognomix, Inc.; Genome Quebec; Canadian
Institutes of Health Research (CIHR); Les Laboratoires Servier, France;
National Health and Medical Research Council of Australia; National
Institutes of Health (NIH) [N01-AG-1-2100, HHSN271201200022C]; National
Institute on Aging Intramural Research Program; Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament); NIH
[R01-AG-18728, R01-HL-088119, U01-GM-074518-04, U01-HL0-72515-06,
U01-HL0-84756, K12-RR0-23250, HHSN268200625226C, UL1-RR0-25005, 2R01LM0-
10098, R01-DK0-76077, DK0-87635]; Baltimore Veterans Administration
Medical Center Geriatric Research Education and Clinical Center; Paul
Beeson Physician Faculty Scholars in Aging Research Program;
Mid-Atlantic Nutrition Obesity Research Center [P30-DK0-72488]; National
Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human
Genome Research Institute [U01-HG0-04402]; NIH Roadmap for Medical
Research; Emmy Noether Programme of the German Research Foundation [KO
3598/2-1]; Intramural Research Program of the NIH, National Institute on
Aging; National Center for Research Resources [M01-RR-00425]; National
Institute of Diabetes and Digestive and Kidney Diseases [DK-063491];
GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne; Swiss
National Science Foundation [33CSCO-122661, 33CM30-124087,
310030_146490]; Medical Research Council U.K.; Ministry of Science,
Education and Sport of the Republic of Croatia [108-1080315-0302];
Medical Research Council; Cancer Research U.K.; Baden-Wurttemberg State
Ministry of Science, Research and Arts; German Federal Ministry of
Education and Research [01ET0717]; CHANCES (Consortium on Health and
Ageing: Network of Cohorts in Europe and the United States) project
[242244]; Medical Research Council [MC_U106179471]; Wellcome Trust;
National Heart, Lung and Blood Institute Framingham Heart Study
[N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans
Endowment of the Boston University School of Medicine Department of
Medicine and Boston Medical Center; Dr. Robert Pfleger-Stiftung; MSD
Stipend Diabetes; University Hospital of Regensburg; KfH Stiftung
Praventivmedizin e.V.; Else Kroner-Fresenius-Stiftung [2012_A147];
University Hospital Regensburg; Else Kroner-Fresenius Stiftung
[2012_A147, P48/08//A11/08]; Wellcome Trust [WT098051, WT091310];
European Union [257082, HEALTH-F5-2011-282510, LSHG-CT-2006-018947];
Munich Center of Health Sciences (MC Health) as part of LMUinnovativ;
Regensburg University Medical Center, Germany; F4 by the University of
Ulm, Germany; Helmholtz Zentrum Munchen; German Research Center for
Environmental Health; German Federal Ministry of Education and Research;
State of Bavaria; University of Regensburg for the Department of
Epidemiology and Preventive Medicine at the Regensburg University
Medical Center; Netherlands Organization of Scientific Research NWO
[175.010.2007.006]; Economic Structure Enhancing Fund (FES) of the Dutch
government; Ministry of Economic Affairs; Ministry of Education, Culture
and Science; Ministry for Health, Welfare and Sports; Northern
Netherlands Collaboration of Provinces; Province of Groningen;
University Medical Center Groningen; University of Groningen; Dutch
Kidney Foundation; Dutch Diabetes Research Foundation; Ministry of
Health and Department of Educational Assistance; University and Research
of the Autonomous Province of Bolzano; South Tyrolean Sparkasse
Foundation; Dutch Kidney Foundation [E033]; EU [FP-6 LSHM CT 2006
037697]; Netherlands Organisation for Health Research and Development
NWO-Groot grant [175.010.2007.006]; NWO VENI [916.761.70]; ZonMw grant
[90.700.441]; Dutch Inter University Cardiology Institute Netherlands
(ICIN); Kamillo Eisner Stiftung; Genomics of Lipidassociated Disorders
(GOLD) of the "Austrian Genome Research Programme GEN-AU"; Federal
Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403,
03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal
State of Mecklenburg-West Pomerania; network "Greifswald Approach to
Individualized Medicine (GANI_MED)" - Federal Ministry of Education and
Research [03IS2061A]; Siemens Healthcare, Erlangen, Germany; Federal
State of Mecklenburg-West Pomerania; Lausanne University Hospital;
Geneva University Hospital; Bern University Hospital, Switzerland; Swiss
School of Public Health Plus (SSPH+); National Institute of General
Medical Sciences (NIGMS) [RC2-GM092318]; Electronic Medical Records and
Genomics (eMERGE) Network; National Human Genome Research Institute;
NIGMS [U01-HG04603]; European Community [305608]; [R01-HL0-87641];
[R01-HL-9367]; [R01-HL0-86694]; [2R01-069321]; [N01-HC-85079];
[N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083];
[N01-HC-85084]; [N01-HC-85085]; [N01-HC-85086]; [N01-HC-35129];
[N01-HC-15103]; [N01-HC-55222]; [N01-HC-75150]; [N01-HC-45133];
[U01-HL0-80295]; [R01-HL0-87652]
FX 3C Study: The work was made possible by the generous participation of
the control subjects, the patients, and their families. The authors
thank Dr. Anne Boland, Centre National de Genotypage, for her technical
help in preparing the DNA samples for analyses. This work was supported
by the National Foundation for Alzheimer's disease and related
disorders, the Institut Pasteur de Lille, and the Centre National de
Genotypage. The Three-City (3C) Study was performed as part of a
collaboration between INSERM, the Victor Segalen Bordeaux II University,
and Sanofi-Synthelabo. The Fondation pour la Recherche Medicale funded
the preparation and initiation of the study. The 3C Study was also
funded by the Caisse Nationale Maladie des Travailleurs Salaries,
Direction Generale de la Sante, MGEN, Institut de la Longevite, Agence
Francaise de Securite Sanitaire des Produits de Sante, the Aquitaine and
Bourgogne Regional Councils, Fondation de France, and the joint French
Ministry of Research/INSERM "Cohortes et collections de donnees
biologiques" programme. Lille Genopole received an unconditional grant
from Eisai.; ADVANCE Study: The genetic epidemiological work was funded
by Prognomix, Inc., and by grants from Genome Quebec and Canadian
Institutes of Health Research (CIHR). The clinical study was managed by
The George Institute for Global Health (University of Sydney, Sydney,
New South Wales, Australia) with grants received from Les Laboratoires
Servier, France, and from the National Health and Medical Research
Council of Australia. The genotyping was performed at the genomic
platform of Centre de Recherche du Centre hospitalier de l'Universite de
Montreal (CRCHUM). The authors acknowledge the technical help of Carole
Long and Mounsif Haloui and the bioinformatic analyses performed by
Gilles Godefroid, Francois-Christophe Blanchet-Marois, and Francois
Harvey (CRCHUM, Universite de Montreal, Montreal, Quebec, Canada). Also
acknowledged are the members of the genetic substudy of ADVANCE, Stephen
Harrap (Department of Physiology, University of Melbourne, Melbourne,
Victoria, Australia) and Michel Marre (Diabetologie, Endocrinologie,
Nutrition at Hopital Bichat, Paris, France). M.W. did not participate in
animal experiments.; AGES Study: The study has been funded by National
Institutes of Health (NIH) contracts N01-AG-1-2100 and
HHSN271201200022C, the National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). The study is approved by the Icelandic
National Bioethics Committee, VSN: 00-063. The researchers are indebted
to the participants for their willingness to participate in the study.;
Amish Study: The authors thank the Amish research volunteers for their
long-standing partnership in research and the research staff at the
Amish Research Clinic for their hard work and dedication. The study is
supported by grants and contracts from the NIH, including R01-AG-18728
(Amish Longevity Study), R01-HL-088119 (Amish Calcification Study),
U01-GM-074518-04 (Pharmacogenomics of Anti-Platelet Intervention [PAPI]
Study), U01-HL0-72515-06 (Heredity and Phenotype Intervention [HAPI]
Study), U01-HL0-84756, and K12-RR0-23250 (University of Maryland
Multidisciplinary Clinical Research Career Development Program), the
University of Maryland General Clinical Research Center, grant
M01-RR-16500, the Baltimore Veterans Administration Medical Center
Geriatric Research Education and Clinical Center, and the Paul Beeson
Physician Faculty Scholars in Aging Research Program. Partial funding
was also provided by the Mid-Atlantic Nutrition Obesity Research Center
(P30-DK0-72488).; ARIC Study: The ARIC is carried out as a collaborative
study supported by National Heart, Lung, and Blood Institute contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C), R01-HL0-87641, R01-HL-9367
and R01-HL0-86694, National Human Genome Research Institute contract
U01-HG0-04402, and NIH contract HHSN268200625226C. The authors thank the
staff and participants of the ARIC study for their important
contributions. Infrastructure was partly supported by grant number
UL1-RR0-25005, a component of the NIH and NIH Roadmap for Medical
Research. This work as well as Y.L. and A.K. were supported by the Emmy
Noether Programme of the German Research Foundation (KO 3598/2-1 to
A.K.).; Baltimore Longitudinal Study of Aging (BLSA): BLSA was supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging.; CHS: The CHS research reported in this article was
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC-45133, and grant numbers
U01-HL0-80295 and R01-HL0-87652, with additional contribution from the
National Institute of Neurological Disorders and Stroke. A full list of
principal CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi. DNA handling and genotyping was supported
in part by National Center for Research Resources grant M01-RR-00425 to
the Cedars-Sinai General Clinical Research Center Genotyping core and
National Institute of Diabetes and Digestive and Kidney Diseases grant
DK-063491 to the Southern California Diabetes Endocrinology Research
Center.; CoLaus Study: The CoLaus study received financial contributions
from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne,
and the Swiss National Science Foundation (33CSCO-122661).;
CROATIA-Split Study: The CROATIA-Split study was supported through
grants from the Medical Research Council U.K., and Ministry of Science,
Education and Sport of the Republic of Croatia (No. 108-1080315-0302).
The authors acknowledge the invaluable contributions of the recruitment
team from the Croatian Centre for Global Health, University of Split,
the administrative teams in Croatia and Edinburgh, and the people of
Split. The SNP genotyping for the Split cohort was performed by AROS
Applied Biotechnology, Aarhus, Denmark.; EPIC-Norfolk Study: The
EPIC-Norfolk Study is supported by program grants from the Medical
Research Council, and Cancer Research U.K. The authors acknowledge the
contribution of the staff and participants of the EPIC-Norfolk Study.;
ESTHER Study: The authors thank all the individuals who took part in the
ESTHER (Epidemiological investigations of the chances of preventing,
recognizing early and optimally treating chronic diseases in an elderly
population) study and all the researchers, clinicians, technicians, and
administrative staff who have enabled this work to be carried out. This
work was supported in part by the Baden-Wurttemberg State Ministry of
Science, Research and Arts, by the German Federal Ministry of Education
and Research (grant number 01ET0717), and by the CHANCES (Consortium on
Health and Ageing: Network of Cohorts in Europe and the United States)
project funded in the Seventh Framework Programme of the
Directorate-General for Research and Innovation in the European
Commission (grant number 242244).; Fenland Study: The Fenland study is
funded by the Medical Research Council (MC_U106179471) and Wellcome
Trust. The authors are grateful to all the volunteers for their time and
help and to the general practitioners and practice staff for assistance
with recruitment. The authors thank the Fenland Study Investigators,
Fenland Study Co-ordination team, and the Epidemiology Field, Data and
Laboratory teams.; Framingham Heart Study: This research was conducted
in part using data and resources from the Framingham Heart Study of the
National Heart, Lung, and Blood Institute of the NIH and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource (SHARe) project.
This work was partially supported by the National Heart, Lung and Blood
Institute Framingham Heart Study (Contract No. N01-HC-25195) and its
contract with Affymetrix, Inc. for genotyping services (Contract No.
N02-HL-6-4278). A portion of this research used the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Boston University School of Medicine Department of Medicine and
Boston Medical Center.; GENDIAN Study: The support of the physicians,
the patients, and the staff of the Diabetes Zentrum Mergentheim (Head:
Prof. Dr. Thomas Haak), the diabetes outpatient clinic Dr. Nusser - Dr.
Kreisel, the dialysis centers KfH Amberg, KfH Bayreuth, KfH Deggendorf,
KfH Donauworth, KfH Freising, KfH Freyung, KfH Furth, KfH Hof, KfH
Ingolstadt, KfH Kelheim, KfH Munchen Elsenheimerstrasse, KfH
Munchen-Schwabing, KfH Neumarkt, KfH Neusass, KfH Oberschleissheim, KfH
Passau, KfH Plauen, KfH Regensburg Gunzstrasse, KfH Regensburg
Caritas-Krankenhaus, KfH Straubing, KfH Sulzbach-Rosenberg, KfH Weiden,
Dialysezentrum Augsburg Dr. Kirschner, Dialysezentrum Bad Alexandersbad,
KfH Bamberg, Dialysezentrum Emmering, Dialysezentrum Klinikum Landshut,
Dialysezentrum Landshut, Dialysezentrum Pfarrkirchen, Dialysezentrum
Schwandorf, Dr. Angela Gotz, the medical doctoral student Johanna
Christ, and the study nurse Ingrid Lugauer. The expert technical
assistance of Claudia Strohmeier is gratefully acknowledged. Phenotyping
was funded by the Dr. Robert Pfleger-Stiftung (C.A.B.), the MSD Stipend
Diabetes (C.A.B.), and the University Hospital of Regensburg (intramural
grant ReForM A to Dr. Angela Gotz, ReForM C to C.A.B.). Genome-wide
genotyping was funded by the KfH Stiftung Praventivmedizin e.V. (C.A.B.,
Dr. Jens Bruning), the Else Kroner-Fresenius-Stiftung (2012_A147 to C.
A. B. and I. M. H.), and the University Hospital Regensburg (C. A. B.).
Data analysis was funded by the Else Kroner-Fresenius Stiftung
(2012_A147 to I. M. H. and C. A. B. and P48/08//A11/08 to C. A. B. and
B. K. K.). GENDIAN Study Group: M. G., I. M. H., B. K. K., M. R.,
Michael Broll, Alexander Lammert, Jens Bruning, M. O., Klaus Stark,
Claudia Strohmeier, Simone Neumeier, Sarah Hufnagel, Petra Jackermeier,
Emilia Ruff, Johanna Christ, Peter Nurnberg, Thomas Haak, and C. A. B.;
INCIPE Study: The INCIPE (Initiative on Nephropathy, of relevance to
public health, which is Chronic, possibly in its Initial stages, and
carries a Potential risk of major clinical End-points) study was
cosponsored by Fondazione Cassa di Risparmio di Verona, Azienda
Ospedaliera di Verona, and University of Verona, Italy. N.S.'s research
is supported by the Wellcome Trust (grant codes WT098051 and WT091310),
the European Union Framework Program 7 (EPIGENESYS grant code 257082 and
BLUEPRINT grant code HEALTH-F5-2011-282510).; KORA-F3/KORA-F4 Study: The
genetic epidemiological work was funded by the Munich Center of Health
Sciences (MC Health) as part of LMUinnovativ, and by the Else
Kroner-Fresenius-Stiftung (P48/08//A11/08 to C. A. B., B. K. K. and
2012_A147 to C. A. B. and I. M. H.). The kidney parameter measurements
in F3 were funded by the Else Kroner-Fresenius-Stiftung (C. A. B., B. K.
K.) and the Regensburg University Medical Center, Germany, and in F4 by
the University of Ulm, Germany (W.K.). De novo genotyping as well as
partly genome-wide genotyping costs in F3 and F4 were funded by the Else
Kroner-Fresenius-Stiftung (C. A. B., B. K. K.). The KORA research
platform and the MONICA (Multinational MONItoring of Trends and
Determinants in CArdiovascular Disease) Augsburg studies were initiated
and financed by the Helmholtz Zentrum Munchen, German Research Center
for Environmental Health, by the German Federal Ministry of Education
and Research and by the State of Bavaria. Genotyping was performed in
the Genome Analysis Center (GAC) of the Helmholtz Zentrum Munchen. The
LINUX platform for computation were funded by the University of
Regensburg for the Department of Epidemiology and Preventive Medicine at
the Regensburg University Medical Center.; LifeLines Study: The
LifeLines Cohort Study and generation and management of GWAS genotype
data for the LifeLines Cohort Study is supported by the Netherlands
Organization of Scientific Research NWO grant 175.010.2007.006, the
Economic Structure Enhancing Fund (FES) of the Dutch government, the
Ministry of Economic Affairs, the Ministry of Education, Culture and
Science, the Ministry for Health, Welfare and Sports, the Northern
Netherlands Collaboration of Provinces (SNN), the Province of Groningen,
University Medical Center Groningen, the University of Groningen, Dutch
Kidney Foundation, and Dutch Diabetes Research Foundation. LifeLines is
a multidisciplinary prospective population-based cohort study examining
in a unique three-generation design the health and health-related
behaviors of 165,000 individuals living in the Northeast region of the
Netherlands. It uses a broad range of investigative procedures in
assessing the biomedical, sociodemographic, behavioral, physical, and
psychological factors that contribute to the health and disease of the
general population, with a special focus on multimorbidity and complex
genetics.; MICROS (Microisolates in South Tyrol) Study: The authors are
grateful to all participants. The authors thank the primary care
practitioners Raffaela Stocker, Stefan Waldner, Toni Pizzecco, Josef
Plangger, Ugo Marcadent, and the personnel of the Hospital of Silandro
Department of Laboratory Medicine for their participation and
collaboration in the research project. The authors thank Dr. Peter
Riegler (Hemodialysis Unit, Hospital of Merano) for the important
discussions. In South Tyrol, the study was supported by the Ministry of
Health and Department of Educational Assistance, University and Research
of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse
Foundation, and the European Union Framework Program 6 EUROSPAN project
(contract No. LSHG-CT-2006-018947).; PREVEND Study: PREVEND (Prevention
of Renal and Vascular End-stage Disease) genetics is supported by the
Dutch Kidney Foundation grant E033; the EU project grant GENECURE (FP-6
LSHM CT 2006 037697); the NIH grant 2R01LM0-10098; The Netherlands
Organisation for Health Research and Development NWO-Groot grant
175.010.2007.006, NWO VENI grant 916.761.70, ZonMw grant 90.700.441; and
the Dutch Inter University Cardiology Institute Netherlands (ICIN).;
SAPHIR Study: The SAPHIR (Salzburg Atherosclerosis Prevention Program in
Subjects at High Individual Risk) study was partially supported by a
grant from the Kamillo Eisner Stiftung to B. P. and by grants from the
Genomics of Lipidassociated Disorders (GOLD) of the "Austrian Genome
Research Programme GEN-AU" to F. K.; SHIP/SHIP-Trend/GANI_MED Study:
SHIP is part of the Community Medicine Research net of the University of
Greifswald, Germany, which is funded by the Federal Ministry of
Education and Research grants 01ZZ9603, 01ZZ0103, and 01ZZ0403; the
Ministry of Cultural Affairs, as well as the Social Ministry of the
Federal State of Mecklenburg-West Pomerania, and the network "Greifswald
Approach to Individualized Medicine (GANI_MED)" funded by the Federal
Ministry of Education and Research grant 03IS2061A. Genome-wide data
have been supported by the Federal Ministry of Education and Research
grant 03ZIK012 and a joint grant from Siemens Healthcare, Erlangen,
Germany, and the Federal State of Mecklenburg-West Pomerania. The
University of Greifswald is a member of the "Center of Knowledge
Interchange" program of the Siemens AG, the German Centre for Diabetes
Research (DZD), and the Cache Campus program of the InterSystems GmbH.
The SHIP authors are grateful to Mario Stanke for the opportunity to use
his Server Cluster for the SNP imputation as well as to Holger Prokisch
and Thomas Meitinger (Helmholtz Zentrum Munchen) for the genotyping of
the SHIP-Trend cohort.; SKIPOGH (Swiss Kidney Project on Genes in
Hypertension) Study: This research was funded by grant 33CM30-124087
from the Swiss National Science Foundation. The study also received
support from Lausanne University Hospital, Geneva University Hospital,
and Bern University Hospital, Switzerland. M. B. received support from
the Swiss School of Public Health Plus (SSPH).; Vanderbilt Study:
Genotyping was supported by National Institute of General Medical
Sciences (NIGMS) RC2-GM092318 (Omni1 and Omni5 array). This work was
supported by the Electronic Medical Records and Genomics (eMERGE)
Network, initiated and funded by the National Human Genome Research
Institute, with additional funding from the NIGMS, through U01-HG04603
(660 array).; Susztak Laboratory: Work in the laboratory of K.S. was
supported by NIH R01-DK0-76077 and DK0-87635.; Jacobs Laboratory: Work
in the H.J.J. and J.L. laboratories was supported by 2R01-069321 to
H.J.J.; Devuyst Laboratory: This work was supported by the European
Community's Seventh Framework Programme (FP7/2007-2013) under grant
agreement no. 305608 (EURenOmics) and the Swiss National Science
Foundation project grant 310030_1464904
NR 41
TC 5
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U1 3
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAR
PY 2016
VL 65
IS 3
BP 803
EP 817
DI 10.2337/db15-1313
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DE9MF
UT WOS:000370961000032
PM 26631737
ER
PT J
AU Tamborlane, WV
Haymond, MW
Dunger, D
Shankar, R
Gubitosi-Klug, R
Bethin, K
Karres, J
Tomasi, P
Libman, I
Hale, PH
Portman, R
Klingensmith, G
Reed, M
Blumer, J
Giacoia, G
AF Tamborlane, William V.
Haymond, Morey W.
Dunger, David
Shankar, Ravi
Gubitosi-Klug, Rose
Bethin, Kathleen
Karres, Janina
Tomasi, Paolo
Libman, Ingrid
Hale, Paula H.
Portman, Ronald
Klingensmith, Georgeanna
Reed, Michael
Blumer, Jeffrey
Giacoia, George
CA NICHD Diabet Working Grp
TI Expanding Treatment Options for Youth With Type 2 Diabetes: Current
Problems and Proposed Solutions: A White Paper From the NICHD Diabetes
Working Group
SO DIABETES CARE
LA English
DT Editorial Material
ID PEDIATRIC-PATIENTS; GLYCEMIC CONTROL; ADOLESCENTS; METFORMIN; CHILDREN;
ONSET; MONOTHERAPY; TRIAL
C1 [Tamborlane, William V.] Yale Univ, Sch Med, New Haven, CT USA.
[Haymond, Morey W.] Baylor Coll Med, Houston, TX 77030 USA.
[Dunger, David] Univ Cambridge, Cambridge, England.
[Shankar, Ravi] Merck & Co Inc, Whitehouse Stn, NJ USA.
[Gubitosi-Klug, Rose] Univ Hosp Rainbow Babies & Childrens Hosp, Cleveland, OH USA.
[Bethin, Kathleen] Womens & Childrens Hosp, Buffalo, NY USA.
[Karres, Janina; Tomasi, Paolo] European Med Agcy, London, England.
[Libman, Ingrid] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Hale, Paula H.] Novo Nordisk Inc, Bagsvaerd, Denmark.
[Portman, Ronald] Novartis Pharmaceut, E Hartford, CT USA.
[Klingensmith, Georgeanna] Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Reed, Michael] Akron Childrens Hosp, Akron, OH USA.
[Blumer, Jeffrey] Univ Toledo, 2801 W Bancroft St, Toledo, OH 43606 USA.
[Giacoia, George] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Tamborlane, WV (reprint author), Yale Univ, Sch Med, New Haven, CT USA.
EM william.tamborlane@yale.edu
OI Zeitler, Philip/0000-0001-5756-7858
FU Medical Research Council [G0800661]
NR 20
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U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2016
VL 39
IS 3
BP 323
EP 329
DI 10.2337/dc15-1649
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DF1HW
UT WOS:000371091500013
PM 26908928
ER
PT J
AU Greco, G
Ferket, BS
D'Alessandro, DA
Shi, W
Horvath, KA
Rosen, A
Welsh, S
Bagiella, E
Neill, AE
Williams, DL
Greenberg, A
Browndyke, JN
Gillinov, AM
Mayer, ML
Keim-Malpass, J
Gupta, LS
Hohmann, SF
Gelijns, AC
O'Gara, PT
Moskowitz, AJ
AF Greco, Giampaolo
Ferket, Bart S.
D'Alessandro, David A.
Shi, Wei
Horvath, Keith A.
Rosen, Alexander
Welsh, Stacey
Bagiella, Emilia
Neill, Alexis E.
Williams, Deborah L.
Greenberg, Ann
Browndyke, Jeffrey N.
Gillinov, A. Marc
Mayer, Mary Lou
Keim-Malpass, Jessica
Gupta, Lopa S.
Hohmann, Samuel F.
Gelijns, Annetine C.
O'Gara, Patrick T.
Moskowitz, Alan J.
TI Diabetes and the Association of Postoperative Hyperglycemia With
Clinical and Economic Outcomes in Cardiac Surgery
SO DIABETES CARE
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; INPATIENT GLYCEMIC
CONTROL; GLUCOSE CONTROL; STRESS HYPERGLYCEMIA; CRITICAL ILLNESS; 3
DOMAINS; MORTALITY; MANAGEMENT; HEALTH
AB OBJECTIVEThe management of postoperative hyperglycemia is controversial and generally does not take into account pre-existing diabetes. We analyzed clinical and economic outcomes associated with postoperative hyperglycemia in cardiac surgery patients, stratifying by diabetes status.RESEARCH DESIGN AND METHODSMulticenter cohort study in 4,316 cardiac surgery patients operated on in 2010. Glucose was measured at 6-h intervals for 48 h postoperatively. Outcomes included cost, hospital length of stay (LOS), cardiac and respiratory complications, major infections, and death. Associations between maximum glucose levels and outcomes were assessed with multivariable regression and recycled prediction analyses.RESULTSIn patients without diabetes, increasing glucose levels were associated with a gradual worsening of outcomes. In these patients, hyperglycemia (180 mg/dL) was associated with an additional cost of $3,192 (95% CI 1,972 to 4,456), an additional hospital LOS of 0.8 days (0.4 to 1.3), an increase in infections of 1.6% (0.5 to 2.8), and an increase in respiratory complications of 2.6% (0.0 to 5.3). However, among patients with insulin-treated diabetes, optimal outcomes were associated with glucose levels considered to be hyperglycemic (180 to 240 mg/dL). This level of hyperglycemia was associated with cost reductions of $6,225 (-12,886 to -222), hospital LOS reductions of 1.6 days (-3.7 to 0.4), infection reductions of 4.1% (-9.1 to 0.0), and reductions in respiratory complication of 12.5% (-22.4 to -3.0). In patients with non-insulin-treated diabetes, outcomes did not differ significantly when hyperglycemia was present.CONCLUSIONSGlucose levels <180 mg/dL are associated with better outcomes in most patients, but worse outcomes in patients with diabetes with a history of prior insulin use. These findings support further investigation of a stratified approach to the management of patients with stress-induced postoperative hyperglycemia based on prior diabetes status.
C1 [Greco, Giampaolo; Ferket, Bart S.; Shi, Wei; Bagiella, Emilia; Williams, Deborah L.; Gupta, Lopa S.; Gelijns, Annetine C.; Moskowitz, Alan J.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res InCHOIR, New York, NY 10029 USA.
[D'Alessandro, David A.] Albert Einstein Coll Med, Montefiore Med Center, Dept Cardiothorac Surg, New York, NY USA.
[Horvath, Keith A.; Greenberg, Ann] NIH, Dept Cardiothorac Surg, Heart Ctr, Suburban Hosp, Bldg 10, Bethesda, MD 20892 USA.
[Rosen, Alexander] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Welsh, Stacey] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA.
[Neill, Alexis E.] Emory Univ, Hosp Midtown, Dept Cardiothorac Surg, Atlanta, GA 30322 USA.
[Browndyke, Jeffrey N.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Gillinov, A. Marc] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Mayer, Mary Lou] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
[Keim-Malpass, Jessica] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA.
[Hohmann, Samuel F.] Univ HealthSyst Consortium, Chicago, IL USA.
[O'Gara, Patrick T.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
RP Greco, G (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res InCHOIR, New York, NY 10029 USA.
EM giampaolo.greco@mountsinai.org
OI Moskowitz, Alan/0000-0002-4412-9450; Browndyke,
Jeffrey/0000-0002-8573-7073
FU National Heart, Lung, and Blood Institute [7U01-HL-088942]; Canadian
Institutes of Health Research; Institute for Health Technology Studies
(InHealth); InHealth; National Institutes of Health; National Heart,
Lung, and Blood Institute
FX This study was funded by National Heart, Lung, and Blood Institute grant
7U01-HL-088942, the Canadian Institutes of Health Research, and the
Institute for Health Technology Studies (InHealth).; G.G. reports grants
from InHealth during the conduct of the study. A.E.N. reports receiving
grants and nonfinancial support from the National Institutes of Health
during the conduct of the study. A.M.G. reports receiving personal fees
from Edwards Lifesciences, Medtronic, St. Jude Medical, On-X, Tendyne,
AtriCure, and Abbott outside of the submitted work. A.C.G. and A.J.M.
report receiving grants from the National Heart, Lung, and Blood
Institute and the Canadian Institutes of Health Research during the
conduct of the study. No other potential conflicts of interest relevant
to this article were reported.
NR 39
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U1 1
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2016
VL 39
IS 3
BP 408
EP 417
DI 10.2337/dc15-1817
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DF1HW
UT WOS:000371091500025
PM 26786574
ER
PT J
AU Chen, LW
Li, SS
He, CY
Zhu, YY
Louis, GMB
Yeung, E
Hu, FB
Zhang, CL
AF Chen, Liwei
Li, Shanshan
He, Chunyan
Zhu, Yeyi
Louis, Germaine M. Buck
Yeung, Edwina
Hu, Frank B.
Zhang, Cuilin
TI Age at Menarche and Risk of Gestational Diabetes Mellitus: A Prospective
Cohort Study Among 27,482 Women
SO DIABETES CARE
LA English
DT Article
ID ASSOCIATION; ADULTHOOD
AB OBJECTIVETo examine the association between age at menarche and risk of gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODSA prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II.RESULTSThe adjusted risk ratios for GDM across the age at menarche categories (11, 12, 13, and 14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI.CONCLUSIONSThese findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity.
C1 [Chen, Liwei] Clemson Univ, Dept Publ Hlth Sci, Clemson, SC USA.
[Li, Shanshan; Zhu, Yeyi; Louis, Germaine M. Buck; Yeung, Edwina; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[He, Chunyan] Indiana Univ Sch Med, Dept Publ Hlth & Melvin, Indianapolis, IN 46202 USA.
[He, Chunyan] Indiana Univ Sch Med, Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA.
[Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Chen, LW (reprint author), Clemson Univ, Dept Publ Hlth Sci, Clemson, SC USA.
EM liweic@clemson.edu
OI Yeung, Edwina/0000-0002-3851-2613; Buck Louis,
Germaine/0000-0002-1774-4490
FU National Institutes of Health [CA-50385, DK-58845]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health
FX The Nurses' Health Study II was funded by research grants CA-50385 and
DK-58845 from the National Institutes of Health. When this study was
conducted, L.C., S.L., Y.Z., G.M.B.L., E.Y., and C.Z. were supported by
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health.
NR 15
TC 1
Z9 1
U1 3
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2016
VL 39
IS 3
BP 469
EP 471
DI 10.2337/dc15-2011
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DF1HW
UT WOS:000371091500033
PM 26813668
ER
PT J
AU Olson, SW
Yoon, S
Baker, T
Prince, LK
Oliver, D
Abbott, KC
AF Olson, S. W.
Yoon, S.
Baker, T.
Prince, L. K.
Oliver, D.
Abbott, K. C.
TI Longitudinal plasma metanephrines preceding pheochromocytoma diagnosis:
a retrospective case-control serum repository study
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID VON-HIPPEL-LINDAU; BIOCHEMICAL-DIAGNOSIS; REFRACTORY HYPERTENSION;
SECONDARY HYPERTENSION; FREE NORMETANEPHRINE; ADRENAL MASS; MANAGEMENT;
PARAGANGLIOMAS; INCIDENTALOMA; LOCALIZATION
AB Objective: Plasma metanephrines (PMN) are highly sensitive for diagnosis of pheochromocytoma, but the natural history of PMN before pheochromocytoma diagnosis has not been previously described. The aim of the study was to compare the progression of PMN before pheochromocytoma diagnosis to matched healthy and essential hypertension disease controls.
Design: A retrospective case-control Department of Defense Serum Repository (DoDSR) study.
Methods: We performed a DoDSR study that compared three longitudinal pre-diagnostic PMN for 30 biopsy-proven pheochromocytoma cases to three longitudinal PMN for age, sex, race, and age of serum sample matched healthy and essential hypertension disease controls. Predominant metanephrine (MN) or normetanephrine (NMN) production was identified for each case and converted to a percentage of the upper limit of normal to allow analysis of all cases together. PMN were measured by Quest Diagnostics.
Results: The predominant plasma metanephrine (PPM) was > 100 and 300% of the upper limit of normal a median of 6.6 and 4.1 years before diagnosis respectively. A greater percentage of pheochromocytoma patients had a PPM > 100 and > 300% of the upper limit of normal compared with combined healthy and essential hypertension disease controls < 2, 2-8, and >8 years prior to diagnosis. For patients with a baseline PPM 90-300% of the upper limit of normal, a 25% rate of rise per year was 100% specific for pheochromocytoma.
Conclusions: PPMs elevate years before diagnosis which suggests that delayed diagnoses are common. For mild PMN elevations, follow-up longitudinal PMN trends may provide a highly specific and economical diagnostic tool.
C1 [Olson, S. W.; Yoon, S.; Prince, L. K.; Oliver, D.] Walter Reed Natl Mil Med Ctr, Dept Nephrol, 8901 Rockville Pike, Bethesda, MD 20889 USA.
[Baker, T.] Joint Pathol Ctr, Dept Chief, 606 Stephen Sitter Ave, Silver Spring, MD 20910 USA.
[Abbott, K. C.] NIDDK, Bethesda, MD 20892 USA.
RP Olson, SW (reprint author), Walter Reed Natl Mil Med Ctr, Dept Nephrol, 8901 Rockville Pike, Bethesda, MD 20889 USA.
EM Stephen.w.olson.mil@mail.mil
NR 48
TC 1
Z9 1
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD MAR
PY 2016
VL 174
IS 3
BP 289
EP 295
DI 10.1530/EJE-15-0651
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DE8HM
UT WOS:000370876800009
PM 26671972
ER
PT J
AU Ngwa, W
Ngoma, T
Zietman, A
Mayr, N
Elzawawy, A
Winningham, TA
Balogun, O
Enwerem-Bromson, N
Ntizimira, C
Olopade, OI
Oluwole, D
Odedina, F
Williams, M
Flanigan, J
Asana, L
Ngwa, K
Avery, S
Pollard, JM
Roland, T
Funwi-gabga, N
Mbarika, V
Hardenbergh, P
Winkfield, K
Pipman, Y
Stefan, C
Ngoma, M
Mohammed, S
Katz, M
Erno, S
Moni, J
Fitzgerald, T
Tonlaar, N
Efstathiou, J
Gierga, D
Ayo, C
Knaul, F
Gospodarowicz, M
Makrigiorgos, GM
Nguyen, PL
AF Ngwa, Wilfred
Ngoma, Twalib
Zietman, Anthony
Mayr, Nina
Elzawawy, Ahmed
Winningham, Thomas A.
Balogun, Onyinye
Enwerem-Bromson, Nelly
Ntizimira, Christian
Olopade, Olufunmilayo I.
Oluwole, Doyin
Odedina, Folakemi
Williams, Makeda
Flanigan, John
Asana, Lydia
Ngwa, Kenneth
Avery, Stephen
Pollard, Julianne M.
Roland, Teboh
Funwi-gabga, Neba
Mbarika, Victor
Hardenbergh, Patricia
Winkfield, Karen
Pipman, Yakov
Stefan, Christina
Ngoma, Mamsau
Mohammed, Sulma
Katz, Matthew
Erno, Sajo
Moni, Janaki
Fitzgerald, Thomas
Tonlaar, Nathan
Efstathiou, Jason
Gierga, David
Ayo, Charles
Knaul, Felicia
Gospodarowicz, Mary
Makrigiorgos, G. Mike
Nguyen, Paul L.
TI Closing the Cancer Divide Through Ubuntu: Information and Communication
Technology-Powered Models for Global Radiation Oncology
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RADIOTHERAPY; RESPONSIBILITY; COUNTRIES; THERAPY; AFRICA; ACCESS; CARE
C1 [Ngwa, Wilfred; Makrigiorgos, G. Mike; Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
[Ngwa, Wilfred; Mayr, Nina; Makrigiorgos, G. Mike; Nguyen, Paul L.] Harvard Univ, Sch Med, 75 Francis St, Boston, MA 02115 USA.
[Ngwa, Wilfred; Erno, Sajo] Univ Massachusetts Lowell, Dept Phys & Appl Phys, Lowell, MA USA.
[Ngoma, Twalib] Muhimbili Univ Hlth & Allied Sci, Dept Clin Oncol, Dar Es Salaam, Tanzania.
[Zietman, Anthony; Winkfield, Karen; Efstathiou, Jason; Gierga, David] Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA USA.
[Mayr, Nina] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Elzawawy, Ahmed; Stefan, Christina] African Org Res & Training Canc, Rondebosch, South Africa.
[Winningham, Thomas A.] Hlth First Canc Inst, Titusville, FL USA.
[Balogun, Onyinye] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY USA.
[Enwerem-Bromson, Nelly] IAEA, Program Act Canc Therapy, A-1400 Vienna, Austria.
[Ntizimira, Christian] Kibagabaga Hosp, Kigali City, Rwanda.
[Olopade, Olufunmilayo I.] Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA.
[Oluwole, Doyin] Pink Ribbon Red Ribbon, Dallas, TX USA.
[Odedina, Folakemi] Univ Florida, Coll Pharm, Gainesville, FL USA.
[Williams, Makeda; Flanigan, John] NCI, Ctr Global Hlth, Rockville, MD USA.
[Asana, Lydia; Ngwa, Kenneth] African Renaissance Ambassador Corp, Orlando, FL USA.
[Avery, Stephen] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Pollard, Julianne M.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Roland, Teboh] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA.
[Funwi-gabga, Neba] Southern Alberta Inst Technol, Calgary, AB, Canada.
[Mbarika, Victor] Informat & Commun Technol Univ, Baton Rouge, LA USA.
[Hardenbergh, Patricia] Shaw Reg Canc Ctr, Edwards, CO USA.
[Pipman, Yakov] Amer Assoc Physicists Med, Int Educ Activ Comm, College Pk, MD USA.
[Stefan, Christina] South African Med Res Council, Cape Town, South Africa.
[Ngoma, Mamsau] Ocean Rd Canc Inst, Dar Es Salaam, Tanzania.
[Mohammed, Sulma] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Mohammed, Sulma] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA.
[Katz, Matthew] Lowell Gen Hosp, Lowell, MA USA.
[Moni, Janaki; Fitzgerald, Thomas] Univ Massachusetts, Sch Med, Dept Radiat Oncol, Worcester, MA USA.
[Tonlaar, Nathan] Radiating Hope, Salt Lake City, UT USA.
[Ayo, Charles] Covenant Univ, Ota, Nigeria.
[Knaul, Felicia] Harvard Univ, Sch Med, Harvard Global Equ Initiat, Boston, MA USA.
[Gospodarowicz, Mary] Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
[Gospodarowicz, Mary] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada.
RP Ngwa, W (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Ngwa, W (reprint author), Harvard Univ, Sch Med, 75 Francis St, Boston, MA 02115 USA.
EM wngwa@lroc.harvard.edu
FU Harvard Radcliffe Institute; Varian Medical Systems; Brigham and Women's
Hospital Center for Community Health and Health Equity
FX This work was supported by Harvard Radcliffe Institute, Varian Medical
Systems, and Brigham and Women's Hospital Center for Community Health
and Health Equity.
NR 26
TC 2
Z9 2
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2016
VL 94
IS 3
BP 440
EP 449
DI 10.1016/j.ijrobp.2015.10.063
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DE7KX
UT WOS:000370816500005
PM 26867873
ER
PT J
AU Zhang, T
Lv, CF
Wang, J
Zheng, WB
Lu, LZ
Liu, SJ
Bao, J
AF Zhang, T.
Lv, C-F.
Wang, J.
Zheng, W-B
Lu, L-Z.
Liu, S-J.
Bao, J.
TI Direct tuberculosis drug susceptibility testing: time-saving and
cost-effective in detecting MDR-TB
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE tuberculosis; multidrug-resistant TB; DR-TB; DST; rifampicin; isoniazid
ID MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; RAPID
DETECTION; GLOBAL BURDEN; METAANALYSIS; DIAGNOSTICS; ASSAY; GENEXPERT;
COUNTRIES; CHINA
AB BACKGROUND: Recent advances have made molecular diagnosis of tuberculosis (TB) and drug susceptibility testing (DST) possible, but the high costs involved present a huge challenge. The refinement and improvement of affordable methods therefore remain a priority. Conventional indirect DST is inexpensive and reliable, but time-consuming. A direct DST method for the direct testing of sputum samples without culture has been developed to reduce the time required for DST, but there have been conflicting results.
METHODS AND RESULTS: Direct and indirect DST against isoniazid and rifampicin were performed on 208 sputum smear-positive specimens, 186 from newly diagnosed patients and 22 from previously treated patients; respectively 169 and 180 of the direct and indirect DST results were reportable. In comparison with indirect DST, direct DST resulted in a saving of on average 10.5 days. The time to direct DST results was inversely correlated with the number of acid-fast bacilli in the sputum samples.
CONCLUSION: Direct DST is highly sensitive, reliable, cost-effective and time-saving in comparison with indirect DST.
C1 [Zhang, T.; Lv, C-F.; Wang, J.; Zheng, W-B; Lu, L-Z.; Liu, S-J.] Shenzhen Nanshan Ctr Chron Dis Control, Shenzhen 518054, Guangdong, Peoples R China.
[Bao, J.] NIAID, HJF DAIDS, Div Henry M Jackson Fdn Adv Mil Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Zhang, T (reprint author), Shenzhen Nanshan Ctr Chron Dis Control, Shenzhen 518054, Guangdong, Peoples R China.; Bao, J (reprint author), Henry M Jackson Fdn Adv Mil Med, 5601 Fishers Lane, Bethesda, MD 20892 USA.
EM taozhang315@126.com; Baoj@mail.nih.gov
FU Research Grants of Shenzhen Science and Technology Project, Shenzhen,
China [JCYJ20130329100436295]; National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Department of Health
and Human Services, Bethesda, MD, USA [HH-SN272200800014C]
FX The study was supported by the Research Grants of Shenzhen Science and
Technology Project, Shenzhen, China (contract no.
JCYJ20130329100436295). JB was funded by the National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services, Bethesda, MD, USA (contract no
HH-SN272200800014C).
NR 31
TC 1
Z9 1
U1 3
U2 5
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD MAR
PY 2016
VL 20
IS 3
BP 323
EP 328
DI 10.5588/ijtld.15.0637
PG 6
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA DF2RU
UT WOS:000371192300010
PM 27046712
ER
PT J
AU Resnik, DB
Tyler, AM
Black, JR
Kissling, G
AF Resnik, David B.
Tyler, Ana M.
Black, Jennifer R.
Kissling, Grace
TI Authorship policies of scientific journals
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID EQUAL CONTRIBUTIONS; CREDIT
AB We analysed the authorship policies of a random sample of 600 journals from the Journal Citation Reports database. 62.5% of the journals we sampled had an authorship policy. Having an authorship policy was positively associated with impact factor. Journals from the biomedical sciences and social sciences/humanities were more likely to have an authorship policy than journals from the physical sciences, engineering or mathematical sciences. Among journals with a policy, the most frequent type of policy was guidance on criteria for authorship (99.7%); followed by guidance on acknowledgments (97.3%); requiring that authors make substantial contributions to the research (94.7%); requiring that authors be accountable for the research as a whole (84.8%); guidance on changes in authorship (77.9%); requiring that authors give final approval to the manuscript (77.6%); requiring that authors draft or critically revise the manuscript (71.7%); providing guidance on corporate authorship (58.9%); prohibiting gift, guest or ghost authorship (31.7%); requiring authors to describe their contributions (5.3%); limiting the number of authors for some types of articles (4.0%) and requiring authors to be accountable for their part in the research (1.1%). None of the policies addressed equal contribution statements. Journals that do not have authorship policies should consider adopting or developing ones.
C1 [Resnik, David B.; Kissling, Grace] NIEHS, NIH, Box 12233,Mail Drop CU 108, Res Triangle Pk, NC 27709 USA.
[Tyler, Ana M.] Case Western Reserve Univ, NIEHS, Cleveland, OH 44106 USA.
[Black, Jennifer R.] Emory Univ, NIEHS, Atlanta, GA 30322 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 108, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural Program of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH)
FX This research was supported by the Intramural Program of the National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH).
NR 23
TC 3
Z9 3
U1 0
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
EI 1473-4257
J9 J MED ETHICS
JI J. Med. Ethics
PD MAR
PY 2016
VL 42
IS 3
BP 199
EP 202
DI 10.1136/medethics-2015-103171
PG 4
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA DE7QB
UT WOS:000370830700015
PM 26714812
ER
PT J
AU Margolin, G
Petrykowska, HM
Jameel, N
Bell, DW
Young, AC
Elnitski, L
AF Margolin, Gennady
Petrykowska, Hanna M.
Jameel, Nader
Bell, Daphne W.
Young, Alice C.
Elnitski, Laura
TI Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus
with in Silico Modeling for Blood-Based Diagnostic Development
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID CIRCULATING TUMOR DNA; NUCLEIC-ACIDS; METHYLATION BIOMARKERS;
LUNG-CANCER; QUALITY; GENOME; QUANTIFICATION; ASSOCIATION; PLASMA;
BREAST
AB Sites that display recurrent, aberrant DNA methylation in cancer represent potential biomarkers for screening and diagnostics. Previously, we identified hypermethylation at the ZNF154 CpG island in 15 solid epithelial tumor types from 13 different organs. In this study, we measure the magnitude and pattern of differential methylation of this region across colon, lung, breast, stomach, and endometrial tumor samples using next generation bisulfite amplicon sequencing. We found that all tumor types and subtypes are hypermethylated at this locus compared with normal tissue. To evaluate this site as a possible pan-cancer marker, we compare the ability of several sequence analysis methods to distinguish the five tumor types (184 tumor samples) from normal tissue samples (n = 34). The classification performance for the strongest method, measured by the area under (the receiver operating characteristic) curve (AUC), is 0.96, close to a perfect value of 1. Furthermore, in a computational simulation of circulating tumor DNA, we were able to detect limited amounts of tumor DNA diluted with normal DNA: 1% tumor DNA in 99% normal DNA yields AUCs of up to 0.79. Our findings suggest that hypermethylation of the ZNF154 CpG island is a relevant biomarker for identifying solid tumor DNA and may have utility as a generalizable biomarker for circulating tumor DNA.
C1 [Margolin, Gennady; Petrykowska, Hanna M.; Jameel, Nader; Elnitski, Laura] NHGRI, Translat & Funct Genom Branch, 5625 Fishers Ln, Rockville, MD 20852 USA.
[Young, Alice C.] NHGRI, Natl Inst Hlth Intramural Sequencing Ctr, Rockville, MD 20852 USA.
[Bell, Daphne W.] NHGRI, Canc Genet & Comparat Genom Branch, Bethesda, MD 20892 USA.
RP Elnitski, L (reprint author), NHGRI, Translat & Funct Genom Branch, 5625 Fishers Ln, Rockville, MD 20852 USA.
EM elnitski@mail.nih.gov
FU Intramural Program of the National Human Genome Research Institute, NIH;
NIH [HG200323]
FX Supported by the Intramural Program of the National Human Genome
Research Institute, NIH, and NIH grant HG200323 (L.E.).
NR 41
TC 5
Z9 5
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAR
PY 2016
VL 18
IS 2
BP 283
EP 298
DI 10.1016/j.jmoldx.2015.11.004
PG 16
WC Pathology
SC Pathology
GA DE9ZA
UT WOS:000370997200014
PM 26857064
ER
PT J
AU Pomeraniec, IJ
Ksendzovsky, A
Awad, AJ
Fezeu, F
Jane, JA
AF Pomeraniec, I. Jonathan
Ksendzovsky, Alexander
Awad, Ahmed J.
Fezeu, Francis
Jane, John A., Jr.
TI Natural and surgical history of Chiari malformation Type I in the
pediatric population
SO JOURNAL OF NEUROSURGERY-PEDIATRICS
LA English
DT Article
DE Chiari malformation; syringomyelia; pediatric neurosurgery; natural
history
ID POSTERIOR-FOSSA DECOMPRESSION; OF-NEUROLOGICAL-SURGEONS; SPONTANEOUS
RESOLUTION; CRANIOCERVICAL JUNCTION; CEREBELLAR TONSILS; CLINICAL
ARTICLE; SYRINGOMYELIA; DURAPLASTY; CHILDREN; OUTCOMES
AB OBJECTIVE The natural and surgical history of Chiari malformation Type I (CM-I) in pediatric patients is currently not well described. In this study the authors discuss the clinical and radiological presentation and outcomes in a large cohort of pediatric CM-I patients treated with either conservative or surgical management.
METHODS The authors retrospectively reviewed 95 cases involving pediatric patients with CM-I who presented between 2004 and 2013. The patients ranged in age from 9 months to 18 years (mean 8 years) at presentation. The cohort was evenly split between the sexes. Twenty-five patients underwent posterior fossa decompression (PFD) with either dural splitting or duraplasty. Seventy patients were managed without surgery. Patients were followed radiologically (mean 44.8 months, range 1.2-196.6 months) and clinically (mean 66.3 months, range 1.2-106.5 months).
RESULTS Seventy patients were treated conservatively and followed with serial outpatient neurological and radiological examinations, whereas 25 patients were treated with PFD. Of these 25 surgical patients, 11 were treated with duraplasty (complete dural opening) and 14 were treated with a dura-splitting technique (incomplete dural opening). Surgical intervention was associated with better clinical resolution of symptoms and radiological resolution of tonsillar ectopia and syringomyelia (p = 0.0392). Over the course of follow-up, 20 (41.7%) of 48 nonsurgical patients who were symptomatic at presentation experienced improvement in symptoms and 18 (75%) of 24 symptomatic surgical patients showed clinical improvement (p = 0.0117). There was no statistically significant difference in resolution of symptoms between duraplasty and dura-splitting techniques (p = 0.3572) or between patients who underwent tonsillectomy and tonsillopexy (p = 0.1667). Neither of the 2 patients in the conservative group with syrinx at presentation showed radiological evidence of resolution of the syrinx, whereas 14 (87.5%) of 16 patients treated with surgery showed improvement or complete resolution of syringomyelia (p = 0.0392). In the nonsurgical cohort, 3 patients (4.3%) developed new or increased syrinx.
CONCLUSIONS The overwhelming majority of CM-I patients (92.9%) managed conservatively do not experience clinical or radiological progression, and a sizeable minority (41.7%) of those who present with symptoms improve. However, appropriately selected symptomatic patients (sleep apnea and dysphagia) and those presenting with syringomyelia should be considered surgical candidates because of the high rates of clinical (75%) and radiological improvement (87.5%).
C1 [Pomeraniec, I. Jonathan; Ksendzovsky, Alexander; Awad, Ahmed J.; Fezeu, Francis; Jane, John A., Jr.] Univ Virginia, Hlth Sci Ctr, Dept Neurol Surg, Charlottesville, VA 22908 USA.
[Ksendzovsky, Alexander] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Pomeraniec, IJ (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Box 800212, Charlottesville, VA 22908 USA.
EM ijp3by@virginia.edu
NR 39
TC 2
Z9 2
U1 1
U2 2
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1933-0707
EI 1933-0715
J9 J NEUROSURG-PEDIATR
JI J. Neurosurg.-Pediatr.
PD MAR
PY 2016
VL 17
IS 3
BP 343
EP 352
DI 10.3171/2015.7.PEDS1594
PG 10
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA DE8VR
UT WOS:000370915300016
PM 26588459
ER
PT J
AU Arora, A
Agarwal, D
Abdel-Fatah, TMA
Lu, HM
Croteau, DL
Moseley, P
Aleskandarany, MA
Green, AR
Ball, G
Rakha, EA
Chan, SYT
Ellis, IO
Wang, LL
Zhao, YL
Balajee, AS
Bohr, VA
Madhusudan, S
AF Arora, Arvind
Agarwal, Devika
Abdel-Fatah, Tarek M. A.
Lu, Huiming
Croteau, Deborah L.
Moseley, Paul
Aleskandarany, Mohammed A.
Green, Andrew R.
Ball, Graham
Rakha, Emad A.
Chan, Stephen Y. T.
Ellis, Ian O.
Wang, Lisa L.
Zhao, Yongliang
Balajee, Adayabalam S.
Bohr, Vilhelm A.
Madhusudan, Srinivasan
TI RECQL4 helicase has oncogenic potential in sporadic breast cancers
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE RECQL4 helicase; breast cancer; tumour suppressor; oncogene
ID ROTHMUND-THOMSON-SYNDROME; GENE; EXPRESSION
AB RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund-Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer predisposition. RECQL4 is widely considered to be a tumour suppressor, although its role in human breast cancer is largely unknown. As the RECQL4 gene is localized to chromosome 8q24, a site frequently amplified in sporadic breast cancers, we hypothesized that it may play an oncogenic role in breast tumourigenesis. To address this, we analysed large cohorts for gene copy number changes (n = 1977), mRNA expression (n = 1977) and protein level (n = 1902). Breast cancer incidence was also explored in 58 patients with type II RTS. DNA replication dynamics and chemosensitivity was evaluated in RECQL4-depleted breast cancer cells in vitro. Amplification or gain in gene copy number (30.6%), high-level mRNA expression (51%) and high levels of protein (23%) significantly associated with aggressive tumour behaviour, including lymph node positivity, larger tumour size, HER2 overexpression, ER-negativity, triple-negative phenotypes and poor survival. RECQL4 depletion impaired the DNA replication rate and increased chemosensitivity in cultured breast cancer cells. Thus, although recognized as a 'safe guardian of the genome', our data provide compelling evidence that RECQL4 is tumour promoting in established breast cancers. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Arora, Arvind; Madhusudan, Srinivasan] Univ Nottingham, Sch Med, Acad Unit Oncol, Div Canc & Stem Cells, Nottingham NG5 1PB, England.
[Arora, Arvind; Abdel-Fatah, Tarek M. A.; Moseley, Paul; Chan, Stephen Y. T.; Madhusudan, Srinivasan] Univ Nottingham Hosp, Dept Oncol, Nottingham, England.
[Agarwal, Devika; Ball, Graham] Nottingham Trent Univ, Sch Sci & Technol, Clifton Campus, Nottingham, England.
[Lu, Huiming; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Aleskandarany, Mohammed A.; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.] Univ Nottingham, Sch Med, Dept Pathol, Nottingham NG5 1PB, England.
[Wang, Lisa L.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Zhao, Yongliang] Chinese Acad Sci, Lab Dis Genom & Individualized Med, Beijing Inst Gen, Beijing, Peoples R China.
[Balajee, Adayabalam S.] Oak Ridge Associated Univ, REAC TS, Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37831 USA.
RP Madhusudan, S (reprint author), Univ Nottingham, Acad Unit Oncol, Div Canc & Stem Cells, Sch Med,Nottingham Univ Hosp, Nottingham NG5 1PB, England.
EM srinivasan.madhusudan@nottingham.ac.uk
OI Madhusudan, Srinivasan/0000-0002-5354-5480
FU Cancer Research UK; NIA NIH HHS [AG000726-24]
NR 13
TC 4
Z9 4
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD MAR
PY 2016
VL 238
IS 4
BP 495
EP 501
DI 10.1002/path.4681
PG 7
WC Oncology; Pathology
SC Oncology; Pathology
GA DE7TQ
UT WOS:000370840000003
PM 26690729
ER
PT J
AU Zhu, RX
Baker, SS
Moylan, CA
Abdelmalek, MF
Guy, CD
Zamboni, F
Wu, DF
Lin, WL
Liu, WS
Baker, RD
Govindarajan, S
Cao, ZW
Farci, P
Diehl, AM
Zhu, LX
AF Zhu, Ruixin
Baker, Susan S.
Moylan, Cynthia A.
Abdelmalek, Manal F.
Guy, Cynthia D.
Zamboni, Fausto
Wu, Dingfeng
Lin, Weili
Liu, Wensheng
Baker, Robert D.
Govindarajan, Sugantha
Cao, Zhiwei
Farci, Patrizia
Diehl, Anna Mae
Zhu, Lixin
TI Systematic transcriptome analysis reveals elevated expression of
alcohol-metabolizing genes in NAFLD livers
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE non-alcoholic; ADH; ALDH; CYP2E1
ID PEDIATRIC NONALCOHOLIC STEATOHEPATITIS; MITOCHONDRIAL DYSFUNCTION;
ALDEHYDE DEHYDROGENASE; INSULIN-RESISTANCE; DISEASE; HEPATITIS;
APOPTOSIS; ETHANOL; PATHOGENESIS; RECEPTORS
AB Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley (c) Sons, Ltd.
C1 [Zhu, Ruixin; Wu, Dingfeng; Lin, Weili; Cao, Zhiwei] Tongji Univ, Dept Bioinformat, Shanghai 200092, Peoples R China.
[Baker, Susan S.; Liu, Wensheng; Baker, Robert D.; Zhu, Lixin] SUNY Buffalo, Dept Pediat, Digest Dis & Nutr Ctr, 3435 Main St,422BRB, Buffalo, NY 14214 USA.
[Moylan, Cynthia A.; Abdelmalek, Manal F.; Diehl, Anna Mae] Duke Univ, Div Gastroenterol & Hepatol, Dept Med, Durham, NC USA.
[Guy, Cynthia D.] Durham Vet Affairs Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Durham, NC USA.
[Guy, Cynthia D.] Duke Univ, Dept Pathol, Durham, NC 27706 USA.
[Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, I-09134 Cagliari, Italy.
[Govindarajan, Sugantha] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA.
[Farci, Patrizia] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, LX (reprint author), SUNY Buffalo, Dept Pediat, Digest Dis & Nutr Ctr, 3435 Main St,422BRB, Buffalo, NY 14214 USA.; Diehl, AM (reprint author), Duke Univ, Dept Med, Durham, NC USA.
EM annamae.diehl@duke.edu; lixinzhu@buffalo.edu
FU Intramural NIH HHS
NR 48
TC 2
Z9 2
U1 3
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD MAR
PY 2016
VL 238
IS 4
BP 531
EP 542
DI 10.1002/path.4650
PG 12
WC Oncology; Pathology
SC Oncology; Pathology
GA DE7TQ
UT WOS:000370840000007
PM 26415102
ER
PT J
AU Eze, N
Smith, LM
LaGasse, LL
Derauf, C
Newman, E
Arria, A
Huestis, MA
Della Grotta, SA
Dansereau, LM
Neal, C
Lester, BM
AF Eze, Nwando
Smith, Lynne M.
LaGasse, Linda L.
Derauf, Chris
Newman, Elana
Arria, Amelia
Huestis, Marilyn A.
Della Grotta, Sheri A.
Dansereau, Lynne M.
Neal, Charles
Lester, Barry M.
TI School-Aged Outcomes following Prenatal Methamphetamine Exposure:
7.5-Year Follow-Up from the Infant Development, Environment, and
Lifestyle Study
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID NEUROBEHAVIORAL DISINHIBITION; BEHAVIOR PROBLEMS; EARLY ADVERSITY;
CHILDREN; AMPHETAMINE; CHILDHOOD; PREGNANCY; MOTHERS; HEALTH; WOMEN
AB Objective To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship.
Study design The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed).
Results PME was significantly associated with an increased early adversity index score (P<.001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P<.05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant.
Conclusions Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems.
C1 [Eze, Nwando; Smith, Lynne M.] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Torrance, CA 90502 USA.
[Eze, Nwando; Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA USA.
[LaGasse, Linda L.; Della Grotta, Sheri A.; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp, Pediat Div,Brown Ctr Study Children Risk, Providence, RI 02912 USA.
[Derauf, Chris; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Arria, Amelia] Univ Maryland, Ctr Substance Abuse Res, College Pk, MD 20742 USA.
[Huestis, Marilyn A.] Natl Inst Drug Abuse, Sect Chem & Drug Metab, Bethesda, MD USA.
[Derauf, Chris] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
RP Smith, LM (reprint author), UCLA, Dept Pediat, David Geffen Sch Med, Los Angeles Biomed Res Inst,Harbor UCLA Med Ctr, 1124 W Carson St,RB-1 Box 446, Torrance, CA 90502 USA.
EM smith@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265
FU National Institute on Drug Abuse [R01DA014918]; National Institutes of
Health/National Center for Advancing Translational Science at the
University of California, Los Angeles [CTSI UL1TR000124]; National
Center for Research Resources [U54RR026136]
FX Supported by the National Institute on Drug Abuse (R01DA014918), the
National Institutes of Health/National Center for Advancing
Translational Science at the University of California, Los Angeles (CTSI
UL1TR000124), and the National Center for Research Resources
(U54RR026136). The authors declare no conflicts of interest.
NR 29
TC 0
Z9 0
U1 11
U2 19
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 34
EP +
DI 10.1016/j.jpeds.2015.11.070
PG 6
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500011
PM 26781836
ER
PT J
AU Chugani, DC
Chugani, HT
Wiznitzer, M
Parikh, S
Evans, PA
Hansen, RL
Nass, R
Janisse, JJ
Dixon-Thomas, P
Behen, M
Rothermel, R
Parker, JS
Kumar, A
Muzik, O
Edwards, DJ
Hirtz, D
AF Chugani, Diane C.
Chugani, Harry T.
Wiznitzer, Max
Parikh, Sumit
Evans, Patricia A.
Hansen, Robin L.
Nass, Ruth
Janisse, James J.
Dixon-Thomas, Pamela
Behen, Michael
Rothermel, Robert
Parker, Jacqueline S.
Kumar, Ajay
Muzik, Otto
Edwards, David J.
Hirtz, Deborah
CA Autism Ctr Excellence Network
TI Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in
Young Children with Autism Spectrum Disorder: A Randomized Trial
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; BRAIN-SEROTONIN SYNTHESIS; BLOOD
SEROTONIN; 5-HT1A RECEPTOR; MICROGLIAL ACTIVATION; LOCOMOTOR-ACTIVITY;
DORSAL RAPHE; MOUSE; ANXIETY; RAT
AB Objectives To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD).
Study design Children 2-6 years of age with ASD (N=166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy.
Results There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P=.400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P=.006); the 2.5-mg buspirone group showed significant improvement (P=.003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P=.018) or if they showed normal levels of blood serotonin (P=.044). Adverse events did not differ significantly among treatment groups.
Conclusions Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions.
C1 [Chugani, Diane C.; Chugani, Harry T.; Dixon-Thomas, Pamela; Behen, Michael; Parker, Jacqueline S.; Kumar, Ajay; Muzik, Otto] Wayne State Univ, Sch Med, Carman & Ann Adams Dept Pediat, Detroit, MI USA.
[Chugani, Diane C.; Chugani, Harry T.; Behen, Michael; Parker, Jacqueline S.; Kumar, Ajay; Muzik, Otto] Childrens Hosp Michigan, Detroit, MI USA.
[Chugani, Harry T.; Kumar, Ajay; Muzik, Otto] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI USA.
[Wiznitzer, Max] Rainbow Babies & Childrens Hosp, Univ Hosp Case Med Ctr, Neurosci Inst, 2101 Adelbert Rd, Cleveland, OH 44106 USA.
[Parikh, Sumit] Case Western Reserve Univ, Cleveland Clin Neurogenet & Metab, Neurosci Inst, Lerner Coll Med, Cleveland, OH 44106 USA.
[Evans, Patricia A.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA.
[Evans, Patricia A.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Hansen, Robin L.] Univ Calif Davis, Med Invest Neurodeve Disorders MIND Inst, Dept Pediat, Davis, CA 95616 USA.
[Nass, Ruth] NYU, Langone Med Ctr, Dept Neurol, New York, NY USA.
[Nass, Ruth] NYU, Langone Med Ctr, Dept Child & Adolescent Psychiat, New York, NY USA.
[Janisse, James J.] Wayne State Univ, Sch Med, Dept Med & Publ Hlth Sci, Detroit, MI USA.
[Rothermel, Robert] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA.
[Kumar, Ajay; Muzik, Otto] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI USA.
[Edwards, David J.] Univ Waterloo, Sch Pharm, Waterloo, ON N2L 3G1, Canada.
[Hirtz, Deborah] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Chugani, DC (reprint author), Nemours Al DuPont Hosp Children, 1600 Rockland Rd,ARB 291, Wilmington, DE 19803 USA.
EM Diane.Chugani@nemours.org
FU National Institute of Neurological Disorders and Stroke [5U01 NS61264]
FX Supported by the National Institute of Neurological Disorders and Stroke
(cooperative agreement 5U01 NS61264). The authors declare no conflicts
of interest.
NR 63
TC 2
Z9 2
U1 2
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 45
EP +
DI 10.1016/j.jpeds.2015.11.033
PG 13
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500013
PM 26746121
ER
PT J
AU Uzark, K
Zak, V
Shrader, P
McCrindle, BW
Radojewski, E
Varni, JW
Daniels, K
Handisides, J
Hill, KD
Lambert, LM
Margossian, R
Pemberton, VL
Lai, WW
Atz, AM
AF Uzark, Karen
Zak, Victor
Shrader, Peter
McCrindle, Brian W.
Radojewski, Elizabeth
Varni, James W.
Daniels, Kaitlyn
Handisides, Jill
Hill, Kevin D.
Lambert, Linda M.
Margossian, Renee
Pemberton, Victoria L.
Lai, Wyman W.
Atz, Andrew M.
CA Pediat Heart Network Investigators
TI Assessment of Quality of Life in Young Patients with Single Ventricle
after the Fontan Operation
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID CONGENITAL HEART-DISEASE; GENERIC CORE SCALES; FUNCTIONAL HEALTH-STATUS;
ADULT SURVIVORS; CHILDREN; ADOLESCENTS; VALIDITY; RELIABILITY;
FEASIBILITY; EXERCISE
AB Objectives To assess self-reported quality of life (QOL) in a large multicenter cohort of adolescent and young adults surviving Fontan.
Study design Cross-sectional. The Pediatric Quality of Life Inventory (PedsQL) was administered to 408 survivors of Fontan ages 13-25 years enrolled in the Pediatric Heart Network Fontan Follow-up Study. Subjects also completed either the Child Health Questionnaire (age <19 years) or Short Form Health Survey (age >= 19 years). PedsQL data were compared with matched controls without a chronic health condition. Correlations between the measures were examined.
Results Mean PedsQL scores for subjects receiving Fontan were significantly lower than those for the control group for physical and psychosocial QOL (P<.001). Overall, 45% of subjects receiving Fontan had scores in the clinically significant impaired range for physical QOL with 30% in the impaired range for psychosocial QOL. For each 1 year increase in age, the physical functioning score decreased by an average of 0.76 points (P=.004) and the emotional functioning score decreased by an average of 0.64 points (P=.03). Among subjects >= 19 years of age, the physical functioning score decreased by an average of 2 points for each year increase in age (P=.02). PedsQL scale scores were significantly correlated with conceptually related Child Health Questionnaire (P<.001) and Short Form Health Survey scores (P<.001).
Conclusions Survivors of Fontan are at risk for significantly impaired QOL which may decline with advancing age. Routine assessment of QOL is essential to inform interventions to improve health outcomes. The PedsQL allowed QOL assessment from pediatrics to young adulthood.
C1 [Uzark, Karen] Univ Michigan, Mott Childrens Hosp, L2110 Womens,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
[Zak, Victor; Shrader, Peter] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
[McCrindle, Brian W.; Radojewski, Elizabeth] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Varni, James W.] Texas A&M Univ, College Stn, TX USA.
[Daniels, Kaitlyn] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Handisides, Jill; Margossian, Renee] Boston Childrens Hosp, Boston, MA USA.
[Hill, Kevin D.] Duke Univ, Med Ctr, Durham, NC USA.
[Lambert, Linda M.] Primary Childrens Med Ctr, Salt Lake City, UT USA.
[Pemberton, Victoria L.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Lai, Wyman W.] Columbia Univ, Med Ctr, New York, NY USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
RP Uzark, K (reprint author), Univ Michigan, Mott Childrens Hosp, L2110 Womens,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM karenu@med.umich.edu
OI Lambert, Linda/0000-0002-4334-700X
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288]; Mapi Research Trust
FX Supported by the National Heart, Lung, and Blood Institute (HL068269,
HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288).
This work is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health/National Heart, Lung, and Blood Institute. J.V. holds the
copyright and the trademark for the PedsQL and receives financial
compensation from the Mapi Research Trust, which is a nonprofit research
institute that charges distribution fees to for-profit companies that
use the Pediatric Quality of Life Inventory. He did not receive
compensation for this project. The other authors declare no conflicts of
interest.
NR 42
TC 7
Z9 7
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 166
EP +
DI 10.1016/j.jpeds.2015.11.016
PG 8
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500036
PM 26685073
ER
PT J
AU Shneider, BL
Magee, JC
Karpen, SJ
Rand, EB
Narkewicz, MR
Bass, LM
Schwarz, K
Whitington, PF
Bezerra, JA
Kerkar, N
Haber, B
Rosenthal, P
Turmelle, YP
Molleston, JP
Murray, KF
Ng, VL
Wang, KS
Romero, R
Squires, RH
Arnon, R
Sherker, AH
Moore, J
Ye, W
Sokol, RJ
AF Shneider, Benjamin L.
Magee, John C.
Karpen, Saul J.
Rand, Elizabeth B.
Narkewicz, Michael R.
Bass, Lee M.
Schwarz, Kathleen
Whitington, Peter F.
Bezerra, Jorge A.
Kerkar, Nanda
Haber, Barbara
Rosenthal, Philip
Turmelle, Yumirle P.
Molleston, Jean P.
Murray, Karen F.
Ng, Vicky L.
Wang, Kasper S.
Romero, Rene
Squires, Robert H.
Arnon, Ronen
Sherker, Averell H.
Moore, Jeffrey
Ye, Wen
Sokol, Ronald J.
CA Childhood Liver Dis Res Network Ch
TI Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts
Short-Term Outcomes in Biliary Atresia
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID KASAIS OPERATION; SURVIVAL; PORTOENTEROSTOMY; EXPERIENCE; MANAGEMENT;
CHILDREN; INFANTS; SURGERY; VARICES; RISK
AB Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life.
Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 mu M) at any time in the first 3 months (TB <2.0, all others TB >= 2) after HPE was examined as a biomarker, using Kaplan-Meier survivaland logistic regression.
Results Fifty percent (68/137) of infants had TB <2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB <2.0 group vs TB >= 2 (86% vs 20%, P < .0001). Infants with TB >= 2 had diminished weight gain (P<.0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P <.0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P <.0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P <.0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001).
Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB < 2.0 mg/dL within 3 months of HPE may enhance early outcomes.
C1 [Shneider, Benjamin L.] Baylor Coll Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Magee, John C.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Karpen, Saul J.] Emory Univ, Sch Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr,Childrens, Atlanta, GA USA.
[Rand, Elizabeth B.] Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA.
[Narkewicz, Michael R.; Sokol, Ronald J.] Univ Colorado, Sch Med, Childrens Hosp Colorado, Sect Pediat Gastroenterol Hepatol & Nutr,Dept Ped, Aurora, CO USA.
[Bass, Lee M.; Whitington, Peter F.] Ann & Robert H Lurie Childrens Hosp Chicago, Pediat Div Gastroenterol Hepatol & Nutr, Chicago, IL 60611 USA.
[Schwarz, Kathleen] Johns Hopkins Sch Med, Baltimore, MD USA.
[Bezerra, Jorge A.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.
[Kerkar, Nanda] Univ So Calif, Childrens Hosp Los Angeles, Div Gastroenterol Hepatol & Nutr, Los Angeles, CA USA.
[Haber, Barbara] Merck Sharp & Dohme Corp, Merck Res Labs, North Wales, PA USA.
[Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, Div Gastroenterol Hepatol & Nutr, San Francisco, CA USA.
[Turmelle, Yumirle P.] Washington Univ, Sch Med, St Louis, MO USA.
[Molleston, Jean P.] Indiana Univ Sch Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA.
[Murray, Karen F.] Univ Washington, Dept Pediat, Div Gastroenterol & Hepatol, Seattle, WA 98195 USA.
[Murray, Karen F.] Seattle Childrens, Seattle, WA USA.
[Ng, Vicky L.] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Wang, Kasper S.] Childrens Hosp, Div Pediat Surg, Los Angeles, CA 90027 USA.
[Romero, Rene] Emory Univ, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA 30322 USA.
[Squires, Robert H.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Arnon, Ronen] Mt Sinai Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, New York, NY 10029 USA.
[Sherker, Averell H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Moore, Jeffrey; Ye, Wen] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
RP Shneider, BL (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, 6701 Fannin St,CCC 1010-00, Houston, TX 77030 USA.
EM Benjamin.Shneider@bcm.edu
FU NCATS NIH HHS [UL1 TR001082, UL1 TR001425, UL1TR000004, UL1TR000005,
UL1TR000077, UL1TR000130, UL1TR000150, UL1TR000423, UL1TR000424,
UL1TR000448, UL1TR000454, UL1TR001082, UL1TR001108]; NCRR NIH HHS
[UL1RR025014]; NIDDK NIH HHS [U01 DK084536, P30 DK026743, U01 DK062436,
U01 DK062445, U01 DK062452, U01 DK062453, U01 DK062456, U01 DK062466,
U01 DK062470, U01 DK062481, U01 DK062497, U01 DK062500, U01 DK062503,
U01 DK084538, U01 DK084575, U01 DK103135, U01 DK103140, U01 DK103149,
U01DK062436, U01DK062445, U01DK062452, U01DK062453, U01DK062456,
U01DK062466, U01DK062470, U01DK062481, U01DK062497, U01DK062500,
U01DK062503, U01DK084536, U01DK084538, U01DK084575, U01DK103135,
U01DK103149]
NR 38
TC 1
Z9 1
U1 2
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 211
EP +
DI 10.1016/j.jpeds.2015.11.058
PG 9
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500044
PM 26725209
ER
PT J
AU Rahman, SH
Papadakis, GZ
Keil, MF
Faucz, FR
Lodish, MB
Stratakis, CA
AF Rahman, Sara H.
Papadakis, Georgios Z.
Keil, Margaret F.
Faucz, Fabio R.
Lodish, Maya B.
Stratakis, Constantine A.
TI Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing
Disease
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID ENDOCRINE NEOPLASIA TYPE-1; VARIABLE PENETRANCE; METABOLIC SYNDROME;
CHILDREN; ADOLESCENTS; CALCIUM; NEPHROLITHIASIS; MANIFESTATIONS;
MANAGEMENT; DIAGNOSIS
AB Objective To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children.
Study design Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones.
Results Among 139 patients, 27 with CD (19.4%) had either radiographic evidence and/or a history of kidney stones. Those with kidney stones had higher urine free cortisol (P = .008) and transsphenoidal surgery at an older age (P = .007). The average urinary calcium/creatinine ratio was elevated in patients with CD (0.22 +/- 0.11). The prevalence of kidney stones was higher in children with CD than in normal children (19.42% vs 1.0%; P < .001).
Conclusion Our results illustrate that kidney stones are an underestimated complication of pediatric CD, especially when compared with the prevalence of nephrolithiasis in the general pediatric population. Long-term consequences for kidney function are not known and need to be studied.
C1 [Rahman, Sara H.; Keil, Margaret F.; Faucz, Fabio R.; Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Bethesda, MD USA.
[Rahman, Sara H.] Quinnipiac Univ, Frank H Netter Sch Med, North Haven, CT USA.
[Papadakis, Georgios Z.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Lodish, MB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol, Bldg 10,Rm 9D42,10 Ctr Dr,MSC 1830, Bethesda, MD 20814 USA.
EM lodishma@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 30
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 273
EP +
DI 10.1016/j.jpeds.2015.11.045
PG 6
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500053
PM 26703870
ER
PT J
AU Ross, AM
White, E
Powell, D
Nelson, S
Horowitz, L
Wharff, E
AF Ross, Abigail M.
White, Erina
Powell, Daniel
Nelson, Sally
Horowitz, Lisa
Wharff, Elizabeth
TI To Ask or Not to Ask? Opinions of Pediatric Medical Inpatients about
Suicide Risk Screening in the Hospital
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID EMERGENCY-DEPARTMENT; MENTAL-HEALTH; ADOLESCENT; BEHAVIOR; CARE;
CHILDREN; FEASIBILITY; IDEATION; CONTACT; HARM
AB Objective To describe opinions about suicide risk screening in a pediatric medical inpatient sample.
Study design As part of a larger instrument validation study, 200 pediatric medical inpatients (ages 10-21 years) were screened for suicide risk. Participants completed demographic self-report forms and were asked their opinions about suicide risk screening. Patient responses were recorded verbatim by trained research social workers. Qualitative data was analyzed using thematic analysis.
Results The majority of adolescents who participated had not been previously asked about suicide (N = 101; 62.3%) and were supportive of suicide risk screening (81.0%). Five salient themes emerged from the qualitative analysis of patient opinions: prevention, elevated risk, emotional benefits, provider responsibility, and lack of harm in asking.
Conclusions The majority of youth screened for suicide risk on medical inpatient units were supportive of suicide risk screening. Opinion data have the potential to inform screening practices and assure clinicians that suicide risk screening will be acceptable to pediatric patients and their parents. Given the lack of screening in these patients' past experiences, the medical setting is a unique opportunity to capture youth at risk for suicide.
C1 [Ross, Abigail M.; White, Erina; Nelson, Sally; Wharff, Elizabeth] Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02215 USA.
[Powell, Daniel; Horowitz, Lisa] NIMH, Bethesda, MD 20892 USA.
[Wharff, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA.
RP Ross, AM (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02215 USA.
EM abigail.ross@childrens.harvard.edu
FU National Institutes of Health Intramural Research Program [NCT02050867,
14-M-N044]
FX This project was supported in part by the National Institutes of Health
Intramural Research Program (NCT02050867, Protocol ID 14-M-N044). The
authors declare no conflicts of interest.
NR 36
TC 1
Z9 1
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2016
VL 170
BP 295
EP 300
DI 10.1016/j.jpeds.2015.11.052
PG 6
WC Pediatrics
SC Pediatrics
GA DE7MH
UT WOS:000370820500056
PM 26725208
ER
PT J
AU Gannon, BM
Williamson, A
Suzuki, M
Rice, KC
Fantegrossi, WE
AF Gannon, Brenda M.
Williamson, Adrian
Suzuki, Masaki
Rice, Kenner C.
Fantegrossi, William E.
TI Stereoselective Effects of Abused "Bath Salt" Constituent
3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor
Activity, and Thermoregulation
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ENANTIOMERS; RATS; MDPV; METHCATHINONE; CATHINONES; STIMULANT; COCAINE;
ANALOGS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; TRANSPORTERS
AB 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28 degrees C) or cool (20 degrees C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse.
C1 [Gannon, Brenda M.; Fantegrossi, William E.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA.
[Williamson, Adrian] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIAAA, Bethesda, MD USA.
RP Fantegrossi, WE (reprint author), Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, 4301 West Markham,Slot 638, Little Rock, AR 72205 USA.
EM WEFantegrossi@uams.edu
FU University of Arkansas for Medical Sciences Center for Translational
Neuroscience [RR020146]; University of Arkansas for Medical Sciences
Translational Research Institute [RR029884]; National Institutes of
Health National Institute on Drug Abuse [T32DA022981]; National
Institutes of Health Intramural Research Programs of the National
Institute on Drug Abuse; National Institute of Alcohol Abuse and
Alcoholism
FX This research was supported by the University of Arkansas for Medical
Sciences Center for Translational Neuroscience [Grant RR020146], the
University of Arkansas for Medical Sciences Translational Research
Institute [Grant RR029884], and the National Institutes of Health
National Institute on Drug Abuse [Grant T32DA022981]. A portion of this
work was supported by the National Institutes of Health Intramural
Research Programs of the National Institute on Drug Abuse and the
National Institute of Alcohol Abuse and Alcoholism. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute on Drug Abuse,
the National Institute of Alcohol Abuse and Alcoholism, or the National
Institutes of Health.
NR 25
TC 5
Z9 5
U1 5
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAR
PY 2016
VL 356
IS 3
BP 615
EP 623
DI 10.1124/jpet.115.229500
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DE4PL
UT WOS:000370611700009
PM 26769917
ER
PT J
AU Hong, WMC
Kopajtic, TA
Xu, LF
Lomenzo, SA
Jean, B
Madura, JD
Surratt, CK
Trudell, ML
Katz, JL
AF Hong, Weimin C.
Kopajtic, Theresa A.
Xu, Lifen
Lomenzo, Stacey A.
Jean, Bernandie
Madura, Jeffry D.
Surratt, Christopher K.
Trudell, Mark L.
Katz, Jonathan L.
TI 2-Substituted 3 beta-Aryltropane Cocaine Analogs Produce Atypical
Effects without Inducing Inward-Facing Dopamine Transporter
Conformations
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID RATS DISCRIMINATING COCAINE; UPTAKE INHIBITORS; IN-VIVO; BENZTROPINE
ANALOGS; 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; NONHUMAN-PRIMATES;
SQUIRREL-MONKEYS; RHESUS-MONKEYS; BINDING; PHARMACOLOGY
AB Previous structure-activity relationship studies indicate that a series of cocaine analogs, 3 beta-aryltropanes with 2 beta-diarylmethoxy substituents, selectively bind to the dopamine transporter (DAT) with nanomolar affinities that are 10-fold greater than the affinities of their corresponding 2 alpha-enantiomers. The present study compared these compounds to cocaine with respect to locomotor effects in mice, and assessed their ability to substitute for cocaine (10 mg/kg, i.p.) in rats trained to discriminate cocaine from saline. Despite nanomolar DAT affinity, only the 2 beta-Ph2COCH2-3 beta-4-Cl-Ph analog fully substituted for cocaine-like discriminative effects. Whereas all of the 2 beta compounds increased locomotion, only the 2 beta-(4-ClPh)PhCOCH2-3 beta-4-Cl-Ph analog had cocaine-like efficacy. None of the 2 alpha-substituted compounds produced either of these cocaine-like effects. To explore the molecular mechanisms of these drugs, their effects on DAT conformation were probed using a cysteine-accessibility assay. Previous reports indicate that cocaine binds with substantially higher affinity to the DAT in its outward (extracellular)- compared with inward-facing conformation, whereas atypical DAT inhibitors, such as benztropine, have greater similarity in affinity to these conformations, and this is postulated to explain their divergent behavioral effects. All of the 2 beta- and 2 alpha-substituted compounds tested altered cysteine accessibility of DAT in a manner similar to cocaine. Furthermore, molecular dynamics of in silico inhibitor-DAT complexes suggested that the 2-substituted compounds reach equilibrium in the binding pocket in a cocaine-like fashion. These behavioral, biochemical, and computational results show that aryltropane analogs can bind to the DAT and stabilize outward-facing DAT conformations like cocaine, yet produce effects that differ from those of cocaine.
C1 [Hong, Weimin C.] Butler Univ, Dept Pharmaceut Sci, Indianapolis, IN 46208 USA.
[Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, US Dept HHS,NIH, Baltimore, MD 21224 USA.
[Xu, Lifen; Lomenzo, Stacey A.; Trudell, Mark L.] Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA.
[Jean, Bernandie; Madura, Jeffry D.] Duquesne Univ, Dept Chem & Biochem, Pittsburgh, PA 15219 USA.
[Surratt, Christopher K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Institute on Drug Abuse [ZIA DA000103-26]; startup funds from
Butler University; National Institute on Drug Abuse [DA027806, DA11528];
National Institutes of Health National Science Foundation [R01DA027806,
XSEDE MCB060069]
FX The work reported herein was supported in various parts by funds as
follows: Work by W.C.H., T.A.K., and J.L.K. was supported by the
Intramural Research Program of the National Institutes of Health
National Institute on Drug Abuse [ZIA DA000103-26]. W.C.H. was also
supported by startup funds from Butler University. The work of J.D.M.
and C.K.S. was supported by a grant from the National Institute on Drug
Abuse [DA027806]. The efforts by J.D.M. and B.J. were funded in part by
National Institutes of Health National Science Foundation grants
[R01DA027806 and XSEDE MCB060069 supercomputers]. The work of M.L.T.,
L.X., and S.A.L. was supported by a grant from the National Institute on
Drug Abuse [DA11528].
NR 43
TC 1
Z9 1
U1 2
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAR
PY 2016
VL 356
IS 3
BP 624
EP 634
DI 10.1124/jpet.115.230722
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DE4PL
UT WOS:000370611700010
PM 26769919
ER
PT J
AU Xu, Y
Yue, WH
Shugart, YY
Yuan, JM
Wang, GQ
Wang, HZ
Lehrman, B
Zhang, FQ
Zhang, D
AF Xu, Yong
Yue, Weihua
Shugart, Yin Yao
Yuan, Jianmin
Wang, Guoqiang
Wang, Harold Z.
Lehrman, Benjamin
Zhang, Fuquan
Zhang, Dai
TI Potential involvement of the interleukin-18 pathway in schizophrenia
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Schizophrenia; IL18; IL18R1
ID CENTRAL-NERVOUS-SYSTEM; INTERFERON-GAMMA; KAPPA-B; CYTOKINE ALTERATIONS;
INTERACTION NETWORKS; GENE-EXPRESSION; TNF-ALPHA; IL-18; INFLAMMATION;
GENOME
AB Objective: Accumulating evidence implicates inflammatory cytokines in the development of psychiatric disorders, including schizophrenia (SZ). IL-18 is one of cytokines that plays a crucial role in immune response and neurodevelopment. We aimed to investigate potential genetic alterations of the cytokine system underpinning SZ.
Methods: We tested the association of genetic variants within the cytokine cytokine receptor interaction (CCRI) pathway with SZ, using GWAS-derived data involving 768 adult SZ patients and 1348 controls, and replicated the association of IL18R1 rs1035130 with SZ in an independent sample of 1957 adult patients and 1509 controls. We compared expression levels of IL18, IL18R1 and IL18RAP in peripheral blood of a cohort of adolescent participants (<18 years), including 14 early-onset SZ patients and 13 healthy controls. Furthermore, we carried out a cis-eQTL (expression Quantitative Trait Loci) and a cis-mQTL (Methylation Quantitative Trait Loci) analysis for IL18R1 rs1035130.
Results: In the discovery stage, we detected association signals within two IL18 pathway genes, IL18R1 and IL18RAP, with the most significant marker being IL18R1 rs1035130 (P = 1.84E-7, OR = 0.70). In the validation stage, we found rs1035130 was associated with SZ (P = 0.028, OR = 0.89). Expressions of IL18 and IL18R1 were altered in blood of SZ patients compared with 13 controls. Furthermore, cis-QTL analyses indicated that rs1035130 was associated with an eQTL and 5 mQTLs.
Conclusion: Our findings suggest the alteration of IL18 pathway may contribute to the psychopathology of SZ. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Xu, Yong] Shanxi Med Univ, Hosp 1, Clin Med Coll 1, Dept Psychiat, Taiyuan 030000, Peoples R China.
[Yue, Weihua; Zhang, Dai] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing 100871, Peoples R China.
[Yue, Weihua; Zhang, Dai] Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China.
[Yue, Weihua; Zhang, Dai] Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing 100871, Peoples R China.
[Shugart, Yin Yao; Wang, Harold Z.; Lehrman, Benjamin] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Yuan, Jianmin; Wang, Guoqiang; Zhang, Fuquan] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi 214151, Peoples R China.
[Zhang, Dai] Peking Univ, McGovern Inst Brain Res, PKU IDG, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
RP Zhang, FQ (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi 214151, Peoples R China.
EM zhangfq@njmu.edu.cn
FU National Natural Science Foundation of China [81471364, 81271482,
81571319]; Joint Medical Research Projects of Wuxi Municipal Hospital
Management Center [YGZXL1315]
FX This work was supported by National Natural Science Foundation of China
(81471364, 81271482, 81571319), Joint Medical Research Projects of Wuxi
Municipal Hospital Management Center (YGZXL1315).
NR 72
TC 0
Z9 0
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD MAR
PY 2016
VL 74
BP 10
EP 16
DI 10.1016/j.jpsychires.2015.12.013
PG 7
WC Psychiatry
SC Psychiatry
GA DE8RS
UT WOS:000370905000003
PM 26736035
ER
PT J
AU Francois, P
Altan-Bonnet, G
AF Francois, Paul
Altan-Bonnet, Gregoire
TI The Case for Absolute Ligand Discrimination: Modeling Information
Processing and Decision by Immune T Cells
SO JOURNAL OF STATISTICAL PHYSICS
LA English
DT Article
DE T Cell; Immune decision; Kinetic proofreading; Adaptive sorting;
Phenotypic variability; Feedback
ID SINGLE-CELL; FLUCTUATING ENVIRONMENTS; BACTERIAL PERSISTENCE;
SIGNAL-TRANSDUCTION; HIGH-AFFINITY; DWELL-TIME; RECEPTOR; ACTIVATION;
TCR; ANTAGONISM
AB Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T Cells. We show how the problem of absolute discrimination can be solved by a process called "adaptive sorting". We review several implementations of adaptive sorting, as well as its generic properties such as antagonism. We show how kinetic proofreading with negative feedback implement an approximate version of adaptive sorting in the immune context. Finally, we revisit the decision problem at the cell population level, showing how phenotypic variability and feedbacks between population and single cells are crucial for proper decision.
C1 [Francois, Paul] McGill Univ, Ernest Rutherford Phys Bldg, Montreal, PQ H3A 2T8, Canada.
[Altan-Bonnet, Gregoire] Mem Sloan Kettering, Program Computat Biol & Immunol, New York, NY USA.
[Altan-Bonnet, Gregoire] NCI, ImmunoDynam Grp, Canc & Inflammat Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Francois, P (reprint author), McGill Univ, Ernest Rutherford Phys Bldg, Montreal, PQ H3A 2T8, Canada.
EM paulf@physics.mcgill.ca
NR 68
TC 1
Z9 1
U1 5
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4715
EI 1572-9613
J9 J STAT PHYS
JI J. Stat. Phys.
PD MAR
PY 2016
VL 162
IS 5
SI SI
BP 1130
EP 1152
DI 10.1007/s10955-015-1444-1
PG 23
WC Physics, Mathematical
SC Physics
GA DF1GP
UT WOS:000371088000003
ER
PT J
AU Sampson, MG
Robertson, CC
Martini, S
Mariani, LH
Lemley, KV
Gillies, CE
Otto, EA
Kopp, JB
Randolph, A
Vega-Warner, V
Eichinger, F
Nair, V
Gipson, DS
Cattran, DC
Johnstone, DB
O'Toole, JF
Bagnasco, SM
Song, PX
Barisoni, L
Troost, JP
Kretzler, M
Sedor, JR
AF Sampson, Matthew G.
Robertson, Catherine C.
Martini, Sebastian
Mariani, Laura H.
Lemley, Kevin V.
Gillies, Christopher E.
Otto, Edgar A.
Kopp, Jeffrey B.
Randolph, Anne
Vega-Warner, Virginia
Eichinger, Felix
Nair, Viji
Gipson, Debbie S.
Cattran, Daniel C.
Johnstone, Duncan B.
O'Toole, John F.
Bagnasco, Serena M.
Song, Peter X.
Barisoni, Laura
Troost, Jonathan P.
Kretzler, Matthias
Sedor, John R.
CA Nephrotic Syndrome Study Network
TI Integrative Genomics Identifies Novel Associations with APOL1 Risk
Genotypes in Black NEPTUNE Subjects
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; UBIQUITIN-LIKE PROTEIN; CHRONIC
KIDNEY-DISEASE; NEPHROTIC SYNDROME; ALLOGRAFT SURVIVAL;
GENETIC-VARIANTS; NETWORK NEPTUNE; CELL-DEATH; NEPHROPATHY; AFRICAN
AB APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOLI-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria >= 0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m2 lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOLI mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.
C1 [Sampson, Matthew G.; Robertson, Catherine C.; Gillies, Christopher E.; Otto, Edgar A.; Vega-Warner, Virginia; Gipson, Debbie S.; Troost, Jonathan P.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Div Nephrol, Ann Arbor, MI 48109 USA.
[Martini, Sebastian; Mariani, Laura H.; Randolph, Anne; Eichinger, Felix; Nair, Viji] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA.
[Martini, Sebastian; Mariani, Laura H.; Randolph, Anne; Eichinger, Felix; Nair, Viji; Kretzler, Matthias] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Lemley, Kevin V.] Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Nephrol,Dept Pediat, Los Angeles, CA USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Cattran, Daniel C.] Univ Toronto, Univ Hlth Network, Dept Nephrol, Toronto, ON, Canada.
[Johnstone, Duncan B.] Temple Univ, Sch Med, Dept Internal Med, Div Nephrol, Philadelphia, PA 19122 USA.
[O'Toole, John F.; Sedor, John R.] Case Western Reserve Univ, Dept Internal Med, Div Nephrol, Cleveland, OH 44106 USA.
[Sedor, John R.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA.
[Sedor, John R.] MetroHealth Syst, Rammelkamp Ctr Educ & Res, Cleveland, OH USA.
[Bagnasco, Serena M.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Song, Peter X.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sampson, Matthew G.; Barisoni, Laura] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA.
RP Sampson, MG (reprint author), Univ Michigan, Sch Med, Div Pediat Nephrol, 8220D MSRB 3,West Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM mgsamps@med.umich.edu
OI Otto, Edgar/0000-0002-2387-9973
FU Charles Woodson Clinical Research Fund; Nephrotic Syndrome Study Network
Consortium [U54-DK083912]; George M. O'Brien Kidney Research Core Center
at the University of Michigan [P30-DK081943]; Office of Rare Diseases
Research (ORDR), NCATS [U54-DK-083912]; National Institute of Diabetes,
Digestive, and Kidney Diseases [U54-DK-083912]; University of Michigan;
NephCure Kidney International; Halpin Foundation; [1K08-DK100662-01]
FX M.S. is a Carl Gottschalk Research Scholar of the American Society of
Nephrology and is supported by the Charles Woodson Clinical Research
Fund and by 1K08-DK100662-01 and M.K. is supported by U54-DK083912
Nephrotic Syndrome Study Network Consortium and P30-DK081943 George M.
O'Brien Kidney Research Core Center at the University of Michigan. The
Nephrotic Syndrome Study Network Consortium (NEPTUNE), U54-DK-083912, is
a part of the National Center for Advancing Translational Sciences
(NCATS) Rare Disease Clinical Research Network (RDCRN), supported
through a collaboration between the Office of Rare Diseases Research
(ORDR), NCATS, and the National Institute of Diabetes, Digestive, and
Kidney Diseases. RDCRN is an initiative of ORDR, NCATS. Additional
funding and/or programmatic support for this project has also been
provided by the University of Michigan, NephCure Kidney International,
and the Halpin Foundation.
NR 37
TC 9
Z9 9
U1 1
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2016
VL 27
IS 3
BP 814
EP 823
DI 10.1681/ASN.2014111131
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA DF1LN
UT WOS:000371101400018
PM 26150607
ER
PT J
AU Peralta, CA
Bibbins-Domingo, K
Vittinghoff, E
Lin, F
Fornage, M
Kopp, JB
Winkler, CA
AF Peralta, Carmen A.
Bibbins-Domingo, Kirsten
Vittinghoff, Eric
Lin, Feng
Fornage, Myriam
Kopp, Jeffrey B.
Winkler, Cheryl A.
TI APOL1 Genotype and Race Differences in Incident Albuminuria and Renal
Function Decline
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; AFRICAN-AMERICANS; VARIANTS ASSOCIATE;
RACIAL-DIFFERENCES; UNITED-STATES; RISK; MICROALBUMINURIA;
INSUFFICIENCY; NEPHROPATHY; PROGRESSION
AB Variants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m(2), and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6-22.1) for high-risk blacks, 7.8 (6.4-9.4) for low-risk blacks, and 3.9 (3.1-4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64-8.94) for high-risk blacks and 2.32 (1.73-3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86-1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors.
C1 [Peralta, Carmen A.; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Vittinghoff, Eric; Lin, Feng] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Branch, Bethesda, MD 20892 USA.
[Winkler, Cheryl A.] Leidos Biomed Inc, Basic Res Lab, Ctr Canc Res, Natl Canc Inst,Frederick Natl Lab, Frederick, MD USA.
RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA.
EM carmenalicia.peralta@ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[5R03-DK095877-03]; Robert Wood Johnson Harold Amos Program; NIDDK
Intramural Research Program; National Cancer Institute, National
Institutes of Health (NIH) [HHSN26120080001E]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; National Heart, Lung, and Blood Institute (NHLBI); University
of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C];
Northwestern University [HHSN268201300027C]; University of Minnesota
[HHSN268201300028C]; Kaiser Foundation Research Institute
[HHSN268201300029C]; Johns Hopkins University School of Medicine
[HHSN268200900041C]; Intramural Research Program of the National
Institute on Aging (NIA); NIA [AG0005]; NHLBI [AG0005]; [R01-DK078124];
[P60006902]; [K24-DK103992]
FX C.P. is funded by grant 5R03-DK095877-03 from National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) and the Robert Wood
Johnson Harold Amos Program.; K.B.D. was funded by R01-DK078124,
P60006902 and K24-DK103992.; J.B.K. was supported by the NIDDK
Intramural Research Program. This project has been funded in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health (NIH), under contract HHSN26120080001E.; The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government. This research was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.; The Coronary Artery Risk Development in
Young Adults Study (CARDIA) is conducted and supported by the National
Heart, Lung, and Blood Institute (NHLBI) in collaboration with the
University of Alabama at Birmingham (HHSN268201300025C and
HHSN268201300026C), Northwestern University (HHSN268201300027C),
University of Minnesota (HHSN268201300028C), Kaiser Foundation Research
Institute (HHSN268201300029C), and Johns Hopkins University School of
Medicine (HHSN268200900041C). CARDIA is also partially supported by the
Intramural Research Program of the National Institute on Aging (NIA) and
an infra-agency agreement between NIA and NHLBI (AG0005). This
manuscript has been reviewed by CARDIA for scientific content.
NR 23
TC 8
Z9 8
U1 1
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2016
VL 27
IS 3
BP 887
EP 893
DI 10.1681/ASN.2015020124
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DF1LN
UT WOS:000371101400024
PM 26180129
ER
PT J
AU Diaz-Lezama, N
Wu, ZJ
Adan-Castro, E
Arnold, E
Vazquez-Membrillo, M
Arredondo-Zamarripa, D
Ledesma-Colunga, MG
Moreno-Carranza, B
de la Escalera, GM
Colosi, P
Clapp, C
AF Diaz-Lezama, Nundehui
Wu, Zhijian
Adan-Castro, Elva
Arnold, Edith
Vazquez-Membrillo, Miguel
Arredondo-Zamarripa, David
Ledesma-Colunga, Maria G.
Moreno-Carranza, Bibiana
Martinez de la Escalera, Gonzalo
Colosi, Peter
Clapp, Carmen
TI Diabetes enhances the efficacy of AAV2 vectors in the retina:
therapeutic effect of AAV2 encoding vasoinhibin and soluble VEGF
receptor 1
SO LABORATORY INVESTIGATION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ADENOASSOCIATED VIRUS VECTORS;
HEPARAN-SULFATE PROTEOGLYCANS; GENE-THERAPY; VIRAL VECTORS; INTRAVITREAL
INJECTION; INDUCED RETINOPATHY; BARRIER BREAKDOWN; TYPE-2 INFECTION;
LAYER THICKNESS
AB Adeno-associated virus (AAV) vector-mediated delivery of inhibitors of blood retinal barrier breakdown (BRBB) offers promise for the treatment of diabetic macular edema. Here, we demonstrated a reversal of blood retinal barrier pathology mediated by AAV type 2 (AAV2) vectors encoding vasoinhibin or soluble VEGF receptor 1 (sFlt-1) when administered intravitreally to diabetic rats. Efficacy and safety of the AAV2 vasoinhibin vector were tested by monitoring its effect on diabetes-induced changes in the retinal vascular bed and thickness, and in the electroretinogram (ERG). Also, the transduction of AAV2 vectors and expression of AAV2 receptors and co-receptors were compared between the diabetic and the non-diabetic rat retinas. AAV2 vasoinhibin or AAV2 sFlt-1 vectors were injected intravitreally before or after enhanced BRBB due to diabetes induced by streptozotocin. The BRBB was examined by the Evans blue method, the vascular bed by fluorescein angiography, expression of the AAV2 EGFP reporter vector by confocal microscopy, and the AAV2 genome, expression of transgenes, receptors, and co-receptors by quantitative PCR. AAV2 vasoinhibin and sFlt-1 vectors inhibited the diabetes-mediated increase in BRBB when injected after, but not before, diabetes was induced. The AAV2 vasoinhibin vector decreased retinal microvascular abnormalities and the diabetes-induced reduction of the B-wave of the ERG, but it had no effect in non-diabetic controls. Also, retinal thickness was not altered by diabetes or by the AAV2 vasoinhibin vector. The AAV2 genome, vasoinhibin and sFlt-1 transgenes, and EGFP levels were higher in the retinas from diabetic rats and were associated with an elevated expression of AAV2 receptors (syndecan, glypican, and perlecan) and co-receptors (fibroblast growth factor receptor 1, alpha v beta 5 integrin, and hepatocyte growth factor receptor). We conclude that retinal transduction and efficacy of AAV2 vectors are enhanced in diabetes, possibly due to their elevated cell entry. AAV2 vectors encoding vasoinhibin and sFlt-1 may be desirable gene therapeutics to target diabetic retinopathy and macular edema.
C1 [Diaz-Lezama, Nundehui; Adan-Castro, Elva; Arnold, Edith; Vazquez-Membrillo, Miguel; Arredondo-Zamarripa, David; Ledesma-Colunga, Maria G.; Moreno-Carranza, Bibiana; Martinez de la Escalera, Gonzalo; Clapp, Carmen] Univ Nacl Autonoma Mexico, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Mexico.
[Wu, Zhijian] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA.
[Colosi, Peter] BioMarin Pharmaceut, Novato, CA USA.
RP Clapp, C (reprint author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Campus UNAM Juriquilla, Queretaro 76230, Mexico.
EM clapp@unam.mx
NR 78
TC 0
Z9 0
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD MAR
PY 2016
VL 96
IS 3
BP 283
EP 295
DI 10.1038/labinvest.2015.135
PG 13
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA DE9WW
UT WOS:000370991600003
PM 26568297
ER
PT J
AU Dallal, CM
Brinton, LA
Matthews, CE
Pfeiffer, RM
Hartman, TJ
Lissowska, J
Falk, RT
Garcia-Closas, M
Xu, X
Veenstra, TD
Gierach, GL
AF Dallal, Cher M.
Brinton, Louise A.
Matthews, Charles E.
Pfeiffer, Ruth M.
Hartman, Terryl J.
Lissowska, Jolanta
Falk, Roni T.
Garcia-Closas, Montserrat
Xu, Xia
Veenstra, Timothy D.
Gierach, Gretchen L.
TI Association of Active and Sedentary Behaviors with Postmenopausal
Estrogen Metabolism
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE SEDENTARY; ACCELEROMETERS; PHYSICAL ACTIVITY; ESTROGEN METABOLITES
ID BREAST-CANCER RISK; MASS SPECTROMETRY METHOD; 15 URINARY ESTROGENS;
PHYSICAL-ACTIVITY; PREMENOPAUSAL WOMEN; EXERCISE INTERVENTION; AEROBIC
EXERCISE; SERUM ESTROGENS; UNITED-STATES; TIME
AB Purpose
Physical activity may reduce endogenous estrogens, but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003).
Methods
Postmenopausal women (N = 542) were ages 40 to 72 yr and not currently using hormone therapy. Accelerometers, worn for 7 d, were used to derive measures of average activity (counts per day) and sedentary behavior (<100 counts per minute per day). Estrogen metabolites were measured in 12-h urine samples using liquid chromatography-tandem mass spectrometry. Estrogen metabolites were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent estrogens. Geometric means of estrogen metabolites by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models.
Results
High activity was associated with lower levels of estrone and estradiol (P trend = 0.01), whereas increased sedentary time was positively associated with these parent estrogens (P trend = 0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol, and 16-epiestriol (P trend = 0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (P trend <= 0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent estrogens (P trend <= 0.02), whereas increased sedentary time was associated with a lower 16-pathway/parent estrogen ratio (P trend = 0.01).
Conclusions
Higher activity was associated with lower urinary estrogens, possibly through increased estrogen hydroxylation and subsequent metabolism, whereas sedentary behavior may reduce metabolism.
C1 [Dallal, Cher M.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
[Brinton, Louise A.; Falk, Roni T.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hartman, Terryl J.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Div Breast Canc Res, London SW3 6JB, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Ctr, London SW3 6JB, England.
[Xu, Xia; Veenstra, Timothy D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD USA.
[Veenstra, Timothy D.] C2N Diagnost, St Louis, MO USA.
RP Dallal, CM (reprint author), Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
EM cdallal@umd.edu
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU Intramural Research Program of the National Cancer Institute; Department
of Health and Human Services, USA; Cancer Prevention Fellowship Program;
Division of Cancer Prevention, National Cancer Institute; National
Cancer Institute Office of Science Planning and Assessment; National
Institutes of Health Office of Research on Women's Health
FX The Polish Breast Cancer Study was supported by the Intramural Research
Program of the National Cancer Institute, Department of Health and Human
Services, USA. Dr Cher Dallal was supported by the Cancer Prevention
Fellowship Program, Division of Cancer Prevention, National Cancer
Institute. This ancillary project was supported through supplemental
funding awarded by the National Cancer Institute Office of Science
Planning and Assessment and the National Institutes of Health Office of
Research on Women's Health.
NR 40
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAR
PY 2016
VL 48
IS 3
BP 439
EP 448
DI 10.1249/MSS.0000000000000790
PG 10
WC Sport Sciences
SC Sport Sciences
GA DE2RW
UT WOS:000370475600013
PM 26460631
ER
PT J
AU Wiemann, S
Pennacchio, C
Hu, YH
Hunter, P
Harbers, M
Amiet, A
Bethel, G
Busse, M
Carninci, P
Diekhans, M
Dunham, I
Hao, T
Harper, JW
Hayashizaki, Y
Heil, O
Hennig, S
Hotz-Wagenblatt, A
Jang, W
Jocker, A
Kawai, J
Koenig, C
Korn, B
Lambert, C
LeBeau, A
Lu, S
Maurer, J
Moore, T
Ohara, O
Park, J
Rolfs, A
Salehi-Ashtiani, K
Seiler, C
Simmons, B
Smith, AV
Steel, J
Wagner, L
Weaver, T
Wellenreuther, R
Yang, SW
Vidal, M
Gerhard, DS
LaBaer, J
Temple, G
Hill, DE
AF Wiemann, Stefan
Pennacchio, Christa
Hu, Yanhui
Hunter, Preston
Harbers, Matthias
Amiet, Alexandra
Bethel, Graeme
Busse, Melanie
Carninci, Piero
Diekhans, Mark
Dunham, Ian
Hao, Tong
Harper, J. Wade
Hayashizaki, Yoshihide
Heil, Oliver
Hennig, Steffen
Hotz-Wagenblatt, Agnes
Jang, Wonhee
Joecker, Anika
Kawai, Jun
Koenig, Christoph
Korn, Bernhard
Lambert, Cristen
LeBeau, Anita
Lu, Sun
Maurer, Johannes
Moore, Troy
Ohara, Osamu
Park, Jin
Rolfs, Andreas
Salehi-Ashtiani, Kourosh
Seiler, Catherine
Simmons, Blake
Smith, Anja van Brabant
Steel, Jason
Wagner, Lukas
Weaver, Tom
Wellenreuther, Ruth
Yang, Shuwei
Vidal, Marc
Gerhard, Daniela S.
LaBaer, Joshua
Temple, Gary
Hill, David E.
CA ORFeome Collaboration
TI The ORFeome Collaboration: a genome-scale human ORF-clone resource
SO NATURE METHODS
LA English
DT Letter
ID PROTEINS
C1 [Wiemann, Stefan; Joecker, Anika; Wellenreuther, Ruth] German Canc Res Ctr, Div Mol Genome Anal, Heidelberg, Germany.
[Wiemann, Stefan; Heil, Oliver; Hotz-Wagenblatt, Agnes] German Canc Res Ctr, Genom & Prote Core Facil, Heidelberg, Germany.
[Pennacchio, Christa] IMAGE Consortium, Lawrence Livermore Natl Labs, Livermore, CA USA.
[Hu, Yanhui] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Hunter, Preston; Park, Jin; Seiler, Catherine; Steel, Jason; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, VGPCPD, Tempe, AZ USA.
[Harbers, Matthias] DNAFORM Inc, Tsurumi Ku, Yokohama, Kanagawa, Japan.
[Harbers, Matthias; Carninci, Piero] RIKEN Yokohama Inst, RIKEN Ctr Life Sci Technol, Div Genom Technol, Tsurumi Ku, Yokohama, Kanagawa, Japan.
[Amiet, Alexandra; Smith, Anja van Brabant] GE Healthcare, Dharmacon, Lafayette, CO USA.
[Bethel, Graeme; Dunham, Ian] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England.
[Busse, Melanie; Weaver, Tom] Source BioSci, Nottingham, England.
[Diekhans, Mark] Univ Calif Santa Cruz, UC Santa Cruz Genom Inst, Santa Cruz, CA 95064 USA.
[Hao, Tong; Salehi-Ashtiani, Kourosh; Vidal, Marc; Hill, David E.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
[Hao, Tong; Salehi-Ashtiani, Kourosh; Vidal, Marc; Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Hao, Tong; Salehi-Ashtiani, Kourosh; Vidal, Marc; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Harper, J. Wade] Harvard Univ, Sch Med, DFHCC, DNA Resource Core, Boston, MA USA.
[Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Hayashizaki, Yoshihide; Kawai, Jun] RIKEN Yokohama Inst, RIKEN Prevent Med & Diag Innovat Program, Wako, Saitama, Japan.
[Hennig, Steffen; Koenig, Christoph; Maurer, Johannes] imaGenes GmbH, Berlin, Germany.
[Jang, Wonhee; Wagner, Lukas] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Korn, Bernhard] Ressourcenzentrum Genomforsch gGmbH, Berlin, Germany.
[Lambert, Cristen; Temple, Gary] NHGRI, NIH, Bethesda, MD 20892 USA.
[LeBeau, Anita; Simmons, Blake] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Lu, Sun; Yang, Shuwei] GeneCopoeia Inc, Rockville, MD USA.
[Lu, Sun] Guangzhou FulenGen Ltd, Guangzhou, Guangdong, Peoples R China.
[Moore, Troy; Simmons, Blake] Open Biosyst Inc, Huntsville, AL USA.
[Ohara, Osamu] Kasusa DNA Res Inst, Kisarazu, Chiba, Japan.
[Rolfs, Andreas] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Harvard Inst Prote, Boston, MA 02115 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA.
[LaBaer, Joshua] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA.
RP Wiemann, S (reprint author), German Canc Res Ctr, Div Mol Genome Anal, Heidelberg, Germany.; Wiemann, S (reprint author), German Canc Res Ctr, Genom & Prote Core Facil, Heidelberg, Germany.; LaBaer, J (reprint author), Arizona State Univ, Biodesign Inst, VGPCPD, Tempe, AZ USA.; Harbers, M (reprint author), DNAFORM Inc, Tsurumi Ku, Yokohama, Kanagawa, Japan.; Harbers, M (reprint author), RIKEN Yokohama Inst, RIKEN Ctr Life Sci Technol, Div Genom Technol, Tsurumi Ku, Yokohama, Kanagawa, Japan.; Vidal, M; Hill, DE (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.; Vidal, M; Hill, DE (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Vidal, M; Hill, DE (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.; Temple, G (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.; LaBaer, J (reprint author), Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA.
EM s.wiemann@dkfz.de; matthias.harbers@riken.jp;
marc_vidal@dfci.harvard.edu; joshua.labaer@asu.edu; gftemple@gmail.com;
david_hill@dfci.harvard.edu
RI Wiemann, Stefan/E-4424-2013; Hayashizaki, Yoshihide/N-6590-2015;
OI Wiemann, Stefan/0000-0003-4683-3174; Dunham, Ian/0000-0003-2525-5598;
Salehi-Ashtiani, Kourosh/0000-0002-6521-5243
NR 6
TC 2
Z9 2
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2016
VL 13
IS 3
BP 191
EP 192
DI 10.1038/nmeth.3776
PG 2
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DF0NU
UT WOS:000371036700006
ER
PT J
AU Sung, MH
Baek, S
Hager, GL
AF Sung, Myong-Hee
Baek, Songjoon
Hager, Gordon L.
TI Genome-wide footprinting: ready for prime time?
SO NATURE METHODS
LA English
DT Article
ID TRANSCRIPTION FACTOR-BINDING; GLUCOCORTICOID-RECEPTOR BINDING; CHROMATIN
ACCESSIBILITY; ANDROGEN RECEPTOR; INTRANUCLEAR DYNAMICS; DNA
INTERACTIONS; PROTEIN; CELLS; SITES; SEQUENCE
AB High-throughput sequencing technologies have allowed many gene locus-level molecular biology assays to become genome-wide profiling methods. DNA-cleaving enzymes such as DNase I have been used to probe accessible chromatin. The accessible regions contain functional regulatory sites, including promoters, insulators and enhancers. Deep sequencing of DNase-seq libraries and computational analysis of the cut profiles have been used to infer protein occupancy in the genome at the nucleotide level, a method introduced as 'digital genomic footprinting'. The approach has been proposed as an attractive alternative to the analysis of transcription factors (TFs) by chromatin immunoprecipitation followed by sequencing (ChIP-seq), and in theory it should overcome antibody issues, poor resolution and batch effects. Recent reports point to limitations of the DNase-based genomic footprinting approach and call into question the scope of detectable protein occupancy, especially for TFs with short-lived chromatin binding. The genomics community is grappling with issues concerning the utility of genomic footprinting and is reassessing the proposed approaches in terms of robust deliverables. Here we summarize the consensus as well as different views emerging from recent reports, and we describe the remaining issues and hurdles for genomic footprinting.
C1 [Sung, Myong-Hee; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Sung, Myong-Hee] NIA, Transcript Syst Dynam & Biol Unit, Lab Mol Biol & Immunol, US Natl Inst Hlth, Baltimore, MD 21224 USA.
RP Sung, MH; Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM sungm@mail.nih.gov; hagerg@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX Computationally intensive tasks were performed using the US National
Institutes of Health (NIH) Biowulf cluster, a GNU-Linux parallel
processing system. We thank the NIH Helix systems staff for the
management of this system. This work was supported by the Intramural
Research Program of the NIH, National Cancer Institute.
NR 58
TC 4
Z9 4
U1 6
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2016
VL 13
IS 3
BP 222
EP 228
DI 10.1038/nmeth.3766
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DF0NU
UT WOS:000371036700019
PM 26914206
ER
PT J
AU Franke, B
Stein, JL
Ripke, S
Anttila, V
Hibar, DP
van Hulzen, KJE
Arias-Vasquez, A
Smoller, JW
Nichols, TE
Neale, MC
McIntosh, AM
Lee, P
McMahon, FJ
Meyer-Lindenberg, A
Mattheisen, M
Andreassen, OA
Gruber, O
Sachdev, PS
Roiz-Santianez, R
Saykin, AJ
Ehrlich, S
Mather, KA
Turner, JA
Wright, MJ
O'Donovan, MC
Thompson, PM
Neale, BM
Medland, SE
Sullivan, PF
AF Franke, Barbara
Stein, Jason L.
Ripke, Stephan
Anttila, Verneri
Hibar, Derrek P.
van Hulzen, Kimm J. E.
Arias-Vasquez, Alejandro
Smoller, Jordan W.
Nichols, Thomas E.
Neale, Michael C.
McIntosh, Andrew M.
Lee, Phil
McMahon, Francis J.
Meyer-Lindenberg, Andreas
Mattheisen, Manuel
Andreassen, Ole A.
Gruber, Oliver
Sachdev, Perminder S.
Roiz-Santianez, Roberto
Saykin, Andrew J.
Ehrlich, Stefan
Mather, Karen A.
Turner, Jessica A.
Wright, Margaret J.
O'Donovan, Michael C.
Thompson, Paul M.
Neale, Benjamin M.
Medland, Sarah E.
Sullivan, Patrick F.
CA Psychiat Genomics Consortium
ENIGMA Consortium
TI Genetic influences on schizophrenia and subcortical brain volumes:
large-scale proof of concept
SO NATURE NEUROSCIENCE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; METAANALYSIS; ENDOPHENOTYPE; INDIVIDUALS;
PERSPECTIVE; PHENOTYPES; DISORDERS; DISCOVERY; RELATIVES; VARIANTS
AB Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
C1 [Franke, Barbara; van Hulzen, Kimm J. E.; Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Franke, Barbara; Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands.
[Franke, Barbara; van Hulzen, Kimm J. E.; Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
[Stein, Jason L.; Hibar, Derrek P.; Thompson, Paul M.] Univ So Calif, Keck Sch Med, Imaging Genet Ctr, Mark & Mary Stevens Neuroimaging & Informat Inst, Marina Del Rey, CA USA.
[Stein, Jason L.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90024 USA.
[Ripke, Stephan; Anttila, Verneri; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ripke, Stephan; Anttila, Verneri; Smoller, Jordan W.; Lee, Phil; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Ripke, Stephan] Charite, Dept Psychiat & Psychotherapy, Campus Charite Mitte, D-13353 Berlin, Germany.
[Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Smoller, Jordan W.; Lee, Phil; Neale, Benjamin M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Smoller, Jordan W.; Lee, Phil] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Nichols, Thomas E.] Univ Oxford, FMRIB Ctr, Oxford, England.
[Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England.
[Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England.
[Neale, Michael C.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Neale, Michael C.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA.
[McIntosh, Andrew M.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[McMahon, Francis J.] NIH, US Dept HHS, Intramural Res Program, Bethesda, MD USA.
[Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany.
[Mattheisen, Manuel] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Mattheisen, Manuel] IPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark.
[Mattheisen, Manuel] IPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark.
[Mattheisen, Manuel] Aarhus Univ, ISEQ, Ctr Integrated Sequencing, Aarhus, Denmark.
[Andreassen, Ole A.] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.
[Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway.
[Gruber, Oliver] Univ Med Ctr, Dept Psychiat & Psychotherapy, Ctr Translat Res Syst Neurosci & Psychia, Gottingen, Germany.
[Sachdev, Perminder S.; Mather, Karen A.] Univ New S Wales, Sch Psychiat, Ctr Healthy Brain Ageing, Sydney, NSW, Australia.
[Sachdev, Perminder S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia.
[Roiz-Santianez, Roberto] Univ Cantabria IDIVAL, Sch Med, Univ Hosp Marques Valdecilla, Dept Psychiat, Santander, Spain.
[Roiz-Santianez, Roberto] Cibersam Ctr Invest Biomed Red Salud Mental, Madrid, Spain.
[Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN 46202 USA.
[Saykin, Andrew J.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA.
[Saykin, Andrew J.] Indiana Univ Sch Med, Med & Mol Genet, Indianapolis, IN 46202 USA.
[Ehrlich, Stefan] Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, D-01062 Dresden, Germany.
[Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp, D-01062 Dresden, Germany.
[Turner, Jessica A.] Georgia State Univ, Atlanta, GA 30303 USA.
[Turner, Jessica A.] Mind Res Network, Albuquerque, NM USA.
[Wright, Margaret J.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Wright, Margaret J.] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia.
[O'Donovan, Michael C.] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Gen, Cardiff CF10 3AX, S Glam, Wales.
[O'Donovan, Michael C.] Cardiff Univ, Natl Ctr Mental Hlth, Cardiff CF10 3AX, S Glam, Wales.
[Neale, Benjamin M.] Broad Inst MIT & Harvard Cambridge, Med & Populat Genet Program, Cambridge, MA USA.
[Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Franke, B (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.; Franke, B (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands.; Franke, B (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.; Sullivan, PF (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.; Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC USA.; Sullivan, PF (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
EM barbara.franke@radboudumc.nl; pfsulliv@med.unc.edu
RI Webb, Bradley/B-1459-2009; Domenici, Enrico/K-8194-2016; McQuillin,
Andrew/C-1623-2008; Luciano, Michelle/F-7277-2010; Hansell,
Narelle/A-4553-2016; Meyer-Lindenberg, Andreas/H-1076-2011; Fernandez,
Guillen/B-3771-2009; Pantelis, Christos/H-7722-2014; Hansen, Thomas
Folkmann/O-5965-2014; Weale, Michael/F-2587-2010; Hardy,
John/C-2451-2009; McMahon, Katie/C-6440-2009; Singleton,
Andrew/C-3010-2009; Simmons, Andrew/B-8848-2008; Zwiers,
Marcel/D-2968-2009; Franke, Barbara/D-4836-2009; Matarin,
Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Ruderfer,
Douglas/M-5795-2016; Karen, Mather/O-9795-2016; de Zubicaray,
Greig/B-1763-2008; McDonald, Colm/C-1430-2009;
OI Webb, Bradley/0000-0002-0576-5366; Domenici, Enrico/0000-0001-7436-6919;
McQuillin, Andrew/0000-0003-1567-2240; Luciano,
Michelle/0000-0003-0935-7682; Hansell, Narelle/0000-0002-8229-9741;
Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Fernandez,
Guillen/0000-0002-5522-0604; Pantelis, Christos/0000-0002-9565-0238;
Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Whelan,
Christopher/0000-0003-0308-5583; McMahon, Francis/0000-0002-9469-305X;
Hansen, Thomas Folkmann/0000-0001-6703-7762; Weale,
Michael/0000-0003-4593-1186; McMahon, Katie/0000-0002-6357-615X;
Simmons, Andrew/0000-0003-2306-5811; Zwiers, Marcel/0000-0001-5483-2935;
Franke, Barbara/0000-0003-4375-6572; Matarin, Mar/0000-0002-4717-5735;
Melle, Ingrid /0000-0002-9783-548X; Ruderfer,
Douglas/0000-0002-2365-386X; Karen, Mather/0000-0003-4143-8941; de
Zubicaray, Greig/0000-0003-4506-0579; Williams,
Robert/0000-0001-8924-4447; de Geus, Eco/0000-0001-6022-2666; McIntosh,
Andrew/0000-0002-0198-4588; Bruggeman, Richard/0000-0002-3238-8471;
O'Neill, Francis Anthony/0000-0002-7531-7657; /0000-0002-8114-7615;
Satizabal, Claudia/0000-0002-1115-4430; Adolfsson,
Rolf/0000-0001-9785-8473; Jonsson, Erik/0000-0001-8368-6332; Nothen,
Markus/0000-0002-8770-2464; Wright, Margaret/0000-0001-7133-4970;
Medland, Sarah/0000-0003-1382-380X; Knight, Joanne/0000-0002-7148-1660
FU US National Institute of Mental Health (NIMH) [U01 MH094421];
Netherlands Scientific Organization [NWO 480-05-003]; Max Planck
Society; Max-Planck-Forderstiftung; DFG Center for Nanoscale Microscopy
& Molecular Physiology of the Brain (CNMPB), Gottingen, Germany; NIMH
[P50 MH080272, U01 MH081928, R01 MH092380, K99 MH101367, MH085548,
MH085542, MH071681, MH061884, MH58693, MH52618, R01 MH083094, R01
MH041953, R01 MH068881]; Massachusetts General Hospital Executive
Committee on Research; NCRR [RR026075]; Department of Veterans Affairs
Merit Review Program; Lundbeck Foundation; Danish Strategic Research
Council; Aarhus University; Stanley Research Foundation; UK Medical
Research Council (MRC) Centre [G0800509]; MRC Programme [G0801418];
European Community's Seventh Framework Programme
[HEALTH-F2-2010-241909]; European Union Seventh Framework Programme
(FP7) [279227]; MRC/Welsh Assembly Government; Margaret Temple Award
from the British Medical Association; Wellcome Trust [076113/C/04/Z,
076113/CI04/Z, 072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B,
068545/Z/02]; National Institute for Health Research programme grant
[RP-PG-0310-1002]; WTCCC2 grant [WTCCC-084710]; Janssen Research
Foundation, Beerse, Belgium; Netherlands Organization for Health
Research and Development (ZonMw) in the Mental Health program; Danish
Council for Strategic Research [09-067048]; Danish National Advanced
Technology Foundation [001-2009-2]; Lundbeck Foundation [R24-A3243]; EU;
Wellcome Trust as part of the WTCCC2 project; MRC; Research Council of
Norway [213837, 217776, 223273]; South-East Norway Health Authority
[2013-123]; K. G. Jebsen Foundation; Donald and Barbara Zucker
Foundation; North Shore - Long Island Jewish Health System Foundation;
Stanley Foundation; NARSAD; SynSys [EU FP7-242167]; Sigrid Juselius
Foundation; Academy of Finland [251704]; Sohlberg Foundation; Swedish
Research Council [2006-4472, 2009-5269, 2009-3413, 345-2003-3883,
315-2004-6977, 80576801, 70374401]; County Council of Vasterbotten,
Sweden; County Council of Norrbotten, Sweden; Bank of Sweden
Tercentenary Foundation; Swedish Council for Planning and Coordination
of Research; Swedish Council for Research in the Humanities and Social
Sciences; Swedish Council for Social Research; Estonian Ministry of
Science and Education [SF0180142s08]; US National Institutes of Health
(NIH) [R01 DK075787]; University of Tartu [SP1GVARENG]; European
Regional Development Fund [3.2.0304.11-0312]; FP7 grant [313010];
Singapore National Medical Research Council [NMRC/TCR/003/2008];
Singapore Biomedical Research Council; Singapore Agency for Science,
Technology and Research (A*STAR); Uppsala University, Uppsala University
Hospital, Science for Life Laboratory; Stockholm County Council;
Karolinska Insititutet; Australian Schizophrenia Research Bank; National
Health and Medical Research Council [386500]; Pratt Foundation; Ramsay
Health Care; Viertel Charitable Foundation; Schizophrenia Research
Institute; NSW Department of Health; National Health and Medical
Research Council (Australia); Australian National Health and Medical
Research Council; German Federal Ministry of Education and Research
(BMBF) through the Integrated Genome Research Network MooDS under the
National Genome Research Network plus (NGFNplus) [01GS08144, 01GS08147];
Integrated Network IntegraMent (Integrated Understanding of Causes and
Mechanisms in Mental Disorders), under e:Med Programme
(GlaxoSmithKline); Bavarian Ministry of Commerce; BMBF [01GS0481];
German Research Foundation (DFG); Alfried Krupp von Bohlen und
Halbach-Stiftung; European Union [279227, HEALTH-F4-2009-242257,
HEALTH-2011-1.1-2]; Stanley Medical Research Institute; Stanley Center
for Psychiatric Research; Sylvan Herman Foundation; Friedman Brain
Institute at the Mount Sinai School of Medicine; Karolinska Institutet,
Karolinska University Hospital; Swedish County Council; Soderstrom
Konigska Foundation; Juvenile Diabetes Research Foundation [WT0618S8];
National Institute of Health Research of England; Walter E. Nichols, M.
D., Professorship in the School of Medicine; Eleanor Nichols Endowment;
Walter F. & Rachael L. Nichols Endowment; William and Mary McIvor
Endowment, Stanford University; NIH [MH67257, MH59588, MH59571, MH59565,
MH59587, MH60870, MH59566, MH59586, MH61675, MH60879, MH81800, MH46276,
MH46289, MH46318, MH79469, MH79470, R01D0042157-01A, MH081802, 1RC2
MH089951, 1RC2 MH089995, R01MH62873, R01 NS080655, R01AG040060, R01
EB008432, R01 MH097268, U01 AG024904, R01 MH085667, R01 MH089722];
Genetic Association Information Network (GAIN); Paul Michael Donovan
Charitable Foundation; National Center for Research Resources [U54
RR020278]; WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z]; MRC
[G0000934]; Hong Kong Research Grants Council project [GRF 774707M,
777511M, 776412M, 776513M]; NIH institutes contributing to the Big Data
to Knowledge (BD2K) initiative [U54 EB020403]; NIBIB; NCI.ADNI;
Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904];
US Department of Defense [W81XWH-12-2-0012]; US National Institute on
Aging; National Institute of Biomedical Imaging and Bioengineering;
Canadian Institutes of Health Research; Northern California Institute
for Research and Education; Knut and Alice Wallenberg Foundation;
Torsten and Ragnar Soderbergs Foundation; HelseVest RHF [911554];
Scottish Mental Health Research Network; National Alliance for Research
on Schizophrenia and Depression (NARSAD) Independent Investigator Award;
Health Foundation Clinician Scientist Fellowship; Biobanking and
Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL);
Hersenstichting Nederland; Netherlands Organization for Scientific
Research (NWO); European Community [602450, 602805]; Vici grant from the
NWO [016.130.669]; Center for Brain Science Neuroinformatics Research
Group; Athinoula A. Martinos Center for Biomedical Imaging; Center for
Human Genetic Research; European Union-funded FP6 Integrated Project
IMAGEN [LSHM-CT-2007-037286]; FP7 projects [602450, 603016]; Innovative
Medicine Initiative Project EU-AIMS [115300-2]; Medical Research Council
programme grant [93558]; NIHR Biomedical Research Center; Swedish
Research Council (FORMAS); BMBF (eMED SysAlc) [01ZX1311A, 1EV0711]; BMBF
through the Integrated Genome Research Network MooDS under the National
Genome Research Network plus (NGFNplus) [01GS08144, 01GS08147,
01GS08148]; Integrated Network IntegraMent, under the auspices of the
e:Med Programme [01ZX1314A, 01ZX1314C, 01ZX1314G]; Exzellenz-Stiftung of
the Max Planck Society; BMBF in the framework of the National Genome
Research Network (NGFN) [FKZ 01GS0481]; Bergen Research Foundation;
University of Bergen; Dr Einar Martens Fund; K. G. Jebsen Foundation and
the Research Council of Norway; Netherlands Organization for Scientific
Research (Geestkracht program grant) [10-000-1002]; Center for Medical
Systems Biology (CSMB, NWO Genomics); Biobanking and Biomolecular
Resources Research Infrastructure (BBMRI-NL); VU University's Institutes
for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam;
University Medical Center Groningen, Leiden University Medical Center;
Genetic Association Information Network (GAIN) of the Foundation for the
National Institutes of Health; NWO; NWO large investment grant
[1750102007010]; Radboud University Nijmegen Medical Center; University
Medical Center Groningen and Accare; VU University Amsterdam; European
Community's Seventh Framework Programme (FP7) [602450, 602805, 278948];
NWO [MW904-61-193, MaGW-nr 400-07-080, MagW 480-04-004, 51.02.060,
668.772, NWO/SPI 56-464-14192]; European Research Council [ERC-230374];
Utrecht University; NWO Brain and Cognition [433-09-220]; Australian
National Health and Medical Research Council (NHMRC)/Australian Research
Council Strategic Award [401162]; NHMRC [1045325, 310667, 401184,
525453, 568940, 389875, 486682, 1009064]; Commonwealth Scientific and
Industrial Research Organisation Flagship Collaboration Fund grant;
Australian Government; Alzheimer's Australia Dementia Research
Foundation; National Science Foundation [BCS-1229450]; Autism Speaks;
Australian Research Council [FT110100548, FT0991634]; NHMRC fellowship
[619667]; BMBF (grants) [01ZZ9603, 01ZZ0103, 01ZZ0403]; DFG [GR
1912/5-1]; German Ministry of Cultural Affairs; Social Ministry of the
Federal State of Mecklenburg-West Pomerania; Siemens Healthcare,
Erlangen, Germany; Federal State of Mecklenburg-West Pomerania;
University Medicine Greifswald; NHMRC program [401184, 350833, 568969];
NHMRC project grant [525453]; NHMRC capacity building grant [568940];
The NIMH [R01 MH078075, MH065580, MH001760, RC2 MH089964, R01 MH084098,
K01 MH085812, R01 MH100141, R01 MH077139, R01 MH095034, R01 MH062276,
R01 MH068922, R01 MH068921, MH 41953, MH083094, K99MH102357]; [CZ.
2.16/3.1.00/24022OPPK]; [NT/13770-4]; [00064203 FN Motol];
[ERC-2010-AdG 268800-NEUROSCHEMA]
FX PGC. The authors are grateful to the many family members who
participated in the studies that recruited these samples, to the many
clinicians who assisted in their recruitment, and to our team members,
without whom this study would have been impossible. Core funding for the
PGC is from the US National Institute of Mental Health (NIMH; U01
MH094421). Statistical analyses were carried out on the Genetic Cluster
Computer (http://www.geneticcluster.org/) hosted by SURFsara and
financially supported by the Netherlands Scientific Organization (NWO
480-05-003), along with a supplement from the Dutch Brain Foundation and
the VU University Amsterdam. The GRAS data collection was supported by
the Max Planck Society, the Max-Planck-Forderstiftung and the DFG Center
for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB),
Gottingen, Germany. The Boston CIDAR project was supported by the NIMH
(P50 MH080272, R. W. M.; U01 MH081928, L. J. S.; R01 MH092380, T. L. P.)
and the Massachusetts General Hospital Executive Committee on Research
(T. L. P.). P. H. L. is supported by NIMH K99 MH101367. ISC Portugal: C.
N. P. and M. T. P. have been supported by NIMH grants MH085548,
MH085542, MH071681, MH061884, MH58693 and MH52618 and NCRR grant
RR026075. C. N. P., M. T. P. and A. H. F. have been supported by grants
from the Department of Veterans Affairs Merit Review Program. The Danish
Aarhus study was supported by grants from Lundbeck Foundation, Danish
Strategic Research Council, Aarhus University, and Stanley Research
Foundation. Work in Cardiff was supported by UK Medical Research Council
(MRC) Centre (G0800509) and MRC Programme (G0801418) grants, the
European Community's Seventh Framework Programme (HEALTH-F2-2010-241909,
Project EU-GEI) the European Union Seventh Framework Programme
(FP7/2007-2013) under grant agreement 279227, a fellowship to J. W. from
the MRC/Welsh Assembly Government and the Margaret Temple Award from the
British Medical Association. We thank Novartis for their input in
obtaining CLOZUK samples, staff at The Doctor's Laboratory (L. Levett
and A. Levett) for help with sample acquisition and data linkage, and
staff in Cardiff (K. Mantripragada and L. Hopkins) for sample
management. CLOZUK and some other samples were genotyped at the Broad
Institute or by the Wellcome Trust Case Control Consortium (WTCCC) and
Wellcome Trust Case Control Consortium 2 (WTCCC2) (WT 083948/Z/07/Z). We
acknowledge use of the British 1958 Birth Cohort DNA (MRC: G0000934) and
the Wellcome Trust (068545/Z/0 and 076113/C/04/Z), the UK Blood Services
Common Controls (UKBS-CC collection), funded by the Wellcome Trust
(076113/C/04/Z) and by a National Institute for Health Research
programme grant to National Health Service Blood and Transplant
(RP-PG-0310-1002). Virginia Commonwealth University investigators were
supported by NIMH grants R01 MH083094, R01 MH041953, and R01 MH068881
and WTCCC2 grant WTCCC-084710. Recruitment of families in Bulgaria was
funded by the Janssen Research Foundation, Beerse, Belgium. We thank the
staff in the Neuroscience Biomarkers Genomic Lab led by R. Favis at
Janssen for sample processing and the staff at Illumina for genotyping
Janssen DNA samples. We also thank A. Santos, N. Bottrel, M.-A. Franc
and W. Cafferty of Janssen Research & Development) for operational
support. Dutch samples were funded by the Netherlands Organization for
Health Research and Development (ZonMw) in the Mental Health program and
by NIMH R01 MH078075. Danish samples were funded by the Danish Council
for Strategic Research (Journ. nr.; 09-067048), the Danish National
Advanced Technology Foundation (Journ. nr. 001-2009-2), the Lundbeck
Foundation (Journ. nr. R24-A3243), and the EU 7th Framework Programme.
The Wellcome Trust supported this study as part of the WTCCC2 project.
E. Bramon holds a MRC New Investigator Award and a MRC Centenary Award.
The TOP Study was supported by the Research Council of Norway (213837,
217776, 223273), South-East Norway Health Authority (2013-123) and K. G.
Jebsen Foundation. This work was supported by the Donald and Barbara
Zucker Foundation, the North Shore - Long Island Jewish Health System
Foundation and grants from the Stanley Foundation (A. K. M.), NARSAD (A.
K. M.), NIMH (MH065580 to T. Lencz; MH001760 to A. K. M.), and NIMH RC2
MH089964 and R01 MH084098. Finnish samples were funded by SynSys (EU
FP7-242167), Sigrid Juselius Foundation, the Academy of Finland (grant
251704), and the Sohlberg Foundation. The Swedish Research Council
(grants 2006-4472, 2009-5269, 2009-3413) and the County Councils of
Vasterbotten and Norrbotten, Sweden, supported the collection of the
Umea samples. The Betula Study, from which the Umea controls were
recruited, is supported by grants from the Swedish Research Council
(grants 345-2003-3883, 315-2004-6977) and the Bank of Sweden
Tercentenary Foundation, the Swedish Council for Planning and
Coordination of Research, the Swedish Council for Research in the
Humanities and Social Sciences and the Swedish Council for Social
Research. We acknowledge support from NIMH K01 MH085812 (M. C. K.) and
NIMH R01 MH100141 (M. C. K.). Estonian Genome Center at the University
of Tartu (EGCUT) work was supported by Targeted Financing from the
Estonian Ministry of Science and Education (SF0180142s08), US National
Institutes of Health (NIH) grant R01 DK075787, the Development Fund of
the University of Tartu (grant SP1GVARENG), the European Regional
Development Fund to the Centre of Excellence in Genomics (EXCEGEN; grant
3.2.0304.11-0312) and FP7 grant 313010. M. Macek was supported by CZ.
2.16/3.1.00/24022OPPK, NT/13770-4 and 00064203 FN Motol. Funding from
the Singapore National Medical Research Council (NMRC/TCR/003/2008) and
the Singapore Biomedical Research Council. We acknowledge the support of
the Singapore Agency for Science, Technology and Research (A*STAR).
Genotyping of the Swedish Hubin sample was performed by the SNP&SEQ
Technology Platform in Uppsala, which is supported by Uppsala
University, Uppsala University Hospital, Science for Life Laboratory and
the Swedish Research Council (contracts 80576801 and 70374401). The
Swedish Hubin sample was supported by Swedish Research Council (I. A.,
E. G. J.) and Stockholm County Council and the Karolinska Insititutet
(E. G. J.). B. J. M., V. J. C., R. J. S., S. V. C., F. A. H., A. V. J.,
C. M. L., P. T. M., C. P. and U. S. were supported by the Australian
Schizophrenia Research Bank, which is supported by an enabling grant
from the National Health and Medical Research Council (386500), the
Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation,
the Schizophrenia Research Institute and the NSW Department of Health.
C. P. is supported by a Senior Principal Research Fellowship from the
National Health and Medical Research Council (Australia). The Perth
sample collection was funded by Australian National Health and Medical
Research Council project grants and the Australian Schizophrenia
Research Bank.; The Bonn/Mannheim sample was genotyped in a study that
was supported by the German Federal Ministry of Education and Research
(BMBF) through the Integrated Genome Research Network MooDS (Systematic
Investigation of the Molecular Causes of Major Mood Disorders and
Schizophrenia; grant 01GS08144 to M. M. N. and S. C., grant 01GS08147 to
M. R.), under the National Genome Research Network plus (NGFNplus), and
the Integrated Network IntegraMent (Integrated Understanding of Causes
and Mechanisms in Mental Disorders), under e:Med Programme
(GlaxoSmithKline control sample; B. M.-M.) This work has been funded by
the Bavarian Ministry of Commerce and by the BMBF in the framework of
the National Genome Research Network, Forderkennzeichen 01GS0481 and the
Bavarian Ministry of Commerce. M. M. N. is a member of the German
Research Foundation (DFG)-funded Excellence Cluster ImmunoSensation. M.
M. N. also received support from the Alfried Krupp von Bohlen und
Halbach-Stiftung. M. R. was supported by the 7th Framework Programme of
the European Union (ADAMS project, HEALTH-F4-2009-242257; CRESTAR
project, HEALTH-2011-1.1-2) grant 279227. J. Knight holds the Joanne
Murphy Professor in Behavioural Science. The Stanley Center for
Psychiatric Research at the Broad Institute acknowledges funding from
the Stanley Medical Research Institute. Support for the Sweden
Schizophrenia Study (principal investigators P. F. S., C. M. H. and P.
Sklar) was provided by the NIMH (R01 MH077139 and R01 MH095034), the
Stanley Center for Psychiatric Research, the Sylvan Herman Foundation,
the Friedman Brain Institute at the Mount Sinai School of Medicine, the
Karolinska Institutet, Karolinska University Hospital, the Swedish
Research Council, the Swedish County Council and the Soderstrom Konigska
Foundation. We acknowledge use of DNA from the UK Blood Services
Collection of Common Controls (UKBS collection), funded by the Wellcome
Trust grant 076113/CI04/Z, by Juvenile Diabetes Research Foundation
grant WT0618S8, and by the National Institute of Health Research of
England. The Multicenter Genetics Studies of Schizophrenia and Molecular
Genetics of Schizophrenia studies study were supported by NIMH grant R01
MH062276 (to D. F. L., C. L., M. J. O. and D. B. W.), grant R01 MH068922
(to P. V. G.), grant R01 MH068921 (to A. E. P.) and grant R01 MH068881
(to B. P. R.). D. F. L. was supported by the Walter E. Nichols, M. D.,
Professorship in the School of Medicine, the Eleanor Nichols Endowment,
the Walter F. & Rachael L. Nichols Endowment and the William and Mary
McIvor Endowment, Stanford University. This study was supported by NIH
R01 grants (MH67257 to N. G. B., MH59588 to B. J. M., MH59571 to P. V.
G., MH59565 to R. F., MH59587 to F. A., MH60870 to W. F. B., MH59566 to
D. W. B., MH59586 to J. M. S., MH61675 to D. F. L., MH60879 to C. R. C.
and MH81800 to P. V. G.), NIH U01 grants (MH46276 to C. R. C., MH46289
to C. Kaufmann, MH46318 to M. T. Tsuang, MH79469 to P. V. G. and MH79470
to D. F. L.), the Genetic Association Information Network (GAIN) and The
Paul Michael Donovan Charitable Foundation. Genotyping was carried out
by the Center for Genotyping and Analysis at the Broad Institute of
Harvard and MIT (S. Gabriel and D. B. Mirel), supported by grant U54
RR020278 from the National Center for Research Resources. D. R. W. and
R. E. S. thank the staff of the Lieber Institute and the Clinical Brain
Disorders Branch of the Intramural Research Program of the NIMH for
their assistance in data collection and management.; We acknowledge the
Irish contribution to the International Schizophrenia Consortium (ISC)
study, the WTCCC2 schizophrenia study and WTCCC2 controls from the
1958BC and UKNBS, the Science Foundation Ireland (08/IN.1/B1916). We
acknowledge use of the Trinity Biobank sample from the Irish Blood
Transfusion Service and the Trinity Centre for High Performance
Computing. Funding for this study was provided by the WTCCC2 project
(085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z,
090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094)
and British 1958 Birth Cohort DNA collection funded by the MRC (grant
G0000934) and the Wellcome Trust (grant 068545/Z/02). Collection of the
UK National Blood Service controls was funded by the Wellcome Trust. We
acknowledge Hong Kong Research Grants Council project grants GRF
774707M, 777511M, 776412M and 776513M. E NIGMA. ENIGMA was supported in
part by a consortium grant (U54 EB020403 to P. M. T.) from the NIH
institutes contributing to the Big Data to Knowledge (BD2K) initiative,
including the NIBIB and NCI.ADNI and ADNI2GO: Data collection and
sharing for this project was funded by the Alzheimer's Disease
Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and US
Department of Defense (award W81XWH-12-2-0012). ADNI is funded by the US
National Institute on Aging, the National Institute of Biomedical
Imaging and Bioengineering, and through generous contributions from the
following: Alzheimer's Association; Alzheimer's Drug Discovery
Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb
Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company;
F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE
Healthcare; Innogenetics, N. V.; IXICO Ltd.; Janssen Alzheimer
Immunotherapy Research & Development, LLC.; Johnson & Johnson
Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co.,
Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier;
Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes
of Health Research is providing funds to support ADNI clinical sites in
Canada. Private sector contributions are facilitated by the Foundation
for the National Institutes of Health. The grantee organization is the
Northern California Institute for Research and Education, and the study
is coordinated by the Alzheimer's Disease Cooperative Study at the
University of California, San Diego. ADNI data are disseminated by the
Laboratory of Neuro Imaging at the University of Southern California.
Betula: this sample collection was supported by a Wallenberg Scholar
grant from the Knut and Alice Wallenberg Foundation and a grant from
Torsten and Ragnar Soderbergs Foundation to L. N., and a grant from
HelseVest RHF (grant 911554) to S. L. H. Bipolar Family Study: The
Bipolar Family Study wishes to thank the Scottish Mental Health Research
Network for research assistant support; the Brain Research Imaging
Centre Edinburgh, a center in the Scottish Funding Council Scottish
Imaging Network-A Platform for Scientific Excellence (SINAPSE)
Collaboration, for image acquisition; and the Wellcome Trust Clinical
Research Facility for genotyping. Genotyping was supported by a National
Alliance for Research on Schizophrenia and Depression (NARSAD)
Independent Investigator Award (to A. M. M.), and data collection was
supported by the Health Foundation Clinician Scientist Fellowship.; BIG:
This work makes use of the BIG (Brain Imaging Genetics) database, first
established in Nijmegen, the Netherlands, in 2007. This resource is now
part of the Cognomics Initiative (http://www.cognomics.nl/), a joint
initiative by researchers of the Donders Centre for Cognitive
Neuroimaging, the Human Genetics and Cognitive Neuroscience departments
of the Radboud University Medical Centre and the Max Planck Institute
for Psycholinguistics in Nijmegen. The Cognomics Initiative is supported
by the participating departments and centers and by external grants from
the Biobanking and Biomolecular Resources Research Infrastructure
(Netherlands) (BBMRI-NL), the Hersenstichting Nederland and the
Netherlands Organization for Scientific Research (NWO). We wish to thank
all persons who kindly participated in the BIG research. The research
leading to these results also receives funding from the European
Community's Seventh Framework Programme (FP7/2007-2013) under grant
agreements 602450 (IMAGEMEND) and 602805 (Aggressotype) and from
ERC-2010-AdG 268800-NEUROSCHEMA. B. F. is supported by a Vici grant from
the NWO (grant 016.130.669). Brain Genomics Superstruct Project (GSP):
Data were provided [ in part] by the Brain GSP of Harvard University and
the Massachusetts General Hospital, with support from the Center for
Brain Science Neuroinformatics Research Group, the Athinoula A. Martinos
Center for Biomedical Imaging and the Center for Human Genetic Research.
Twenty individual investigators at Harvard and Massachusetts General
Hospital generously contributed data to GSP. GIG: The GIG (Genomic
Imaging Gottingen) sample was established at the Center for
Translational Research in Systems Neuroscience and Psychiatry at
Gottingen University. We thank M. Keil, E. Diekhof, T. Melcher and I.
Henseler for assistance in MRI data acquisition, and E. Binder and H.
Mohr for help with genotyping. We are grateful to all persons who kindly
participated in the GIG study. IMAGEN: IMAGEN was supported by the
European Union-funded FP6 Integrated Project IMAGEN
(Reinforcement-Related Behaviour in Normal Brain Function and
Psychopathology) (LSHM-CT-2007-037286), the FP7 projects IMAGEMEND
(602450) and MATRICS (603016), and the Innovative Medicine Initiative
Project EU-AIMS (115300-2), the Medical Research Council programme grant
"Developmental pathways into adolescent substance abuse" (93558), as
well as the NIHR Biomedical Research Center "Mental Health". Further
support was provided by the Swedish Research Council (FORMAS) and the
BMBF (eMED SysAlc 01ZX1311A; Forschungsnetz AERIAL; 1EV0711). MooDS: The
establishment of the MooDS sample was funded by the BMBF through the
Integrated Genome Research Network MooDS (grant 01GS08144 to M. M. N.
and S. C., grant 01GS08147 to M. R. and A. M.-L. and grant 01GS08148 to
A. Heinz), under the auspices of the National Genome Research Network
plus (NGFNplus), and through the Integrated Network IntegraMent, under
the auspices of the e:Med Programme (grant 01ZX1314A to M. M. N., grant
01ZX1314C to H. Walter, grant 01ZX1314G to M. R.). MPIP: The MPIP Munich
Morphometry Sample comprises images acquired as part of the Munich
Antidepressant Response Signature Study and the Recurrent Unipolar
Depression (RUD) Case-Control study performed at the MPIP, and control
subject data acquired at the Ludwig Maximilians University, Munich,
Department of Psychiatry. We wish to acknowledge A. Olynyik and
radiographers R. Schirmer, E. Schreiter, R. Borschke and I. Eidner for
image acquisition and data preparation. We thank D. P.; Auer for local
study management in the initial phase of the RUD study. We are grateful
to GlaxoSmithKline for providing the genotypes of the RUD case-control
sample. We thank the staff of the Center of Applied Genotyping for
generating the genotypes of the MARS cohort. The study is supported by a
grant of the Exzellenz-Stiftung of the Max Planck Society. This work has
also been funded by the BMBF in the framework of the National Genome
Research Network (NGFN), FKZ 01GS0481. NCNG: Sample collection was
supported by grants from the Bergen Research Foundation and the
University of Bergen, the Dr Einar Martens Fund, the K. G. Jebsen
Foundation and the Research Council of Norway, to S. L. H., V. M. S. and
T. E. NESDA: Funding was obtained from the Netherlands Organization for
Scientific Research (Geestkracht program grant 10-000-1002), the Center
for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and
Biomolecular Resources Research Infrastructure (BBMRI-NL), VU
University's Institutes for Health and Care Research (EMGO+) and
Neuroscience Campus Amsterdam, University Medical Center Groningen,
Leiden University Medical Center and NIH (R01D0042157-01A, MH081802,
Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the
genotyping and analyses were funded by the Genetic Association
Information Network (GAIN) of the Foundation for the National Institutes
of Health. Computing was supported by BiG Grid, the Dutch e-Science
Grid, which is financially supported by NWO. NeuroIMAGE: NeuroIMAGE was
supported by NIH grant R01MH62873 (to S. V. Faraone), NWO large
investment grant 1750102007010 (to J. Buitelaar) and grants from Radboud
University Nijmegen Medical Center, University Medical Center Groningen
and Accare, and VU University Amsterdam. The research leading to these
results also receives funding from the European Community's Seventh
Framework Programme (FP7/2007-2013) under grant agreements 602450
(IMAGEMEND), 278948 (TACTICS) and 602805 (Aggressotype). NTR-Adults and
Brainscale: We would like to thank all twin participants from the
Netherlands Twin Register. The NTR-Adult and Brainscale studies were
supported by the NWO (MW904-61-193 (E. J. C. d. G. and D. I. B.),
MaGW-nr 400-07-080 (D. v. t. E.), MagW 480-04-004 (D. B), (51.02.060 (H.
H.), 668.772 (D. B. and H. H.); NWO/SPI 56-464-14192 (D. B.), the
European Research Council (ERC-230374) (D. B.), High Potential Grant
Utrecht University (H. H.), NWO Brain and Cognition 433-09-220 (H. H.)
and the Neuroscience Campus Amsterdam. Older Australian Twins Study
(OATS): We would like to acknowledge and thank the OATS participants,
their supporters and respective research teams. OATS is supported by
Australian National Health and Medical Research Council
(NHMRC)/Australian Research Council Strategic Award 401162 and NHMRC
project grant 1045325 to P. S. S. and colleagues. OATS was facilitated
through access to the Australian Twin Registry, a national research
resource supported by NHMRC enabling grant 310667, administered by the
University of Melbourne. DNA was extracted by Genetic Repositories
Australia, an Enabling Facility supported by NHMRC grant 401184. OATS
genotyping was partly funded by a Commonwealth Scientific and Industrial
Research Organisation Flagship Collaboration Fund grant. H. B. is
supported by the Australian Government funded Dementia Collaborative
Research Centre, UNSW. N. J. A. was supported by NHMRC project grant
525453 and K. A. M.; is supported by an Alzheimer's Australia Dementia
Research Foundation postdoctoral fellowship and NHMRC capacity building
grant 568940. QTIM: D. P. H., N. J., C. R. K. C. and P. M. T. are
supported, in part, by NIH grants R01 NS080655, R01AG040060, R01
EB008432, R01 MH097268, U01 AG024904, R01 MH085667, R01 MH089722, P41
EB015922 and R01 MH094343. R. K. W. is supported by National Science
Foundation (BCS-1229450). J. L. S. was supported by the NIMH
(K99MH102357) and Autism Speaks. S. E. M. and G. I. d. Z. are supported
by Future Fellowships (FT110100548, FT0991634) from the Australian
Research Council, and G. W. M. is supported by an NHMRC fellowship
(619667). The QTIM study is supported by grants from the NIH (R01
HD050735) and the NHMRC (389875, 486682, 1009064). We thank the twins
and siblings for their participation, M. Grace and A. Eldridge for twin
recruitment, A. Al Najjar and other radiographers for scanning, K.
McAloney and D. Park for research support, and A. Henders and staff for
DNA sample processing and preparation. SHIP: The Study of Health in
Pomerania (SHIP) is supported by the BMBF (grants 01ZZ9603, 01ZZ0103 and
01ZZ0403) and the DFG (GR 1912/5-1). Genome-wide data and MRI scans were
supported by a joint grant from Siemens Healthcare, Erlangen, Germany,
and the Federal State of Mecklenburg-West Pomerania. SHIP-TREND-0: This
cohort is part of the Community Medicine Research (CMR) net of the
University of Greifswald, which is funded by the BMBF and the German
Ministry of Cultural Affairs, as well as by the Social Ministry of the
Federal State of Mecklenburg-West Pomerania. CMR encompasses several
research projects that share data from SHIP. MRI scans were supported by
a joint grant from Siemens Healthcare, Erlangen, Germany, and the
Federal State of Mecklenburg-West Pomerania. The SHIP authors are
grateful to M. Stanke for the opportunity to use his server cluster for
SNP imputation as well as to H. Prokisch and T. Meitinger
(HelmholtzZentrum Munchen) for genotyping the SHIP-TREND cohort, which
was supported by the BMBF (grant 03ZIK012). We thank all staff members
and participants of the SHIP studies, as well as all of the genotyping
staff for generating the SHIP SNP data set. D. J. is supported by a
scholarship from the Gerhard-Domagk Programme of the University Medicine
Greifswald. Sydney Memory and Ageing Study (Sydney MAS): We would like
to thank the Sydney MAS participants, their supporters and respective
research teams. Sydney MAS was supported by NHMRC program grants 350833
and 568969 to P. S. S., H. B. and G. Andrews. DNA was extracted by
Genetic Repositories Australia, an Enabling Facility supported by NHMRC
grant 401184. H. B. is supported by the Australian Government funded
Dementia Collaborative Research Centre, UNSW. N. J. A. was supported by
NHMRC project grant 525453 and K. A. M. is supported by an Alzheimer's
Australia Dementia Research Foundation postdoctoral fellowship. Both S.
Reppermund and K. A. M. are supported by NHMRC capacity building grant
568940. Data used in preparing this article were obtained from the ADNI
database (http://adni.loni.usc.edu/). Many investigators in ADNI
contributed to the design and implementation of ADNI and/or provided
data but did not participate in analysis or writing of this report. A
complete listing of ADNI investigators can be found at
http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledg
ement_List.pdf.
NR 38
TC 10
Z9 10
U1 6
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAR
PY 2016
VL 19
IS 3
BP 420
EP +
DI 10.1038/nn.4228
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA DE7MU
UT WOS:000370822200014
PM 26854805
ER
PT J
AU Kueider, AM
Tanaka, T
An, Y
Kitner-Triolo, MH
Palchamy, E
Ferrucci, L
Thambisetty, M
AF Kueider, Alexandra M.
Tanaka, Toshiko
An, Yang
Kitner-Triolo, Melissa H.
Palchamy, Elango
Ferrucci, Luigi
Thambisetty, Madhav
TI State- and trait-dependent associations of vitamin-D with brain function
during aging
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Vitamin D; Cognitive performance; Mendelian randomization
ID GENOME-WIDE ASSOCIATION; 25-HYDROXYVITAMIN D LEVELS; COGNITIVE
PERFORMANCE; GENETIC-VARIANTS; DISEASE; RISK; POPULATION; ALZHEIMERS;
DEMENTIA; DECLINE
AB We investigated whether (1) serum levels of 25-hydroxyvitamin D [25(OH)D] and single nucleotide polymorphisms (SNPs) in the group-specific component (GC) gene-regulating serum 25(OH)D levels are associated with cognition in older individuals; and (2) whether causal relationships exist between 25(OH)D and cognition during aging. Data from 1207 participants in the Baltimore Longitudinal Study of Aging were analyzed (mean follow-up, 10.4 years) to test associations between serum 25(OH)D and cognition. Two GC SNPs were used to derive a composite genetic risk score associated with lower 25(OH)D concentrations. Lower serum 25(OH)D and higher GC composite scores were associated with lower executive function at baseline. Mendelian randomization analyses suggested a causal relationship between lower serum 25(OH)D and poorer executive function and psychomotor speed. The SNP score was also associated with lower performance on measures of visuospatial abilities at baseline but with attenuated declines over time in visuospatial abilities and executive function. Widespread associations between vitamin-D regulatory SNPs and cognition suggest a mechanistic basis for the relationship between serum 25(OH)D levels and cognition during aging. Published by Elsevier Inc.
C1 [Kueider, Alexandra M.; Thambisetty, Madhav] NIA, Unit Clin & Translat Neurosci, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Tanaka, Toshiko; Palchamy, Elango] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[An, Yang; Kitner-Triolo, Melissa H.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Thambisetty, M (reprint author), NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, 251 Bayview Blvd,Room 4B311, Baltimore, MD 21224 USA.
EM thambisettym@mail.nih.gov
OI Kueider, Alexandra/0000-0001-7132-5003
FU National Institute of Health (NIH), National Institute on Aging (NIA)
FX The authors are grateful to the Baltimore Longitudinal Study of Aging
participants and staff for their dedication to these studies. This work
was supported entirely by the Intramural Research Program of the
National Institute of Health (NIH), National Institute on Aging (NIA).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the article.
NR 46
TC 0
Z9 0
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2016
VL 39
BP 38
EP 45
DI 10.1016/j.neurobiolaging.2015.11.002
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DE8IW
UT WOS:000370880700004
PM 26923400
ER
PT J
AU Korthauer, LE
Nowak, NT
Moffat, SD
An, Y
Rowland, LM
Barker, PB
Resnick, SM
Driscoll, I
AF Korthauer, Laura E.
Nowak, Nicole T.
Moffat, Scott D.
An, Yang
Rowland, Laura M.
Barker, Peter B.
Resnick, Susan M.
Driscoll, Ira
TI Correlates of virtual navigation performance in older adults
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Normal aging; Place learning; Memory; Virtual navigation; Hippocampus;
DTI
ID MILD COGNITIVE IMPAIRMENT; CEREBRAL WHITE-MATTER;
MAGNETIC-RESONANCE-SPECTROSCOPY; POSTERIOR CINGULATE FASCICULUS;
DIFFUSION-TENSOR ANALYSIS; HUMAN SPATIAL NAVIGATION; EARLY
ALZHEIMERS-DISEASE; AGE-RELATED DIFFERENCES; MORRIS WATER MAZE; UNCINATE
FASCICULUS
AB Despite considerable evidence for deleterious effects of aging on place learning and memory, less is known about the trajectory and the putative neural mechanisms of these decrements. The virtual Morris water task (vMWT) is a human analog of a nonhuman spatial navigation task. The present study investigated longitudinal changes in place learning in 51 healthy, nondemented adults (age 30-83 years) who completed the vMWT and a neuropsychological battery at 2 time-points (interval = similar to 8 years). We also assessed cross-sectional associations between vMWT and brain structure, biochemical integrity, and standardized neuropsychological measures in a subset of 22 individuals who underwent magnetic resonance imaging at follow-up. Despite no longitudinal decrement in vMWT performance, there were cross-sectional age differences on the vMWT favoring younger adults. Negative associations were observed between vMWT latency and gray matter volumes in the right hippocampus, bilateral thalamus, and right medial orbitofrontal cortex and between vMWT latency and white matter fractional anisotropy in the bilateral uncinate fasciculus. Collectively, these results suggest a pattern of differences in the structural integrity of regions supporting successful navigation even in the absence of longitudinal performance decrements. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Korthauer, Laura E.; Nowak, Nicole T.; Driscoll, Ira] Univ Wisconsin, Dept Psychol, 2441 E Hartford Ave, Milwaukee, WI 53211 USA.
[Moffat, Scott D.] Georgia Inst Technol, Sch Psychol, Atlanta, GA 30332 USA.
[An, Yang; Resnick, Susan M.; Driscoll, Ira] NIA, NIH, Baltimore, MD 21224 USA.
[Rowland, Laura M.] Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Barker, Peter B.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.
RP Driscoll, I (reprint author), Univ Wisconsin, Dept Psychol, 2441 E Hartford Ave, Milwaukee, WI 53211 USA.
EM driscoli@uwm.edu
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 102
TC 1
Z9 1
U1 3
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2016
VL 39
BP 118
EP 127
DI 10.1016/j.neurobiolaging.2015.12.003
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DE8IW
UT WOS:000370880700012
PM 26923408
ER
PT J
AU Sandrini, M
Manenti, R
Brambilla, M
Cobelli, C
Cohen, LG
Cotelli, M
AF Sandrini, Marco
Manenti, Rosa
Brambilla, Michela
Cobelli, Chiara
Cohen, Leonardo G.
Cotelli, Maria
TI Older adults get episodic memory boosting from noninvasive stimulation
of prefrontal cortex during learning
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE tDCS; Aging; Encoding; Episodic memory; Prefrontal cortex
ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM-MEMORY; MILD COGNITIVE
IMPAIRMENT; HUMAN MOTOR CORTEX; BRAIN-STIMULATION; ASSOCIATIVE MEMORY;
SKILL ACQUISITION; CAUSAL ROLE; HEALTHY; RTMS
AB Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Sandrini, Marco] Univ Roehampton, Dept Psychol, London, England.
[Manenti, Rosa; Brambilla, Michela; Cobelli, Chiara; Cotelli, Maria] IRCCS Ist Ctr San Giovanni di Dio Fatebenefratell, Neuropsychol Unit, Brescia, Italy.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Sandrini, M (reprint author), Univ Roehampton, Dept Psychol, Whitelands Coll, Parkstead House,Holybourne Ave, London SW15 4JD, England.
EM marco.sandrini@roehampton.ac.uk
RI Brambilla, Michela/J-2288-2016; Manenti, Rosa/J-7656-2016; Cotelli,
Maria/K-1355-2016; Sandrini, Marco/J-2276-2014; Cobelli,
Chiara/D-6908-2017
OI Brambilla, Michela/0000-0003-0761-2037; Manenti,
Rosa/0000-0002-5955-2323; Cotelli, Maria/0000-0003-3208-3798; Sandrini,
Marco/0000-0002-1664-5722; Cobelli, Chiara/0000-0002-9193-8912
FU Intramural NIH HHS [Z99 NS999999]
NR 78
TC 4
Z9 4
U1 8
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2016
VL 39
BP 210
EP 216
DI 10.1016/j.neurobiolaging.2015.12.010
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DE8IW
UT WOS:000370880700022
PM 26923418
ER
PT J
AU Barber, IS
Garcia-Cardenas, JM
Sakdapanichkul, C
Deacon, C
Erazo, GZ
Guerreiro, R
Bras, J
Hernandez, D
Singleton, A
Guetta-Baranes, T
Braae, A
Clement, N
Patel, T
Brookes, K
Medway, C
Chappell, S
Mann, DM
Morgan, K
AF Barber, Imelda S.
Garcia-Cardenas, Jennyfer M.
Sakdapanichkul, Chidchanok
Deacon, Christopher
Erazo, Gabriela Zapata
Guerreiro, Rita
Bras, Jose
Hernandez, Dena
Singleton, Andrew
Guetta-Baranes, Tamar
Braae, Anne
Clement, Naomi
Patel, Tulsi
Brookes, Keeley
Medway, Christopher
Chappell, Sally
Mann, David M.
Morgan, Kevin
CA ARUK Consortium
TI Screening exons 16 and 17 of the amyloid precursor protein gene in
sporadic early-onset Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Early-onset; Sporadic; Screening; APP; rs367709245
ID MUTATION; LOCUS
AB Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset <= 65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 knowncausative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a nonsignificantly increased minor allele frequency in our sEOADcohort (0.006) compared to LOAD(0.002) and controls (0.002). To assess the effect of the 6-bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harboring the deletion found no evidence of transcripts with exon 17 removed. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Barber, Imelda S.; Garcia-Cardenas, Jennyfer M.; Sakdapanichkul, Chidchanok; Deacon, Christopher; Erazo, Gabriela Zapata; Guetta-Baranes, Tamar; Braae, Anne; Clement, Naomi; Patel, Tulsi; Brookes, Keeley; Medway, Christopher; Chappell, Sally; Morgan, Kevin] Univ Nottingham, Human Genet, Sch Life Sci, Nottingham NG7 2RD, England.
[Guerreiro, Rita; Bras, Jose] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Mann, David M.] Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Clin & Cognit Sci Res Grp, Manchester, Lancs, England.
RP Morgan, K (reprint author), Queens Med Ctr, Human Genom & Mol Genet, Inst Genet, Sch Mol Med Sci, A Floor,West Block,Room 1306, Nottingham NG7 2UH, England.
EM kevin.morgan@nottingham.ac.uk
RI Singleton, Andrew/C-3010-2009;
OI Todd, Stephen/0000-0002-2312-9195
FU Alzheimer's Research UK; Big Lottery Fund; School of Life Sciences at
The University of Nottingham; Alzheimer's Society
FX The University of Nottingham laboratory is funded by Alzheimer's
Research UK and the Big Lottery Fund. IB's PhD studentship is jointly
funded by Alzheimer's Research UK and the School of Life Sciences at The
University of Nottingham. JB and RG's Fellowships are funded by The
Alzheimer's Society.
NR 17
TC 2
Z9 2
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2016
VL 39
AR 220.e1
DI 10.1016/j.neurobiolaging.2015.12.011
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DE8IW
UT WOS:000370880700029
PM 26803359
ER
PT J
AU Chio, A
Mora, G
Sabatelli, M
Caponnetto, C
Lunetta, C
Traynor, BJ
Johnson, JO
Nalls, MA
Calvo, A
Moglia, C
Borghero, G
Trojsi, F
La Bella, V
Volanti, P
Simone, I
Salvi, F
Logullo, FO
Riva, N
Carrera, P
Giannini, F
Mandrioli, J
Tanel, R
Capasso, M
Tremolizzo, L
Battistini, S
Murru, MR
Origone, P
Zollino, M
Penco, S
Mazzini, L
D'Alfonso, S
Restagno, G
Brunetti, M
Barberis, M
Conforti, FL
AF Chio, Adriano
Mora, Gabriele
Sabatelli, Mario
Caponnetto, Claudia
Lunetta, Christian
Traynor, Bryan J.
Johnson, Janel O.
Nalls, Mike A.
Calvo, Andrea
Moglia, Cristina
Borghero, Giuseppe
Trojsi, Francesca
La Bella, Vincenzo
Volanti, Paolo
Simone, Isabella
Salvi, Fabrizio
Logullo, Francesco O.
Riva, Nilo
Carrera, Paola
Giannini, Fabio
Mandrioli, Jessica
Tanel, Raffaella
Capasso, Margherita
Tremolizzo, Lucio
Battistini, Stefania
Murru, Maria Rita
Origone, Paola
Zollino, Marcella
Penco, Silvana
Mazzini, Letizia
D'Alfonso, Sandra
Restagno, Gabriella
Brunetti, Maura
Barberis, Marco
Conforti, Francesca L.
CA ITALSGEN Consortium
SARDINIALS Consortium
TI ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis
patients with C9ORF72 GGGGCC expansion
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; Phenotype; ATXN2; C9ORF72
ID FRONTOTEMPORAL DEMENTIA; REPEAT EXPANSIONS; ALS; CARRIERS; SIZE
AB There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (>= 28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender-and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Restagno, Gabriella; Brunetti, Maura; Barberis, Marco; ITALSGEN Consortium] Univ Turin, Dept Neurosci Neurol 2, ALS Ctr Rita Levi Montalcini, Turin, Italy.
[Chio, Adriano; Calvo, Andrea; SARDINIALS Consortium] Azienda Osped Univ Citta Salute Sci, Turin, Italy.
[Mora, Gabriele] IRCCS, Ist Sci Milano, Fdn Salvatore Maugeri, Dept Neurol Rehabil, Milan, Italy.
[Sabatelli, Mario] Catholic Univ, Neurol Inst, Ctr Clinico NEMO Roma, Rome, Italy.
[Sabatelli, Mario] ICOMM Assoc ALS Res, Rome, Italy.
[Caponnetto, Claudia; Origone, Paola] IRCCS, Azienda Osped Univ San Martino IST, Rehabil Maternal & Child Hlth, Dept Neurosci Ophthalmol Genet, Genoa, Italy.
[Lunetta, Christian] Serena Onlus Fdn, NEuroMusc Omnicenter, Milan, Italy.
[Traynor, Bryan J.; Johnson, Janel O.] Natl Inst Hlth, Natl Inst Aging, Neurogenet Lab, Neuromusc Dis Res Sect, Bethesda, MD USA.
[Johnson, Janel O.] Neuromusc Ctr Cleveland Clin, Dept Neurol Neurol Inst, Cleveland, OH USA.
[Nalls, Mike A.] Natl Inst Hlth, Natl Inst Aging, Neurogenet Lab, Mol Genet Sect, Bethesda, MD USA.
[Borghero, Giuseppe] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy.
[Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy.
[Trojsi, Francesca] Univ Naples 2, Surg Neurol Metab & Aging Sci, Dept Med, Naples, Italy.
[La Bella, Vincenzo] Univ Palermo, ALS Clin Res Ctr Bio Ne C, Palermo, Italy.
[Volanti, Paolo] IRCCS, Sci Inst Mistretta, Salvatore Maugeri Fdn, Neurorehabilitat Unit ALS Ctr, Mistretta, Italy.
[Simone, Isabella] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
[Salvi, Fabrizio] IRCCS, Inst Neurol Sci, Dept Neurol, Ctr Diag & Cure Rare Dis, Bologna, Italy.
[Logullo, Francesco O.] Marche Polytech Univ, Neurol Clin, Ancona, Italy.
[Riva, Nilo] IRCCS, San Raffaele Sci Inst, Dept Neurol & Inst Expt Neurol INSPE, Milan, Italy.
[Carrera, Paola] IRCCS, San Raffaele Sci Inst, Unit Genom human Dis Diag, Div Genet & Cell Biol, Milan, Italy.
[Giannini, Fabio; Battistini, Stefania] Univ Siena, Dept Med Surg & Neurol Sci, Via Laterina 8, I-53100 Siena, Italy.
[Mandrioli, Jessica] S Agostino Estense Hosp, Dept Neurosci, Modena, Italy.
[Mandrioli, Jessica] Univ Modena & Reggio Emilia, Modena, Italy.
[Tanel, Raffaella] Santa Chiara Hosp, Dept Neurol, Trento, Italy.
[Capasso, Margherita] Univ G dAnnunzio, Dept Neurol, Chieti, Italy.
[Tremolizzo, Lucio] Univ Milano Bicocca, Sch Med & Surg & NeuroMI, Neurol Unit, Monza, Italy.
[Murru, Maria Rita] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Multiple Sclerosis Ctr ASL 8 Cagliari, Cagliari, Italy.
[Zollino, Marcella] Catholic Univ, Inst Med Genet, Rome, Italy.
[Penco, Silvana] Osped Niguarda Ca Granda, Dept Lab Med Med Genet, Milan, Italy.
[Mazzini, Letizia] Amedeo Avogadro Univ Eastern Piedmont, IRCAD, Dept Hlth Sci, Novara, Italy.
[D'Alfonso, Sandra] Azienda Osped Univ Maggiore Carita, Dept Neurol, ALS Ctr, Novara, Italy.
[Restagno, Gabriella; Brunetti, Maura; Barberis, Marco] Azienda Osped Univ Citta Salute Sci, Mol Genet Lab, Dept Lab Med, Turin, Italy.
[Conforti, Francesca L.] Natl Res Council Mangone, Inst Neurol Sci, Cosenza, Italy.
RP Chio, A (reprint author), Univ Turin, Dept Neurosci Neurol 2, ALS Ctr Rita Levi Montalcini, Turin, Italy.
EM achio@usa.net
RI MANDRIOLI, JESSICA/K-7235-2016; Moglia, Cristina/K-4142-2016;
Battistini, Stefania/N-2596-2015; benigni, michele/J-7830-2016; Mosca,
Lorena/K-4015-2016; LOGROSCINO, GIANCARLO/K-5148-2016; riva,
nilo/J-7187-2012; Lunetta, Christian/K-9214-2016; La Bella,
Vincenzo/H-4532-2012; mancardi, giovanni luigi/K-8656-2016;
OI MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli,
Mario/0000-0001-6635-4985; Moglia, Cristina/0000-0001-7377-7222; Penco,
Silvana/0000-0003-1050-095X; Marrosu, Maria
Giovanna/0000-0003-2334-2081; Ilardi, Antonio/0000-0002-8305-0518;
Battistini, Stefania/0000-0003-2887-7624; Mosca,
Lorena/0000-0002-6767-2368; LOGROSCINO, GIANCARLO/0000-0003-0423-3242;
riva, nilo/0000-0002-0513-9517; Lunetta, Christian/0000-0002-4788-1875;
mancardi, giovanni luigi/0000-0001-8427-118X; Cammarosano,
Stefania/0000-0002-0981-5252; BENIGNI, MICHELE/0000-0002-3270-4761
FU Italian Ministry of Health [RF-2010-2309849]; European Community's
Health Seventh Framework Programme (FP7) [259867]; Joint Programme -
Neurodegenerative Disease Research (Italian Ministry of Education and
University) (Sophia Project); Agenzia Italiana per la Ricerca sulla SLA
(ARISLA) (Sardinials project); Associazione Piemontese per l'Assistenza
alla SLA (APASLA), Torino, Italy; Uniti per la Ricerca sulla Sclerosi
Laterale Amiotrofica (URSLA) Association, Novara, Italy; Fondazione
Mario e Anna Magnetto, Alpignano, Torino; Joint Programme -
Neurodegenerative Disease Research (Italian Ministry of Education and
University) (Strength Project); Joint Programme - Neurodegenerative
Disease Research (Italian Ministry of Education and University)
(ALS-Care Project); Agenzia Italiana per la Ricerca sulla SLA (ARISLA)
(RepeatALS project); NIH
FX This work was in part supported by the Italian Ministry of Health
(Ricerca Sanitaria Finalizzata 2010, grant RF-2010-2309849), the
European Community's Health Seventh Framework Programme (FP7/2007-2013
under grant agreement 259867), the Joint Programme - Neurodegenerative
Disease Research (Italian Ministry of Education and University) (Sophia,
Strength and ALS-Care Projects), the Agenzia Italiana per la Ricerca
sulla SLA (ARISLA) (Sardinials and RepeatALS projects), the Associazione
Piemontese per l'Assistenza alla SLA (APASLA), Torino, Italy, the Uniti
per la Ricerca sulla Sclerosi Laterale Amiotrofica (URSLA) Association,
Novara, Italy, and the Fondazione Mario e Anna Magnetto, Alpignano,
Torino. Intramural Research Program of the NIH.
NR 23
TC 0
Z9 0
U1 7
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2016
VL 39
AR 218.e5
DI 10.1016/j.neurobiolaging.2015.11.027
PG 4
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DE8IW
UT WOS:000370880700027
PM 26733254
ER
PT J
AU Brooks, BP
Thompson, AH
Sloan, JL
Manoli, I
Carrillo-Carrasco, N
Zein, WM
Venditti, CP
AF Brooks, Brian P.
Thompson, Amy H.
Sloan, Jennifer L.
Manoli, Irini
Carrillo-Carrasco, Nuria
Zein, Wadih M.
Venditti, Charles P.
TI Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with
Cobalamin C Deficiency
SO OPHTHALMOLOGY
LA English
DT Article
ID METHYLMALONIC ACIDURIA; RETINAL DEGENERATION; CBLC-TYPE;
NATURAL-HISTORY; DRUG-DELIVERY; HOMOCYSTINURIA; DEFECT; HOMOCYSTEINE;
CHILDREN; ACIDEMIA
AB Purpose: To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism.
Design: Retrospective, observational case series.
Participants: Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health between August 2004 and September 2012. Patient ages ranged from 2 to 27 years at last ophthalmic visit, and follow-up ranged from 0 to 83 months (median, 37 months; range, 13-83 months) over a total of 69 visits.
Methods: Best-corrected visual acuity, slit-lamp biomicroscopy, dilated fundus examination, wide-field photography, fundus autofluorescence imaging, sedated electroretinography, optical coherence tomography, genetics and metabolite assessment.
Main Outcome Measures: Visual acuity and presence and degree of retinal degeneration and optic nerve pallor.
Results: Nystagmus (64%), strabismus (52%), macular degeneration (72%), optic nerve pallor (68%), and vascular changes (64%) were present. c.271dupA (p.R91KfsX14) homozygous patients (n = 14) showed early and extensive macular degeneration. Electroretinography showed that scotopic and photopic responses were reduced and delayed, but were preserved remarkably in some patients despite severe degeneration. Optical coherence tomography images through the central macular lesion of a patient with severe retinal degeneration showed extreme thinning, some preservation of retinal lamination, and nearly complete loss of the outer nuclear layer. Despite hyperhomocysteinemia, no patients exhibited lens dislocation.
Conclusions: This longitudinal study reports ocular outcomes in the largest group of patients with cblC deficiency systematically examined at a single center over an extended period. Differences in progression and severity of macular degeneration, optic nerve pallor, and vascular attenuation between homozygous c.271dupA (p.R91KfsX14) patients and compound heterozygotes were noted. The pace and chronicity of ophthalmic manifestations lacked strict correlation to metabolic status as measured during visits. Prenatal or early treatment, or both, may have mitigated ocular disease, leading to better functional acuity, but patients still progressed to severe macular degeneration. The effects of prenatal or early treatment, or both, in siblings; the manifestation of severe disease in infancy; the presence of comorbid developmental abnormalities; and the possible laminar structural defect noted in many patients are findings showing that cblC deficiency displays a developmental as well as a degenerative ocular phenotype. (C) 2016 Published by Elsevier on behalf of the American Academy of Ophthalmology.
C1 [Brooks, Brian P.; Thompson, Amy H.; Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Brooks, Brian P.; Sloan, Jennifer L.; Manoli, Irini; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Carrillo-Carrasco, Nuria] NIH, Natl Ctr Adv Translat Sci Therapeut Rare & Neglec, Bldg 10, Bethesda, MD 20892 USA.
RP Brooks, BP (reprint author), NEI, NIH, Bldg 10,Room 10B16, Bethesda, MD 20892 USA.
EM brooksb@mail.nih.gov
RI Carrillo-Carrasco, Nuria/B-9034-2009;
OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; Sloan,
Jennifer/0000-0003-4520-0949; Thompson, Amy/0000-0002-6435-062X
FU Intramural Research Program of the National Eye Institute; National
Institutes of Health; National Human Genome Research Institute,
Bethesda, Maryland
FX Supported by the Intramural Research Program of the National Eye
Institute, National Institutes of Health, and the National Human Genome
Research Institute, Bethesda, Maryland.
NR 58
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2016
VL 123
IS 3
BP 571
EP 582
DI 10.1016/j.ophtha.2015.10.041
PG 12
WC Ophthalmology
SC Ophthalmology
GA DE4UQ
UT WOS:000370626300032
PM 26825575
ER
PT J
AU Patel, AK
Newcomb, CW
Liesegang, TL
Pujari, SS
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Sen, HN
Artornsombudh, P
Kothari, S
Kempen, JH
AF Patel, Apurva K.
Newcomb, Craig W.
Liesegang, Teresa L.
Pujari, Siddharth S.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Sen, H. Nida
Artornsombudh, Pichaporn
Kothari, Srishti
Kempen, John H.
CA Systemic Immunosuppressive Therapy
TI Risk of Retinal Neovascularization in Cases of Uveitis
SO OPHTHALMOLOGY
LA English
DT Article
ID INFLAMMATORY OCULAR NEOVASCULARIZATION; ENDOTHELIAL GROWTH-FACTOR;
INTRAVITREAL BEVACIZUMAB; POSTERIOR UVEITIS; PARS PLANITIS; DISC
NEOVASCULARIZATION; OPTIC DISC; RETINOPATHY; PATHOGENESIS; MECHANISMS
AB Purpose: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis.
Design: Retrospective cohort study.
Participants: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices.
Methods: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate.
Main Outcome Measures: Prevalence and incidence of NV.
Results: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13 810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26 465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27-0.41). Factors associated with incident NV include age <35 years compared with >35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed >5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within <1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus.
Conclusions: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection. (C) 2016 by the American Academy of Ophthalmology.
C1 [Patel, Apurva K.; Artornsombudh, Pichaporn; Kothari, Srishti; Kempen, John H.] Univ Penn, Scheie Eye Inst, Ophthalmol, Philadelphia, PA 19104 USA.
[Newcomb, Craig W.; Kempen, John H.] Univ Penn, Scheie Eye Inst, Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Scheie Eye Inst, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Patel, Apurva K.] Retina Northwest PC, Portland, OR USA.
[Liesegang, Teresa L.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Casey Eye Inst, Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Casey Eye Inst, Internal Med, Portland, OR 97201 USA.
[Pujari, Siddharth S.] Om Eye Care Hosp, Belgaum, Karnataka, India.
[Pujari, Siddharth S.; Foster, C. Stephen; Artornsombudh, Pichaporn; Kothari, Srishti] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Ophthalmol, New York, NY 10029 USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Med, New York, NY 10029 USA.
[Nussenblatt, Robert B.; Sen, H. Nida] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.; Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA.
[Levy-Clarke, Grace A.] Tampa Bay Uveitis Ctr, Safety Harbor, FL USA.
[Artornsombudh, Pichaporn] Chulalongkorn Univ, Div Ophthalmol, Naval Med Dept, Royal Thai Navy,Dept Ophthalmol,Fac Med,Somdech P, Bangkok, Thailand.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
FU National Eye Institute [EY014943]; Research to Prevent Blindness (RPB);
Paul and Evanina Mackall Foundation; Lois Pope Life Foundation; RPB
James S. Adams Special Scholar Award; R.P.B. Harrington Special Scholar
Award; Research to Prevent Blindness Senior Scientific Investigator
Award; intramural funds of the National Eye Institute; Department of
Veterans' Affairs
FX Supported primarily by National Eye Institute Grant EY014943 (J.H.K.).
Additional support was provided by Research to Prevent Blindness (RPB),
the Paul and Evanina Mackall Foundation, and the Lois Pope Life
Foundation. J.H.K. was an RPB James S. Adams Special Scholar Award
recipient, J.E.T. was an R.P.B. Harrington Special Scholar Award
recipient, and D.A.J. and J.T.R. were Research to Prevent Blindness
Senior Scientific Investigator Award recipients during the course of the
study. G.A.L.-C. was previously supported by and RBN and HNS continues
to be supported by intramural funds of the National Eye Institute.
E.B.S. receives support from the Department of Veterans' Affairs. None
of the sponsors had any role in the design and conduct of the report;
the collection, management, analysis, and interpretation of the data; or
the preparation, review, and approval of this manuscript.
NR 32
TC 1
Z9 2
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2016
VL 123
IS 3
BP 646
EP 654
DI 10.1016/j.ophtha.2015.10.056
PG 9
WC Ophthalmology
SC Ophthalmology
GA DE4UQ
UT WOS:000370626300042
PM 26686964
ER
PT J
AU Weaver, MS
Heinze, KE
Bell, CJ
Wiener, L
Garee, AM
Kelly, KP
Casey, RL
Watson, A
Hinds, PS
AF Weaver, Meaghann S.
Heinze, Katherine E.
Bell, Cynthia J.
Wiener, Lori
Garee, Amy M.
Kelly, Katherine P.
Casey, Robert L.
Watson, Anne
Hinds, Pamela S.
CA Childrens Natl Hlth Syst
TI Establishing psychosocial palliative care standards for children and
adolescents with cancer and their families: An integrative review
SO PALLIATIVE MEDICINE
LA English
DT Review
DE Literature review; palliative care; psychosocial; pediatric oncology;
integrative
ID END-OF-LIFE; YOUNG-ADULT ONCOLOGY; PEDIATRIC ONCOLOGY; DECISION-MAKING;
SUPPORTIVE CARE; BRAIN-TUMORS; PARENTS; QUALITY; DEATH; PERSPECTIVES
AB Background: Despite standardization in disease assessments and curative interventions for childhood cancer, palliative assessments and psychosocial interventions remain diverse and disparate.
Aim: Identify current approaches to palliative care in the pediatric oncology setting to inform development of comprehensive psychosocial palliative care standards for pediatric and adolescent patients with cancer and their families. Analyze barriers to implementation and enabling factors.
Design: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines framed the search strategy and reporting. Data analysis followed integrative review methodology.
Data sources: Four databases were searched in May 2014 with date restrictions from 2000 to 2014: PubMed, Cochrane, PsycINFO, and Scopus. A total of 182 studies were included for synthesis. Types of studies included randomized and non-randomized trials with or without comparison groups, qualitative research, prior reviews, expert opinion, and consensus report.
Results: Integration of patient, parent, and clinician perspectives on end-of-life needs as gathered from primary manuscripts (using NVivo coding for first-order constructs) revealed mutual themes across stakeholders: holding to hope, communicating honestly, striving for relief from symptom burden, and caring for one another. Integration of themes from primary author palliative care outcome reports (second-order constructs) revealed the following shared priorities in cancer settings: care access; cost analysis; social support to include primary caregiver support, sibling care, bereavement outreach; symptom assessment and interventions to include both physical and psychological symptoms; communication approaches to include decision-making; and overall care quality.
Conclusion: The study team coordinated landmark psychosocial palliative care papers into an informed conceptual model (third-order construct) for approaching pediatric palliative care and psychosocial support in oncology settings.
C1 [Weaver, Meaghann S.] Childrens Natl Hlth Syst, Dept Oncol, Washington, DC USA.
[Weaver, Meaghann S.] St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
[Heinze, Katherine E.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Bell, Cynthia J.] Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA.
[Bell, Cynthia J.] Hosp Michigan Inst, Detroit, MI USA.
[Wiener, Lori] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Garee, Amy M.] Nationwide Childrens Hosp, Dept Oncol, Columbus, OH USA.
[Kelly, Katherine P.; Hinds, Pamela S.] Childrens Natl Hlth Syst, Dept Nursing Res & Qual Outcomes, Washington, DC USA.
[Casey, Robert L.] Univ Colorado, Dept Psychol, Denver, CO 80202 USA.
[Watson, Anne] Childrens Natl Hlth Syst, Dept Crit Care Med, Washington, DC USA.
RP Weaver, MS (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM Meaghann.Weaver@StJude.org
OI Bell, Cynthia/0000-0002-9026-0986
FU Intramural Program of National Cancer Institute, Center for Cancer
Research; ONS Foundation/Genentech, Inc.
FX This research received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors. This work was supported
in part by the Intramural Program of the National Cancer Institute,
Center for Cancer Research. This work is supported in part by ONS
Foundation/Genentech, Inc.
NR 82
TC 10
Z9 11
U1 10
U2 19
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-2163
EI 1477-030X
J9 PALLIATIVE MED
JI Palliat. Med.
PD MAR
PY 2016
VL 30
IS 3
SI SI
BP 212
EP 223
DI 10.1177/0269216315583446
PG 12
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Medicine, General & Internal
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; General & Internal Medicine
GA DE7KW
UT WOS:000370816400003
PM 25921709
ER
PT J
AU Brynildsen, JK
Najar, J
Hsu, LM
Vaupel, DB
Lu, HB
Ross, TJ
Yang, YH
Stein, EA
AF Brynildsen, Julia K.
Najar, Julie
Hsu, Li-Ming
Vaupel, D. Bruce
Lu, Hanbing
Ross, Thomas J.
Yang, Yihong
Stein, Elliot A.
TI A novel method to induce nicotine dependence by intermittent drug
delivery using osmotic minipumps
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Nicotine; Nicotine dependence; Nicotine withdrawal; Osmotic minipump;
Mecamylamine HCl
ID ABSTINENCE SYNDROME; TOBACCO WITHDRAWAL; LOCOMOTOR-ACTIVITY;
UP-REGULATION; RAT-BRAIN; RECEPTORS; EXPOSURE; SMOKING; REWARD; SYMPTOMS
AB Although osmotic minipumps are a reliable method for inducing nicotine dependence in rodents, continuous nicotine administration does not accurately model the intermittent pattern of nicotine intake in cigarette smokers. Our objectives, therefore, were to investigate whether intermittent nicotine delivery via osmotic minipumps could induce dependence in rats, and to compare the magnitude and duration of withdrawal following forced abstinence from intermittent nicotine to that induced by continuous nicotine administration. In order to administer nicotine intermittently, rats were surgically implanted with saline-filled osmotic minipumps attached to polyethylene tubing that contained hourly unit doses of nicotine alternating with mineral oil to mimic "injections". Three doses of nicotine (1.2, 2.4, and 4.8 mg/kg/day) and saline were administered for 14 days using this method. In order to compare our intermittent delivery method with the more traditional continuous nicotine delivery, a second group of rats was implanted with minipumps attached to tubing that delivered continuous nicotine for 14 days. Rats were administered a 1.5 mg/kg subcutaneous (SC) mecamylamine challenge and observed for somatic signs of withdrawal on days 7,14, 21, and 28 following minipump implantation. Fifteen somatic withdrawal signs were summed within a 50-minute observation period to obtain a composite Dependence Score. A generalized linear mixed-effects model revealed a significant Day x Dose x Method interaction. Amongst continuously-treated rats, only 4.8 mg/kg/d nicotine resulted in dependence scores significantly greater than those of controls at 14 days of exposure. In contrast, all intermittent nicotine groups showed significantly higher scores beginning at 7 days of exposure and persisting beyond 7 days of abstinence. In general, intermittent delivery produced a more robust withdrawal syndrome than continuous delivery, and did so at a lower dose threshold and with greater persistence after forced abstinence. Published by Elsevier Inc.
C1 [Brynildsen, Julia K.; Najar, Julie; Hsu, Li-Ming; Vaupel, D. Bruce; Lu, Hanbing; Ross, Thomas J.; Yang, Yihong; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD USA.
RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD USA.
EM EStein@intra.nida.nih.gov
FU FDA Center for Tobacco Products [NDA13001-001-00000]; Intramural
Research Program of NIDA/NIH [ZIA DA000572-06, ZIA DA000597-01]
FX This research was supported by a grant from the FDA Center for Tobacco
Products (grant number: NDA13001-001-00000 to EAS) and the Intramural
Research Program of NIDA/NIH (grant numbers: ZIA DA000572-06; ZIA
DA000597-01).
NR 36
TC 0
Z9 0
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD MAR
PY 2016
VL 142
BP 79
EP 84
DI 10.1016/j.pbb.2015.12.010
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA DF2PR
UT WOS:000371186700011
PM 26751248
ER
PT J
AU Waugh, DS
AF Waugh, David S.
TI Crystal structures of MBP fusion proteins
SO PROTEIN SCIENCE
LA English
DT Review
DE chaperone-assisted crystallization; crystallization chaperone;
crystallization tag; maltose-binding protein; MBP fusion protein;
surface entropy reduction mutagenesis
ID MALTOSE-BINDING-PROTEIN; CASPASE-RECRUITMENT DOMAIN; ESCHERICHIA-COLI;
COUPLED-RECEPTOR; LIGAND-BINDING; HIGH-AFFINITY; MOLECULAR RECOGNITION;
PARATHYROID-HORMONE; SURFACE ENTROPY; INSIGHTS
AB Although chaperone-assisted protein crystallization remains a comparatively rare undertaking, the number of crystal structures of polypeptides fused to maltose-binding protein (MBP) that have been deposited in the Protein Data Bank (PDB) has grown dramatically during the past decade. Altogether, 102 fusion protein structures were detected by Basic Local Alignment Search Tool (BLAST) analysis. Collectively, these structures comprise a range of sizes, space groups, and resolutions that are typical of the PDB as a whole. While most of these MBP fusion proteins were equipped with short inter-domain linkers to increase their rigidity, fusion proteins with long linkers have also been crystallized. In some cases, surface entropy reduction mutations in MBP appear to have facilitated the formation of crystals. A comparison of the structures of fused and unfused proteins, where both are available, reveals that MBP-mediated structural distortions are very rare.
C1 [Waugh, David S.] NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
EM waughd@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX Grant sponsors: Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 84
TC 2
Z9 2
U1 4
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD MAR
PY 2016
VL 25
IS 3
BP 559
EP 571
DI 10.1002/pro.2863
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DE9JN
UT WOS:000370952900002
PM 26682969
ER
PT J
AU Simen, P
Vlasov, K
Papadakis, S
AF Simen, Patrick
Vlasov, Ksenia
Papadakis, Samantha
TI Scale (In)Variance in a Unified Diffusion Model of Decision Making and
Timing
SO PSYCHOLOGICAL REVIEW
LA English
DT Article
DE diffusion; decision making; interval timing; Weber; scalar invariance
ID RESPONSE-TIME DISTRIBUTION; TEMPORAL DISCRIMINATION; PERCEPTUAL
DECISION; NEURAL COMPUTATIONS; CORTICAL CIRCUITS; SENSORY STIMULI;
REWARD RATE; INTERVAL; CHOICE; REPRESENTATION
AB Weber's law is the canonical scale-invariance law in psychology: when the intensities of 2 stimuli are scaled by any value k, the just-noticeable-difference between them also scales by k. A diffusion model that approximates a spike-counting process accounts for Weber's law (Link, 1992), but there exist surprising corollaries of this account that have not yet been described or tested. We show that (a) this spike-counting diffusion model predicts time-scale invariant decision time distributions in perceptual decision making, and time-scale invariant response time (RT) distributions in interval timing; (b) for 2-choice perceptual decisions, the model predicts equal accuracy but faster responding for stimulus pairs with equally scaled-up intensities; (c) the coefficient of variation (CV) of decision times should remain constant across average intensity scales, but should otherwise decrease as a specific function of stimulus discriminability and speed-accuracy trade-off; and (d) for timing tasks, RT CVs should be constant for all durations, and RT skewness should always equal 3 times the CV. We tested these predictions using visual, auditory and vibrotactile decision tasks and visual interval timing tasks in humans. The data conformed closely to the predictions in all modalities. These results support a unified theory of decision making and timing in terms of a common, underlying spike-counting process, compactly represented as a diffusion process.
C1 [Simen, Patrick; Papadakis, Samantha] Oberlin Coll, Dept Neurosci, 119 Woodland St, Oberlin, OH 44074 USA.
[Vlasov, Ksenia] NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA.
RP Simen, P (reprint author), Oberlin Coll, Dept Neurosci, 119 Woodland St, Oberlin, OH 44074 USA.
EM psimen@oberlin.edu
NR 87
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Z9 4
U1 4
U2 14
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0033-295X
EI 1939-1471
J9 PSYCHOL REV
JI Psychol. Rev.
PD MAR
PY 2016
VL 123
IS 2
BP 151
EP 181
DI 10.1037/rev0000014
PG 31
WC Psychology; Psychology, Multidisciplinary
SC Psychology
GA DF2AQ
UT WOS:000371141900002
PM 26461957
ER
PT J
AU Bennett, AV
Reeve, BB
Basch, EM
Mitchell, SA
Meeneghan, M
Battaglini, CL
Smith-Ryan, AE
Phillips, B
Shea, TC
Wood, WA
AF Bennett, Antonia V.
Reeve, Bryce B.
Basch, Ethan M.
Mitchell, Sandra A.
Meeneghan, Mathew
Battaglini, Claudio L.
Smith-Ryan, Abbie E.
Phillips, Brett
Shea, Thomas C.
Wood, William A.
TI Evaluation of pedometry as a patient-centered outcome in patients
undergoing hematopoietic cell transplant (HCT): a comparison of
pedometry and patient reports of symptoms, health, and quality of life
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE PRO-CTCAE; PROMIS Global-10; Fitbit; Pedometry; Hematopoietic cell
transplant; Oncology; Validation
ID ACTIVITY MONITORS; CANCER; INSTRUMENTS; CRITERIA; STEPS
AB We evaluated pedometry as a novel patient-centered outcome because it enables passive continuous assessment of activity and may provide information about the consequences of symptomatic toxicity complementary to self-report.
Adult patients undergoing hematopoietic cell transplant (HCT) wore pedometers and completed PRO assessments during transplant hospitalization (4 weeks) and 4 weeks post-discharge. Patient reports of symptomatic treatment toxicities (single items from PRO-CTCAE, http://healthcaredelivery.cancer.gov/pro-ctcae ) and symptoms, physical health, mental health, and quality of life (PROMISA (R) Global-10, http://nih.promis.org ), assessed weekly with 7-day recall on Likert scales, were compared individually with pedometry data, summarized as average daily steps per week, using linear mixed models.
Thirty-two patients [mean age 55 (SD = 14), 63 % male, 84 % white, 56 % autologous, 43 % allogeneic] completed a mean 4.6 (SD = 1.5, range 1-8) evaluable assessments. Regression model coefficients (beta) indicated within-person decrements in average daily steps were associated with increases in pain (beta = -852; 852 fewer steps per unit increase in pain score, p < 0.001), fatigue (beta = -886, p < 0.001), vomiting (beta = -518, p < 0.01), shaking/chills (beta = -587, p < 0.01), diarrhea (beta = -719, p < 0.001), shortness of breath (beta = -1018, p < 0.05), reduction in carrying out social activities (beta = 705, p < 0.01) or physical activities (beta = 618, p < 0.01), and global physical health (beta = 101, p < 0.001), but not global mental health or quality of life.
In this small sample of HCT recipients, more severe symptoms, impaired physical health, and restrictions in the performance of usual daily activities were associated with statistically significant decrements in objectively measured daily steps. Pedometry may be a valuable outcome measure and validation anchor in clinical research.
C1 [Bennett, Antonia V.; Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Campus Box 7411, Chapel Hill, NC 27599 USA.
[Basch, Ethan M.; Meeneghan, Mathew; Shea, Thomas C.; Wood, William A.] Univ N Carolina, Dept Med, Campus Box 7305, Chapel Hill, NC 27599 USA.
[Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, 9609 Med Ctr Dr,East Tower,Room 3-448, Rockville, MD 20850 USA.
[Battaglini, Claudio L.; Smith-Ryan, Abbie E.] Univ N Carolina, Dept Exercise & Sports Sci, Campus Box 8700, Chapel Hill, NC 27599 USA.
[Bennett, Antonia V.; Reeve, Bryce B.; Basch, Ethan M.; Meeneghan, Mathew; Battaglini, Claudio L.; Phillips, Brett; Shea, Thomas C.; Wood, William A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Campus Box 7295, Chapel Hill, NC 27599 USA.
RP Bennett, AV (reprint author), Univ N Carolina, Dept Hlth Policy & Management, Campus Box 7411, Chapel Hill, NC 27599 USA.; Bennett, AV (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Campus Box 7295, Chapel Hill, NC 27599 USA.
EM avbenn@unc.edu
FU University of North Carolina Cancer Research Fund
FX This study was supported by the University of North Carolina Cancer
Research Fund.
NR 23
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U1 4
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD MAR
PY 2016
VL 25
IS 3
BP 535
EP 546
DI 10.1007/s11136-015-1179-0
PG 12
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA DE7EB
UT WOS:000370796700006
PM 26577763
ER
PT J
AU Brock, B
Choi, K
Boyle, RG
Moilanen, M
Schillo, BA
AF Brock, Betsy
Choi, Kelvin
Boyle, Raymond G.
Moilanen, Molly
Schillo, Barbara A.
TI Tobacco product prices before and after a statewide tobacco tax increase
SO TOBACCO CONTROL
LA English
DT Article
ID CIGARETTE TAXES; TAXATION; STRATEGY; COUPONS; SMOKING
AB Background In 2013, the State of Minnesota Legislature passed a tobacco tax increase that increased the combined cigarette excise and sales tax by US$1.75 (from US$1.60 to US$3.35) and increased the tax on non-cigarette tobacco products from 70% to 95% of the wholesale price. The current study explores the change in tobacco prices in retail locations and whether the tax increase was fully passed to consumers.
Methods An observational study of tobacco retail prices was performed in a sample of 61 convenience stores in Minnesota, North Dakota, South Dakota and Wisconsin. Six rounds of data were collected between May 2013 and January 2014. In each round, purchases were made at the same stores for the same four tobacco products (Camel Blue cigarettes, Marlboro Gold cigarettes, Grizzly Wintergreen moist smokeless tobacco and Copenhagen Wintergreen moist smokeless tobacco).
Results For all studied tobacco products, prices in Minnesota increased significantly after the tax increase (Round 1-Round 6). After controlling for price changes in neighbouring states, the average price difference in Minnesota for the two cigarette brands increased by US$1.89 and US$1.81, which are both more than the US$1.75 tax increase. For moist smokeless, the average price difference increased by US$0.90 and US$0.94. Significant price changes were not observed in the comparison states. After the introduction of the minimum moist smokeless tax, a significantly higher proportion of Minnesota stores offered price promotions on smokeless tobacco.
Conclusions A large tobacco tax resulted in an average retail cigarette price exceeding the tax, suggesting the industry over-shifted the cigarette tax increase to consumers in Minnesota. The findings support the known public health benefit of tobacco tax increases while highlighting the need for additional information about how, or if, tobacco companies use price promotions to blunt the impact of tax increases.
C1 [Brock, Betsy] Assoc Nonsmokers Minnesota, Res Dept, St Paul, MN USA.
[Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD USA.
[Boyle, Raymond G.; Moilanen, Molly; Schillo, Barbara A.] ClearWay MinnesotaSM, Res Dept, Minneapolis, MN USA.
RP Brock, B (reprint author), Assoc Nonsmokers Minnesota, 2395 Univ Ave West,Suite 310, St Paul, MN 55114 USA.
EM betsy@ansrmn.org
FU ClearWay MinnesotaSM [PA-2014-0003]; National Institutes of
Health, National Institute on Minority Health and Health Disparities,
Division of Intramural Research
FX This work was supported by ClearWay MinnesotaSM contract
#PA-2014-0003. Dr Choi's effort on the manuscript was supported by the
National Institutes of Health, National Institute on Minority Health and
Health Disparities, Division of Intramural Research. The study was
designed and partly implemented while Dr Choi was at the University of
Minnesota.
NR 22
TC 1
Z9 1
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
EI 1468-3318
J9 TOB CONTROL
JI Tob. Control
PD MAR
PY 2016
VL 25
IS 2
BP 166
EP 173
DI 10.1136/tobaccocontrol-2014-052018
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DE7YH
UT WOS:000370852500008
PM 25564283
ER
PT J
AU Choi, K
AF Choi, Kelvin
TI The associations between exposure to tobacco coupons and predictors of
smoking behaviours among US youth
SO TOBACCO CONTROL
LA English
DT Article
ID YOUNG-ADULTS; ADOLESCENTS
AB Introduction A recent report showed that 13.1% of US middle and high school students were exposed to tobacco coupons in the past 30 days in 2012. The current study reanalysed data from the National Youth Tobacco Survey 2012 to examine the associations between exposure to tobacco coupons in the past 30 days and predictors of smoking among US youth, by smoking status.
Methods 24 658 middle and high school students were asked if and where they had received tobacco coupons in the past 30 days. Demographics, smoking behaviours, smoking-related beliefs, susceptibility to smoking and confidence in quitting smoking were assessed. Analyses were stratified by smoking status (never smokers, experimenters and current smokers). Data were weighted to be representative of the US youth.
Results Exposure to tobacco coupons was associated with lower likelihood of denying the social benefits of cigarette smoking and believing all tobacco products are dangerous; higher likelihood of being susceptible to smoking (among never smokers); lower likelihood to feel confident in quitting cigarettes completely (among current smokers); and higher likelihood to intend to purchase cigarettes in the next 30 days (among experimenters and current smokers; p<0.05).
Conclusions Tobacco coupons may promote smoking and hinder smoking cessation among youth. Regulating tobacco coupons may reduce youth smoking in the USA. Further research is needed to determine the effect of tobacco coupons on youth tobacco use globally.
C1 [Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kelvin.choi@nih.gov
FU National Institutes of Health, National Institute on Minority Health and
Health Disparities
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Minority Health and
Health Disparities.
NR 17
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U1 1
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
EI 1468-3318
J9 TOB CONTROL
JI Tob. Control
PD MAR
PY 2016
VL 25
IS 2
BP 232
EP 235
DI 10.1136/tobaccocontrol-2014-052147
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DE7YH
UT WOS:000370852500017
PM 25882686
ER
PT J
AU Hoover, KC
Barker, CM
AF Hoover, Kara C.
Barker, Christopher M.
TI West Nile virus, climate change, and circumpolar vulnerability
SO WILEY INTERDISCIPLINARY REVIEWS-CLIMATE CHANGE
LA English
DT Article
ID CULEX-TARSALIS DIPTERA; COMPLETE GENOME SEQUENCES; LOUIS
ENCEPHALITIS-VIRUS; UNITED-STATES; VECTOR COMPETENCE; CENTRAL-EUROPE;
LINEAGE 2; NEW-YORK; EXTRINSIC INCUBATION; MOSQUITOS DIPTERA
AB Climate has strong impacts on the spatial ranges of vector-borne infectious diseases as well as the timing and intensity of disease outbreaks; these and shifting challenges to human health driven by future climate change are critical concerns. Many diseases of tropical origin, including West Nile virus (WNV), are sensitive to climate and likely to change their distributions in the coming decades. The 1999 outbreak of WNV in North America is an example of rapid viral adaptation to a new geographic area while recent outbreaks in Europe demonstrate the capacity of multiple viral strains to expand rapidly. WNV is one of the most widely distributed arboviruses and has displayed high rates of mutability, adaptability, and virulence. Northward expansion of WNV is happening in Europe and North America and may make WNV an increasingly worrying health risk at higher latitudes. Circumpolar northward expansion of WNV's enzootic range appears unlikely over the coming centuryat least for sustained enzootic transmissionbut isolated and ephemeral transmission events might occur if the virus were to be introduced by migrating birds during warm months. Human populations in this area are at greater risk for health impacts from WNV transmission due to limited healthcare in rural areas, higher underlying morbidity in indigenous populations, and prolonged human-environment interactions (in populations engaging in traditional lifestyles). This review presents a multidisciplinary synthesis on WNV and climate change, potential for WNV expansion, and the vulnerability of the circumpolar north. WIREs Clim Change 2016, 7:283-300. doi: 10.1002/wcc.382 For further resources related to this article, please visit the .
C1 [Hoover, Kara C.] Univ Alaska Fairbanks, Dept Anthropol, Fairbanks, AK USA.
[Hoover, Kara C.] Univ Alaska Fairbanks, Dept Chem & Biochem, Fairbanks, AK USA.
[Barker, Christopher M.] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Barker, Christopher M.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA.
[Barker, Christopher M.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA.
RP Hoover, KC (reprint author), Univ Alaska Fairbanks, Dept Anthropol, Fairbanks, AK USA.; Hoover, KC (reprint author), Univ Alaska Fairbanks, Dept Chem & Biochem, Fairbanks, AK USA.
EM kchoover@alaska.edu
FU Centers for Disease Control and Prevention [U01EH000418]; Research and
Policy for Infectious Disease Dynamics (RAPIDD) program of the Science
and Technology Directorate, Department of Homeland Security and Fogarty
International Center, National Institutes of Health; Alaska EPSCoR NSF
[EPS-0701898]; state of Alaska; National Center for Research Resources,
a component of the National Institutes of Health [5P20RR016466]
FX CMB acknowledges support from Centers for Disease Control and Prevention
grant U01EH000418 to study the impacts of climate change on
mosquito-borne virus transmission and additional support from the
Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, Department of Homeland Security
and Fogarty International Center, National Institutes of Health. KCH
acknowledges support from Alaska EPSCoR NSF award #EPS-0701898 and the
state of Alaska. Alaska INBRE Grant Number 5P20RR016466 from the
National Center for Research Resources, a component of the National
Institutes of Health (contents are solely the responsibility of the
authors and do not necessarily represent the official views of NCRR or
NIH).
NR 181
TC 1
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U1 10
U2 49
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-7780
EI 1757-7799
J9 WIRES CLIM CHANGE
JI Wiley Interdiscip. Rev.-Clim. Chang.
PD MAR-APR
PY 2016
VL 7
IS 2
BP 283
EP 300
DI 10.1002/wcc.382
PG 18
WC Environmental Studies; Meteorology & Atmospheric Sciences
SC Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
GA DE5AW
UT WOS:000370643800008
ER
PT J
AU Khoury, MJ
Iademarco, MF
Riley, WT
AF Khoury, Muin J.
Iademarco, Michael F.
Riley, William T.
TI Precision Public Health for the Era of Precision Medicine
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
C1 [Khoury, Muin J.; Iademarco, Michael F.] CDC, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA.
[Khoury, Muin J.; Riley, William T.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Iademarco, Michael F.] US PHS, Commissioned Corps, Washington, DC 20201 USA.
RP Khoury, MJ (reprint author), CDC, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30329 USA.
EM muk1@cdc.gov
FU Intramural CDC HHS [CC999999]; Intramural NIH HHS [Z99 CA999999]
NR 12
TC 11
Z9 13
U1 3
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2016
VL 50
IS 3
BP 398
EP 401
DI 10.1016/j.amepre.2015.08.031
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DD9QI
UT WOS:000370260300017
PM 26547538
ER
PT J
AU Buchanan, LR
Rooks-Peck, CR
Finnie, RKC
Wethington, HR
Jacob, V
Fulton, JE
Johnson, DB
Kahwati, LC
Pratt, CA
Ramirez, G
Glanz, K
AF Buchanan, Leigh Ramsey
Rooks-Peck, Cherie R.
Finnie, Ramona K. C.
Wethington, Holly R.
Jacob, Verughese
Fulton, Janet E.
Johnson, Donna B.
Kahwati, Leila C.
Pratt, Charlotte A.
Ramirez, Gilbert
Glanz, Karen
CA Community Preventive Serv Task
TI Reducing Recreational Sedentary Screen Time A Community Guide Systematic
Review
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID RANDOMIZED-CONTROLLED-TRIAL; BODY-MASS INDEX; OBESITY PREVENTION
PROGRAM; PROMOTE PHYSICAL-ACTIVITY; PRIMARY-SCHOOL CHILDREN; OPEN-LOOP
FEEDBACK; PRESCHOOL-CHILDREN; PRIMARY-CARE; INTERDISCIPLINARY
INTERVENTION; DECISION-MAKING
AB Context: Sedentary time spent with screen media is associated with obesity among children and adults. Obesity has potentially serious health consequences, such as heart disease and diabetes. This Community Guide systematic review examined the effectiveness and economic efficiency of behavioral interventions aimed at reducing recreational (i.e., neither school-nor work-related) sedentary screen time, as measured by screen time, physical activity, diet, and weight-related outcomes.
Evidence acquisition: For this review, an earlier ("original") review (search period, 1966 through July 2007) was combined with updated evidence (search period, April 2007 through June 2013) to assess effectiveness of behavioral interventions aimed at reducing recreational sedentary screen time. Existing Community Guide systematic review methods were used. Analyses were conducted in 2013-2014.
Evidence synthesis: The review included 49 studies. Two types of behavioral interventions were evaluated that either (1) focus on reducing recreational sedentary screen time only (12 studies); or (2) focus equally on reducing recreational sedentary screen time and improving physical activity or diet (37 studies). Most studies targeted children aged <= 13 years. Children's composite screen time (TV viewing plus other forms of recreational sedentary screen time) decreased 26.4 (interquartile interval = -74.4, -12.0) minutes/day and obesity prevalence decreased 2.3 (interquartile interval = -4.5, -1.2) percentage points versus a comparison group. Improvements in physical activity and diet were reported. Three study arms among adults found composite screen time decreased by 130.2 minutes/day.
Conclusions: Among children, these interventions demonstrated reduced screen time, increased physical activity, and improved diet- and weight-related outcomes. More research is needed among adolescents and adults. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Buchanan, Leigh Ramsey; Rooks-Peck, Cherie R.; Finnie, Ramona K. C.; Wethington, Holly R.; Jacob, Verughese] CDC, Community Guide Branch, Div Publ Hlth Informat Disseminat, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA.
[Fulton, Janet E.] CDC, Phys Act & Hlth Branch, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Pratt, Charlotte A.] NHLBI, Clin Applicat & Prevent Branch, Prevent & Populat Sci Program, Div Cardiovasc Sci,NIH, Bldg 10, Bethesda, MD 20892 USA.
[Johnson, Donna B.] Univ Washington, Ctr Publ Hlth Nutr, Seattle, WA 98195 USA.
[Kahwati, Leila C.] RTI Int, Res Triangle Pk, NC USA.
[Ramirez, Gilbert] Texas A&M, Sch Publ Hlth, College Stn, TX USA.
[Glanz, Karen] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Glanz, Karen] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
RP Wethington, HR (reprint author), CDC, Community Guide Branch, 1600 Clifton Rd,Mailstop E69, Atlanta, GA 30329 USA.
EM hwethington@cdc.gov
FU Oak Ridge Institute for Science and Education
FX The work of Cherie R. Rooks-Peck and Ramona K. C. Finnie was supported
with funds from the Oak Ridge Institute for Science and Education.
NR 89
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U1 4
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2016
VL 50
IS 3
BP 402
EP 415
DI 10.1016/j.amepre.2015.09.030
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DD9QI
UT WOS:000370260300018
ER
PT J
AU Singh, D
Schaaper, RM
Hochkoeppler, A
AF Singh, Deepa
Schaaper, Roel M.
Hochkoeppler, Alejandro
TI A continuous spectrophotometric enzyme-coupled assay for deoxynucleoside
triphosphate triphosphohydrolases
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Enzyme-coupled assay; Deoxynucleoside triphosphatase; Escherichia coli
Dgt; Purine nucleoside phosphorylase; Xanthine oxidase; 8-Oxoguanine
ID NUCLEOSIDE DIPHOSPHATE KINASES; RESTRICTION FACTOR SAMHD1;
ESCHERICHIA-COLI; DGTP TRIPHOSPHOHYDROLASE; ALLOSTERIC ACTIVATION;
ENTEROCOCCUS-FAECALIS; XANTHINE-OXIDASE; PURIFICATION; PHOSPHATE;
MUTAGENESIS
AB We describe a continuous, spectrophotometric, enzyme-coupled assay useful to monitor reactions catalyzed by nucleoside triphosphohydrolases. In particular, using Escherichia coli deoxynucleoside triphosphohydrolase (Dgt), which hydrolyzes dGTP to deoxyguanosine and tripolyphosphate (PPPi) as the enzyme to be tested, we devised a procedure relying on purine nucleoside phosphorylase (PNPase) and xanthine oxidase (XOD) as the auxiliary enzymes. The deoxyguanosine released by Dgt can indeed be conveniently subjected to phosphorolysis by PNPase, yielding deoxyribose-l-phosphate and guanine, which in turn can be oxidized to 8-oxoguanine by XOD. By this means, it was possible to continuously detect Dgt activity at 297 nm, at which wavelength the difference between the molar extinction coefficients of 8-oxoguanine (8000 M-1 cm(-1)) and guanine (1090 M-1 cm(-1)) is maximal. The initial velocities of Dgt-catalyzed reactions were then determined in parallel with the enzyme-coupled assay and with a discontinuous high-performance liquid chromatography (HPLC) method able to selectively detect deoxyguanosine. Under appropriate conditions of excess auxiliary enzymes, the activities determined with our continuous enzyme-coupled assay were quantitatively comparable to those observed with the HPLC method. Moreover, the enzyme-coupled assay proved to be more sensitive than the chromatographic procedure, permitting reliable detection of Dgt activity at low dGTP substrate concentrations. (c) 2015 Elsevier Inc. All rights reserved.
C1 [Singh, Deepa; Schaaper, Roel M.] NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Hochkoeppler, Alejandro] Univ Bologna, Dept Pharm & Biotechnol, Viale Risorgimento 4, I-40136 Bologna, Italy.
[Hochkoeppler, Alejandro] Univ Florence, CSGI, I-50019 Sesto Fiorentino, FI, Italy.
RP Hochkoeppler, A (reprint author), Univ Bologna, Dept Pharm & Biotechnol, Viale Risorgimento 4, I-40136 Bologna, Italy.
EM a.hochkoeppler@unibo.it
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIEHS [Z01 ES101905]
FX We thank Mark Itsko and Clinton Orebaugh of the National Institute of
Environmental Health Sciences (NIEHS) for helpful comments on a draft of
the manuscript. This work was supported, in part, by project Z01
ES101905 of the Intramural Research Program of the National Institute of
Environmental Health Sciences, NIEHS.
NR 35
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Z9 1
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
EI 1096-0309
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD MAR 1
PY 2016
VL 496
BP 43
EP 49
DI 10.1016/j.ab.2015.11.027
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DE0GW
UT WOS:000370304100008
PM 26723493
ER
PT J
AU Patel, D
Mehta, A
Nilubol, N
Dieckmann, W
Pacak, K
Kebebew, E
AF Patel, Dhaval
Mehta, Amit
Nilubol, Naris
Dieckmann, William
Pacak, Karel
Kebebew, Electron
TI Total 18F-FDG PET/CT Metabolic Tumor Volume Is Associated With
Postoperative Biochemical Response in Patients With Metastatic
Pheochromocytomas and Paragangliomas
SO ANNALS OF SURGERY
LA English
DT Article
DE 18F-FDG PET; CT; metabolic tumor volume; metastatic pheochromocytoma;
paraganglioma; total lesion glycolysis
ID POSITRON-EMISSION-TOMOGRAPHY; TOTAL LESION GLYCOLYSIS; BODY
RADIATION-THERAPY; B GENE-MUTATIONS; MALIGNANT PHEOCHROMOCYTOMAS;
PROGNOSTIC VALUE; PANCREATIC-CANCER; F-18-FDG PET/CT; FDG PET/CT;
PARAMETERS
AB Objective:The aim of this pilot study was to determine if metabolic tumor volume (MTV) and total lesion glycolysis (TLG) could serve as predictors of biochemical remission and pharmacotherapy-free interval in patients with metastatic pheochromocytomas (PCCs) and paragangliomas (PGLs).Background:Patients with metastatic PCCs/PGLs have a high rate of biochemical recurrence, which can be associated with increased cardiovascular morbidity. Predictors of biochemical response are needed to guide and select patients who may benefit from therapy.Methods:Whole body MTV and TLG was calculated from preoperative 18F-FDG PET/CT scans and analyzed as marker of biochemical response and pharmacotherapy-free interval.Results:Seventeen patients underwent a total of 19 procedures, with a median follow-up time of 26.4 months. Whole body MTV of patients with biochemical recurrence (n=13, mean 73.8mL) was higher than those who had a biochemical response (n=6, mean 14.7mL, P=0.05). Patients with low MTV (<37.2mL) had an improved durable partial biochemical response (P<0.05), and a statistical trend for complete biochemical remission (P=0.07) and pharmacotherapy-free interval (P=0.06). In 8 patients with metastatic disease outside the abdomen, 4 patients had less than 35% of their disease burden outside the abdomen and these patients had a more durable partial biochemical response compared to patients with greater than 35% of their disease burden outside the abdomen (P<0.05).Conclusions:Whole body MTV and TLG represents novel and valuable predictors of biochemical response for patients with metastatic PCCs and PGLs. A larger prospective study should be performed to validate these findings.
C1 [Patel, Dhaval; Mehta, Amit; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH USA.
[Dieckmann, William] NIH, PET Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
OI Patel, Dhaval/0000-0002-5744-568X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the intramural research program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 28
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U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2016
VL 263
IS 3
BP 582
EP 587
DI 10.1097/SLA.0000000000001018
PG 6
WC Surgery
SC Surgery
GA DD8JY
UT WOS:000370174000021
PM 25405562
ER
PT J
AU Townsley, E
O'Connor, G
Cosgrove, C
Woda, M
Co, M
Thomas, SJ
Kalayanarooj, S
Yoon, IK
Nisalak, A
Srikiatkhachorn, A
Green, S
Stephens, HAF
Gostick, E
Price, DA
Carrington, M
Alter, G
McVicar, DW
Rothman, AL
Mathew, A
AF Townsley, E.
O'Connor, G.
Cosgrove, C.
Woda, M.
Co, M.
Thomas, S. J.
Kalayanarooj, S.
Yoon, I. -K.
Nisalak, A.
Srikiatkhachorn, A.
Green, S.
Stephens, H. A. F.
Gostick, E.
Price, D. A.
Carrington, M.
Alter, G.
McVicar, D. W.
Rothman, A. L.
Mathew, A.
TI Interaction of a dengue virus NS1-derived peptide with the inhibitory
receptor KIR3DL1 on natural killer cells
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE dengue; HLA; KIR; NK; pathogenesis
ID NK-CELLS; DISEASE SEVERITY; HLA-B; ETHNIC THAIS; T-CELLS;
ANTIBODY-RESPONSE; INFECTION; ASSOCIATIONS; RECOGNITION; CORRELATE
AB Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.
C1 [Townsley, E.; Woda, M.; Co, M.; Srikiatkhachorn, A.; Green, S.; Mathew, A.] Univ Massachusetts, Med Ctr, Div Infect Dis & Immunol, Worcester, MA USA.
[O'Connor, G.; Carrington, M.; McVicar, D. W.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA.
[Cosgrove, C.; Carrington, M.; Alter, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Thomas, S. J.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Kalayanarooj, S.] Queen Sirikit Natl Inst Child Hlth, Bangkok, Thailand.
[Yoon, I. -K.; Nisalak, A.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
[Stephens, H. A. F.] UCL, Ctr Nephrol & Anthony Nolan Trust, Royal Free Campus, London, England.
[Gostick, E.; Price, D. A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales.
[Price, D. A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Rothman, A. L.] Univ Rhode Isl, Inst Immunol & Informat, 825 Chalkstone Ave, Providence, RI 02908 USA.
RP Mathew, A (reprint author), Univ Massachusetts, Div Infect Dis & Immunol, Sch Med, S6-862,55 Lake Ave North, Worcester, MA 01655 USA.
EM anuja.mathew@umassmed.edu
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU National Institutes of Health (NIH) [P01 AI34533, U19 AI57319, R21
AI113479, P30 DK032520]; Frederick National Laboratory for Cancer
Research [HHSN261200800001E]; NIH, Frederick National Laboratory, Center
for Cancer Research
FX We thank the subjects who generously donated peripheral blood samples
for use in our studies, the NIAID Tetramer Core Facility for provision
of the B57-NS126-34 tetramer, Brenda Hartman for expert assistance with
graphics and Dr Suchitra Nimmannitya and staff at the Queen Sirikit
National Institute for Child Health, the Department of Virology, Armed
Forces Research Institute of Medical Sciences and the Department of
Transfusion Medicine, Siriraj Hospital, for patient recruitment, sample
collection and clinical, virological and HLA typing information. This
work was funded by the National Institutes of Health (NIH) via Grants
P01 AI34533, U19 AI57319 and R21 AI113479 with core support from NIH P30
DK032520 and federal funds from the Frederick National Laboratory for
Cancer Research under Contract No. HHSN261200800001E. Additional support
was provided by the Intramural Research Program of the NIH, Frederick
National Laboratory, Center for Cancer Research. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government. D. A. P. is a Wellcome Trust Senior Investigator.
NR 48
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U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
EI 1365-2249
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD MAR
PY 2016
VL 183
IS 3
BP 419
EP 430
DI 10.1111/cei.12722
PG 12
WC Immunology
SC Immunology
GA DD8NU
UT WOS:000370184600011
PM 26439909
ER
PT J
AU Khangura, SK
Kamal, N
Ho, N
Quezado, M
Zhao, XC
Marciano, B
Simpson, J
Zerbe, C
Uzel, G
Yao, MD
DeRavin, SS
Hadigan, C
Kuhns, DB
Gallin, JI
Malech, HL
Holland, SM
Heller, T
AF Khangura, Sajneet K.
Kamal, Natasha
Ho, Nancy
Quezado, Martha
Zhao, Xiongce
Marciano, Beatriz
Simpson, Jennifer
Zerbe, Christa
Uzel, Gulbu
Yao, Michael D.
DeRavin, Suk See
Hadigan, Colleen
Kuhns, Douglas B.
Gallin, John I.
Malech, Harry L.
Holland, Steven M.
Heller, Theo
TI Gastrointestinal Features of Chronic Granulomatous Disease Found During
Endoscopy
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Database Analysis; GI; Intestine; Disease Phenotype
ID MIMICKING CROHNS-DISEASE; ULCERATIVE-COLITIS; MANIFESTATIONS;
MANAGEMENT; CHILDHOOD; THERAPY; ADULT
AB BACKGROUND & AIMS: Chronic granulomatous disease (CGD) is an inherited disorder of the reduced nicotinamide adenine dinucleotide phosphate oxidase complex within phagocytic cells that predisposes people to bacterial and fungal infections. Approximately 40% of patients with CGD have gastrointestinal involvement. We aimed to characterize the endoscopic features of gastrointestinal CGD and define the role of endoscopy in patients.
METHODS: We created a database of all patients with CGD seen at the National Institutes of Health from 1990 through 2010. We identified patients who had an endoscopy, and collected information from those with CGD-associated inflammatory bowel disease. We analyzed clinical data (demographic information and symptoms), endoscopic data (indication, preparation quality, degree of inflammation, mucosal findings, and complications), and pathologic data.
RESULTS: A total of 211 endoscopies (96 esophagogastroduodenoscopies, 82 colonoscopies, and 33 flexible sigmoidoscopies) were performed at the National Institutes of Health on 78 patients with CGD. Esophageal, gastric, and duodenal inflammation were detected in 21%, 74%, and 37% of patients, respectively. Esophageal dysmotility and structural abnormalities were noted in 26%. Of the patients who had colonic CGD-inflammatory bowel disease, 74% had skip lesions and 93% had anorectal disease. Enteric fistulae were found in 18% of patients; 73% of these were perianal. Colonic strictures were observed in 24% of patients; 80% were in the anorectal area.
CONCLUSIONS: Based on an analysis of clinical and endoscopic data from 78 patients, CGD-inflammatory bowel disease is a distinct entity, primarily involving the anus and rectum, with skip lesions in the remaining bowel. Bowel strictures and fistulae are present in a significant number of patients. Upper gastrointestinal tract inflammatory disease is common, although typically not as severe as colonic disease. Upper and lower endoscopies are important in characterizing the gastrointestinal features of CGD.
C1 [Khangura, Sajneet K.; Kamal, Natasha; Ho, Nancy; Quezado, Martha; Zhao, Xiongce; Marciano, Beatriz; Simpson, Jennifer; Zerbe, Christa; Uzel, Gulbu; Yao, Michael D.; DeRavin, Suk See; Hadigan, Colleen; Gallin, John I.; Malech, Harry L.; Holland, Steven M.; Heller, Theo] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Khangura, Sajneet K.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Kuhns, Douglas B.] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
RP Heller, T (reprint author), NIDDK, LDB, NIH, 10 Ctr Dr,Bldg 10,Room 9C432B, Bethesda, MD 20892 USA.
EM theoh@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases; National Cancer
Institute; clinical center of the National Institutes of Health;
National Cancer Institute [HHSN261200800001E]
FX This study was funded by the intramural program in the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institute of Allergy and Infectious Diseases, National Cancer Institute,
and the clinical center of the National Institutes of Health. Douglas B.
Kuhns is funded in whole or part by National Cancer Institute contract
HHSN261200800001E.
NR 29
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD MAR
PY 2016
VL 14
IS 3
BP 395
EP +
DI 10.1016/j.cgh.2015.10.030
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DE1HC
UT WOS:000370376700016
PM 26545803
ER
PT J
AU Kaphingst, KA
Ivanovich, J
Biesecker, BB
Dresser, R
Seo, J
Dressler, LG
Goodfellow, PJ
Goodman, MS
AF Kaphingst, K. A.
Ivanovich, J.
Biesecker, B. B.
Dresser, R.
Seo, J.
Dressler, L. G.
Goodfellow, P. J.
Goodman, M. S.
TI Preferences for return of incidental findings from genome sequencing
among women diagnosed with breast cancer at a young age
SO CLINICAL GENETICS
LA English
DT Article
DE breast cancer; genome sequencing; incidental findings; patient
preferences; return of results
ID INFORMED-CONSENT; ACMG RECOMMENDATIONS; GENETIC RESEARCH; CLINICAL
GENOME; EXOME; PERSPECTIVES; MUTATIONS; ATTITUDES; PROFESSIONALS;
PARTICIPANTS
AB While experts have made recommendations, information is needed regarding what genome sequencing results patients would want returned. We investigated what results women diagnosed with breast cancer at a young age would want returned and why. We conducted 60 semi-structured, in-person individual interviews with women diagnosed with breast cancer at age 40 or younger. We examined interest in six types of incidental findings and reasons for interest or disinterest in each type. Two coders independently coded interview transcripts; analysis was conducted using NVivo 10. Most participants were at least somewhat interested in all six result types, but strongest interest was in actionable results (i.e. variants affecting risk of a preventable or treatable disease and treatment response). Reasons for interest varied between different result types. Some participants were not interested or ambivalent about results not seen as currently actionable. Participants wanted to be able to choose what results are returned. Participants distinguished between types of individual genome sequencing results, with different reasons for wanting different types of information. The findings suggest that a focus on actionable results can be a common ground for all stakeholders in developing a policy for returning individual genome sequencing results.
C1 [Kaphingst, K. A.] Univ Utah, Dept Commun, 255 Cent Campus Dr, Salt Lake City, UT 84112 USA.
[Kaphingst, K. A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Ivanovich, J.; Seo, J.; Goodman, M. S.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA.
[Biesecker, B. B.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Dresser, R.] Washington Univ, Sch Law, St Louis, MO USA.
[Dressler, L. G.] Mission HealthCare, Asheville, NC USA.
[Goodfellow, P. J.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
RP Kaphingst, KA (reprint author), Univ Utah, Dept Commun, 255 Cent Campus Dr, Salt Lake City, UT 84112 USA.
EM kim.kaphingst@hci.utah.edu
OI Goodman, Melody/0000-0001-8932-624X
FU National Cancer Institute, National Institutes of Health [R01CA168608];
National Human Genome Research Institute, National Institutes of Health
FX This work was supported by the National Cancer Institute, National
Institutes of Health (R01CA168608). This research was supported in part
by the Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health. The authors thank the women
who agreed to participate in the study and Keri Walton, Suzanne Bell,
and Mackenzie Ray for valuable assistance in coding interview
transcripts. The funding agency had no role in collection, analysis and
interpretation of data, writing of the manuscript, or decision to submit
the report for publication.
NR 40
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
EI 1399-0004
J9 CLIN GENET
JI Clin. Genet.
PD MAR
PY 2016
VL 89
IS 3
BP 378
EP 384
DI 10.1111/cge.12597
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA DE4TI
UT WOS:000370622800017
PM 25871653
ER
PT J
AU Sampat, HN
Brandao, LR
Tamburro, RF
Kees-Folts, D
Dandekar, S
AF Sampat, Hemal N.
Brandao, Leonardo R.
Tamburro, Robert F.
Kees-Folts, Deborah
Dandekar, Smita
TI HIT or Miss: The Sequential Diagnostic Approach to Heparin-Induced
Thrombocytopenia Illustrated in a Child With Acute Post-Streptococcal
Glomerulonephritis
SO CLINICAL PEDIATRICS
LA English
DT Article
ID 4TS SCORING SYSTEM
C1 [Sampat, Hemal N.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA.
[Sampat, Hemal N.; Tamburro, Robert F.; Kees-Folts, Deborah; Dandekar, Smita] Penn State Hershey Childrens Hosp, Hershey, PA USA.
[Brandao, Leonardo R.] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Tamburro, Robert F.] NICHHD, Bethesda, MD 20892 USA.
RP Sampat, HN (reprint author), Penn State Hershey Childrens Hosp, Penn State Milton S Hershey Med Ctr, Dept Med, Dept Pediat, 500 Univ Dr,POB 850, Hershey, PA 17033 USA.
EM hsampat@hmc.psu.edu
NR 10
TC 1
Z9 1
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
EI 1938-2707
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD MAR
PY 2016
VL 55
IS 3
BP 294
EP 297
DI 10.1177/0009922815586055
PG 4
WC Pediatrics
SC Pediatrics
GA DE1VN
UT WOS:000370414700014
PM 25963179
ER
PT J
AU Pool, LR
Wagner, RM
Scott, LL
RoyChowdhury, D
Berhane, R
Wu, C
Pearson, K
Sutton, JA
Schaffer, WT
AF Pool, Lindsay R.
Wagner, Robin M.
Scott, Lindsey L.
RoyChowdhury, Deepshikha
Berhane, Rediet
Wu, Charles
Pearson, Katrina
Sutton, Jennifer A.
Schaffer, Walter T.
TI Size and characteristics of the biomedical research workforce associated
with US National Institutes of Health extramural grants
SO FASEB JOURNAL
LA English
DT Article
DE researcher census; occupation; career stage; educational attainment;
personnel age distribution
AB The U.S. National Institutes of Health (NIH) annually invests approximately $22 billion in biomedical research through its extramural grant programs. Since fiscal year (FY) 2010, all persons involved in research during the previous project year have been required to be listed on the annual grant progress report. These new data have enabled the production of the first-ever census of the NIH-funded extramural research workforce. Data were extracted from All Personnel Reports submitted for NIH grants funded in FY 2009, including position title, months of effort, academic degrees obtained, and personal identifiers. Data were de-duplicated to determine a unique person count. Person-years of effort (PYE) on NIH grants were computed. In FY 2009, NIH funded 50,885 grant projects, which created 313,049 full- and part-time positions spanning all job functions involved in biomedical research. These positions were staffed by 247,457 people at 2,604 institutions. These persons devoted 121,465 PYE to NIH grant-supported research. Research project grants each supported 6 full- or part-time positions, on average. Over 20% of positions were occupied by postdoctoral researchers and graduate and undergraduate students. These baseline data were used to project workforce estimates for FYs 2010-2014 and will serve as a foundation for future research.
C1 [Pool, Lindsay R.; Wagner, Robin M.; Pearson, Katrina; Sutton, Jennifer A.; Schaffer, Walter T.] NIH, Off Extramural Res, Off Director, Dept Hlth & Human Serv, Bethesda, MD USA.
[Wagner, Robin M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Wagner, RM (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Sci Serv, 2500 Century Ctr Blvd NE,Room 5202,Mailstop E33, Atlanta, GA 30345 USA.
EM riw8@cdc.gov
FU NIH Evaluation Set-Aside Program [11-6002 OD-OER]
FX The authors thank Drs. D. Hann, R. Ikeda, J. Onken, S. Rockey, R. Ulane,
and D. Zuk for the insights and comments on drafts of this manuscript,
provided by the U.S. National Institutes of Health (NIH) senior staff,
and NIH financial specialist, S. Schiaffino, who provided able
assistance in securing contract support for the study. This study was
partially supported by a project, Reference Number 11-6002 OD-OER,
funded by the NIH Evaluation Set-Aside Program, administered by the
Office of Program Evaluation and Performance, Division of Program,
Coordination, Planning, and Strategic Initiatives, Office of the
Director, NIH. The funders played no role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. The coauthors who were federal employees (L.R.P., R.M.W.,
J.A.S., K.P., and W.T.S.) conducted this research as part of their
salaried duties. The work by L.L.S., D.R., R.B., and C.W. was contracted
by the NIH. L.R.P., R.M.W., J.A.S., and W.T.S. conceived of and designed
the study; L.R.P, L.L.S., D.R., R.B., C.W., K.P. and R.M.W. analyzed the
data; L.R.P., R.M.W., K.P., J.A.S., and W.T.S. made significant
contributions to interpretation of the results; and L.R.P. and R.M.W.
wrote the manuscript. The OCR extraction of data was performed by
Discovery Logic (Rockville, MD, USA), a Thomson Reuters business. Drs.
L. Haak and J. Schnell served as the OCR project managers, and K.
Barden, M. Cissel, and M. Probus performed the analyses. The authors
declare no conflicts of interest.
NR 23
TC 1
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U1 4
U2 10
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAR
PY 2016
VL 30
IS 3
BP 1023
EP 1036
DI 10.1096/fj.14-264358
PG 14
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA DE1LF
UT WOS:000370387800003
PM 26625903
ER
PT J
AU Park, JJ
Wong, DK
Wahed, AS
Lee, WM
Feld, JJ
Terrault, N
Khalili, M
Sterling, RK
Kowdley, KV
Bzowej, N
Lau, DT
Kim, WR
Smith, C
Carithers, RL
Torrey, KW
Keith, JW
Levine, DL
Traum, D
Ho, S
Valiga, ME
Johnson, GS
Doo, E
Lok, ASF
Chang, KM
AF Park, Jang-June
Wong, David K.
Wahed, Abdus S.
Lee, William M.
Feld, Jordan J.
Terrault, Norah
Khalili, Mandana
Sterling, Richard K.
Kowdley, Kris V.
Bzowej, Natalie
Lau, Daryl T.
Kim, W. Ray
Smith, Coleman
Carithers, Robert L.
Torrey, Keith W.
Keith, James W.
Levine, Danielle L.
Traum, Daniel
Ho, Suzanne
Valiga, Mary E.
Johnson, Geoffrey S.
Doo, Edward
Lok, Anna S. F.
Chang, Kyong-Mi
CA Hepatitis B Res Network
TI Hepatitis B Virus-Specific and Global T-Cell Dysfunction in Chronic
Hepatitis B
SO GASTROENTEROLOGY
LA English
DT Article
DE HBRN; LPS; IFN; IL10
ID IMMUNE-RESPONSE; VIRAL-HEPATITIS; SUSTAINED RESPONSE; PROGRAMMED
DEATH-1; HBV INFECTION; E-ANTIGEN; PATHOGENESIS; ETHNICITY; GENOTYPE;
THERAPY
AB BACKGROUND & AIMS: T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). METHODS: We enrolled 200 adults with CHB who participated in the National Institutes of Health-supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyteassociated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. RESULTS: Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3(+)CD127(-) regulatory T cells and CD4(+) T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg)(+) than HBeAg- patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyteassociated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg+ than HBeAg- patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. CONCLUSIONS: HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell-based immune signatures for clinical phenotypes. These findings suggest additional T-cell-independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.
C1 [Park, Jang-June; Torrey, Keith W.; Keith, James W.; Levine, Danielle L.; Traum, Daniel; Ho, Suzanne; Valiga, Mary E.; Chang, Kyong-Mi] Philadelphia Corporal Michael J Crescenz VA Med C, Philadelphia, PA USA.
[Park, Jang-June; Torrey, Keith W.; Keith, James W.; Levine, Danielle L.; Traum, Daniel; Ho, Suzanne; Valiga, Mary E.; Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Wong, David K.; Feld, Jordan J.] Univ Toronto, Toronto, ON, Canada.
[Wahed, Abdus S.; Johnson, Geoffrey S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Lee, William M.] Univ Texas Southwestern, Dallas, TX USA.
[Terrault, Norah; Khalili, Mandana] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Richmond, VA USA.
[Kowdley, Kris V.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Bzowej, Natalie] Calif Pacific Med Ctr, San Francisco, CA USA.
[Lau, Daryl T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Kim, W. Ray] Mayo Clin, Rochester, MN USA.
[Smith, Coleman] Univ Minnesota, Minneapolis, MN USA.
[Carithers, Robert L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Doo, Edward] NIDDK, NIH, Bethesda, MD 20892 USA.
[Lok, Anna S. F.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Chang, KM (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.; Chang, KM (reprint author), Univ Penn, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM kmchang@mail.med.upenn.edu
OI Wahed, Abdus/0000-0001-6911-7221; Wong, David/0000-0002-3310-3538
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01, DK 082843, DK082863, DK082864, DK082866, DK082867, DK082871, U01
DK082872, DK082874, DK082919, DK082923, DK082927, DK082943, U01
DK082944]; NIDDK [A-DK-3002-001]; intramural program, NIDDK, National
Institutes of Health (NIH); Immunology Center (NIH/NIDDK Center of
Molecular Studies in Digestive and Liver Diseases) [P30DK50306];
Immunology Center (NIH Public Health Service Research Grant)
[M01-RR00040]; Immunology Center (VA Merit Review) [BX000649,
UL1TR000058]; NCATS (National Center for Advancing Translational
Sciences, NIH) [UL1TR000058]; CTSA [UL1TR000004, UL1RR024986]; Clinical
and Translational Science Award [CTSA] [UL1TR001111]; Gilead Sciences,
Inc.; Roche Molecular Systems through the NIDDK; NIH [UO-1DK082866,
R01-AI-47519]; Philadelphia VA Medical Research; NIH/NIDDK Center of
Molecular Studies in Digestive and Liver Diseases [P30DK50306];
Molecular Biology and Cell Culture Core Facilities; NIH Public Health
Service Research Grant [M01-RR00040]; Office of Research and
Development, Department of Veterans Affairs
FX The HBRN was funded by a U01 grant from the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) to the following
investigators Lewis R. Roberts, MB, ChB, PhD (DK 082843), Anna Suk-Fong
Lok, MD (DK082863), Steven H. Belle, PhD, MScHyg (DK082864), Kyong-Mi
Chang, MD (DK082866), Michael W. Fried, MD (DK082867), Adrian M. Di
Bisceglie, MD (DK082871), William M. Lee, MD (U01 DK082872), Harry L. A.
Janssen, MD, PhD (DK082874), Daryl T.-Y. Lau, MD, MPH (DK082919),
Richard K. Sterling, MD, MSc (DK082923), Steven-Huy B. Han, MD
(DK082927), Robert C. Carithers, MD (DK082943), Norah A. Terrault, MD,
MPH (U01 DK082944), an interagency agreement with NIDDK: Lilia M.
Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural
program, NIDDK, National Institutes of Health (NIH): Marc G. Ghany, MD.
Additional funding to support this study was provided to Kyong-Mi Chang,
MD, the Immunology Center (NIH/NIDDK Center of Molecular Studies in
Digestive and Liver Diseases P30DK50306, NIH Public Health Service
Research Grant M01-RR00040, VA Merit Review BX000649), Richard K.
Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing
Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA grant
number UL1TR000004), Michael W. Fried, MD (Clinical and Translational
Science Award [CTSA] grant number UL1TR001111), and Anna Suk-Fong Lok
(CTSA grant number UL1RR024986). Additional support was provided by
Gilead Sciences, Inc. and Roche Molecular Systems via a cooperative
research and development agreement through the NIDDK. This study was
supported by NIH grants UO-1DK082866 and R01-AI-47519; the Philadelphia
VA Medical Research; NIH/NIDDK Center of Molecular Studies in Digestive
and Liver Diseases P30DK50306 and its Molecular Biology and Cell Culture
Core Facilities; the NIH Public Health Service Research Grant
M01-RR00040. This material is based on work supported in part by the
Office of Research and Development, Department of Veterans Affairs and
with the resources and the use of facilities at the Philadelphia
Corporal Michael J. Crescenz VA Medical Center. The contents of this
work do not represent the views of the Department of Veterans Affairs or
the United States Government.
NR 52
TC 6
Z9 9
U1 5
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2016
VL 150
IS 3
BP 684
EP +
DI 10.1053/j.gastro.2015.11.050
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DE5CH
UT WOS:000370648100029
PM 26684441
ER
PT J
AU Singh, A
Bryan, MM
Roney, JC
Cullinane, AR
Gahl, WA
Khurana, N
Kapoor, S
AF Singh, Ankur
Bryan, Melanie M.
Roney, Joseph C.
Cullinane, Andrew R.
Gahl, William A.
Khurana, Nita
Kapoor, Seema
TI A clinical report of Chediak-Higashi syndrome in infancy with a novel
genotype from the Indian subcontinent
SO INTERNATIONAL JOURNAL OF DERMATOLOGY
LA English
DT Article
AB Chediak-Higashi syndrome (CHS; OMIM no. 214500) is an inherited multisystem disorder presenting with hypopigmentation and a propensity to infections due to immunological dysfunction. CHS generally presents in infancy with a fatal outcome, but less severe cases can present in adulthood. Treatment with bone marrow transplantation can be life-saving, so establishing a correct diagnosis is critical. The presence of large granules on examination of peripheral blood smears is suggestive of the diagnosis of CHS in most centers. However, sequencing of the lysosomal trafficking, LYST, gene confirms the diagnosis and can provide a prognosis regarding disease severity. In the case presented here, we performed molecular testing to identify the causative mutation and tabulated published mutation data from 2009 to 2014. We found a novel frameshift mutation in our case and concluded that frameshift and nonsense are the most common types of mutation in CHS, but this may be biased due to underdiagnosis of the milder and atypical forms of the disease.
C1 [Singh, Ankur] Banaras Hindu Univ, Inst Med Sci, Dept Pediat, Varanasi 221005, Uttar Pradesh, India.
[Bryan, Melanie M.; Roney, Joseph C.; Cullinane, Andrew R.; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Khurana, Nita] MAMC Associated Lok Nayak Hosp, Dept Pathol, New Delhi, India.
[Kapoor, Seema] MAMC Associated Lok Nayak Hosp, Dept Pediat, Div Genet, New Delhi, India.
RP Kapoor, S (reprint author), M-439,Ground Floor, New Delhi, India.
EM drseemakapoor@gmail.com
FU National Human Genome Research Institute
FX This study was supported in part by the Intramural Research Program of
the National Human Genome Research Institute. We acknowledge and thank
the family for their support of the project.
NR 20
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0011-9059
EI 1365-4632
J9 INT J DERMATOL
JI Int. J. Dermatol.
PD MAR
PY 2016
VL 55
IS 3
BP 317
EP 321
DI 10.1111/ijd.13019
PG 5
WC Dermatology
SC Dermatology
GA DD8CE
UT WOS:000370151100027
PM 26499269
ER
PT J
AU Korzeniewski, SJ
Feldman, JF
Lorenz, JM
Pinto-Martin, JA
Whitaker, AH
Paneth, N
AF Korzeniewski, Steven J.
Feldman, Judith F.
Lorenz, John M.
Pinto-Martin, Jennifer A.
Whitaker, Agnes H.
Paneth, Nigel
TI Persistence of Cerebral Palsy Diagnosis: Assessment of a
Low-Birth-Weight Cohort at Ages 2, 6, and 9 Years
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE motor disorder improvement; transient cerebral palsy
ID GROSS MOTOR FUNCTION; FUNCTION CLASSIFICATION-SYSTEM; ULTRASOUND
ABNORMALITIES; COGNITIVE OUTCOMES; INFANTS; STABILITY; CHILDREN;
ADOLESCENTS; GRAMS; LIFE
AB We examined the stability of nondisabling and disabling cerebral palsy at age 2 in a longitudinally followed tri-county low-birth-weight (<2000 g) birth cohort. A total of 1105 newborns were enrolled, 901 (81.5%) survived to age 2, and 86% (n = 777) were followed up. Of the 113 cerebral palsy diagnoses at age 2, 61 (9% of the cohort, n = 61/777) had disabling cerebral palsy and 52 (7%, n = 52/777) had nondisabling cerebral palsy. Of 48 followed children diagnosed with disabling cerebral palsy at age 2, 98% were again classified as having cerebral palsy at school age, and 1 had an uncertain cerebral palsy status. By contrast, 41% (n = 17) of the 43 children diagnosed with nondisabling cerebral palsy at age 2 were classified as not having cerebral palsy. Of the 517 followed children who were not diagnosed with cerebral palsy at age 2, 7% (n = 35) were classified as having late emerging nondisabling cerebral palsy at school age.
C1 [Korzeniewski, Steven J.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Korzeniewski, Steven J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Korzeniewski, Steven J.; Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Feldman, Judith F.; Whitaker, Agnes H.] Columbia Univ, Med Ctr, New York State Psychiat Inst, Dept Psychiat,Div Child & Adolescent Psychiat, New York, NY 10032 USA.
[Lorenz, John M.] Columbia Univ, Med Ctr, Dept Pediat, Div Neonatol, New York, NY USA.
[Pinto-Martin, Jennifer A.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
[Pinto-Martin, Jennifer A.] Sch Med, Philadelphia, PA USA.
[Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, E Lansing, MI 48824 USA.
RP Korzeniewski, SJ (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.; Korzeniewski, SJ (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.; Korzeniewski, SJ (reprint author), Michigan State Univ, Coll Human Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.; Korzeniewski, SJ (reprint author), Wayne State Univ, Hutzel Womens Hosp, Sch Med, Dept Obstet & Gynecol, 4 Brush Off 4817,3990 John R, Detroit, MI 48201 USA.
EM skorzeni@med.wayne.edu
FU Wayne State University Perinatal Research Initiative; [NS-20713];
[R01MH073807]; [R01 MH57514-05]; [12-FY03-46]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: The original
birth data collection funding came from NS-20713 (PI Nigel Paneth), and
follow-up funding was provided by R01MH073807 (PI Jennifer A.
Pinto-Martin), R01 MH57514-05 (PI Agnes Whitaker), and 12-FY03-46 (PI
Agnes Whitaker). This work was also supported, in part, by the Wayne
State University Perinatal Research Initiative.
NR 26
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U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
EI 1708-8283
J9 J CHILD NEUROL
JI J. Child Neurol.
PD MAR
PY 2016
VL 31
IS 4
BP 461
EP 467
DI 10.1177/0883073815599260
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA DE6CD
UT WOS:000370719900009
PM 26271791
ER
PT J
AU Daniere, A
Drummond, L
NaRanong, A
Tran, VAT
AF Daniere, Amrita
Drummond, Lisa
NaRanong, Anchana
Van Anh Thi Tran
TI Sustainable Flows: Water Management and Municipal Flexibility in Bangkok
and Hanoi
SO JOURNAL OF ENVIRONMENT & DEVELOPMENT
LA English
DT Article
DE water; urban; sustainable; management; Southeast Asia; social learning
ID URBAN-POOR; THAILAND; VIETNAM; DEMAND; CITIES; SOUTH; ASIA
AB There is widespread recognition that cities in the Global South need to transition toward sustainable water practices. This is particularly true of places experiencing growth and impacts from climate change concomitantly, as are Bangkok and Hanoi. We evaluate case studies in each of these two Southeast Asian cities to explore possible sustainable water management practices that their urban communities, and others experiencing similar issues, could adopt in the near term. Our analysis of these case studies supports four key conclusions: Simple expansion of rigid infrastructure does not necessarily meet local needs for water, communities can themselves provide insights and creative models, governments at any scale can be flexible and such flexibility can achieve appropriate solutions, and small-scale experimentation can and does work and can be successfully scaled up with government encouragement and support.
C1 [Daniere, Amrita] Univ Toronto, Dept Geog & Planning, Toronto, ON M5S 3G3, Canada.
[Drummond, Lisa] York Univ, Dept Social Sci, Urban Studies, Toronto, ON M3J 2R7, Canada.
[NaRanong, Anchana] NIDA, Grad Sch Publ Adm, Bangkok, Thailand.
[Van Anh Thi Tran] Vietnam Acad Social Sci, Inst Family & Gender Studies, Hanoi, Vietnam.
RP Daniere, A (reprint author), Univ Toronto, 100 St George St, Toronto, ON M5S 3G3, Canada.
EM amrita.daniere@utoronto.ca
FU Social Science and Humanities Research Council of Canada
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: The authors
gratefully acknowledge the support of the Social Science and Humanities
Research Council of Canada, and the valuable research assistance of Lo
Viet Phuong, Tran Thi Hong, Danny Marks, Nhusha Vu, and Sawanya
Phakphian.
NR 39
TC 0
Z9 0
U1 5
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1070-4965
EI 1552-5465
J9 J ENVIRON DEV
JI J. Environ. Dev.
PD MAR
PY 2016
VL 25
IS 1
BP 47
EP 72
DI 10.1177/1070496515625091
PG 26
WC Environmental Studies; Planning & Development
SC Environmental Sciences & Ecology; Public Administration
GA DE2AL
UT WOS:000370428400003
ER
PT J
AU Jo, JH
Kennedy, EA
Kong, HH
AF Jo, Jay-Hyun
Kennedy, Elizabeth A.
Kong, Heidi H.
TI Research Techniques Made Simple: Bacterial 16S Ribosomal RNA Gene
Sequencing in Cutaneous Research
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID HUMAN SKIN MICROBIOME; DIVERSITY; CONTAMINATION; CHILDREN; DISEASE;
SHIFTS; ARB
AB Skin serves as a protective barrier and also harbors numerous microorganisms collectively comprising the skin microbiome. As a result of recent advances in sequencing (next-generation sequencing), our understanding of microbial communities on skin has advanced substantially. In particular, the 16S ribosomal RNA gene sequencing technique has played an important role in efforts to identify the global communities of bacteria in healthy individuals and patients with various disorders in multiple topographical regions over the skin surface. Here, we describe basic principles, study design, and a workflow of 16S ribosomal RNA gene sequencing methodology, primarily for investigators who are not familiar with this approach. This article will also discuss some applications and challenges of 16S ribosomal RNA sequencing as well as directions for future development.
C1 [Jo, Jay-Hyun; Kennedy, Elizabeth A.; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20852 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20852 USA.
EM konghe@mail.nih.gov
NR 23
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U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2016
VL 136
IS 3
BP E23
EP E27
DI 10.1016/j.jid.2016.01.005
PG 5
WC Dermatology
SC Dermatology
GA DE4TL
UT WOS:000370623100001
PM 26902128
ER
PT J
AU Ferre, S
Sebastiao, AM
AF Ferre, Sergi
Sebastiao, Ana Maria
TI Dissecting striatal adenosine-cannabinoid receptor interactions. New
clues from rats over-expressing adenosine A2A receptors
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Editorial Material
ID MEDIATED INHIBITION; A(2A); CAFFEINE; MEMORY
AB This Editorial highlights a study by Chiodi etal. () showing that the effects mediated by cannabinoid CB1 receptor (CB1R) activation in the striatum are significantly reduced in rats with neuronal over-expression of adenosine A2A receptors (A2AR). Two hypotheses are derived from that study. Hypothesis A: two subpopulations of pre-synaptic CB1R in corticostriatal glutamatergic terminals exist, one forming and another not forming heteromers with A2AR. Hypothesis B: CB1R are predominantly forming heteromers with A2AR. In the case of hypothesis A, the A2AR might be required for CB1R-A2AR heteromeric signaling, whereas non-heteromeric CB1R activity is inhibited by A2ARs. In the case of hypothesis B, up-regulation of A2ARs may perturb heteromeric stoichiometry, thus reducing CB1R functioning. In any case, pre-synaptic striatal A2AR-CB1R heteromers emerge as important targets of the effects of cannabinoids demonstrated at the neuronal and behavioral level.
Read the highlighted article Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A(2A) receptors' on page 907.
C1 [Ferre, Sergi] NIDA, Integrat Neurobiol Sect, NIH, Baltimore, MD USA.
[Sebastiao, Ana Maria] Univ Lisbon, Fac Med, Inst Farmacol & Neurociencias, P-1699 Lisbon, Portugal.
[Sebastiao, Ana Maria] Univ Lisbon, Inst Mol Med, P-1699 Lisbon, Portugal.
RP Sebastiao, AM (reprint author), Univ Lisbon, Inst Pharmacol & Neurosci, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal.; Sebastiao, AM (reprint author), Univ Lisbon, Inst Mol Med, Fac Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal.
EM anaseb@fm.ul.pt
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
FU Intramural NIH HHS [Z01 DA000493-03]
NR 11
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U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2016
VL 136
IS 5
BP 897
EP 899
DI 10.1111/jnc.13520
PG 3
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DE5BT
UT WOS:000370646500001
PM 26806455
ER
PT J
AU Ravishankar, C
Gerstenberger, E
Sleeper, LA
Atz, AM
Affolter, JT
Bradley, TJ
Gaynor, JW
Goldstein, BH
Henderson, HT
Jacobs, JP
Lewis, AB
Dunbar-Masterson, C
Menon, SC
Pemberton, VL
Petit, CJ
Pike, NA
Pizarro, C
Schumacher, KR
Williams, IA
Newburger, JW
AF Ravishankar, Chitra
Gerstenberger, Eric
Sleeper, Lynn A.
Atz, Andrew M.
Affolter, Jeremy T.
Bradley, Timothy J.
Gaynor, J. William
Goldstein, Bryan H.
Henderson, Heather T.
Jacobs, Jeffrey P.
Lewis, Alan B.
Dunbar-Masterson, Carolyn
Menon, Shaji C.
Pemberton, Victoria L.
Petit, Christopher J.
Pike, Nancy A.
Pizarro, Christian
Schumacher, Kurt R.
Williams, Ismee A.
Newburger, Jane W.
CA Pediat Heart Network Investigators
TI Factors affecting Fontan length of stay: Results from the Single
Ventricle Reconstruction trial
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
DE Fontan; hypoplastic left heart syndrome; Single Ventricle Reconstruction
trial
ID LEFT-HEART SYNDROME; FLOW CARDIOPULMONARY BYPASS; NORWOOD PROCEDURE;
CONSECUTIVE PATIENTS; CIRCULATORY ARREST; RISK-FACTORS; SHUNT TYPE;
OPERATION; PALLIATION; COMPLETION
AB Background: In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation.
Methods: Fontan postoperative course was ascertained from medical record review. Cox proportional hazards modeling was used to identify factors associated with LOS.
Results: Of 327 subjects who underwent Fontan, 323 were analyzed (1 death, 1 biventricular repair, 2 with missing data). Median age and weight at Fontan were 2.8 years (interquartile range [IQR]: 2.3, 3.4) and 12.7 kg (IQR: 11.4, 14.1), respectively. Fontan type was extracardiac in 55% and lateral tunnel in 45%; 87% were fenestrated. The RVPAS and MBTS subjects had similar LOS (median 11 days [IQR: 9, 18] vs 10 days [IQR: 9, 13]; P = .23). Independent risk factors for longer LOS were treatment center (P < .01), LOS at stage II (hazard ratio [HR] 1.02 for each additional day; P < .01), and pre-Fontan complications (HR 1.03 for each additional complication; P = .04). Use of deep hypothermic circulatory arrest at Fontan (HR 0.64; P = .02) was independently associated with shorter LOS. When center was excluded from the model, pre-Fontan complications and use of circulatory arrest were no longer significant; instead, older age at stage II (HR 1.08 for each additional month; P = .01) predicted longer LOS. In 254 subjects who had a pre-Fontan echocardiogram, at least moderate tricuspid regurgitation was independently associated with longer LOS, both with center (HR 1.72; P < .01) and without center in the model (HR 1.49; P = .02).
Conclusions: In this multicenter prospective cohort of subjects with HLHS, Norwood shunt type was not associated with Fontan LOS. Rather, global measures of earlier medical complexity indicate greater likelihood of longer LOS after the Fontan operation.
C1 [Ravishankar, Chitra] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Gerstenberger, Eric; Sleeper, Lynn A.] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
[Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA.
[Affolter, Jeremy T.] Childrens Hosp Wisconsin, Dept Crit Care Med, Milwaukee, WI 53201 USA.
[Bradley, Timothy J.] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Gaynor, J. William] Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[Goldstein, Bryan H.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[Henderson, Heather T.] Duke Med Ctr, Dept Pediat, Durham, NC USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, Div Cardiothorac Surg, St Petersburg, FL USA.
[Lewis, Alan B.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA.
[Dunbar-Masterson, Carolyn; Newburger, Jane W.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Menon, Shaji C.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Pemberton, Victoria L.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Petit, Christopher J.] Sibley Heart Ctr, Dept Pediat, Atlanta, GA USA.
[Pike, Nancy A.] Univ Calif Los Angeles, Dept Nursing, Los Angeles, CA USA.
[Pizarro, Christian] Alfred I DuPont Hosp Children, Div Cardiothorac Surg, Wilmington, DE USA.
[Schumacher, Kurt R.] Univ Michigan, Dept Pediat, Hlth Ctr, Ann Arbor, MI 48109 USA.
[Williams, Ismee A.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA.
RP Ravishankar, C (reprint author), Childrens Hosp Philadelphia, Div Cardiol, Perelman Sch Med, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA.
EM ravishankar@email.chop.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HL068269, HL068270,
HL068279, HL068281, HL068285, HL068288, HL068290, HL068292, HL085057]
FX This work was supported by grants HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, and HL085057, from the
National Heart, Lung, and Blood Institute (NHLBI). This work is solely
the responsibility of the authors and does not necessarily represent the
official views of NHLBI or the National Institutes of Health.
NR 25
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U1 1
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD MAR
PY 2016
VL 151
IS 3
BP 669
EP +
DI 10.1016/j.jtcvs.2015.09.061
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DD9KR
UT WOS:000370244700028
PM 26519244
ER
PT J
AU De Santis, O
Audran, R
Pothin, E
Warpelin-Decrausaz, L
Vallotton, L
Wuerzner, G
Cochet, C
Estoppey, D
Steiner-Monard, V
Lonchampt, S
Thieny, AC
Mayor, C
Bailer, RT
Mbaya, OT
Zhou, Y
Ploquin, A
Sullivan, NJ
Graham, BS
Roman, F
De Ryck, I
Ballou, WR
Kieny, MP
Moorthy, V
Spertini, F
Genton, B
AF De Santis, Olga
Audran, Regine
Pothin, Emilie
Warpelin-Decrausaz, Loane
Vallotton, Laure
Wuerzner, Gregoire
Cochet, Camille
Estoppey, Daniel
Steiner-Monard, Viviane
Lonchampt, Sophie
Thieny, Anne-Christine
Mayor, Carole
Bailer, Robert T.
Mbaya, Olivier Tshiani
Zhou, Yan
Ploquin, Aurelie
Sullivan, Nancy J.
Graham, Barney S.
Roman, Francois
De Ryck, Iris
Ballou, W. Ripley
Kieny, Marie Paule
Moorthy, Vasee
Spertini, Francois
Genton, Blaise
TI Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola
vaccine in healthy adults: a randomised, double-blind,
placebo-controlled, dose-finding, phase 1/2a study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID I CLINICAL-TRIAL; VIRUS; PRIMATES
AB Background The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z).
Methods We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 x 10(10) viral particles), low-dose vaccine (2.5 x 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027.
Findings Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 mu g/mL (95% CI 41.1-63.3) in the high-dose group, 44.9 mu g/mL (25.8-56.3) in the low-dose group, and 5.2 mu g/mL (3.5-7.6) in the placebo group, with respective response rates of 96% (95% CI 85.7-99.5), 96% (86.5-99.5), and 5% (0.1-24.9). Geometric mean concentrations decreased by day 180 to 25.5 mu g/mL (95% CI 20.6-31.5) in the high-dose group, 22.1 mu g/mL (19.3-28.6) in the low-dose group, and 3.2 mu g/mL (2.4-4.9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31(61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses.
Interpretation ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa.
C1 [De Santis, Olga; Cochet, Camille; Estoppey, Daniel; Lonchampt, Sophie; Genton, Blaise] Policlin Med Univ, CH-1011 Lausanne, Switzerland.
[Audran, Regine; Steiner-Monard, Viviane; Thieny, Anne-Christine; Mayor, Carole; Spertini, Francois] Univ Lausanne Hosp, Div Immunol & Allergy, Lausanne, Switzerland.
[Warpelin-Decrausaz, Loane; Vallotton, Laure; Wuerzner, Gregoire] Univ Lausanne Hosp, Clin Trial Unit, Lausanne, Switzerland.
[Genton, Blaise] Univ Lausanne Hosp, Infect Dis Serv, Dept Med, Lausanne, Switzerland.
[Pothin, Emilie; Genton, Blaise] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
[Bailer, Robert T.; Mbaya, Olivier Tshiani; Zhou, Yan; Ploquin, Aurelie; Sullivan, Nancy J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Roman, Francois; De Ryck, Iris; Ballou, W. Ripley] GSK Vaccines, Rixensart, Belgium.
[Kieny, Marie Paule; Moorthy, Vasee] WHO, Geneva, Switzerland.
RP De Santis, O (reprint author), Policlin Med Univ, CH-1011 Lausanne, Switzerland.
EM olga.de-santis@hospvd.ch
FU Swiss State Secretariat for Education, Research, and Innovation (SERI)
[14.0001]; EU Horizon Research and Innovation Programme (EbolaVac
project) [666085]
FX We thank all persons interested, but eventually not screened, and all
volunteers for their generous and reliable participation in this trial;
Loredana Otgon, Emmanuelle Paccou, Christiana Pellet, Sylvie Poget, and
Francoise Secretan, the clinical research nurses of the Clinic Trial
Unit of the Centre Hospitalier Universitaire Vaudois (CHUV) for their
exceptional expertise and commitment; Stephanie Dartevelle and Isabelle
Angelstorf from the CHUV pharmacy for the randomisation and daily
preparation of the vaccine doses; Claudia Rochat and all laboratory
members for the accurate handling and analyses of a large amount of
blood samples; Kristina Moemi Geiger and Tom Stometta for their generous
assistance in blood sample preparations; Fady Fares and Ali Maghraoui
from the Clinical Trial Unit of the CHUV for data management; Pascal
Savary and Alexia Kaeser from the Legal Unit of the CHUV for contracts
revision; Richard Pink for his contribution to manuscript writing;
Patrick Francioli (Chairman of the Commission cantonale d'ethique de la
recherche sur l'etre humain) and his team, and the WHO Research Ethics
Review Committee for their rapid review and approval; Eric Huber and
Marek Sochor from the Swiss Tropical and Public Health Institute for
monitoring; Peter Smith, Pierre-Alexandre Bart, and Pierre
Landry-members of the Data and Safety Monitoring Board; the Vaccine
Research Centre team for their support in development of study
documentation, for making the vaccine doses available, and for doing the
intracellular cytokine staining analysis; Adrian Hill (Oxford
University, London, UK) with his team for providing documentation and
assistance in initiating a simian adenoviral vectored vaccine trial.
This work was supported by the Swiss State Secretariat for Education,
Research, and Innovation (SERI; contract number 14.0001) through the EU
Horizon 2020 Research and Innovation Programme (EbolaVac project) under
grant agreement number 666085. The opinions expressed and arguments
employed herein do not 20 necessarily reflect the official views of the
Swiss Government or the World Health Organization.
NR 25
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U1 5
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD MAR
PY 2016
VL 16
IS 3
BP 311
EP 320
DI 10.1016/S1473-3099(15)00486-7
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA DE4FQ
UT WOS:000370585000036
PM 26725450
ER
PT J
AU Amaratunga, C
Lim, P
Suon, S
Sreng, S
Mao, S
Sopha, C
Sam, B
Dek, D
Try, V
Amato, R
Blessborn, D
Song, LJ
Tullo, GS
Fay, MP
Anderson, JM
Tarning, J
Fairhurst, RM
AF Amaratunga, Chanaki
Lim, Pharath
Suon, Seila
Sreng, Sokunthea
Mao, Sivanna
Sopha, Chantha
Sam, Baramey
Dek, Dalin
Try, Vorleak
Amato, Roberto
Blessborn, Daniel
Song, Lijiang
Tullo, Gregory S.
Fay, Michael P.
Anderson, Jennifer M.
Tarning, Joel
Fairhurst, Rick M.
TI Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum
malaria in Cambodia: a multisite prospective cohort study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID UNCOMPLICATED FALCIPARUM; ARTEMISININ RESISTANCE; PARASITE CLEARANCE;
POPULATION PHARMACOKINETICS; ARTEMETHER-LUMEFANTRINE; WESTERN CAMBODIA;
MALIAN CHILDREN; SOUTHEAST-ASIA; VIVAX MALARIA; NETWORK WWARN
AB Background Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia.
Methods In this prospective cohort study, we enrolled patients aged 2-65 years with uncomplicated P falciparum malaria in three Cambodian provinces: Pursat, Preah Vihear, and Ratanakiri. Participants were given standard 3-day courses of dihydroartemisinin piperaquine. Peripheral blood parasite densities were measured until parasites cleared and then weekly to 63 days. The primary outcome was recrudescent P falciparum parasitaemia within 63 days. We measured piperaquine plasma concentrations at baseline, 7 days, and day of recrudescence. We assessed phenotypic and genotypic markers of drug resistance in parasite isolates. The study is registered with ClinicalTrials.gov, number NCT01736319.
Findings Between Sept 4, 2012, and Dec 31, 2013, we enrolled 241 participants. In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did. Patients with recrudescent P falciparum infections were more likely to have detectable piperaquine plasma concentrations at baseline compared with non-recrudescent patients, but did not differ significantly in age, initial parasite density, or piperaquine plasma concentrations at 7 days. Recrudescent parasites had a higher prevalence of kelch13 mutations, higher piperaquine 50% inhibitory concentration (IC50) values, and lower mefloquine ICE values; none had multiple pfmdr1 copies, a genetic marker of mefloquine resistance.
Interpretation Dihydroartemisinin piperaquine failures are caused by both artemisinin and piperaquine resistance, and commonly occur in places where dihydroartemisinin piperaquine has been used in the private sector. In Cambodia, artesunate plus mefloquine may be a viable option to treat dihydroartemisinin piperaquine failures, and a more effective first-line ACT in areas where dihydroartemisinin piperaquine failures are common. The use of single low-dose primaquine to eliminate circulating gametocytes is needed in areas where artemisinin and ACT resistance is prevalent.
C1 [Amaratunga, Chanaki; Lim, Pharath; Anderson, Jennifer M.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA.
[Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Dek, Dalin; Try, Vorleak] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
[Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia.
[Sopha, Chantha] Makara 16 Referral Hosp, Preah Vihear, Cambodia.
[Sam, Baramey] Ratanakiri Referral Hosp, Ratanakiri, Cambodia.
[Amato, Roberto] Wellcome Trust Sanger Inst, Hinxton, England.
[Amato, Roberto] Univ Oxford, Med Res Council, Ctr Genom & Global Hlth, Oxford, England.
[Blessborn, Daniel; Song, Lijiang; Tarning, Joel] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England.
[Blessborn, Daniel; Song, Lijiang; Tarning, Joel] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20852 USA.
EM rfairhurst@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX Funding National Institute of Allergy and Infectious Diseases.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD MAR
PY 2016
VL 16
IS 3
BP 357
EP 365
DI 10.1016/S1473-3099(15)00487-9
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA DE4FQ
UT WOS:000370585000041
PM 26774243
ER
PT J
AU Filippi, M
Rocca, MA
Ciccarelli, O
De Stefano, N
Evangelou, N
Kappos, L
Rovira, A
Sastre-Garriga, J
Tintore, M
Frederiksen, JL
Gasperini, C
Palace, J
Reich, DS
Banwell, B
Montalban, X
Barkhof, F
AF Filippi, Massimo
Rocca, Maria A.
Ciccarelli, Olga
De Stefano, Nicola
Evangelou, Nikos
Kappos, Ludwig
Rovira, Alex
Sastre-Garriga, Jaume
Tintore, Mar
Frederiksen, Jette L.
Gasperini, Claudio
Palace, Jacqueline
Reich, Daniel S.
Banwell, Brenda
Montalban, Xavier
Barkhof, Frederik
CA MAGNIMS Study Grp
TI MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus
guidelines
SO LANCET NEUROLOGY
LA English
DT Review
ID CLINICALLY ISOLATED SYNDROMES; RADIOLOGICALLY ISOLATED SYNDROME; 2010
MCDONALD CRITERIA; SENSITIVE INVERSION-RECOVERY; WHITE-MATTER LESIONS;
HIGH-FIELD MRI; CORTICAL-LESIONS; SPINAL-CORD; MS LESIONS; OPTIC
NEURITIS
AB In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has, improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.
C1 [Filippi, Massimo; Rocca, Maria A.] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Div Neurosci, Neuroimaging Res Unit,Inst Expt Neurol, Milan, Italy.
[Ciccarelli, Olga] UCL Inst Neurol, Dept Neuroinflammat, Queen Sq MS Ctr, London, England.
[Ciccarelli, Olga] UCL UCLH Biomed Res Ctr, NIHR, London, England.
[De Stefano, Nicola] Univ Siena, Dept Med Surg & Neurosci, Via Laterina 8, I-53100 Siena, Italy.
[Evangelou, Nikos] Univ Nottingham, Div Neurosci, Queens Med Ctr Campus, Nottingham NG7 2RD, England.
[Kappos, Ludwig] Univ Basel, Dept Neurol, Basel, Switzerland.
[Rovira, Alex] Univ Autonoma Barcelona, Hosp Univ Vail dHebron, Dept Radiol IDI, Magnet Resonance Unit, E-08193 Barcelona, Spain.
[Sastre-Garriga, Jaume; Tintore, Mar; Montalban, Xavier] Univ Autonoma Barcelona, Hosp Univ Vail dHebron, Dept Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, E-08193 Barcelona, Spain.
[Frederiksen, Jette L.] Glostrup Cty Hosp, Dept Neurol, Copenhagen, Denmark.
[Frederiksen, Jette L.] Univ Copenhagen, Copenhagen, Denmark.
[Gasperini, Claudio] San Camillo Forlanini Hosp, Dept Neurosci, Rome, Italy.
[Palace, Jacqueline] Univ Oxford Hosp Trust, Dept Clin Neurol, Oxford, England.
[Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Banwell, Brenda] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Child Neurol,Dept Neurol, Philadelphia, PA 19104 USA.
[Barkhof, Frederik] Vrije Univ Amsterdam Med Ctr, MS Ctr Amsterdam, Amsterdam, Netherlands.
RP Filippi, M (reprint author), Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Div Neurosci, Neuroimaging Res Unit,Inst Expt Neurol, Milan, Italy.
EM filippi.massimo@hsr.it
RI Reich, Daniel/E-5701-2010; gasperini, claudio/K-5093-2016
OI Reich, Daniel/0000-0002-2628-4334; Tintore, Mar/0000-0001-9999-5359;
Sastre Garriga, Jaume/0000-0002-1589-2254; gasperini,
claudio/0000-0002-3959-4067
FU Novartis; Swiss MS Society; Swiss National Research Foundation; European
Union; Multiple Sclerosis Society UK; Guthy-Jackson Foundation;
Neugrid4you (FP7 European committee); Dutch Foundation for MS
Research-centre grant
FX The workshop that formed the basis of this Review was supported by an
unrestricted educational grant from Novartis. The funding source had no
role in the preparation of this article. We are very grateful to Douglas
Arnold (Brain Imaging Center, Montreal Neurological Institute, McGill
University, Montreal, QC, Canada) for his fruitful discussion during the
meeting and his subsequent thoughtful comments on the manuscript. We
also thank Martina Absinta (Neuroimaging Research Unit, Institute of
Experimental Neurology, Division of Neuroscience, San Raffaele
Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy)
and Pascal Sari (Translational Neuroradiology Unit, National Institute
of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD, USA) for providing figures 3 and 4. LK has received
research grants from the Swiss MS Society, the Swiss National Research
Foundation, and the European Union. JP has received research grants from
the Multiple Sclerosis Society UK, and the Guthy-Jackson Foundation. FB
receives research support from Neugrid4you (FP7 European committee) and
the Dutch Foundation for MS Research-centre grant 2010-14.
NR 94
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAR
PY 2016
VL 15
IS 3
BP 292
EP 303
DI 10.1016/S1474-4422(15)00393-2
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA DE1ON
UT WOS:000370396400017
PM 26822746
ER
PT J
AU Nomura, M
Liu, J
Rovira, II
Gonzalez-Hurtado, E
Lee, J
Wolfgang, MJ
Finkel, T
AF Nomura, Mitsunori
Liu, Jie
Rovira, Ilsa I.
Gonzalez-Hurtado, Elsie
Lee, Jieun
Wolfgang, Michael J.
Finkel, Toren
TI Fatty acid oxidation in macrophage polarization
SO NATURE IMMUNOLOGY
LA English
DT Letter
ID INFLAMMATION; ACTIVATION
C1 [Nomura, Mitsunori; Liu, Jie; Rovira, Ilsa I.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Gonzalez-Hurtado, Elsie; Lee, Jieun; Wolfgang, Michael J.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.; Wolfgang, MJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
EM mwolfgal@jhmi.edu; finkelt@nih.gov
FU NINDS NIH HHS [NS072241]
NR 7
TC 13
Z9 13
U1 3
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAR
PY 2016
VL 17
IS 3
BP 216
EP 217
PG 2
WC Immunology
SC Immunology
GA DE2PN
UT WOS:000370469300002
PM 26882249
ER
PT J
AU Meng, X
Yang, JM
Dong, M
Zhang, K
Tu, E
Gao, Q
Chen, WJ
Zhang, C
Zhang, Y
AF Meng, Xiao
Yang, Jianmin
Dong, Mei
Zhang, Kai
Tu, Eric
Gao, Qi
Chen, Wanjun
Zhang, Cheng
Zhang, Yun
TI Regulatory T cells in cardiovascular diseases
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Review
ID PULMONARY ARTERIAL-HYPERTENSION; E-KNOCKOUT MICE; GROWTH-FACTOR-BETA;
EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; INTRAVENOUS IMMUNOGLOBULIN THERAPY;
ISCHEMIA-INDUCED ANGIOGENESIS; ABDOMINAL AORTIC-ANEURYSM; REDUCED
EJECTION FRACTION; RHEUMATIC HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN
AB Inflammation is essential in the initial development and progression of many cardiovascular diseases involving innate and adaptive immune responses. The role of CD4(+)CD25(+)FOXP3(+) regulatory T (T-REG) cells in the modulation of inflammation and immunity has received increasing attention. Given the important role of T-REG cells in the induction and maintenance of immune homeostasis and tolerance, dysregulation in the generation or function of T-REG cells can trigger abnormal immune responses and lead to pathology. A wealth of evidence from experimental and clinical studies has indicated that T-REG cells might have an important role in protecting against cardiovascular disease, in particular atherosclerosis and abdominal aortic aneurysm. In this Review, we provide an overview of the roles of T-REG cells in the pathogenesis of a number of cardiovascular diseases, including atherosclerosis, hypertension, ischaemic stroke, abdominal aortic aneurysm, Kawasaki disease, pulmonary arterial hypertension, myocardial infarction and remodelling, postischaemic neovascularization, myocarditis and dilated cardiomyopathy, and heart failure. Although the exact molecular mechanisms underlying the cardioprotective effects of T-REG cells are still to be elucidated, targeted therapies with T-REG cells might provide a promising and novel future approach to the prevention and treatment of cardiovascular diseases.
C1 [Meng, Xiao; Yang, Jianmin; Dong, Mei; Zhang, Kai; Zhang, Cheng; Zhang, Yun] Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodelling & Funct Res, 107 Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China.
[Meng, Xiao; Yang, Jianmin; Dong, Mei; Zhang, Kai; Zhang, Cheng; Zhang, Yun] Shandong Univ, Qilu Hosp, Chinese Minist Hlth, 107 Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China.
[Tu, Eric; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA.
[Gao, Qi] Shandong Univ, Shandong Prov Hosp, Dept Clin Lab, 324 Jingwu Weiqi Rd, Jinan 250021, Peoples R China.
RP Zhang, C (reprint author), Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodelling & Funct Res, 107 Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China.; Zhang, C (reprint author), Shandong Univ, Qilu Hosp, Chinese Minist Hlth, 107 Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China.
EM zhangc@sdu.edu.cn
FU National 973 Basic Research Program of China [2011CB503906,
2012CB518603, 2013CB530703]; National High-Tech Research and Development
Program of China [2012AA02A510]; Program of Introducing Talents of
Discipline to Universities [B07035]; State Program of National Natural
Science Foundation of China for Innovative Research Group [81321061];
State Key Program of National Natural Science of China [61331001];
International Collaboration and Exchange Program of China [81320108004];
National Natural Science Foundation of China [81100207, 81173251,
81270350, 81300234]; Intramural Research Program of NIH, NIDCR
FX X.M, J.Y., M.D, K.Z., C.Z. and Y.Z. are supported by the National 973
Basic Research Program of China (2011CB503906, 2012CB518603,
2013CB530703), the National High-Tech Research and Development Program
of China (2012AA02A510), the Program of Introducing Talents of
Discipline to Universities (B07035), the State Program of National
Natural Science Foundation of China for Innovative Research Group
(81321061), the State Key Program of National Natural Science of China
(61331001), the International Collaboration and Exchange Program of
China (81320108004), and research grants from the National Natural
Science Foundation of China (81100207, 81173251, 81270350, and
81300234). E.T. and W.C. are supported by the Intramural Research
Program of NIH, NIDCR.
NR 177
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5002
EI 1759-5010
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD MAR
PY 2016
VL 13
IS 3
BP 167
EP U2222
DI 10.1038/nrcardio.2015.169
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DE2RD
UT WOS:000370473600008
PM 26525543
ER
PT J
AU Chung, ST
Sumner, AE
AF Chung, Stephanie T.
Sumner, Anne E.
TI T2DM risk prediction in populations of African descent
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Editorial Material
ID HEMOGLOBIN A(1C); PREVALENCE
AB Although the prevalence of type 2 diabetes mellitus (T2DM) is higher in African-American than in white individuals, equations developed to predict T2DM are more effective in white individuals. A new study by Lacy and colleagues highlights the need to re-examine current paradigms and identify new biomarkers to determine the earliest features of T2DM risk in populations of African descent.
C1 [Chung, Stephanie T.; Sumner, Anne E.] NIDDK, Sect Ethn & Hlth, Diabet Endocrinol & Obes Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Sumner, AE (reprint author), NIDDK, Sect Ethn & Hlth, Diabet Endocrinol & Obes Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM annes@intra.niddk.nih.gov
FU Intramural NIH HHS
NR 10
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD MAR
PY 2016
VL 12
IS 3
BP 131
EP 132
DI 10.1038/nrendo.2016.2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DE2RP
UT WOS:000370474800004
PM 26794440
ER
PT J
AU Long, MT
Fox, CS
AF Long, Michelle T.
Fox, Caroline S.
TI The Framingham Heart Study-67 years of discovery in metabolic disease
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Article
ID BODY-FAT DISTRIBUTION; INCIDENT CARDIOVASCULAR-DISEASE; TYPE-2
DIABETES-MELLITUS; GENOME-WIDE ASSOCIATION; COMMUNITY-BASED SAMPLE;
ALL-CAUSE MORTALITY; MIDDLE-AGED ADULTS; RISK-FACTORS; AMINOTRANSFERASE
LEVELS; FASTING GLUCOSE
AB The Framingham Heart Study (FHS), initiated in 1948, is the longest running prospective cohort study in the USA. Through >65 years of discovery, the FHS has contributed to our understanding of obesity, type 2 diabetes mellitus and prediabetes mellitus, the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD), and to how these conditions relate to our overall and cardiovascular-related mortality. This Timeline gives an overview of the substantial role the FHS has played in advancing the understanding of obesity, diabetes mellitus and NAFLD, and considers the direction the FHS will take in the years to come.
C1 [Long, Michelle T.] Boston Univ, Div Gastroenterol, Boston Med Ctr, Sch Med, 7th Floor,85 East Concord St, Boston, MA 02118 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
RP Long, MT (reprint author), Boston Univ, Div Gastroenterol, Boston Med Ctr, Sch Med, 7th Floor,85 East Concord St, Boston, MA 02118 USA.
EM mtlong@bu.edu
FU Boston University School of Medicine; National Heart, Lung, and Blood
Institute's Framingham Heart Study [HHSN268201500001I]; Division of
Intramural Research of the National Heart, Lung, and Blood Institute
FX The authors acknowledge funding by the Boston University School of
Medicine and the National Heart, Lung, and Blood Institute's Framingham
Heart Study (contract HHSN268201500001I) and the Division of Intramural
Research of the National Heart, Lung, and Blood Institute.
NR 65
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U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD MAR
PY 2016
VL 12
IS 3
BP 177
EP 183
DI 10.1038/nrendo.2015.226
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DE2RP
UT WOS:000370474800009
PM 26775764
ER
PT J
AU van Gelderen, P
Jiang, X
Duyn, JH
AF van Gelderen, Peter
Jiang, Xu
Duyn, Jeff H.
TI Effects of magnetization transfer on T-1 contrast in human brain white
matter
SO NEUROIMAGE
LA English
DT Article
DE Brain tissue; White matter; Myelin; T-1 contrast; Magnetization
transfer; Macromolecular content
ID MACROMOLECULAR PROTON FRACTION; IN-VIVO; CROSS-RELAXATION;
WATER-CONTENT; LONGITUDINAL RELAXATION; PHOSPHOLIPID-VESICLES;
MULTIPLE-SCLEROSIS; RESONANCE; RECOVERY; MYELIN
AB MRI based on T-1 relaxation contrast is increasingly being used to study brain morphology and myelination. Although it provides for excellent distinction between the major tissue types of gray matter, white matter, and CSF, reproducible quantification of T-1 relaxation rates is difficult due to the complexity of the contrast mechanism and dependence on experimental details. In this work, we perform simulations and inversion-recovery MRI measurements at 3 T and 7 T to show that substantial measurement variability results from unintended and uncontrolled perturbation of the magnetization of MRI-invisible H-1 protons of lipids and macromolecules. This results in bi-exponential relaxation, with a fast component whose relative contribution under practical conditions can reach 20%. This phenomenon can strongly affect apparent relaxation rates, affect contrast between tissue types, and result in contrast variations over the brain. Based on this novel understanding, ways are proposed to minimize this experimental variability and its effect on T-1 contrast, quantification accuracy and reproducibility. Published by Elsevier Inc.
C1 [van Gelderen, Peter; Jiang, Xu; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
FU Intramural program of NINDS
FX This work has been supported by the Intramural program of NINDS.
NR 60
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U1 2
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2016
VL 128
BP 85
EP 95
DI 10.1016/j.neuroimage.2015.12.032
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DE1KN
UT WOS:000370386000009
PM 26724780
ER
PT J
AU Langen, ES
Weiner, SJ
Bloom, SL
Rouse, DJ
Varner, MW
Reddy, UM
Ramin, SM
Caritis, SN
Peaceman, AM
Sorokin, Y
Sciscione, A
Carpenter, MW
Mercer, BM
Thorp, JM
Malone, FD
Iams, JD
AF Langen, Elizabeth S.
Weiner, Steven J.
Bloom, Steven L.
Rouse, Dwight J.
Varner, Michael W.
Reddy, Uma M.
Ramin, Susan M.
Caritis, Steve N.
Peaceman, Alan M.
Sorokin, Yoram
Sciscione, Anthony
Carpenter, Marshall W.
Mercer, Brian M.
Thorp, John M., Jr.
Malone, Fergal D.
Iams, Jay D.
CA Eunice Kennedy Shriver Natl Inst C
Maternal-Fetal Med Units MFMU
TI Association of Cervical Effacement With the Rate of Cervical Change in
Labor Among Nulliparous Women
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CESAREAN DELIVERY
AB OBJECTIVE:
To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women.
METHODS:
We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin.
RESULTS:
A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001).
CONCLUSION:
The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement.
CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov,
[GRAPHICS]
, NCT00098709.
C1 Stanford Univ, Dept Obstet, Stanford, CA 94305 USA.
Stanford Univ, Dept Gynecol, Stanford, CA 94305 USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Univ Texas Houston, Childrens Mem Hermann Hosp, Hlth Sci Ctr, Houston, TX USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Northwestern Univ, Chicago, IL 60611 USA.
Wayne State Univ, Detroit, MI USA.
Drexel Univ, Philadelphia, PA 19104 USA.
Brown Univ, Providence, RI 02912 USA.
Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
Univ N Carolina, Chapel Hill, NC USA.
Columbia Univ, New York, NY USA.
Ohio State Univ, Columbus, OH 43210 USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
NICHHD, Bethesda, MD 20892 USA.
RP Langen, ES (reprint author), Floor 9,Room 109 VVWH,1540 W Hosp Dr,SPC 4264, Ann Arbor, MI 48109 USA.
EM elangen@med.umich.edu
RI Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD21410, HD27860, HD27869, HD27915, HD27917,
HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, M01
RR00080, HD40545, HD40560, HD36801]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) (HD21410, HD27860,
HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40485, HD40500,
HD40512, HD40544, M01 RR00080 (NCRR); HD40545, HD40560, and HD36801).
NR 14
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAR
PY 2016
VL 127
IS 3
BP 489
EP 495
DI 10.1097/AOG.0000000000001299
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DE6DI
UT WOS:000370723400006
PM 26855099
ER
PT J
AU Venkatramani, R
Murray, J
Helman, L
Meyer, W
Hicks, MJ
Krance, R
Lau, C
Jo, E
Chintagumpala, M
AF Venkatramani, Rajkumar
Murray, Jeffrey
Helman, Lee
Meyer, William
Hicks, M. John
Krance, Robert
Lau, Ching
Jo, Eunji
Chintagumpala, Murali
TI Risk-Based Therapy for Localized Osteosarcoma
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE clinical trials; high-dose chemotherapy; necrosis; osteosarcoma; stem
cell transplantation
ID PEDIATRIC-ONCOLOGY-GROUP; HIGH-DOSE CHEMOTHERAPY; STEM-CELL RESCUE;
NONMETASTATIC OSTEOSARCOMA; NEOADJUVANT CHEMOTHERAPY; ADJUVANT
CHEMOTHERAPY; OSTEOGENIC-SARCOMA; PREOPERATIVE CHEMOTHERAPY; HISTOLOGIC
RESPONSE; MURAMYL TRIPEPTIDE
AB BackgroundThe outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival.
ProcedurePatients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion.
ResultsFifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths.
ConclusionsPostoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.
C1 [Venkatramani, Rajkumar; Krance, Robert; Lau, Ching; Chintagumpala, Murali] Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, 6701 Fannin St,Suite 1510, Houston, TX 77030 USA.
[Murray, Jeffrey] Cook Childrens Med Ctr, Ft Worth, TX USA.
[Helman, Lee] NIH, Ctr Clin, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Meyer, William] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA.
[Hicks, M. John] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Hicks, M. John] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Jo, Eunji] Baylor Coll Med, Dan L Duncan Canc Ctr, Biostat & Informat Shared Resource, Houston, TX 77030 USA.
RP Venkatramani, R (reprint author), Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, 6701 Fannin St,Suite 1510, Houston, TX 77030 USA.
EM venkatra@bcm.edu
NR 27
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAR
PY 2016
VL 63
IS 3
BP 412
EP 417
DI 10.1002/pbc.25808
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DD9LU
UT WOS:000370247900005
PM 26501936
ER
PT J
AU Gorlick, R
Kolb, EA
Keir, ST
Maris, JM
Lock, RB
Carol, H
Reynolds, CP
Kang, MH
Billups, CA
Collins, J
Kurmashev, D
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Gorlick, Richard
Kolb, E. Anders
Keir, Stephen T.
Maris, John M.
Lock, Richard B.
Carol, Hernan
Reynolds, C. Patrick
Kang, Min H.
Billups, Catherine A.
Collins, Jerry
Kurmashev, Dias
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric
Tumor Models by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; NSC 750854; preclinical testing; purine
analogs
ID SUBSTRATE-ASSISTED INHIBITION; STAGE 1
AB BackgroundNSC 750854 is a purine analog with an antitumor activity profile distinctive from that of other anticancer purines. It has shown significant activity against adult cancer preclinical models.
ProcedureNSC 750854 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10 M and against the PPTP in vivo xenograft panels administered intraperitoneally at a dose of 5 mg/kg daily for 5 days repeated at day 15.
ResultsThe median relative IC50 (rIC(50)) value for the PPTP cell lines was 32 nM (range from 11 to 124 nM), with consistent cytotoxicity across all cell lines. Acute lymphoblastic leukemia (ALL) cell lines were more sensitive to NSC 750854 than non-ALL cell lines. NSC 750854 induced significant differences in EFS distribution compared to control in 31 of 35 (89%) solid tumor xenografts. It induced tumor growth inhibition meeting criteria for intermediate or high event free survival (EFS) T/C activity in 17 of 32 (53%) evaluable solid tumor xenografts (most consistently in the rhabdomyosarcoma panel). Objective responses were observed in 15 of 37 (41%) solid tumor xenografts and in all eight leukemia models with complete response (CR) or maintained complete response (MCR) in seven of eight leukemia models.
ConclusionsNSC 750854 has a unique spectrum of antitumor activity compared with other agents tested by the PPTP as it induces regression in tumor models with limited sensitivity to most agents tested to date. Given the promising level of activity observed for NSC 750854 against PPTP preclinical models, further exploration of its mechanism of action is warranted.
C1 [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Maris, John M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Lock, Richard B.; Carol, Hernan] Univ New S Wales, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Billups, Catherine A.] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Collins, Jerry] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA.
[Kurmashev, Dias; Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Gorlick, R (reprint author), Montefiore Med Ctr, Dept Pediat, 3415 Bainbridge Ave, Bronx, NY 10467 USA.
EM rgorlick@montefiore.org
RI Lock, Richard/G-4253-2013;
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786];
Developmental Therapeutics Program (DTP), NCI Frederick [NSC 750854]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, and CA108786; Grant sponsor: Developmental Therapeutics Program
(DTP), NCI Frederick; Grant number: NSC 750854.
NR 12
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAR
PY 2016
VL 63
IS 3
BP 443
EP 450
DI 10.1002/pbc.25826
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DD9LU
UT WOS:000370247900009
PM 26797892
ER
PT J
AU Richards, EM
Mathews, DC
Luckenbaugh, DA
Ionescu, DF
Machado-Vieira, R
Niciu, MJ
Duncan, WC
Nolan, NM
Franco-Chaves, JA
Hudzik, T
Maciag, C
Li, S
Cross, A
Smith, MA
Zarate, CA
AF Richards, Erica M.
Mathews, Daniel C.
Luckenbaugh, David A.
Ionescu, Dawn F.
Machado-Vieira, Rodrigo
Niciu, Mark J.
Duncan, Wallace C.
Nolan, Neal M.
Franco-Chaves, Jose A.
Hudzik, Thomas
Maciag, Carla
Li, Shuang
Cross, Alan
Smith, Mark A.
Zarate, Carlos A., Jr.
TI A randomized, placebo-controlled pilot trial of the delta opioid
receptor agonist AZD2327 in anxious depression
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Anxiety; Anxious depression; Anxiolytic; Major depressive disorder;
Opiate; BDNF; EEG; Preclinical; Biomarkers; AZD2327
ID MESSENGER-RNA EXPRESSION; FORCED-SWIM TEST; STAR-ASTERISK-D; ENDOTHELIAL
GROWTH-FACTOR; MAJOR DEPRESSION; ANXIETY DISORDERS; MOOD DISORDERS;
NONANXIOUS DEPRESSION; OPIATE RECEPTORS; SUICIDE VICTIMS
AB Patients with anxious major depressive disorder (AMDD) have more severe symptoms and poorer treatment response than patients with non-AMDD. Increasing evidence implicates the endogenous opioid system in the pathophysiology of depression. AZD2327 is a selective delta opioid receptor (DOR) agonist with anxiolytic and antidepressant activity in animal models.
This double-blind, parallel group design, placebo-controlled pilot study evaluated the safety and efficacy of AZD2327 in a preclinical model and in patients with AMDD.
We initially tested the effects of AZD2327 in an animal model of AMDD. Subsequently, 22 subjects with AMDD were randomized to receive AZD2327 (3 mg BID) or placebo for 4 weeks. Primary outcome measures included the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). We also evaluated neurobiological markers implicated in mood and anxiety disorders, including vascular endothelial growth factor (VEGF) and electroencephalogram (EEG).
Seven (54 %) patients responded to active drug and three (33 %) responded to placebo. No significant main drug effect was found on either the HAM-D (p = 0.39) or the HAM-A (p = 0.15), but the HAM-A had a larger effect size. Levels of AZ12311418, a major metabolite of AZD2327, were higher in patients with an anti-anxiety response to treatment compared to nonresponders (p = 0.03). AZD2327 treatment decreased VEGF levels (p = 0.02). There was a trend (p < 0.06) for those with an anti-anxiety response to have higher EEG gamma power than nonresponders.
These results suggest that AZD2327 has larger potential anxiolytic than antidepressant efficacy. Additional research with DOR agonists should be considered.
C1 [Richards, Erica M.; Mathews, Daniel C.; Luckenbaugh, David A.; Ionescu, Dawn F.; Machado-Vieira, Rodrigo; Niciu, Mark J.; Duncan, Wallace C.; Nolan, Neal M.; Franco-Chaves, Jose A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Dept Hlth & Human Serv, NIH, 10 Ctr Dr CRC,Room 7-5545, Bethesda, MD 20892 USA.
[Hudzik, Thomas; Maciag, Carla; Li, Shuang; Cross, Alan; Smith, Mark A.] AstraZeneca Neurosci Innovat Med, Cambridge, MA USA.
[Mathews, Daniel C.] Lundbeck LLC, Chicago, IL USA.
[Ionescu, Dawn F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Franco-Chaves, Jose A.] Vet Affairs Caribbean Healthcare Syst, San Juan, PR USA.
[Hudzik, Thomas] AbbVie, Chicago, IL USA.
[Maciag, Carla] Sage Therapeut, Cambridge, MA USA.
RP Richards, EM (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Dept Hlth & Human Serv, NIH, 10 Ctr Dr CRC,Room 7-5545, Bethesda, MD 20892 USA.
EM erica.richards@nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; Ionescu,
Dawn/K-5675-2015; Cross, Alan/L-5456-2016
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu,
Mark/0000-0002-5612-3021; Cross, Alan/0000-0002-2992-2258
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH) [NCT00759395, 08-M-0196];
NARSAD; Brain & Behavior Mood Disorders Research Award
FX Funding for this work was supported in part by the Intramural Research
Program at the National Institute of Mental Health, National Institutes
of Health (IRP-NIMH-NIH; NCT00759395, protocol 08-M-0196), by a NARSAD
Independent Investigator to Dr. Zarate, and by a Brain & Behavior Mood
Disorders Research Award to Dr. Zarate. These funding sources had no
further role in study design; in the collection, analysis, or
interpretation of data; in the writing of the report; or in the decision
to submit the paper for publication. A patent for the use of ketamine in
depression has been awarded that lists Dr. Zarate among the inventors;
he has assigned his rights on the patent to the US government, but will
share a percentage of any royalties that may be received by the
government. Carla Maciag and Drs. Mark Smith, Thomas Hudzik, and Alan
Cross were full-time employees of AstraZeneca Neuroscience Innovative
Medicines at the time the study was conducted. AstraZeneca
Pharmaceuticals provided the study compound.
NR 57
TC 5
Z9 5
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2016
VL 233
IS 6
BP 1119
EP 1130
DI 10.1007/s00213-015-4195-4
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DE8ER
UT WOS:000370869100019
PM 26728893
ER
PT J
AU Kozak, MJ
Cuthbert, BN
AF Kozak, Michael J.
Cuthbert, Bruce N.
TI The NIMH Research Domain Criteria Initiative: Background, Issues, and
Pragmatics
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Research Domain Criteria; Psychopathology; Psychometrics; Biometrics;
Hypothetical constructs; Diagnostic and Statistical Manual; National
Institute of Mental Health
ID PSYCHOPATHOLOGY RESEARCH; HYPOTHETICAL CONSTRUCTS; INTERVENING
VARIABLES; SOCIAL ANHEDONIA; MENTAL-DISORDERS; ANIMAL-MODELS; DSM-V;
ANXIETY; SPECTRUM; FEAR
AB This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct grain size, and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design.
C1 [Kozak, Michael J.; Cuthbert, Bruce N.] NIMH, Bethesda, MD 20892 USA.
RP Kozak, MJ (reprint author), NIMH, Bethesda, MD 20892 USA.; Kozak, MJ (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM KozakM@mail.nih.gov
NR 56
TC 43
Z9 43
U1 5
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0048-5772
EI 1469-8986
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD MAR
PY 2016
VL 53
IS 3
SI SI
BP 286
EP 297
DI 10.1111/psyp.12518
PG 12
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA DE2VL
UT WOS:000370485200002
PM 26877115
ER
PT J
AU Morrison, LJ
Schmicker, RH
Weisfeldt, ML
Bigham, BL
Berg, RA
Topjian, AA
Abramson, BL
Atkins, DL
Egan, D
Sopko, G
Rac, VE
AF Morrison, Laurie J.
Schmicker, Robert H.
Weisfeldt, Myron L.
Bigham, Blair L.
Berg, Robert A.
Topjian, Alexis A.
Abramson, Beth L.
Atkins, Dianne L.
Egan, Debra
Sopko, George
Rac, Valeria E.
CA Resuscitation Outcomes Consortium
TI Effect of gender on outcome of out of hospital cardiac arrest in the
Resuscitation Outcomes Consortium
SO RESUSCITATION
LA English
DT Article
DE Heart arrest; Out of hospital cardiac arrest; Cardiopulmonary
resuscitation; Gender; Adult population
ID AMERICAN-HEART-ASSOCIATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS;
INTERNATIONAL LIAISON COMMITTEE; EMERGENCY CARDIOVASCULAR CARE;
TRAUMATIC BRAIN-INJURY; MYOCARDIAL-INFARCTION; SEX-DIFFERENCES;
CARDIOPULMONARY-RESUSCITATION; HEALTH-CARE; THERAPEUTIC HYPOTHERMIA
AB Introduction: This study examined the relationship between gender and outcomes of non-traumatic out of -hospital cardiac arrest (OHCA).
Methods: All eligible, consecutive, non-traumatic Emergency Medical Services (EMS) treated OHCA patients in the Resuscitation Outcomes Consortium between December 2005 and May 2007. Patient age was analyzed as a continuous variable and stratified in two age cohorts: 15-45 and >55 years of age (yoa). Unadjusted and adjusted (based on Utstein characteristics) chi square tests and logistic regression models were employed to examine the relationship between gender, age, and survival outcomes.
Results: This study enrolled 14,690 patients: of which 36.4% were women with a mean age of 68.3 and 63.6% of them men with a mean age of 64.2. Women survived to hospital discharge less often than men (6.4% vs. 9.1%, p < 0.001); the unadjusted OR was 0.69, 95%CI: 0.60, 0.77 whereas when adjusted for all Utstein predictors the difference was not significant (OR: 1.16, 95%CI: 0.98, 1.36, p = 0.07). The adjusted survival rate for younger women (15-45 yoa) was 11.1% vs. 9.8% for younger men (OR: 1.66, 95%CI: 1.04, 2.64, p = 0.03) but no difference in discharge rates was observed in the >55 cohort (OR: 0.94, 95%CI: 0.78, 1.15, p = 0.57).
Conclusions: Women who suffer OHCAs have lower rates of survival and have unfavourable Utstein predictors. When survival is adjusted for these predictors survival is similar between men and women except in younger women suggesting that age modifies the association of gender and survival from OHCA; a result that supports a protective hormonal effect among premenopausal women. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Morrison, Laurie J.; Bigham, Blair L.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Rescu, Toronto, ON, Canada.
[Morrison, Laurie J.] Univ Toronto, Dept Med, Div Emergency Med, Toronto, ON, Canada.
[Morrison, Laurie J.; Rac, Valeria E.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Schmicker, Robert H.] Univ Washington, Clin Trials Ctr, Seattle, WA 98195 USA.
[Weisfeldt, Myron L.] Johns Hopkins Med, Baltimore, MD USA.
[Berg, Robert A.; Topjian, Alexis A.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Abramson, Beth L.] Univ Toronto, St Michaels Hosp, Cardiac Prevent Ctr, Toronto, ON, Canada.
[Abramson, Beth L.] Univ Toronto, St Michaels Hosp, Womens Cardiovasc Hlth, Toronto, ON, Canada.
[Atkins, Dianne L.] Univ Iowa, Childrens Hosp, Carver Coll Med, Iowa City, IA USA.
[Egan, Debra; Sopko, George] NHLBI, Div Cardiovasc Dis, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Rac, Valeria E.] Univ Toronto, Univ Hlth Network, Toronto Gen Res Insitute, Toronto Hlth Econ & Technol Assessment Collaborat, Toronto, ON, Canada.
[Rac, Valeria E.] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON, Canada.
RP Morrison, LJ (reprint author), St Michaels Hosp, Rescu, 30 Bond St, Toronto, ON M5B 1W8, Canada.
EM morrisonl@smh.ca
RI morrison, laurie/A-6325-2012
OI morrison, laurie/0000-0001-8369-9774
FU National Heart, Lung and Blood Institute [5U01 HL077863, HL077865,
HL077866, HL077867, HL077871, HL077872, HL077873, HL077881, HL077885,
HL077887, HL077908]; National Institute of Neurological Disorders and
Stroke; US Army Medical Research & Material Command; Canadian Institutes
of Health Research (CIHR) - Institute of Circulatory and Respiratory
Health, Defence Research and Development Canada; Heart, Stroke
Foundation of Canada; American Heart Association
FX The ROC is supported by a series of cooperative agreements to 10
regional clinical centres and one Data Coordinating Centre (5U01
HL077863-University of Washington Data Coordinating Centre,
HL077865-University of Iowa, HL077866-Medical College of Wisconsin,
HL077867-University of Washington, HL077871-University of Pittsburgh,
HL077872-St. Michael's Hospital, HL077873-Oregon Health and Science
University, HL077881-University of Alabama at Birmingham,
HL077885-Ottawa Hospital Research Institute, HL077887-University of
Texas SW Medical Ctr/Dallas, HL077908-University of California San
Diego) from the National Heart, Lung and Blood Institute in partnership
with the National Institute of Neurological Disorders and Stroke, US
Army Medical Research & Material Command, The Canadian Institutes of
Health Research (CIHR) - Institute of Circulatory and Respiratory
Health, Defence Research and Development Canada, the Heart, Stroke
Foundation of Canada and the American Heart Association. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Heart, Lung and Blood
Institute or the National Institutes of Health.
NR 60
TC 4
Z9 5
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-9572
J9 RESUSCITATION
JI Resuscitation
PD MAR
PY 2016
VL 100
BP 76
EP 81
DI 10.1016/j.resuscitation.2015.12.002
PG 6
WC Critical Care Medicine; Emergency Medicine
SC General & Internal Medicine; Emergency Medicine
GA DD8MP
UT WOS:000370181300017
PM 26705971
ER
PT J
AU Sankineni, S
Brown, A
Cieciera, M
Choyke, PL
Turkbey, B
AF Sankineni, Sandeep
Brown, Anna
Cieciera, Matthaeus
Choyke, Peter L.
Turkbey, Baris
TI Imaging of renal cell carcinoma
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Renal cell carcinoma; MRI; CT; Ultrasound
ID DUAL-ENERGY CT; CLEAR-CELL; DIAGNOSTIC PERFORMANCE; MULTIDETECTOR CT;
UNENHANCED CT; VISIBLE FAT; HELICAL CT; MASSES; DIFFERENTIATION; LESIONS
AB Renal cell carcinoma (RCC) is the most common kidney cancer in adults. Early and accurate imaging plays an important role in the detection, staging, and follow-up of RCC. Patient care and case management revolves heavily around diagnostic imaging so it is imperative that appropriate and adequate imaging is acquired. There are well-established standard imaging protocols available to patients and their providers, although at the same time, there is also extensive ongoing research on improving the various modalities.
Ultrasound has been the most commonly used imaging technique for renal imaging in general. However, computed tomography (CT) is the first choice for imaging of renal masses, and has been the mainstay for several decades. High resolution, reproducibility, reasonable preparation and acquisition time, and acceptable cost allow CT to remain as the primary choice for radiologic imaging. Magnetic resonance imaging (MRI) is considered as an important alternative in patients requiring further imaging or in cases of allergies, pregnancy, or surveillance. With increasing concern over radiation exposure, there has been a trend toward the higher use of MRI.
It is important to understand the various imaging options available, as well as the current status of and results from recent RCC imaging studies. In this review we discuss these modalities, including the current state of ultrasound, CT, and MRI in RCC. Published by Elsevier Inc.
C1 [Sankineni, Sandeep; Brown, Anna; Cieciera, Matthaeus; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
OI Cieciera, Matthaeus/0000-0003-2186-3326
NR 71
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD MAR
PY 2016
VL 34
IS 3
BP 147
EP 155
DI 10.1016/j.urolonc.2015.05.020
PG 9
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA DD9RA
UT WOS:000370262100017
PM 26094171
ER
PT J
AU Machado-Vieira, R
Otaduy, MC
Zanetti, MV
De Sousa, RT
Dias, VV
Leite, CC
Forlenza, OV
Busatto, GF
Soares, JC
Gattaz, WF
AF Machado-Vieira, R.
Otaduy, M. C.
Zanetti, M. V.
De Sousa, R. T.
Dias, V. V.
Leite, C. C.
Forlenza, O. V.
Busatto, G. F.
Soares, J. C.
Gattaz, W. F.
TI A Selective Association between Central and Peripheral Lithium Levels in
Remitters in Bipolar Depression: A 3T-Li-7 Magnetic Resonance
Spectroscopy Study
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE bipolar disorder; depression; lithium; imaging; spectroscopy; treatment;
magnetic resonance spectroscopy
ID MAINTENANCE TREATMENT; DISORDER; BRAIN; TRANSPORT; TRIAL; MRS
AB ObjectiveThe objective of this study was to evaluate brain lithium levels using Li-7 magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement.
MethodTwenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naive. At endpoint, patients underwent a Li-7-MRS scan and brain lithium concentrations were calculated.
ResultsA significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects.
ConclusionThese findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with Li-7-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted.
C1 [Machado-Vieira, R.; Zanetti, M. V.; De Sousa, R. T.; Forlenza, O. V.; Gattaz, W. F.] Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci LIM 27, Rua Dr Ovidio Pires Campos, BR-785 Sao Paulo, Brazil.
[Machado-Vieira, R.; Otaduy, M. C.; Zanetti, M. V.; Dias, V. V.; Leite, C. C.; Forlenza, O. V.; Busatto, G. F.; Gattaz, W. F.] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-785 Sao Paulo, Brazil.
[Machado-Vieira, R.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Otaduy, M. C.; Leite, C. C.] Univ Sao Paulo, Inst & Dept Radiol, Lab Magnet Resonance Neuroradiol LIM 44, BR-785 Sao Paulo, Brazil.
[Busatto, G. F.] Univ Sao Paulo, Inst & Dept Psychiat, Lab Psychiat Neuroimaging LIM 21, BR-785 Sao Paulo, Brazil.
[Soares, J. C.] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci LIM 27, Rua Dr Ovidio Pires Campos, BR-785 Sao Paulo, Brazil.
EM machadovieirar@gmail.com
RI Busatto, Geraldo/D-4431-2009; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU Sao Paulo Research Foundation (Fapesp, Brazil); grant ClnAPCe
[05/56464-9]; Associacao Beneficente Alzira Denise Hertzog da Silva
(ABADHS) [LIM27]; JNK Empreendimentos Ltda; [2009/14891-9]
FX This study was sponsored by Sao Paulo Research Foundation (Fapesp,
Brazil) and grants 2009/14891-9 (RM-V) and ClnAPCe (project 05/56464-9).
The Laboratory of Neuroscience, (LIM27) is also supported by the
Associacao Beneficente Alzira Denise Hertzog da Silva (ABADHS) and by
the JNK Empreendimentos Ltda.
NR 18
TC 0
Z9 0
U1 4
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0001-690X
EI 1600-0447
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD MAR
PY 2016
VL 133
IS 3
BP 214
EP 220
DI 10.1111/acps.12511
PG 7
WC Psychiatry
SC Psychiatry
GA DD7BF
UT WOS:000370078000006
PM 26513535
ER
PT J
AU Lynes, C
Phillips, J
Keane, C
Sloan, D
Berger, A
AF Lynes, Chelsea
Phillips, Jayne
Keane, Cynthia
Sloan, Danetta
Berger, Ann
TI An Evaluation of a Bereavement Program in a US Research Hospital
SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE
LA English
DT Article
DE bereavement; grief; loss; program evaluation; support; research subjects
ID FAMILIES; GRIEF
AB The Bereavement Program at the National Institutes of Health (NIH) Clinical Center was established in 2005. The program makes contact with the next of kin on 4 occasions postnotification of death. The objective of this analysis was to evaluate program effectiveness for those individuals who we successfully made contact with on all 4 occasions (N = 39). At 12 months postnotification, the majority viewed the NIH as a source of support (56%), and the frequency of positive emotional ratings increased (59%). There are limitations to this analysis, and biases may be present. In sum, this analysis serves as an example of a successful hospital-based bereavement program that enrolls patients who have been treated at the institution in any capacity who are also patients enrolled in institutional review board-approved research protocols.
C1 [Lynes, Chelsea] Univ S Carolina, Arnold Sch Publ Hlth, Discovery Bldg,Room 432,915 Greene St, Columbia, SC 29209 USA.
[Phillips, Jayne; Keane, Cynthia; Sloan, Danetta; Berger, Ann] NIH, Pain & Palliat Care Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Lynes, C (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Discovery Bldg,Room 432,915 Greene St, Columbia, SC 29209 USA.
EM clynes@email.sc.edu
FU National Institutes of Health
FX The Project was completed through National Institutes of Health Clinical
Center Intramural Research Training Award (summer 2014).
NR 8
TC 0
Z9 0
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-9091
EI 1938-2715
J9 AM J HOSP PALLIAT ME
JI Am. J. Hosp. Palliat. Med.
PD MAR
PY 2016
VL 33
IS 2
BP 150
EP 153
DI 10.1177/1049909114557538
PG 4
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DD8TW
UT WOS:000370200800007
PM 25376226
ER
PT J
AU Schwantes-An, TH
Zhang, J
Chen, LS
Hartz, SM
Culverhouse, RC
Chen, XN
Coon, H
Frank, J
Kamens, HM
Konte, B
Kovanen, L
Latvala, A
Legrand, LN
Maher, BS
Melroy, WE
Nelson, EC
Reid, MW
Robinson, JD
Shen, PH
Yang, BZ
Andrews, JA
Aveyard, P
Beltcheva, O
Brown, SA
Cannon, DS
Cichon, S
Corley, RP
Dahmen, N
Degenhardt, L
Foroud, T
Gaebel, W
Giegling, I
Glatt, SJ
Grucza, RA
Hardin, J
Hartmann, AM
Heath, AC
Herms, S
Hodgkinson, CA
Hoffmann, P
Hops, H
Huizinga, D
Ising, M
Johnson, EO
Johnstone, E
Kaneva, RP
Kendler, KS
Kiefer, F
Kranzler, HR
Krauter, KS
Levran, O
Lucae, S
Lynskey, MT
Maier, W
Mann, K
Martin, NG
Mattheisen, M
Montgomery, GW
Muller-Myhsok, B
Murphy, MF
Neale, MC
Nikolov, MA
Nishita, D
Nothen, MM
Nurnberger, J
Partonen, T
Pergadia, ML
Reynolds, M
Ridinger, M
Rose, RJ
Rouvinen-Lagerstrom, N
Scherbaum, N
Schmal, C
Soyka, M
Stallings, MC
Steffens, M
Treutlein, J
Tsuang, M
Wall, TL
Wodarz, N
Yuferov, V
Zill, P
Bergen, AW
Chen, JC
Cinciripini, PM
Edenberg, HJ
Ehringer, MA
Ferrell, RE
Gelernter, J
Goldman, D
Hewitt, JK
Hopfer, CJ
Iacono, WG
Kaprio, J
Kreek, MJ
Kremensky, IM
Madden, PAF
McGue, M
Munafo, MR
Philibert, RA
Rietschel, M
Roy, A
Rujescu, D
Saarikoski, ST
Swan, GE
Todorov, AA
Vanyukov, MM
Weiss, RB
Bierut, LJ
Saccone, NL
AF Schwantes-An, Tae-Hwi
Zhang, Juan
Chen, Li-Shiun
Hartz, Sarah M.
Culverhouse, Robert C.
Chen, Xiangning
Coon, Hilary
Frank, Josef
Kamens, Helen M.
Konte, Bettina
Kovanen, Leena
Latvala, Antti
Legrand, Lisa N.
Maher, Brion S.
Melroy, Whitney E.
Nelson, Elliot C.
Reid, Mark W.
Robinson, Jason D.
Shen, Pei-Hong
Yang, Bao-Zhu
Andrews, Judy A.
Aveyard, Paul
Beltcheva, Olga
Brown, Sandra A.
Cannon, Dale S.
Cichon, Sven
Corley, Robin P.
Dahmen, Norbert
Degenhardt, Louisa
Foroud, Tatiana
Gaebel, Wolfgang
Giegling, Ina
Glatt, Stephen J.
Grucza, Richard A.
Hardin, Jill
Hartmann, Annette M.
Heath, Andrew C.
Herms, Stefan
Hodgkinson, Colin A.
Hoffmann, Per
Hops, Hyman
Huizinga, David
Ising, Marcus
Johnson, Eric O.
Johnstone, Elaine
Kaneva, Radka P.
Kendler, Kenneth S.
Kiefer, Falk
Kranzler, Henry R.
Krauter, Ken S.
Levran, Orna
Lucae, Susanne
Lynskey, Michael T.
Maier, Wolfgang
Mann, Karl
Martin, Nicholas G.
Mattheisen, Manuel
Montgomery, Grant W.
Mueller-Myhsok, Bertram
Murphy, Michael F.
Neale, Michael C.
Nikolov, Momchil A.
Nishita, Denise
Noethen, Markus M.
Nurnberger, John
Partonen, Timo
Pergadia, Michele L.
Reynolds, Maureen
Ridinger, Monika
Rose, Richard J.
Rouvinen-Lagerstrom, Noora
Scherbaum, Norbert
Schmael, Christine
Soyka, Michael
Stallings, Michael C.
Steffens, Michael
Treutlein, Jens
Tsuang, Ming
Wall, Tamara L.
Wodarz, Norbert
Yuferov, Vadim
Zill, Peter
Bergen, Andrew W.
Chen, Jingchun
Cinciripini, Paul M.
Edenberg, Howard J.
Ehringer, Marissa A.
Ferrell, Robert E.
Gelernter, Joel
Goldman, David
Hewitt, John K.
Hopfer, Christian J.
Iacono, William G.
Kaprio, Jaakko
Kreek, Mary Jeanne
Kremensky, Ivo M.
Madden, Pamela A. F.
McGue, Matt
Munafo, Marcus R.
Philibert, Robert A.
Rietschel, Marcella
Roy, Alec
Rujescu, Dan
Saarikoski, Sirkku T.
Swan, Gary E.
Todorov, Alexandre A.
Vanyukov, Michael M.
Weiss, Robert B.
Bierut, Laura J.
Saccone, Nancy L.
TI Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific
Liability to Substance Dependence in a Collaborative de novo
Meta-Analysis of European-Ancestry Cohorts
SO BEHAVIOR GENETICS
LA English
DT Article
DE Addiction; Substance dependence; OPRM1; Opioid receptor; Single
nucleotide polymorphism (SNP); Genetic association
ID MU-OPIOID-RECEPTOR; GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE
POLYMORPHISM; FAMILY-BASED ASSOCIATION; QUANTITATIVE TRAIT LOCI;
MINNESOTA TWIN FAMILY; ALCOHOL DEPENDENCE; NICOTINE DEPENDENCE; GENE
OPRM1; SMOKING-CESSATION
AB The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day > 20 vs. a parts per thousand currency sign10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95 % C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.
C1 [Schwantes-An, Tae-Hwi; Zhang, Juan; Saccone, Nancy L.] Washington Univ, Sch Med, Dept Genet, 4523 Clayton Ave,Campus Box 8232, St Louis, MO 63110 USA.
[Schwantes-An, Tae-Hwi] NHGRI, Genometr Sect, Computat & Stat Genom Branch, Div Intramural Res,US Natl Inst Hlth NIH, Baltimore, MD 21224 USA.
[Chen, Li-Shiun; Hartz, Sarah M.; Nelson, Elliot C.; Grucza, Richard A.; Heath, Andrew C.; Nikolov, Momchil A.; Pergadia, Michele L.; Madden, Pamela A. F.; Todorov, Alexandre A.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Culverhouse, Robert C.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Chen, Xiangning; Kendler, Kenneth S.; Neale, Michael C.; Chen, Jingchun] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Coon, Hilary; Cannon, Dale S.] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84108 USA.
[Frank, Josef; Treutlein, Jens; Rietschel, Marcella] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
[Kamens, Helen M.; Melroy, Whitney E.; Corley, Robin P.; Krauter, Ken S.; Stallings, Michael C.; Ehringer, Marissa A.; Hewitt, John K.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Kamens, Helen M.; Melroy, Whitney E.; Ehringer, Marissa A.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA.
[Kamens, Helen M.] Penn State Univ, Dept Behav Hlth, University Pk, PA 16802 USA.
[Konte, Bettina; Giegling, Ina; Hartmann, Annette M.; Rujescu, Dan] Univ Klinikum Halle Saale, Dept Psychiat, D-06112 Halle, Saale, Germany.
[Kovanen, Leena; Partonen, Timo; Rouvinen-Lagerstrom, Noora; Kaprio, Jaakko; Saarikoski, Sirkku T.] Natl Inst Hlth & Welf, Dept Mental Hlth, Helsinki 00271, Finland.
[Kovanen, Leena; Partonen, Timo; Rouvinen-Lagerstrom, Noora; Kaprio, Jaakko; Saarikoski, Sirkku T.] Natl Inst Hlth & Welf, Subst Abuse Serv, Helsinki 00271, Finland.
[Latvala, Antti; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland.
[Legrand, Lisa N.; Iacono, William G.; McGue, Matt] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Maher, Brion S.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
[Reid, Mark W.; Andrews, Judy A.; Hops, Hyman] Oregon Res Inst, Eugene, OR 97403 USA.
[Robinson, Jason D.; Cinciripini, Paul M.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA.
[Shen, Pei-Hong; Hodgkinson, Colin A.; Goldman, David] NIAAA, Sect Human Neurogenet, Bethesda, MD 20892 USA.
[Yang, Bao-Zhu; Gelernter, Joel] Yale Univ, Dept Psychiat, New Haven, CT 06516 USA.
[Aveyard, Paul] Univ Oxford, Dept Primary Care Hlth Sci, Oxford OX2 6GG, England.
[Beltcheva, Olga; Kaneva, Radka P.; Nikolov, Momchil A.; Kremensky, Ivo M.] Med Univ Sofia, Mol Med Ctr, Dept Med Chem & Biochem, Sofia 1431, Bulgaria.
[Brown, Sandra A.; Tsuang, Ming; Wall, Tamara L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Cichon, Sven; Herms, Stefan; Hoffmann, Per; Mattheisen, Manuel; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, Inst Human Genet, D-53127 Bonn, Germany.
[Cichon, Sven; Herms, Stefan; Hoffmann, Per] Univ Basel, Univ Basel Hosp, Dept Biomed, Div Med Genet, CH-4003 Basel, Switzerland.
[Dahmen, Norbert] Okumen Hainich Klinikum, Muhlhausen Thuringen, Germany.
[Degenhardt, Louisa] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Randwick, NSW 2031, Australia.
[Degenhardt, Louisa] Univ Melbourne, Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Gaebel, Wolfgang] Univ Dusseldorf, D-40225 Dusseldorf, Germany.
[Glatt, Stephen J.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA.
[Hardin, Jill; Nishita, Denise; Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Biosci Div, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
[Maier, Wolfgang] Univ Bonn, D-53113 Bonn, Germany.
[Huizinga, David] Univ Colorado, Inst Behav Sci, Boulder, CO 80309 USA.
[Ising, Marcus; Lucae, Susanne; Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Johnson, Eric O.] Res Triangle Inst Int, Behav Hlth Res Div, Durham, NC 27709 USA.
[Johnstone, Elaine] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England.
[Kiefer, Falk] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Dept Addict Behav & Addict Med, D-68159 Mannheim, Germany.
[Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Krauter, Ken S.] Univ Colorado, Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
[Levran, Orna; Yuferov, Vadim; Kreek, Mary Jeanne] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA.
[Lynskey, Michael T.] Kings Coll London, Inst Psychiat, Addict Dept, London SE5 8BB, England.
[Mann, Karl; Schmael, Christine] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, D-68159 Mannheim, Germany.
[Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, Dept Genet Epidemiol, Brisbane, Qld 4029, Australia.
[Mattheisen, Manuel] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mattheisen, Manuel] Aarhus Univ, DK-8000 Aarhus, Denmark.
[Murphy, Michael F.] Univ Oxford, Childhood Canc Res Grp, Oxford OX3 7LG, England.
[Nurnberger, John] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Reynolds, Maureen; Vanyukov, Michael M.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA.
[Ridinger, Monika; Wodarz, Norbert] Univ Regensburg, Univ Med Ctr Regensburg, Dept Psychiat, D-8548 Regensburg, Germany.
[Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Scherbaum, Norbert] Univ Duisburg Gesamthsch, LVR Hosp Essen, Dept Psychiat & Psychotherapy, Addict Res Grp, D-45147 Essen, Germany.
[Soyka, Michael] Univ Munich, Dept Psychiat, D-3860 Munich, Germany.
[Soyka, Michael] Private Hosp Meiringen, Meiringen, Switzerland.
[Stallings, Michael C.; Hewitt, John K.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Steffens, Michael] Fed Inst Drugs & Med Devices BfArM, Res Dept, Kurt Georg Kiesinger Allee 3, D-53175 Bonn, Germany.
[Zill, Peter] Univ Munich, Munich, Germany.
[Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Gelernter, Joel] Yale Univ, Dept Genet, New Haven, CT 06516 USA.
[Gelernter, Joel] Yale Univ, Dept Neurobiol, New Haven, CT 06516 USA.
[Hopfer, Christian J.] Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO 80045 USA.
[Kaprio, Jaakko] Univ Helsinki, Inst Mol Med FIMM, FIN-00014 Helsinki, Finland.
[Munafo, Marcus R.] Univ Bristol, UK Ctr Tobacco & Alcohol Studies, MRC Integrat Epidemiol Unit, Bristol BS8 1TU, Avon, England.
[Munafo, Marcus R.] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TU, Avon, England.
[Philibert, Robert A.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Roy, Alec] New Jersey VA Hlth Care Syst, Dept Veteran Affairs, Psychiat Serv, E Orange, NJ 07018 USA.
[Weiss, Robert B.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Ridinger, Monika] Hosp Psychiat, Konigsfelden, Windisch, Switzerland.
[Swan, Gary E.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Med, Stanford, CA 94304 USA.
[Zhang, Juan] Univ Sci & Technol China, Chinese Acad Sci, Sch Life Sci, Key Lab Brain Funct & Dis, Hefei 230026, Anhui, Peoples R China.
RP Saccone, NL (reprint author), Washington Univ, Sch Med, Dept Genet, 4523 Clayton Ave,Campus Box 8232, St Louis, MO 63110 USA.
EM nlims@genetics.wustl.edu
RI Degenhardt, Louisa/D-4515-2012; Goldman, David/F-9772-2010;
OI Aveyard, Paul/0000-0002-1802-4217; Degenhardt,
Louisa/0000-0002-8513-2218; Goldman, David/0000-0002-1724-5405; Kamens,
Helen/0000-0001-5085-8847; Latvala, Antti/0000-0001-5695-117X; Kovanen,
Leena/0000-0002-3552-124X; Nurnberger, John/0000-0002-7674-1767; Bergen,
Andrew/0000-0002-1237-7644; Nothen, Markus/0000-0002-8770-2464;
Edenberg, Howard/0000-0003-0344-9690; Kaprio, Jaakko/0000-0002-3716-2455
FU National Institute on Drug Abuse (NIDA) [R01 DA026911]; NIDA [R01
DA018823, R01 DA021905, R01 AA017889, P60 DA011015, R01 DA012845, T32
DA017637, R01 DA021913, K24 DA032555, K01 AA019447, R01 DA035804]; NIAAA
[U10 AA008401, R01 AA009367, R01 AA0011886, R01 AA075356, R01 AA07728,
R01 AA13220, R01 AA13321, R01 AA13322, R01 AA11998, R01 AA17688, R01
AA017535, R01 AA11330]; Australian National Health and Medical Research
Council (NHMRC) [1041472]; Australian Government under Substance Misuse
Prevention and Service Improvements Grant Fund; NCI; Genes and
Environment Initiative (GEI) [U01 HG004438]; National Institutes of
Health (NIH) [HHSN268200782096C]; National Cancer Institute (NCI); NIH
[HHSN268200782096C]; Finnish National Institute for Health and Welfare;
National Institute on Alcohol Abuse and Alcoholism (NIAAA) [K02
AA018755, R01 AA-09203, R37 AA-12502, 141054, 263278]; Academy of
Finland [213506, 129680]; GRAND (Kaprio) from Pfizer Inc.; European
Union [Health-F4-2007-201413]; ENGAGE project from NIDA [DA12854];
Wellcome Trust Sanger Institute; Sigrid Juselius Foundation; Jenny &
Antti Wihuri Foundation; German Federal Ministry of Education and
Research (BMBF) [01EB0410, 01GS0852, BMBF 01ZX1311A]; National Genome
Research Network (NGFN Plus) [FZK 01GS08152]; Alfried Krupp von Bohlen
und Halbach-Stiftung; Adelson Medical Research Foundation; National
Institute of Mental Health (NIMH) [R01 MH066140]; NARSAD: The Brain and
Behavior Research Foundation; Sidney R. Baer, Jr. Foundation; Gerber
Foundation; Australian National Health and Medical Research Council;
Cancer Research UK [C53/A6281]; British Heart Foundation; Cancer
Research UK; Economic and Social Research Council; Medical Research
Council; National Institute for Health Research under UK Clinical
Research Collaboration; University of California Tobacco-Related Disease
Research Program [7PT2000-2004]; NHLBI; NARSAD: the Brain and Behavior
Research Fund; Division of Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health; The NIDA
[R01 DA026911, P01 CA089392, K08 DA030398, K08 DA032680, R01 DA038076,
R21 DA038241, R01 DA036583, R01 DA015789, P50 DA05130, R01 DA005147, R01
DA036216, R01 U01 DA024417, R01 DA012846, R01 DA12690, R01 DA12849, R01
DA18432, K01 DA24758]; NIDA. [R01 DA017305, R01 DA019157, P50 DA005605,
R01 DA011922, R01 DA11822, K07 CA92209, R21 CA81649, P50 CA070907, R01
DA019963, R01 DA013423, RC2 DA028793K08 DA019951R01 DA003706
U01 DA020830 P01 HL72903DA019498R01 DA18673RC2
DA028909]; [1 X01 HG005274-01]; [U01 HG004446]
FX R01 DA026911 from The National Institute on Drug Abuse (NIDA) supported
this project and the coordinating team at Washington University. BG/ROMA
are supported by R01 DA018823 (Todorov) from NIDA. CADD/GADD/NYS are
supported by R01 DA021905 (Brown, Wall), R01 AA017889 (Ehringer), P60
DA011015 (Hewitt), R01 DA012845 (Hewitt), T32 DA017637 (Hewitt), R01
DA021913 (Hopfer), K24 DA032555 (Hopfer), K01 AA019447 (Kamens), and R01
DA035804 (Wall, Hopfer, Stallings) from NIDA and NIAAA. CATS is
supported by R01 DA017305 (Nelson) from NIDA. Dr. Degenhardt is
supported by an Australian National Health and Medical Research Council
(NHMRC) principal research fellowship (#1041472). The National Drug and
Alcohol Research Centre at UNSW Australia is supported by funding from
the Australian Government under the Substance Misuse Prevention and
Service Improvements Grant Fund. CEDAR-SADS is supported by R01 DA019157
(Vanyukov) from NIDA. CEDAR is supported by P50 DA005605 (Tarter) from
NIDA. SADS is supported by R01 DA011922 (Vanyukov) from NIDA. The
following studies made up the Cinciripini study: CASSI is supported by
R01 DA11822 (Cinciripini), PEERS EMA is supported by K07 CA92209
(Carter), PEERS NS is supported by R21 CA81649 (Cinciripini) and PEERS
WS, PEERS NS and SCOPE are supported by P50 CA070907 (Cinciripini) from
NIDA and NCI. COGA is supported by U10 AA008401 (Bierut, Nurnberger,
Edenberg, Hesselbrock, Porjesz) from NIAAA and genotyping was supported
by U01 HG004438 (Valle) from The Genes and Environment Initiative (GEI)
and HHSN268200782096C from the National Institutes of Health (NIH).
Contributions from COGEND are supported by R01 DA019963 (Bierut), R01
DA013423 (Bierut), P01 CA089392 (Bierut), K08 DA030398 (L.-S. Chen), K08
DA032680 (Hartz), R01 DA019963 (Bierut), R01 DA038076 (L.-S. Chen), R21
DA038241 (Culverhouse), R01 DA026911 (Saccone) and R01 DA036583 (Bierut)
from NIDA and the National Cancer Institute (NCI). Funding for COGEND
genotyping was provided by 1 X01 HG005274-01 and performed at Center for
Inherited Disease Research (CIDR) which is funded through a federal
contract from NIH to JHU (HHSN268200782096C). Finnish Health 2000 is
supported by Finnish National Institute for Health and Welfare
institutional funding. FSCD is supported by R01 DA013423 (Bierut) from
NIDA. Gene Environment Association Studies (GENEVA) Coordinating Center
assisted with genotype cleaning as well as general study coordination,
for FSCD; GENEVA is supported by U01 HG004446. FTC/FT12 is supported by
K02 AA018755 (Rose), R01 AA-09203 (Rose), R37 AA-12502 (Rose), 141054
(Kaprio) and 263278 (Kaprio) from the National Institute on Alcohol
Abuse and Alcoholism (NIAAA) and Academy of Finland. FTC/NAG-FIN is
funded by GRAND (Kaprio) from Pfizer Inc., 213506 (Kaprio) and 129680
(Kaprio) from Academy of Finland, Health-F4-2007-201413 (Kaprio) from
European Union Seventh Framework Programme, ENGAGE project, DA12854
(Madden) from NIDA, Wellcome Trust Sanger Institute, Sigrid Juselius
Foundation and Jenny & Antti Wihuri Foundation. GESGA is supported by
01EB0410 (Mann), 01GS0852 (Kiefer), and BMBF 01ZX1311A (Kiefer,
Rietschel) (e:Med program) from the German Federal Ministry of Education
and Research (BMBF), FZK 01GS08152 (Nothen, Rietschel) from National
Genome Research Network (NGFN Plus). Drs. Cichon and Nothen are
supported by Alfried Krupp von Bohlen und Halbach-Stiftung. IAS is
supported by R01 DA015789 (Philibert) from NIDA. Kreek is supported by
P50 DA05130 (Kreek) from NIDA and The Adelson Medical Research
Foundation (Kreek).; MCTFR is supported by R01 DA005147 (Iacono), R01
DA036216 (Iacono) and R01 U01 DA024417 (Iacono) from NIDA, R01 AA009367
(McGue) and R01 AA0011886 (McGue) from NIAAA and R01 MH066140 (McGue)
from the National Institute of Mental Health (NIMH). MGHD is supported
by R01 DA012846 (Tsuang) from NIDA and grants from NARSAD: The Brain and
Behavior Research Foundation (Tsuang, Glatt), the Sidney R. Baer, Jr.
Foundation (Tsuang), and the Gerber Foundation (Glatt). OYSUP is
supported by RC2 DA028793 (Andrews) from NIDA. OZALC-NAG is supported by
R01 AA075356 (Heath), R01 AA07728 (Heath), R01 AA13220 (Martin), R01
AA13321 (Heath), R01 AA13322 (Heath), R01 AA11998 (Heath) and R01
AA17688 (Heath) from NIAAA, R01 DA12854 (Madden) and K08 DA019951
(Pergadia) from NIDA and grants from the Australian National Health and
Medical Research Council. Patch II/PiP are supported by C53/A6281
(Aveyard) from Cancer Research UK. Marcus Munafo and Paul Aveyard are
members of the United Kingdom Centre for Tobacco and Alcohol Studies, a
UKCRC Public Health Research: Centre of Excellence. Funding from British
Heart Foundation, Cancer Research UK, Economic and Social Research
Council, Medical Research Council, and the National Institute for Health
Research, under the auspices of the UK Clinical Research Collaboration,
is gratefully acknowledged. SMOFAM is supported by R01 DA003706 (Hops),
U01 DA020830 (Lerman) from NIDA and 7PT2000-2004 (Swan) from University
of California Tobacco-Related Disease Research Program. Utah is
supported by P01 HL72903 (Hoidal) from NIDA and NHLBI. VA-Twin is
supported by DA019498 (X. Chen) from NIDA; support was also provided by
R01 DA18673 (Neale) from NIDA. Yale-Penn is supported by RC2 DA028909
(Gelernter), R01 DA12690 (Gelernter), R01 DA12849 (Gelernter), R01
DA18432 (Kranzler) and K01 DA24758 (Yang) from NIDA, R01 AA017535
(Gelernter) and R01 AA11330 (Gelernter) from NIAAA and Dr. Yang is
supported by a Young Investigator Award from NARSAD: the Brain and
Behavior Research Fund. Dr. Schwantes-An is also supported by the
Division of Intramural Research Program of the National Human Genome
Research Institute, National Institutes of Health. Funding sources had
no further role in the study design; in the collection, analysis and
interpretation of data; in the writing; or in the decision to submit the
paper for publication.
NR 118
TC 5
Z9 5
U1 7
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
EI 1573-3297
J9 BEHAV GENET
JI Behav. Genet.
PD MAR
PY 2016
VL 46
IS 2
BP 151
EP 169
DI 10.1007/s10519-015-9737-3
PG 19
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA DD7WO
UT WOS:000370135800001
PM 26392368
ER
PT J
AU van den Berg, SM
de Moor, MHM
Verweij, KJH
Krueger, RF
Luciano, M
Vasquez, AA
Matteson, LK
Derringer, J
Esko, T
Amin, N
Gordon, SD
Hansell, NK
Hart, AB
Seppala, I
Huffman, JE
Konte, B
Lahti, J
Lee, M
Miller, M
Nutile, T
Tanaka, T
Teumer, A
Viktorin, A
Wedenoja, J
Abdellaoui, A
Abecasis, GR
Adkins, DE
Agrawal, A
Allik, J
Appel, K
Bigdeli, TB
Busonero, F
Campbell, H
Costa, PT
Smith, GD
Davies, G
de Wit, H
Ding, J
Engelhardt, BE
Eriksson, JG
Fedko, IO
Ferrucci, L
Franke, B
Giegling, I
Grucza, R
Hartmann, AM
Heath, AC
Heinonen, K
Henders, AK
Homuth, G
Hottenga, JJ
Iacono, WG
Janzing, J
Jokela, M
Karlsson, R
Kemp, JP
Kirkpatrick, MG
Latvala, A
Lehtimaki, T
Liewald, DC
Madden, PAF
Magri, C
Magnusson, PKE
Marten, J
Maschio, A
Mbarek, H
Medland, SE
Mihailov, E
Milaneschi, Y
Montgomery, GW
Nauck, M
Nivard, MG
Ouwens, KG
Palotie, A
Pettersson, E
Polasek, O
Qian, Y
Pulkki-Raback, L
Raitakari, OT
Realo, A
Rose, RJ
Ruggiero, D
Schmidt, CO
Slutske, WS
Sorice, R
Starr, JM
St Pourcain, B
Sutin, AR
Timpson, NJ
Trochet, H
Vermeulen, S
Vuoksimaa, E
Widen, E
Wouda, J
Wright, MJ
Zgaga, L
Porteous, D
Minelli, A
Palmer, AA
Rujescu, D
Ciullo, M
Hayward, C
Rudan, I
Metspalu, A
Kaprio, J
Deary, IJ
Raikkonen, K
Wilson, JF
Keltikangas-Jarvinen, L
Bierut, LJ
Hettema, JM
Grabe, HJ
Penninx, BWJH
van Duijn, CM
Evans, DM
Schlessinger, D
Pedersen, NL
Terracciano, A
McGue, M
Martin, NG
Boomsma, DI
AF van den Berg, Stephanie M.
de Moor, Marleen H. M.
Verweij, Karin J. H.
Krueger, Robert F.
Luciano, Michelle
Vasquez, Alejandro Arias
Matteson, Lindsay K.
Derringer, Jaime
Esko, Tonu
Amin, Najaf
Gordon, Scott D.
Hansell, Narelle K.
Hart, Amy B.
Seppala, Ilkka
Huffman, Jennifer E.
Konte, Bettina
Lahti, Jari
Lee, Minyoung
Miller, Mike
Nutile, Teresa
Tanaka, Toshiko
Teumer, Alexander
Viktorin, Alexander
Wedenoja, Juho
Abdellaoui, Abdel
Abecasis, Goncalo R.
Adkins, Daniel E.
Agrawal, Arpana
Allik, Jueri
Appel, Katja
Bigdeli, Timothy B.
Busonero, Fabio
Campbell, Harry
Costa, Paul T.
Smith, George Davey
Davies, Gail
de Wit, Harriet
Ding, Jun
Engelhardt, Barbara E.
Eriksson, Johan G.
Fedko, Iryna O.
Ferrucci, Luigi
Franke, Barbara
Giegling, Ina
Grucza, Richard
Hartmann, Annette M.
Heath, Andrew C.
Heinonen, Kati
Henders, Anjali K.
Homuth, Georg
Hottenga, Jouke-Jan
Iacono, William G.
Janzing, Joost
Jokela, Markus
Karlsson, Robert
Kemp, John P.
Kirkpatrick, Matthew G.
Latvala, Antti
Lehtimaki, Terho
Liewald, David C.
Madden, Pamela A. F.
Magri, Chiara
Magnusson, Patrik K. E.
Marten, Jonathan
Maschio, Andrea
Mbarek, Hamdi
Medland, Sarah E.
Mihailov, Evelin
Milaneschi, Yuri
Montgomery, Grant W.
Nauck, Matthias
Nivard, Michel G.
Ouwens, Klaasjan G.
Palotie, Aarno
Pettersson, Erik
Polasek, Ozren
Qian, Yong
Pulkki-Raback, Laura
Raitakari, Olli T.
Realo, Anu
Rose, Richard J.
Ruggiero, Daniela
Schmidt, Carsten O.
Slutske, Wendy S.
Sorice, Rossella
Starr, John M.
St Pourcain, Beate
Sutin, Angelina R.
Timpson, Nicholas J.
Trochet, Holly
Vermeulen, Sita
Vuoksimaa, Eero
Widen, Elisabeth
Wouda, Jasper
Wright, Margaret J.
Zgaga, Lina
Porteous, David
Minelli, Alessandra
Palmer, Abraham A.
Rujescu, Dan
Ciullo, Marina
Hayward, Caroline
Rudan, Igor
Metspalu, Andres
Kaprio, Jaakko
Deary, Ian J.
Raikkonen, Katri
Wilson, James F.
Keltikangas-Jarvinen, Liisa
Bierut, Laura J.
Hettema, John M.
Grabe, Hans J.
Penninx, Brenda W. J. H.
van Duijn, Cornelia M.
Evans, David M.
Schlessinger, David
Pedersen, Nancy L.
Terracciano, Antonio
McGue, Matt
Martin, Nicholas G.
Boomsma, Dorret I.
CA Generation Scotland
TI Meta-analysis of Genome-Wide Association Studies for Extraversion:
Findings from the Genetics of Personality Consortium
SO BEHAVIOR GENETICS
LA English
DT Article
DE Personality; Phenotype harmonization; Common genetic variants;
Imputation; Polygenic risk
ID COMMON SNPS EXPLAIN; CLONINGERS TEMPERAMENT SCALES; NEUROTROPHIC FACTOR
BDNF; PSYCHOBIOLOGICAL MODEL; LARGE PROPORTION; 5-FACTOR MODEL; HUMAN
HEIGHT; HERITABILITY; NEUROTICISM; DIMENSIONS
AB Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
C1 [van den Berg, Stephanie M.; Wouda, Jasper] Univ Twente, Fac Behav Management & Social Sci, Dept Res Methodol Measurement & Data Anal OMD, POB 217, NL-7500 AE Enschede, Netherlands.
[de Moor, Marleen H. M.; Abdellaoui, Abdel; Fedko, Iryna O.; Hottenga, Jouke-Jan; Mbarek, Hamdi; Nivard, Michel G.; Ouwens, Klaasjan G.; Wouda, Jasper; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[de Moor, Marleen H. M.] Vrije Univ Amsterdam, Dept Clin Child & Family Studies, Amsterdam, Netherlands.
[de Moor, Marleen H. M.] Vrije Univ Amsterdam, Dept Methods, Amsterdam, Netherlands.
[Verweij, Karin J. H.; Gordon, Scott D.; Hansell, Narelle K.; Henders, Anjali K.; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Verweij, Karin J. H.] Vrije Univ Amsterdam, Dept Dev Psychol, Amsterdam, Netherlands.
[Verweij, Karin J. H.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Krueger, Robert F.; Matteson, Lindsay K.; Miller, Mike; Iacono, William G.; McGue, Matt] Univ Minnesota, Dept Psychol, Minneapolis, MN USA.
[Luciano, Michelle; Davies, Gail; Liewald, David C.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Luciano, Michelle; Davies, Gail; Liewald, David C.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Vasquez, Alejandro Arias; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara; Janzing, Joost] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara; Vermeulen, Sita] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Derringer, Jaime] Univ Illinois, Dept Psychol, Champaign, IL USA.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, Ulikooli 18, EE-50090 Tartu, Estonia.
[Amin, Najaf; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Hart, Amy B.; Palmer, Abraham A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Seppala, Ilkka; Lehtimaki, Terho] Tampere Univ, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland.
[Seppala, Ilkka; Lehtimaki, Terho] Tampere Univ, Sch Med, FIN-33101 Tampere, Finland.
[Huffman, Jennifer E.; Marten, Jonathan; Trochet, Holly; Hayward, Caroline; Wilson, James F.] Univ Edinburgh, Western Gen Hosp, MRC IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Konte, Bettina; Giegling, Ina; Hartmann, Annette M.; Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany.
[Lahti, Jari; Heinonen, Kati; Jokela, Markus; Pulkki-Raback, Laura; Raikkonen, Katri; Keltikangas-Jarvinen, Liisa] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Lahti, Jari; Eriksson, Johan G.; Terracciano, Antonio] Folkhalsan Res Ctr, Helsinki, Finland.
[Lee, Minyoung; Bigdeli, Timothy B.; Hettema, John M.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA.
[Nutile, Teresa; Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy.
[Tanaka, Toshiko; Ferrucci, Luigi; Sutin, Angelina R.; Terracciano, Antonio] NIA, NIH, Baltimore, MD 21224 USA.
[Teumer, Alexander; Schmidt, Carsten O.] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Viktorin, Alexander; Karlsson, Robert; Magnusson, Patrik K. E.; Pettersson, Erik; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Wedenoja, Juho; Latvala, Antti; Vuoksimaa, Eero; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
[Adkins, Daniel E.] Virginia Commonwealth Univ, Pharmacotherapy & Outcomes Sci, Richmond, VA USA.
[Agrawal, Arpana; Grucza, Richard; Heath, Andrew C.; Madden, Pamela A. F.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA.
[Allik, Jueri; Realo, Anu] Univ Tartu, Dept Psychol, Ulikooli 18, EE-50090 Tartu, Estonia.
[Allik, Jueri; Metspalu, Andres] Estonian Acad Sci, EE-200103 Tallinn, Estonia.
[Appel, Katja; Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Busonero, Fabio; Maschio, Andrea] CNR, IRGB, Monserrato, Italy.
[Campbell, Harry; Zgaga, Lina; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Costa, Paul T.] Duke Univ, Sch Med, Behav Med Res Ctr, Durham, NC USA.
[Smith, George Davey; Kemp, John P.; St Pourcain, Beate; Timpson, Nicholas J.; Evans, David M.] Univ Bristol, Sch Social & Community Med, Med Res Council, Integrat Epidemiol Unit, Bristol, Avon, England.
[de Wit, Harriet; Kirkpatrick, Matthew G.; Palmer, Abraham A.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Engelhardt, Barbara E.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
[Eriksson, Johan G.; Latvala, Antti; Kaprio, Jaakko] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Unit Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Kemp, John P.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia.
[Magri, Chiara; Minelli, Alessandra] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy.
[Mihailov, Evelin] Univ Tartu, Dept Biotechnol, Ulikooli 18, EE-50090 Tartu, Estonia.
[Milaneschi, Yuri; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, EMGO Inst, Dept Psychiat, Med Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Palotie, Aarno] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England.
[Palotie, Aarno; Widen, Elisabeth; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
[Slutske, Wendy S.] Univ Missouri, Dept Psychol Sci, Columbia, MO USA.
[Slutske, Wendy S.] Univ Missouri, Missouri Alcoholism Res Ctr, Columbia, MO USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[St Pourcain, Beate] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England.
[St Pourcain, Beate] Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
[Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Vermeulen, Sita] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Zgaga, Lina] Trinity Coll Dublin, Dept Publ Hlth & Primary Care, Dublin, Ireland.
Collaborat Univ Med Sch & NHS, Scottish Family Hlth Study, Aberdeen, Scotland.
Collaborat Univ Med Sch & NHS, Scottish Family Hlth Study, Dundee, Scotland.
Collaborat Univ Med Sch & NHS, Scottish Family Hlth Study, Edinburgh, Midlothian, Scotland.
[Generation Scotland] Collaborat Univ Med Sch & NHS, Scottish Family Hlth Study, Glasgow, Lanark, Scotland.
[Porteous, David] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Med Genet Sect,Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.
[Grabe, Hans J.] HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany.
[Ding, Jun; Qian, Yong; Schlessinger, David] NIA, NIH, Genet Lab, Baltimore, MD 21224 USA.
[McGue, Matt] Univ Southern Denmark, Inst Publ Hlth, Odense, Denmark.
RP van den Berg, SM (reprint author), Univ Twente, Fac Behav Management & Social Sci, Dept Res Methodol Measurement & Data Anal OMD, POB 217, NL-7500 AE Enschede, Netherlands.
EM stephanie.vandenberg@utwente.nl
RI Franke, Barbara/D-4836-2009; Jokela, Markus/A-4669-2009; Magnusson,
Patrik/C-4458-2017; Polasek, Ozren/B-6002-2011; ruggiero,
daniela/K-5638-2016; Vermeulen, H.H.M./L-4716-2015; Realo,
Anu/M-9524-2016; Fox, Laura /C-6249-2016; Luciano, Michelle/F-7277-2010;
Hansell, Narelle/A-4553-2016; Davey Smith, George/A-7407-2013;
OI Franke, Barbara/0000-0003-4375-6572; Jokela, Markus/0000-0003-0117-0012;
Polasek, Ozren/0000-0002-5765-1862; ruggiero,
daniela/0000-0003-3898-7827; St Pourcain, Beate/0000-0002-4680-3517;
Luciano, Michelle/0000-0003-0935-7682; Hansell,
Narelle/0000-0002-8229-9741; Davey Smith, George/0000-0002-1407-8314;
Latvala, Antti/0000-0001-5695-117X; NUTILE, TERESA/0000-0001-7062-8352;
Mbarek, Hamdi/0000-0002-1108-0371; Viktorin,
Alexander/0000-0003-2141-2816; Timpson, Nicholas/0000-0002-7141-9189;
Wright, Margaret/0000-0001-7133-4970; Kemp, John/0000-0002-9105-2249;
Evans, David/0000-0003-0663-4621; Nivard, Michel/0000-0003-2015-1888;
Medland, Sarah/0000-0003-1382-380X; Lahti, Jari/0000-0002-4310-5297;
Ouwens, Klaasjan/0000-0002-3864-7710
FU Netherlands Organization for Scientific Research [NWO 480-05-003]; UK
Medical Research Council [74882]; Wellcome Trust [076467]; University of
Bristol; 23andMe; Intramural Research Program of the NIH, National
Institute on Aging; Italian Ministry of Health (RC) [RF2007 Conv. 42];
Regione Lombardia [ID: 17387 SAL-13]; NIH [DA007255, HG006265, DA02812,
DA021336, DA024845, HHSN268200782096C, T32 MH016880]; Bioinformatics
Research Development Fund; NIH Genes, Environment and Health Initiative
[GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA)
under GEI; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse
and Alcoholism; National Institute on Drug Abuse; NIH from National
Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA008401];
National Institute on Drug Abuse (NIDA); NIH from National Cancer
Institute [P01 CA089392]; NIDA [HHSN271200477451C]; FP7 Grants [201413
ENGAGE, 212111 BBMRI, ECOGENE (205419)]; OpenGENE; Estonian Government
[SF0180142s08]; EU via European Regional Development Fund; Estonian
Ministry of Science and Education [SF0180029s08]; European Commission
FP6 STRP Grant [018947 (LSHG-CT-2006-01947)]; European Community
[HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; ENGAGE consortium; CMSB;
Netherlands Organisation for Scientific Research; Russian Foundation for
Basic Research (NWO-RFBR) [047.017.043]; ZonMw Grant [91111025]; Academy
of Finland Center of Excellence in Complex Disease Genetics [213506,
129680]; Academy of Finland [100499, 205585, 118555, 141054, 257075];
Global Research Awards for Nicotine Dependence (GRAND); ENGAGE (European
Network for Genetic and Genomic Epidemiology [FP7-HEALTH-F4-2007,
201413]; Academy of Finland; Finnish Diabetes Research Society;
Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska
Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of
Helsinki; Ministry of Education; Ahokas Foundation; Emil Aaltonen
Foundation; Medical Research Council (UK); European Commission
[LSHG-CT2006-018947]; Republic of Croatia Ministry of Science, Education
and Sports [108-1080315-0302]; Research Into Ageing; Age UK (The
Disconnected Mind); Biotechnology and Biological Sciences Research
Council (BBSRC); Medical Research Council (MRC); Wellcome Trust
Strategic Award [104036/Z/14/Z]; National Institutes of Health
[R37DA005147, R01AA009367, R01AA011886, R01DA013240, R01MH066140,
U01DA024417]; NIMH Schizophrenia Genetics Initiative [MH46276, MH46289,
MH46318]; Netherlands Organization for Scientific Research (Geestkracht
program) [10-000-1002]; Center for Medical Systems Biology (CMSB, NWO
Genomics); Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI-NL); VU University's EMGO Institute for Health and Care Research;
Neuroscience Campus Amsterdam; US National Institute of Mental Health as
part of the American Recovery and Reinvestment Act [RC2MH089951];
NWO-VIDI [91811602]; Netherlands Organization for Scientific Research
(NWO) [575-25-006, 480-04-004, 904-61-090, 904-61-193, 400-05-717,
Spinozapremie SPI 56-464-14192]; European Research Council [ERC-230374];
NWO VENI [016-115-035]; Genetic Association Information Network (GAIN)
of the Foundation for the US National Institutes of Health; Genetic
Association Information Network; NIMH [MH081802]; Chief Scientist Office
of the Scottish Government; Royal Society; MRC Human Genetics Unit;
Arthritis Research UK; European Union [LSHG-CT-2006-018947]; Australian
Research Council [A79600334, A79906588, A79801419, DP0212016, DP0343921,
DP0664638, DP1093900]; Beyond Blue and the Borderline Personality
Disorder Research Foundation; NIH Grants [DA12854, AA07728, AA07580,
AA11998, AA13320, AA13321, MH66206]; Australian National Health and
Medical Research Council; National Health and Medical Research Council
(Medical Bioinformatics Genomics Proteomics Program) [389891]; National
Health and Medical Research Council; NIH, National Institute on Aging;
National Institute on Aging, NIH [NO1-AG-1-2109]; Federal Ministry of
Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; Ministry of
Cultural Affairs; Social Ministry of the Federal State of
Mecklenburg-West Pomerania; Federal Ministry of Education and Research
Grant [03ZIK012]; Siemens Healthcare, Erlangen, Germany; Federal State
of Mecklenburg-West Pomerania; German Research Foundation [DFG: GR
1912/5-1]; Ministry for Higher Education; Swedish Research Council
[M-2005-1112, 2009-2298]; GenomEUtwin [QLG2-CT-2002-01254,
EU/QLRT-2001-01254]; NIH Grant [DK U01-066134]; Swedish Foundation for
Strategic Research (SSF) [ICA08-0047]; Swedish Heart-Lung Foundation;
Royal Swedish Academy of Science; ENGAGE within European Union
[HEALTH-F4-2007-201413]; Republic of Croatia Ministry of Science,
Education and Sports research Grant [108-1080315-0302]; Academy of
Finland Grants [126925, 121584, 124282, 129378, 117787, 41071, 265869];
Social Insurance Institution of Finland, Kuopio; Tampere and Turku
University Hospital Medical Funds [9N035]; Juho Vainio Foundation; Paavo
Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Finnish
Cultural Foundation; Tampere Tuberculosis Foundation; Scottish Executive
Health Department, Chief Scientist Office [CZD/16/6]; Medical Research
Council UK; [AA-12502]; [AA-00145]; [AA-09203]; [AA15416];
[K02AA018755]; [MH67257]; [MH59588]; [MH59571]; [MH59565];
[MH59587]; [MH60870]; [MH60879]; [MH59566]; [MH59586]; [MH61675];
[MH79469]; [MH79470]; [DA019951]
FX We would like to thank all participating subjects. Analyses were carried
out on the Genetic Cluster Computer (http://www.geneticcluster.org),
which is financially supported by the Netherlands Organization for
Scientific Research (NWO 480-05-003).; ALSPAC We are extremely grateful
to all the families who took part in this study, the midwives for their
help in recruiting them and the whole ALSPAC team, which includes
interviewers, computer and laboratory technicians, clerical workers,
research scientists, volunteers, managers, receptionists and nurses. The
UK Medical Research Council (Grant 74882), the Wellcome Trust (Grant
076467) and the University of Bristol provide core support for ALSPAC.
We thank 23andMe for funding the genotyping of the ALSPAC children's
sample. This publication is the work of the authors, and they will serve
as guarantors for the contents of this paper.; BLSA We acknowledge
support from the Intramural Research Program of the NIH, National
Institute on Aging. We thank Robert McCrae.; BRESCIA We acknowledge
support from the Italian Ministry of Health (RC and RF2007 Conv. 42) and
Regione Lombardia (ID: 17387 SAL-13). We thank Ilaria Gandin for
imputation analysis support.; CHICAGO This work was supported by NIH
Grants, DA007255 (ABH), HG006265 (to BEE), DA02812 (to HdW), and
DA021336 and DA024845 (to AAP). BEE was also funded through the
Bioinformatics Research Development Fund, supported by Kathryn and
George Gould. We wish to thank Andrew D. Skol for providing advice about
genotype calling.; SAGE - COGA/CONGEND Funding support for the Study of
Addiction: Genetics and Environment (SAGE) was provided through the NIH
Genes, Environment and Health Initiative [GEI] (U01 HG004422). SAGE is
one of the genome-wide association studies funded as part of the Gene
Environment Association Studies (GENEVA) under GEI. Assistance with
phenotype harmonization and genotype cleaning, as well as with general
study coordination, was provided by the GENEVA Coordinating Center (U01
HG004446). Assistance with data cleaning was provided by the National
Center for Biotechnology Information. Support for collection of datasets
and samples was provided by the Collaborative Study on the Genetics of
Alcoholism (COGA; U10 AA008401) and the Collaborative Genetic Study of
Nicotine Dependence (COGEND; P01 CA089392). Funding support for
genotyping, which was performed at the Johns Hopkins University Center
for Inherited Disease Research, was provided by the NIH GEI
(U01HG004438), the National Institute on Alcohol Abuse and Alcoholism,
the National Institute on Drug Abuse, and the NIH contract "High
throughput genotyping for studying the genetic contributions to human
disease"(HHSN268200782096C). The Collaborative Study on the Genetics of
Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock,
H. Edenberg, L. Bierut, includes ten different centers: University of
Connecticut (V. Hesselbrock); Indiana University (H. J. Edenberg, J.
Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer);
SUNY Downstate (B. Porjesz); Washington University in St. Louis (L.
Bierut, A. Goate, J. Rice, K. Bucholz); University of California at San
Diego (M. Schuckit); Rutgers University (J. Tischfield); Texas
Biomedical Research Institute (L. Almasy), Howard University (R. Taylor)
and Virginia Commonwealth University (D. Dick). Other COGA collaborators
include: L. Bauer (University of Connecticut); D. Koller, S. O'Connor,
L. Wetherill, X. Xuei (Indiana University); Grace Chan (University of
Iowa); S. Kang, N. Manz, M. Rangaswamy (SUNY Downstate); J. Rohrbaugh,
J-C Wang (Washington University in St. Louis); A. Brooks (Rutgers
University); and F. Aliev (Virginia Commonwealth University). A. Parsian
and M. Reilly are the NIAAA Staff Collaborators. This national
collaborative study is supported by NIH Grant U10AA008401 from the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the
National Institute on Drug Abuse (NIDA). The Collaborative Genetic Study
of Nicotine Dependence (COGEND) project is a collaborative research
group and part of the NIDA Genetics Consortium. Subject collection was
supported by NIH Grant P01 CA089392 (L. J. Bierut) from the National
Cancer Institute. Phenotypic and genotypic data are stored in the NIDA
Center for Genetic Studies (NCGS) at http://zork.wustl.edu/ under NIDA
Contract HHSN271200477451C (J. Tischfield and J. Rice). Jaime Derringer
was supported by NIH T32 MH016880.; EGCUT AM and TE received support
from FP7 Grants (201413 ENGAGE, 212111 BBMRI, ECOGENE (No. 205419, EBC))
and OpenGENE. AM and TE also received targeted financing from Estonian
Government SF0180142s08 and by EU via the European Regional Development
Fund, in the frame of Centre of Excellence in Genomics. The genotyping
of the Estonian Genome Project samples were performed in Estonian
Biocentre Genotyping Core Facility, AM and TE thank Mari Nelis and Viljo
Soo for their contributions. AR and JA were supported by a grant from
the Estonian Ministry of Science and Education (SF0180029s08).; ERF The
ERF study as a part of EUROSPAN (European Special Populations Research
Network) was supported by European Commission FP6 STRP Grant Number
018947 (LSHG-CT-2006-01947) and also received funding from the European
Community's Seventh Framework Programme (FP7/2007-2013)/Grant agreement
HEALTH-F4-2007-201413 by the European Commission under the programme
"Quality of Life and Management of the Living Resources" of 5th
Framework Programme (no. QLG2-CT-2002-01254). The ERF study was further
supported by ENGAGE consortium and CMSB. High-throughput analysis of the
ERF data was supported by joint grant from Netherlands Organisation for
Scientific Research and the Russian Foundation for Basic Research
(NWO-RFBR 047.017.043). ERF was further supported by the ZonMw Grant
(Project 91111025). We are grateful to all study participants and their
relatives, general practitioners and neurologists for their
contributions and to P. Veraart for her help in genealogy, J. Vergeer
for the supervision of the laboratory work and P. Snijders for his help
in data collection.; Finnish Twin Cohort (FTC) We acknowledge support
from the Academy of Finland Center of Excellence in Complex Disease
Genetics (Grant Numbers: 213506, 129680), the Academy of Finland (Grants
100499, 205585, 118555 and 141054 to JK, Grant 257075 to EV), Global
Research Awards for Nicotine Dependence (GRAND), ENGAGE (European
Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, Grant
Agreement Number 201413), DA12854 to P A F Madden, and AA-12502,
AA-00145, and AA-09203 to RJRose, AA15416 and K02AA018755 to DM Dick.;
HBCS We thank all study participants as well as everybody involved in
the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been
supported by grants from the Academy of Finland, the Finnish Diabetes
Research Society, Folkhalsan Research Foundation, Novo Nordisk
Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg
Foundation, University of Helsinki, Ministry of Education, Ahokas
Foundation, Emil Aaltonen Foundation.; CROATIA-Korcula The
CROATIA-Korcula study was funded by grants from the Medical Research
Council (UK), European Commission Framework 6 project EUROSPAN (Contract
No. LSHG-CT2006-018947) and Republic of Croatia Ministry of Science,
Education and Sports research Grants to I.R. (108-1080315-0302). We
would like to acknowledge the invaluable contributions of the
recruitment team in Korcula, the administrative teams in Croatia and
Edinburgh and the people of Korcula. The SNP genotyping for the
CROATIA-Korcula cohort was performed in Helmholtz Zentrum Munchen,
Neuherberg, Germany.; LBC1921 & LBC1936 For the Lothian Birth Cohorts,
we thank Paul Redmond for database management; Alan Gow, Michelle
Taylor, Janie Corley, Caroline Brett and Caroline Cameron for data
collection and data entry; nurses and staff at the Wellcome Trust
Clinical Research Facility, where blood extraction and genotyping was
performed; staff at the Lothian Health Board, and the staff at the SCRE
Centre, University of Glasgow. The research was supported by a program
grant from Research Into Ageing. The research continues with program
grants from Age UK (The Disconnected Mind). The work was undertaken by
The University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology, part of the cross council Lifelong Health and Wellbeing
Initiative (MR/K026992/1). Funding from the Biotechnology and Biological
Sciences Research Council (BBSRC) and Medical Research Council (MRC) is
gratefully acknowledged. IJD, DJP and colleagues receive support from
Wellcome Trust Strategic Award 104036/Z/14/Z.; Research reported in this
publication was supported by the National Institutes of Health under
award numbers R37DA005147, R01AA009367, R01AA011886, R01DA013240,
R01MH066140, and U01DA024417.; MGS Samples were collected under the
following grants: NIMH Schizophrenia Genetics Initiative U01s: MH46276,
MH46289, and MH46318; and Molecular Genetics of Schizophrenia Part 1
(MGS1) and Part 2 (MGS2) R01s: MH67257, MH59588, MH59571, MH59565,
MH59587, MH60870, MH60879, MH59566, MH59586, and MH61675. Genotyping and
analyses were funded under the MGS U01s: MH79469 and MH79470.; NBS
Principal investigators of the Nijmegen Biomedical Study are L.A.L.M.
Kiemeney, M. den Heijer, A.L.M. Verbeek, D.W. Swinkels and B. Franke.;
NESDA The Netherlands Study of Depression and Anxiety (NESDA) were
funded by the Netherlands Organization for Scientific Research
(Geestkracht program Grant 10-000-1002); the Center for Medical Systems
Biology (CMSB, NWO Genomics), Biobanking and Biomolecular Resources
Research Infrastructure (BBMRI-NL), VU University's EMGO Institute for
Health and Care Research and Neuroscience Campus Amsterdam. Genotyping
was funded by the US National Institute of Mental Health (RC2MH089951)
as part of the American Recovery and Reinvestment Act of 2009. BP is
financially supported by NWO-VIDI Grant No. 91811602.; NTR We
acknowledge financial support from the Netherlands Organization for
Scientific Research (NWO): Grants 575-25-006, 480-04-004, 904-61-090;
904-61-193, 400-05-717 and Spinozapremie SPI 56-464-14192 and the
European Research Council (ERC-230374). MHMdeM is supported by NWO VENI
Grant No. 016-115-035. Genotyping was funded by the Genetic Association
Information Network (GAIN) of the Foundation for the US National
Institutes of Health, and analysis was supported by grants from Genetic
Association Information Network and the NIMH (MH081802). Genotype data
were obtained from dbGaP (http://www.ncbi.nlm.nih.gov/dbgap, accession
number phs000020.v1.p1).; ORCADES was supported by the Chief Scientist
Office of the Scottish Government, the Royal Society, the MRC Human
Genetics Unit, Arthritis Research UK and the European Union framework
program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA
extractions were performed at the Wellcome Trust Clinical Research
Facility in Edinburgh. We would like to acknowledge the research nurses
in Orkney, the administrative team in Edinburgh and the people of
Orkney.; QIMR Berghofer adolescents/adults We thank Marlene Grace and
Ann Eldridge for sample collection; Megan Campbell, Lisa Bowdler, Steven
Crooks and staff of the Molecular Epidemiology Laboratory for sample
processing and preparation; Harry Beeby, David Smyth and Daniel Park for
IT support. We acknowledge support from the Australian Research Council
Grants A79600334, A79906588, A79801419, DP0212016, DP0343921, DP0664638,
and DP1093900 (to NGM and MJW), Beyond Blue and the Borderline
Personality Disorder Research Foundation (to NGM), NIH Grants DA12854
(to PAFM), AA07728, AA07580, AA11998, AA13320, AA13321 (to ACH) and
MH66206 (to WSS); and grants from the Australian National Health and
Medical Research Council; MLP is supported by DA019951. Genotyping was
partly funded by the National Health and Medical Research Council
(Medical Bioinformatics Genomics Proteomics Program, 389891) and the 5th
Framework Programme (FP-5) GenomEUtwin Project (QLG2-CT-2002-01254).
Further genotyping at the Center for Inherited Disease Research was
supported by a grant to the late Richard Todd, M.D., Ph.D., former
Principal Investigator of Grant AA13320. SEM and GWM are supported by
the National Health and Medical Research Council Fellowship Scheme.
Further, we gratefully acknowledge Dr Dale R Nyholt for his substantial
involvement in the QC and preparation of the QIMR GWA data sets. Dr
Nyholt also contributed 8 % of the GWAS for the QIMR adult cohort (NHMRC
IDs 339462, 442981, 389938, 496739).; SardiNIA We acknowledge support
from the Intramural Research Program of the NIH, National Institute on
Aging. Funding was provided by the National Institute on Aging, NIH
Contract No. NO1-AG-1-2109 to the SardiNIA ('ProgeNIA') team.; SHIP SHIP
is part of the Community Medicine Research net of the University of
Greifswald, Germany, which is funded by the Federal Ministry of
Education and Research (Grants No. 01ZZ9603, 01ZZ0103, and 01ZZ0403),
the Ministry of Cultural Affairs and the Social Ministry of the Federal
State of Mecklenburg-West Pomerania. Genome-wide data have been
supported by the Federal Ministry of Education and Research (Grant No.
03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany
and the Federal State of Mecklenburg-West Pomerania. The University of
Greifswald is a member of the 'Center of Knowledge Interchange' program
of the Siemens AG. This work was also funded by the German Research
Foundation (DFG: GR 1912/5-1).; STR The STR was supported by grants from
the Ministry for Higher Education, the Swedish Research Council
(M-2005-1112 and 2009-2298), GenomEUtwin (EU/QLRT-2001-01254;
QLG2-CT-2002-01254), NIH Grant DK U01-066134, The Swedish Foundation for
Strategic Research (SSF; ICA08-0047), the Swedish Heart-Lung Foundation,
the Royal Swedish Academy of Science, and ENGAGE (within the European
Union Seventh Framework Programme, HEALTH-F4-2007-201413).; CROATIA-Vis
The CROATIA-Vis study was funded by grants from the Medical Research
Council (UK) and Republic of Croatia Ministry of Science, Education and
Sports research Grants to I. R. (108-1080315-0302). We would like to
acknowledge the staff of several institutions in Croatia that supported
the field work, including but not limited to The University of Split and
Zagreb Medical Schools, the Institute for Anthropological Research in
Zagreb and Croatian Institute for Public Health. The SNP genotyping for
the CROATIA-Vis cohort was performed in the core genotyping laboratory
of the Wellcome Trust Clinical Research Facility at the Western General
Hospital, Edinburgh, Scotland.; YFS The Young Finns Study has been
financially supported by the Academy of Finland (Grants 126925, 121584,
124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi), and 265869
(Mind)), the Social Insurance Institution of Finland, Kuopio, Tampere
and Turku University Hospital Medical Funds (Grant 9N035 for Dr.
Lehtimaki), Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish
Foundation of Cardiovascular Research and Finnish Cultural Foundation,
Tampere Tuberculosis Foundation and Emil Aaltonen Foundation (for Dr.
Lehtimaki). The expert technical assistance in statistical analysis by
Irina Lisinen, Mika Helminen, and Ville Aalto is gratefully
acknowledged.; GS: SHFHS GS: SFHS is funded by the Scottish Executive
Health Department, Chief Scientist Office, Grant Number CZD/16/6. Exome
array genotyping for GS: SFHS was funded by the Medical Research Council
UK and performed at the Wellcome Trust Clinical Research Facility
Genetics Core at Western General Hospital, Edinburgh, UK. We would like
to acknowledge the invaluable contributions of the families who took
part in the GS: SFHS, the general practitioners and Scottish School of
Primary Care for their help in recruiting them, and the whole GS: SFHS
team, which includes academic researchers, IT staff, laboratory
technicians, statisticians and research managers.
NR 52
TC 7
Z9 7
U1 17
U2 49
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
EI 1573-3297
J9 BEHAV GENET
JI Behav. Genet.
PD MAR
PY 2016
VL 46
IS 2
BP 170
EP 182
DI 10.1007/s10519-015-9735-5
PG 13
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA DD7WO
UT WOS:000370135800002
PM 26362575
ER
PT J
AU Toth, JT
Gulyas, G
Toth, DJ
Balla, A
Hammond, GRV
Hunyady, L
Balla, T
Varnai, P
AF Toth, Jozsef T.
Gulyas, Gergo
Toth, Daniel J.
Balla, Andras
Hammond, Gerald R. V.
Hunyady, Laszlo
Balla, Tamas
Varnai, Peter
TI BRET-monitoring of the dynamic changes of inositol lipid pools in living
cells reveals a PKC-dependent PtdIns4P increase upon EGF and M3 receptor
activation
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Phosphoinositides; PI4-kinase; BRET; EGF receptor; GPCR; PKC
ID PLECKSTRIN-HOMOLOGY DOMAINS; EPIDERMAL-GROWTH-FACTOR;
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE LEVELS; RESONANCE ENERGY-TRANSFER;
PHOSPHOLIPASE-C; PHOSPHOINOSITIDE KINASES; BINDING-PROTEIN; MULTIPLE
POOLS; LIVE CELLS; 4-PHOSPHATE
AB Deciphering many roles played by inositol lipids in signal transduction and membrane function demands experimental approaches that can detect their dynamic accumulation with subcellular accuracy and exquisite sensitivity. The former criterion is met by imaging of fluorescence biosensors in living cells, whereas the latter is facilitated by biochemical measurements from populations. Here, we introduce BRET-based biosensors able to detect rapid changes in inositol lipids in cell populations with both high sensitivity and subcellular resolution in a single, convenient assay. We demonstrate robust and sensitive measurements of PtdIns4P, Ptdlns(4,5)P-2 and PtdIns(3,4,5)P-3 dynamics, as well as changes in cytoplasmic Ins(1,4,5)P-3 levels. Measurements were made during either experimental activation of lipid degradation, or PI 3-kinase and phospholipase C mediated signal transduction. Our results reveal a previously unappreciated synthesis of PtdIns4P that accompanies moderate activation of phospholipase C signaling downstream of both EGF and muscarinic M3 receptor activation. This signaling-induced PtdIns4P synthesis relies on protein kinase C, and implicates a feedback mechanism in the control of inositol lipid metabolism during signal transduction. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Toth, Jozsef T.; Gulyas, Gergo; Toth, Daniel J.; Balla, Andras; Hunyady, Laszlo; Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, POB 259, H-1444 Budapest, Hungary.
[Toth, Jozsef T.; Balla, Andras; Hunyady, Laszlo] MTA SE Lab Mol Physiol, Budapest, Hungary.
[Hammond, Gerald R. V.; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, NIH, Bethesda, MD USA.
[Hammond, Gerald R. V.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA USA.
RP Varnai, P (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, POB 259, H-1444 Budapest, Hungary.
EM varnai.peter@med.semmelweis-univ.hu
RI Hammond, Gerald/A-5759-2016
OI Toth, Daniel/0000-0001-6670-3348; Balla, Tamas/0000-0002-9077-3335;
Hammond, Gerald/0000-0002-6660-3272
FU National Research, Development and Innovation Fund [NKFI K105006];
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institutes of Health; Department of Cell Biology, University of
Pittsburgh School of Medicine
FX P.V. was supported by the National Research, Development and Innovation
Fund (NKFI K105006). T.B. was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development of the National Institutes of Health. G.H. is
supported by funds from the Department of Cell Biology, University of
Pittsburgh School of Medicine. The technical assistance of Kata
Szabolcsi is highly appreciated.
NR 58
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U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD MAR
PY 2016
VL 1861
IS 3
BP 177
EP 187
DI 10.1016/j.bbalip.2015.12.005
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DD7IQ
UT WOS:000370097300004
PM 26692031
ER
PT J
AU Alkaitis, MS
Nardone, G
Chertow, JH
Ackerman, HC
AF Alkaitis, Matthew S.
Nardone, Glenn
Chertow, Jessica H.
Ackerman, Hans C.
TI Resolution and quantification of arginine, monomethylarginine,
asymmetric dimethylarginine, and symmetric dimethylarginine in plasma
using HPLC with internal calibration
SO BIOMEDICAL CHROMATOGRAPHY
LA English
DT Article
DE ADMA; SDMA; L-NMMA; Arginine; Nitric Oxide Synthase; Vascular
Homeostasis
ID TANDEM MASS-SPECTROMETRY; CORONARY-ARTERY-DISEASE; PERFORMANCE
LIQUID-CHROMATOGRAPHY; PRECOLUMN DERIVATIZATION; ENDOTHELIAL
DYSFUNCTION; BIOLOGICAL SAMPLES; RENAL-FUNCTION; ADMA; HYPERTENSION;
DERIVATIVES
AB N-G,N-G-dimethyl-l-arginine (asymmetric dimethylarginine, ADMA),N-G-monomethyl-l-arginine (l-NMMA) and N-G,N-G'-dimethyl-l-arginine (symmetric dimethylarginine, SDMA) are released during hydrolysis of proteins containing methylated arginine residues. ADMA and l-NMMA inhibit nitric oxide synthase by competing with l-arginine substrate. All three methylarginine derivatives also inhibit arginine transport. To enable investigation of methylarginines in diseases involving impaired nitric oxide synthesis, we developed a high-performance liquid chromatography (HPLC) assay to simultaneously quantify arginine, ADMA, l-NMMA and SDMA. Our assay requires 12L of plasma and is ideal for applications where sample availability is limited. We extracted arginine and methylarginines with mixed-mode cation-exchange columns, using synthetic monoethyl-l-arginine as an internal standard. Metabolites were derivatized with ortho-phthaldialdeyhde and 3-mercaptopropionic acid, separated by reverse-phase HPLC and quantified with fluorescence detection. Standard curve linearity was 0.9995 for all metabolites. Inter-day coefficient of variation (CV) values were 5% for arginine, ADMA and SDMA in human plasma and for arginine and ADMA in mouse plasma. The CV value for l-NMMA was higher in human (10.4%) and mouse (15.8%) plasma because concentrations were substantially lower than ADMA and SDMA. This assay provides unique advantages of small sample volume requirements, excellent separation of target metabolites from contaminants and validation for both human and mouse plasma samples. (c) 2015 The Authors Biomedical Chromatography published by John Wiley & Sons, Ltd.
C1 [Alkaitis, Matthew S.; Chertow, Jessica H.; Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA.
[Alkaitis, Matthew S.] Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Oxford OX3 9DU, England.
[Nardone, Glenn] NIAID, Res Technol Branch, Rockville, MD USA.
RP Ackerman, HC (reprint author), NHLBI, Sickle Cell Branch, Bldg 10 Room 7D05, Bethesda, MD 20892 USA.; Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, Rockville, MD USA.
EM hans.ackerman@nih.gov
FU NIAID Division of Intramural Research
FX This work was funded by the NIAID Division of Intramural Research.
NR 33
TC 0
Z9 0
U1 5
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-3879
EI 1099-0801
J9 BIOMED CHROMATOGR
JI Biomed. Chromatogr.
PD MAR
PY 2016
VL 30
IS 3
BP 294
EP 300
DI 10.1002/bmc.3548
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA DD2EP
UT WOS:000369735700002
PM 26130049
ER
PT J
AU Devkota, L
Lin, CM
Strecker, TE
Wang, YF
Tidmore, JK
Chen, Z
Guddneppanavar, R
Jelinek, CJ
Lopez, R
Liu, L
Hamel, E
Mason, RP
Chaplin, DJ
Trawick, ML
Pinney, KG
AF Devkota, Laxman
Lin, Chen-Ming
Strecker, Tracy E.
Wang, Yifan
Tidmore, Justin K.
Chen, Zhi
Guddneppanavar, Rajsekhar
Jelinek, Christopher J.
Lopez, Ramona
Liu, Li
Hamel, Ernest
Mason, Ralph P.
Chaplin, David J.
Trawick, Mary Lynn
Pinney, Kevin G.
TI Design, synthesis, and biological evaluation of water-soluble amino acid
prodrug conjugates derived from combretastatin, dihydronaphthalene, and
benzosuberene-based parent vascular disrupting agents
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Small-molecule synthesis; Inhibitors of tubulin polymerization; Vascular
disrupting agents; Amino acid prodrug salts; Anti-cancer agents;
Combretastatin analogs; Benzosuberene analogs; Dihydronaphthalene
analogs
ID SERUM LEUCINE AMINOPEPTIDASE; ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS;
A4 PHOSPHATE; COLORIMETRIC ASSAY; ESTER DERIVATIVES; TUMOR VASCULATURE;
BLOOD-VESSELS; SOLID TUMORS; CELL-GROWTH
AB Targeting tumor vasculature represents an intriguing therapeutic strategy in the treatment of cancer. In an effort to discover new vascular disrupting agents with improved water solubility and potentially greater bioavailability, various amino acid prodrug conjugates (AAPCs) of potent amino combretastatin, amino dihydronaphthalene, and amino benzosuberene analogs were synthesized along with their corresponding water-soluble hydrochloride salts. These compounds were evaluated for their ability to inhibit tubulin polymerization and for their cytotoxicity against selected human cancer cell lines. The amino-based parent anticancer agents 7, 8, 32 (also referred to as KGP05) and 33 (also referred to as KGP156) demonstrated potent cytotoxicity (GI(50) = 0.11-40 nM) across all evaluated cell lines, and they were strong inhibitors of tubulin polymerization (IC50 = 0.62-1.5 mu M). The various prodrug conjugates and their corresponding salts were investigated for cleavage by the enzyme leucine aminopeptidase (LAP). Four of the glycine water-soluble AAPCs (16, 18, 44 and 45) showed quantitative cleavage by LAP, resulting in the release of the highly cytotoxic parent drug, whereas partial cleavage (<10-90%) was observed for other prodrugs (15, 17, 24, 38 and 39). Eight of the nineteen AAPCs (13-16, 42-45) showed significant cytotoxicity against selected human cancer cell lines. The previously reported CA1-diamine analog and its corresponding hydrochloride salt (8 and 10, respectively) caused extensive disruption (at a concentration of 1.0 mu M) of human umbilical vein endothelial cells growing in a two-dimensional tubular network on matrigel. In addition, compound 10 exhibited pronounced reduction in bioluminescence (greater than 95% compared to saline control) in a tumor bearing (MDA-MB-231-luc) SCID mouse model 2 h post treatment (80 mg/kg), with similar results observed upon treatment (15 mg/kg) with the glycine amino-dihydronaphthalene AAPC (compound 44). Collectively, these results support the further pre-clinical development of the most active members of this structurally diverse collection of water-soluble prodrugs as promising anticancer agents functioning through a mechanism involving vascular disruption. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Devkota, Laxman; Lin, Chen-Ming; Strecker, Tracy E.; Wang, Yifan; Tidmore, Justin K.; Chen, Zhi; Guddneppanavar, Rajsekhar; Jelinek, Christopher J.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G.] Baylor Univ, Dept Chem & Biochem, One Bear Pl 97348, Waco, TX 76798 USA.
[Lopez, Ramona; Liu, Li; Mason, Ralph P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21702 USA.
[Chaplin, David J.] OXiGENE Inc, 701 Gateway Blvd,Suite 210, San Francisco, CA 94080 USA.
RP Trawick, ML; Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, One Bear Pl 97348, Waco, TX 76798 USA.
EM Mery_Lynn_Trawick@baylor.edu; Kevin_Pin-ney@baylor.edu
RI Mason, Ralph/C-8472-2012
OI Mason, Ralph/0000-0001-7517-3721
FU National Cancer Institute of the National Institutes of Health
[5R01CA140674]; Cancer Prevention and Research Institute of Texas
(CPRIT) [RP140399]; OXiGENE, Inc.; National Institutes of Health
National Cancer Institute Cancer Center Support Grant [1P30 CA142543]
FX The authors are grateful to the National Cancer Institute of the
National Institutes of Health (Grant No. 5R01CA140674 to K.G.P., M.L.T.,
and R.P.M.), the Cancer Prevention and Research Institute of Texas
(CPRIT, Grant No. RP140399 to K.G.P., M.L.T., and R.P.M.), and OXiGENE,
Inc. (Grant to K.G.P. and M.L.T.) for their financial support of this
project. The content is solely the responsibility of the authors and
does not necessarily reflect the official views of the National
Institutes of Health. The authors also thank Dr. Michelle Nemec
(Director) for the use of the shared Molecular Biosciences Center at
Baylor University and Dr. Alejandro Ramirez (Mass Spectrometry Core
Facility, Baylor University). The authors are grateful to Mr. Jarrod
Tunnell (Baylor University) for his contributions to the synthesis of an
advanced intermediate, and to Jeni Gerberich (UTSW) for valuable
technical assistance. Imaging (at UTSW) was facilitated with the
assistance of Resources of the Harold C. Simmons Cancer Center supported
through an National Institutes of Health National Cancer Institute
Cancer Center Support Grant [Grant 1P30 CA142543], specifically, the
Southwestern Small Animal Imaging Resource, and Live Cell Imaging
Resource. The IVIS Spectrum was purchased with support of 1S10RR024757.
NR 87
TC 5
Z9 5
U1 12
U2 41
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD MAR 1
PY 2016
VL 24
IS 5
BP 938
EP 956
DI 10.1016/j.bmc.2016.01.007
PG 19
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA DD5UH
UT WOS:000369989500002
PM 26852340
ER
PT J
AU Lindenberg, L
Choyke, P
Dahut, W
AF Lindenberg, Liza
Choyke, Peter
Dahut, William
TI Prostate Cancer Imaging with Novel PET Tracers
SO CURRENT UROLOGY REPORTS
LA English
DT Article
DE F-18 NaF; C-11 acetate; C-11/F-18 choline; F-18 DHT; F-18 FACBC; F-18
DCFBC; Ga-68 PSMA
ID POSITRON-EMISSION-TOMOGRAPHY; ANDROGEN-DEPRIVATION THERAPY;
GA-68-LABELED PSMA LIGAND; RADICAL PROSTATECTOMY; C-11-CHOLINE PET/CT;
BIOCHEMICAL RELAPSE; F-18-FLUORIDE PET; C-11-ACETATE PET/CT; GA-68-PSMA
PET/CT; BONE METASTASES
AB Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.
C1 [Lindenberg, Liza; Choyke, Peter; Dahut, William] NCI, Ctr Canc Res, BG 10 CRC RM 3-2571 MSC 1206,10 Ctr Dr, Bethesda, MD 20892 USA.
[Lindenberg, Liza; Choyke, Peter] NCI, Mol Imaging Program, BG 10 RM B3B69F MS 1002,10 Ctr Dr, Bethesda, MD 20814 USA.
[Dahut, William] NCI, Genitourinary Malignancies Branch, BG 10 RM B3B402 MS 1088,10 Ctr Dr, Bethesda, MD 20814 USA.
RP Dahut, W (reprint author), NCI, Ctr Canc Res, BG 10 CRC RM 3-2571 MSC 1206,10 Ctr Dr, Bethesda, MD 20892 USA.; Dahut, W (reprint author), NCI, Genitourinary Malignancies Branch, BG 10 RM B3B402 MS 1088,10 Ctr Dr, Bethesda, MD 20814 USA.
EM liza.lindenberg@mail.nih.gov; pchoyke@mail.nih.gov; dahutw@mail.nih.gov
NR 50
TC 7
Z9 7
U1 4
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2737
J9 CURR UROL REP
JI Curr. Urol. Rep.
PD MAR
PY 2016
VL 17
IS 3
AR 18
DI 10.1007/s11934-016-0575-5
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA DD6ZC
UT WOS:000370072300002
PM 26874530
ER
PT J
AU Mitchell, EM
Hinkle, SN
Schisterman, EF
AF Mitchell, Emily M.
Hinkle, Stefanie N.
Schisterman, Enrique F.
TI It's About Time A Survival Approach to Gestational Weight Gain and
Preterm Delivery
SO EPIDEMIOLOGY
LA English
DT Article
ID BODY-MASS INDEX; PROPORTIONAL HAZARDS; LOGISTIC-REGRESSION; MODELS;
RISK; PREGNANCY; BIRTH; WOMEN; COHORT; BIAS
AB There is substantial interest in understanding the impact of gestational weight gain on preterm delivery (delivery <37 weeks). The major difficulty in analyzing the association between gestational weight gain and preterm delivery lies in their mutual dependence on gestational age, as weight naturally increases with increasing pregnancy duration. In this study, we untangle this inherent association by reframing preterm delivery as time to delivery and assessing the relationship through a survival framework, which is particularly amenable to dealing with time-dependent covariates, such as gestational weight gain. We derive the appropriate analytical model for assessing the relationship between weight gain and time to delivery when weight measurements at multiple time points are available. Since epidemiologic data may be limited to weight gain measurements taken at only a few time points or at delivery only, we conduct simulation studies to illustrate how several strategically timed measurements can yield unbiased risk estimates. Analysis of the study of successive small-for-gestational-age births demonstrates that a naive analysis that does not account for the confounding effect of time on gestational weight gain suggests a strong association between higher weight gain and later delivery (hazard ratio: 0.89, 95% confidence interval = 0.84, 0.93). Properly accounting for the confounding effect of time using a survival model, however, mitigates this bias (hazard ratio: 0.98, 95% confidence interval = 0.97, 1.00). These results emphasize the importance of considering the effect of gestational age on time-varying covariates during pregnancy, and the proposed methods offer a convenient mechanism to appropriately analyze such data. See Video Abstract at http://links.lww.com/EDE/B13.
C1 [Mitchell, Emily M.; Hinkle, Stefanie N.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Bethesda, MD 20852 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Bethesda, MD 20852 USA.
EM schistee@mail.nih.gov
OI Hinkle, Stefanie/0000-0003-4312-708X; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; Long-Range Research Initiative of the American Chemistry Council
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health, and by the Long-Range Research Initiative
of the American Chemistry Council.
NR 31
TC 1
Z9 1
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAR
PY 2016
VL 27
IS 2
BP 182
EP 187
DI 10.1097/EDE.0000000000000413
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DD4BH
UT WOS:000369866900004
PM 26489043
ER
PT J
AU Ellefsen, KN
Concheiro, M
Pirard, S
Gorelick, DA
Huestis, MA
AF Ellefsen, Kayla N.
Concheiro, Marta
Pirard, Sandrine
Gorelick, David A.
Huestis, Marilyn A.
TI Oral fluid cocaine and benzoylecgonine concentrations following
controlled intravenous cocaine administration
SO FORENSIC SCIENCE INTERNATIONAL
LA English
DT Article
DE Cocaine; Benzoylecgonine; Oral Fluid; Oral-Eze (R); Pharmacokinetics;
StatSure Saliva Sampler (TM)
ID CANNABINOID STABILITY; SALIVA; PLASMA; BLOOD; DRUGS; METABOLITES; URINE;
ELIMINATION; DRIVERS; SAMPLE
AB Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze (R) (OE) and StatSure Saliva Sampler (TM) (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed C-max median (range) concentrations were 932 (394-1574) mg/L for cocaine and 248 (96.9-953) mg/L for BE. SS observed cocaine and BE C-max median (range) concentrations trended lower at 732 (83.3-1892) mg/L and 360 (77.2-836) mg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 mg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. Published by Elsevier Ireland Ltd.
C1 [Ellefsen, Kayla N.; Pirard, Sandrine; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD USA.
[Ellefsen, Kayla N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Concheiro, Marta] CUNY John Jay Coll Criminal Justice, Dept Sci, New York, NY 10019 USA.
[Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program (IRP), National Institute on Drug Abuse
(NIDA), National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program (IRP),
National Institute on Drug Abuse (NIDA), National Institutes of Health
(NIH). Oral-Eze and StatSure oral fluid collection devices were provided
to NIH through Materials Transfer Agreements. The authors acknowledge
the contributions of the clinical staff of the NIDA-IRP and the Clinical
Research Unit, Johns Hopkins Bayview Medical Center, as well as the
University of Maryland, Baltimore, a member of the Graduate Partnership
Program, NIH, Drs. Sebastien Anizan and Jose Luiz da Costa, and Allan
Barnes.
NR 33
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Z9 4
U1 5
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0379-0738
EI 1872-6283
J9 FORENSIC SCI INT
JI Forensic Sci.Int.
PD MAR
PY 2016
VL 260
BP 95
EP 101
DI 10.1016/j.forsciint.2016.01.013
PG 7
WC Medicine, Legal
SC Legal Medicine
GA DD8MC
UT WOS:000370179900016
PM 26851651
ER
PT J
AU Mazor, R
Onda, M
Pastan, I
AF Mazor, Ronit
Onda, Masanori
Pastan, Ira
TI Immunogenicity of therapeutic recombinant immunotoxins
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE anti-drug antibodies; neutralizing antibodies; immunotherapy;
mesothelin; mesothelioma
ID PHASE-I TRIAL; T-CELL EPITOPE; ADVANCED SOLID TUMORS; SURFACE-EXPOSED
RESIDUES; SITE-SPECIFIC MANNER; EXOTOXIN-A MUTANTS; PSEUDOMONAS
EXOTOXIN; B-CELL; HEMATOLOGIC MALIGNANCIES; REDUCED IMMUNOGENICITY
AB Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38-kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less-immunogenic RITs by identifying and removing T- and B-cell epitopes to hide the RIT from the immune system.
C1 [Mazor, Ronit; Onda, Masanori; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NIH, Mol Biol Lab, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research;
Hoffman-LaRoche Inc./F. Hoffman-LaRoche Ltd. [2791]
FX We thank Dr. B. K. Sathyanarayana for editing Fig. 1 and to Dr. Alan
Hoofring for editing Fig. 3. We thank Dr. Robert J. Kreitman for
providing unpublished immunogenicity data that is shown in Fig. 2A. This
research was supported in part by the Intramural Research Program of
NIH, National Cancer Institute, Center for Cancer Research and a
Cooperative Research and Development Agreement (#2791) with
Hoffman-LaRoche Inc./F. Hoffman-LaRoche Ltd. The authors declare no
conflict of interest.
NR 89
TC 9
Z9 9
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2016
VL 270
IS 1
SI SI
BP 152
EP 164
DI 10.1111/imr.12390
PG 13
WC Immunology
SC Immunology
GA DD7CZ
UT WOS:000370082600011
PM 26864110
ER
PT J
AU Liu, EJ
McCree, R
Mtisi, E
Fawzi, WW
Aris, E
Lema, IA
Hertzmark, E
Chalamilla, G
Li, N
Vermund, SH
Spiegelman, D
AF Liu, Enju
McCree, Renicha
Mtisi, Expeditho
Fawzi, Wafaie W.
Aris, Eric
Lema, Irene A.
Hertzmark, Ellen
Chalamilla, Guerino
Li, Nan
Vermund, Sten H.
Spiegelman, Donna
TI Prevalence and risk factors of cervical squamous intraepithelial lesions
among HIV-infected women in Dar es Salaam, Tanzania
SO INTERNATIONAL JOURNAL OF STD & AIDS
LA English
DT Article
DE HIV; AIDS; human papillomavirus; HPV; prevalence; risk factors; cervical
squamous intraepithelial lesions; Papanicolaou (Pap) smear; HIV-infected
women; Tanzania
ID HUMAN-PAPILLOMAVIRUS PREVALENCE; HUMAN-IMMUNODEFICIENCY-VIRUS;
ANTIRETROVIRAL THERAPY; POSITIVE WOMEN; CANCER; PREDICTORS; PREVENTION;
OUTCOMES
AB To determine the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Tanzania, a cross-sectional study was conducted among HIV-infected women at HIV care and treatment clinics. A Papanicolaou (Pap) smear was used as a screening tool for detection of cervical SIL. From December 2006 to August 2009, 1365 HIV-infected women received cervical screening. The median age was 35 (interquartile range [IQR]: 30-42) years, and the median CD4+cell count was 164 (IQR: 80-257) cells/mm(3). The prevalence of cervical SIL was 8.7% (119/1365). In multivariate analysis, older age (50 versus 30-<40 years: prevalence ratio [PR], 2.36; 95% confidence interval [CI], 1.45-3.84, p for trend=0.001), lower CD4+cell counts (<100 versus 200cells/mm(3): PR, 1.55; 95% CI, 1.01-2.36, p for trend=0.03) and cervical inflammation (PR, 1.73; 95% CI, 1.16-2.60, p=0.008) were associated with an increased risk of cervical SIL. Women with advanced WHO HIV disease stage (IV versus I/II: PR, 3.45; 95% CI, 1.35-8.85, p for trend=0.01) had an increased risk for high-grade SIL. In resource-limited settings where it is not feasible to provide cervical cancer prevention services to all HIV-infected women, greater efforts should focus on scaling-up services among those who are older than 50 years, with lower CD4 cell counts and advanced HIV disease stage.
C1 [Liu, Enju; Fawzi, Wafaie W.; Li, Nan; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.
[McCree, Renicha] Natl Canc Inst, Ctr Global Hlth, Rockville, MD USA.
[Mtisi, Expeditho] Africa Acad Publ Hlth, Dar Es Salaam, Tanzania.
[Fawzi, Wafaie W.; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.
[Fawzi, Wafaie W.; Hertzmark, Ellen; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.
[Aris, Eric; Lema, Irene A.; Chalamilla, Guerino] Management & Dev Hlth, Dar Es Salaam, Tanzania.
[Vermund, Sten H.] Vanderbilt Univ, Vanderbilt Inst Global Hlth, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.
RP Spiegelman, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.; Spiegelman, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.; Spiegelman, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.; Spiegelman, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave,Kresge Bldg,Room 802, Boston, MA 02115 USA.
EM stdls@hsph.harvard.edu
FU President's Emergency Plan for AIDS Relief (PEPFAR) [U51HA02522]; Center
of Disease Control in United States [5U2GPS001966]; Ministry of Health
and Social Welfare, Tanzania
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This study is
supported by the President's Emergency Plan for AIDS Relief (PEPFAR
Grant Number U51HA02522), Center of Disease Control in United States
(Grant Number 5U2GPS001966), and the Ministry of Health and Social
Welfare, Tanzania.
NR 27
TC 0
Z9 0
U1 3
U2 7
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0956-4624
EI 1758-1052
J9 INT J STD AIDS
JI Int. J. STD AIDS
PD MAR
PY 2016
VL 27
IS 3
BP 219
EP 225
DI 10.1177/0956462415584466
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DD5UJ
UT WOS:000369989700008
PM 25957324
ER
PT J
AU Kapitonov, VV
Makarova, KS
Koonin, EV
AF Kapitonov, Vladimir V.
Makarova, Kira S.
Koonin, Eugene V.
TI ISC, a Novel Group of Bacterial and Archaeal DNA Transposons That Encode
Cas9 Homologs
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; STRUCTURE PREDICTION; INSERTION SEQUENCES;
MAXIMUM-LIKELIHOOD; ADAPTIVE IMMUNITY; ENDONUCLEASE; SYSTEMS; EVOLUTION;
MECHANISM; DATABASE
AB Bacterial genomes encode numerous homologs of Cas9, the effector protein of the type II CRISPR-Cas systems. The homology region includes the arginine-rich helix and the HNH nuclease domain that is inserted into the RuvC-like nuclease domain. These genes, however, are not linked to cas genes or CRISPR. Here, we show that Cas9 homologs represent a distinct group of nonautonomous transposons, which we denote ISC (insertion sequences Cas9-like). We identify many diverse families of full-length ISC transposons and demonstrate that their terminal sequences (particularly 3' termini) are similar to those of IS605 superfamily transposons that are mobilized by the Y1 tyrosine transposase encoded by the TnpA gene and often also encode the TnpB protein containing the RuvC-like endonuclease domain. The terminal regions of the ISC and IS605 transposons contain palindromic structures that are likely recognized by the Y1 transposase. The transposons from these two groups are inserted either exactly in the middle or upstream of specific 4-bp target sites, without target site duplication. We also identify autonomous ISC transposons that encode TnpA-like Y1 transposases. Thus, the nonautonomous ISC transposons could be mobilized in trans either by Y1 transposases of other, autonomous ISC transposons or by Y1 transposases of the more abundant IS605 transposons. These findings imply an evolutionary scenario in which the ISC transposons evolved from IS605 family transposons, possibly via insertion of a mobile group II intron encoding the HNH domain, and Cas9 subsequently evolved via immobilization of an ISC transposon.
IMPORTANCE
Cas9 endonucleases, the effectors of type II CRISPR-Cas systems, represent the new generation of genome-engineering tools. Here, we describe in detail a novel family of transposable elements that encode the likely ancestors of Cas9 and outline the evolutionary scenario connecting different varieties of these transposons and Cas9.
C1 [Kapitonov, Vladimir V.; Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU U.S. Department of Health and Human Services
FX The U.S. Department of Health and Human Services provided funding to
Vladimir V. Kapitonov, Kira S. Makarova, and Eugene V. Koonin through
the intramural funding program.
NR 35
TC 3
Z9 3
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD MAR
PY 2016
VL 198
IS 5
BP 797
EP 807
DI 10.1128/JB.00783-15
PG 11
WC Microbiology
SC Microbiology
GA DD5IH
UT WOS:000369956200008
ER
PT J
AU Halim, MFA
Karch, KR
Zhou, YT
Haft, DH
Garcia, BA
Pohlschroder, M
AF Halim, Mohd Farid Abdul
Karch, Kelly R.
Zhou, Yitian
Haft, Daniel H.
Garcia, Benjamin A.
Pohlschroder, Mechthild
TI Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent
C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax
volcanii S-Layer Glycoprotein
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID CELL-SURFACE GLYCOPROTEIN; INNER MEMBRANE-PROTEINS; POSTTRANSLATIONAL
MODIFICATION; N-GLYCOSYLATION; TRANSLOCATION; MECHANISM; BIOSYNTHESIS;
DIVERSITY; SYSTEMS
AB For years, the S-layer glycoprotein (SLG), the sole component of many archaeal cell walls, was thought to be anchored to the cell surface by a C-terminal transmembrane segment. Recently, however, we demonstrated that the Haloferax volcanii SLG C terminus is removed by an archaeosortase (ArtA), a novel peptidase. SLG, which was previously shown to be lipid modified, contains a C-terminal tripartite structure, including a highly conserved proline-glycine-phenylalanine (PGF) motif. Here, we demonstrate that ArtA does not process an SLG variant where the PGF motif is replaced with a PFG motif (slg(G796F,F797G)). Furthermore, using radiolabeling, we show that SLG lipid modification requires the PGF motif and is ArtA dependent, lending confirmation to the use of a novel C-terminal lipid-mediated protein-anchoring mechanism by prokaryotes. Similar to the case for the Delta artA strain, the growth, cellular morphology, and cell wall of the slg(G796F, F797G) strain, in which modifications of additional H. volcanii ArtA substrates should not be altered, are adversely affected, demonstrating the importance of these posttranslational SLG modifications. Our data suggest that ArtA is either directly or indirectly involved in a novel proteolysis-coupled, covalent lipid-mediated anchoring mechanism. Given that archaeosortase homologs are encoded by a broad range of prokaryotes, it is likely that this anchoring mechanism is widely conserved.
IMPORTANCE
Prokaryotic proteins bound to cell surfaces through intercalation, covalent attachment, or protein-protein interactions play critical roles in essential cellular processes. Unfortunately, the molecular mechanisms that anchor proteins to archaeal cell surfaces remain poorly characterized. Here, using the archaeon H. volcanii as a model system, we report the first in vivo studies of a novel protein-anchoring pathway involving lipid modification of a peptidase-processed C terminus. Our findings not only yield important insights into poorly understood aspects of archaeal biology but also have important implications for key bacterial species, including those of the human microbiome. Additionally, insights may facilitate industrial applications, given that photosynthetic cyanobacteria encode uncharacterized homologs of this evolutionarily conserved enzyme, or may spur development of unique drug delivery systems.
C1 [Halim, Mohd Farid Abdul; Zhou, Yitian; Pohlschroder, Mechthild] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Karch, Kelly R.; Garcia, Benjamin A.] Univ Penn, Perelman Sch Med, Dept Biochem & Mol Biophys, Penn Med Epigenet Program, Philadelphia, PA 19104 USA.
[Haft, Daniel H.] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
RP Pohlschroder, M (reprint author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
EM pohlschr@sas.upenn.edu
FU U.S. Department of Defense (DOD) [W81XWH-13-1-0426]; NSF \ BIO \
Division of Molecular and Cellular Biosciences (MCB) [MCB-1413158];
National Aeronautics and Space Administration (NASA) [NNX10AR84G]
FX U.S. Department of Defense (DOD) provided funding to Kelly R. Karch and
Benjamin A. Garcia under grant number W81XWH-13-1-0426. NSF vertical bar
BIO vertical bar Division of Molecular and Cellular Biosciences (MCB)
provided funding to Mohd Farid Abdul Halim and Mechthild Pohlschroder
under grant number MCB-1413158. National Aeronautics and Space
Administration (NASA) provided funding to Yitian Zhou under grant number
NNX10AR84G.
NR 36
TC 3
Z9 4
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD MAR
PY 2016
VL 198
IS 5
BP 808
EP 815
DI 10.1128/JB.00849-15
PG 8
WC Microbiology
SC Microbiology
GA DD5IH
UT WOS:000369956200009
ER
PT J
AU Cheng, ER
Park, H
Wisk, LE
Mandell, KC
Wakeel, F
Litzelman, K
Chatterjee, D
Witt, WP
AF Cheng, Erika R.
Park, Hyojun
Wisk, Lauren E.
Mandell, Kara C.
Wakeel, Fathima
Litzelman, Kristin
Chatterjee, Debanjana
Witt, Whitney P.
TI Examining the link between women's exposure to stressful life events
prior to conception and infant and toddler health: the role of birth
weight
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Article
ID MATERNAL BEREAVEMENT; UNITED-STATES; IMPACT; RISK; PRECONCEPTION;
MORTALITY; TRENDS; AGE
AB Background The life course perspective suggests a pathway may exist among maternal exposure to stressful life events prior to conception (PSLEs), infant birth weight and subsequent offspring health, whereby PSLEs are part of a 'chains-of-risk' that set children on a certain health pathway. No prior study has examined the link between PSLEs and offspring health in a nationally representative sample of US mothers and their children. We used longitudinal, nationally representative data to evaluate the relation between maternal exposure to PSLEs and subsequent measures of infant and toddler health, taking both maternal and obstetric characteristics into account.
Methods We examined 6900 mother - child dyads participating in 2 waves of the nationally representative Early Childhood Longitudinal Study - Birth Cohort (n= 6900). Infant and toddler health outcomes assessed at 9 and 24 months included overall health status, special healthcare needs and severe health conditions. Adjusted path analyses examined associations between PSLEs, birth weight and child health outcomes.
Results In adjusted analyses, PSLEs increased the risk for very low birth weight (VLBW, < 1500 g), which, in turn, predicted poor health at both 9 and 24 months of age. Path analyses demonstrated that PSLEs had small indirect effects on children's subsequent health that operated through VLBW.
Conclusions Our analysis suggests a chains - of - risk model in which women's exposure to PSLEs increases the risk for giving birth to a VLBW infant, which, in turn, adversely affects infant and toddler health. Addressing women's preconception health may have important downstream benefits for their children, although more research is needed to replicate these findings.
C1 [Cheng, Erika R.] Indiana Univ Sch Med, Dept Pediat, Childrens Hlth Serv Res, Indianapolis, IN 46202 USA.
[Park, Hyojun; Mandell, Kara C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
[Wisk, Lauren E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA USA.
[Wisk, Lauren E.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Wakeel, Fathima] Ferris State Univ, Coll Hlth Profess, Publ Hlth Programs, Big Rapids, MI USA.
[Litzelman, Kristin] NCI, Bethesda, MD 20892 USA.
[Chatterjee, Debanjana] Univ Minnesota, Dept Pediat, Div Gen Pediat & Adolescent Hlth, Minneapolis, MN 55455 USA.
[Witt, Whitney P.] Truven Hlth Analyt, 4819 Emperor Blvd,Suite 125, Durham, NC 27703 USA.
RP Witt, WP (reprint author), Truven Hlth Analyt, 4819 Emperor Blvd,Suite 125, Durham, NC 27703 USA.; Witt, WP (reprint author), Truven Hlth Analyt, Ctr Maternal & Child Hlth Res, 4819 Emperor Blvd,Suite 125, Durham, NC 27703 USA.
EM whitney.witt@truvenhealth.com
FU Health Resources and Services Administrative (HRSA) [R40MC23625]; Agency
for Healthcare Research and Quality [T32 HS00083]; National Research
Service Award [T32-HD075727]; Thomas O. Pyle Fellowship; Agency for
Healthcare Research and Quality Postdoctoral Training Grant
[T32HS000063-20]; National Research Service Award (NRSA) in Primary
Medical Care Grant [T32HP22239]; US Department of Health and Human
Services; National Institutes of Health; National Institute of Child
Health and Human Development [T32HD075727-01]
FX This project was made possible by a Health Resources and Services
Administrative (HRSA) (W. P. Witt, L. E. Wisk, and D. Chatterjee:
R40MC23625; principal in-vestigator W. P. Witt) grant. Additional
funding for this research was provided by grants from the Agency for
Healthcare Research and Quality (K. Mandell T32 HS00083; principal
investigator M. Smith), and a National Research Service Award
institutional training grant (E. R. Cheng: T32-HD075727; principal
investigator J. A. Finkelstein). L. E. Wisk was supported by the Thomas
O. Pyle Fellowship and an Agency for Healthcare Research and Quality
Postdoctoral Training Grant T32HS000063-20 (principal investigator J. A.
Finkelstein). D. Chatterjee was additionally supported by National
Research Service Award (NRSA) in Primary Medical Care Grant T32HP22239
(principal investigator: I. Borowsky). US Department of Health and
Human\ Services >Agency for Healthcare Research and Quality.
T32HS000063-20. T32HS00083; US Department of Health and Human Services >
Health Resources and Services Administration. R40MC23625. T32HP22239; US
Department of Health and Human Services > National Institutes of Health
> National Institute of Child Health and Human Development.
T32HD075727-01.
NR 36
TC 2
Z9 2
U1 3
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
EI 1470-2738
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD MAR
PY 2016
VL 70
IS 3
BP 245
EP 252
DI 10.1136/jech-2015-205848
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DD5KU
UT WOS:000369963400008
PM 26500337
ER
PT J
AU Spencer, PBS
Yurchenko, AA
David, VA
Scott, R
Koepfli, KP
Driscoll, C
O'Brien, SJ
Menotti-Raymond, M
AF Spencer, Peter B. S.
Yurchenko, Andrey A.
David, Victor A.
Scott, Rachael
Koepfli, Klaus-Peter
Driscoll, Carlos
O'Brien, Stephen J.
Menotti-Raymond, Marilyn
TI The Population Origins and Expansion of Feral Cats in Australia
SO JOURNAL OF HEREDITY
LA English
DT Article
DE Felis catus; Felis silvestris silvestris; genetic structure;
microsatellite; population ecology; wild cat
ID FELIS-CATUS; GENETIC-STRUCTURE; WESTERN-AUSTRALIA; DOMESTIC CAT;
MICROSATELLITE DATA; EASTERN AUSTRALIA; VERTEBRATE FAUNA; NATIVE FAUNA;
MANAGEMENT; PATTERNS
AB The historical literature suggests that in Australia, the domestic cat (Felis catus) had a European origin [similar to 200 years before present (ybp)], but it is unclear if cats arrived from across the Asian land bridge contemporaneously with the dingo (4000 ybp), or perhaps immigrated similar to 40 000 ybp in association with Aboriginal settlement from Asia. The origin of cats in Australia is important because the continent has a complex and ancient faunal assemblage that is dominated by endemic rodents and marsupials and lacks the large placental carnivores found on other large continents. Cats are now ubiquitous across the entire Australian continent and have been implicit in the range contraction or extinction of its small to medium sized (<3.5 kg) mammals. We analyzed the population structure of 830 cats using 15 short tandem repeat (STR) genomic markers. Their origin appears to come exclusively from European founders. Feral cats in continental Australia exhibit high genetic diversity in comparison with the low diversity found in populations of feral cats living on islands. The genetic structure is consistent with a rapid westerly expansion from eastern Australia and a limited expansion in coastal Western Australia. Australian cats show modest if any population structure and a close genetic alignment with European feral cats as compared to cats from Asia, the Christmas and Cocos (Keeling) Islands (Indian Ocean), and European wildcats (F. silvestris silvestris).
C1 [Spencer, Peter B. S.] Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA 6150, Australia.
[Yurchenko, Andrey A.; O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199004, Russia.
[David, Victor A.; Scott, Rachael; Driscoll, Carlos; Menotti-Raymond, Marilyn] NCI, Lab Genom Div, Frederick, MD 21702 USA.
[Scott, Rachael; Driscoll, Carlos] Univ Maryland, College Pk, MD 20742 USA.
[Koepfli, Klaus-Peter] NIAAA, NIH, Bethesda, MD 20892 USA.
[O'Brien, Stephen J.] Nova SE Univ, Oceanog Ctr, Ft Lauderdale, FL 33314 USA.
[Menotti-Raymond, Marilyn] 5115 Westridge Rd, Bethesda, MA USA.
RP Spencer, PBS (reprint author), Murdoch Univ, Sch Vet & Life Sci, Murdoch, WA 6150, Australia.
EM P.Spencer@murdoch.edu.au
RI Yurchenko, Andrey/N-2698-2015;
OI Yurchenko, Andrey/0000-0002-2239-6902; Driscoll,
Carlos/0000-0003-2392-505X
FU Australian Research Council [LP0775356]; Western Australian Department
of Parks and Wildlife, Wildlife Identification laboratory, Murdoch
University; Laboratory of Genomic Diversity, National Cancer
Institute-Frederick; Russian Ministry of Science [11.G34.31.0068]
FX Australian Research Council (LP0775356); Western Australian Department
of Parks and Wildlife, Wildlife Identification laboratory, Murdoch
University and the Laboratory of Genomic Diversity, National Cancer
Institute-Frederick. Andrey Yurchenko and Stephen O'Brien were supported
by a Russian Ministry of Science (Mega-grant no. 11.G34.31.0068).
NR 75
TC 1
Z9 1
U1 8
U2 54
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
EI 1465-7333
J9 J HERED
JI J. Hered.
PD MAR
PY 2016
VL 107
IS 2
BP 104
EP 114
DI 10.1093/jhered/esv095
PG 11
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA DD6VY
UT WOS:000370063900002
PM 26647063
ER
PT J
AU Parker, EM
Johnson, SRL
Jones, VC
Haynie, DL
Cheng, TL
AF Parker, Elizabeth M.
Johnson, Sarah R. Lindstrom
Jones, Vanya C.
Haynie, Denise L.
Cheng, Tina L.
TI Discrepant Perspectives on Conflict Situations Among Urban
Parent-Adolescent Dyads
SO JOURNAL OF INTERPERSONAL VIOLENCE
LA English
DT Article
DE youth violence; community violence; cultural contexts
ID COMMUNITY VIOLENCE EXPOSURE; SOCIAL COGNITION; CHILDREN; ADJUSTMENT;
BEHAVIORS; ATTITUDES; MESSAGES; CONTEXT; SCHOOL; FAMILY
AB Parents influence urban youths' violence-related behaviors. To provide effective guidance, parents should understand how youth perceive conflict, yet little empirical research has been conducted regarding parent and youth perceptions of conflict. The aims of this article are to (a) report on the nature of discrepancies in attribution of fault, (b) present qualitative data about the varying rationales for fault attribution, and (c) use quantitative data to identify correlates of discrepancy including report of attitudes toward violence, parental communication, and parents' messages about retaliatory violence. Interviews were conducted with 101 parent/adolescent dyads. The study population consisted of African American female caretakers (n = 92; that is, mothers, grandmothers, aunts) and fathers (n = 9) and their early adolescents (mean age = 13.6). A total of 53 dyads were discrepant in identifying instigators in one or both videos. When discrepancy was present, the parent was more likely to identify the actor who reacted to the situation as at fault. In the logistic regression models, parental attitudes about retaliatory violence were a significant correlate of discrepancy, such that as parent attitudes supporting retaliatory violence increased, the odds of discrepancy decreased. The results suggest that parents and adolescents do not always view conflict situations similarly, which may inhibit effective parent-child communication, parental advice, and discipline. Individuals developing and implementing family-based violence prevention interventions need to be cognizant of the complexity of fault attribution and design strategies to promote conversations around attribution of fault and effective conflict management.
C1 [Parker, Elizabeth M.; Johnson, Sarah R. Lindstrom; Jones, Vanya C.; Cheng, Tina L.] Johns Hopkins Univ, Baltimore, MD USA.
[Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Parker, EM (reprint author), Johns Hopkins Univ, Dept Mental Hlth, Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Rm 895, Baltimore, MD 21205 USA.
EM emparker@jhsph.edu
OI Haynie, Denise/0000-0002-8270-6079
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) [N01-HD-2-3344];
DC-Baltimore Research Center on Child Health Disparities from the
National Institute on Minority Health and Health Disparities [P20
MD000198]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
publication was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) Contract Number N01-HD-2-3344 and the DC-Baltimore
Research Center on Child Health Disparities P20 MD000198 from the
National Institute on Minority Health and Health Disparities (TLC).
NR 32
TC 1
Z9 1
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0886-2605
EI 1552-6518
J9 J INTERPERS VIOLENCE
JI J. Interpers. Violence
PD MAR
PY 2016
VL 31
IS 6
BP 1007
EP 1025
DI 10.1177/0886260514564064
PG 19
WC Criminology & Penology; Family Studies; Psychology, Applied
SC Criminology & Penology; Family Studies; Psychology
GA DD5RO
UT WOS:000369982100003
PM 25535252
ER
PT J
AU Onega, T
Goldman, LE
Walker, RL
Miglioretti, DL
Buist, DSM
Taplin, S
Geller, BM
Hill, DA
Smith-Bindman, R
AF Onega, Tracy
Goldman, L. Elizabeth
Walker, Rod L.
Miglioretti, Diana L.
Buist, Diana S. M.
Taplin, Stephen
Geller, Berta M.
Hill, Deirdre A.
Smith-Bindman, Rebecca
TI Facility Mammography Volume in Relation to Breast Cancer Screening
Outcomes
SO JOURNAL OF MEDICAL SCREENING
LA English
DT Article
DE Cancer detection; mammography; breast cancer screening; volume
ID PERFORMANCE BENCHMARKS; DIAGNOSTIC MAMMOGRAPHY; INTERPRETIVE ACCURACY;
VARIABILITY; MORTALITY; QUALITY; PROGRAM
AB Objectives: To clarify the relationship between facility-level mammography interpretive volume and breast cancer screening outcomes.
Methods: We calculated annual mammography interpretive volumes from 2000-2009 for 116 facilities participating in the U.S. Breast Cancer Surveillance Consortium (BCSC). Radiology, pathology, cancer registry, and women's self-report information were used to determine the indication for each exam, cancer characteristics, and patient characteristics. We examined the effect of annual total volume and percentage of mammograms that were screening on cancer detection rates using multinomial logistic regression adjusting for age, race/ethnicity, time since last mammogram, and BCSC registries. Good prognosis tumours were defined as screen-detected invasive cancers that were <15mm, early stage, and lymph node negative at diagnosis.
Results: From 3,098,481 screening mammograms, 9,899 cancers were screen-detected within one year of the exam. Approximately 80% of facilities had annual total interpretive volumes of >2,000 mammograms, and 42% had >5,000. Higher total volume facilities were significantly more likely to diagnose invasive tumours with good prognoses (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.10-1.60, for total volume of 5,000-10,000/year v. 1,000-2,000/year; p-for-trend <0.001). A concomitant decrease in tumours with poor prognosis was seen (OR 0.78; 95%CI 0.63-0.98 for total volume of 5,000-10,000/year v. 1,000-2,000/year).
Conclusions: Mammography facilities with higher total interpretive volumes detected more good prognosis invasive tumours and fewer poor prognosis invasive tumours, suggesting that women attending these facilities may be more likely to benefit from screening.
C1 [Onega, Tracy] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dartmouth Inst Hlth Policy & Clin Practice, Dept Epidemiol,Dept Biomed Data Sci, Lebanon, NH USA.
[Goldman, L. Elizabeth] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Walker, Rod L.; Miglioretti, Diana L.; Buist, Diana S. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Miglioretti, Diana L.] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Taplin, Stephen] NCI, Rockville, MD USA.
[Geller, Berta M.] Univ Vermont, Dept Radiol, Burlington, VT USA.
[Geller, Berta M.] Univ Vermont, Off Hlth Promot Res, Burlington, VT USA.
[Hill, Deirdre A.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
RP Onega, T (reprint author), HB 7927 Rubin 8 DHMN,One Med Ctr Dr, Lebanon, NH USA.
EM Tracy.L.Onega@dartmouth.edu
FU American Cancer Society [SIRSG-07-271, SIRSG-07-272, SIRSG-07-273,
SIRSG-07-274, SIRSG-07-275, SIRGS-06-281, SIRSG-09-270, SIRSG-09-271];
Breast Cancer Stamp Fund; National Cancer Institute Breast Cancer
Surveillance Consortium [HHSN261201100031C]; National Cancer Institute
[R21 CA131698, K24 CA125036]
FX This work was supported by the American Cancer Society, made possible by
a generous donation from the Longaberger Company's Horizon of Hope (R)
Campaign (SIRSG-07-271, SIRSG-07-272, SIRSG-07-273, SIRSG-07-274,
SIRSG-07-275, SIRGS-06-281, SIRSG-09-270, SIRSG-09-271], the Breast
Cancer Stamp Fund, and the National Cancer Institute Breast Cancer
Surveillance Consortium (HHSN261201100031C]. This study was also
supported by the National Cancer Institute R21 CA131698 and K24
CA125036. The collection of cancer and vital status data used in this
study was supported in part by several state public health departments
and cancer registries throughout the U.S. For a full description of
these sources, please see:
http://www.breastscreening.cancer.gov/work/acknowledgement. html. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Cancer
Institute or the National Institutes of Health. Their work was
invaluable to the success of this project. We also thank the
participating women, mammography facilities and radiologists for the
data they have provided for this study. A list of the BCSC investigators
and procedures for requesting BCSC data for research purposes are
provided at: http://breastscreening.cancer.gov/
NR 24
TC 0
Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0969-1413
EI 1475-5793
J9 J MED SCREEN
JI J. Med. Screen.
PD MAR
PY 2016
VL 23
IS 1
BP 31
EP 37
DI 10.1177/0969141315595254
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DD6XF
UT WOS:000370067200005
PM 26265482
ER
PT J
AU DeMaster, LK
Liu, XH
VanBelzen, DJ
Trinite, B
Zheng, LJ
Agosto, LM
Migueles, SA
Connors, M
Sambucetti, L
Levy, DN
Pasternak, AO
O'Doherty, U
AF DeMaster, Laura K.
Liu, Xiaohe
VanBelzen, D. Jake
Trinite, Benjamin
Zheng, Lingjie
Agosto, Luis M.
Migueles, Stephen A.
Connors, Mark
Sambucetti, Lidia
Levy, David N.
Pasternak, Alexander O.
O'Doherty, Una
TI A Subset of CD4/CD8 Double-Negative T Cells Expresses HIV Proteins in
Patients on Antiretroviral Therapy
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 DOWN-MODULATION; REVERSE
TRANSCRIPTION; TRANSACTIVATOR GENE; PRIMATE LENTIVIRUSES; INFECTED
INDIVIDUALS; VIRAL REPLICATION; LATENT INFECTION; SAMHD1 RESTRICTS;
PLASMA VIREMIA
AB A major goal in HIV eradication research is characterizing the reservoir cells that harbor HIV in the presence of antiretroviral therapy (ART), which reseed viremia after treatment is stopped. In general, it is assumed that the reservoir consists of CD4(+) T cells that express no viral proteins. However, recent findings suggest that this may be an overly simplistic view and that the cells that contribute to the reservoir may be a diverse population that includes both CD4(+) and CD4(-) cells. In this study, we directly infected resting CD4(+) T cells and used fluorescence-activated cell sorting (FACS) and fiber-optic array scanning technology (FAST) to identify and image cells expressing HIV Gag. We found that Gag expression from integrated proviruses occurred in resting cells that lacked surface CD4, likely resulting from Nef- and Env-mediated receptor internalization. We also extended our approach to detect cells expressing HIV proteins in patients suppressed on ART. We found evidence that rare Gag(+) cells persist during ART and that these cells are often negative for CD4. We propose that these double-negative alpha/beta T cells that express HIV protein may be a component of the long-lived reservoir.
IMPORTANCE
A reservoir of infected cells persists in HIV-infected patients during antiretroviral therapy (ART) that leads to rebound of virus if treatment is stopped. In this study, we used flow cytometry and cell imaging to characterize protein expression in HIV-infected resting cells. HIV Gag protein can be directly detected in infected resting cells and occurs with simultaneous loss of CD4, consistent with the expression of additional viral proteins, such as Env and Nef. Gag(+) CD4(-) cells can also be detected in suppressed patients, suggesting that a subset of infected cells express proteins during ART. Understanding the regulation of viral protein expression during ART will be key to designing effective strategies to eradicate HIV reservoirs.
C1 [DeMaster, Laura K.; VanBelzen, D. Jake; Zheng, Lingjie; O'Doherty, Una] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Liu, Xiaohe; Sambucetti, Lidia] SRI Int, Ctr Canc & Metab, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
[Trinite, Benjamin; Levy, David N.] NYU, Coll Dent, Dept Basic Sci, New York, NY USA.
[Agosto, Luis M.] Boston Univ, Sch Med, Infect Dis Sect, Boston, MA 02118 USA.
[Agosto, Luis M.] Boston Med Ctr, Boston, MA USA.
[Migueles, Stephen A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Pasternak, Alexander O.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, Lab Expt Virol,Ctr Infect & Immun, NL-1105 AZ Amsterdam, Netherlands.
RP O'Doherty, U (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM unao@mail.med.upenn.edu
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [AI007632, AI116216, AI120011]
FX HHS vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Laura K. DeMaster under
grant number AI007632. HHS vertical bar NIH vertical bar National
Institute of Allergy and Infectious Diseases (NIAID) provided funding to
Una O'Doherty under grant numbers AI116216 and AI120011.
NR 90
TC 7
Z9 7
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2165
EP 2179
DI 10.1128/JVI.01913-15
PG 15
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400002
ER
PT J
AU Aoki, M
Hayashi, H
Yedidi, RS
Martyr, CD
Takamatsu, Y
Aoki-Ogata, H
Nakamura, T
Nakata, H
Das, D
Yamagata, Y
Ghosh, AK
Mitsuya, H
AF Aoki, Manabu
Hayashi, Hironori
Yedidi, Ravikiran S.
Martyr, Cuthbert D.
Takamatsu, Yuki
Aoki-Ogata, Hiromi
Nakamura, Teruya
Nakata, Hirotomo
Das, Debananda
Yamagata, Yuriko
Ghosh, Arun K.
Mitsuya, Hiroaki
TI C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors
(PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants
Highly Resistant to Various PIs, including Darunavir
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS TYPE-1 VARIANTS; DIMERIZATION INHIBITION; IN-VITRO; AMPRENAVIR
RESISTANCE; RETROVIRAL PROTEASES; EXPERIENCED PATIENTS;
MOLECULAR-DYNAMICS; GENETIC BARRIER; MUTATIONS; ACQUISITION
AB We identified three nonpeptidic HIV-1 protease inhibitors (PIs), GRL-015, -085, and -097, containing tetrahydropyrano-tetrahydrofuran (Tp-THF) with a C-5 hydroxyl. The three compounds were potent against a wild-type laboratory HIV-1 strain (HIV-1(WT)), with 50% effective concentrations (EC(50)s) of 3.0 to 49 nM, and exhibited minimal cytotoxicity, with 50% cytotoxic concentrations (CC50) for GRL-015, -085, and -097 of 80,>100, and >100 mu M, respectively. All the three compounds potently inhibited the replication of highly PI-resistant HIV-1 variants selected with each of the currently available PIs and recombinant clinical HIV-1 isolates obtained from patients harboring multidrug-resistant HIV-1 variants (HIVMDR). Importantly, darunavir (DRV) was > 1,000 times less active against a highly DRV-resistant HIV-1 variant (HIV-1(DRVRP51)); the three compounds remained active against HIV-1(DRVRP51) with only a 6.8- to 68-fold reduction. Moreover, the emergence of HIV-1 variants resistant to the three compounds was considerably delayed compared to the case of DRV. In particular, HIV-1 variants resistant to GRL-085 and -097 did not emerge even when two different highly DRV-resistant HIV-1 variants were used as a starting population. In the structural analyses, Tp-THF of GRL-015, -085, and -097 showed strong hydrogen bond interactions with the backbone atoms of active-site amino acid residues (Asp29 and Asp30) of HIV-1 protease. A strong hydrogen bonding formation between the hydroxyl moiety of Tp-THF and a carbonyl oxygen atom of Gly48 was newly identified. The present findings indicate that the three compounds warrant further study as possible therapeutic agents for treating individuals harboring wild-type HIV and/or HIVMDR.
IMPORTANCE
Darunavir (DRV) inhibits the replication of most existing multidrug-resistant HIV-1 strains and has a high genetic barrier. However, the emergence of highly DRV-resistant HIV-1 strains (HIVDRVR) has recently been observed in vivo and in vitro. Here, we identified three novel HIV-1 protease inhibitors (PIs) containing a tetrahydropyrano-tetrahydrofuran (Tp-THF) moiety with a C-5 hydroxyl (GRL-015, -085, and -097) which potently suppress the replication of HIVDRVR. Moreover, the emergence of HIV-1 strains resistant to the three compounds was considerably delayed compared to the case of DRV. The C-5 hydroxyl formed a strong hydrogen bonding interaction with the carbonyl oxygen atom of Gly48 of protease as examined in the structural analyses. Interestingly, a compound with Tp-THF lacking the hydroxyl moiety substantially decreased activity against HIVDRVR. The three novel compounds should be further developed as potential drugs for treating individuals harboring wild-type and multi-PI-resistant HIV variants as well as HIVDRVR.
C1 [Aoki, Manabu; Yedidi, Ravikiran S.; Takamatsu, Yuki; Aoki-Ogata, Hiromi; Das, Debananda; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Aoki, Manabu; Hayashi, Hironori; Aoki-Ogata, Hiromi; Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto, Japan.
[Aoki, Manabu; Hayashi, Hironori; Aoki-Ogata, Hiromi; Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto, Japan.
[Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto, Japan.
[Hayashi, Hironori; Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Res Inst, Tokyo, Japan.
[Hayashi, Hironori; Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Tokyo, Japan.
[Martyr, Cuthbert D.; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Martyr, Cuthbert D.; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Nakamura, Teruya; Yamagata, Yuriko] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kumamoto, Japan.
[Yedidi, Ravikiran S.] GSL Med Coll & Gen Hosp, Dept Pharmacol, Rajahmundry, Andhra Pradesh, India.
RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.; Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto, Japan.; Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto, Japan.; Mitsuya, H (reprint author), Natl Ctr Global Hlth & Med, Res Inst, Tokyo, Japan.; Mitsuya, H (reprint author), Natl Ctr Global Hlth & Med, Ctr Clin Sci, Tokyo, Japan.
EM mitsuyah@helix.nih.gov
OI Yedidi, Ravikiran/0000-0003-2755-1307
FU HHS/National Institutes of Health (NIH); Ministry of Health, Welfare,
and Labor of Japan; Japan Agency for Medical Research and Development
(AMED); Ministry of Education, Culture, Sports, Science and Technology
(MEXT) of Japan; National Center for Global Health & Medicine (NCGM);
Platform Project for Supporting Drug Discovery and Life Science Research
- MEXT; AMED; HHS/NIH
FX The HHS/National Institutes of Health (NIH), the Ministry of Health,
Welfare, and Labor of Japan, the Japan Agency for Medical Research and
Development (AMED), the Ministry of Education, Culture, Sports, Science
and Technology (MEXT) of Japan, the National Center for Global Health &
Medicine (NCGM), and the Platform Project for Supporting Drug Discovery
and Life Science Research supported by MEXT and AMED provided funding to
Hiroaki Mitsuya. HHS/NIH provided funding to Arun K. Ghosh.
NR 60
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2180
EP 2194
DI 10.1128/JVI.01829-15
PG 15
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400003
ER
PT J
AU de Castro-Amarante, MF
Pise-Masison, CA
McKinnon, K
Parks, RW
Galli, V
Omsland, M
Andresen, V
Massoud, R
Brunetto, G
Caruso, B
Venzon, D
Jacobson, S
Franchini, G
AF de Castro-Amarante, Maria Fernanda
Pise-Masison, Cynthia A.
McKinnon, Katherine
Parks, Robyn Washington
Galli, Veronica
Omsland, Maria
Andresen, Vibeke
Massoud, Raya
Brunetto, Giovanna
Caruso, Breanna
Venzon, David
Jacobson, Steven
Franchini, Genoveffa
TI Human T Cell Leukemia Virus Type 1 Infection of the Three Monocyte
Subsets Contributes to Viral Burden in Humans
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; I-ASSOCIATED MYELOPATHY; ACTIVE
ANTIRETROVIRAL THERAPY; CHEMOKINE RECEPTOR EXPRESSION; BREAST-MILK
MACROPHAGES; BLOOD MONONUCLEAR-CELLS; HUMAN PERIPHERAL-BLOOD; HTLV-1
PROVIRAL LOAD; DENDRITIC CELLS; MULTIPLE-SCLEROSIS
AB Because the viral DNA burden correlates with disease development, we investigated the contribution of monocyte subsets (classical, intermediate, and nonclassical monocytes) to the total viral burden in 22 human T cell leukemia virus type 1 (HTLV-1)-infected individuals by assessing their infectivity status, frequency, as well as chemotactic and phagocytic functions. All three monocyte subsets sorted from HTLV-1-infected individuals were positive for viral DNA, and the frequency of classical monocytes was lower in the blood of HTLV-1-infected individuals than in that of uninfected individuals, while the expression levels of the chemokine receptors CCR5, CXCR3, and CX3CR1 in classical monocytes were higher in HTLV-1-infected individuals than uninfected individuals; the percentage of intermediate monocytes and their levels of chemokine receptor expression did not differ between HTLV-1-infected and uninfected individuals. However, the capacity of intermediate monocytes to migrate to CCL5, the ligand for CCR5, was higher, and a higher proportion of nonclassical monocytes expressed CCR1, CXCR3, and CX3CR1. The level of viral DNA in the monocyte subsets correlated with the capacity to migrate to CCL2, CCL5, and CX3CL1 for classical monocytes, with lower levels of phagocytosis for intermediate monocytes, and with the level of viral DNA in CD8(+) and CD4(+) T cells for nonclassical monocytes. These data suggest a model whereby HTLV-1 infection augments the number of classical monocytes that migrate to tissues and become infected and the number of infected nonclassical monocytes that transmit virus to CD4(+) and CD8(+) T cells. These results, together with prior findings in a macaque model of HTLV-1 infection, support the notion that infection of monocytes by HTLV-1 is likely a requisite for viral persistence in humans.
IMPORTANCE
Monocytes have been implicated in immune regulation and disease progression in patients with HTLV-1-associated inflammatory diseases. We detected HTLV-1 DNA in all three monocyte subsets and found that infection impacts surface receptor expression, migratory function, and subset frequency. The frequency of nonclassical patrolling monocytes is increased in HTLV-1-infected individuals, and they have increased expression of CCR1, CXCR3, and CX3CR1. The viral DNA level in nonclassical monocytes correlated with the viral DNA level in CD4(+) and CD8(+) T cells. Altogether, these data suggest an increased recruitment of classical monocytes to inflammation sites that may result in virus acquisition and, in turn, facilitate virus dissemination and viral persistence. Our findings thus provide new insight into the importance of monocyte infection in viral spread and suggest targeting of monocytes for therapeutic intervention.
C1 [de Castro-Amarante, Maria Fernanda; Pise-Masison, Cynthia A.; McKinnon, Katherine; Parks, Robyn Washington; Galli, Veronica; Omsland, Maria; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[Omsland, Maria; Andresen, Vibeke] Univ Bergen, Dept Clin Sci, Translat Hematooncol Grp, Ctr Canc Biomarkers CCBIO, Bergen, Norway.
[Massoud, Raya; Brunetto, Giovanna; Caruso, Breanna; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
RP Pise-Masison, CA; Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
EM masisonc@mail.nih.gov; franchig@mail.nih.gov
FU NIH
FX This work was funded entirely by the NIH intramural program.
NR 89
TC 0
Z9 0
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2195
EP 2207
DI 10.1128/JVI.02735-15
PG 13
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400004
ER
PT J
AU Ranasinghe, S
Soghoian, DZ
Lindqvist, M
Ghebremichael, M
Donaghey, F
Carrington, M
Seaman, MS
Kaufmann, DE
Walker, BD
Porichis, F
AF Ranasinghe, Srinika
Soghoian, Damien Z.
Lindqvist, Madelene
Ghebremichael, Musie
Donaghey, Faith
Carrington, Mary
Seaman, Michael S.
Kaufmann, Daniel E.
Walker, Bruce D.
Porichis, Filippos
TI HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced
HIV-Specific CD4(+) T Cell Responses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FOLLICULAR HELPER-CELLS; VACCINE DEVELOPMENT; VIRAL-PROTEINS;
RHESUS-MONKEYS; IMMUNE CONTROL; INFECTION; BROAD; GAG; ENVELOPE;
HEMAGGLUTININ
AB Antigen-specific CD4(+) T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4(+) T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4(+) T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4(+) T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4(+) T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4(+) T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4(+) T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4(+) T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4(+) T cells and, to a lesser extent, gp41-specific CD4(+) T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.
IMPORTANCE
One of the earliest discoveries related to CD4(+) T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4(+) T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4(+) T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4(+) T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4(+) T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag-and gp41-specific CD4(+) T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.
C1 [Ranasinghe, Srinika; Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Kaufmann, Daniel E.; Walker, Bruce D.; Porichis, Filippos] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Ranasinghe, Srinika; Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Kaufmann, Daniel E.; Walker, Bruce D.; Porichis, Filippos] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Ranasinghe, Srinika; Kaufmann, Daniel E.; Walker, Bruce D.; Porichis, Filippos] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Carrington, Mary] NCI, Canc & Inflammat Program, HLA Immunogenet Sect, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Seaman, Michael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Kaufmann, Daniel E.] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ, Canada.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Ranasinghe, S; Porichis, F (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.; Ranasinghe, S; Porichis, F (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.; Ranasinghe, S; Porichis, F (reprint author), Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
EM sranasinghe@mgh.harvard.edu; fporichis@mgh.harvard.edu
FU U.S. National Institutes of Health (NIH) Scripps Center for HIV/AIDS
Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1-AI100663];
Bill and Melinda Gates Foundation [1066973, 1032144]; NIH [1R01
AI118544]; Research Scholar Career Award of the Quebec Health Research
Fund; Harvard CFAR [2P30 AI060354, P30 AI060354]; Mark and Lisa Schwartz
Foundation; CAVD; International HIV Controllers Study - Bill and Melinda
Gates Foundation; AIDS Healthcare Foundation; Intramural Research
Program of the NIH; Center for Cancer Research [HHSN261200800001E];
Frederick National Lab
FX This study was funded by the U.S. National Institutes of Health (NIH)
Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery
(CHAVI-ID and 1UM1-AI100663) to B.D.W. and D.E.K. This project has also
been funded in part by the Bill and Melinda Gates Foundation
Collaboration for AIDS Vaccine Discovery, CAVD grant 1066973 to B.D.W.
and CAVD grant 1032144 to M.S.S. F.P is funded by a NIH 1R01 AI118544.
D.E.K is supported by a Research Scholar Career Award of the Quebec
Health Research Fund. M.G. is supported by Harvard CFAR 2P30 AI060354.
The HIV Controller Cohort was supported by the Mark and Lisa Schwartz
Foundation, the CAVD, and in part by the International HIV Controllers
Study, funded by the Bill and Melinda Gates Foundation, the AIDS
Healthcare Foundation, and Harvard CFAR (P30 AI060354). This research
was also supported in part by funding from the Intramural Research
Program of the NIH, Frederick National Lab, and Center for Cancer
Research to M.C. under contract number HHSN261200800001E.
NR 42
TC 5
Z9 5
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2208
EP 2220
DI 10.1128/JVI.02278-15
PG 13
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400005
ER
PT J
AU Riddick, NE
Wu, F
Matsuda, K
Whitted, S
Ourmanov, I
Goldstein, S
Goeken, RM
Plishka, RJ
Buckler-White, A
Brenchley, JM
Hirsch, VM
AF Riddick, Nadeene E.
Wu, Fan
Matsuda, Kenta
Whitted, Sonya
Ourmanov, Ilnour
Goldstein, Simoy
Goeken, Robert M.
Plishka, Ronald J.
Buckler-White, Alicia
Brenchley, Jason M.
Hirsch, Vanessa M.
TI Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry
Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15
and CXCR6 as Viral Coreceptors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; INFECTED SOOTY MANGABEYS; IN-VIVO REPLICATION; IMMUNE
ACTIVATION; MANDRILLUS-SPHINX; RHESUS MACAQUES; DOWN-REGULATION;
HIV-INFECTION; NATURAL HOST; CCR5
AB African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4(+) T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4(+) T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals.
IMPORTANCE
African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4(+) T cells, the preferred target cells of SIV.
C1 [Riddick, Nadeene E.; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M.; Plishka, Ronald J.; Buckler-White, Alicia; Brenchley, Jason M.; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
FU NIAID
FX Intramural Program of NIAID provided funding to Vanessa M Hirsch.
NR 71
TC 4
Z9 4
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2316
EP 2331
DI 10.1128/JVI.02529-15
PG 16
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400015
PM 26656714
ER
PT J
AU Xia, C
Vijayan, M
Pritzl, CJ
Fuchs, SY
McDermott, AB
Hahm, B
AF Xia, Chuan
Vijayan, Madhuvanthi
Pritzl, Curtis J.
Fuchs, Serge Y.
McDermott, Adrian B.
Hahm, Bumsuk
TI Hemagglutinin of Influenza A Virus Antagonizes Type I Interferon (IFN)
Responses by Inducing Degradation of Type I IFN Receptor 1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SENSOR RIG-I; V-PROTEIN; ALPHA RECEPTOR; NS1 PROTEIN; C-PROTEIN; SURFACE
EXPRESSION; DENDRITIC CELLS; DOWN-REGULATION; SUBUNIT IFNAR1;
INFECTED-CELLS
AB Influenza A virus (IAV) employs diverse strategies to circumvent type I interferon (IFN) responses, particularly by inhibiting the synthesis of type I IFNs. However, it is poorly understood if and how IAV regulates the type I IFN receptor (IFNAR)-mediated signaling mode. In this study, we demonstrate that IAV induces the degradation of IFNAR subunit 1 (IFNAR1) to attenuate the type I IFN-induced antiviral signaling pathway. Following infection, the level of IFNAR1 protein, but not mRNA, decreased. Indeed, IFNAR1 was phosphorylated and ubiquitinated by IAV infection, which resulted in IFNAR1 elimination. The transiently overexpressed IFNAR1 displayed antiviral activity by inhibiting virus replication. Importantly, the hemagglutinin (HA) protein of IAV was proved to trigger the ubiquitination of IFNAR1, diminishing the levels of IFNAR1. Further, influenza A viral HA1 subunit, but not HA2 subunit, downregulated IFNAR1. However, viral HA-mediated degradation of IFNAR1 was not caused by the endoplasmic reticulum (ER) stress response. IAV HA robustly reduced cellular sensitivity to type I IFNs, suppressing the activation of STAT1/STAT2 and induction of IFN-stimulated antiviral proteins. Taken together, our findings suggest that IAV HA causes IFNAR1 degradation, which in turn helps the virus escape the powerful innate immune system. Thus, the research elucidated an influenza viral mechanism for eluding the IFNAR signaling pathway, which could provide new insights into the interplay between influenza virus and host innate immunity.
IMPORTANCE
Influenza A virus (IAV) infection causes significant morbidity and mortality worldwide and remains a major health concern. When triggered by influenza viral infection, host cells produce type I interferon (IFN) to block viral replication. Although IAV was shown to have diverse strategies to evade this powerful, IFN-mediated antiviral response, it is not well-defined if IAV manipulates the IFN receptor-mediated signaling pathway. Here, we uncovered that influenza viral hemagglutinin (HA) protein causes the degradation of type I IFN receptor subunit 1 (IFNAR1). HA promoted phosphorylation and polyubiquitination of IFNAR1, which facilitated the degradation of this receptor. The HA-mediated elimination of IFNAR1 notably decreased the cells' sensitivities to type I IFNs, as demonstrated by the diminished expression of IFN-induced antiviral genes. This discovery could help us understand how IAV regulates the host innate immune response to create an environment optimized for viral survival in host cells.
C1 [Xia, Chuan; Vijayan, Madhuvanthi; Pritzl, Curtis J.; Hahm, Bumsuk] Univ Missouri, Dept Surg, Columbia, MO USA.
[Xia, Chuan; Vijayan, Madhuvanthi; Pritzl, Curtis J.; Hahm, Bumsuk] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO USA.
[Fuchs, Serge Y.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA.
[McDermott, Adrian B.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Hahm, B (reprint author), Univ Missouri, Dept Surg, Columbia, MO USA.; Hahm, B (reprint author), Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO USA.
EM hahmb@health.missouri.edu
FU HHS \ NIH \ National Cancer Institute (NCI) [R01CA092900]; HHS \ NIH \
National Institute of Allergy and Infectious Diseases (NIAID)
[R01AI091797]; Intramural Research Program, Vaccine Research Center,
National Institute of Allergy and Infectious Diseases (NIAID)
FX HHS vertical bar NIH vertical bar National Cancer Institute (NCI)
provided funding to Serge Y. Fuchs under grant number R01CA092900. HHS
vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Bumsuk Hahm under grant
number R01AI091797. Intramural Research Program, Vaccine Research
Center, National Institute of Allergy and Infectious Diseases (NIAID)
provided funding to Adrian B. McDermott.
NR 87
TC 4
Z9 4
U1 2
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAR
PY 2016
VL 90
IS 5
BP 2403
EP 2417
DI 10.1128/JVI.02749-15
PG 15
WC Virology
SC Virology
GA DD6AF
UT WOS:000370005400021
ER
PT J
AU Schwartz, DP
Dastgir, J
Salman, A
Lear, B
Bonnemann, CG
Lehky, TJ
AF Schwartz, Daniel P.
Dastgir, Jahannaz
Salman, Anam
Lear, Barbara
Boennemann, Carsten G.
Lehky, Tanya J.
TI ELECTRICAL IMPEDANCE MYOGRAPHY DISCRIMINATES CONGENITAL MUSCULAR
DYSTROPHY FROM CONTROLS
SO MUSCLE & NERVE
LA English
DT Article
DE congenital muscular dystrophy; electrical impedance myography; handheld
array; pediatric; subcutaneous fat
ID HELD ELECTRODE ARRAY; DISEASE; ATROPHY
AB Introduction: Electrical impedance myography (EIM) is an emerging non-invasive, highly reproducible electrophysiological technique that objectively characterizes muscle structure and composition by measuring bioimpedance. We assessed the ability of EIM ability to discriminate 2 forms of congenital muscular dystrophy (CMD), laminin alpha 2 (LAMA2)-deficient CMD and collagen VI-deficient (COL6) CMD, from a group of healthy children. We also investigated correlations between subcutaneous fat thickness and EIM parameters. Methods: Twenty-eight children with LAMA2 CMD (n=12) or COL6 (n=16) CMD and 18 normal children underwent EIM testing. Results: The EIM 50-kHZ phase was decreased in LAMA2 and COL6 CMD when compared with controls (P<0.001). Reactance, however, was decreased in COL6 but not LAMA2 CMD compared with controls (P<0.001). Conclusions: Our findings suggest that EIM may be useful in discriminating CMD from controls and may serve as a useful biomarker to follow disease progression in clinical trials.
C1 [Schwartz, Daniel P.; Salman, Anam; Lear, Barbara; Lehky, Tanya J.] NINDS, Electromyog Sect, NIH, Bldg 10,CRC Room 7SW-5680,10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA.
[Dastgir, Jahannaz; Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Dastgir, Jahannaz] Columbia Univ, Med Ctr, Dept Neurol, Div Pediat Neurol Neuromuscular Med, New York, NY USA.
RP Lehky, TJ (reprint author), NINDS, Electromyog Sect, NIH, Bldg 10,CRC Room 7SW-5680,10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA.
EM lehkyt@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Healthy [NINDS 13-N-0165, NINDS 12-N0095]
FX The authors wish to thank the Congenital Muscular Dystrophy Comparative
Outcome Measures (CMD-COM) study group. This study was supported by the
Intramural Research Program at the National Institute of Neurological
Disorders and Stroke, National Institutes of Healthy (NINDS 13-N-0165
and NINDS 12-N0095).
NR 14
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
EI 1097-4598
J9 MUSCLE NERVE
JI Muscle Nerve
PD MAR
PY 2016
VL 53
IS 3
BP 402
EP 406
DI 10.1002/mus.24770
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DD3QI
UT WOS:000369837200010
PM 26179210
ER
PT J
AU Morris, LS
Baek, K
Kundu, P
Harrison, NA
Frank, MJ
Voon, V
AF Morris, Laurel S.
Baek, Kwangyeol
Kundu, Prantik
Harrison, Neil A.
Frank, Michael J.
Voon, Valerie
TI Biases in the Explore-Exploit Tradeoff in Addictions: The Role of
Avoidance of Uncertainty
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID PREFRONTAL CORTEX; DECISION-MAKING; INDIVIDUAL-DIFFERENCES; FRONTOPOLAR
CORTEX; NEURAL MECHANISMS; DRUG-ADDICTION; FRONTAL POLE; RISK; ALCOHOL;
IMPULSIVITY
AB We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.
C1 [Morris, Laurel S.; Voon, Valerie] Univ Cambridge, Inst Behav & Clin Neurosci, Cambridge, England.
[Baek, Kwangyeol; Kundu, Prantik; Voon, Valerie] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Level E4,Box 189,Hills Rd, Cambridge CB2 0QQ, England.
[Baek, Kwangyeol; Kundu, Prantik; Voon, Valerie] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Kundu, Prantik] Brighton & Sussex Med Sch, Dept Psychiat, Brighton, E Sussex, England.
[Harrison, Neil A.] Brown Univ, Brown Inst Brain Sci Psychiat & Human Behav, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA.
[Frank, Michael J.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England.
[Voon, Valerie] NIHR Cambridge Biomed Res Ctr, Cambridge, England.
RP Voon, V (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Level E4,Box 189,Hills Rd, Cambridge CB2 0QQ, England.
EM vv247@cam.ac.uk
OI Harrison, Neil/0000-0002-9584-3769; Kundu, Prantik/0000-0001-9367-3068
FU Wellcome Trust Fellowship grant [093705/Z/10/Z]; Cambridge NIHR
Biomedical Research Centre; NIMH; NSF grants
FX The study was funded by the Wellcome Trust Fellowship grant for VV
(093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. MJF is
funded by NIMH and NSF grants, and is consultant for Hoffmann-LaRoche
pharmaceuticals. The remaining authors declare no conflict of interest.
NR 43
TC 2
Z9 2
U1 3
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2016
VL 41
IS 4
BP 940
EP 948
DI 10.1038/npp.2015.208
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DD2YA
UT WOS:000369786900003
PM 26174598
ER
PT J
AU Soto, PL
Hiranita, T
Xu, M
Hursh, SR
Grandy, DK
Katz, JL
AF Soto, Paul L.
Hiranita, Takato
Xu, Ming
Hursh, Steven R.
Grandy, David K.
Katz, Jonathan L.
TI Dopamine D-2-Like Receptors and Behavioral Economics of Food
Reinforcement
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID MICE LACKING DOPAMINE-D-2; INDUCED LOCOMOTOR-ACTIVITY; MUTANT MICE;
DEFICIENT MICE; D2 RECEPTORS; COCAINE DISCRIMINATION; NEGATIVE SYMPTOMS;
KNOCKOUT MICE; ANIMAL-MODEL; MOTIVATION
AB Previous studies suggest dopamine (DA) D-2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D-2-like receptor subtypes, knockout (KO) mice completely lacking DA D-2, D-3, or D-4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KOthan WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D-2-like receptor subtype mediating the reinforcing effectiveness of food.
C1 [Soto, Paul L.] Texas Tech Univ, Dept Educ Psychol & Leadership, 3008 18th St, Lubbock, TX 79410 USA.
[Hiranita, Takato; Katz, Jonathan L.] NIDA, Psychobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD USA.
[Xu, Ming] Univ Chicago, Dept Anesthesia & Crit Care, Box 428, Chicago, IL 60637 USA.
[Hursh, Steven R.] Inst Behav Resources, Baltimore, MD USA.
[Grandy, David K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
[Grandy, David K.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA.
RP Soto, PL (reprint author), Texas Tech Univ, Dept Educ Psychol & Leadership, 3008 18th St, Lubbock, TX 79410 USA.
EM paul.soto@ttu.edu
FU National Institute on Drug Abuse (NIDA) Intramural Research Program
(IRP) [R01-DA025088, R21-DA036921]; Shands Hospital at the University of
Florida
FX The current studies were supported by funding from the National
Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) to JLK
and by R01-DA025088 and R21-DA036921 to MX. Neither the NIDA IRP nor the
extramural program had a role in the design of the study, collection and
analysis of data, or the decision to publish. SRH has received funding
from the Federal Aviation Administration, Federal Rail Road
Administration, Washington Metropolitan Area Transit Authority, NASA,
UPS, Airline Pilots Association, and FedEx. PLS has received funding
from Shands Hospital at the University of Florida. The authors declare
no conflict of interest.
NR 39
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2016
VL 41
IS 4
BP 971
EP 978
DI 10.1038/npp.2015.223
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DD2YA
UT WOS:000369786900006
PM 26205210
ER
PT J
AU You, ZB
Wang, B
Liu, QR
Wu, Y
Otvos, L
Wise, RA
AF You, Zhi-Bing
Wang, Bin
Liu, Qing-Rong
Wu, Yan
Otvos, Laszlo
Wise, Roy A.
TI Reciprocal Inhibitory Interactions Between the Reward-Related Effects of
Leptin and Cocaine
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; CORTICOTROPIN-RELEASING-FACTOR; CONDITIONED
PLACE PREFERENCE; DOPAMINE NEURONS; DRUG-ADDICTION; NUCLEUS-ACCUMBENS;
INTRAVENTRICULAR INSULIN; SECONDARY REINFORCEMENT; MAINTENANCE
TREATMENT; MOLECULAR-MECHANISMS
AB Cocaine is habit-forming because of its ability to enhance dopaminergic neurotransmission in the forebrain. In addition to neuronal inputs, forebrain dopamine circuits are modulated by hormonal influences; one of these is leptin, an adipose-derived hormone that attenuates the rewarding effects of food-and hunger-associated brain stimulation reward. Here we report reciprocal inhibition between the rewardrelated effects of leptin and the reward-related effects of cocaine in rats. First, we report that cocaine and the expectancy of cocaine each depresses plasma leptin levels. Second, we report that exogenous leptin, given systemically or directly into the ventral tegmental area, attenuates the ability of cocaine to elevate dopamine levels in the nucleus accumbens, the ability of cocaine to establish a conditioned place preference, and the ability of cocaine-predictive stimuli to prolong responding in extinction of cocaine-seeking. Thus, whereas leptin represents an endogenous antagonist of the habit-forming and habit-sustaining effects of cocaine, this antagonism is attenuated by cocaine and comes to be attenuated by the expectancy of cocaine.
C1 [You, Zhi-Bing; Wang, Bin; Liu, Qing-Rong; Wise, Roy A.] NIDA, Dept Hlth & Human Serv, Behav Neurosci Branch, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
[Wu, Yan] Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Zhejiang, Peoples R China.
[Otvos, Laszlo] Temple Univ, Dept Biol, Philadelphia, PA 19122 USA.
RP Wise, RA (reprint author), NIDA, Dept Hlth & Human Serv, Behav Neurosci Branch, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rwise@intra.nida.nih.gov
RI Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU Intramural Research Program of the National Institute on Drug Abuse
FX This study was funded by the Intramural Research Program of the National
Institute on Drug Abuse.
NR 67
TC 2
Z9 2
U1 6
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2016
VL 41
IS 4
BP 1024
EP 1033
DI 10.1038/npp.2015.230
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DD2YA
UT WOS:000369786900011
PM 26243270
ER
PT J
AU Martinez, PE
Rubinow, DR
Nieman, LK
Koziol, DE
Morrow, L
Schiller, CE
Cintron, D
Thompson, KD
Khine, KK
Schmidt, PJ
AF Martinez, Pedro E.
Rubinow, David R.
Nieman, Lynnette K.
Koziol, Deloris E.
Morrow, Leslie
Schiller, Crystal E.
Cintron, Dahima
Thompson, Karla D.
Khine, Khursheed K.
Schmidt, Peter J.
TI 5 alpha-Reductase Inhibition Prevents the Luteal Phase Increase in
Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with
Premenstrual Dysphoric Disorder
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID 5 ALPHA-PREGNANE-3,20-DIONE; MENSTRUAL-CYCLE; MOOD DISORDERS; HUMAN
BRAIN; RECEPTOR; SENSITIVITY; EXPRESSION; STEROIDS; ANXIETY;
PROGESTERONE
AB Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5a-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, doubleblind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/ day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the lowdose dutasteride on 5a-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5a-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.
C1 [Martinez, Pedro E.; Thompson, Karla D.; Khine, Khursheed K.; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Bldg 10CRC,Room 25330,10 Ctr Dr MSC 1277, Bethesda, MD 20892 USA.
[Rubinow, David R.; Morrow, Leslie; Schiller, Crystal E.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Reprod & Adult Endocrinol, NIH, DHSS, Bethesda, MD USA.
[Koziol, Deloris E.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Cintron, Dahima] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA.
RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10CRC,Room 25330,10 Ctr Dr MSC 1277, Bethesda, MD 20892 USA.
EM peterschmidt@mail.nih.gov
FU NIMH; NIH
FX The Intramural Research Program of the NIMH, NIH supported this study
and GlaxoSmithKline Pharmaceuticals provided material support; however,
neither institution was involved in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; and
preparation, review, or approval of the manuscript. Dr Nieman receives
compensation from UpToDate, Inc. for contributing to the adrenal
section. Dr Schmidt had full access to all the data in this study and
takes responsibility for the integrity of the data and the accuracy of
the data analysis. Drs. Martinez, Schmidt and Koziol performed data
analyses for this study. This work was written as part of Peter J
Schmidt's official duties as a Government employee. The views expressed
in this article do not necessarily represent the views of the NIMH, NIH,
HHS, or the United States Government. This research was supported by the
Intramural Research Program of the NIMH, NIH. The authors declare no
conflict of interest.
NR 47
TC 4
Z9 4
U1 4
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2016
VL 41
IS 4
BP 1093
EP 1102
DI 10.1038/npp.2015.246
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DD2YA
UT WOS:000369786900017
PM 26272051
ER
PT J
AU Atkinson, JC
Clark, DB
AF Atkinson, J. C.
Clark, D. B.
TI Design and interpretation of clinical research studies in oral medicine:
a brief review
SO ORAL DISEASES
LA English
DT Review
DE clinical research; epidemiology; oral medicine
ID RISK; SELECTION; CANCER; METAANALYSES; QUALITY; TRIALS
AB The objective of this short review is to help researchers improve the designs of their clinical studies. Also included is a discussion of the level of evidence provided by the various clinical research study designs.
C1 [Atkinson, J. C.] Natl Inst Dent & Craniofacial Res, Clin Res Ctr, NIH, 6701 Democracy Blvd,Room 634,MSC 4878, Bethesda, MD 20892 USA.
[Clark, D. B.] Natl Inst Dent & Craniofacial Res, Behav & Social Sci Res Branch, NIH, Bethesda, MD 20892 USA.
RP Atkinson, JC (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res Ctr, NIH, 6701 Democracy Blvd,Room 634,MSC 4878, Bethesda, MD 20892 USA.
EM jatkinso@mail.nih.gov
FU Intramural NIH HHS [Z99 DE999999]
NR 21
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Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD MAR
PY 2016
VL 22
IS 2
BP 87
EP 92
DI 10.1111/odi.12385
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DD6SG
UT WOS:000370053900004
PM 26519096
ER
PT J
AU Michels, KA
Hartmann, KE
Archer, KR
Ye, F
Edwards, DRV
AF Michels, Kara A.
Hartmann, Katherine E.
Archer, Kristin R.
Ye, Fei
Edwards, Digna R. Velez
TI The Relationship between Total Fibroid Burden and First Trimester
Bleeding and Pain
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE leiomyoma; pregnancy; prospective studies; uterine haemorrhage; pain
ID UTERINE LEIOMYOMAS; PREGNANCY; COMPLICATIONS; DIAGNOSIS; RACE; AGE
AB BackgroundFew studies comment on the association between fibroids and symptoms among pregnant women. These studies generally are retrospective and do not to assess the influence of number of tumours or their volume on risk of symptoms.
MethodsRight from the Start is a prospective cohort that enrolled pregnant women from the southeastern USA between 2000 and 2012. In the first trimester, all participants had standardised ultrasounds to determine the presence or absence of fibroids. Symptoms were queried in a telephone survey. We used polytomous logistic regression to model odds of bleeding, pain, or both symptoms in relation to increasing total fibroid number and volume among white and black women.
ResultsAmong 4509 participants, the prevalence of fibroids was 11%. Among those reporting symptoms (70%), 11% reported only bleeding, 59% reported only pain, and 30% reported both symptoms. After adjusting for age, race, parity, hypertension, smoking, alcohol use, and study site, increasing number of fibroids was associated with pain [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.00, 1.33] and both symptoms [OR 1.25, 95% CI 1.08, 1.45] but not with bleeding among all women. Fibroid volume was not associated with symptoms among black women, but white women with the smallest fibroid volumes were more likely to report both symptoms than those without fibroids [OR 1.79, 95% CI 1.17, 2.72].
ConclusionsVery large tumours are not requisite for experiencing symptoms, as small fibroids and increasing number of tumours are associated with pain and both symptoms.
C1 [Michels, Kara A.; Hartmann, Katherine E.; Edwards, Digna R. Velez] Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Genet Inst, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Hartmann, Katherine E.; Edwards, Digna R. Velez] Vanderbilt Univ, Sch Med, Dept Obstet & Gynecol, Nashville, TN 37212 USA.
[Archer, Kristin R.] Vanderbilt Univ, Sch Med, Dept Orthoped Surg, Nashville, TN 37212 USA.
[Archer, Kristin R.] Vanderbilt Univ, Sch Med, Dept Phys Med & Rehabil, Nashville, TN 37212 USA.
[Ye, Fei] Vanderbilt Univ, Sch Med, Div Canc Stat, Dept Biostat, Nashville, TN 37212 USA.
[Michels, Kara A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
RP Edwards, DRV (reprint author), Vanderbilt Epidemiol Ctr, 2525 West End Ave,Suite 600 6th Floor, Nashville, TN 37203 USA.
EM digna.r.velez.edwards@vanderbilt.edu
OI Michels, Kara/0000-0003-2431-2079
FU Eunice Kennedy Shriver National Institute of Child and Human Development
[R01HD043883, R01HD049675]; American Water Works Association Research
Foundation [2579]; Building Interdisciplinary Research Careers in
Women's Health career development program [K12HD043483-12]; NIH
[1R01HD074711, 1R03HD078567]; Vanderbilt CTSA from NCATS/NIH
[5TL1RR024978, ULTR000445]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health
FX None of the authors has any relevant financial, personal, political,
intellectual, or religious interests to disclose. This research was
supported by grants from the Eunice Kennedy Shriver National Institute
of Child and Human Development (R01HD043883 and R01HD049675) and the
American Water Works Association Research Foundation (2579). Additional
funds were provided by the Building Interdisciplinary Research Careers
in Women's Health career development program (K12HD043483-12), NIH grant
1R01HD074711 and NIH grant 1R03HD078567. This research was supported in
part by an a TL1 training grant (5TL1RR024978) through the Vanderbilt
CTSA grant ULTR000445 from NCATS/NIH and in part by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health
(co-author KAM).
NR 17
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAR
PY 2016
VL 30
IS 2
BP 115
EP 123
DI 10.1111/ppe.12256
PG 9
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA DD9ME
UT WOS:000370249000003
PM 26525634
ER
PT J
AU Koks, N
Ghassabian, A
Greaves-Lord, K
Hofman, A
Jaddoe, VWV
Verhulst, FC
Tiemeier, H
AF Koks, Natasja
Ghassabian, Akhgar
Greaves-Lord, Kirstin
Hofman, Albert
Jaddoe, Vincent W. V.
Verhulst, Frank C.
Tiemeier, Henning
TI Maternal C-Reactive Protein Concentration in Early Pregnancy and Child
Autistic Traits in the General Population
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE C-reactive protein; pregnancy; autistic traits; longitudinal; children
ID MENDELIAN RANDOMIZATION; SPECTRUM DISORDERS; HEART-DISEASE; ASSOCIATION;
WOMEN; CBCL; MEN
AB BackgroundExposure to elevated levels of inflammatory markers during pregnancy has been suggested as possible aetiologic factor in the occurrence of autism spectrum disorder (ASD). In this study, we investigated the prospective relation between maternal C-reactive protein (CRP) during early pregnancy and children's autistic traits in the general population.
MethodsIn a large population-based cohort in the Netherlands, we measured maternal CRP levels before 18 weeks of gestation (N=4165). Parents reported on their children's autistic traits at age 6 years using the Social Responsiveness Scale, and the Pervasive Developmental Problem scale. Regression models were used to examine the relation between maternal CRP levels and autistic traits in children.
ResultsCompared with the reference group (CRP<2.3mg/L), elevated levels of CRP (>7.8mg/L) in pregnant women were associated with higher Social Responsiveness Scale scores in children [=0.055, 95% confidence interval (CI) 0.033, 0.078]; however, the effect was strongly attenuated after adjustment for several socioeconomic factors and in particular by maternal health-related factors including body mass index (fully adjusted model =0.018, 95% CI -0.005, 0.042). We found no relation between maternal CRP levels and pervasive developmental problem.
ConclusionsOur results suggest that the association between elevated levels of maternal CRP in pregnancy and autistic traits in children is confounded by maternal health-related and socioeconomic factors. Further studies are needed to explore whether other maternal inflammatory markers during pregnancy, as a response to maternal inflammation, are associated with the development of autistic traits in the offspring.
C1 [Koks, Natasja; Ghassabian, Akhgar; Jaddoe, Vincent W. V.] Erasmus Univ, Generat Study Grp R, Med Ctr, Rotterdam, Netherlands.
[Hofman, Albert; Jaddoe, Vincent W. V.; Tiemeier, Henning] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Tiemeier, Henning] Erasmus Univ, Med Ctr, Dept Psychiat, Rotterdam, Netherlands.
[Koks, Natasja; Ghassabian, Akhgar; Greaves-Lord, Kirstin; Verhulst, Frank C.; Tiemeier, Henning] Erasmus Univ, Dept Child & Adolescent Psychiat Psychol, Sophia Childrens Hosp Rotterdam, Med Ctr, Rotterdam, Netherlands.
[Jaddoe, Vincent W. V.] Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Pediat, Rotterdam, Netherlands.
[Greaves-Lord, Kirstin] Yulius, Yulius Acad, Dordrecht, Netherlands.
[Ghassabian, Akhgar] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
RP Ghassabian, A (reprint author), Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, POB 2060, NL-3000 CB Rotterdam, Netherlands.
EM a.ghassabian@erasmusmc.nl
OI Ghassabian, Akhgar/0000-0001-9551-4706
FU Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam;
Netherlands Organization for Health Research and Development [ZonMw
10.000.1003]; Netherlands Organization for Scientific Research (NWO);
Ministry of Health, Welfare and Sport; Ministry of Youth and Families;
European Community [212652]; VIDI grant of ZonMw [2009-017.106.370];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD)
FX The general design of Generation R Study is made possible by financial
support from the Erasmus Medical Center, Rotterdam, the Erasmus
University Rotterdam, the Netherlands Organization for Health Research
and Development (ZonMw 10.000.1003), the Netherlands Organization for
Scientific Research (NWO), the Ministry of Health, Welfare and Sport and
the Ministry of Youth and Families. The authors gratefully acknowledge
the contribution of general practitioners, hospitals, midwifes, and
pharmacies in Rotterdam. The work of Dr. H. Tiemeier and Dr. A.
Ghassabian was supported by a research grant sponsored by the European
Community's 7th Framework Programme (FP7/2008-13) under Grant Number
212652 (NUTRIMENTHE project, 'The Effect of Diet on the Mental
Performance of Children'). Dr. H. Tiemeier was also supported by the
VIDI grant of ZonMw (2009-017.106.370). Also, Dr. A. Ghassabian was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD).
NR 35
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD MAR
PY 2016
VL 30
IS 2
BP 181
EP 189
DI 10.1111/ppe.12261
PG 9
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA DD9ME
UT WOS:000370249000010
PM 26860445
ER
PT J
AU Guo, L
Hamre, J
Davis, M
Parchment, RE
AF Guo, Liang
Hamre, John, III
Davis, Myrtle
Parchment, Ralph E.
TI Human CD34(+) progenitor hematopoiesis in liquid culture for in vitro
assessment of drug-induced myelotoxicity
SO TOXICOLOGY IN VITRO
LA English
DT Article
DE Hematotoxicity; CD34(+) progenitors; CD11b/CD13; Microplate culture;
High content analysis (HCA); High throughput screening (HTS); FACS
analysis
ID COLONY-FORMING CELLS; CHRONIC MYELOID-LEUKEMIA; CFU-GM ASSAY;
FLOW-CYTOMETRY; TOXICITY; VIVO; SENSITIVITY; MARROW; MURINE; MODEL
AB Utilization of validated CFU-GM assays for myelotoxicity screening is hampered by its labor-intensive and low throughput nature. Herein, we transformed the defined CFU-GM assay conditions and IC90 endpoint into a higher throughput format Human CD34(+) hematopoietic progenitors were cultured in a 96-well plate for 14 days with the same cytokine (rhGM-CSF) used in the CFU-GM assay. Expansion and differentiation toward myeloid lineages were manifested by characteristic changes in nuclear and cytoplasmic morphology and by temporal expression patterns of CD34, CD11b and CD13 markers. Inhibition of CD34(+) cell myelopoiesis by 12 anticancer drugs known to induce myelotoxicity in the clinic was quantifiable using either general cytotoxicity endpoints (cell growth area or total nucleus count) or lineage specific readouts (count of cells expressing CD11b and/or CD13). The IC50 and IC90 values derived from the concentration-response curves of 14-day drug exposure in CD34(+) cell culture were highly correlated with those from the international validation study of the CFU-GM assay, demonstrating capability to assess general cytotoxicity, cell proliferation and myelopoiesis simultaneously. These results suggest that this human CD34(+) hematopoietic progenitor cell assay can be used as a direct replacement for the validated, low throughput CFU-GM assay, and could expand application of in vitro myelotoxicity testing. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Guo, Liang; Hamre, John, III; Davis, Myrtle; Parchment, Ralph E.] Frederick Natl Lab Canc Res, Lab Invest Toxicol, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
Frederick Natl Lab Canc Res, Appl & Dev Res Directorate, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
RP Parchment, RE (reprint author), Frederick Natl Lab Canc Res, Appl & Dev Res Directorate, Leidos Biomed Res Inc, 1050 Boyles St,Bldg 425, Frederick, MD 21702 USA.
EM liang.guo@fnlcr.nih.gov; john.hamre@fnlcr.nih.gov;
davismillinm@mail.nih.gov; parchmentr@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Developmental Therapeutics Program in the Division
of Cancer Treatment and Diagnosis of the National Cancer Institute
FX The authors would like to thank Dr. Holger Behrsing for exploratory work
on other testing formats and methods to replace the validated CFU-GM
assay, Dr. Sandy Eldridge at the Division of Cancer Treatment and
Diagnosis (DUD), National Cancer Institute (NCI) for evaluation of
cytospin slides from cultured CD34 + cells, and Dr. William Kopp, Bernie
Thompson and Refika Turnier at the Frederick National Laboratory for
Cancer Research for conducting the FACS analysis, and Dr. Joseph
Tomaszewski at DCTD, NCI for programmatic support. This project has been
funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported [in part] by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute.
NR 31
TC 0
Z9 0
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-2333
J9 TOXICOL IN VITRO
JI Toxicol. Vitro
PD MAR
PY 2016
VL 31
BP 103
EP 113
DI 10.1016/j.tiv.2015.11.017
PG 11
WC Toxicology
SC Toxicology
GA DD4GE
UT WOS:000369879700012
PM 26616282
ER
PT J
AU Lopes, FL
Hou, L
Boldt, ABW
Kassem, L
Alves, VM
Nardi, AE
McMahon, FJ
AF Lopes, Fabiana L.
Hou, Liping
Boldt, Angelica B. W.
Kassem, Layla
Alves, Veronica M.
Nardi, Antonio E.
McMahon, Francis J.
TI Finding Rare, Disease-Associated Variants in Isolated Groups: Potential
Advantages of Mennonite Populations
SO HUMAN BIOLOGY
LA English
DT Article
DE AMISH; ANABAPTIST; BIPOLAR; BOTTLENECK; DRIFT; ISOLATE; MENNONITE;
MIGRATION
ID DUTCH-GERMAN MENNONITE; BIPOLAR DISORDER; IDENTIFIES RARE;
LOW-FREQUENCY; PLAIN PEOPLE; AMISH; MUTATIONS; GENETICS; ARCHITECTURE;
SUSCEPTIBILITY
AB Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses.
C1 [Lopes, Fabiana L.; Hou, Liping; Kassem, Layla; McMahon, Francis J.] Natl Inst Hlth, US Dept Hlth & Human Serv, Human Genet Branch, Natl Inst Mental Hlth,Intramural Res Program, Bethesda, MD USA.
[Lopes, Fabiana L.; Alves, Veronica M.; Nardi, Antonio E.] Univ Fed Rio de Janeiro, Inst Psychiat, Lab Pan & Respirat, Rio De Janeiro, Brazil.
[Boldt, Angelica B. W.] Univ Fed Parana, Lab Genet Mol Humana, Dept Genet, Curitiba, Parana, Brazil.
RP McMahon, FJ (reprint author), Natl Inst Hlth, US Dept Hlth & Human Serv, Human Genet Branch, Natl Inst Mental Hlth,Intramural Res Program, Bethesda, MD USA.; McMahon, FJ (reprint author), Human Genet Branch, 35 Convent Dr, Bethesda, MD 20892 USA.
EM mcmahonf@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
Bethesda, MD, USA; Federal University of Rio de Janeiro, Rio de Janeiro,
Brazil; Federal University of Parana, Curitiba, Brazil
FX This review was written with the support of the Intramural Research
Program of the National Institute of Mental Health, Bethesda, MD, USA;
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; and
Federal University of Parana, Curitiba, Brazil.
NR 77
TC 0
Z9 0
U1 0
U2 0
PU WAYNE STATE UNIV PRESS
PI DETROIT
PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA
SN 0018-7143
EI 1534-6617
J9 HUM BIOL
JI Hum. Biol.
PD SPR
PY 2016
VL 88
IS 2
BP 109
EP 120
PG 12
WC Anthropology; Biology; Genetics & Heredity
SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics &
Heredity
GA EM2CR
UT WOS:000395124500003
PM 28162000
ER
PT J
AU Subramaniam, R
Low, D
Lin, L
Aomatsu, T
Mizoguchi, A
Ng, A
Degrutttola, A
Lee, CG
Elias, J
Andoh, A
Mino-Kenudson, M
Mizoguchi, E
AF Subramaniam, Renuka
Low, Daren
Lin, Li
Aomatsu, Tomoki
Mizoguchi, Atsushi
Ng, Aylwin
Degrutttola, Arianna
Lee, Chun Geun
Elias, Jack
Andoh, Akira
Mino-Kenudson, Mari
Mizoguchi, Emiko
TI Chitinase 3-Like 1 and RAGE Interaction Induces Survival and
Proliferation of Intestinal Epithelial Cells in Colitis-Associated
Cancer
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Meeting Abstract
CT Advances-in-Inflammatory-Bowel-Diseases-Crohn's-and-Colitis Foundation's
National Clinical and Research Conference
CY DEC 10-12, 2015
CL Orlando, FL
SP Advances Inflammatory Bowel Dis Crohns & Colitis Fdn
C1 [Subramaniam, Renuka; Low, Daren; Ng, Aylwin; Degrutttola, Arianna; Mino-Kenudson, Mari; Mizoguchi, Emiko] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Subramaniam, Renuka; Low, Daren; Ng, Aylwin; Degrutttola, Arianna; Mino-Kenudson, Mari; Mizoguchi, Emiko] Harvard Med Sch, Boston, MA USA.
[Lin, Li] NIA, Baltimore, MD 21224 USA.
[Aomatsu, Tomoki] Shiga Univ Med Sci, Otsu, Shiga, Japan.
[Mizoguchi, Atsushi] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan.
[Lee, Chun Geun; Elias, Jack] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA.
[Andoh, Akira] Shiga Univ Med Sci, Div Mucosal Immunol, Otsu, Shiga, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD MAR
PY 2016
VL 22
SU 1
MA P-131
BP S49
EP S50
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA EK4KU
UT WOS:000393896400154
ER
PT J
AU Hart, PS
Hart, TC
AF Hart, P. Suzanne
Hart, Thomas C.
TI Invited commentary: The need for human genetics and genomics in dental
school curricula
SO MOLECULAR GENETICS & GENOMIC MEDICINE
LA English
DT Editorial Material
ID MUTATIONS; CARE
C1 [Hart, P. Suzanne] NHGRI, NIH, Bethesda, MD 20892 USA.
[Hart, Thomas C.] Amer Dent Assoc Fdn, Volpe Res Ctr, Gaithersburg, MD USA.
RP Hart, PS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2324-9269
J9 MOL GENET GENOM MED
JI Mol. Genet. Genom. Med.
PD MAR
PY 2016
VL 4
IS 2
BP 123
EP 125
DI 10.1002/mgg3.216
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA EJ7OA
UT WOS:000393410700001
PM 27066512
ER
PT J
AU Landoure, G
Samassekou, O
Traore, M
Meilleur, KG
Guinto, CO
Burnett, BG
Sumner, CJ
Fischbeck, KH
AF Landoure, Guida
Samassekou, Oumar
Traore, Mahamadou
Meilleur, Katherine G.
Guinto, Cheick Oumar
Burnett, Barrington G.
Sumner, Charlotte J.
Fischbeck, Kenneth H.
TI Genetics and genomic medicine in Mali: challenges and future
perspectives
SO MOLECULAR GENETICS & GENOMIC MEDICINE
LA English
DT Article
ID SUB-SAHARAN AFRICA; BREAST-CANCER; WOMEN; FREQUENCY; MUTATION; DISEASE;
ATAXIA
C1 [Landoure, Guida; Guinto, Cheick Oumar] Ctr Hosp Univ Point G, Serv Neurol, Bamako, Mali.
[Landoure, Guida; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Samassekou, Oumar] Univ Manibota, Manitoba Inst Cell Biol, Winnipeg, MB, Canada.
[Samassekou, Oumar; Traore, Mahamadou] INRSP, Serv Cytogenet & Biol Reprod, Bamako, Mali.
[Meilleur, Katherine G.] NINR, Tissue Injury Branch, NIH, Bethesda, MD 20892 USA.
[Burnett, Barrington G.] Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA.
[Burnett, Barrington G.] Uniformed Serv Univ Hlth Sci, Dept Physiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
[Burnett, Barrington G.] Uniformed Serv Univ Hlth Sci, Dept Genet, Bethesda, MD 20814 USA.
[Sumner, Charlotte J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
RP Landoure, G (reprint author), Ctr Hosp Univ Point G, Serv Neurol, Bamako, Mali.; Landoure, G (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
FU [U01HG007044]
FX G.L., O.S., and M.T. are supported by grant number U01HG007044
administered by the National Human Genome Research Institute as part of
the NIH Common Fund H3Africa Initiative.
NR 30
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2324-9269
J9 MOL GENET GENOM MED
JI Mol. Genet. Genom. Med.
PD MAR
PY 2016
VL 4
IS 2
BP 126
EP 134
DI 10.1002/mgg3.212
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA EJ7OA
UT WOS:000393410700002
PM 27066513
ER
PT J
AU Cush, SS
Reynoso, GV
Kamenyeva, O
Bennink, JR
Yewdell, JW
Hickman, HD
AF Cush, Stephanie S.
Reynoso, Glennys V.
Kamenyeva, Olena
Bennink, Jack R.
Yewdell, Jonathan W.
Hickman, Heather D.
TI Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread
SO PLOS PATHOGENS
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; REGULATORY T-CELLS; ACTIVATED MACROPHAGES;
CYTOKINE PRODUCTION; ECZEMA VACCINATUM; TISSUE-REPAIR; IMMUNE CELLS;
INFECTION; INTERLEUKIN-10; ANTIGEN
AB Skin infection with the poxvirus vaccinia (VV) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. Given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. To better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mRNA expression levels after epicutaneous (ec.) VV infection and found a large increase the anti-inflammatory cytokine IL-10. Ex vivo analyses revealed that T cells in the skin were the primary IL-10-producing cells. To understand the distribution of IL-10-producing T cells in vivo, we performed multiphoton intravital microscopy (MPM) of VV-infected mice, assessing the location and dynamic behavior of IL-10 producing cells. Although virus-specific T cells were distributed throughout areas of the inflamed skin lacking overt virus-infection, IL-10(+) cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific CD8(+) T cells. Paradoxically, neutralizing secreted IL-10 in vivo with an anti-IL-10 antibody increased viral lesion size and viral replication. Additional analyses demonstrated that IL-10 antibody administration decreased recruitment of CCR2(+) inflammatory monocytes, which were important for reducing viral burden in the infected skin. Based upon these findings, we conclude that spatially concentrated IL-10 production limits cutaneous viral replication and dissemination, likely through modulation of the innate immune repertoire at the site of viral growth.
C1 [Cush, Stephanie S.; Reynoso, Glennys V.; Bennink, Jack R.; Yewdell, Jonathan W.; Hickman, Heather D.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kamenyeva, Olena] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Hickman, HD (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM hhickman@mail.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 63
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2016
VL 12
IS 3
AR e1005493
DI 10.1371/journal.ppat.1005493
PG 23
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA EL8TB
UT WOS:000394891800003
PM 26991092
ER
PT J
AU Sereti, I
Altfeld, M
AF Sereti, Irini
Altfeld, Marcus
TI Immune activation and HIV: an enduring relationship
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Editorial Material
ID T-CELLS; INFECTION; LOAD
C1 [Sereti, Irini] NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Altfeld, Marcus] Leibniz Inst Expt Virol, Heinrich Pette Inst, Dept Viral Immunol, Hamburg, Germany.
RP Sereti, I (reprint author), 10 Ctr Dr,Bldg 10,Room 11B-07A, Bethesda, MD USA.
EM isereti@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999, ZIA AI001121-01]
NR 6
TC 0
Z9 0
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2016
VL 11
IS 2
BP 129
EP +
DI 10.1097/COH.0000000000000244
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DD1AE
UT WOS:000369652400001
PM 26845672
ER
PT J
AU Boulougoura, A
Sereti, I
AF Boulougoura, Afroditi
Sereti, Irini
TI HIV infection and immune activation: the role of coinfections
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE biomarkers; immune reconstitution inflammatory syndrome; innate
immunity; myeloid cells; tuberculosis
ID RECONSTITUTION INFLAMMATORY SYNDROME; HERPES-SIMPLEX-VIRUS;
T-CELL-ACTIVATION; PLACEBO-CONTROLLED TRIAL; INTIMA-MEDIA THICKNESS;
HEPATITIS-C VIRUS; ANTIRETROVIRAL THERAPY; OPPORTUNISTIC INFECTIONS;
CRYPTOCOCCAL MENINGITIS; TUBERCULOSIS INFECTION
AB Purpose of reviewThis article explores new data from recent studies addressing the role of coinfections in immune activation in HIV-1-infected patients, with a focus on immune reconstitution inflammatory syndrome (IRIS), an aberrant inflammatory response occurring shortly after antiretroviral therapy (ART) initiation.Recent findingsChronic HIV infection is associated with several coinfections that contribute to immune activation in various settings including early after ART initiation in the most noticeable form of IRIS and also in chronic-treated infection, with chronic viral infections like cytomegalovirus and hepatitis C or hepatitis B virus contributing to immune activation and also morbidity and mortality. Expanding on older studies, the role of T cells in IRIS has been further elucidated with evidence of more pronounced effector activity in patients with IRIS that may be leading to excessive tissue disorder. Newer studies are also continuing to shed light on the role of myeloid cells as well as the contribution of antigen load in IRIS. In addition, preliminary data are beginning to suggest a possible role of inflammasome formation in IRIS. In cryptococcal IRIS, the role of activated immune cells (T cell and myeloid) and biomarkers were evaluated in more detail at the site of infection (cerebrospinal fluid). Finally, important differences of patients developing IRIS versus those who die from tuberculosis despite ART initiation were reported, a distinction that may have important implications for participant selection in studies aiming to prevent IRIS with immunosuppressive agents.SummaryBetter understanding of the role of opportunistic infections at ART initiation and IRIS pathogenesis will assist in improved strategies for prevention and treatment. The long-term consequences of IRIS remain unclear. Chronic viral coinfections with herpesviruses and hepatitis C virus are important factors in persistent immune activation in chronic-treated HIV.
C1 [Boulougoura, Afroditi; Sereti, Irini] NIAID, HIV Pathogenesis Sect, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11B07A, Bethesda, MD USA.
RP Sereti, I (reprint author), NIAID, HIV Pathogenesis Sect, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11B07A, Bethesda, MD USA.
EM isereti@niaid.nih.gov
FU Intramural Research Program, National Institutes of Allergy and
Infectious Diseases; National Institutes of Health
FX The work of the authors was supported by the Intramural Research
Program, National Institutes of Allergy and Infectious Diseases, and
National Institutes of Health.
NR 89
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Z9 5
U1 3
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2016
VL 11
IS 2
BP 191
EP 200
DI 10.1097/COH.0000000000000241
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DD1AE
UT WOS:000369652400009
PM 26720550
ER
PT J
AU McDaniel, JR
DeKosky, BJ
Tanno, H
Ellington, AD
Georgiou, G
AF McDaniel, Jonathan R.
DeKosky, Brandon J.
Tanno, Hidetaka
Ellington, Andrew D.
Georgiou, George
TI Ultra-high-throughput sequencing of the immune receptor repertoire from
millions of lymphocytes
SO NATURE PROTOCOLS
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; IMMUNOGLOBULIN
HEAVY; MICROSPHERES; AFFINITY; ANTIGEN; CHAINS; VIRUS; GENES; PCR
AB High-throughput sequencing of the variable domains of immune receptors (antibodies and T cell receptors (TCRs)) is of key importance in the understanding of adaptive immune responses in health and disease. However, the sequencing of both immune receptor chains (VH+VL or TCR beta/delta+TCR alpha/gamma) at the single-cell level for typical samples containing > 10(4) lymphocytes is problematic, because immune receptors comprise two polypeptide chains that are encoded by separate mRNAs. Here we present a technology that allows rapid and low-cost determination of a paired immune receptor repertoire from millions of cells with high precision (> 97%). Flow focusing is used to encapsulate single cells in emulsions containing magnetic beads for mRNA capture. The mRNA transcripts are then reverse-transcribed, physically linked to their partners by overlap extension PCR, and interrogated by high-throughput paired-end Illumina sequencing. This protocol describes the construction and operation of the flow-focusing device in detail, as well as the bioinformatics pipeline used to interpret the data. The entire procedure can be performed by a single researcher in under 12 h of effort per sample.
C1 [McDaniel, Jonathan R.; DeKosky, Brandon J.; Tanno, Hidetaka; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.
[McDaniel, Jonathan R.; Tanno, Hidetaka; Ellington, Andrew D.; Georgiou, George] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.
[Ellington, Andrew D.] Univ Texas Austin, Ctr Syst & Synthet Biol, Austin, TX 78712 USA.
[Georgiou, George] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
[DeKosky, Brandon J.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Georgiou, G (reprint author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.; Georgiou, G (reprint author), Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.; Georgiou, G (reprint author), Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
EM gg@che.utexas.edu
OI McDaniel, Jonathan/0000-0001-8575-3535
FU Defense Threat Reduction Agency [HDTRA1-12-C-0105]; National Institutes
of Health (NIH) [R01AI096228]; Hertz Foundation; University of Texas
Donald D. Harrington Foundation; National Science Foundation; Japan
Society for the Promotion of Science (JSPS)
FX We thank A. Kennedy for his assistance in making the borosilicate glass
nozzles. Funding for this work was provided by Defense Threat Reduction
Agency HDTRA1-12-C-0105 (G. G.), National Institutes of Health (NIH)
Grant R01AI096228 (G. G.), and fellowships to B.J.D. from the Hertz
Foundation, the University of Texas Donald D. Harrington Foundation and
the National Science Foundation. H.T. was supported by Japan Society for
the Promotion of Science (JSPS) Postdoctoral Fellowships for Research
Abroad.
NR 32
TC 9
Z9 9
U1 4
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD MAR
PY 2016
VL 11
IS 3
BP 429
EP 442
DI 10.1038/nprot.2016.024
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DC6II
UT WOS:000369322900003
PM 26844430
ER
PT J
AU Sare, RM
Levine, M
Hildreth, C
Picchioni, D
Smith, CB
AF Sare, R. Michelle
Levine, Merlin
Hildreth, Christine
Picchioni, Dante
Smith, Carolyn Beebe
TI Chronic sleep restriction during development can lead to long-lasting
behavioral effects
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Sleep restriction; Gentle handling; Social behavior; Open field
activity; Repetitive behavior
ID FEMALE RATS; BRAIN; DEPRIVATION; CHILDREN; MICE; MASCULINIZATION;
ACTIVATION; MICROGLIA; AUTISM
AB Sleep abnormalities are highly correlated with neurodevelopmental disorders, and the severity of behavioral abnormalities correlates with the presence of sleep abnormalities. Given the importance of sleep in developmental plasticity, we sought to determine the effects of chronic sleep-restriction during development on subsequent adult behavior. We sleep-restricted developing wild-type mice from P5-P42 for 3 h per day by means of gentle handling (n = 30) and compared behavioral outputs to controls that were handled 10 min daily (n = 33). We assayed activity in the open field, social behavior, repetitive behavior, and anxiety immediately following sleep restriction and after four weeks of recovery. At six weeks of age, immediately following chronic sleep restriction, mice were less active in an open field arena. Sociability was increased, but repetitive behaviors were unchanged in both males and females. After a 4-week period of recovery, some behavioral abnormalities persisted and some became apparent. Sleep-restricted mice had decreased activity in the beginning of an open field test. Female mice continued to have increased sociability and, in addition, increased preference for social novelty. In contrast, male mice demonstrated decreased sociability with medium effect sizes. Repetitive behavior was decreased in sleep-restricted female mice and increased in males. Measures of anxiety were not affected in the sleep-restricted mice. These results indicate that chronic sleep restriction during development can lead to long-lasting behavioral changes that are modulated by sex. Our study may have implications for a role of disrupted sleep in childhood on the unfolding of neurodevelopmental disorders. Published by Elsevier Inc.
C1 [Sare, R. Michelle; Levine, Merlin; Hildreth, Christine; Picchioni, Dante; Smith, Carolyn Beebe] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Picchioni, Dante] NINDS, Adv MRI Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Sare, RM (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM Rachel.Sare@nih.gov; beebe@mail.nih.gov
OI Hildreth, Christine/0000-0001-7125-8461
FU National Institute of Mental Health; Autism Speaks [8679]; Irene & Eric
Simon Brain Research Foundation
FX This work was funded by the Intramural Research Program of the National
Institute of Mental Health, a postdoctoral fellowship (# 8679) from
Autism Speaks awarded to R. Michelle Reith (Sare), and a summer
fellowship from the Irene & Eric Simon Brain Research Foundation awarded
to Christine Hildreth.
NR 27
TC 1
Z9 1
U1 3
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD MAR 1
PY 2016
VL 155
BP 208
EP 217
DI 10.1016/j.physbeh.2015.12.019
PG 10
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA DC8FL
UT WOS:000369455200026
PM 26712276
ER
PT J
AU Taieb, D
Hicks, RJ
Pacak, K
AF Taieb, David
Hicks, Rodney J.
Pacak, Karel
TI Radiopharmaceuticals in paraganglioma imaging: too many members on
board?
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Editorial Material
ID EXTRAADRENAL PARAGANGLIOMA; PHEOCHROMOCYTOMA; PET/CT
C1 [Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, European Ctr Res Med Imaging, Dept Nucl Med, 264 Rue St Pierre, F-13385 Marseille, France.
[Hicks, Rodney J.] Peter MacCallum Canc Ctr, Canc Imaging & Neuroendocrine Tumour Serv, Melbourne, Vic, Australia.
[Hicks, Rodney J.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Taieb, D (reprint author), Aix Marseille Univ, La Timone Univ Hosp, European Ctr Res Med Imaging, Dept Nucl Med, 264 Rue St Pierre, F-13385 Marseille, France.
EM david.taieb@ap-hm.fr
FU Intramural NIH HHS [ZIA HD008735-15]
NR 13
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
EI 1619-7089
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD MAR
PY 2016
VL 43
IS 3
BP 391
EP 393
DI 10.1007/s00259-015-3213-4
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DC1XT
UT WOS:000369012300001
PM 26459050
ER
PT J
AU Balamurugan, K
AF Balamurugan, Kuppusamy
TI HIF-1 at the crossroads of hypoxia, inflammation, and cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Review
DE hypoxia; inflammation; HIF-1; microenvironment; cancer stem cells; drug
resistance
ID EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; ENDOTHELIAL
GROWTH-FACTOR; INDUCIBLE FACTOR 1-ALPHA; TUMOR-ASSOCIATED MACROPHAGES;
DENDRITIC CELL ACTIVATION; ACUTE MYELOID-LEUKEMIA;
CARBONIC-ANHYDRASE-IX; BREAST-CANCER; STEM-CELLS
AB The complex cross-talk of intricate intercellular signaling networks between the tumor and stromal cells promotes cancer progression. Hypoxia is one of the most common conditions encountered within the tumor microenvironment that drives tumorigenesis. Most responses to hypoxia are elicited by a family of transcription factors called hypoxia-inducible factors (HIFs), which induce expression of a diverse set of genes that assist cells to adapt to hypoxic environments. Among the three HIF protein family members, the role of HIF-1 is well established in cancer progression. HIF-1 functions as a signaling hub to coordinate the activities of many transcription factors and signaling molecules that impact tumorigenesis. This mini review discusses the complex role of HIF-1 and its context-dependent partners under various cancer-promoting events including inflammation and generation of cancer stem cells, which are implicated in tumor metastasis and relapse. In addition, the review highlights the importance of therapeutic targeting of HIF-1 for cancer prevention.
C1 [Balamurugan, Kuppusamy] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
[Balamurugan, Kuppusamy] NCI, 1050 Boyles St, Frederick, MD 21702 USA.
RP Balamurugan, K (reprint author), NCI, Lab Cell & Dev Signaling, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
EM kuppusamyb@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX I thank Esta Sterneck, Howard Young, Shyam Sharan, Chhavi Chauhan, Ira
Daar, Namratha Sheshadri, Michael D. Hall, Snehalata Pawar, Vijay Walia,
Devikala Gurusamy, Matthew D. Anderson and Emilee Senkevitch and the NIH
Fellows Editorial Board for their critical comments and suggestions, and
Allen Kane and Joseph Meyer for preparation of the figures. The author
is supported by the Intramural Research Program of the NIH, National
Cancer Institute.
NR 154
TC 11
Z9 12
U1 23
U2 74
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2016
VL 138
IS 5
BP 1058
EP 1066
DI 10.1002/ijc.29519
PG 9
WC Oncology
SC Oncology
GA DC4BL
UT WOS:000369164700002
PM 25784597
ER
PT J
AU Izano, M
Wei, EK
Tai, C
Swede, H
Gregorich, S
Harris, TB
Klepin, H
Satterfield, S
Murphy, R
Newman, AB
Rubin, SM
Braithwaite, D
AF Izano, Monika
Wei, Esther K.
Tai, Caroline
Swede, Helen
Gregorich, Steven
Harris, Tamara B.
Klepin, Heidi
Satterfield, Suzanne
Murphy, Rachel
Newman, Anne B.
Rubin, Susan M.
Braithwaite, Dejana
CA Hlth ABC Study
TI Chronic inflammation and risk of colorectal and other obesity-related
cancers: The health, aging and body composition study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE colorectal cancer; inflammatory markers; incidence; cohort study
ID C-REACTIVE PROTEIN; SWEDISH CONSTRUCTION WORKERS; PROSTATE-CANCER; MASS
INDEX; WEIGHT CHANGE; FOLLOW-UP; INSULIN-RESISTANCE; METABOLIC SYNDROME;
PHYSICAL-ACTIVITY; RECTAL-CANCER
AB Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-alpha, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-a were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-alpha were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR52.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-a. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults.
C1 [Izano, Monika; Tai, Caroline; Rubin, Susan M.; Braithwaite, Dejana] Univ Calif San Francisco, Dept Epidemiol & Biostat, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.
[Izano, Monika] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Wei, Esther K.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Klepin, Heidi] Wake Forest Sch Med, Winston Salem, NC USA.
[Swede, Helen] Univ Connecticut, Ctr Hlth, Dept Community Med & Hlth Care, Farmington, CT USA.
[Harris, Tamara B.; Murphy, Rachel] NIA, NIH, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Gregorich, Steven] Univ Calif San Francisco, Div Gen Internal Med, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.
[Braithwaite, Dejana] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
RP Braithwaite, D (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.; Braithwaite, D (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.
EM Dejana.braithwaite@ucsf.edu
FU National Institute on Aging; National Institutes of Health
[P30-AG15272]; American Cancer Society [121891-MRSG-12-007-01-CPHPS];
National Institute on Aging (NIA; Health ABC study) [N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106]; NIA [P30-AG15272, R01-AG028050]; NIH
(National Institute on Aging; Intramural Research Program)
FX Grant sponsor: National Institute on Aging; National Institutes of
Health; Grant number: P30-AG15272 (PI Eliseo Perez-Stable); Grant
sponsor: American Cancer Society (PI Dejana Braithwaite); Grant number:
121891-MRSG-12-007-01-CPHPS; Grant sponsor: National Institute on Aging
(NIA; Health ABC study); Grant numbers: N01-AG-6-2101, N01-AG-6-2103,
and N01-AG-6-2106; NIA; Grant numbers: R01-AG028050 and P30-AG15272;
Grant sponsor: NIH (National Institute on Aging; Intramural Research
Program)
NR 58
TC 2
Z9 2
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2016
VL 138
IS 5
BP 1118
EP 1128
DI 10.1002/ijc.29868
PG 11
WC Oncology
SC Oncology
GA DC4BL
UT WOS:000369164700009
PM 26413860
ER
PT J
AU Ek, WE
Lagergren, K
Cook, M
Wu, AH
Abnet, CC
Levine, D
Chow, WH
Bernstein, L
Risch, HA
Shaheen, NJ
Bird, NC
Corley, DA
Hardie, LJ
Fitzgerald, RC
Gammon, MD
Romero, Y
Liu, G
Ye, WM
Vaughan, TL
MacGregor, S
Whiteman, DC
Westberg, L
Lagergren, J
AF Ek, Weronica E.
Lagergren, Katarina
Cook, Michael
Wu, Anna H.
Abnet, Christian C.
Levine, David
Chow, Wong-Ho
Bernstein, Leslie
Risch, Harvey A.
Shaheen, Nicholas J.
Bird, Nigel C.
Corley, Douglas A.
Hardie, Laura J.
Fitzgerald, Rebecca C.
Gammon, Marilie D.
Romero, Yvonne
Liu, Geoffrey
Ye, Weimin
Vaughan, Thomas L.
MacGregor, Stuart
Whiteman, David C.
Westberg, Lars
Lagergren, Jesper
TI Polymorphisms in genes in the androgen pathway and risk of Barrett's
esophagus and esophageal adenocarcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE genome-wide association study; Barrett esophagus; esophageal neoplasms;
neoplasm; hormones; gonadal steroid hormone
ID GENOME-WIDE ASSOCIATION; GASTROESOPHAGEAL-REFLUX; ABDOMINAL OBESITY;
CANCER-RISK; METAANALYSIS; HORMONES; DISEASE; CYP17; LOCUS; MEN
AB The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p=0.002) and in males (p=0.003), but not in females separately (p=0.3). This association was found in tobacco smokers (p=0.003) and in BE patients without reflux (p=0.004), but not in nonsmokers (p=0.2) or those with reflux (p=0.036). SNPs within JMJD1C were associated with risk of EAC in females (p=0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.
C1 [Ek, Weronica E.] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden.
[Ek, Weronica E.; MacGregor, Stuart] QIMR Berghofer Med Res Inst, Stat Genet, Herston, Qld, Australia.
[Lagergren, Katarina; Lagergren, Jesper] Karolinska Inst, Upper Gastrointestinal Surg, Dept Mol Med & Surg, Stockholm, Sweden.
[Cook, Michael] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wu, Anna H.] Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA.
[Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Levine, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Chow, Wong-Ho] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Bernstein, Leslie] Hope Comprehens Canc Ctr, Duarte, CA 91010 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Bird, Nigel C.] Univ Sheffield, Sch Med, Dept Oncol, Sheffield S10 2TN, S Yorkshire, England.
[Corley, Douglas A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Hardie, Laura J.] Univ Leeds, Div Epidemiol, Leeds LS2 9JT, W Yorkshire, England.
[Fitzgerald, Rebecca C.] Univ Cambridge, MRC, Canc Unit, Hutchison MRC Res Ctr, Cambridge CB2 1TN, England.
[Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Romero, Yvonne] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Liu, Geoffrey] Univ Toronto, Princess Margaret Canc Ctr, Dalla Lana Sch Publ Hlth, Dept Med, Toronto, ON M5S 1A1, Canada.
[Liu, Geoffrey] Univ Toronto, Princess Margaret Canc Ctr, Dalla Lana Sch Publ Hlth, Dept Epidemiol, Toronto, ON M5S 1A1, Canada.
[Liu, Geoffrey] Univ Toronto, Princess Margaret Canc Ctr, Dalla Lana Sch Publ Hlth, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
[Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Whiteman, David C.] QIMR Berghofer Med Res Inst, Canc Control Grp, Herston, Qld, Australia.
[Westberg, Lars] Univ Gothenburg, Dept Pharmacol, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Lagergren, Jesper] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
RI Cook, Michael/A-5641-2009; Abnet, Christian/C-4111-2015; Macgregor,
Stuart/C-6442-2009; Liu, Geoffrey/N-4421-2016;
OI Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843;
Macgregor, Stuart/0000-0001-6731-8142; Whiteman,
David/0000-0003-2563-9559
FU NIH [R01CA136725]; California Tobacco Related Research Program
[3RT-0122, 10RT-0251]; Cancer Research UK [C490/A10119, C490/A10124];
Swedish Cancer Society [4559-B01-01XAA, 4758-B02-01XAB]; National Health
and Medical Research Council (NHMRC), Australia [552429]; U.S. National
Institutes of Health [P01CA091955, R01CA001833, R01CA072866,
R01CA057947, R01CA059636, R01CA100264, P30CA016672, R01CA133996,
P50CA093459, U01CA057949, U01CA057983, U01CA057923, R01DK63616]; Medical
Research Council, Cambridge; Cambridge NIHR Biomedical Research Centre;
Cambridge Experimental Cancer Medicine Centre; Marit Peterson Fund for
Melanoma Research [HHSN268200782096C]; Wellcome Trust [076113, 090355];
Australian Research Council Future Fellowship; Research Fellowship from
the National Health; Medical Research Council of Australia
FX Grant sponsor: NIH; Grant number: R01CA136725; Grant sponsor: California
Tobacco Related Research Program; Grant number: 3RT-0122 and 10RT-0251;
Grant sponsor: Cancer Research UK; Grant number: C490/A10119 and
C490/A10124; Grant sponsor: Swedish Cancer Society; Grant number:
4559-B01-01XAA and 4758-B02-01XAB; Grant sponsor: National Health and
Medical Research Council (NHMRC), Australia; Grant number: 552429; Grant
sponsor: U.S. National Institutes of Health; Grant numbers: P01CA091955,
R01CA001833, R01CA072866, R01CA057947, R01CA059636, R01CA100264,
P30CA016672, R01CA133996, P50CA093459, U01CA057949, U01CA057983,
U01CA057923 and R01DK63616; Grant sponsor: Medical Research Council,
Cambridge; Grant sponsor: The Cambridge NIHR Biomedical Research Centre;
Grant sponsor: Cambridge Experimental Cancer Medicine Centre; Grant
sponsor: Marit Peterson Fund for Melanoma Research; Grant sponsor:
HHSN268200782096C; Grant sponsor: Wellcome Trust; Grant number: 076113
and 090355; Grant sponsor: Australian Research Council Future
Fellowship; Grant sponsor: Research Fellowship from the National Health;
Grant sponsor: Medical Research Council of Australia
NR 33
TC 2
Z9 2
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2016
VL 138
IS 5
BP 1146
EP 1152
DI 10.1002/ijc.29863
PG 7
WC Oncology
SC Oncology
GA DC4BL
UT WOS:000369164700012
PM 26414697
ER
PT J
AU Matsuura, K
Isogawa, M
Tanaka, Y
AF Matsuura, Kentaro
Isogawa, Masanori
Tanaka, Yasuhito
TI Host Genetic Variants Influencing the Clinical Course of Hepatitis B
Virus Infection
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Review
DE HBV; GWAS; fibrosis; HCC; HLA
ID GENOME-WIDE ASSOCIATION; RECEPTOR-ALPHA POLYMORPHISMS;
HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; TUMOR-SUPPRESSOR; PROMOTER
VARIANT; INTERFERON-GAMMA; HAN CHINESE; T-CELLS; RISK
AB The clinical course of hepatitis B virus (HBV) infection greatly differs in individuals. Various viral, host, and environmental factors influence the natural history of HBV infection. Recent genome-wide association studies identified several host genetic factors influencing the clinical course of HBV infection. Genetic variations in HLA class II loci were significantly associated with susceptibility to persistent HBV infection. Other polymorphisms in or near the genes EHMT2, TCF19, and HLA-C, located near HLA class II loci, and UBE2L3 were also associated with persistent HBV infection. Meanwhile, polymorphisms in KIF1B, GRIK1, and STAT4 were associated with HBV-related hepatocellular carcinoma (HCC). Interestingly, HLA class II genetic variations were strongly associated with not only persistent HBV infection, but also disease progression and HBV-related HCC in chronic hepatitis B. Understanding the various genetic factors associated with the clinical course of HBV infection is essential for personalized treatment and surveillance of disease progression and HCC. (C) 2015 Wiley Periodicals, Inc.
C1 [Matsuura, Kentaro; Isogawa, Masanori; Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi 4678601, Japan.
[Matsuura, Kentaro; Isogawa, Masanori; Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi 4678601, Japan.
[Matsuura, Kentaro] Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol & Metab, Nagoya, Aichi 4678601, Japan.
[Matsuura, Kentaro] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Tanaka, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi 4678601, Japan.; Tanaka, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi 4678601, Japan.; Tanaka, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Mizuho Ku, Nagoya, Aichi 4678601, Japan.; Tanaka, Y (reprint author), Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
EM ytanaka@med.nagoya-cu.ac.jp
FU Japan Agency for Medical Research and development; Uehara Memorial
Foundation
FX Grant sponsor: Japan Agency for Medical Research and development; Grant
sponsor: Uehara Memorial Foundation
NR 77
TC 2
Z9 2
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0146-6615
EI 1096-9071
J9 J MED VIROL
JI J. Med. Virol.
PD MAR
PY 2016
VL 88
IS 3
BP 371
EP 379
DI 10.1002/jmv.24350
PG 9
WC Virology
SC Virology
GA DC4II
UT WOS:000369184000003
PM 26255971
ER
PT J
AU Herman, MA
Varodayan, FP
Oleata, CS
Luu, G
Kirson, D
Heilig, M
Ciccocioppo, R
Roberto, M
AF Herman, Melissa A.
Varodayan, Florence P.
Oleata, Christopher S.
Luu, George
Kirson, Dean
Heilig, Markus
Ciccocioppo, Roberto
Roberto, Marisa
TI Glutamatergic transmission in the central nucleus of the amygdala is
selectively altered in Marchigian Sardinian alcohol-preferring rats:
Alcohol and CRF effects
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Amygdala; Glutamate; Alcohol; CRF; CRF1 antagonist; Electrophysiology
ID CORTICOTROPIN-RELEASING-FACTOR; PAIRED-PULSE FACILITATION;
AMINOBUTYRIC-ACID RELEASE; CHRONIC ETHANOL EXPOSURE; LONG-TERM
POTENTIATION; SYNAPTIC-TRANSMISSION; NMDA RECEPTORS; MSP RATS; GABAERGIC
TRANSMISSION; DEPENDENT RATS
AB The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. (c) 2015 Elsevier Ltd. All rights reserved.
C1 [Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, SP30-1150,10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
[Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna delle Carceri, I-62032 Camerino, Italy.
[Heilig, Markus] NIAAA, Lab Clin & Translat Sci, NIH, Bldg 10 CRC Rm 1-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Roberto, M (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, SP30-1150,10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM mroberto@scripps.edu
FU NIH [AA017447, AA015566, AA06420, AA021491, AA013498]
FX This is manuscript number 29167 from The Scripps Research Institute.
This work was supported by NIH grants AA017447, AA015566, AA06420,
AA021491, AA013498. We thank J. Rivier of the Salk Institute for
Biological Studies for the generous gift of r/hCRF and Jenica Tapocik
and Hui Sun (NIH/NIAAA) for genotyping of the msP rats.
NR 49
TC 4
Z9 4
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD MAR
PY 2016
VL 102
BP 21
EP 31
DI 10.1016/j.neuropharm.2015.10.027
PG 11
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DC1AY
UT WOS:000368950400002
PM 26519902
ER
PT J
AU Rashid, MA
Kim, HY
AF Rashid, Mohammad Abdur
Kim, Hee-Yong
TI N-Docosahexaenoylethanolamine ameliorates ethanol-induced impairment of
neural stem cell neurogenic differentiation
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Synaptamide; Neurogenesis; cAMP; Adenylyl cyclase; Docosahexaenoic acid
(DHA, 22:6n-3); G-protein
ID ELEMENT-BINDING PROTEIN; INDUCED APOPTOTIC NEURODEGENERATION; ALCOHOLIC
LIVER-DISEASE; VIII ADENYLYL-CYCLASE; ADULT-RAT HIPPOCAMPUS;
DOCOSAHEXAENOIC ACID; CEREBRAL-CORTEX; TNF EXPRESSION; NERVOUS-SYSTEM;
MOUSE-BRAIN
AB Previous studies demonstrated that prenatal exposure to ethanol interferes with embryonic and fetal development, and causes abnormal neurodevelopment. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid highly enriched in the brain, was shown to be essential for proper brain development and function. Recently, we found that N-docosahexenoyethanolamine (synaptamide), an endogenous metabolite of DHA, is a potent PICA-dependent neurogenic factor for neural stem cell (NSC) differentiation. In this study, we demonstrate that ethanol at pharmacologically relevant concentrations downregulates cAMP signaling in NSC and impairs neurogenic differentiation. In contrast, synaptamide reverses ethanol-impaired NSC neurogenic differentiation through counter-acting on the cAMP production system. NSC exposure to ethanol (25-50 mM) for 4 days dose-dependently decreased the number of Tuj-1 positive neurons and PICA/CREB phosphorylation with a concomitant reduction of cellular cAMP. Ethanol-induced cAMP reduction was accompanied by the inhibition of G-protein activation and expression of adenylyl cyclase (AC) 7 and AC8, as well as PDE4 upregulation. In contrast to ethanol, synaptamide increased cAMP production, GTP gamma S binding, and expression of AC7 and AC8 iso-forms in a cAMP-dependent manner, offsetting the ethanol-induced impairment in neurogenic differentiation. These results indicate that synaptamide can reduce ethanol-induced impairment of neuronal differentiation by counter-affecting shared targets in G-protein coupled receptor (GPCR)/cAMP signaling. The synaptamide-mediated mechanism observed in this study may offer a possible avenue for ameliorating the adverse impact of fetal alcohol exposure on neurodevelopment. Published by Elsevier Ltd.
C1 [Rashid, Mohammad Abdur; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, DICBR, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
EM hykim@nih.gov
FU National Institute of Alcohol Abuse and Alcoholism, National Institutes
of Health
FX Authors wish to thank Dr. Jiwon Lee for technical assistance with GTP
gamma S binding assay, Dr. Bill X. Huang for graphics and Dr. Arthur A.
Spector for editorial help. This work was supported by the Intramural
Research Program of the National Institute of Alcohol Abuse and
Alcoholism, National Institutes of Health.
NR 65
TC 6
Z9 7
U1 0
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD MAR
PY 2016
VL 102
BP 174
EP 185
DI 10.1016/j.neuropharm.2015.11.011
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DC1AY
UT WOS:000368950400016
PM 26586023
ER
PT J
AU Preussler, JM
Mau, LW
Majhail, NS
Bevans, M
Clancy, E
Messner, C
Parran, L
Pederson, KA
Ferguson, SS
Walters, K
Murphy, EA
Denzen, EM
AF Preussler, Jaime M.
Mau, Lih-Wen
Majhail, Navneet S.
Bevans, Margaret
Clancy, Emilie
Messner, Carolyn
Parran, Leslie
Pederson, Kate A.
Ferguson, Stacy Stickney
Walters, Kent
Murphy, Elizabeth A.
Denzen, Ellen M.
TI Patient housing barriers to hematopoietic cell transplantation: results
from a mixed-methods study of transplant center social workers
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Hematopoietic cell transplantation; Housing; Barriers
ID HEALTH-CARE PROVIDERS; CANCER-PATIENTS; RECIPIENTS; CAPACITY
AB Hematopoietic cell transplantation (HCT) is performed in select centers in the United States (U.S.), and patients are often required to temporarily relocate to receive care. The purpose of this study was to identify housing barriers impacting access to HCT and potential solutions.
A mixed-methods primary study of HCT social workers was conducted to learn about patient housing challenges and solutions in place that help address those barriers. Three telephone focus groups were conducted with adult and pediatric transplant social workers (n = 15). Focus group results informed the design of a national survey. The online survey was e-mailed to a primary social worker contact at 133 adult and pediatric transplant centers in the U.S. Transplant centers were classified based on the patient population cared for by the social worker.
The survey response rate was 49 %. Among adult programs (n = 45), 93 % of centers had patients that had to relocate closer to the transplant center to proceed with HCT. The most common type of housing option offered was discounted hotel rates. Among pediatric programs (n = 20), 90 % of centers had patients that had to relocate closer to the transplant center to proceed with HCT. Ronald McDonald House was the most common option available.
This study is the first to explore housing challenges faced by patients undergoing HCT in the U.S. from the perspective of social workers and to highlight solutions that centers use. Transplant centers will benefit from this knowledge by learning about options for addressing housing barriers for their patients.
C1 [Preussler, Jaime M.; Mau, Lih-Wen; Clancy, Emilie; Pederson, Kate A.; Ferguson, Stacy Stickney; Murphy, Elizabeth A.; Denzen, Ellen M.] Natl Marrow Donor Program Be The Match, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA.
[Majhail, Navneet S.] Cleveland Clin, Cleveland, OH 44106 USA.
[Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Messner, Carolyn] CancerCare, New York, NY USA.
[Parran, Leslie] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Walters, Kent] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Preussler, JM (reprint author), Natl Marrow Donor Program Be The Match, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA.
EM jpreussl@nmdp.org
FU National Marrow Donor Program's System Capacity Initiative Program
FX Our sincere thanks to the National Marrow Donor Program's System
Capacity Initiative Program for supporting this study. We also thank
William Vaughn, MD (University of Alabama) for participating in the
study protocol team, Linda Burns, MD (NMDP) for reviewing and providing
comments on the draft manuscript, Diane W. Carr, MPH and Viengneesee
Thao, MS (NMDP) for their help in reaching out to potential survey
participants, and Tammy Payton (NMDP) for her coding of focus group
responses. Finally, we thank the social workers who participated in the
focus groups and survey.
NR 18
TC 0
Z9 0
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD MAR
PY 2016
VL 24
IS 3
BP 1167
EP 1174
DI 10.1007/s00520-015-2872-9
PG 8
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA DC1WY
UT WOS:000369010000018
PM 26275767
ER
PT J
AU Majithia, N
Temkin, SM
Ruddy, KJ
Beutler, AS
Hershman, DL
Loprinzi, CL
AF Majithia, Neil
Temkin, Sarah M.
Ruddy, Kathryn J.
Beutler, Andreas S.
Hershman, Dawn L.
Loprinzi, Charles L.
TI National Cancer Institute-supported chemotherapy-induced peripheral
neuropathy trials: outcomes and lessons
SO SUPPORTIVE CARE IN CANCER
LA English
DT Review
DE Chemotherapy; Peripheral neuropathy; Cancer; Clinical trials
ID PLACEBO-CONTROLLED TRIAL; ACETYL-L-CARNITINE; QUALITY-OF-LIFE;
OXALIPLATIN-INDUCED NEUROPATHY; PAINFUL DIABETIC-NEUROPATHY; RANDOMIZED
CONTROLLED-TRIAL; ADVANCED COLORECTAL-CANCER; VITAMIN-E SUPPLEMENTATION;
DOUBLE-BLIND CROSSOVER; ALPHA-LIPOIC ACID
AB Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional-yet unsubstantiated-practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity.
C1 [Majithia, Neil] Mayo Clin, Dept Internal Med, 200 First St SW, Rochester, MN 55905 USA.
[Temkin, Sarah M.] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Ruddy, Kathryn J.; Beutler, Andreas S.; Loprinzi, Charles L.] Mayo Clin, Dept Med Oncol, 200 First St SW, Rochester, MN 55905 USA.
[Hershman, Dawn L.] Columbia Univ Coll Phys & Surg, New York Presbyterian Hosp, Herbert Irving Comprehens Canc Ctr, Mailman Sch Publ Hlth,Dept Med,Dept Epidemiol, 161 Ft Washington Ave 1068, New York, NY 10032 USA.
RP Majithia, N (reprint author), Mayo Clin, Dept Internal Med, 200 First St SW, Rochester, MN 55905 USA.
EM majithia.neil@mayo.edu
FU NCI NIH HHS [U10 CA180802]; NINR NIH HHS [R01 NR015259]
NR 50
TC 5
Z9 5
U1 3
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD MAR
PY 2016
VL 24
IS 3
BP 1439
EP 1447
DI 10.1007/s00520-015-3063-4
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA DC1WY
UT WOS:000369010000048
PM 26686859
ER
PT J
AU Egervari, K
Potter, G
Guzman-Hernandez, ML
Salmon, P
Soto-Ribeiro, M
Kastberger, B
Balla, T
Wehrle-Haller, B
Kiss, JZ
AF Egervari, Kristof
Potter, Gael
Guzman-Hernandez, Maria Luisa
Salmon, Patrick
Soto-Ribeiro, Martinho
Kastberger, Birgit
Balla, Tamas
Wehrle-Haller, Bernhard
Kiss, Jozsef Zoltan
TI Astrocytes spatially restrict VEGF signaling by polarized secretion and
incorporation of VEGF into the actively assembling extracellular matrix
SO GLIA
LA English
DT Article
DE extracellular matrix; fibrillar adhesion; fibronectin; growth factor
signaling
ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; IN-VITRO;
ALPHA(V)BETA(3) INTEGRIN; BIOLOGICAL-ACTIVITY; CELL PROLIFERATION;
PLASMA-MEMBRANE; FOCAL ADHESIONS; NERVOUS-SYSTEM; AXON GROWTH
AB The spatial organization of vascular endothelial growth factor (VEGF) signaling is a key determinant of vascular patterning during development and tissue repair. How VEGF signaling becomes spatially restricted and the role of VEGF secreting astrocytes in this process remains poorly understood. Using a VEGF-GFP fusion protein and confocal time-lapse microscopy, we observed the intracellular routing, secretion and immobilization of VEGF in scratch-activated living astrocytes. We found VEGF to be directly transported to cell-extracellular matrix attachments where it is incorporated into fibronectin fibrils. VEGF accumulated at 1 integrin containing fibrillar adhesions and was translocated along the cell surface prior to internalization and degradation. We also found that only the astrocyte-derived, matrix-bound, and not soluble VEGF decreases 1 integrin turnover in fibrillar adhesions. We suggest that polarized VEGF release and ECM remodeling by VEGF secreting cells is key to control the local concentration and signaling of VEGF. Our findings highlight the importance of astrocytes in directing VEGF functions and identify these mechanisms as promising target for angiogenic approaches. GLIA 2016;64:440-456
C1 [Egervari, Kristof; Potter, Gael; Salmon, Patrick; Kiss, Jozsef Zoltan] Univ Geneva, Dept Neurosci, CH-1211 Geneva 4, Switzerland.
[Guzman-Hernandez, Maria Luisa; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA.
[Soto-Ribeiro, Martinho; Kastberger, Birgit; Wehrle-Haller, Bernhard] Univ Geneva, Dept Cell Physiol & Metab, CH-1211 Geneva 4, Switzerland.
RP Kiss, JZ (reprint author), Univ Geneva, Sch Med, Dept Fundamental Neurosci, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
EM Jozsef.kiss@unige.ch
OI Salmon, Patrick/0000-0002-1993-4984; Balla, Tamas/0000-0002-9077-3335
FU Swiss National Foundation [31003A_140940/1]
FX Grant sponsor: Swiss National Foundation; Grant number: 31003A_140940/1
NR 92
TC 2
Z9 2
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
EI 1098-1136
J9 GLIA
JI Glia
PD MAR
PY 2016
VL 64
IS 3
BP 440
EP 456
DI 10.1002/glia.22939
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA DA3EF
UT WOS:000367678800009
PM 26539695
ER
PT J
AU Watt, DL
Buckland, RJ
Lujan, SA
Kunkel, TA
Chabes, A
AF Watt, Danielle L.
Buckland, Robert J.
Lujan, Scott A.
Kunkel, Thomas A.
Chabes, Andrei
TI Genome-wide analysis of the specificity and mechanisms of replication
infidelity driven by imbalanced dNTP pools
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DNA-POLYMERASE-DELTA; FRAMESHIFT MUTATIONS; STRUCTURAL BASIS; IN-VIVO;
FIDELITY; NUCLEOTIDE; CANCER; MUTAGENESIS; STABILITY; EPSILON
AB The absolute and relative concentrations of the four dNTPs are key determinants of DNA replication fidelity, yet the consequences of altered dNTP pools on replication fidelity have not previously been investigated on a genome-wide scale. Here, we use deep sequencing to determine the types, rates and locations of uncorrected replication errors that accumulate in the nuclear genome of a mismatch repair-deficient diploid yeast strain with elevated dCTP and dTTP concentrations. These imbalanced dNTP pools promote replication errors in specific DNA sequence motifs suggesting increased misinsertion and increased mismatch extension at the expense of proofreading. Interestingly, substitution rates are similar for leading and lagging strand replication, but are higher in regions replicated late in S phase. Remarkably, the rate of single base deletions is preferentially increased in coding sequences and in short rather than long mononucleotides runs. Based on DNA sequence motifs, we propose two distinct mechanisms for generating single base deletions in vivo. Collectively, the results indicate that elevated dCTP and dTTP pools increase mismatch formation and decrease error correction across the nuclear genome, and most strongly increases mutation rates in coding and late replicating sequences.
C1 [Watt, Danielle L.; Buckland, Robert J.; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
[Watt, Danielle L.; Lujan, Scott A.; Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Buckland, Robert J.; Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
RP Chabes, A (reprint author), Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.; Chabes, A (reprint author), Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
EM andrei.chabes@umu.se
RI Buckland, Robert/L-6137-2014
OI Buckland, Robert/0000-0001-9749-5422
FU Swedish Cancer Society; Knut and Alice Wallenberg Foundation; Swedish
Research Council; Division of Intramural Research of the National
Institutes of Health, National Institute of Environmental Health
Sciences [Z01 ES065070]
FX Swedish Cancer Society (to A.C.); Knut and Alice Wallenberg Foundation
(to A.C.); Swedish Research Council (to A.C.); Division of Intramural
Research of the National Institutes of Health, National Institute of
Environmental Health Sciences [Project Z01 ES065070 to T.A.K.]. Funding
for open access charge: Swedish Research Council.
NR 46
TC 4
Z9 4
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 29
PY 2016
VL 44
IS 4
BP 1669
EP 1680
DI 10.1093/nar/gkv1298
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF7ED
UT WOS:000371519700026
PM 26609135
ER
PT J
AU Zheng, XH
Pedersen, LC
Gabel, SA
Mueller, GA
DeRose, EF
London, RE
AF Zheng, Xunhai
Pedersen, Lars C.
Gabel, Scott A.
Mueller, Geoffrey A.
DeRose, Eugene F.
London, Robert E.
TI Unfolding the HIV-1 reverse transcriptase RNase H domain - how to lose a
molecular tug-of-war
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RIBONUCLEASE-H; FOLDING INTERMEDIATE; BACKBONE DYNAMICS; STRUCTURAL
BASIS; DRUG-RESISTANCE; ACTIVE-SITE; DIMERIZATION; INHIBITORS; BINDING;
CRYSTALLIZATION
AB Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. This study demonstrates the feasibility of directly targeting RT maturation with therapeutics.
C1 [Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences (NIEHS) [Z01-ES050147]; NIEHS
[HHSN273200700046U]; U. S. Department of Energy, Office of Science,
Office of Basic Energy Sciences [W-31-109-Eng-38]; NIH; [ZIA ES102645]
FX Intramural Research Program of the NIH and National Institute of
Environmental Health Sciences (NIEHS) [Research Project Number
Z01-ES050147 to R.E.L.]; E.F.D. is supported by NIH and NIEHS under
delivery order HHSN273200700046U; L.C.P. is supported by Research
Project Number ZIA ES102645. Use of the Advanced Photon Source was
supported by the U. S. Department of Energy, Office of Science, Office
of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. Funding
for open access charge: Intramural Research Program of the NIH and
National Institute of Environmental Health Sciences (NIEHS) [Research
Project Number Z01-ES050147 to R.E.L.].
NR 52
TC 2
Z9 2
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 29
PY 2016
VL 44
IS 4
BP 1776
EP 1788
DI 10.1093/nar/gkv1538
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF7ED
UT WOS:000371519700034
PM 26773054
ER
PT J
AU Ajiro, M
Jia, R
Yang, YQ
Zhu, J
Zheng, ZM
AF Ajiro, Masahiko
Jia, Rong
Yang, Yanqin
Zhu, Jun
Zheng, Zhi-Ming
TI A genome landscape of SRSF3-regulated splicing events and gene
expression in human osteosarcoma U2OS cells
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PRE-MESSENGER-RNA; EPITHELIAL OVARIAN-CANCER; ACUTE MYELOID-LEUKEMIA;
ZIPPER KINASE MELK; FACTOR SRP20; SR PROTEINS; FACTOR SRSF3; IN-VIVO;
DIFFERENTIAL EXPRESSION; CELLULAR SENESCENCE
AB Alternative RNA splicing is an essential process to yield proteomic diversity in eukaryotic cells, and aberrant splicing is often associated with numerous human diseases and cancers. We recently described serine/arginine-rich splicing factor 3 (SRSF3 or SRp20) being a proto-oncogene. However, the SRSF3-regulated splicing events responsible for its oncogenic activities remain largely unknown. By global profiling of the SRSF3-regulated splicing events in human osteosarcoma U2OS cells, we found that SRSF3 regulates the expression of 60 genes including ERRFI1, ANXA1 and TGFB2, and 182 splicing events in 164 genes, including EP300, PUS3, CLINT1, PKP4, KIF23, CHK1, SMC2, CKLF, MAP4, MBNL1, MELK, DDX5, PABPC1, MAP4K4, Sp1 and SRSF1, which are primarily associated with cell proliferation or cell cycle. Two SRSF3-binding motifs, CCAGC(G)C and A(G)CAGCA, are enriched to the alternative exons. An SRSF3-binding site in the EP300 exon 14 is essential for exon 14 inclusion. We found that the expression of SRSF1 and SRSF3 are mutually dependent and coexpressed in normal and tumor tissues/cells. SRSF3 also significantly regulates the expression of at least 20 miRNAs, including a subset of oncogenic or tumor suppressive miRNAs. These data indicate that SRSF3 affects a global change of gene expression to maintain cell homeostasis.
C1 [Ajiro, Masahiko; Jia, Rong; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Yang, Yanqin; Zhu, Jun] NHLBI, DNA Sequencing & Genom Core, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Jia, Rong] Wuhan Univ, Sch Stomatol, Chinese Minist Educ, Key Lab Oral Biomed, Wuhan 430079, Hunan, Peoples R China.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM zhengt@exchange.nih.gov
FU Intramural Research Program of National Cancer Institute and National
Heart, Lung, and Blood Institute; National Institutes of Health;
Intramural Research Program of National Cancer Institute, National
Institutes of Health
FX Intramural Research Program of National Cancer Institute and National
Heart, Lung, and Blood Institute; National Institutes of Health. Funding
for open access charge: Intramural Research Program of National Cancer
Institute, National Institutes of Health.
NR 111
TC 4
Z9 4
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 29
PY 2016
VL 44
IS 4
BP 1854
EP 1870
DI 10.1093/nar/gkv1500
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF7ED
UT WOS:000371519700040
PM 26704980
ER
PT J
AU Kiliszek, A
Banaszak, K
Dauter, Z
Rypniewski, W
AF Kiliszek, Agnieszka
Banaszak, Katarzyna
Dauter, Zbigniew
Rypniewski, Wojciech
TI The first crystal structures of RNA-PNA duplexes and a PNA-PNA duplex
containing mismatches-toward anti-sense therapy against TREDs
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PEPTIDE NUCLEIC-ACIDS; MYOTONIC-DYSTROPHY; POLYGLUTAMINE DISEASES;
MUTANT HUNTINGTIN; CAG REPEATS; CUG REPEATS; HYBRIDIZATION; TOXICITY;
DNA; VISUALIZATION
AB PNA is a promising molecule for antisense therapy of trinucleotide repeat disorders. We present the first crystal structures of RNA-PNA duplexes. They contain CUG repeats, relevant to myotonic dystrophy type I, and CAG repeats associated with poly-glutamine diseases. We also report the first PNA-PNA duplex containing mismatches. A comparison of the PNA homoduplex and the PNA-RNA heteroduplexes reveals PNA's intrinsic structural properties, shedding light on its reported sequence selectivity or intolerance of mismatches when it interacts with nucleic acids. PNA has a much lower helical twist than RNA and the resulting duplex has an intermediate conformation. PNA retains its overall conformation while locally there is much disorder, especially peptide bond flipping. In addition to the Watson-Crick pairing, the structures contain interesting interactions between the RNA's phosphate groups and the I electrons of the peptide bonds in PNA.
C1 [Kiliszek, Agnieszka; Banaszak, Katarzyna; Rypniewski, Wojciech] Polish Acad Sci, Inst Bioorgan Chem, Noskowskiego 12-14, PL-61704 Poznan, Poland.
[Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
RP Rypniewski, W (reprint author), Polish Acad Sci, Inst Bioorgan Chem, Noskowskiego 12-14, PL-61704 Poznan, Poland.
EM wojtekr@ibch.poznan.pl
FU National Science Centre (Poland) [UMO-2011/01/B/NZ1/04429]; Ministry of
Science and Higher Education (Poland) [0450/IP1/2013/72, 01/KNOW2/2014];
European Commission (the Seventh Framework Programme); BioStruct-X
project [283570]; Institute of Bioorganic Chemistry, Polish Academy of
Sciences
FX National Science Centre (Poland) [UMO-2011/01/B/NZ1/04429]; Ministry of
Science and Higher Education (Poland) [0450/IP1/2013/72, 01/KNOW2/2014];
European Commission (the Seventh Framework Programme); BioStruct-X
project [Contract No. 283570]. Funding for open access charge: Institute
of Bioorganic Chemistry, Polish Academy of Sciences.
NR 48
TC 0
Z9 0
U1 4
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 29
PY 2016
VL 44
IS 4
BP 1937
EP 1943
DI 10.1093/nar/gkv1513
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF7ED
UT WOS:000371519700045
PM 26717983
ER
PT J
AU Gonese, E
Mushavi, A
Mungati, M
Mhangara, M
Dzangare, J
Mugurungi, O
Dee, J
Kilmarx, PH
Shambira, G
Tshimanga, MT
Hargrove, J
AF Gonese, E.
Mushavi, A.
Mungati, M.
Mhangara, M.
Dzangare, J.
Mugurungi, O.
Dee, J.
Kilmarx, P. H.
Shambira, G.
Tshimanga, M. T.
Hargrove, J.
TI Is Zimbabwe ready to transition from anonymous unlinked
sero-surveillance to using prevention of mother to child transmission of
HIV (PMTCT) program data for HIV surveillance?: results of PMTCT utility
study, 2012
SO BMC INFECTIOUS DISEASES
LA English
DT Article
AB Background: Prevention of mother-to-child transmission of HIV (PMTCT) programs collect socio-demographic and HIV testing information similar to that collected by unlinked anonymous testing sero-surveillance (UAT) in antenatal settings. Zimbabwe evaluated the utility of PMTCT data in replacing UAT.
Methods: A UAT dataset was created by capturing socio-demographic, testing practices from the woman's booking-card and testing remnant blood at a laboratory from 1 June to 30 September 2012. PMTCT data were collected retrospectively from ANC registers. UAT and PMTCT data were linked by bar-code labels that were temporarily affixed to the ANC register. A questionnaire was used to obtain facility-level data at 53 sites.
Results: Pooled HIV prevalence was 15.8 % (95 % CI 15.3-16.4) among 17,349 women sampled by UAT, and 16.3 % (95 % CI 15.8 %-16.9 %) among 17,150 women in PMTCT datasets for 53 sites. Pooled national percent-positive agreement (PPA) was 91.2 %, and percent-negative agreement (PNA) was 98.7 % for 16,782 women with matched UAT and PMTCT data. Based on UAT methods, overall median prevalence was 12.9 % (Range 4.0 %-19.4 %) among acceptors and refusers of HIV test in PMTCT compared to 12.5 % ((Range 3.4 %-19.5 %) among acceptors in ANC registers. There were variations in prevalence by site.
Conclusion: Although, there is no statistical difference between pooled HIV prevalence in UAT compared to PMTCT program, the overall PPA of 91.2 % and PNA of 98.7 % fall below World Health Organisation (WHO) benchmarks of 97.6 % and 99.6 % respectively. Zimbabwe will need to strengthen quality assurance (QA) of rapid HIV testing and data collection practices. Sites with good performance should be prioritised for transitioning.
C1 [Gonese, E.] Ctr Dis Control & Prevent, 38 Nelson Mandela Rd,Box 3088, Harare, Zimbabwe.
[Mushavi, A.; Mungati, M.; Mhangara, M.; Dzangare, J.; Mugurungi, O.] Ministry Hlth & Child Care Zimbabwe, Mukwati Bldg,Corner Livingstone Fifth St, Harare, Zimbabwe.
[Dee, J.] Ctr Dis Control & Prevent, 1600 Clifton Rd, Atlanta, GA 30329 USA.
[Kilmarx, P. H.] NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Shambira, G.; Tshimanga, M. T.] Univ Zimbabwe, Parirenyatwa Hosp, Dept Community Med, Mazoe St, Harare, Zimbabwe.
[Hargrove, J.] Univ Stellenbosch, South Africa Ctr Epidemiol Modelling & Anal, 19 Jonkershoek Rd, ZA-7602 Stellenbosch, South Africa.
RP Gonese, E (reprint author), Ctr Dis Control & Prevent, 38 Nelson Mandela Rd,Box 3088, Harare, Zimbabwe.
EM egonese@cdc.gov
FU Ministry of Health Child Care; AIDS & TB Unit, Zimbabwe; U.S. Centers
for Disease Control and Prevention (CDC) [1U2GGH000315-01]; Department
of Community Medicine [1U2GGH000315-01]
FX We would like to thank the Ministry of Health & Child Care and the AIDS
& TB Unit, Zimbabwe for their support and granting us permission to
conduct the study. The survey was supported by the President's Emergency
Plan for AIDS Relief (PEPFAR) through a cooperative agreement between
the U.S. Centers for Disease Control and Prevention (CDC) and the
Department of Community Medicine (#1U2GGH000315-01). We acknowledge
technical support in data collection and analysis from CDC Zimbabwe and
CDC Atlanta.
NR 19
TC 1
Z9 1
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD FEB 29
PY 2016
VL 16
AR 97
DI 10.1186/s12879-016-1425-2
PG 13
WC Infectious Diseases
SC Infectious Diseases
GA DF5GS
UT WOS:000371380400001
PM 26923185
ER
PT J
AU Lee, JH
Ying, JF
Bax, A
AF Lee, Jung Ho
Ying, Jinfa
Bax, Ad
TI Quantitative evaluation of positive phi angle propensity in flexible
regions of proteins from three-bond J couplings
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID DISORDERED PROTEINS; CHEMICAL-SHIFTS; ONE-BOND; C-13,N-15-LABELED
PROTEINS; SECONDARY-STRUCTURE; KARPLUS EQUATIONS; NMR-SPECTROSCOPY;
ALPHA-SYNUCLEIN; HUMAN UBIQUITIN; H-ALPHA
AB (3)J(HNH alpha) and (3)J(C'C') couplings can be readily measured in isotopically enriched proteins and were shown to contain precise information on the backbone torsion angles, phi, sampled in disordered regions of proteins. However, quantitative interpretation of these couplings required the population of conformers with positive phi angles to be very small. Here, we demonstrate that this restriction can be removed by measurement of (3)J(C'H alpha) values. Even though the functional forms of the (3)J(C'H alpha) and (3)J(HNH alpha) Karplus equations are the same, large differences in their coefficients enable accurate determination of the fraction of time that positive phi angles are sampled. A four-dimensional triple resonance HACANH[C '] E.COSY experiment is introduced to simultaneously measure (3)J(C'H alpha), and (3)J(HNC') in the typically very congested spectra of disordered proteins. High resolution in these spectra is obtained by non-uniform sampling (in the 0.1-0.5% range). Application to the intrinsically disordered protein alpha-synuclein shows that while most residues have close-to-zero positive phi angle populations, up to 16% positive phi population is observed for Asn residues. Positive phi angle populations determined with the new approach agree closely with consensus values from protein coil libraries and prior analysis of a large set of other NMR parameters. The combination of (3)J(HNC') and (3)J(C'C'), provides information about the amplitude of phi angle dynamics.
C1 [Lee, Jung Ho; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Intramural Antiviral Target Program of
the Office of the Director, NIH; KVSTA Fellowship
FX We thank F. Li for providing GB3 and ubiquitin samples, and J. L. Baber,
Y. Shen, and A. Grishaev for technical support. NUS reconstruction
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, Md.
(http://biowulf.nih.gov). This work was supported by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases and by the Intramural Antiviral Target Program of the
Office of the Director, NIH. J.H.L. is the recipient of a KVSTA
Fellowship.
NR 53
TC 0
Z9 0
U1 3
U2 12
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
EI 1463-9084
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PD FEB 28
PY 2016
VL 18
IS 8
BP 5759
EP 5770
DI 10.1039/c5cp04542h
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DG3ET
UT WOS:000371953000009
PM 26415896
ER
PT J
AU Gill, ML
Byrd, RA
Palmer, AG
AF Gill, Michelle L.
Byrd, R. Andrew
Palmer, Arthur G., III
TI Dynamics of GCN4 facilitate DNA interaction: a model-free analysis of an
intrinsically disordered region
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID MAGNETIC-RESONANCE RELAXATION; UNSTRUCTURED PROTEINS; LEUCINE-ZIPPER;
BASIC REGION; NMR-SPECTROSCOPY; BINDING DOMAIN; INDUCED FIT; SENSITIVITY
IMPROVEMENT; N-15 RELAXATION; SPIN RELAXATION
AB Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) are known to play important roles in regulatory and signaling pathways. A critical aspect of these functions is the ability of IDP/IDRs to form highly specific complexes with target molecules. However, elucidation of the contributions of conformational dynamics to function has been limited by challenges associated with structural heterogeneity of IDP/IDRs. Using NMR spin relaxation parameters (N-15 R-1, N-15 R-2, and {H-1}-N-15 heteronuclear NOE) collected at four static magnetic fields ranging from 14.1 to 21.1 T, we have analyzed the backbone dynamics of the basic leucine-zipper (bZip) domain of the Saccharomyces cerevisiae transcription factor GCN4, whose DNA binding domain is intrinsically disordered in the absence of DNA substrate. We demonstrate that the extended model-free analysis can be applied to proteins with IDRs such as apo GCN4 and that these results significantly extend previous NMR studies of GCN4 dynamics performed using a single static magnetic field of 11.74 T [Bracken, et al., J. Mol. Biol., 1999, 285, 2133-2146] and correlate well with molecular dynamics simulations [Robustelli, et al., J. Chem. Theory Comput., 2013, 9, 5190-5200]. In contrast to the earlier work, data at multiple static fields allows the time scales of internal dynamics of GCN4 to be reliably quantified. Large amplitude dynamic fluctuations in the DNA-binding region have correlation times (tau(S) approximate to 1.4-2.5 ns) consistent with a two-step mechanism in which partially ordered bZip conformations of GCN4 form initial encounter complexes with DNA and then rapidly rearrange to the high affinity state with fully formed basic region recognition helices.
C1 [Gill, Michelle L.; Palmer, Arthur G., III] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
[Gill, Michelle L.; Byrd, R. Andrew] NCI, Struct Biophys Lab, NIH, Frederick, MD 21702 USA.
RP Palmer, AG (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
EM agp6@columbia.edu
OI Byrd, R. Andrew/0000-0003-3625-4232
FU National Institute of Health [GM50291, GM089047]; NIH [RR026540,
P41GM066354]; NYSTAR grant; ORIP/NIH [CO6RR015495]; Keck Foundation; New
York State Assembly; U. S. Department of Defense; Intramural Research
Program of the National Cancer Institute
FX A. G. P. and M. L. G acknowledge support from National Institute of
Health grants GM50291 and GM089047, respectively. The AVANCE 600 NMR
spectrometer at Columbia University was purchased with the support of
NIH grant RR026540. A. G. P. is a member of the New York Structural
Biology Center (NYSBC). The data acquired at 16.45, 18.8 and 21.1 T were
collected at NYSBC, which was made possible by a NYSTAR grant and
ORIP/NIH facility improvement grant CO6RR015495. The 900 MHz NMR
spectrometers were purchased with funds from NIH grant P41GM066354, the
Keck Foundation, New York State Assembly, and U. S. Department of
Defense. This research was partially supported by the Intramural
Research Program of the National Cancer Institute.
NR 68
TC 3
Z9 3
U1 4
U2 13
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
EI 1463-9084
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PD FEB 28
PY 2016
VL 18
IS 8
BP 5839
EP 5849
DI 10.1039/c5cp06197k
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DG3ET
UT WOS:000371953000016
PM 26661739
ER
PT J
AU Verdel, R
Dagdug, L
Berezhkovskii, AM
Bezrukov, SM
AF Verdel, Roberto
Dagdug, Leonardo
Berezhkovskii, Alexander M.
Bezrukov, Sergey M.
TI Unbiased diffusion in two-dimensional channels with corrugated walls
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
AB This paper deals with diffusion of point particles in linearly corrugated two-dimensional channels. Such geometry allows one to obtain an approximate analytical expression that gives the particle effective diffusivity as a function of the geometric parameters of the channel. To establish its accuracy and the range of applicability, the expression is tested against Brownian dynamics simulation results. The test shows that the expression works very well for long channel periods, but fails when the period is not long enough compared to the minimum width of the channel. To fix this deficiency, we propose a simple empirical correction to the analytical expression. The resulting corrected expression for the effective diffusivity is in excellent agreement with the simulation results for all values of the channel period. (C) 2016 AIP Publishing LLC.
C1 [Verdel, Roberto; Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico.
[Berezhkovskii, Alexander M.] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bldg 10, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Program Phys Biol, Bethesda, MD 20892 USA.
RP Verdel, R (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico.
OI Bezrukov, Sergey/0000-0002-8209-8050
FU Consejo Nacional de Ciencia y Tecnologia (CONACyT) [176452]; Intramural
Research Program of the NIH; Center for Information Technology; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX L.D. thanks Consejo Nacional de Ciencia y Tecnologia (CONACyT) for
partial support under Grant No. 176452. This study was supported by the
Intramural Research Program of the NIH, Center for Information
Technology and Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
NR 10
TC 3
Z9 3
U1 6
U2 10
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD FEB 28
PY 2016
VL 144
IS 8
AR 084106
DI 10.1063/1.4942470
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DF8OX
UT WOS:000371618800009
PM 26931680
ER
PT J
AU Berger, VW
Bejleri, K
Agnor, R
AF Berger, Vance W.
Bejleri, Klejda
Agnor, Rebecca
TI Comparing MTI randomization procedures to blocked randomization
SO STATISTICS IN MEDICINE
LA English
DT Article
DE inertia; maximal procedure; MTI procedures; permuted blocks;
randomization
ID CLINICAL-TRIALS; PHASE-II; CANCER; CARBOPLATIN; BIAS
AB Randomization is one of the cornerstones of the randomized clinical trial, and there is no shortage of methods one can use to randomize patients to treatment groups. When deciding which one to use, researchers must bear in mind that not all randomization procedures are equally adept at achieving the objective of randomization, namely, balanced treatment groups. One threat is chronological bias, and permuted blocks randomization does such a good job at controlling chronological bias that it has become the standard randomization procedure in clinical trials. But permuted blocks randomization is especially vulnerable to selection bias, so as a result, the maximum tolerated imbalance (MTI) procedures were proposed as better alternatives. In comparing the procedures, we have somewhat of a false controversy, in that actual practice goes uniformly one way (permuted blocks), whereas scientific arguments go uniformly the other way (MTI procedures). There is no argument in the literature to suggest that the permuted block design is better than or even as good as the MTI procedures, but this dearth is matched by an equivalent one regarding actual trials using the MTI procedures. So the controversy', if we are to call it that, pits misguided precedent against sound advice that tends to be ignored in practice. We shall review the issues to determine scientifically which of the procedures is better and, therefore, should be used. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Berger, Vance W.] NCI, Biometry Res Grp, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Berger, Vance W.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
[Bejleri, Klejda] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
[Agnor, Rebecca] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA.
RP Agnor, R (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA.
EM rcagnor@live.unc.edu
NR 24
TC 6
Z9 6
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD FEB 28
PY 2016
VL 35
IS 5
BP 685
EP 694
DI 10.1002/sim.6637
PG 10
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DC0YW
UT WOS:000368945000003
PM 26337607
ER
PT J
AU Takaku, M
Grimm, SA
Shimbo, T
Perera, L
Menafra, R
Stunnenberg, HG
Archer, TK
Machida, S
Kurumizaka, H
Wade, PA
AF Takaku, Motoki
Grimm, Sara A.
Shimbo, Takashi
Perera, Lalith
Menafra, Roberta
Stunnenberg, Hendrik G.
Archer, Trevor K.
Machida, Shinichi
Kurumizaka, Hitoshi
Wade, Paul A.
TI GATA3-dependent cellular reprogramming requires activation-domain
dependent recruitment of a chromatin remodeler
SO GENOME BIOLOGY
LA English
DT Article
DE GATA3; Mesenchymal-to-epithelial transition; Breast cancer; Pioneer
factor; Chromatin remodeling; Enhancer establishment
ID PIONEER TRANSCRIPTION FACTORS; HUMAN BREAST-TUMORS; DNA-BINDING;
GENE-EXPRESSION; CRYSTAL-STRUCTURE; OCTAMER TRANSFER; HISTONE OCTAMER;
HUMAN GATA-3; HUMAN GENOME; NUCLEOSOME
AB Background: Transcription factor-dependent cellular reprogramming is integral to normal development and is central to production of induced pluripotent stem cells. This process typically requires pioneer transcription factors (TFs) to induce de novo formation of enhancers at previously closed chromatin. Mechanistic information on this process is currently sparse.
Results: Here we explore the mechanistic basis by which GATA3 functions as a pioneer TF in a cellular reprogramming event relevant to breast cancer, the mesenchymal to epithelial transition (MET). In some instances, GATA3 binds previously inaccessible chromatin, characterized by stable, positioned nucleosomes where it induces nucleosome eviction, alters local histone modifications, and remodels local chromatin architecture. At other loci, GATA3 binding induces nucleosome sliding without concomitant generation of accessible chromatin. Deletion of the transactivation domain retains the chromatin binding ability of GATA3 but cripples chromatin reprogramming ability, resulting in failure to induce MET.
Conclusions: These data provide mechanistic insights into GATA3-mediated chromatin reprogramming during MET, and suggest unexpected complexity to TF pioneering. Successful reprogramming requires stable binding to a nucleosomal site; activation domain-dependent recruitment of co-factors including BRG1, the ATPase subunit of the SWI/SNF chromatin remodeling complex; and appropriate genomic context. The resulting model provides a new conceptual framework for de novo enhancer establishment by a pioneer TF.
C1 [Takaku, Motoki; Shimbo, Takashi; Archer, Trevor K.; Wade, Paul A.] NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Grimm, Sara A.] NIEHS, Integrat Bioinformat, POB 12233, Res Triangle Pk, NC 27709 USA.
[Perera, Lalith] NIEHS, Lab Genome Integr & Struct Biol, POB 12233, Res Triangle Pk, NC 27709 USA.
[Menafra, Roberta; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Fac Sci & Med, Dept Mol Biol, NL-6525 ED Nijmegen, Netherlands.
[Machida, Shinichi; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Lab Struct Biol, Tokyo, Japan.
RP Wade, PA (reprint author), NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH [ES101965, ES071006, ES043010]; MEXT KAKENHI Grant
[25116002]; Japan Society for the Promotion of Science
FX We gratefully acknowledge Jason Williams, Jeff Tucker, Christine Malone,
Robert Petrovich, and Jason Malphurs for outstanding technical
assistance during the course of this work, and Guang Hu for expression
vectors. This manuscript was substantially improved by critical comments
from Paula Vertino, Guang Hu, and Raja Jothi. This work was supported,
in part, by the Intramural Research Program of the National Institute of
Environmental Health Sciences, NIH (ES101965 to PAW; ES071006 to TKA;
and ES043010 to LP), by MEXT KAKENHI Grant Number 25116002 (to HK) and
by a Fellowship Award from the Japan Society for the Promotion of
Science (to MT).
NR 65
TC 3
Z9 3
U1 3
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD FEB 27
PY 2016
VL 17
AR 36
DI 10.1186/s13059-016-0897-0
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DF3VD
UT WOS:000371275300001
PM 26922637
ER
PT J
AU Ganz, PA
Cecchini, RS
Julian, TB
Margolese, RG
Costantino, JP
Vallow, LA
Albain, KS
Whitworth, PW
Cianfrocca, ME
Brufsky, AM
Gross, HM
Soori, GS
Hopkins, JO
Fehrenbacher, L
Sturtz, K
Wozniak, TF
Seay, TE
Mamounas, EP
Wolmark, N
AF Ganz, Patricia A.
Cecchini, Reena S.
Julian, Thomas B.
Margolese, Richard G.
Costantino, Joseph P.
Vallow, Laura A.
Albain, Kathy S.
Whitworth, Patrick W.
Cianfrocca, Mary E.
Brufsky, Adam M.
Gross, Howard M.
Soori, Gamini S.
Hopkins, Judith O.
Fehrenbacher, Louis
Sturtz, Keren
Wozniak, Timothy F.
Seay, Thomas E.
Mamounas, Eleftherios P.
Wolmark, Norman
TI Patient-reported outcomes with anastrozole versus tamoxifen for
postmenopausal patients with ductal carcinoma in situ treated with
lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind,
phase 3 clinical trial
SO LANCET
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; QUALITY-OF-LIFE; CANCER PREVENTION TRIAL;
FIRST-LINE THERAPY; BOWEL PROJECT P-1; RADIATION-THERAPY; SHORT-FORM;
WOMEN; COMBINATION; SYMPTOMS
AB Background The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms.
Methods The study was done at 333 hospitals in North America. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were randomly assigned to receive either tamoxifen (20 mg/day) or anastrazole (1 mg/day) for 5 years, stratified by age (<60 years vs >= 60 years). Patients and investigators were masked to treatment allocation. Patients completed questionnaires at baseline and every 6 months thereafter for 6 years. The primary outcomes were SF-12 physical and mental health component scale scores, and vasomotor symptoms (as per the BCPT symptom scale). Secondary outcomes were vaginal symptoms and sexual functioning. Exploratory outcomes were musculoskeletal pain, bladder symptoms, gynaecological symptoms, cognitive symptoms, weight problems, vitality, and depression. We did the analyses by intention to treat, including patients who completed questionnaires at baseline and at least once during follow-up. This study is registered with ClinicalTrials.gov, NCT00053898.
Findings Between Jan 6, 2003, and June 15, 2006, 3104 patients were enrolled in the study, of whom 1193 were included in the quality-of-life substudy: 601 assigned to tamoxifen and 592 assigned to anastrozole. We detected no significant difference between treatment groups for: physical health scores (mean severity score 46.72 for tamoxifen vs 45.85 for anastrozole; p= 0.20), mental health scores (52.38 vs 51.48; p= 0.38), energy and fatigue (58.34 vs 57.54; p= 0.86), or symptoms of depression (6.19 vs 6.39; p= 0.46) over 5 years. Vasomotor symptoms (1.33 vs 1.17; p= 0.011), difficulty with bladder control (0.96 vs 0.80; p= 0.0002), and gynaecological symptoms (0.29 vs 0.18; p< 0.0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1.50 vs 1.72; p= 0.0006) and vaginal symptoms (0.76 vs 0.86; p= 0.035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43.65 vs 45.29; p= 0.56). Younger age was significantly associated with more severe vasomotor symptoms (mean severity score 1.45 for age < 60 years vs 0.65 for age >= 60 years; p= 0.0006), vaginal symptoms (0.98 vs 0.65; p< 0.0001), weight problems (1.32 vs 1.02; p< 0.0001), and gynaecological symptoms (0.26 vs 0.22; p= 0.014).
Interpretation Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug. For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative.
C1 [Ganz, Patricia A.; Julian, Thomas B.; Margolese, Richard G.; Vallow, Laura A.; Albain, Kathy S.; Whitworth, Patrick W.; Cianfrocca, Mary E.; Brufsky, Adam M.; Gross, Howard M.; Soori, Gamini S.; Hopkins, Judith O.; Fehrenbacher, Louis; Sturtz, Keren; Wozniak, Timothy F.; Seay, Thomas E.; Mamounas, Eleftherios P.; Wolmark, Norman] NRG Oncol Natl Surg Adjuvant Breast & Bowel Proje, Pittsburgh, PA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Cecchini, Reena S.; Costantino, Joseph P.] NRG Oncol, Pittsburgh, PA USA.
[Cecchini, Reena S.; Costantino, Joseph P.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Julian, Thomas B.; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Dept Surg Oncol, Pittsburgh, PA 15212 USA.
[Margolese, Richard G.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Vallow, Laura A.] Mayo Clin, Dept Radiat Oncol, Jacksonville, FL 32224 USA.
[Albain, Kathy S.; Cianfrocca, Mary E.] Southwest Oncol Grp, San Antonio, TX USA.
[Albain, Kathy S.] Loyola Univ, Sch Med, Stritch Sch Med, Chicago, IL 60611 USA.
[Whitworth, Patrick W.] Amer Coll Surg Oncol, Alliance Clin Trials Oncol, Chicago, IL USA.
[Whitworth, Patrick W.] Nashville Breast Ctr, Nashville, TN USA.
[Cianfrocca, Mary E.] Amer Coll Radiol Imaging Network, Eastern Cooperat Oncol Grp, Philadelphia, PA USA.
[Cianfrocca, Mary E.] Banner MD Anderson Canc Ctr, Dept Hematol Oncol, Gilbert, AZ USA.
[Brufsky, Adam M.] Univ Pittsburgh, Magee Womens Hosp, Dept Hematol, Pittsburgh, PA 15213 USA.
[Gross, Howard M.] Dayton Phys, Dayton, OH USA.
[Soori, Gamini S.] Missouri Valley Canc Consortium, Omaha, NE USA.
[Hopkins, Judith O.] NCI, Southeast Clin Oncol Res Consortium, Community Oncol Res Program, Winston Salem, NC USA.
[Hopkins, Judith O.] Forsyth Reg Canc Ctr, Dept Hematol Oncol, Winston Salem, NC USA.
[Fehrenbacher, Louis] Kaiser Permanente, Dept Med Oncol, Northern Calif Vallejo, CA USA.
[Sturtz, Keren] Colorado Canc Res Program, Dept Med Oncol, Denver, CO USA.
[Wozniak, Timothy F.] Christiana Care Hlth Syst, Community Clin Oncol Program, Wilmington, DE USA.
[Seay, Thomas E.] Atlanta Reg Community Clin Oncol Program, Atlanta, GA USA.
[Mamounas, Eleftherios P.] Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA.
RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90049 USA.
EM pganz@mednet.ucla.edu
OI Cecchini, Reena/0000-0002-9075-9357
FU US National Cancer Institute; AstraZeneca Pharmaceuticals
FX US National Cancer Institute, AstraZeneca Pharmaceuticals.
NR 26
TC 5
Z9 5
U1 5
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 27
PY 2016
VL 387
IS 10021
BP 857
EP 865
DI 10.1016/S0140-6736(15)01169-1
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DE9RA
UT WOS:000370974400030
PM 26686960
ER
PT J
AU Ossoli, A
Neufeld, EB
Thacker, SG
Vaisman, B
Pryor, M
Freeman, LA
Brantner, CA
Baranova, I
Francone, NO
Demosky, SJ
Vitali, C
Locatelli, M
Abbate, M
Zoja, C
Franceschini, G
Calabresi, L
Remaley, AT
AF Ossoli, Alice
Neufeld, Edward B.
Thacker, Seth G.
Vaisman, Boris
Pryor, Milton
Freeman, Lita A.
Brantner, Christine A.
Baranova, Irina
Francone, Nicolas O.
Demosky, Stephen J., Jr.
Vitali, Cecilia
Locatelli, Monica
Abbate, Mauro
Zoja, Carlamaria
Franceschini, Guido
Calabresi, Laura
Remaley, Alan T.
TI Lipoprotein X Causes Renal Disease in LCAT Deficiency
SO PLOS ONE
LA English
DT Article
ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; APOLIPOPROTEIN-A-I; FAMILIAL
LECITHIN; GLOMERULAR ENDOTHELIUM; MESANGIAL CELLS; METABOLISM;
PODOCYTES; PATIENT; BIOLOGY; MICE
AB Human familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat(-/-) mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat(-/-) mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat(-/-) mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA(2) and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat(-/-) mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.
C1 [Ossoli, Alice; Vitali, Cecilia; Franceschini, Guido; Calabresi, Laura] Univ Milan, Ctr Grossi Paoletti, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
[Neufeld, Edward B.; Thacker, Seth G.; Vaisman, Boris; Pryor, Milton; Freeman, Lita A.; Francone, Nicolas O.; Demosky, Stephen J., Jr.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brantner, Christine A.] NIH, NHLBI Elect Microscopy Core Facil, Bldg 10, Bethesda, MD 20892 USA.
[Baranova, Irina] NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Locatelli, Monica; Abbate, Mauro] IRCCS Ist Ric Farmacol Mario Negri, Ctr Anna Maria Astori, Sci & Technol Pk Kilometro Rosso, Bergamo, Italy.
RP Neufeld, EB (reprint author), NHLBI, Lipoprot Metab Sect, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM neufelde@mail.nih.gov
RI Ossoli, Alice/K-5917-2016
OI Ossoli, Alice/0000-0002-9902-252X
FU Division of Intramural Research, National Heart, Lung and Blood
Institute of the NIH [GGP14125]; Telethon - Italy; MedImmune, Inc. as a
CRADA-NIH Grant
FX Research support for this study came from the Division of Intramural
Research, National Heart, Lung and Blood Institute of the NIH, grant
number: GGP14125. Funding Institution: Telethon - Italy
(www.Telethon.it). Additional funding to ATR was provided by MedImmune,
Inc. as a CRADA-NIH Grant. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 59
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 26
PY 2016
VL 11
IS 2
AR e0150083
DI 10.1371/journal.pone.0150083
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF3UU
UT WOS:000371274400084
PM 26919698
ER
PT J
AU Li, ZZ
Xu, X
Feng, XM
Murphy, PM
AF Li, Zhanzhuo
Xu, Xin
Feng, Xingmin
Murphy, Philip M.
TI The Macrophage-depleting Agent Clodronate Promotes Durable Hematopoietic
Chimerism and Donor-specific Skin Allograft Tolerance in Mice
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MIXED CHIMERISM; TRANSPLANTATION TOLERANCE; CELL TRANSPLANTATION;
STEM-CELLS; MOBILIZATION; THERAPY
AB Hematopoietic chimerism is known to promote donor-specific organ allograft tolerance; however, clinical translation has been impeded by the requirement for toxic immunosuppression and large doses of donor bone marrow (BM) cells. Here, we investigated in mice whether durable chimerism might be enhanced by pre-treatment of the recipient with liposomal clodronate, a macrophage depleting agent, with the goal of vacating BM niches for preferential reoccupation by donor hematopoietic stem cells (HSC). We found that liposomal clodronate pretreatment of C57BL/6 mice permitted establishment of durable hematopoietic chimerism when the mice were given a low dose of donor BM cells and transient immunosuppression. Moreover, clodronate pre-treatment increased durable donor-specific BALB/c skin allograft tolerance. These results provide proof-of-principle that clodronate is effective at sparing the number of donor BM cells required to achieve durable hematopoietic chimerism and donor-specific skin allograft tolerance and justify further development of a tolerance protocol based on this principle.
C1 [Li, Zhanzhuo; Xu, Xin; Murphy, Philip M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Feng, Xingmin] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM pmm@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, NIH [AI000615-25]
FX The authors thank Dr. Estefania Claudio Etienne of the Laboratory of
Molecular Immunology, NIAID; and Drs. Victoria Hoffmann and Lauren
Brinster of the Division of Veterinary Resources (DVR), Office of
Research Services (ORS), NIH for technical assistance. This work was
supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases (Project Number AI000615-25), NIH.
NR 26
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 26
PY 2016
VL 6
AR 22143
DI 10.1038/srep22143
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE8CT
UT WOS:000370864100002
PM 26917238
ER
PT J
AU Brudno, J
Tadmor, T
Pittaluga, S
Nicolae, A
Polliack, A
Dunleavy, K
AF Brudno, Jennifer
Tadmor, Tamar
Pittaluga, Stefania
Nicolae, Alina
Polliack, Aaron
Dunleavy, Kieron
TI Discordant bone marrow involvement in non-Hodgkin lymphoma
SO BLOOD
LA English
DT Review
ID B-CELL LYMPHOMA; POSITRON-EMISSION-TOMOGRAPHY; INTERNATIONAL PROGNOSTIC
INDEX; CHRONIC LYMPHOCYTIC-LEUKEMIA; FOLLICULAR LYMPHOMA; FDG-PET/CT;
DIAGNOSTIC PERFORMANCE; BIOPSY INVOLVEMENT; MALIGNANT-LYMPHOMA;
CLINICAL-FEATURES
AB A discordant lymphoma occurs where 2 distinct histologic subtypes coexist in at least 2 separate anatomic sites. Histologic discordance is most commonly observed between the bone marrow (BM) and lymph nodes (LNs), where typically aggressive lymphoma is found in a LN biopsy with indolent lymphoma in a BM biopsy. Although the diagnosis of discordance relied heavily on histopathology alone in the past, the availability of flow cytometry and molecular studies have aided the identification of this entity. The true prevalence and clinical ramifications of discordance remain controversial as available data are principally retrospective, and there is therefore little consensus to guide optimal management strategies. In this review, we examine the available literature on discordant lymphoma and its outcome, and discuss current therapeutic approaches. Future studies in discordant lymphoma should ideally focus on a large series of patients with adequate tissue samples and in corporate molecular analyses.
C1 [Brudno, Jennifer; Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Tadmor, Tamar] Bnai Zion Med Ctr, Hematol Unit, Haifa, Israel.
[Tadmor, Tamar] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
[Pittaluga, Stefania; Nicolae, Alina] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Polliack, Aaron] Hadassah Univ Hosp, Dept Hematol, POB 12000, IL-91120 Jerusalem, Israel.
[Polliack, Aaron] Hebrew Univ Jerusalem, Sch Med, Jerusalem, Israel.
RP Dunleavy, K (reprint author), NCI, Lymphoid Malignancies Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
FU National Cancer Institute
FX J.B. and K. D. received funding from the Intramural Program of the
National Cancer Institute. The remaining authors declare no competing
financial interests.
NR 57
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD FEB 25
PY 2016
VL 127
IS 8
BP 965
EP 970
DI 10.1182/blood-2015-06-651968
PG 6
WC Hematology
SC Hematology
GA DI3KP
UT WOS:000373397800006
PM 26679865
ER
PT J
AU Sheikh, V
Porter, BO
DerSimonian, R
Kovacs, SB
Thompson, WL
Perez-Diez, A
Freeman, AF
Roby, G
Mican, J
Pau, A
Rupert, A
Adelsberger, J
Higgins, J
Bourgeois, JS
Jensen, SMR
Morcock, DR
Burbelo, PD
Osnos, L
Maric, I
Natarajan, V
Croughs, T
Yao, MD
Estes, JD
Sereti, I
AF Sheikh, Virginia
Porter, Brian O.
DerSimonian, Rebecca
Kovacs, Stephen B.
Thompson, William L.
Perez-Diez, Ainhoa
Freeman, Alexandra F.
Roby, Gregg
Mican, JoAnn
Pau, Alice
Rupert, Adam
Adelsberger, Joseph
Higgins, Jeanette
Bourgeois, Jeffrey S., Jr.
Jensen, Stig M. R.
Morcock, David R.
Burbelo, Peter D.
Osnos, Leah
Maric, Irina
Natarajan, Ven
Croughs, Therese
Yao, Michael D.
Estes, Jacob D.
Sereti, Irini
TI Administration of interleukin-7 increases CD4 T cells in idiopathic CD4
lymphocytopenia
SO BLOOD
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RECOMBINANT HUMAN
INTERLEUKIN-7; 1ST CASE-REPORT; CRYPTOCOCCAL MENINGITIS; VISCERAL
LEISHMANIASIS; YOUNG PATIENT; CD4+LYMPHOCYTOPENIA; PROLIFERATION;
LYMPHOPENIA; INFECTION
AB Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/mu L) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436.
C1 [Sheikh, Virginia; Porter, Brian O.; DerSimonian, Rebecca; Thompson, William L.; Perez-Diez, Ainhoa; Freeman, Alexandra F.; Roby, Gregg; Mican, JoAnn; Pau, Alice; Bourgeois, Jeffrey S., Jr.; Jensen, Stig M. R.; Osnos, Leah; Yao, Michael D.; Sereti, Irini] NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11C422, Bethesda, MD 20892 USA.
[Kovacs, Stephen B.; Rupert, Adam; Adelsberger, Joseph; Higgins, Jeanette; Natarajan, Ven] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Morcock, David R.; Estes, Jacob D.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Burbelo, Peter D.] NIDCR, Dent Clin Res Core, NIH, Bethesda, MD USA.
[Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Croughs, Therese] Cytheris Inc, Subsidiary Cytheris SA, Issy Les Moulineaux, France.
RP Sheikh, V (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11C422, Bethesda, MD 20892 USA.
EM sheikhv@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institute of Dental and Craniofacial Research; National Institutes of
Health (NIH); National Cancer Institute, NIH [HHSN261200800001E]
FX This work was supported in whole or in part by the intramural research
programs of the National Institute of Allergy and Infectious Diseases,
the National Institute of Dental and Craniofacial Research, an
intramural Bench-to-Bedside grant from the National Institutes of Health
(NIH), and by federal funding from the National Cancer Institute, NIH,
under Contract No. HHSN261200800001E.
NR 51
TC 1
Z9 1
U1 2
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD FEB 25
PY 2016
VL 127
IS 8
BP 977
EP 988
DI 10.1182/blood-2015-05-645077
PG 12
WC Hematology
SC Hematology
GA DI3KP
UT WOS:000373397800008
PM 26675348
ER
PT J
AU Domanova, W
Krycer, JR
Chaudhuri, R
Yang, PY
Vafaee, F
Fazakerley, DJ
Humphrey, SJ
James, DE
Kuncic, Z
AF Domanova, Westa
Krycer, James R.
Chaudhuri, Rima
Yang, Pengyi
Vafaee, Fatemeh
Fazakerley, Daniel J.
Humphrey, Sean J.
James, David E.
Kuncic, Zdenka
TI Unravelling signal coordination from large scale phosphorylation kinetic
data
SO BMC BIOINFORMATICS
LA English
DT Meeting Abstract
CT 11th ISCB-Student-Council Symposium held in conjunction with the
Intelligent Systems for Molecular Biology (ISMB) Conference / European
Conference on Computational Biology (ECCB)
CY JUL 10, 2015
CL Dublin, IRELAND
SP Int Soc Computat Biol, Student Council
C1 [Domanova, Westa; Krycer, James R.; Chaudhuri, Rima; Vafaee, Fatemeh; Fazakerley, Daniel J.; James, David E.; Kuncic, Zdenka] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia.
[Domanova, Westa; Kuncic, Zdenka] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.
[Krycer, James R.; Chaudhuri, Rima; Fazakerley, Daniel J.; James, David E.] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia.
[James, David E.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Vafaee, Fatemeh] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
[Yang, Pengyi] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Humphrey, Sean J.] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18A, D-82152 Martinsried, Germany.
EM zdenka.kuncic@sydney.edu.au
NR 0
TC 0
Z9 0
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 25
PY 2016
VL 17
SU 3
MA O7
BP 208
EP 209
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DG2HC
UT WOS:000371886800009
ER
PT J
AU Jee, YH
Sadowski, SM
Celi, FS
Xi, LQ
Raffeld, M
Sacks, DB
Remaley, AT
Wellstein, A
Kebebew, E
Baron, J
AF Jee, Youn Hee
Sadowski, Samira M.
Celi, Francesco S.
Xi, Liqiang
Raffeld, Mark
Sacks, David B.
Remaley, Alan T.
Wellstein, Anton
Kebebew, Electron
Baron, Jeffrey
TI Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer
SO PLOS ONE
LA English
DT Article
ID FOLLICULAR LESIONS; CELL-GROWTH; MIDKINE MK; EXPRESSION; NODULES;
MANAGEMENT; DIAGNOSIS; BENIGN; FAMILY; MOUSE
AB Background
Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown.
Method and Findings
74 subjects (age 47 +/- 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 +/- 6 vs 0.3 +/- 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 +/- 0.6 vs 0.3 +/- 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells.
Conclusion
In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules.
C1 [Jee, Youn Hee; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Sadowski, Samira M.; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Div Endocrinol & Metab, Richmond, VA USA.
[Xi, Liqiang; Raffeld, Mark] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sacks, David B.; Remaley, Alan T.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Wellstein, Anton] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Wellstein, Anton] Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Baron, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM jeffrey.baron@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK); Center for Cancer Research, National Cancer
Institute (NCI); Clinical Center of the National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), the Center for Cancer Research, National
Cancer Institute (NCI), and the Clinical Center of the National
Institutes of Health.
NR 25
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 25
PY 2016
VL 11
IS 2
AR e0149383
DI 10.1371/journal.pone.0149383
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2LW
UT WOS:000371175700014
PM 26914549
ER
PT J
AU Valenstein, ML
Roll-Mecak, A
AF Valenstein, Max L.
Roll-Mecak, Antonina
TI Graded Control of Microtubule Severing by Tubulin Glutamylation
SO CELL
LA English
DT Article
ID SPASTIC PARAPLEGIA PROTEIN; ALPHA-TUBULIN; BETA-TUBULIN;
POSTTRANSLATIONAL MODIFICATIONS; MULTISITE PHOSPHORYLATION; AXON
REGENERATION; KATANIN; POLYGLUTAMYLATION; DROSOPHILA; BINDING
AB Microtubule-severing enzymes are critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles, and cilia where tubulin detyrosination, acetylation, and glutamylation are abundant. These modifications exhibit stereotyped patterns suggesting spatial and temporal control of microtubule functions. Using human-engineered and differentiallymodified microtubuleswefind that glutamylation is themain regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per tubulin. Unexpectedly, glutamylation is a nonlinear biphasic tuner and becomes inhibitory beyond a threshold. Furthermore, the inhibitory effect of localized glutamylationpropagates across neighboring microtubules, modulating severing in trans. Our work provides the first quantitative evidence for a graded response to a tubulin posttranslational modification and a biochemical link between tubulin glutamylation and complex architectures of microtubule arrays such as those in neurons where spastin deficiency causes disease.
C1 [Valenstein, Max L.; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Roll-Mecak, Antonina] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Roll-Mecak, A (reprint author), NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.; Roll-Mecak, A (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM antonina@mail.nih.gov
FU Searle Scholar award; intramural program of NINDS; intramural program of
NHLBI
FX We thank C.P. Garnham and I. Yu, National Institute of Neurological
Disorders and Stroke (NINDS) for purified TTLL7, A. Syzk (NINDS) for
recombinant tubulin, Y. Li of the NINDS Mass Spectrometry facility for
MS/MS, D.-Y. Lee and the National Heart, Lung and Blood Institute
(NHLBI) Biochemistry facility for access to mass spectrometers, Y. He
(NHLBI) for large-scale cultures. A.R.-M. thanks H. Bourne, A.
Ferre-D'Amare, E. Giniger, S. Gottesman, and M. Maurizi for helpful
discussions. M.L.V. thanks C.C. Valenstein for feedback. This work was
supported by a Searle Scholar award to A.R.-M. and the intramural
programs of NINDS and NHLBI.
NR 77
TC 14
Z9 24
U1 13
U2 23
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD FEB 25
PY 2016
VL 164
IS 5
BP 911
EP 921
DI 10.1016/j.cell.2016.01.019
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DE8DZ
UT WOS:000370867300015
PM 26875866
ER
PT J
AU Cross, R
Olivieri, L
O'Brien, K
Kellman, P
Xue, H
Hansen, M
AF Cross, Russell
Olivieri, Laura
O'Brien, Kendall
Kellman, Peter
Xue, Hui
Hansen, Michael
TI Improved workflow for quantification of left ventricular volumes and
mass using free-breathing motion corrected cine imaging
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Retrospective reconstruction; Cardiac function; Cardiac volume; Motion
correction; Real-time imaging; Cardiovascular MR; Breath-held;
Free-breathing; Cine; Reconstruction time
ID CARDIOVASCULAR MAGNETIC-RESONANCE; RETROSPECTIVE RECONSTRUCTION;
REPRODUCIBILITY; IMAGES; MRI; ECHOCARDIOGRAPHY; GADGETRON; HOLD
AB Background: Traditional cine imaging for cardiac functional assessment requires breath-holding, which can be problematic in some situations. Free-breathing techniques have relied on multiple averages or real-time imaging, producing images that can be spatially and/or temporally blurred. To overcome this, methods have been developed to acquire real-time images over multiple cardiac cycles, which are subsequently motion corrected and reformatted to yield a single image series displaying one cardiac cycle with high temporal and spatial resolution. Application of these algorithms has required significant additional reconstruction time. The use of distributed computing was recently proposed as a way to improve clinical workflow with such algorithms. In this study, we have deployed a distributed computing version of motion corrected re-binning reconstruction for free-breathing evaluation of cardiac function.
Methods: Twenty five patients and 25 volunteers underwent cardiovascular magnetic resonance (CMR) for evaluation of left ventricular end-systolic volume (ESV), end-diastolic volume (EDV), and end-diastolic mass. Measurements using motion corrected re-binning were compared to those using breath-held SSFP and to free-breathing SSFP with multiple averages, and were performed by two independent observers. Pearson correlation coefficients and Bland-Altman plots tested agreement across techniques. Concordance correlation coefficient and Bland-Altman analysis tested inter-observer variability. Total scan plus reconstruction times were tested for significant differences using paired t-test.
Results: Measured volumes and mass obtained by motion corrected re-binning and by averaged free-breathing SSFP compared favorably to those obtained by breath-held SSFP (r = 0.9863/0.9813 for EDV, 0.9550/0.9685 for ESV, 0.9952/0.9771 for mass). Inter-observer variability was good with concordance correlation coefficients between observers across all acquisition types suggesting substantial agreement. Both motion corrected re-binning and averaged free-breathing SSFP acquisition and reconstruction times were shorter than breath-held SSFP techniques (p < 0.0001). On average, motion corrected re-binning required 3 min less than breath-held SSFP imaging, a 37 % reduction in acquisition and reconstruction time.
Conclusions: The motion corrected re-binning image reconstruction technique provides robust cardiac imaging that can be used for quantification that compares favorably to breath-held SSFP as well as multiple average free-breathing SSFP, but can be obtained in a fraction of the time when using cloud-based distributed computing reconstruction.
C1 [Cross, Russell; Olivieri, Laura; O'Brien, Kendall] Childrens Natl Hlth Syst, Div Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA.
[Kellman, Peter; Xue, Hui; Hansen, Michael] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Cross, R (reprint author), Childrens Natl Hlth Syst, Div Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM rcross@childrensnational.org
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood
Institute.
NR 21
TC 2
Z9 2
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD FEB 25
PY 2016
VL 18
AR 10
DI 10.1186/s12968-016-0231-8
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DE9AU
UT WOS:000370928600001
PM 26915830
ER
PT J
AU Grandhi, A
Guo, WG
Peddada, SD
AF Grandhi, Anjana
Guo, Wenge
Peddada, Shyamal D.
TI A multiple testing procedure for multi-dimensional pairwise comparisons
with application to gene expression studies
SO BMC BIOINFORMATICS
LA English
DT Article
DE mdFDR; BH procedure; Multiple testing; Differential gene expression;
Tumor size
ID FALSE DISCOVERY RATE; DIRECTIONAL ERRORS; TUMOR SIZE; GROWTH; CANCER;
INHIBITION; LEIOMYOMA
AB Background: Often researchers are interested in comparing multiple experimental groups (e.g. tumor size) with a reference group (e.g. normal tissue) on the basis of thousands of features (e.g. genes) and determine if a differentially expressed feature is up or down regulated in a pairwise comparison. There are two sources of false discoveries, one due to multiple testing involving several pairwise comparisons and the second due to falsely declaring a feature to be up (or down) regulated when it is not (known as directional error). Together, the total error rate is called the mixed directional false discovery rate (mdFDR).
Results: We develop a general powerful mdFDR controlling testing procedure and illustrate the methodology by analyzing uterine fibroid gene expression data (PLoS ONE 8:63909, 2013). We identify several differentially expressed genes (DEGs) and pathways that are specifically enriched according to the size of a uterine fibroid.
Conclusions: The proposed general procedure strongly controls mdFDR. Several specific methodologies can be derived from this general methodology by using appropriate testing procedures at different steps of the general procedure. Thus we are providing a general framework for making multiple pairwise comparisons. Our analysis of the uterine fibroid growth gene expression data suggests that molecular characteristics of a fibroid changes with size. Our powerful methodology allowed us to draw several interesting conclusions regarding the molecular characteristics of uterine fibroids. For example, IL-1 signaling pathway (Sci STKE 2003:3, 2003), associated with inflammation and known to activate prostaglandins that are implicated in the progression of fibroids, is significantly enriched only in small tumors (volume < 5.7 cm(3)). It appears that the molecular apparatus necessary for fibroid growth and development is established during tumor development. A complete list of all DEGs and the corresponding enriched pathways according to tumor size is provided for researchers to mine these data. Identification of these DEGs and the pathways may potentially have clinical implications.
C1 [Peddada, Shyamal D.] NIEHS, Biostat & Computat Biol Branch, TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
[Grandhi, Anjana] Merck Res Labs, BARDS, RY34-A3086h,126 E Lincoln Ave, Rahway, NJ 07065 USA.
[Guo, Wenge] New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
RP Peddada, SD (reprint author), NIEHS, Biostat & Computat Biol Branch, TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM peddada@niehs.nih.gov
OI Guo, Wenge/0000-0003-3777-2058
FU NSF [DMS-1006021, DMS-1309162]; Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences [Z01 ES101744]
FX Authors thank Dr. Donna Baird and Dr. Barbara Davis for carefully
reading the manuscript and making suggestions which improved the
presentation. The research of AG and WG is supported by NSF Grant
DMS-1006021 and DMS-1309162 and the research of SDP is supported [in
part] by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (Z01 ES101744).
NR 36
TC 0
Z9 0
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 25
PY 2016
VL 17
AR 104
DI 10.1186/s12859-016-0937-5
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DE6WM
UT WOS:000370775200002
PM 26917217
ER
PT J
AU Kabat, AM
Harrison, OJ
Riffelmacher, T
Moghaddam, AE
Pearson, CF
Laing, A
Abeler-Dorner, L
Forman, SP
Grencis, RK
Sattentau, Q
Simon, AK
Pott, J
Kevin, JM
AF Kabat, Agnieszka M.
Harrison, Oliver J.
Riffelmacher, Thomas
Moghaddam, Amin E.
Pearson, Claire F.
Laing, Adam
Abeler-Doerner, Lucie
Forman, Simon P.
Grencis, Richard K.
Sattentau, Quentin
Simon, Anna Katharina
Pott, Johanna
Maloy, Kevin J.
TI The autophagy gene Atg16I1 differentially regulates T-reg and T(H)2
cells to control intestinal inflammation
SO ELIFE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FATTY-ACID-METABOLISM; CROHN-DISEASE; IMPAIRED
AUTOPHAGY; BOWEL-DISEASE; IBD GENETICS; LYMPHOCYTES; VARIANT;
DEGRADATION; PROTEIN
AB A polymorphism in the autophagy gene Atg1611 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg1611 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) T-reg cells. Specific ablation of Atg1611 in Foxp3(+) T-reg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal T(H)2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal T-H cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders.
C1 [Kabat, Agnieszka M.; Harrison, Oliver J.; Moghaddam, Amin E.; Sattentau, Quentin; Pott, Johanna; Maloy, Kevin J.] Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
[Harrison, Oliver J.] NIAID, Immun Barrier Sites Initiat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Riffelmacher, Thomas] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England.
[Riffelmacher, Thomas; Simon, Anna Katharina] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England.
[Pearson, Claire F.] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England.
[Laing, Adam; Abeler-Doerner, Lucie] Kings Coll London, Peter Gorer Dept Immunobiol, London WC2R 2LS, England.
[Forman, Simon P.; Grencis, Richard K.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
RP Pott, J; Kevin, JM (reprint author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
EM johanna.pott@path.ox.ac.uk; kevin.maloy@path.ox.ac.uk
FU Wellcome Trust [097112, 100290, 100156, 102972]; Medical Research
Council [MR/K011898/1]
FX Wellcome Trust Graduate Student Scholarship 097112 Agnieszka Martyna
Kabat; Wellcome Trust 100290 Simon P Forman Richard K Grencis; Wellcome
Trust 100156 Simon P Forman Richard K Grencis; Medical Research Council
MR/K011898/1 Johanna Pott Kevin J Maloy; Wellcome Trust 102972 Kevin J
Maloy
NR 74
TC 8
Z9 8
U1 1
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 24
PY 2016
VL 5
AR e12444
DI 10.7554/eLife.12444
PG 29
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DG2GP
UT WOS:000371885300001
PM 26910010
ER
PT J
AU Tan, HX
Gilbertson, BP
Jegaskanda, S
Alcantara, S
Amarasena, T
Stambas, J
McAuley, JL
Kent, SJ
De Rose, R
AF Tan, Hyon-Xhi
Gilbertson, Brad P.
Jegaskanda, Sinthujan
Alcantara, Sheilajen
Amarasena, Thakshila
Stambas, John
McAuley, Julie L.
Kent, Stephen J.
De Rose, Robert
TI Recombinant influenza virus expressing HIV-1 p24 capsid protein induces
mucosal HIV-specific CD8 T-cell responses
SO VACCINE
LA English
DT Article
DE Vaccine; Influenza; HIV; Mucosal immunity; CD8 T-cell; Prime-boost
ID SIMIAN IMMUNODEFICIENCY VIRUS; A VIRUS; IMMUNE-RESPONSES; PRIMARY
INFECTION; FITNESS COST; VIRAL LOAD; TYPE-1; VACCINE; MEMORY;
IMMUNIZATION
AB Influenza viruses are promising mucosal vaccine vectors for HIV but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. We developed recombinant influenza viruses incorporating the HIV-1 p24 gag capsid into the NS-segment of PR8 (H1N1) and X31 (H3N2) influenza viruses with the use of multiple 2A ribosomal skip sequences. Despite the insertion of a sizable HIV-1 gene into the influenza genome, recombinant viruses were readily rescued to high titers. Intracellular expression of p24 capsid was confirmed by in vitro infection assays. The recombinant influenza viruses were subsequently tested as mucosal vaccines in BALB/c mice. Recombinant viruses were attenuated and safe in immunized mice. Systemic and mucosal HIV-specific CD8 T-cell responses were elicited in mice that were immunized via intranasal route with a prime-boost regimen. Isolated HIV-specific CD8 T-cells displayed polyfunctional cytokine and degranulation profiles. Mice boosted via intravaginal route induced recall responses from the distal lung mucosa and developed heightened HIV specific CD8 T-cell responses in the vaginal mucosa. These findings demonstrate the potential utility of recombinant influenza viruses as vaccines for mucosal immunity against HIV-1 infection. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Tan, Hyon-Xhi; Gilbertson, Brad P.; Jegaskanda, Sinthujan; Alcantara, Sheilajen; Amarasena, Thakshila; Stambas, John; McAuley, Julie L.; Kent, Stephen J.; De Rose, Robert] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, 792 Elizabeth St, Melbourne, Vic 3010, Australia.
[Stambas, John] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia.
[Stambas, John] CSIRO, Anim Hlth Labs, Geelong, Vic, Australia.
[Kent, Stephen J.] Monash Univ, Cent Clin Sch, Alfred Hosp, Melbourne Sexual Hlth Ctr, Clayton, Vic 3800, Australia.
[Kent, Stephen J.] Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Techn, Melbourne, Vic 3010, Australia.
[Jegaskanda, Sinthujan] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Kent, SJ (reprint author), Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, 792 Elizabeth St, Melbourne, Vic 3010, Australia.
EM skent@unimelb.edu.au
FU Australian Research Council; National Health and Medical Research
Council, Australia
FX This research was supported by the Australian Research Council and
National Health and Medical Research Council, Australia. We thank St.
Jude Children's Hospital, Memphis, TN, for providing the pHW2000
plasmid. We also thank Wendy Winnall for her insightful advice for the
statistical analysis of this study.
NR 46
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD FEB 24
PY 2016
VL 34
IS 9
BP 1172
EP 1179
DI 10.1016/j.vaccine.2016.01.030
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DF7OZ
UT WOS:000371548600005
PM 26826545
ER
PT J
AU Sandoz, KM
Popham, DL
Beare, PA
Sturdevant, DE
Hansen, B
Nair, V
Heinzen, RA
AF Sandoz, Kelsi M.
Popham, David L.
Beare, Paul A.
Sturdevant, Daniel E.
Hansen, Bryan
Nair, Vinod
Heinzen, Robert A.
TI Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell
Wall Remodeling in the Small Cell Variant Developmental Form
SO PLOS ONE
LA English
DT Article
ID LEGIONELLA-PNEUMOPHILA ENHC; GRAM-NEGATIVE BACTERIA; Q-FEVER;
MYCOBACTERIUM-TUBERCULOSIS; ESCHERICHIA-COLI; STATIONARY-PHASE;
HOST-CELL; PEPTIDOGLYCAN DEACETYLASE; STREPTOCOCCUS-PNEUMONIAE;
SALMONELLA-TYPHIMURIUM
AB A hallmark of Coxiella burnetii, the bacterial cause of human Q fever, is a biphasic developmental cycle that generates biologically, ultrastructurally, and compositionally distinct large cell variant (LCV) and small cell variant (SCV) forms. LCVs are replicating, exponential phase forms while SCVs are non-replicating, stationary phase forms. The SCV has several properties, such as a condensed nucleoid and an unusual cell envelope, suspected of conferring enhanced environmental stability. To identify genetic determinants of the LCV to SCV transition, we profiled the C. burnetii transcriptome at 3 (early LCV), 5 (late LCV), 7 (intermediate forms), 14 (early SCV), and 21 days (late SCV) post-infection of Vero epithelial cells. Relative to early LCV, genes downregulated in the SCV were primarily involved in intermediary metabolism. Upregulated SCV genes included those involved in oxidative stress responses, arginine acquisition, and cell wall remodeling. A striking transcriptional signature of the SCV was induction (>7-fold) of five genes encoding predicted L, D transpeptidases that catalyze nonclassical 3-3 peptide cross-links in peptidoglycan (PG), a modification that can influence several biological traits in bacteria. Accordingly, of cross-links identified, muropeptide analysis showed PG of SCV with 46% 3-3 cross-links as opposed to 16% 3-3 cross-links for LCV. Moreover, electron microscopy revealed SCV with an unusually dense cell wall/ outer membrane complex as compared to LCV with its clearly distinguishable periplasm and inner and outer membranes. Collectively, these results indicate the SCV produces a unique transcriptome with a major component directed towards remodeling a PG layer that likely contributes to Coxiella's environmental resistance.
C1 [Sandoz, Kelsi M.; Beare, Paul A.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Popham, David L.] Virginia Tech, Dept Biol Sci, Blacksburg, VA USA.
[Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Hansen, Bryan; Nair, Vinod] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
EM rheinzen@niaid.nih.gov
OI Popham, David/0000-0002-2614-143X
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (RAH).
NR 121
TC 2
Z9 2
U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 24
PY 2016
VL 11
IS 2
AR e0149957
DI 10.1371/journal.pone.0149957
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2IA
UT WOS:000371164700056
PM 26909555
ER
PT J
AU Koonin, EV
Wolf, YI
AF Koonin, Eugene V.
Wolf, Yuri I.
TI Just how Lamarckian is CRISPR-Cas immunity: the continuum of
evolvability mechanisms
SO BIOLOGY DIRECT
LA English
DT Article
DE CRISPR-Cas; Self-nonself discrimination; Lamarckian evolution; Darwinian
evolution; DNA repair
ID ADAPTIVE IMMUNITY; ESCHERICHIA-COLI; DNA-REPAIR; SPACER ACQUISITION;
FOREIGN DNA; SYSTEMS; ADAPTATION; EVOLUTION; ELEMENTS; BACTERIA
AB The CRISPR-Cas system of prokaryotic adaptive immunity displays features of a mechanism for directional, Lamarckian evolution. Indeed, this system modifies a specific locus in a bacterial or archaeal genome by inserting a piece of foreign DNA into a CRISPR array which results in acquired, heritable resistance to the cognate selfish element. A key element of the Lamarckian scheme is the specificity and directionality of the mutational process whereby an environmental cue causes only mutations that provide specific adaptations to the original challenge. In the case of adaptive immunity, the specificity of mutations is equivalent to self-nonself discrimination. Recent studies on the CRISPR mechanism have shown that the levels of discrimination can substantially differ such that in some CRISPR-Cas variants incorporation of DNA is random whereas discrimination occurs by selection of cells that carry cognate inserts. In other systems, a higher level of specificity appears to be achieved via specialized mechanisms. These findings emphasize the continuity between random and directed mutations and the critical importance of evolved mechanisms that govern the mutational process.
C1 [Koonin, Eugene V.; Wolf, Yuri I.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU intramural funds of the US Departmaent of Health and Human Services
FX The authors' research is supported by intramural funds of the US
Departmaent of Health and Human Services (to the National Library of
Medicine).
NR 63
TC 6
Z9 6
U1 6
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD FEB 24
PY 2016
VL 11
AR 9
DI 10.1186/s13062-016-0111-z
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DE7TN
UT WOS:000370839700001
PM 26912144
ER
PT J
AU Chen, JS
Sprague, BL
Klabunde, CN
Tosteson, ANA
Bitton, A
Onega, T
MacLean, CD
Harris, K
Schapira, MM
Haas, JS
AF Chen, Jane S.
Sprague, Brian L.
Klabunde, Carrie N.
Tosteson, Anna N. A.
Bitton, Asaf
Onega, Tracy
MacLean, Charles D.
Harris, Kimberly
Schapira, Marilyn M.
Haas, Jennifer S.
CA PROSPR Population-Based Res Optim
TI Take the money and run? Redemption of a gift card incentive in a
clinician survey
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Survey methods; Provider surveys
ID SURVEY RESPONSE RATES; PHYSICIANS; BREAST
AB Background: Clinician surveys provide critical information about many facets of health care, but are often challenging to implement. Our objective was to assess use by participants and non-participants of a prepaid gift card incentive that could be later reclaimed by the researchers if unused.
Methods: Clinicians were recruited to participate in a mailed or online survey as part of a study to characterize women's primary health care provider attitudes towards breast and cervical cancer screening guidelines and practices (n = 177). An up-front incentive of a $50 gift card to a popular online retailer was included with the study invitation. Clinicians were informed that the gift card would expire if it went unused after 4 months. Outcome measures included use of gift cards by participants and non-participants and comparison of hypothetical costs of different incentive strategies.
Results: 63.5 % of clinicians who responded to the survey used the gift card, and only one provider who didn't participate used the gift card (1.6 %). Many of those who participated did not redeem their gift cards (36.5 % of respondents). The price of the incentives actually claimed totaled $3700, which was less than half of the initial outlay. Since some of the respondents did not redeem their gift cards, the cost of incentives was less than it might have been if we had provided a conditional incentive of $50 to responders after they had completed the survey.
Conclusions: Redeemable online gift card codes may provide an effective way to motivate clinicians to participate in surveys.
C1 [Chen, Jane S.; Bitton, Asaf; Harris, Kimberly; Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA.
[Bitton, Asaf; Haas, Jennifer S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Sprague, Brian L.; MacLean, Charles D.] Univ Vermont, Burlington, VT USA.
[Tosteson, Anna N. A.; Onega, Tracy] Dartmouth & Norris Cotton Canc Ctr, Geisel Sch Med, Lebanon, NH USA.
[Klabunde, Carrie N.] NIH, Off Director, Off Dis Prevent, Bethesda, MD USA.
[Haas, Jennifer S.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Schapira, Marilyn M.] Univ Penn, Philadelphia, PA 19104 USA.
[Schapira, Marilyn M.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Chen, Jane S.] Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA.; Haas, JS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM jhaas@partners.org
FU [U54 CA163307]; [U54 CA 163313]; [U54 CA163303]
FX The authors thank the participating PROSPR Research Centers for the data
they have provided for this study. A list of the PROSPR investigators
and contributing research staff are provided at:
http://healthcaredelivery.cancer.gov/prospr/. (Grant numbers U54
CA163307, U54 CA 163313, U54 CA163303).
NR 9
TC 1
Z9 1
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD FEB 24
PY 2016
VL 16
AR 25
DI 10.1186/s12874-016-0126-2
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DE7SH
UT WOS:000370836500002
PM 26911445
ER
PT J
AU Hong, CS
Hsieh, JK
Edwards, NA
Ray-Chaudhury, A
Zaghloul, KA
AF Hong, Christopher S.
Hsieh, Jason K.
Edwards, Nancy A.
Ray-Chaudhury, Abhik
Zaghloul, Kareem A.
TI IDH mutations may not preclude distant, trans-tentorial spread in
gliomas: a case report and review of the literature
SO WORLD JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Review
DE Cerebellum; Glioma; Isocitrate dehydrogenase; Recurrence
ID OLIGODENDROGLIAL TUMORS; GLIOBLASTOMA; TEMOZOLOMIDE; RADIOTHERAPY;
SURVIVAL; ASTROCYTOMAS; PATHOGENESIS; RESECTION; THERAPY; BENEFIT
AB Background: IDH mutations have been demonstrated to confer prolonged survival in patients suffering from gliomas, but the mechanisms underlying the improved prognosis are unclear. While some studies have attributed these observations to an enhanced sensitivity to genotoxic therapies, others have postulated that IDH-mutated gliomas exhibit less aggressive intrinsic biological behavior, including the propensity to invade distant sites. Although most gliomas recur local to the site of initial presentation, some tumors demonstrate distant recurrence, the vast majority of which involve the contralateral hemisphere. Trans-tentorial spread has been described once before, in which a supratentorial glioblastoma was reported to recur infratentorially in the cerebellum.
Case presentation: We describe a patient who underwent surgical resection, followed by adjuvant radiation and temozolomide of a World Health Organization (WHO) III anaplastic astrocytoma in the right temporal lobe, exhibiting an IDH1 (R132H) mutation. Twenty-two months after surgery, he developed a second lesion, located in the right cerebellum, suspicious for recurrent tumor versus radiation necrosis. A second surgery was performed, and pathology demonstrated recurrent tumor, consistent with IDH1-mutated anaplastic astrocytoma.
Conclusions: This is the first example of trans-tentorial spread in an IDH-mutated glioma, suggesting that despite improved survival, IDH mutations may not preclude gliomas from exhibiting the ability to invade distant sites of the brain.
C1 [Hong, Christopher S.; Hsieh, Jason K.; Edwards, Nancy A.; Ray-Chaudhury, Abhik; Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
[Hong, Christopher S.] Ohio State Univ, Coll Med, 410 W 10th Ave, Columbus, OH 43210 USA.
[Hsieh, Jason K.] Cleveland Clin, Lerner Coll Med, 9500 Euclid Ave NA21, Cleveland, OH 44195 USA.
RP Zaghloul, KA (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM kareem.zaghloul@nih.gov
FU Intramural Research Program at the National Institute of Neurological
Disorders and Stroke; National Cancer Institute at the National
Institutes of Health (NIH); NIH
FX All co-authors were supported by the Intramural Research Program at the
National Institute of Neurological Disorders and Stroke and National
Cancer Institute at the National Institutes of Health (NIH). J.K.H. was
additionally supported by the NIH Medical Research Scholars Program, a
public-private partnership supported jointly by the NIH and generous
contributions to the Foundation for the NIH from Pfizer, Inc., the Doris
Duke Charitable Foundation, Alexandria Real Estate Equities, Inc., and
Mr. and Mrs. Joel S. Marcus and the Howard Hughes Medical Research
Institute, as well as other private donors. For a complete list, please
visit
http://fnih.org/what-we-do/current-education-andtraining-programs/mrsp.
NR 18
TC 0
Z9 0
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7819
J9 WORLD J SURG ONCOL
JI World J. Surg. Oncol.
PD FEB 24
PY 2016
VL 14
AR 53
DI 10.1186/s12957-016-0814-8
PG 5
WC Oncology; Surgery
SC Oncology; Surgery
GA DF0FR
UT WOS:000371015000013
PM 26911558
ER
PT J
AU Reardon, PK
Clasen, L
Giedd, JN
Blumenthal, J
Lerch, JP
Chakravarty, MM
Raznahan, A
AF Reardon, Paul Kirkpatrick
Clasen, Liv
Giedd, Jay N.
Blumenthal, Jonathan
Lerch, Jason P.
Chakravarty, M. Mallar
Raznahan, Armin
TI An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on
Subcortical Anatomy in Humans
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE allometry; aneuploidy; morphometry; sex; subcortex
ID HUMAN BASAL GANGLIA; BRAIN-DEVELOPMENT; Y-CHROMOSOMES; FUNCTIONAL
CONNECTIVITY; MENTAL-HEALTH; ANEUPLOIDIES; CHILDREN; NEUROANATOMY;
ORGANIZATION; ADOLESCENCE
AB Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. Wefind large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X-and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings.
C1 [Reardon, Paul Kirkpatrick; Clasen, Liv; Blumenthal, Jonathan; Raznahan, Armin] NIMH, Dev Neurogen Unit, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Giedd, Jay N.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Lerch, Jason P.] Univ Toronto, Dept Psychiat, 100 Coll St, Toronto, ON M5T 1R8, Canada.
[Lerch, Jason P.] Univ Toronto, Inst Biomat & Biomed Engn, 100 Coll St, Toronto, ON M5T 1R8, Canada.
[Chakravarty, M. Mallar] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Computat Brain Anat Lab, Verdun, PQ H4H 1R3, Canada.
[Chakravarty, M. Mallar] McGill Univ, Dept Psychiat, Montreal, PQ H3A 1A1, Canada.
[Chakravarty, M. Mallar] McGill Univ, Dept Biomed Engn, Montreal, PQ H3A 1A1, Canada.
RP Reardon, PK (reprint author), Dev Neurogen Unit, Child Psychiat Branch, 10 Ctr Dr,Bldg 10,Room 3D42, Bethesda, MD 20892 USA.
EM kirk.reardon@nih.gov
FU National Institutes of Health (NIH); NIH Medical Research Scholars
Program; NIH
FX This work was supported by the National Institutes of Health (NIH)
Intramural Research Program and the NIH Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH from the Doris Duke
Charitable Foundation, The American Association for Dental Research, The
Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as
well as other private donors. We thank the participants and families who
took part in this study. The views expressed in this article do not
necessarily represent the views of the NIMH, NIH, HHS, or the United
States Government.
NR 46
TC 3
Z9 3
U1 5
U2 15
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 24
PY 2016
VL 36
IS 8
BP 2438
EP 2448
DI 10.1523/JNEUROSCI.3195-15.2016
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DE7LX
UT WOS:000370819400012
PM 26911691
ER
PT J
AU Kovar, H
Amatruda, J
Brunet, E
Burdach, S
Cidre-Aranaz, F
de Alava, E
Dirksen, U
van der Ent, W
Grohar, P
Grunewald, TGP
Helman, L
Houghton, P
Iljin, K
Korsching, E
Ladanyi, M
Lawlor, E
Lessnick, S
Ludwig, J
Meltzer, P
Metzler, M
Mora, J
Moriggl, R
Nakamura, T
Papamarkou, T
Sarikas, BR
Redini, F
Richter, GHS
Rossig, C
Schadler, K
Schafer, BW
Scotlandi, K
Sheffield, NC
Shelat, A
Snaar-Jagalska, E
Sorensen, P
Stegmaier, K
Stewart, E
Sweet-Cordero, A
Szuhai, K
Tirado, OM
Tirode, F
Toretsky, J
Tsafou, K
Uren, A
Zinovyev, A
Delattre, O
AF Kovar, Heinrich
Amatruda, James
Brunet, Erika
Burdach, Stefan
Cidre-Aranaz, Florencia
de Alava, Enrique
Dirksen, Uta
van der Ent, Wietske
Grohar, Patrick
Grunewald, Thomas G. P.
Helman, Lee
Houghton, Peter
Iljin, Kristiina
Korsching, Eberhard
Ladanyi, Marc
Lawlor, Elizabeth
Lessnick, Stephen
Ludwig, Joseph
Meltzer, Paul
Metzler, Markus
Mora, Jaume
Moriggl, Richard
Nakamura, Takuro
Papamarkou, Theodore
Sarikas, Branka Radic
Redini, Francoise
Richter, Guenther H. S.
Rossig, Claudia
Schadler, Keri
Schaefer, Beat W.
Scotlandi, Katia
Sheffield, Nathan C.
Shelat, Anang
Snaar-Jagalska, Ewa
Sorensen, Poul
Stegmaier, Kimberly
Stewart, Elizabeth
Sweet-Cordero, Alejandro
Szuhai, Karoly
Tirado, Oscar M.
Tirode, Franck
Toretsky, Jeffrey
Tsafou, Kalliopi
Uren, Aykut
Zinovyev, Andrei
Delattre, Olivier
TI The second European interdisciplinary Ewing sarcoma research summit - A
joint effort to deconstructing the multiple layers of a complex disease
SO ONCOTARGET
LA English
DT Article
DE Ewing sarcoma; epigenetics; development; therapy; microenvironment
ID GENOMIC LANDSCAPE; TUMOR; SENSITIVITY; INHIBITION; EWS-FLI1;
TRABECTEDIN; GROWTH; CANCER; GENES
AB Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNA-sequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter-and intratumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits.
C1 [Kovar, Heinrich] St Anna Kinderkrebsforsch, Childrens Canc Res Inst, Vienna, Austria.
[Kovar, Heinrich] Med Univ Vienna, Dept Pediat, Vienna, Austria.
[Amatruda, James] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Amatruda, James] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
[Amatruda, James] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Brunet, Erika] Museum Natl Hist Nat, INSERM, U1154, CNRS 7196, F-75231 Paris, France.
[Burdach, Stefan; Richter, Guenther H. S.] Tech Univ Munich, Klinikum Rechts Isar, Childrens Canc Res Ctr, D-80290 Munich, Germany.
[Burdach, Stefan; Richter, Guenther H. S.] Tech Univ Munich, Klinikum Rechts Isar, Dept Pediat, D-80290 Munich, Germany.
[Burdach, Stefan; Richter, Guenther H. S.] Comprehens Canc Ctr Munich CCCM, Munich, Germany.
[Cidre-Aranaz, Florencia] Inst Salud Carlos III, Unidad Tumores Solidos Infantiles, Area Genet Humana, Inst Invest Enfermedades Raras, Madrid, Spain.
[de Alava, Enrique] Univ Seville, CSIC, Virgen del Rocio Univ Hosp, Inst Biomed Sevilla IBiS,Dept Pathol, Seville, Spain.
[Dirksen, Uta; Rossig, Claudia] Univ Childrens Hosp Muenster, Pediat Hematol & Oncol, Munster, Germany.
[van der Ent, Wietske; Tirode, Franck; Zinovyev, Andrei; Delattre, Olivier] Inst Curie, Lab Genet & Biol Canc, U830, INSERM, Paris, France.
[van der Ent, Wietske; Snaar-Jagalska, Ewa] Leiden Univ, Inst Biol, Leiden, Netherlands.
[Grohar, Patrick] Van Andel Inst, Ctr Canc & Cell Biol, Grand Rapids, MI USA.
[Grohar, Patrick] Helen DeVos Childrens Hosp, Grand Rapids, MI USA.
[Grunewald, Thomas G. P.] Univ Munich, Inst Pathol, Lab Pediat Sarcoma Biol, Thalkirchner Str 36, D-80539 Munich, Germany.
[Helman, Lee] NCI, Ctr Canc Rearch, NIH, Bethesda, MA USA.
[Houghton, Peter] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Iljin, Kristiina] VTT Tech Res Ctr Finland Ltd, Espoo, Finland.
[Korsching, Eberhard] Univ Munster, Fac Med, Inst Bioinformat, D-48149 Munster, Germany.
[Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol & Human Oncol, 1275 York Ave, New York, NY 10021 USA.
[Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA.
[Lawlor, Elizabeth] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Lawlor, Elizabeth] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Lessnick, Stephen] Ohio State Univ, Nationwide Childrens Hosp, Ctr Childhood Canc & Blood Disorders, Columbus, OH 43210 USA.
[Lessnick, Stephen] Ohio State Univ, Div Pediat Hematol Oncol BMT, Columbus, OH 43210 USA.
[Ludwig, Joseph] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA.
[Meltzer, Paul] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Metzler, Markus] Univ Hosp Erlangen, Pediat Oncol & Hematol, Erlangen, Germany.
[Mora, Jaume] Sant Joan de Deu Hosp, Dept Pediat Oncol, Barcelona, Spain.
[Moriggl, Richard] Ludwig Boltzmann Inst Canc Res, Vienna, Austria.
[Moriggl, Richard] Univ Vet Med & Med Univ, Inst Anim Breeding & Genet, Vienna, Austria.
[Nakamura, Takuro] Japanese Fdn Canc Res, Inst Canc, Div Carcinogenesis, Tokyo 170, Japan.
[Papamarkou, Theodore] Univ Glasgow, Sch Math & Stat, Glasgow, Lanark, Scotland.
[Sarikas, Branka Radic; Sheffield, Nathan C.] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria.
[Redini, Francoise] Univ Nantes, UMR957, INSERM, Nantes, France.
[Schadler, Keri] Univ Texas MD Anderson Canc Ctr, Dept Pediat Res, Houston, TX 77030 USA.
[Schaefer, Beat W.] Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland.
[Schaefer, Beat W.] Univ Childrens Hosp, Childrens Res Ctr, Zurich, Switzerland.
[Scotlandi, Katia] Rizzoli Inst, Expt Oncol Lab, CRS Dev Biomol Therapies, Bologna, Italy.
[Shelat, Anang] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Sorensen, Poul] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada.
[Stegmaier, Kimberly; Stewart, Elizabeth] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Stegmaier, Kimberly; Stewart, Elizabeth] Boston Childrens Hosp, Boston, MA USA.
St Jude Childrens Res Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Sweet-Cordero, Alejandro] Stanford Univ, Dept Pediat, Div Hematol & Oncol, Stanford, CA 94305 USA.
[Szuhai, Karoly] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands.
[Tirado, Oscar M.] Bellvitge Biomed Res Inst IDIBELL, Mol Oncol Lab, Sarcoma Res Grp, Barcelona, Spain.
[Toretsky, Jeffrey; Tsafou, Kalliopi; Uren, Aykut] Georgetown Univ, Sch Med, Dept Oncol, Washington, DC USA.
[Zinovyev, Andrei] INSERM, U900, Paris, France.
[Zinovyev, Andrei] Ecole Mines ParisTech, Fontainebleau, France.
RP Kovar, H (reprint author), St Anna Kinderkrebsforsch, Childrens Canc Res Inst, Vienna, Austria.; Kovar, H (reprint author), Med Univ Vienna, Dept Pediat, Vienna, Austria.
EM heinrich.kovar@ccri.at
RI Papamarkou, Theodore/A-2958-2012; REDINI, Francoise/K-7981-2015;
Grunewald, Thomas/O-2317-2013
OI Papamarkou, Theodore/0000-0002-9689-543X; Szuhai,
Karoly/0000-0002-1228-4245; Grunewald, Thomas/0000-0003-0920-7377
FU European Union [261743, 259348]
FX We thank Anirah Amber and Nuno Andrade for excellent organization of the
meeting. The conference was supported by the European Union's Seventh
Framework Programme grants 261743(ENCCA) and 259348 (ASSET).
NR 35
TC 1
Z9 1
U1 7
U2 10
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 23
PY 2016
VL 7
IS 8
BP 8613
EP 8624
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DL4OW
UT WOS:000375618100014
PM 26802024
ER
PT J
AU Pluchino, KM
Hall, MD
Moen, JK
Chufan, EE
Fetsch, PA
Shukla, S
Gill, DR
Hyde, SC
Xia, D
Ambudkar, SV
Gottesman, MM
AF Pluchino, Kristen M.
Hall, Matthew D.
Moen, Janna K.
Chufan, Eduardo E.
Fetsch, Patricia A.
Shukla, Suneet
Gill, Deborah R.
Hyde, Stephen C.
Xia, Di
Ambudkar, Suresh V.
Gottesman, Michael M.
TI Human-Mouse Chimeras with Normal Expression and Function Reveal That
Major Domain Swapping Is Tolerated by P-Glycoprotein (ABCB1)
SO BIOCHEMISTRY
LA English
DT Article
ID EXCHANGING HOMOLOGOUS DOMAINS; CATALYTIC TRANSITION-STATE;
DRUG-RESISTANCE PROFILES; ANTIGEN-PROCESSING TAP; MULTIDRUG TRANSPORTER;
ATPASE ACTIVITY; PHOSPHATIDYLCHOLINE FLIPPASE; CRYSTAL-STRUCTURE;
INTERACTION SITES; MAMMALIAN-CELLS
AB The efflux transporter P-glycoprotein (P-gp) plays a vital role in the transport of molecules across cell membranes and has been shown to interact with a panoply of functionally and structurally unrelated compounds. How human P-gp interacts with this large number of drugs has not been well understood, although structural flexibility has been implicated. To gain insight into this transporter's broad substrate specificity and to assess its ability to accommodate a variety of molecular and structural changes, we generated human mouse P-gp chimeras by the exchange of homologous transmembrane and nucleotide-binding domains. High-level expression of these chimeras by BacMam- and baculovirus-mediated transduction in mammalian (HeLa) and insect cells, respectively, was achieved. There were no detectable differences between wild-type and chimeric P-gp in terms of cell surface expression, ability to efflux the P-gp substrates rhodamine 123, calcein-AM, and JC-1, or to be inhibited by the substrate cyclosporine A and the inhibitors tariquidar and elacridar. Additionally, expression of chimeric P-gp was able to confer a paclitaxel-resistant phenotype to HeLa cells characteristic of P-gp-mediated drug resistance. P-gp ATPase assays and photo-cross linking with [I-125]iodoarylazidoprazosin confirmed that transport and biochemical properties of P-gp chimeras were similar to those of wild-type P-gp, although differences in drug binding were detected when human and mouse transmembrane domains were combined. Overall, chimeras with one or two mouse P-gp domains were deemed functionally equivalent to human wild type P-gp, demonstrating the ability of human P-gp to tolerate major structural changes.
C1 [Pluchino, Kristen M.; Hall, Matthew D.; Moen, Janna K.; Chufan, Eduardo E.; Shukla, Suneet; Xia, Di; Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
[Pluchino, Kristen M.; Gill, Deborah R.; Hyde, Stephen C.] Univ Oxford, Radcliffe Dept Med, Nuffield Dept Clin Lab Sci, Gene Med Res Grp, Oxford OX3 9DU, England.
[Fetsch, Patricia A.] NCI, Pathol Lab, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This project was funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract
HHN261200800001E, and the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 54
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 23
PY 2016
VL 55
IS 7
BP 1010
EP 1023
DI 10.1021/acs.biochem.5b01064
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DE9VQ
UT WOS:000370987900005
PM 26820614
ER
PT J
AU Chaudhuri, P
Rosenbaum, MA
Sinharoy, P
Damron, DS
Birnbaumer, L
Graham, LM
AF Chaudhuri, Pinaki
Rosenbaum, Michael A.
Sinharoy, Pritam
Damron, Derek S.
Birnbaumer, Lutz
Graham, Linda M.
TI Membrane translocation of TRPC6 channels and endothelial migration are
regulated by calmodulin and PI3 kinase activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE endothelial; calmodulin; PI3 kinase; TRPC6
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE;
TYROSINE PHOSPHORYLATION; BINDING-PROTEIN; CELL MOTILITY; ION-CHANNEL;
C-SRC; CALCIUM; LYSOPHOSPHATIDYLCHOLINE; INHIBITION
AB Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels leading to inhibition of endothelial cell (EC) migration in vitro and delayed EC healing of arterial injuries in vivo. The precise mechanism through which lysoPC activates TRPC6 channels is not known, but calmodulin (CaM) contributes to the regulation of TRPC channels. Using site-directed mutagenesis, cDNAs were generated in which Tyr(99) or Tyr(138) of CaM was replaced with Phe, generating mutant CaM, Phe(99)-CaM, or Phe(138)-CaM, respectively. In ECs transiently transfected with pcDNA3.1-myc-His-Phe(99)-CaM, but not in ECs transfected with pcDNA3.1-myc-His-Phe(138)-CaM, the lysoPC-induced TRPC6-CaM dissociation and TRPC6 externalization was disrupted. Also, the lysoPC-induced increase in intracellular calcium concentration was inhibited in ECs transiently transfected with pcDNA3.1-myc-His-Phe(99)-CaM. Blocking phosphorylation of CaM at Tyr(99) also reduced CaM association with the p85 subunit and subsequent activation of phosphatidylinositol 3-kinase (PI3K). This prevented the increase in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the translocation of TRPC6 to the cell membrane and reduced the inhibition of EC migration by lysoPC. These findings suggest that lysoPC induces CaM phosphorylation at Tyr(99) by a Src family kinase and that phosphorylated CaM activates PI3K to produce PIP3, which promotes TRPC6 translocation to the cell membrane.
C1 [Chaudhuri, Pinaki; Graham, Linda M.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA.
[Rosenbaum, Michael A.] Louis Stokes Cleveland Vet Affairs Med Ctr, Surg Serv, Cleveland, OH 44106 USA.
[Sinharoy, Pritam; Damron, Derek S.] Kent State Univ, Dept Biol Sci, Kent, OH 44240 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Graham, Linda M.] Cleveland Clin, Dept Vasc Surg, Cleveland, OH 44195 USA.
RP Graham, LM (reprint author), Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA.; Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.; Graham, LM (reprint author), Cleveland Clin, Dept Vasc Surg, Cleveland, OH 44195 USA.
EM Birnbau1@gmail.com; grahamL@ccf.org
OI Sinharoy, Pritam/0000-0002-6322-260X
FU NIH National Heart, Lung, and Blood Institute [R01-HL-064357];
Intramural Research Program of the NIH [Z01-ES-101684]
FX This work was supported by NIH National Heart, Lung, and Blood Institute
Grant R01-HL-064357 (to L.M.G.) and by the Intramural Research Program
of the NIH Project Z01-ES-101684 (to L.B.).
NR 33
TC 1
Z9 2
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 23
PY 2016
VL 113
IS 8
BP 2110
EP 2115
DI 10.1073/pnas.1600371113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE4SK
UT WOS:000370620300054
PM 26858457
ER
PT J
AU Bi, M
Zhao, SM
Said, JW
Merino, MJ
Adeniran, AJ
Xie, ZQ
Nawaf, CB
Choi, J
Belldegrun, AS
Pantuck, AJ
Kluger, HM
Bilguevar, K
Lifton, RP
Shuch, B
AF Bi, Mark
Zhao, Siming
Said, Jonathan W.
Merino, Maria J.
Adeniran, Adebowale J.
Xie, Zuoquan
Nawaf, Cayce B.
Choi, Jaehyuk
Belldegrun, Arie S.
Pantuck, Allan J.
Kluger, Harriet M.
Bilguevar, Kaya
Lifton, Richard P.
Shuch, Brian
TI Genomic characterization of sarcomatoid transformation in clear cell
renal cell carcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE kidney cancer; sarcomatoid; transformation; p53; dedifferentiation
ID EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR GENE; PROLIFERATIVE
ACTIVITY; MUTATIONAL LANDSCAPE; CANCER GENOMICS; PD-1 BLOCKADE; P53
GENE; EXPRESSION; DIFFERENTIATION; THERAPY
AB The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 x 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 x 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.
C1 [Bi, Mark; Zhao, Siming; Bilguevar, Kaya; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06511 USA.
[Bi, Mark; Zhao, Siming; Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06511 USA.
[Said, Jonathan W.; Shuch, Brian] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
[Merino, Maria J.] NCI, Translat Surg Pathol Div, Rockville, MD 20850 USA.
[Adeniran, Adebowale J.] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06511 USA.
[Xie, Zuoquan; Nawaf, Cayce B.] Yale Univ, Sch Med, Dept Urol, 333 Cedar St, New Haven, CT 06511 USA.
[Choi, Jaehyuk] Yale Univ, Sch Med, Dept Dermatol, 333 Cedar St, New Haven, CT 06511 USA.
[Belldegrun, Arie S.; Pantuck, Allan J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Kluger, Harriet M.] Yale Univ, Sch Med, Div Oncol, Dept Med, 333 Cedar St, New Haven, CT 06511 USA.
RP Lifton, RP (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06511 USA.; Lifton, RP (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06511 USA.; Shuch, B (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
EM richard.lifton@yale.edu; brian.shuch@yale.edu
OI Choi, Jaehyuk/0000-0003-2379-2226
FU National Center for Research Resources [KL2 TR000140]; National Center
for Advancing Translational Science; National Cancer Institute
[K08-CA191019]; Gilead Sciences
FX We thank the staff of the Yale Center for Genome analysis for technical
excellence in sample preparation, capture, and DNA sequencing, and Marta
Boeke, PhD, and Brandon Castor assisted with specimen acquisition. This
publication was made possible by Clinical and Translational Science
Awards (CTSA) Grant KL2 TR000140 (to B.S.) from the National Center for
Research Resources and the National Center for Advancing Translational
Science. J.C. was supported through National Cancer Institute Grant
K08-CA191019. This work was supported in part by Gilead Sciences. R.P.L.
is an Investigator of the Howard Hughes Medical Institute.
NR 63
TC 12
Z9 12
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 23
PY 2016
VL 113
IS 8
BP 2170
EP 2175
DI 10.1073/pnas.1525735113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE4SK
UT WOS:000370620300064
PM 26864202
ER
PT J
AU Morozov, GI
Zhao, HY
Mage, MG
Boyd, LF
Jiang, JS
Dolan, MA
Venna, R
Norcross, MA
McMurtrey, CP
Hildebrand, W
Schuck, P
Natarajan, K
Margulies, DH
AF Morozov, Giora I.
Zhao, Huaying
Mage, Michael G.
Boyd, Lisa F.
Jiang, Jiansheng
Dolan, Michael A.
Venna, Ramesh
Norcross, Michael A.
McMurtrey, Curtis P.
Hildebrand, William
Schuck, Peter
Natarajan, Kannan
Margulies, David H.
TI Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes
peptide editing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antigen presentation; peptide loading; major histocompatibility complex;
protein interactions; SAXS
ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN PRESENTATION;
ENDOPLASMIC-RETICULUM; BIOLOGICAL MACROMOLECULES; PRESENTATION PATHWAY;
SOLUTION SCATTERING; ESCHERICHIA-COLI; HEAVY-CHAIN; TRANSPORTER;
BETA(2)-MICROGLOBULIN
AB Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.
C1 [Morozov, Giora I.; Mage, Michael G.; Boyd, Lisa F.; Jiang, Jiansheng; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromolecular Biophys, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Venna, Ramesh; Norcross, Michael A.] US FDA, Ctr Drug Evaluat & Res, Immunol Lab, Silver Spring, MD 20993 USA.
[McMurtrey, Curtis P.; Hildebrand, William] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dhm@nih.gov
RI ID, BioCAT/D-2459-2012;
OI Morozov, Giora/0000-0002-2605-6075
FU DOE Office of Science [DE-AC02-06CH11357]; National Institute of General
Medical Sciences of the National Institutes of Health [9 P41 GM103622];
National Institute of Allergy and Infectious Diseases [AI0000394];
National Institute of Biomedical Imaging and Bioengineering/National
Institutes of Health [EB000008]; Center for Drug Evaluation and
Review/Federal Drug Administration [1617]
FX We thank Drs. David Garboczi [National Institute of Allergy and
Infectious Diseases (NIAID)] and Rick Willis and John Altman of the
NIAID tetramer facility for plasmids used for generating some MHC
constructs; Drs. Ted Hansen, Rose Mage, Nathan May, and Rajat Varma for
comments on the manuscript; and Robert Tampe for discussion. We
appreciate the help of Dr. Tengchuan Jin with fluorescence polarization.
Drs. Srinivas Chakravarthy and Weifeng Shang at Bio-CAT/APS (18IDD)
assisted with small-angle X-ray scattering (SAXS) data collection. SAXS
research used resources of the Advanced Photon Source, a US Department
of Energy (DOE) Office of Science User Facility operated for the DOE
Office of Science by Argonne National Laboratory under Contract
DE-AC02-06CH11357, a project supported by Grant 9 P41 GM103622 from the
National Institute of General Medical Sciences of the National
Institutes of Health. Our research was supported by the intramural
research programs of the National Institute of Allergy and Infectious
Diseases (Project AI0000394) and National Institute of Biomedical
Imaging and Bioengineering (Project EB000008)/National Institutes of
Health and the Center for Drug Evaluation and Review/Federal Drug
Administration (Project 1617).
NR 51
TC 3
Z9 3
U1 2
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 23
PY 2016
VL 113
IS 8
BP E1006
EP E1015
DI 10.1073/pnas.1519894113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE4SK
UT WOS:000370620300011
PM 26869717
ER
PT J
AU Triplett, TA
Cardenas, KT
Lancaster, JN
Hu, ZC
Selden, HJ
Jasso, GJ
Balasubramanyam, S
Chan, K
Li, LQ
Chen, X
Marcogliese, AN
Dave, UP
Love, PE
Ehrlich, LIR
AF Triplett, Todd A.
Cardenas, Kim T.
Lancaster, Jessica N.
Hu, Zicheng
Selden, Hilary J.
Jasso, Guadalupe J.
Balasubramanyam, Sadhana
Chan, Kathy
Li, LiQi
Chen, Xi
Marcogliese, Andrea N.
Dave, Utpal P.
Love, Paul E.
Ehrlich, Lauren I. R.
TI Endogenous dendritic cells from the tumor microenvironment support T-ALL
growth via IGF1R activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE T-ALL; leukemia; dendritic cell; tumor microenvironment; IGF1R
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR-I RECEPTOR; CHRONIC
LYMPHOCYTIC-LEUKEMIA; DELTA-LIKE 4; STROMAL CELLS; MACROPHAGES;
LYMPHOMA; SURVIVAL; EXPRESSION; CANCER
AB Primary T-cell acute lymphoblastic leukemia (T-ALL) cells require stromal-derived signals to survive. Although many studies have identified cell-intrinsic alterations in signaling pathways that promote T-ALL growth, the identity of endogenous stromal cells and their associated signals in the tumor microenvironment that support T-ALL remains unknown. By examining the thymic tumor microenvironments in multiple murine T-ALL models and primary patient samples, we discovered the emergence of prominent epithelial-free regions, enriched for proliferating tumor cells and dendritic cells (DCs). Systematic evaluation of the functional capacity of tumor-associated stromal cells revealed that myeloid cells, primarily DCs, are necessary and sufficient to support T-ALL survival ex vivo. DCs support T-ALL growth both in primary thymic tumors and at secondary tumor sites. To identify a molecular mechanism by which DCs support T-ALL growth, we first performed gene expression profiling, which revealed up-regulation of platelet-derived growth factor receptor beta (Pdgfrb) and insulin-like growth factor I receptor (Igf1r) on T-ALL cells, with concomitant expression of their ligands by tumor-associated DCs. Both Pdgfrb and Igf1r were activated in ex vivo T-ALL cells, and co-culture with tumor-associated, but not normal thymic DCs, sustained IGF1R activation. Furthermore, IGF1R signaling was necessary for DC-mediated T-ALL survival. Collectively, these studies provide the first evidence that endogenous tumor-associated DCs supply signals driving T-ALL growth, and implicate tumor-associated DCs and their mitogenic signals as auspicious therapeutic targets.
C1 [Triplett, Todd A.; Cardenas, Kim T.; Lancaster, Jessica N.; Hu, Zicheng; Selden, Hilary J.; Jasso, Guadalupe J.; Balasubramanyam, Sadhana; Chan, Kathy; Ehrlich, Lauren I. R.] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
[Li, LiQi; Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Hematopoiesis & Lymphocyte Biol, NIH, Bethesda, MD 20892 USA.
[Chen, Xi] Univ Miami, Miller Sch Med, Dept Hlth Sci, Div Biostat, Miami, FL 33136 USA.
[Chen, Xi] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Marcogliese, Andrea N.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Dave, Utpal P.] Tennessee Valley Healthcare Syst, Div Hematol Oncol, Nashville, TN 37232 USA.
[Dave, Utpal P.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
[Cardenas, Kim T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78240 USA.
RP Ehrlich, LIR (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
EM lehrlich@austin.utexas.edu
FU Cancer Prevention and Research Institute of Texas [R1003]; NIH
[1ZIAHD001803-22]; American Cancer Society [PF-14-216-01-TBG]
FX We thank Coby Tran for assistance with immunostaining, Ellen R. Richie
for helpful discussions, and Michele Redell for her advice and expertise
in human hematologic malignancies. We also thank the staff at The
University of Texas at Austin Animal Facilities. This work was supported
by Recruitment Award R1003 from the Cancer Prevention and Research
Institute of Texas (to L.I.R.E.) and by the Intramural Research Program
of the NIH (PEL: Project number: 1ZIAHD001803-22). T.A.T. was supported
by Postdoctoral Fellowship PF-14-216-01-TBG from the American Cancer
Society.
NR 62
TC 1
Z9 1
U1 2
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 23
PY 2016
VL 113
IS 8
BP E1016
EP E1025
DI 10.1073/pnas.1520245113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE4SK
UT WOS:000370620300012
PM 26862168
ER
PT J
AU Jendryke, T
Prochazkova, M
Hall, BE
Nordmann, GC
Schladt, M
Milenkovic, VM
Kulkarni, AB
Wetzel, CH
AF Jendryke, Thomas
Prochazkova, Michaela
Hall, Bradford E.
Nordmann, Gregory C.
Schladt, Moritz
Milenkovic, Vladimir M.
Kulkarni, Ashok B.
Wetzel, Christian H.
TI TRPV1 function is modulated by Cdk5-mediated phosphorylation: insights
into the molecular mechanism of nociception
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PROTEIN-KINASE-C; CAPSAICIN RECEPTOR VR1; RAT SENSORY NEURONS; POTENTIAL
VANILLOID-1; SINGLE-CHANNEL; ION-CHANNEL; HEAT; PAIN; DESENSITIZATION;
ACTIVATION
AB TRPV1 is a polymodally activated cation channel acting as key receptor in nociceptive neurons. Its function is strongly affected by kinase-mediated phosphorylation leading to hyperalgesia and allodynia. We present behavioral and molecular data indicating that TRPV1 is strongly modulated by Cdk5-mediated phosphorylation at position threonine-407(mouse)/T406(rat). Increasing or decreasing Cdk5 activity in genetically engineered mice has severe consequences on TRPV1-mediated pain perception leading to altered capsaicin consumption and sensitivity to heat. To understand the molecular and structural/functional consequences of TRPV1 phosphorylation, we generated various rTRPV1(T406) receptor variants to mimic phosphorylated or dephosphorylated receptor protein. We performed detailed functional characterization by means of electrophysiological whole-cell and single-channel recordings as well as Ca2+-imaging and challenged recombinant rTRPV1 receptors with capsaicin, low pH, or heat. We found that position T406 is critical for the function of TRPV1 by modulating ligand-sensitivity, activation, and desensitization kinetics as well as voltage-dependence. Based on high resolution structures of TRPV1, we discuss T406 being involved in the molecular transition pathway, its phosphorylation leading to a conformational change and influencing the gating of the receptor. Cdk5-mediated phosphorylation of T406 can be regarded as an important molecular switch modulating TRPV1-related behavior and pain sensitivity.
C1 [Jendryke, Thomas; Nordmann, Gregory C.; Schladt, Moritz; Milenkovic, Vladimir M.; Wetzel, Christian H.] Univ Regensburg, Dept Psychiat & Psychotherapy, Mol Neurosci, D-93053 Regensburg, Germany.
[Prochazkova, Michaela; Hall, Bradford E.; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Wetzel, CH (reprint author), Univ Regensburg, Dept Psychiat & Psychotherapy, Mol Neurosci, D-93053 Regensburg, Germany.
EM Christian.Wetzel@ukr.de
FU Division of Intramural Research of the National Institute of Dental and
Craniofacial research, National Institutes of Health, Bethesda, MD, USA;
DFG [WE 2298/4-1]
FX We thank D. Julius for providing wild-type rTRPV1 cDNA and T. Jahner for
technical assistance. We appreciate the help of E. Kerkhoff with the
TIRF experiments. These studies were supported by the Division of
Intramural Research of the National Institute of Dental and Craniofacial
research, National Institutes of Health, Bethesda, MD, USA and the DFG
(WE 2298/4-1).
NR 36
TC 2
Z9 2
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 23
PY 2016
VL 6
AR 22007
DI 10.1038/srep22007
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5QE
UT WOS:000370685500001
PM 26902776
ER
PT J
AU Lu, SY
Jang, H
Nussinov, R
Zhang, J
AF Lu, Shaoyong
Jang, Hyunbum
Nussinov, Ruth
Zhang, Jian
TI The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small
GTPase K-Ras4B
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HYPERVARIABLE REGION; MOLECULAR-DYNAMICS; RAS MUTATIONS; K-RAS;
CONFORMATIONAL DYNAMICS; GUANOSINE TRIPHOSPHATE; SIGNAL-TRANSDUCTION;
CRYSTAL-STRUCTURE; ARGININE FINGER; ACTIVE-SITE
AB Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP -> GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 mu s molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. In addition, we simulated 'exchanged' nucleotide states. These comprehensive simulations reveal that in solution K-Ras4B(WT)-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4B(G12C/G12D)-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4-Bdriven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer.
C1 [Lu, Shaoyong; Zhang, Jian] Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai 200025, Peoples R China.
[Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth] Leidos Biomed Res Inc, Frederick Natl Lab, NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
[Zhang, Jian] Jiangsu Univ Technol, Sch Elect & Informat Engn, Inst Bioinformat & Med Engn, Changzhou 213001, Peoples R China.
RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai 200025, Peoples R China.; Nussinov, R (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab, NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.; Zhang, J (reprint author), Jiangsu Univ Technol, Sch Elect & Informat Engn, Inst Bioinformat & Med Engn, Changzhou 213001, Peoples R China.
EM NussinoR@helix.nih.gov; jian.zhang@sjtu.edu.cn
FU National Basic Research Program of China (973 Program) [2015CB910403];
National Natural Science Foundation of China [81322046, 81302698,
81473137]; Shanghai Rising-Star Program [13QA1402300]; Program for New
Century Excellent Talents in University [NCET-12-0355]; Shanghai Health
and Family Planning Commission [20154Y0058]; Frederick National
Laboratory for Cancer Research, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of NIH, Frederick
National Lab, Center for Cancer Research
FX We thank Mrs. Haiming Jiang for helpful discussions. This work was
supported by National Basic Research Program of China (973 Program)
(2015CB910403); National Natural Science Foundation of China (81322046,
81302698, 81473137); Shanghai Rising-Star Program (13QA1402300); Program
for New Century Excellent Talents in University (NCET-12-0355); Shanghai
Health and Family Planning Commission (20154Y0058); This project has
also been funded in whole or in part with Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN261200800001E. This research was supported
[in part] by the Intramural Research Program of NIH, Frederick National
Lab, Center for Cancer Research. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the US Government.
NR 68
TC 8
Z9 8
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 23
PY 2016
VL 6
AR 21949
DI 10.1038/srep21949
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5LT
UT WOS:000370673200001
PM 26902995
ER
PT J
AU Keteyian, SJ
Patel, M
Kraus, WE
Brawner, CA
McConnell, TR
Pina, IL
Leifer, ES
Fleg, JL
Blackburn, G
Fonarow, GC
Chase, PJ
Piner, L
Vest, M
O'Connor, CM
Ehrman, JK
Walsh, MN
Ewald, G
Bensimhon, D
Russell, SD
AF Keteyian, Steven J.
Patel, Mahesh
Kraus, William E.
Brawner, Clinton A.
McConnell, Timothy R.
Pina, Ileana L.
Leifer, Eric S.
Fleg, Jerome L.
Blackburn, Gordon
Fonarow, Gregg C.
Chase, Paul J.
Piner, Lucy
Vest, Marianne
O'Connor, Christopher M.
Ehrman, Jonathan K.
Walsh, Mary N.
Ewald, Gregory
Bensimhon, Dan
Russell, Stuart D.
CA HF-ACTION Investigators
TI Variables Measured During Cardiopulmonary Exercise Testing as Predictors
of Mortality in Chronic Systolic Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE peak VO2; respiratory exchange ratio; sex; survival
ID PEAK OXYGEN-CONSUMPTION; TRIAL INVESTIGATING OUTCOMES; HF-ACTION;
CARDIAC TRANSPLANTATION; VENTILATORY EFFICIENCY; CLASSIFICATION-SYSTEM;
AMBULATORY PATIENTS; PROGNOSTIC VALUE; GUIDELINES; MODEL
AB BACKGROUND Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. OBJECTIVES The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER).
METHODS Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [VO2], exercise duration, percent predicted peak VO2 [% ppVO(2)], ventilatory efficiency) were examined.
RESULTS Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both % ppVO(2) and exercise duration were equally able to predict (Wald chi-square: similar to 141) and discriminate (c-index: 0.69) mortality. Peak VO2 (ml.kg(-1).min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that % ppVO(2), exercise duration, and peak VO2 (ml.kg(-1).min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak VO2 of 10.9 ml.kg(-1).min(-1) versus 5.3 ml.kg(-1).min(-1) in women.
CONCLUSIONS Peak VO2, exercise duration, and % ppVO(2) carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak VO2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437) (C) 2016 by the American College of Cardiology Foundation.
C1 [Keteyian, Steven J.; Brawner, Clinton A.; Ehrman, Jonathan K.] Henry Ford Hosp, Div Cardiovasc Med, 6525 Second Ave, Detroit, MI 48202 USA.
[Patel, Mahesh; Kraus, William E.; Piner, Lucy; O'Connor, Christopher M.; Bensimhon, Dan] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA.
[McConnell, Timothy R.] Bloomsburg Univ, Dept Exercise Sci, Bloomsburg, PA USA.
[Pina, Ileana L.] Montefiore Med Ctr, Albert Einstein Coll Med, 111 E 210th St, Bronx, NY 10467 USA.
[Leifer, Eric S.; Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
[Blackburn, Gordon] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Fonarow, Gregg C.] Ronald Regan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
[Chase, Paul J.] Cone Hlth, Div Cardiol, Greensboro, NC USA.
[Vest, Marianne] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Walsh, Mary N.] St Vincent Heart Ctr Indiana, Indianapolis, IN USA.
[Ewald, Gregory] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA.
[Russell, Stuart D.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA.
RP Keteyian, SJ (reprint author), Henry Ford Hosp, Div Cardiovasc Med, 6525 Second Ave, Detroit, MI 48202 USA.
EM Sketeyi1@hfhs.org
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland
FX This work was supported by the National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland. The
contents of this manuscript are entirely the responsibility of the
authors and do not necessarily reflect the views of the National
Institutes of Health or the Department of Health and Human Services. Dr.
Patel is an employee of and owns stock in Merck Research Laboratories.
All other authors have reported that they have no relationships relevant
to the contents of this paper to disclose. Stanley A. Rubin, MD, served
as Guest Editor for this paper.
NR 33
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Z9 7
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 23
PY 2016
VL 67
IS 7
BP 780
EP 789
DI 10.1016/j.jacc.2015.11.050
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DD6GK
UT WOS:000370022500007
PM 26892413
ER
PT J
AU Harrison, JS
Jacobs, TM
Houlihan, K
Van Doorslaer, K
Kuhlman, B
AF Harrison, Joseph S.
Jacobs, Tim M.
Houlihan, Kevin
Van Doorslaer, Koenraad
Kuhlman, Brian
TI UbSRD: The Ubiquitin Structural Relational Database
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE ubiquitin; SUMO; Rosetta; structural database; protein-protein
interaction
ID SEQUENCE ALIGNMENT; E3 LIGASE; RECOGNITION; PROTEINS; SPECIFICITY;
DOMAIN; CONJUGATION; EVOLUTION; CASCADES; COMPLEX
AB The structurally defined ubiquitin-like homology fold (UBL) can engage in several unique protein protein interactions and many of these complexes have been characterized with high-resolution techniques. Using Rosetta's structural classification tools, we have created the Ubiquitin Structural Relational Database (UbSRD), an SQL database of features for all 509 UBL-containing structures in the PDB, allowing users to browse these structures by protein protein interaction and providing a platform for quantitative analysis of structural features. We used UbSRD to define the recognition features of ubiquitin (UBQ) and SUMO observed in the PDB and the orientation of the UBQ tail while interacting with certain types of proteins. While some of the interaction surfaces on UBQ and SUMO overlap, each molecule has distinct features that aid in molecular discrimination. Additionally, we find that the UBQ tail is malleable and can adopt a variety of conformations upon binding. UbSRD is accessible as an online resource at rosettadesign.med.unc.edu/ubsrd. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Harrison, Joseph S.; Jacobs, Tim M.; Houlihan, Kevin; Kuhlman, Brian] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Harrison, Joseph S.; Kuhlman, Brian] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Van Doorslaer, Koenraad] NIAID, DNA Tumor Virus Sect, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Harrison, JS (reprint author), Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
FU National Institutes of Health (NIH) from Lineberger Comprehensive Cancer
Center at University of North Carolina [T32-CA009156]; NIH, the National
Institute of Allergy and Infectious Diseases intramural program; NIH
[GM073960]
FX J.S.H. was supported though a National Institutes of Health (NIH)
postdoctoral training grant from the Lineberger Comprehensive Cancer
Center at University of North Carolina (T32-CA009156). This research was
supported in part by the NIH, the National Institute of Allergy and
Infectious Diseases intramural program, and from an NIH research grant
(GM073960).
NR 39
TC 3
Z9 3
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD FEB 22
PY 2016
VL 428
IS 4
BP 679
EP 687
DI 10.1016/j.jmb.2015.09.011
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DH1RE
UT WOS:000372561800003
PM 26392143
ER
PT J
AU Hoffmann, M
Hernandez, MG
Berger, E
Marzi, A
Pohlmann, S
AF Hoffmann, Markus
Hernandez, Mariana Gonzalez
Berger, Elisabeth
Marzi, Andrea
Poehlmann, Stefan
TI The Glycoproteins of All Filovirus Species Use the Same Host Factors for
Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent
SO PLOS ONE
LA English
DT Article
ID EBOLA-VIRUS GLYCOPROTEIN; RESPIRATORY SYNDROME CORONAVIRUS; VESICULAR
STOMATITIS-VIRUS; NIEMANN-PICK C1; LECTINS DC-SIGN; MARBURG VIRUS; FRUIT
BATS; PROTEOLYTIC ACTIVATION; ROUSETTUS-AEGYPTIACUS; ENVELOPE
GLYCOPROTEIN
AB Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.
C1 [Hoffmann, Markus; Hernandez, Mariana Gonzalez; Berger, Elisabeth; Poehlmann, Stefan] German Primate Ctr, Infect Biol Unit, Gottingen, Germany.
[Marzi, Andrea] NIAID, Lab Virol Div Intramural Res, NIH, Hamilton, MT USA.
RP Hoffmann, M; Pohlmann, S (reprint author), German Primate Ctr, Infect Biol Unit, Gottingen, Germany.
EM mhoffmann@dpz.eu; spoehlmann@dpz.eu
FU BMBF (EBOKON Verbund); Leibniz foundation (Graduate School for Emerging
Infectious Diseases); Division of Intramural Research, NIAID, NIH; DAAD
(Deutscher Akademischer Austauschdienst); CONACYT (Consejo Nacional de
Ciencia y Tecnologia) by the National Council for Science and Technology
in Mexico
FX This study was funded by BMBF (EBOKON Verbund)
(https://www.bmbf.de/presse/bmbf-staerkt-forschung-zu-ebola-721.html),
the Leibniz foundation (Graduate School for Emerging Infectious
Diseases)
(http://www.dpz.eu/en/career/graduate-training/emerging-infectious-disea
ses/leibniz-graduate-school-for-emerging-infectious-diseases-eidis.html)
and partly by the Division of Intramural Research, NIAID, NIH. MGH is
supported within a German-Mexican cooperation program of the DAAD
(Deutscher Akademischer Austauschdienst) and CONACYT (Consejo Nacional
de Ciencia y Tecnologia) by the National Council for Science and
Technology in Mexico. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 79
TC 3
Z9 3
U1 6
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2016
VL 11
IS 2
AR e0149651
DI 10.1371/journal.pone.0149651
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF3VL
UT WOS:000371276100122
PM 26901159
ER
PT J
AU Finn, EH
Misteli, T
Shachar, S
AF Finn, Elizabeth H.
Misteli, Tom
Shachar, Sigal
TI Painting a Clearer Picture of Chromatin
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID OLIGOPAINT FISH PROBES; SAM DOMAIN; POLYMERIZATION
AB Elucidating chromatin's 3D shape is critical to understanding its function, but the fine structure of chromatin domains remains poorly resolved. In a recent report in Nature, Boettiger et al. (2016) visualize chromatin in super-resolution, gaining unprecedented insight into chromatin architecture.
C1 [Finn, Elizabeth H.; Misteli, Tom; Shachar, Sigal] NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
NR 9
TC 0
Z9 0
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD FEB 22
PY 2016
VL 36
IS 4
BP 356
EP 357
DI 10.1016/j.devcel.2016.02.002
PG 3
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DF0QF
UT WOS:000371043300003
PM 26906730
ER
PT J
AU Dasso, M
AF Dasso, Mary
TI Kar9 Controls the Cytoplasm by Visiting the Nucleus
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID BUDDING YEAST; SUMOYLATION; ASYMMETRY; SUMO
AB Kar9 positions mitotic spindles during budding yeast cell division. Reporting in this issue of Developmental Cell, Schweiggert et al. (2016) show that modulation of Kar9 stability mediates crosstalk between cytoplasmic and nuclear microtubules, using an elaborate mechanism that involves regulated nuclear transport as well as SUMOylation and ubiquitination.
C1 [Dasso, Mary] NICHHD, NIH, Div Mol & Cellular Biol, Bethesda, MD 20892 USA.
RP Dasso, M (reprint author), NICHHD, NIH, Div Mol & Cellular Biol, Bethesda, MD 20892 USA.
EM dassom@mail.nih.gov
OI Dasso, Mary/0000-0002-5410-1371
FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD001902]
NR 9
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD FEB 22
PY 2016
VL 36
IS 4
BP 360
EP 361
DI 10.1016/j.devcel.2016.02.007
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DF0QF
UT WOS:000371043300005
PM 26906732
ER
PT J
AU Pan, M
Xu, XH
Chen, Y
Jin, T
AF Pan, Miao
Xu, Xuehua
Chen, Yong
Jin, Tian
TI Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic
Acid that Controls Both Chemotaxis and Phagocytosis
SO DEVELOPMENTAL CELL
LA English
DT Article
ID DIRECTED CELL-MIGRATION; DICTYOSTELIUM-DISCOIDEUM; MULTICELLULAR
DEVELOPMENT; EUKARYOTIC CHEMOTAXIS; LEADING-EDGE; PHOSPHORYLATION;
ACTIVATION; NETWORKS; DYNAMICS; SUBUNIT
AB Eukaryotic phagocytes search and destroy invading microorganisms via chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum is a professional phagocyte that chases bacteria through chemotaxis and engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs) are known for detecting chemoattractants and directing cell migration, but their roles in phagocytosis are not clear. Here, we developed a quantitative phosphoproteomic technique to discover signaling components. Using this approach, we discovered the long sought after folic acid receptor, fAR1, in D. discoideum. We showed that the seven-transmembrane receptor fAR1 is required for folic acid-mediated signaling events. Significantly, we discovered that fAR1 is essential for both chemotaxis and phagocytosis of bacteria, thereby representing a chemoattractant GPCR that mediates not only chasing but also ingesting bacteria. We revealed that a phagocyte is able to internalize particles via a chemoattractant-mediated engulfment process. We propose that mammalian phagocytes may also use this mechanism to engulf and ingest bacterial pathogens.
C1 [Pan, Miao; Xu, Xuehua; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Chen, Yong] NHLBI, Prote Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Pan, M; Jin, T (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM miao.pan@nih.gov; tjin@niaid.nih.gov
FU NIAID, NIH
FX We thank D. Hereld, J. Brzostowski, and X. Xiang for critical reading;
M. Gucek, L. Olano, G. Nardone, and C. Hammer for technical support on
mass spectrometry analyses; P. van Haastert for suggestions on the folic
acid binding assay; C. Huang and P. Devreotes for providing plasmids; X.
Wen, W. Quan, J. Lu, and J. Manzella-Lapeira for help with the
chemotaxis analyses; and L. Tian, R. Wang, and A. Grunfeld for the
phagocytosis assay. The work is supported by intramural funding from
NIAID, NIH.
NR 46
TC 4
Z9 4
U1 7
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD FEB 22
PY 2016
VL 36
IS 4
BP 428
EP 439
DI 10.1016/j.devcel.2016.01.012
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DF0QF
UT WOS:000371043300011
PM 26906738
ER
PT J
AU Akassoglou, K
Agalliu, D
Chang, CJ
Davalos, D
Grutzendler, J
Hillman, EMC
Khakh, BS
Kleinfeld, D
McGavern, DB
Nelson, SJ
Zlokovic, BV
AF Akassoglou, Katerina
Agalliu, Dritan
Chang, Christopher J.
Davalos, Dimitrios
Grutzendler, Jaime
Hillman, Elizabeth M. C.
Khakh, Baljit S.
Kleinfeld, David
McGavern, Dorian B.
Nelson, Sarah J.
Zlokovic, Berislav V.
TI Neurovascular and Immuno-Imaging: From Mechanisms to Therapies.
Proceedings of the Inaugural Symposium
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE neuroinflammation; multiple sclerosis; traumatic brain injury;
Alzheimer's disease; blood-brain barrier; microglia; myelin; two-photon
microscopy
ID BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS LESIONS;
FLUORESCENT-PROBES; BIOLOGICAL-SYSTEMS; HYDROGEN-SULFIDE; LIVING
SYSTEMS; DISEASE; ABNORMALITIES; TRANSITION
AB Breakthrough advances in intravital imaging have launched a new era for the study of dynamic interactions at the neurovascular interface in health and disease. The first Neurovascular and Immuno-Imaging Symposium was held at the Gladstone Institutes, University of California, San Francisco in March, 2015. This highly interactive symposium brought together a group of leading researchers who discussed how recent studies have unraveled fundamental biological mechanisms in diverse scientific fields such as neuroscience, immunology, and vascular biology, both under physiological and pathological conditions. These Proceedings highlight how advances in imaging technologies and their applications revolutionized our understanding of the communication between brain, immune, and vascular systems and identified novel targets for therapeutic intervention in neurological diseases.
C1 [Akassoglou, Katerina] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94143 USA.
[Akassoglou, Katerina] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Agalliu, Dritan] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Agalliu, Dritan] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York, NY USA.
[Agalliu, Dritan] Columbia Univ, Dept Pharmacol, Med Ctr, New York, NY USA.
[Chang, Christopher J.] Univ Calif Berkeley, Howard Hughes Med Inst, Helen Wills Neurosci Inst, Dept Chem, Berkeley, CA 94720 USA.
[Chang, Christopher J.] Univ Calif Berkeley, Howard Hughes Med Inst, Helen Wills Neurosci Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Davalos, Dimitrios] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Grutzendler, Jaime] Yale Univ, Dept Neurol, New Haven, CT USA.
[Hillman, Elizabeth M. C.] Columbia Univ, Kavli Inst Brain Sci, Lab Funct Opt Imaging, Dept Biomed Engn, New York, NY USA.
[Hillman, Elizabeth M. C.] Columbia Univ, Kavli Inst Brain Sci, Lab Funct Opt Imaging, Dept Radiol, New York, NY USA.
[Khakh, Baljit S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Khakh, Baljit S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
[Kleinfeld, David] Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA.
[McGavern, Dorian B.] NINDS, Viol Immunol & Intravital Imagibg Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Nelson, Sarah J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Zlokovic, Berislav V.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
RP Akassoglou, K (reprint author), Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94143 USA.; Akassoglou, K (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
EM kakassoglou@gladstone.ucsf.edu
OI Hillman, Elizabeth M. C./0000-0001-5511-1451
FU Gladstone Institutes of Neurological Disease and Lundbeck A/S; National
Institutes of Health (NIH) NINDS [NS052189, NS51470, NS082976]; National
Multiple Sclerosis Society (NMSS) [RG4985A3]; Conrad N. Hilton
Foundation Multiple Sclerosis Innovation Award; NIH NHLBI [HL116995-01,
EB003832]; NMSS [RG4673A1/1, FG2035-A1, RG4595A1/T]; NIH NIGMS
[GM79465]; American Heart Association [13SDG17210051]; Race to Erase
Multiple Sclerosis Foundation; NIH NIA [R21AG048181]; NHLBI
[R0111L106815]; NINDS [R21NS087511, NS082097]; NIH [R01NS063226,
R01NS076628, NS060677, MH104069, ROICA127612, R01NS34467, R01AG23084,
R01AG039452, R01NS090904]; NSF CAREER [0954796, UL1 TR000040]; Human
Frontier Science Program; CHDI Foundation; NINTH [MH108503]; NIH
intramural program
FX We are grateful to the artist Elizabeth Jameson for "Mind on Fire",
Lennart Mucke and Mark Fllisman for discussions, Linda Turney for
administrative support, Chris Goodfellow and Teresa Roberts for
graphics. The Symposium was supported by funds from the Gladstone
Institutes of Neurological Disease and Lundbeck A/S. Work in the
authors' labs was funded by the National Institutes of Health (NIH)
NINDS grants NS052189, NS51470, NS082976, the National Multiple
Sclerosis Society (NMSS) RG4985A3, and Conrad N. Hilton Foundation
Multiple Sclerosis Innovation Award to KA; NIH NHLBI HL116995-01 and
NMSS RG4673A1/1 and FG2035-A1 to DA; NIH NIGMS GM79465 to CC; NMSS
RG4595A1/T, American Heart Association 13SDG17210051, and a Young
Investigator Award from the Race to Erase Multiple Sclerosis Foundation
to DD; NIH NIA R21AG048181, NHLBI R0111L106815, NINDS R21NS087511 to JG;
NIH R01NS063226, R01NS076628, NSF CAREER 0954796, UL1 TR000040 and the
Human Frontier Science Program to EH; CHDI Foundation and NIH NS060677
and MH104069 to BK; NIH NIBIB EB003832, NINDS NS082097, and NINTH
MH108503 to DK; DM is supported by the NIH intramural program.; NIH
ROICA127612 to SN; NIH R01NS34467, R01AG23084, R01AG039452 and
R01NS090904 to BZ. CC is an Investigator with the Howard Hughes Medical
Institute.
NR 70
TC 1
Z9 1
U1 3
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD FEB 22
PY 2016
VL 10
AR 46
DI 10.3389/fnins.2016.00046
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DE4IJ
UT WOS:000370592100001
PM 26941593
ER
PT J
AU Munster, VJ
Adney, DR
van Doremalen, N
Brown, VR
Miazgowicz, KL
Milne-Price, S
Bushmaker, T
Rosenke, R
Scott, D
Hawkinson, A
de Wit, E
Schountz, T
Bowen, RA
AF Munster, Vincent J.
Adney, Danielle R.
van Doremalen, Neeltje
Brown, Vienna R.
Miazgowicz, Kerri L.
Milne-Price, Shauna
Bushmaker, Trenton
Rosenke, Rebecca
Scott, Dana
Hawkinson, Ann
de Wit, Emmie
Schountz, Tony
Bowen, Richard A.
TI Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus
jamaicensis)
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; DIPEPTIDYL PEPTIDASE 4; TO-HUMAN
TRANSMISSION; DROMEDARY CAMELS; SAUDI-ARABIA; HUMAN BETACORONAVIRUS;
PHYLOGENETIC ANALYSIS; NEOTROPICAL BATS; VIRUS-INFECTION; PTEROPID BATS
AB The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.
C1 [Munster, Vincent J.; van Doremalen, Neeltje; Miazgowicz, Kerri L.; Milne-Price, Shauna; Bushmaker, Trenton; de Wit, Emmie; Bowen, Richard A.] NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT USA.
[Adney, Danielle R.; Brown, Vienna R.; Bowen, Richard A.] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA.
[Rosenke, Rebecca; Scott, Dana] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA.
[Hawkinson, Ann] Univ No Colorado, Dept Biol, Greeley, CO 80639 USA.
[Schountz, Tony] Colorado State Univ, Dept Microbiol Immunol & Pathol, Arthropodborne & Infect Dis Lab, Ft Collins, CO 80523 USA.
RP Munster, VJ; Bowen, RA (reprint author), NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT USA.
EM vincent.munster@nih.gov; Richard.Bowen@colostate.edu
OI Munster, Vincent/0000-0002-2288-3196
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Animal Models Core at Colorado State University;
Department of Microbiology and immunology, CSU; NIH [R15-AI089419];
Colorado State University
FX The authors would like to thank Drs. Bart Haagmans and Ron Fouchier at
the Erasmus Medical Center, Rotterdam, The Netherlands for providing
MERS-CoV strain EMC/2012. We thank Anita Mora for help with the Figures
and Bob Fischer for excellent technical assistance. This research was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health, the
Animal Models Core at Colorado State University, funds provided by the
Department of Microbiology and immunology, CSU, and the Vice President
of Research, Colorado State University and NIH grant R15-AI089419. DRA
was supported through the Infectious Disease: Translational Research
Training Program at Colorado State University.
NR 64
TC 8
Z9 8
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 22
PY 2016
VL 6
AR 21878
DI 10.1038/srep21878
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE3HA
UT WOS:000370517100001
PM 26899616
ER
PT J
AU Sirur, A
De Sancho, D
Best, RB
AF Sirur, Anshul
De Sancho, David
Best, Robert B.
TI Markov state models of protein misfolding
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; CONFORMATIONAL DYNAMICS; TRANSITION
NETWORKS; ENERGY LANDSCAPES; FOLDING DYNAMICS; BETA-HAIRPIN; BINDING;
IDENTIFICATION; MECHANISM; KINETICS
AB Markov state models (MSMs) are an extremely useful tool for understanding the conformational dynamics of macromolecules and for analyzing MD simulations in a quantitative fashion. They have been extensively used for peptide and protein folding, for small molecule binding, and for the study of native ensemble dynamics. Here, we adapt the MSM methodology to gain insight into the dynamics of misfolded states. To overcome possible flaws in root-mean-square deviation (RMSD)-based metrics, we introduce a novel discretization approach, based on coarse-grained contact maps. In addition, we extend the MSM methodology to include "sink" states in order to account for the irreversibility (on simulation time scales) of processes like protein misfolding. We apply this method to analyze the mechanism of misfolding of tandem repeats of titin domains, and how it is influenced by confinement in a chaperonin-like cavity. (C) 2016 AIP Publishing LLC.
C1 [Sirur, Anshul; De Sancho, David; Best, Robert B.] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
[De Sancho, David] CIC nanoGUNE, Tolosa Hiribidea 76, Donostia San Sebastian 20018, Spain.
[De Sancho, David] Basque Fdn Sci, Ikerbasque, Maria Diaz de Haro 3, Bilbao 48013, Spain.
[Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Sirur, A; De Sancho, D; Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.; De Sancho, D (reprint author), CIC nanoGUNE, Tolosa Hiribidea 76, Donostia San Sebastian 20018, Spain.; De Sancho, D (reprint author), Basque Fdn Sci, Ikerbasque, Maria Diaz de Haro 3, Bilbao 48013, Spain.; Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM as2122@cam.ac.uk; d.desancho@nanogune.eu; robertbe@helix.nih.gov
RI De Sancho, David/C-4995-2009; nanoGUNE, CIC/A-2623-2015
OI De Sancho, David/0000-0002-8985-2685;
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institute of Health; Ikerbasque
FX This work was supported by the Intramural Research Programme of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institute of Health (R.B.B.) and a Research Fellowship from
Ikerbasque (D.D.S.).
NR 52
TC 3
Z9 3
U1 3
U2 17
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD FEB 21
PY 2016
VL 144
IS 7
AR 075101
DI 10.1063/1.4941579
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DL7CM
UT WOS:000375797200032
PM 26897000
ER
PT J
AU Sadowski, SM
Neychev, V
Millo, C
Shih, J
Nilubol, N
Herscovitch, P
Pacak, K
Marx, SJ
Kebebew, E
AF Sadowski, Samira M.
Neychev, Vladimir
Millo, Corina
Shih, Joanna
Nilubol, Naris
Herscovitch, Peter
Pacak, Karel
Marx, Stephen J.
Kebebew, Electron
TI Prospective Study of Ga-68-DOTATATE Positron Emission
Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic
Neuroendocrine Tumors and Unknown Primary Sites
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SOMATOSTATIN RECEPTORS; UNITED-STATES; PET/CT; MANAGEMENT; GUIDELINES;
DIAGNOSIS; IMPACT; EPIDEMIOLOGY; SCINTIGRAPHY; METASTASES
AB Purpose
Gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. Ga-68-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs.
Patients and Methods
One hundred thirty-one patients were enrolled in a prospective study of patients undergoing 68Ga-DOTATATE PET/CT, (1111)n-pentetreotide single-photon emission computed tomography (SPECT)/CT and multiphasic CT scan, and/or magnetic resonance imaging in a blinded fashion with comprehensive biochemical testing. The primary outcome measure was the detection of lesions by each imaging study.
Results
68Ga-DOTATATE PET/CT imaging detected 95.1% of lesions (95% CI, 92.4% to 96.8%) with an average maximum standardized uptake value of 65.4 +/- 47 (range, 6.9 to 244), anatomic imaging detected 45.3% of lesions (95% CI, 37.9% to 52.9%), and (1111)n-pentetreotide SPECT/CT detected 30.9% of lesions (95% CI, 25.0% to 37.5%), with a significant difference between imaging modalities (P <.001). In four of 14 patients (28.6%), 68Ga-DOTATATE PET/CT found a previously unknown primary tumor, and detected primary GEPNET, lymph node, and distant metastases correctly in 72 of 113 lesions (63.7%) when compared with histopathology, with 22.1% and 38.9% detected by using 1111n-pentetreotide SPECT/CT and anatomic imaging, respectively. On the basis of findings with 68Ga-DOTATATE PET/CT, 43 of 131 patients (32.8%) had a change in management recommendation. In patients with carcinoid symptoms but negative biochemical testing, 68Ga-DOTATATE PET/CT detected lesions in 65.2% of patients, 40% of which were detected neither by anatomic imaging nor by (1111)n-pentetreotide SPECT/CT.
Conclusion
68Ga-DOTATATE PET/CT imaging provides important information for accurate staging of GEPNETs and selection of appropriate treatment interventions even in the absence of biochemical evidence of disease in symptomatic patients. (C) 2015 by American Society of Clinical Oncology
C1 [Sadowski, Samira M.; Neychev, Vladimir; Millo, Corina; Shih, Joanna; Nilubol, Naris; Herscovitch, Peter; Pacak, Karel; Marx, Stephen J.; Kebebew, Electron] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Clin Res Ctr, Bldg 10-CRC, Bethesda, MD 20892 USA.
EM electron.kebebew@nih.gov
FU Intramural Research Programs of the Center for Cancer Research, National
Cancer Institute; National Institute of Diabetes and Digestive and
Kidney Diseases at the National Institutes of Health
FX Supported by the Intramural Research Programs of the Center for Cancer
Research, National Cancer Institute, and the National Institute of
Diabetes and Digestive and Kidney Diseases at the National Institutes of
Health.
NR 34
TC 15
Z9 15
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2016
VL 34
IS 6
BP 588
EP +
DI 10.1200/JCO.2015.64.0987
PG 12
WC Oncology
SC Oncology
GA DJ6ON
UT WOS:000374332900016
PM 26712231
ER
PT J
AU O'Sullivan, CC
Holmes, E
Campbell, C
Bradbury, I
Zujewski, JA
Gelber, RD
AF O'Sullivan, Ciara C.
Holmes, Eileen
Campbell, Christine
Bradbury, Ian
Zujewski, Jo Anne
Gelber, Richard D.
TI Treatment of Lymph Node-Negative, Early-Stage HER2-Positive Breast
Cancer Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID ADJUVANT TRASTUZUMAB; SERIES
C1 [O'Sullivan, Ciara C.; Zujewski, Jo Anne] NCI, NIH, Bethesda, MD 20892 USA.
[Holmes, Eileen; Campbell, Christine; Bradbury, Ian] Frontier Sci, Kingussie, Inverness, Scotland.
[Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Gelber, Richard D.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
RP O'Sullivan, CC (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2016
VL 34
IS 6
BP 640
EP +
DI 10.1200/JCO.2015.65.1034
PG 2
WC Oncology
SC Oncology
GA DJ6ON
UT WOS:000374332900025
PM 26644531
ER
PT J
AU Tolstorukov, MY
Virnik, K
Zhurkin, VB
Adhya, S
AF Tolstorukov, Michael Y.
Virnik, Konstantin
Zhurkin, Victor B.
Adhya, Sankar
TI Organization of DNA in a bacterial nucleoid
SO BMC MICROBIOLOGY
LA English
DT Article
DE Bacterial; Nucleoid; MNase; Digestion; Sequencing; Genomic; DNA;
Packaging; Structural; Organization
ID ESCHERICHIA-COLI CHROMOSOME; SEQUENCE-DIRECTED CURVATURE; PROKARYOTIC
DNA; GENE-EXPRESSION; MICROCOCCAL NUCLEASE; ELECTRON-MICROSCOPY; FOLDED
CHROMOSOMES; BINDING PROTEINS; CHIP-SEQ; H-NS
AB Background: It is unclear how DNA is packaged in a bacterial cell in the absence of nucleosomes. To investigate the initial level of DNA condensation in bacterial nucleoid we used in vivo DNA digestion coupled with high-throughput sequencing of the digestion-resistant fragments. To this end, we transformed E. coli cells with a plasmid expressing micrococcal nuclease. The nuclease expression was under the control of AraC repressor, which enabled us to perform an inducible digestion of bacterial nucleoid inside a living cell.
Results: Analysis of the genomic localization of the digestion-resistant fragments revealed their non-random distribution. The patterns observed in the distribution of the sequenced fragments indicate the presence of short DNA segments protected from the enzyme digestion, possibly because of interaction with DNA-binding proteins. The average length of such digestion-resistant segments is about 50 bp and the characteristic repeat in their distribution is about 90 bp. The gene starts are depleted of the digestion-resistant fragments, suggesting that these genomic regions are more exposed than genomic sequences on average. Sequence analysis of the digestion-resistant segments showed that while the GC-content of such sequences is close to the genome-wide value, they are depleted of A-tracts as compared to the bulk genomic DNA or to the randomized sequence of the same nucleotide composition.
Conclusions: Our results suggest that DNA is packaged in the bacterial nucleoid in a non-random way that facilitates interaction of the DNA binding factors with regulatory regions of the genome.
C1 [Tolstorukov, Michael Y.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Tolstorukov, Michael Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Virnik, Konstantin] FDA, Ctr Biol, Off Vaccines, Lab Immunoregulat,Div Viral Prod, Silver Spring, MD 20993 USA.
[Zhurkin, Victor B.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA.
[Adhya, Sankar] NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Adhya, S (reprint author), NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
EM adhyas@mail.nih.gov
NR 77
TC 1
Z9 1
U1 4
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD FEB 20
PY 2016
VL 16
AR 22
DI 10.1186/s12866-016-0637-3
PG 11
WC Microbiology
SC Microbiology
GA DE2RK
UT WOS:000370474300001
PM 26897370
ER
PT J
AU Pszenny, V
Ehrenman, K
Romano, JD
Kennard, A
Schultz, A
Roos, DS
Grigg, ME
Carruthers, VB
Coppens, I
AF Pszenny, Viviana
Ehrenman, Karen
Romano, Julia D.
Kennard, Andrea
Schultz, Aric
Roos, David S.
Grigg, Michael E.
Carruthers, Vern B.
Coppens, Isabelle
TI A Lipolytic Lecithin:Cholesterol Acyltransferase Secreted by Toxoplasma
Facilitates Parasite Replication and Egress
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE cell surface enzyme; host-pathogen interaction; parasitology;
Phospholipase A; Toxoplasma gondii
ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; PHOSPHOLIPASE A(2); HOST-CELLS;
PLASMA LECITHIN; DIACYLGLYCEROL ACYLTRANSFERASE; PARASITOPHOROUS
VACUOLE; APICOMPLEXAN PARASITES; HEADGROUP SPECIFICITY; GONDII;
LYSOPHOSPHATIDYLCHOLINE
AB The protozoan parasite Toxoplasma gondii develops within a parasitophorous vacuole (PV) in mammalian cells, where it scavenges cholesterol. When cholesterol is present in excess in its environment, the parasite expulses this lipid into the PV or esterifies it for storage in lipid bodies. Here, we characterized a unique T. gondii homologue of mammalian lecithin:cholesterol acyltransferase (LCAT), a key enzyme that produces cholesteryl esters via transfer of acyl groups from phospholipids to the 3-OH of free cholesterol, leading to the removal of excess cholesterol from tissues. TgLCAT contains a motif characteristic of serine lipases AHSLG and the catalytic triad consisting of serine, aspartate, and histidine (SDH) from LCAT enzymes. TgLCAT is secreted by the parasite, but unlike other LCAT enzymes it is cleaved into two proteolytic fragments that share the residues of the catalytic triad and need to be reassembled to reconstitute enzymatic activity. TgLCAT uses phosphatidylcholine as substrate to form lysophosphatidylcholine that has the potential to disrupt membranes. The released fatty acid is transferred to cholesterol, but with a lower transesterification activity than mammalian LCAT. TgLCAT is stored in a subpopulation of dense granule secretory organelles, and following secretion, it localizes to the PV and parasite plasma membrane. LCAT-null parasites have impaired growth in vitro, reduced virulence in animals, and exhibit delays in egress from host cells. Parasites overexpressing LCAT show increased virulence and faster egress. These observations demonstrate that TgLCAT influences the outcome of an infection, presumably by facilitating replication and egress depending on the developmental stage of the parasite.
C1 [Pszenny, Viviana; Ehrenman, Karen; Romano, Julia D.; Coppens, Isabelle] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Pszenny, Viviana; Kennard, Andrea; Grigg, Michael E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Schultz, Aric; Carruthers, Vern B.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Roos, David S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
RP Coppens, I (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
EM icoppens@jhsph.edu
FU National Institutes of Health from NIAID [AI060767]; NIAID [AI001018]
FX This work was supported by National Institutes of Health Grant AI060767
from NIAID (to I. C.) and in part by the Intramural Research Program
Grant AI001018 from NIAID (to M. E. G.). The authors declare that they
have no conflicts of interest with the contents of this article. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 73
TC 4
Z9 4
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 19
PY 2016
VL 291
IS 8
BP 3725
EP 3746
DI 10.1074/jbc.M115.671974
PG 22
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF4RQ
UT WOS:000371338400004
PM 26694607
ER
PT J
AU Xie, Q
McGreal, R
Harris, R
Gao, CY
Liu, W
Reneker, LW
Musil, LS
Cvekl, A
AF Xie, Qing
McGreal, Rebecca
Harris, Raven
Gao, Chun Y.
Liu, Wei
Reneker, Lixing W.
Musil, Linda S.
Cvekl, Ales
TI Regulation of c-Maf and alpha A-Crystallin in Ocular Lens by Fibroblast
Growth Factor Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE crystallin; differentiation; fibroblast growth factor (FGF); lens;
signaling; A-crystallin; FGF signaling; c-Maf
ID FIBER CELL-DIFFERENTIATION; TRANSCRIPTION FACTORS; DNA-BINDING; T-CELLS;
EMBRYONIC-DEVELOPMENT; EPITHELIAL-CELLS; HEPARAN-SULFATE;
GENE-EXPRESSION; ETS-FAMILY; IN-VIVO
AB Fibroblast growth factor (FGF) signaling regulates a multitude of cellular processes, including cell proliferation, survival, migration, and differentiation. In the vertebrate lens, FGF signaling regulates fiber cell differentiation characterized by high expression of crystallin proteins. However, a direct link between FGF signaling and crystallin gene transcriptional machinery remains to be established. Previously, we have shown that the bZIP proto-oncogene c-Maf regulates expression of A-crystallin (Cryaa) through binding to its promoter and distal enhancer, DCR1, both activated by FGF2 in cell culture. Herein, we identified and characterized a novel FGF2-responsive region in the c-Maf promoter (-272/-70, FRE). Both c-Maf and Cryaa regulatory regions contain arrays of AP-1 and Ets-binding sites. Chromatin immunoprecipitation (ChIP) assays established binding of c-Jun (an AP-1 factor) and Etv5/ERM (an Ets factor) to these regions in lens chromatin. Analysis of temporal and spatial expression of c-Jun, phospho-c-Jun, and Etv5/ERM in wild type and ERK1/2 deficient lenses supports their roles as nuclear effectors of FGF signaling in mouse embryonic lens. Collectively, these studies show that FGF signaling up-regulates expression of A-crystallin both directly and indirectly via up-regulation of c-Maf. These molecular mechanisms are applicable for other crystallins and genes highly expressed in terminally differentiated lens fibers.
C1 [Xie, Qing; McGreal, Rebecca; Liu, Wei; Cvekl, Ales] Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10461 USA.
[Xie, Qing; Harris, Raven; Liu, Wei; Cvekl, Ales] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.
[Gao, Chun Y.] NEI, Lab Mol & Dev Biol, Bethesda, MD 20892 USA.
[Reneker, Lixing W.] Univ Missouri, Mason Eye Inst, Dept Ophthalmol, Columbia, MO 65212 USA.
[Musil, Linda S.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Xie, Qing] Univ Calif Santa Cruz, Dept Mol Cellular & Dev Biol, Santa Cruz, CA 95064 USA.
RP Cvekl, A (reprint author), Albert Einstein Coll Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM ales.cvekl@einstein.yu.edu
FU National Institutes of Health [R01 EY014237, EY016422, EY022113,
EY013146, EY022645]; Research to Prevent Blindness
FX This work was supported by National Institutes of Health Grants R01
EY014237 (to A. C.), EY016422 and EY022113 (to L. S. M.), EY013146 (to
L. W. R.), EY022645 (to W. L.), and an unrestricted grant from Research
to Prevent Blindness to the Department of Ophthalmology and Visual
Sciences. The authors declare that they have no conflicts of interest
with the contents of this article. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 65
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U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 19
PY 2016
VL 291
IS 8
BP 3947
EP 3958
DI 10.1074/jbc.M115.705103
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF4RQ
UT WOS:000371338400022
PM 26719333
ER
PT J
AU Reidy, M
Sharma, R
Roberts, BL
Masison, DC
AF Reidy, Michael
Sharma, Ruchika
Roberts, Brittany-Lee
Masison, Daniel C.
TI Human J-protein DnaJB6b Cures a Subset of Saccharomyces cerevisiae
Prions and Selectively Blocks Assembly of Structurally Related Amyloids
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE amyloid; chaperone; heat shock protein (HSP); prion; yeast; DnaJB6
ID YEAST PRIONS; POLYGLUTAMINE AGGREGATION; CHAPERONE SUBFAMILY; HSP104
CHAPERONE; SHUTTLE VECTORS; IN-VITRO; PROPAGATION; HSP40; TOXICITY;
HSP70
AB Human chaperone DnaJB6, an Hsp70 co-chaperone whose defects cause myopathies, protects cells from polyglutamine toxicity and prevents purified polyglutamine and A peptides from forming amyloid. Yeast prions [URE3] and [PSI+] propagate as amyloid forms of Ure2 and Sup35 proteins, respectively. Here we find DnaJB6-protected yeast cells from polyglutamine toxicity and cured yeast of both [URE3] prions and weak variants of [PSI+] prions but not strong [PSI+] prions. Weak and strong variants of [PSI+] differ only in the structural conformation of their amyloid cores. In line with its anti-prion effects, DnaJB6 prevented purified Sup35NM from forming amyloids at 37 degrees C, which produce predominantly weak [PSI+] variants when used to infect yeast, but not at 4 degrees C, which produces mostly strong [PSI+] variants. Thus, structurally distinct amyloids composed of the same protein were differentially sensitive to the anti-amyloid activity of DnaJB6 both in vitro and in vivo. These findings have important implications for strategies using DnaJB6 as a target for therapy in amyloid disorders.
C1 [Reidy, Michael; Sharma, Ruchika; Roberts, Brittany-Lee; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rd 324, Bethesda, MD 20892 USA.
[Sharma, Ruchika] Univ Wisconsin, HF DeLuca Biochem Labs, Madison, WI 53706 USA.
[Roberts, Brittany-Lee] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
RP Masison, DC (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rd 324, Bethesda, MD 20892 USA.
EM danielmas@helix.nih.gov
FU National Institutes of Health, NIDDK
FX This work was supported by the Intramural Program of the National
Institutes of Health, NIDDK. The authors declare that they have no
conflicts of interest with the contents of this article. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 57
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U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 19
PY 2016
VL 291
IS 8
BP 4035
EP 4047
DI 10.1074/jbc.M115.700393
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF4RQ
UT WOS:000371338400029
PM 26702057
ER
PT J
AU Bennett, AV
Dueck, AC
Mitchell, SA
Mendoza, TR
Reeve, BB
Atkinson, TM
Castro, KM
Denicoff, A
Rogak, LJ
Harness, JK
Bearden, JD
Bryant, D
Siegel, RD
Schrag, D
Basch, E
AF Bennett, Antonia V.
Dueck, Amylou C.
Mitchell, Sandra A.
Mendoza, Tito R.
Reeve, Bryce B.
Atkinson, Thomas M.
Castro, Kathleen M.
Denicoff, Andrea
Rogak, Lauren J.
Harness, Jay K.
Bearden, James D.
Bryant, Donna
Siegel, Robert D.
Schrag, Deborah
Basch, Ethan
CA Natl Canc Inst PRO-CTCAE Study Grp
TI Mode equivalence and acceptability of tablet computer-, interactive
voice response system-, and paper-based administration of the US
National Cancer Institute's Patient-Reported Outcomes version of the
Common Terminology Criteria for Adverse Events (PRO-CTCAE)
SO HEALTH AND QUALITY OF LIFE OUTCOMES
LA English
DT Article
DE PRO-CTCAE; Patient-Reported Outcomes; Symptoms; Adverse Events; Mode of
Administration; Interactive Voice Response System
ID PRACTICES TASK-FORCE; CLINICAL-TRIALS; RELIABILITY; METAANALYSIS;
ONCOLOGY; QLQ-C30; DESIGNS; SAMPLE
AB Background: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.
Methods: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed.
Results: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were >= 0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper.
Conclusions: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration.
C1 [Bennett, Antonia V.; Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Campus Box 7411, Chapel Hill, NC 27599 USA.
[Dueck, Amylou C.] Mayo Clin, Coll Med, Div Hlth Sci Res, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
[Mitchell, Sandra A.; Castro, Kathleen M.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, 9609 Med Ctr Dr,East Tower,Suite 3-448, Rockville, MD 20850 USA.
[Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1400 Pressler St,Unit 1450, Houston, TX 77030 USA.
[Atkinson, Thomas M.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA.
[Denicoff, Andrea] NCI, Canc Therapy Evaluat Program, 9609 Med Ctr Dr,MSC 9737, Bethesda, MD 20892 USA.
[Rogak, Lauren J.; Schrag, Deborah] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,2nd Floor, New York, NY 10017 USA.
[Harness, Jay K.] St Joseph Hosp Orange, Ctr Canc Prevent & Treatment, 1100 West Stewart Dr, Orange, CA 92868 USA.
[Bearden, James D.] Spartanburg Reg Healthcare Syst, Gibbs Canc Ctr, 101 East Wood St, Spartanburg, SC 29303 USA.
[Bearden, James D.] Spartanburg Reg Healthcare Syst, Res Inst, 101 East Wood St, Spartanburg, SC 29303 USA.
[Bryant, Donna] Canc Program Our Lady Lake & Mary Bird Perkins, 1950 Essen Lane, Baton Rouge, LA 70809 USA.
[Siegel, Robert D.] Hartford Hosp, Helen & Harry Gray Canc Ctr, 85 Retreat Ave, Hartford, CT 06106 USA.
[Schrag, Deborah] Dana Farber Canc Inst, 450 Brookline Ave,D 1008, Boston, MA 02215 USA.
[Basch, Ethan] Univ N Carolina, Dept Med, Campus Box 7305, Chapel Hill, NC 27599 USA.
RP Mitchell, SA (reprint author), NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, 9609 Med Ctr Dr,East Tower,Suite 3-448, Rockville, MD 20850 USA.
EM mitchlls@mail.nih.gov
FU U.S. National Cancer Institute [HHSN261200800043C, HHSN261201000063C,
HHSN261200800001E]
FX Work described in this paper was supported by contracts from the U.S.
National Cancer Institute, HHSN261200800043C, HHSN261201000063C, and
HHSN261200800001E
NR 27
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Z9 3
U1 4
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7525
J9 HEALTH QUAL LIFE OUT
JI Health Qual. Life Outcomes
PD FEB 19
PY 2016
VL 14
AR 24
DI 10.1186/s12955-016-0426-6
PG 12
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DE1SH
UT WOS:000370406200001
PM 26892667
ER
PT J
AU Damien, GB
Djenontin, A
Chaffa, E
Yamadjako, S
Drame, PM
Ndille, EE
Henry, MC
Corbel, V
Remoue, F
Rogier, C
AF Damien, Georgia Barikissou
Djenontin, Armel
Chaffa, Evelyne
Yamadjako, Sandra
Drame, Papa Makhtar
Ndille, Emmanuel Elanga
Henry, Marie-Claire
Corbel, Vincent
Remoue, Franck
Rogier, Christophe
TI Effectiveness of insecticidal nets on uncomplicated clinical malaria: a
case-control study for operational evaluation
SO MALARIA JOURNAL
LA English
DT Article
DE Effectiveness; Case-control study; Evaluation; Malaria; LLIN
ID TREATED BED NETS; WESTERN KENYA; ANOPHELES-GAMBIAE; BENIN; AREA;
TRANSMISSION; VECTORS; AFRICA
AB Background: In a context of large-scale implementation of malaria vector control tools, such as the distribution of long-lasting insecticide nets (LLIN), it is necessary to regularly assess whether strategies are progressing as expected and then evaluate their effectiveness. The present study used the case-control approach to evaluate the effectiveness of LLIN 42 months after national wide distribution. This study design offers an alternative to cohort study and randomized control trial as it permits to avoid many ethical issues inherent to them.
Methods: From April to August 2011, a case-control study was conducted in two health districts in Benin; Ouidah-Kpomasse-Tori (OKT) in the south and Djougou-Copargo-Ouake (DCO) in the north. Children aged 0-60 months randomly selected from community were included. Cases were children with a high axillary temperature (>= 37.5 degrees C) or a reported history of fever during the last 48 h with a positive rapid diagnostic test (RDT). Controls were children with neither fever nor signs suggesting malaria with a negative RDT. The necessary sample size was at least 396 cases and 1188 controls from each site. The main exposure variable was "sleeping every night under an LLIN for the 2 weeks before the survey" (SL). The protective effectiveness (PE) of LLIN was calculated as PE = 1 - odds ratio.
Results: The declared SL range was low, with 17.0 and 27.5 % in cases and controls in the OKT area, and 44.9 and 56.5 % in cases and controls, in the DCO area, respectively. The declared SL conferred 40.5 % (95 % CI 22.2-54.5 %) and 55.5 % (95 % CI 28.2-72.4 %) protection against uncomplicated malaria in the OKT and the DCO areas, respectively. Significant differences in PE were observed according to the mother's education level.
Conclusion: In the context of a mass distribution of LLIN, their use still conferred protection in up to 55 % against the occurrence of clinical malaria cases in children. Social factors, the poor use and the poor condition of an LLIN can be in disfavour with its effectiveness. In areas, where LLIN coverage is assumed to be universal or targeted at high-risk populations, case-control studies should be regularly conducted to monitor the effectiveness of LLIN. The findings will help National Malaria Control Programme and their partners to improve the quality of malaria control according to the particularity of each area or region as far as possible.
C1 [Drame, Papa Makhtar; Corbel, Vincent; Remoue, Franck] Univ Montpellier I, IRD224, CNRS5290, UMR MIVEGEC,IRD, F-34394 Montpellier, France.
[Drame, Papa Makhtar; Corbel, Vincent; Remoue, Franck] Univ Montpellier 2, IRD224, CNRS5290, UMR MIVEGEC,IRD, F-34394 Montpellier, France.
[Damien, Georgia Barikissou; Djenontin, Armel; Yamadjako, Sandra; Drame, Papa Makhtar; Ndille, Emmanuel Elanga; Henry, Marie-Claire; Corbel, Vincent; Remoue, Franck] Univ Montpellier I, IRD224, CNRS5290, UMR MIVEGEC,IRD,CREC, Cotonou, Benin.
[Damien, Georgia Barikissou; Djenontin, Armel; Yamadjako, Sandra; Drame, Papa Makhtar; Ndille, Emmanuel Elanga; Henry, Marie-Claire; Corbel, Vincent; Remoue, Franck] Univ Montpellier 2, IRD224, CNRS5290, UMR MIVEGEC,IRD,CREC, Cotonou, Benin.
[Djenontin, Armel] Univ Abomey Calavi, Fac Sci & Tech, Lab Evolut Biodiversite Arthropodes & Assainissem, Abomey Calavi, Benin.
[Chaffa, Evelyne] Minist Sante, Direct Natl Sante Publ, PNLP, Cotonou, Benin.
[Drame, Papa Makhtar] NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
[Rogier, Christophe] Inst Pasteur Madagascar, Antananarivo, Madagascar.
[Rogier, Christophe] Inst Rech Biomed Armees, Bretigny Sur Orge, France.
[Rogier, Christophe] Aix Marseille Univ, CNRS 7278, Unite Rech Malad Infect & Trop Emergentes, UM 63,IRD 198,INSERM 1095, Marseille, France.
RP Damien, GB (reprint author), Univ Montpellier I, IRD224, CNRS5290, UMR MIVEGEC,IRD,CREC, Cotonou, Benin.; Damien, GB (reprint author), Univ Montpellier 2, IRD224, CNRS5290, UMR MIVEGEC,IRD,CREC, Cotonou, Benin.
EM barikiss2000@yahoo.fr
RI Corbel, VIncent/G-9576-2016
FU World Bank via Booster Programme for Malaria Control in Africa; Malaria
National Control Program of Benin [555/MS/DC/SGM/DNPS/PNLP/PALP/DNP du
30/12/2010]
FX We thank populations of Djougou-Copargo-Ouake and Ouidah-Kpomasse-Tori
Bossito health districts, especially the head of family and the
guardians of children for their kind support and great collaboration.
Funding received from the World Bank via Booster Programme for Malaria
Control in Africa and Malaria National Control Program of Benin
(Reference No. 555/MS/DC/SGM/DNPS/PNLP/PALP/DNP du 30/12/2010).
NR 34
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Z9 1
U1 3
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 19
PY 2016
VL 15
AR 102
DI 10.1186/s12936-016-1156-2
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DE3WC
UT WOS:000370560100001
PM 26891758
ER
PT J
AU Reid, MC
McKenzie, FE
AF Reid, Molly C.
McKenzie, F. Ellis
TI The contribution of agricultural insecticide use to increasing
insecticide resistance in African malaria vectors
SO MALARIA JOURNAL
LA English
DT Review
ID ANOPHELES-GAMBIAE-S.L.; WEST-AFRICA; BURKINA-FASO; PYRETHROID
RESISTANCE; NORTHERN CAMEROON; URBAN AGRICULTURE; PEST-MANAGEMENT;
POPULATIONS; BENIN; MECHANISMS
AB The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malaria vectors were identified. In 23 of the 25 relevant recent publications from across Africa, higher resistance in mosquito populations was associated with agricultural insecticide use. This association appears to be affected by crop type, farm pest management strategy and urban development.
C1 [Reid, Molly C.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, 22242 Valley Dr, College Pk, MD 20742 USA.
[Reid, Molly C.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Reid, MC (reprint author), Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, 22242 Valley Dr, College Pk, MD 20742 USA.; Reid, MC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM mollyreid5@gmail.com
NR 49
TC 5
Z9 6
U1 4
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 19
PY 2016
VL 15
AR 107
DI 10.1186/s12936-016-1162-4
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DE3WC
UT WOS:000370560100006
PM 26895980
ER
PT J
AU Banerjee, S
Bartesaghi, A
Merk, A
Rao, P
Bulfer, SL
Yan, Y
Green, N
Mroczkowski, B
Neitz, RJ
Wipf, P
Falconieri, V
Deshaies, RJ
Milne, JLS
Huryn, D
Arkin, M
Subramaniam, S
AF Banerjee, Soojay
Bartesaghi, Alberto
Merk, Alan
Rao, Prashant
Bulfer, Stacie L.
Yan, Yongzhao
Green, Neal
Mroczkowski, Barbara
Neitz, R. Jeffrey
Wipf, Peter
Falconieri, Veronica
Deshaies, Raymond J.
Milne, Jacqueline L. S.
Huryn, Donna
Arkin, Michelle
Subramaniam, Sriram
TI 2.3 angstrom resolution cryo-EM structure of human p97 and mechanism of
allosteric inhibition
SO SCIENCE
LA English
DT Article
ID AAA ATPASE P97; PLUS CHAPERONE P97; CANCER-CELL DEATH; P97/VCP; COMPLEX;
DOMAIN; MUTANTS; ANALOGS; BINDING; SYSTEM
AB p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of similar to 3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPgS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.
C1 [Banerjee, Soojay; Bartesaghi, Alberto; Merk, Alan; Rao, Prashant; Falconieri, Veronica; Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
[Bulfer, Stacie L.; Neitz, R. Jeffrey; Arkin, Michelle] Univ Calif San Francisco, Sch Pharm, Small Mol Discovery Ctr, Pharmaceut Chem, San Francisco, CA 94143 USA.
[Yan, Yongzhao; Wipf, Peter; Huryn, Donna] Univ Pittsburgh, Chem Divers Ctr, Pittsburgh, PA 15260 USA.
[Green, Neal] Leidos Biomed Res Inc, Frederick, MD 21702 USA.
[Mroczkowski, Barbara] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Deshaies, Raymond J.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91107 USA.
[Deshaies, Raymond J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91107 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU Center for Cancer Research, National Cancer Institute; National Cancer
Institute under Chemical Biology Consortium Contract [HHSN261200800001E,
29XS127TO15]
FX This research was supported by funds from the Center for Cancer
Research, National Cancer Institute, and with federal funds from the
National Cancer Institute under Chemical Biology Consortium Contract No.
HHSN261200800001E Agreement No. 29XS127TO15. R.J.D. is an investigator
of the Howard Hughes Medical Institute. This work used the computational
resources of the NIH High-Performance Computing Biowulf cluster
(http://hpc.nih.gov). We thank K. Moynihan, R. Mueller, and J. Cometa
for technical assistance with electron microscopy; F. Ulmer, P. Mooney,
and C. Booth for advice and assistance with optimizing K2 detector
performance; and M. G. Laporte for contributions to the medicinal
chemistry program. The University of Pittsburgh has filed a provisional
patent application that covers the inhibitor compound described in this
manuscript. R.J.D. is on the Scientific Advisory Board of Cleave
Biosciences. The density maps and refined atomic models have been
deposited in the Electron Microscopy Data Bank with accession numbers
EMD-3295, 3296, 3297, 3298, and 3299, and in the Protein Data Bank with
matching accession numbers of PDB-5FTJ, 5FTK, 5FTL, 5FTM, and 5FTN,
respectively, for native p97 in the presence and absence of bound
inhibitor, and for p97 conformational states I, II, and III observed in
the presence of ATP gamma S.
NR 37
TC 36
Z9 36
U1 11
U2 37
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD FEB 19
PY 2016
VL 351
IS 6275
BP 871
EP 875
DI 10.1126/science.aad7974
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PB
UT WOS:000370325700047
PM 26822609
ER
PT J
AU Shi, Y
Chen, X
Elsasser, S
Stocks, BB
Tian, G
Lee, BH
Shi, YH
Zhang, NX
de Poot, SAH
Tuebing, F
Sun, SW
Vannoy, J
Tarasov, SG
Engen, JR
Finley, D
Walters, KJ
AF Shi, Yuan
Chen, Xiang
Elsasser, Suzanne
Stocks, Bradley B.
Tian, Geng
Lee, Byung-Hoon
Shi, Yanhong
Zhang, Naixia
de Poot, Stefanie A. H.
Tuebing, Fabian
Sun, Shuangwu
Vannoy, Jacob
Tarasov, Sergey G.
Engen, John R.
Finley, Daniel
Walters, Kylie J.
TI Rpn1 provides adjacent receptor sites for substrate binding and
deubiquitination by the proteasome
SO SCIENCE
LA English
DT Article
ID MULTIUBIQUITIN-CHAIN-BINDING; EXCHANGE MASS-SPECTROMETRY; 26S
PROTEASOME; SACCHAROMYCES-CEREVISIAE; UBIQUITIN RECEPTORS; PROTEIN DDI1;
H/D EXCHANGE; CYCLIN B1; DEGRADATION; SUBUNIT
AB Hundreds of pathways for degradation converge at ubiquitin recognition by a proteasome. Here, we found that the five known proteasomal ubiquitin receptors in yeast are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site (T1) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like (UBL) domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine 48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine 48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site (T2) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a two-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.
C1 [Shi, Yuan; Elsasser, Suzanne; Tian, Geng; Lee, Byung-Hoon; de Poot, Stefanie A. H.; Tuebing, Fabian; Sun, Shuangwu; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
[Chen, Xiang; Shi, Yanhong; Vannoy, Jacob; Walters, Kylie J.] NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Stocks, Bradley B.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Shi, Yanhong; Zhang, Naixia] Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China.
[Vannoy, Jacob] Linganore High Sch, Frederick, MD 21701 USA.
[Tarasov, Sergey G.] NCI, Biophys Resource, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Engen, JR; Finley, D (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.; Walters, KJ (reprint author), NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.; Engen, JR (reprint author), Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
EM j.engen@neu.edu; daniel_finley@hms.harvard.edu; walters@nih.gov
FU National Institutes of Health [R37-GM043601, CA136472, R01-GM101135];
NIH, National Cancer Institute, Center for Cancer Research; Waters
Corporation
FX For advice, assistance, or comments on the manuscript, we thank D.
Chandler-Militello, M. Gill, J. Hanna, A. Kajava, R. King, Y. Lu, Y. Li,
M. Pahre, and J. Roelofs. For gifts of reagents we thank D. Clarke, M.
Glickman, F. He, Y. Ye, D. Komander, C. Larsen, J. Li, U. Nowicka, S.
Sadis, and W. Tansey. This research was funded by grants from the
National Institutes of Health (R37-GM043601 to D. F., CA136472 to
K.J.W., and R01-GM101135 to J.R.E.), by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research to
K.J.W., and by a research collaboration with the Waters Corporation
(J.R.E). Atomic coordinates for the Rpn1 T1 site, Rpn1 T1: ubiquitin,
and Rpn1 T1: K48 diubiquitin are available through the Protein Data Bank
with accession codes 2n3t, 2n3u, and 2n3v/2n3w, respectively.
NR 49
TC 23
Z9 23
U1 4
U2 29
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD FEB 19
PY 2016
VL 351
IS 6275
AR aad9421
DI 10.1126/science.aad9421
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PB
UT WOS:000370325700037
ER
PT J
AU Li, P
Li, H
Chen, Y
Fleischner, H
Lai, HJ
AF Li, Ping
Li, Hao
Chen, Ye
Fleischner, Herbert
Lai, Hong-Jian
TI Supereulerian graphs with width s and s-collapsible graphs
SO DISCRETE APPLIED MATHEMATICS
LA English
DT Article
DE Supereulerian graphs; Collapsible graphs; Edge-connectivity;
Edge-disjoint trails; Supereulerian graphs with width s; The
supereulerian width of a graph s-collapsible graphs; Eulerian-connected
graphs
ID DISJOINT SPANNING-TREES; HAMILTONIAN LINE GRAPHS; EULERIAN GRAPHS;
CONNECTIVITY; TRAILS
AB For an integers > 0 and for u, v is an element of V(G) with u not equal v, an (s; u, v)-trail-system of G is a subgraph H consisting of s edge-disjoint (u, v)-trails. A graph is supereulerian with width s if for any u, v is an element of V(G) with u not equal v, G has a spanning (s; u, v)-trail-system. The supereulerian width mu'(G) of a graph G is the largest integer s such that G is supereulerian with width k for every integer k with 0 <= k <= s. Thus a graph G with mu'(G) >= 2 has a spanning Eulerian subgraph. Catlin (1988) introduced collapsible graphs to study graphs with spanning Eulerian subgraphs, and showed that every collapsible graph G satisfies mu'(G) >= 2 (Catlin, 1988; Lai et al., 2009). Graphs G with mu'(G) >= 2 have also been investigated by Luo et al. (2006) as Eulerian-connected graphs. In this paper, we extend collapsible graphs to s collapsible graphs and develop a new related reduction method to study mu'(G) for a graph G. In particular, we prove that K-3,K-3 is the smallest 3-edge-connected graph with mu' < 3. These results and the reduction method will be applied to determine a best possible degree condition for graphs with supereulerian width at least 3, which extends former results in Catlin (1988) and Lai (1988). (C) 2015 Elsevier B.V. All rights reserved.
C1 [Li, Ping] Beijing Jiaotong Univ, Dept Math, Beijing 100044, Peoples R China.
[Li, Hao] Renmin Univ China, Dept Math, Beijing 100872, Peoples R China.
[Chen, Ye] NHLBI, Bioinformat & Syst Biol Core, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Fleischner, Herbert] TU Wien, DBAI, Fac Informat, Vienna, Austria.
[Lai, Hong-Jian] W Virginia Univ, Dept Math, Morgantown, WV 26506 USA.
RP Lai, HJ (reprint author), W Virginia Univ, Dept Math, Morgantown, WV 26506 USA.
EM pingli@bjtu.edu.cn; lihao1982@gmail.com; yechent@gmail.com;
fleisch@dbai.tuwien.ac.at; hongjianlai@gmail.com
FU National Natural Science Foundation of China [11301023, 11301538];
Fundamental Research Funds for the Central Universities [2015JBM105];
FWF Project [P27615-N25]
FX The research of Ping Li is partially supported by National Natural
Science Foundation of China (11301023) and the Fundamental Research
Funds for the Central Universities (2015JBM105). The research of Hao Li
is supported in part by the National Natural Science Foundation of China
(No. 11301538). The research of Herbert Fleischner is supported in part
by FWF Project P27615-N25.
NR 26
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-218X
EI 1872-6771
J9 DISCRETE APPL MATH
JI Discret Appl. Math.
PD FEB 19
PY 2016
VL 200
BP 79
EP 94
DI 10.1016/j.dam.2015.07.013
PG 16
WC Mathematics, Applied
SC Mathematics
GA DC8ES
UT WOS:000369453300009
ER
PT J
AU Boshoff, HI
AF Boshoff, Helena I.
TI Uncovering the Serine Hydrolytic Landscape of Mycobacterium tuberculosis
SO Cell Chemical Biology
LA English
DT Editorial Material
ID HYDROLASES; PROTEASE
AB In this issue of Cell Chemical Biology, Ortega et al. (2016) present a study utilizing a click-chemistry-enabled fluorophosphonate for activity-based identification of serine hydrolases, pinpointing a range of proteins including previously annotated hypotheticals. The application of this technology on both actively replicating and non-replicating Mycobacterium tuberculosis gives us a glimpse of its serine hydrolytic landscape during different stages of metabolic activity.
C1 [Boshoff, Helena I.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Boshoff, HI (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hboshoff@niaid.nih.gov
FU Intramural NIH HHS
NR 11
TC 1
Z9 1
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2451-9448
J9 CELL CHEM BIOL
JI Cell Chem. Biol.
PD FEB 18
PY 2016
VL 23
IS 2
BP 209
EP 211
DI 10.1016/j.chembiol.2016.02.002
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT5FW
UT WOS:000381508000006
PM 26971871
ER
PT J
AU Gianella, S
Tsibris, A
Barr, L
Godfrey, C
AF Gianella, Sara
Tsibris, Athe
Barr, Liz
Godfrey, Catherine
TI Barriers to a cure for HIV in women
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Review
DE HIV eradication; HIV cure; women's health; immune system; female genital
tract; anatomic compartments
ID ACTIVE ANTIRETROVIRAL THERAPY; FEMALE GENITAL-TRACT; PLASMACYTOID
DENDRITIC CELLS; SEX-BASED DIFFERENCES; REGULATORY T-CELLS; LOW-LEVEL
VIREMIA; HUMAN-PAPILLOMAVIRUS INFECTION; ESTROGEN-RECEPTOR-ALPHA;
GENDER-DIFFERENCES; IMMUNE ACTIVATION
AB Introduction: Distinct biological factors exist that affect the natural history of HIV and the host immune response between women and men. These differences must be addressed to permit the optimal design of effective HIV eradication strategies for much of the HIV-positive population.
Methods and results: Here, we review the literature on sex-based differences in HIV pathogenesis and natural history in tissues and anatomic compartments, HIV latency and transcriptional activity, and host immunity including the role of sex hormones. We then outline the potential effects of these differences on HIV persistence, and on the safety and efficacy of HIV eradication and curative interventions. Finally, we discuss the next steps necessary to elucidate these factors to achieve a cure for HIV, taking in account the complex ethical issues and the regulatory landscape in the hopes of stimulating further research and awareness in these areas.
Conclusions: Targeted enrolment of women in clinical trials and careful sex-based analysis will be crucial to gain further insights into sex-based differences in HIV persistence and to design sex-specific approaches to HIV eradication, if required.
C1 [Gianella, Sara] Univ Calif San Diego, Sch Med, Div Infect Dis, San Diego, CA 92103 USA.
[Tsibris, Athe] Harvard Univ, Brigham & Womens Hosp, Div Infect Dis, Sch Med, Boston, MA 02115 USA.
[Barr, Liz] AIDS Clin Trials Grp Community Sci Subcomm, Madison, WI USA.
[Godfrey, Catherine] NIH, Div Aids, Bldg 10, Bethesda, MD 20892 USA.
RP Godfrey, C (reprint author), NIAID, TRP, DAIDS, NIH,HIVRB,HIV Res Branch, 5601 Fishers Lane Room 9E 49,MSC 9830, Bethesda, MD 20892 USA.
EM cgodfrey@niaid.nih.gov
FU Department of Veterans Affairs; National Institutes of Health [AI43638,
AI100665, MH097520, DA034978, AI036214, AI007384, AI106039, AI074621,
AI110181, AI068636-07, P30-AI027763, UL1TR000100]; James B. Pendleton
Charitable Trust; Robert F. and Jean E. Holtz Centre for Science and
Technology Studies at the University of Wisconsin-Madison
FX This work was supported by the Department of Veterans Affairs and grants
from the National Institutes of Health: AI43638, AI100665, MH097520,
DA034978, AI036214, AI007384, AI106039, AI074621, AI110181, AI068636-07,
P30-AI027763, UL1TR000100, the James B. Pendleton Charitable Trust, and
the Robert F. and Jean E. Holtz Centre for Science and Technology
Studies at the University of Wisconsin-Madison.
NR 147
TC 1
Z9 1
U1 2
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD FEB 18
PY 2016
VL 19
AR 20706
DI 10.7448/IAS.19.1.20706
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DM2IZ
UT WOS:000376171600001
PM 26900031
ER
PT J
AU Kanakry, JA
Luznik, L
AF Kanakry, Jennifer A.
Luznik, Leo
TI Might haplo "be the (better) match"?
SO BLOOD
LA English
DT Editorial Material
ID POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; MARROW-TRANSPLANTATION; LYMPHOMA;
OUTCOMES; LEUKEMIA
AB In this issue of Blood, in a registry study by Kanate et al of reduced-intensity conditioning allogeneic blood or marrow transplantation (BMT) outcomes for lymphoma, HLA-haploidentical (haplo) transplantation with posttransplantation cyclophosphamide (PTCy) is associated with similar rates of relapse and survival as HLA-matched unrelated donor (MUD) transplantation but lower rates of grades III to IV acute and chronic graft-versus-host disease (GVHD).
C1 [Kanakry, Jennifer A.] Natl Inst Hlth, Bethesda, MD 20892 USA.
[Luznik, Leo] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
RP Kanakry, JA (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD FEB 18
PY 2016
VL 127
IS 7
BP 799
EP 800
DI 10.1182/blood-2016-01-689042
PG 4
WC Hematology
SC Hematology
GA DI3JW
UT WOS:000373395900006
PM 26893397
ER
PT J
AU Burgers, PMJ
Gordenin, D
Kunkel, TA
AF Burgers, Peter M. J.
Gordenin, Dmitry
Kunkel, Thomas A.
TI Who Is Leading the Replication Fork, Pol epsilon or Pol delta?
SO MOLECULAR CELL
LA English
DT Letter
ID GENOME; DNA
C1 [Burgers, Peter M. J.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Gordenin, Dmitry; Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU NIGMS NIH HHS [R01 GM032431]
NR 11
TC 9
Z9 9
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD FEB 18
PY 2016
VL 61
IS 4
BP 492
EP 493
DI 10.1016/j.molcel.2016.01.017
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG8IF
UT WOS:000372326300002
PM 26895421
ER
PT J
AU Fu, QS
Fu, TM
Cruz, AC
Sengupta, P
Thomas, SK
Wang, SQ
Siegel, RM
Wu, H
Chou, JJ
AF Fu, Qingshan
Fu, Tian-Min
Cruz, Anthony C.
Sengupta, Prabuddha
Thomas, Stacy K.
Wang, Shuqing
Siegel, Richard M.
Wu, Hao
Chou, James J.
TI Structural Basis and Functional Role of Intramembrane Trimerization of
the Fas/CD95 Death Receptor
SO MOLECULAR CELL
LA English
DT Article
ID NECROSIS-FACTOR RECEPTOR; PLASMA-MEMBRANE; PROTON CHANNEL; FAS
MUTATIONS; EGF RECEPTOR; DOMAIN; COMPLEX; REVEALS; ARCHITECTURE;
ASSOCIATION
AB Fas (CD95, Apo-1, or TNFRSF6) is a prototypical apoptosis-inducing death receptor in the tumor necrosis factor receptor (TNFR) superfamily. While the extracellular domains of TNFRs form trimeric complexes with their ligands and the intracellular domains engage in higher-order oligomerization, the role of the transmembrane (TM) domains is unknown. We determined the NMR structures of mouse and human Fas TM domains in bicelles that mimic lipid bilayers. Surprisingly, these domains use proline motifs to create optimal packing in homotrimer assembly distinct from classical trimeric coiled-coils in solution. Cancer-associated and structure-based mutations in Fas TM disrupt trimerization in vitro and reduce apoptosis induction in vivo, indicating the essential role of intramembrane trimerization in receptor activity. Our data suggest that the structures represent the signaling-active conformation of Fas TM, which appears to be different from the pre-ligand conformation. Analysis of other TNFR sequences suggests proline-containing sequences as common motifs for receptor TM trimerization.
C1 [Fu, Qingshan; Fu, Tian-Min; Wu, Hao; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Fu, Tian-Min; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Cruz, Anthony C.; Thomas, Stacy K.; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, NIH, Bethesda, MD 20892 USA.
[Sengupta, Prabuddha] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, NIH, Bethesda, MD 20892 USA.
[Wang, Shuqing] Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China.
RP Wu, H; Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Wu, H (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM wu@crystal.harvard.edu; chou@crystal.harvard.edu
FU NIH [P41 EB-002026, HL103526, AI050872]; NIH NIAMS [Z01-AR041133]
FX The NMR data were collected at MIT-Harvard CMR (supported by NIH grant
P41 EB-002026). We thank the NIAMS Flow Cytometry Core for technical
assistance. This work was supported by NIH grants HL103526 to J.J.C. and
AI050872 to H.W. and by NIH NIAMS intramural research program and
project grant Z01-AR041133 to R.M.S. We would like to thank Timothy
Springer for the insightful discussion.
NR 42
TC 10
Z9 11
U1 6
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD FEB 18
PY 2016
VL 61
IS 4
BP 602
EP 613
DI 10.1016/j.molcel.2016.01.009
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DG8IF
UT WOS:000372326300012
PM 26853147
ER
PT J
AU Chereji, RV
Kan, TW
Grudniewska, MK
Romashchenko, AV
Berezikov, E
Zhimulev, IF
Guryev, V
Morozov, AV
Moshkin, YM
AF Chereji, Razvan V.
Kan, Tsung-Wai
Grudniewska, Magda K.
Romashchenko, Alexander V.
Berezikov, Eugene
Zhimulev, Igor F.
Guryev, Victor
Morozov, Alexandre V.
Moshkin, Yuri M.
TI Genome-wide profiling of nucleosome sensitivity and chromatin
accessibility in Drosophila melanogaster
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID STEM-CELL DEVELOPMENT; BASE-PAIR RESOLUTION; IN-VIVO; EUKARYOTIC GENOME;
YEAST GENOME; DNA-SEQUENCE; DOUBLE HELIX; ORGANIZATION; MODEL;
TRANSCRIPTION
AB Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/Trich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10 degrees C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to 'phasing' off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequence-dependent models.
C1 [Chereji, Razvan V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Kan, Tsung-Wai; Moshkin, Yuri M.] Erasmus MC, Dept Biochem, POB 2040, NL-3000 CA Rotterdam, Netherlands.
[Grudniewska, Magda K.; Berezikov, Eugene; Guryev, Victor] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, NL-9713 AD Groningen, Netherlands.
[Romashchenko, Alexander V.; Moshkin, Yuri M.] RAS, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia.
[Zhimulev, Igor F.; Moshkin, Yuri M.] RAS, Siberian Branch, Inst Mol & Cellular Biol, Novosibirsk 630090, Russia.
[Morozov, Alexandre V.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
[Morozov, Alexandre V.] Rutgers State Univ, BioMaPS Inst Quantitat Biol, Piscataway, NJ 08854 USA.
RP Moshkin, YM (reprint author), Erasmus MC, Dept Biochem, POB 2040, NL-3000 CA Rotterdam, Netherlands.; Moshkin, YM (reprint author), RAS, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia.; Morozov, AV (reprint author), Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.; Morozov, AV (reprint author), Rutgers State Univ, BioMaPS Inst Quantitat Biol, Piscataway, NJ 08854 USA.
EM morozov@physics.rutgers.edu; yury.moshkin@gmail.com
RI Morozov, Alexandre/E-1984-2016; Zhimulev, Igor/N-7978-2015;
OI Morozov, Alexandre/0000-0003-2598-7000; Chereji,
Razvan/0000-0002-0572-6412
FU Russian Science Foundation [RNF 14-14-00934, RNF 141-14-0021];
Trans-regional Research Centre [TRR81]; Netherlands Proteomics Centre;
National Institutes of Health [R01 HG004708]
FX Funding for open access charge: Russian Science Foundation [RNF
14-14-00934, RNF 141-14-0021]; Trans-regional Research Centre [TRR81];
Netherlands Institute for Regenerative Medicine consortium [FES0908];
Netherlands Proteomics Centre; the National Institutes of Health [R01
HG004708].
NR 72
TC 5
Z9 5
U1 5
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 18
PY 2016
VL 44
IS 3
BP 1036
EP 1051
DI 10.1093/nar/gkv978
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3ST
UT WOS:000371268700015
PM 26429969
ER
PT J
AU Metser, G
Shin, HY
Wang, C
Yoo, KH
Oh, S
Villarino, AV
O'Shea, JJ
Kang, K
Hennighausen, L
AF Metser, Gil
Shin, Ha Youn
Wang, Chaochen
Yoo, Kyung Hyun
Oh, Sumin
Villarino, Alejandro V.
O'Shea, John J.
Kang, Keunsoo
Hennighausen, Lothar
TI An autoregulatory enhancer controls mammary-specific STAT5 functions
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN GENE PROMOTER; TRANSCRIPTION FACTOR; GLAND DEVELOPMENT;
TRANSGENIC MICE; SIGNAL TRANSDUCER; EPITHELIAL-CELLS; GROWTH-HORMONE;
ZINC TRANSPORT; BODY GROWTH; EXPRESSION
AB Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development and function. We report that the ubiquitously expressed Stat5a/b locus is subject to additional lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitivity, H3K27 acetylation and binding by GR, NFIB, ELF5 and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these sites in mice and determine their biological function. Mutant animals exhibited an 80% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that contributes to the remarkable abundance of STAT5 and, in turn, to the efficacy of STAT5-dependent mammary physiology.
C1 [Metser, Gil; Shin, Ha Youn; Wang, Chaochen; Yoo, Kyung Hyun; Oh, Sumin; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Oh, Sumin; Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan 330714, Chungnam, South Korea.
[Villarino, Alejandro V.; O'Shea, John J.] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
EM lotharh@mail.nih.gov
FU IPR of the NIDDK/NIH; NIAMS/NIH; Intramural research program of the NIH
FX IPR of the NIDDK/NIH and NIAMS/NIH. Funding for open access charge:
Intramural research program of the NIH.
NR 57
TC 8
Z9 8
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 18
PY 2016
VL 44
IS 3
BP 1052
EP 1063
DI 10.1093/nar/gkv999
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3ST
UT WOS:000371268700016
PM 26446995
ER
PT J
AU Xu, ZL
Niu, L
Li, LP
Taylor, JA
AF Xu, Zongli
Niu, Liang
Li, Leping
Taylor, Jack A.
TI ENmix: a novel background correction method for Illumina
HumanMethylation450 BeadChip
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EPIGENOME-WIDE ASSOCIATION; DNA METHYLATION; QUANTILE NORMALIZATION;
MATERNAL SMOKING; SUBSET-QUANTILE; ARRAY; PREGNANCY; CANCER
AB The Illumina HumanMethylation450 BeadChip is increasingly utilized in epigenome-wide association studies, however, this array-based measurement of DNA methylation is subject to measurement variation. Appropriate data preprocessing to remove background noise is important for detecting the small changes that may be associated with disease. We developed a novel background correction method, ENmix, that uses a mixture of exponential and truncated normal distributions to flexibly model signal intensity and uses a truncated normal distribution to model background noise. Depending on data availability, we employ three approaches to estimate background normal distribution parameters using (i) internal chip negative controls, (ii) out-ofband Infinium I probe intensities or (iii) combined methylated and unmethylated intensities. We evaluate ENmix against other available methods for both reproducibility among duplicate samples and accuracy of methylation measurement among laboratory control samples. ENmix out-performed other background correction methods for both these measures and substantially reduced the probe-design type bias between Infinium I and II probes. In reanalysis of existing EWAS data we show that ENmix can identify additional CpGs, and results in smaller P-value estimates for previously-validated CpGs. We incorporated the method into R package ENmix, which is freely available from Bioconductor website.
C1 [Xu, Zongli; Taylor, Jack A.] NIEHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Niu, Liang; Li, Leping] NIEHS, Biostat & Computat Biol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Niu, Liang] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA.
[Taylor, Jack A.] NIEHS, Lab Mol Carcinogenesis, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Li, LP (reprint author), NIEHS, Biostat & Computat Biol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.; Taylor, JA (reprint author), NIEHS, Lab Mol Carcinogenesis, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM li3@niehs.nih.gov; taylor@niehs.nih.gov
OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES044005, Z01 ES101765, Z01 ES049033,
Z01 ES049032]; National Institute of Health, US
FX Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES044005, Z01 ES101765, Z01 ES049033,
Z01 ES049032]. Funding for open access charge: National Institute of
Health, US.
NR 19
TC 6
Z9 6
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD FEB 18
PY 2016
VL 44
IS 3
AR e20
DI 10.1093/nar/gkv907
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3ST
UT WOS:000371268700001
PM 26384415
ER
PT J
AU Thompson, B
Varticovski, L
Baek, S
Hager, GL
AF Thompson, Bethtrice
Varticovski, Lyuba
Baek, Songjoon
Hager, Gordon L.
TI Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in
Early Commitment to Osteoblast Differentiation
SO PLOS ONE
LA English
DT Article
ID WNT SIGNALING PATHWAY; OSTEOGENIC DIFFERENTIATION;
GLUCOCORTICOID-RECEPTOR; TRANSCRIPTION FACTORS; STEM-CELLS; EXPRESSION;
RUNX2; INTERLEUKIN-11; OSTEOPOROSIS; ANTAGONISTS
AB Bone continuously undergoes remodeling by a tightly regulated process that involves osteoblast differentiation from Mesenchymal Stem Cells ( MSC). However, commitment of MSC to osteoblastic lineage is a poorly understood process. Chromatin organization functions as a molecular gatekeeper of DNA functions. Detection of sites that are hypersensitive to Dnase I has been used for detailed examination of changes in response to hormones and differentiation cues. To investigate the early steps in commitment of MSC to osteoblasts, we used a model human temperature-sensitive cell line, hFOB. When shifted to non-permissive temperature, these cells undergo "spontaneous" differentiation that takes several weeks, a process that is greatly accelerated by osteogenic induction media. We performed Dnase I hypersensitivity assays combined with deep sequencing to identify genome-wide potential regulatory events in cells undergoing early steps of commitment to osteoblasts. Massive reorganization of chromatin occurred within hours of differentiation. Whereas similar to 30% of unique DHS sites were located in the promoters, the majority was outside of the promoters, designated as enhancers. Many of them were at novel genomic sites and need to be confirmed experimentally. We developed a novel method for identification of cellular networks based solely on DHS enhancers signature correlated to gene expression. The analysis of enhancers that were unique to differentiating cells led to identification of bone developmental program encompassing 147 genes that directly or indirectly participate in osteogenesis. Identification of these pathways provided an unprecedented view of genomic regulation during early steps of differentiation and changes related to WNT, AP-1 and other pathways may have therapeutic implications.
C1 [Thompson, Bethtrice; Varticovski, Lyuba; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Thompson, Bethtrice] Clark Atlanta Univ, Ctr Canc Res & Therapeut Dev, Atlanta, GA 30314 USA.
RP Varticovski, L (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM varticol@mail.nih.gov
FU Intramural NIH program
FX Government funding was provided: Intramural NIH program. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 43
TC 3
Z9 3
U1 4
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 18
PY 2016
VL 11
IS 2
AR e0148619
DI 10.1371/journal.pone.0148619
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF3CO
UT WOS:000371221500010
PM 26890492
ER
PT J
AU Fauci, AS
Morens, DM
AF Fauci, Anthony S.
Morens, David M.
TI Zika Virus in the Americas - Yet Another Arbovirus Threat
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Fauci, Anthony S.; Morens, David M.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 5
TC 169
Z9 186
U1 17
U2 47
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 601
EP 604
DI 10.1056/NEJMp1600297
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000003
PM 26761185
ER
PT J
AU Snyder, PJ
Bhasin, S
Cunningham, GR
Matsumoto, AM
Stephens-Shields, AJ
Cauley, JA
Gill, TM
Barrett-Connor, E
Swerdloff, RS
Wang, C
Ensrud, KE
Lewis, CE
Farrar, JT
Cella, D
Rosen, RC
Pahor, M
Crandall, JP
Molitch, ME
Cifelli, D
Dougar, D
Fluharty, L
Resnick, SM
Storer, TW
Anton, S
Basaria, S
Diem, SJ
Hou, X
Mohler, ER
Parsons, JK
Wenger, NK
Zeldow, B
Landis, JR
Ellenberg, SS
AF Snyder, P. J.
Bhasin, S.
Cunningham, G. R.
Matsumoto, A. M.
Stephens-Shields, A. J.
Cauley, J. A.
Gill, T. M.
Barrett-Connor, E.
Swerdloff, R. S.
Wang, C.
Ensrud, K. E.
Lewis, C. E.
Farrar, J. T.
Cella, D.
Rosen, R. C.
Pahor, M.
Crandall, J. P.
Molitch, M. E.
Cifelli, D.
Dougar, D.
Fluharty, L.
Resnick, S. M.
Storer, T. W.
Anton, S.
Basaria, S.
Diem, S. J.
Hou, X.
Mohler, E. R., III
Parsons, J. K.
Wenger, N. K.
Zeldow, B.
Landis, J. R.
Ellenberg, S. S.
CA Testosterone Trials Investigators
TI Effects of Testosterone Treatment in Older Men
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MYOCARDIAL-INFARCTION; PHYSICAL FUNCTION; BODY-COMPOSITION; MUSCLE
STRENGTH; ELDERLY-MEN; THERAPY; TRIALS; RISK; METAANALYSIS; MORTALITY
AB BACKGROUND
Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.
METHODS
We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials - the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants.
RESULTS
Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P = 0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups.
CONCLUSIONS
In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.)
C1 [Snyder, P. J.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Stephens-Shields, A. J.; Farrar, J. T.; Hou, X.; Zeldow, B.; Landis, J. R.; Ellenberg, S. S.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Cifelli, D.; Dougar, D.; Fluharty, L.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Mohler, E. R., III] Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Dis,Sect Vasc Med, Philadelphia, PA 19104 USA.
[Bhasin, S.; Storer, T. W.; Basaria, S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Res Program Mens Hlth Aging & Metab, Boston, MA 02115 USA.
[Rosen, R. C.] New England Res Inst, Watertown, MA USA.
[Cunningham, G. R.] Baylor Coll Med, Dept Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
[Cunningham, G. R.] Baylor Coll Med, Dept Mol & Cellular Biol, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
[Cunningham, G. R.] Baylor St Lukes Med Ctr, Houston, TX USA.
[Matsumoto, A. M.] Univ Washington, Sch Med, Dept Vet Affairs VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Matsumoto, A. M.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA.
[Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Gill, T. M.] Yale Univ, Sch Med, Div Geriatr Med, New Haven, CT USA.
[Barrett-Connor, E.] Univ Calif San Diego, Sch Med, Dept Internal Med, La Jolla, CA 92093 USA.
[Barrett-Connor, E.] Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA.
[Swerdloff, R. S.; Wang, C.] Harbor UCLA Med Ctr, Div Endocrinol, Torrance, CA 90509 USA.
[Swerdloff, R. S.; Wang, C.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Parsons, J. K.] Univ Calif San Diego, Moores Comprehens Canc Ctr, Dept Urol, San Diego, CA 92103 USA.
[Ensrud, K. E.; Diem, S. J.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Box 736 UMHC, Minneapolis, MN 55455 USA.
[Ensrud, K. E.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA.
[Lewis, C. E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
[Cella, D.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Molitch, M. E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Pahor, M.; Anton, S.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Crandall, J. P.] Albert Einstein Coll Med, Div Endocrinol, Bronx, NY 10467 USA.
[Crandall, J. P.] Albert Einstein Coll Med, Div Geriatr, Bronx, NY 10467 USA.
[Resnick, S. M.] NIA, NIH, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Wenger, N. K.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA USA.
RP Snyder, PJ (reprint author), Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
EM pjs@mail.med.upenn.edu
RI Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU National Institutes of Health
FX Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT00799617.
NR 34
TC 84
Z9 84
U1 14
U2 30
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 611
EP 624
DI 10.1056/NEJMoa1506119
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000007
PM 26886521
ER
PT J
AU Uyeki, TM
Mehta, AK
Davey, RT
Liddell, AM
Wolf, T
Vetter, P
Schmiedel, S
Grunewald, T
Jacobs, M
Arribas, JR
Evans, L
Hewlett, AL
Brantsaeter, AB
Ippolito, G
Rapp, C
Hoepelman, AIM
Rapp, C
Hoepelman, AIM
Gutman, J
AF Uyeki, Timothy M.
Mehta, Aneesh K.
Davey, Richard T., Jr.
Liddell, Allison M.
Wolf, Timo
Vetter, Pauline
Schmiedel, Stefan
Gruenewald, Thomas
Jacobs, Michael
Arribas, Jose R.
Evans, Laura
Hewlett, Angela L.
Brantsaeter, Arne B.
Ippolito, Giuseppe
Rapp, Christophe
Hoepelman, Andy I. M.
Rapp, Christophe
Hoepelman, Andy I. M.
Gutman, Julie
CA US-European Clinical Network
TI Clinical Management of Ebola Virus Disease in the United States and
Europe
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CONVALESCENT PLASMA; SIERRA-LEONE; WEST-AFRICA; CRITICAL-CARE; PATIENT;
EPIDEMIC; FEATURES
AB BACKGROUND
Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited.
METHODS
We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015.
RESULTS
A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renalreplacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%.
CONCLUSIONS
Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.
C1 [Uyeki, Timothy M.; Gutman, Julie] Ctr Dis Control & Prevent, Mail Stop A-20,1600 Clifton Rd NE, Atlanta, GA 30329 USA.
[Mehta, Aneesh K.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA.
[Davey, Richard T., Jr.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Liddell, Allison M.] Texas Hlth Presbyterian Hosp Dallas, Dallas, TX USA.
[Wolf, Timo] Univ Hosp Frankfurt, Dept Infect Dis, Frankfurt, Germany.
[Schmiedel, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany.
[Gruenewald, Thomas] Klinikum St Georg, Leipzig Treatment Ctr Highly Contagious Dis, Leipzig, Germany.
[Vetter, Pauline] Univ Hosp Geneva, Div Infect Dis & Lab Virol, Geneva, Switzerland.
[Jacobs, Michael] Royal Free London NHS Fdn Trust, Dept Infect, London, England.
[Arribas, Jose R.] Hosp La Paz Carlos III IdiPAZ, Infect Dis Unit Madrid, Dept Internal Med, Madrid, Spain.
[Evans, Laura] NYU, Bellevue Hosp Ctr, Sch Med, New York, NY 10016 USA.
[Hewlett, Angela L.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Brantsaeter, Arne B.] Oslo Univ Hosp, Dept Infect Dis, Oslo, Norway.
[Brantsaeter, Arne B.] Oslo Univ Hosp, Dept Acute Med, Oslo, Norway.
[Ippolito, Giuseppe] Lazzaro Spallanzani Natl Inst Infect Dis, Rome, Italy.
[Rapp, Christophe] Begin Mil Hosp, Infect & Trop Dis Dept, St Mande, France.
[Hoepelman, Andy I. M.] Univ Med Ctr Utrecht, Dept Internal Med & Infect Dis, Utrecht, Netherlands.
RP Uyeki, TM (reprint author), Ctr Dis Control & Prevent, Mail Stop A-20,1600 Clifton Rd NE, Atlanta, GA 30329 USA.
EM tuyeki@cdc.gov
RI Martin, Daniel/F-7997-2010; Castilletti, Concetta/B-6545-2016;
OI Castilletti, Concetta/0000-0001-9819-236X; Mora-Rillo,
Marta/0000-0002-2735-5931; Di Caro, Antonino/0000-0001-6027-3009
FU Intramural CDC HHS [CC999999]
NR 26
TC 29
Z9 29
U1 2
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 636
EP 646
DI 10.1056/NEJMoa1504874
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000009
PM 26886522
ER
PT J
AU Boyden, SE
Desai, A
Cruse, G
Young, ML
Bolan, HC
Scott, LM
Eisch, AR
Long, RD
Lee, CCR
Satorius, CL
Pakstis, AJ
Olivera, A
Mullikin, JC
Chouery, E
Megarbane, A
Medlej-Hashim, M
Kidd, KK
Kastner, DL
Metcalfe, DD
Komarow, HD
AF Boyden, Steven E.
Desai, Avanti
Cruse, Glenn
Young, Michael L.
Bolan, Hyejeong C.
Scott, Linda M.
Eisch, A. Robin
Long, R. Daniel
Lee, Chyi-Chia R.
Satorius, Colleen L.
Pakstis, Andrew J.
Olivera, Ana
Mullikin, James C.
Chouery, Eliane
Megarbane, Andre
Medlej-Hashim, Myrna
Kidd, Kenneth K.
Kastner, Daniel L.
Metcalfe, Dean D.
Komarow, Hirsh D.
TI Vibratory Urticaria Associated with a Missense Variant in ADGRE2
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HUMAN EMR2; RECEPTOR; CELLS; CD97; LIGATION; CLEAVAGE; MOTIF
AB Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.)
C1 [Boyden, Steven E.; Satorius, Colleen L.; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Desai, Avanti; Cruse, Glenn; Bolan, Hyejeong C.; Scott, Linda M.; Eisch, A. Robin; Olivera, Ana; Metcalfe, Dean D.; Komarow, Hirsh D.] NIAID, Mast Cell Biol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia R.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Young, Michael L.] Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Leidos Biomed Res, Frederick, MD USA.
[Long, R. Daniel] NIAID, Vet Pathol Sect, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Pakstis, Andrew J.; Kidd, Kenneth K.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Chouery, Eliane] St Josephs Univ, Med Genet Unit, Beirut, Lebanon.
[Medlej-Hashim, Myrna] Lebanese Univ, Dept Life & Earth Sci, Fac Sci 2, Fanar, Lebanon.
[Megarbane, Andre] Inst Jerome Lejeune, Paris, France.
RP Komarow, HD (reprint author), NIAID, NIH, Bldg 10,Rm 1C129A1,MSC 1960, Bethesda, MD 20892 USA.
EM komarowh@mail.nih.gov
FU National Institutes of Health
FX Funded by the National Institutes of Health.
NR 24
TC 8
Z9 8
U1 2
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 656
EP 663
DI 10.1056/NEJMoa1500611
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000011
PM 26841242
ER
PT J
AU Mammen, AL
AF Mammen, Andrew L.
TI Statin-Associated Autoimmune Myopathy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID MEDIATED NECROTIZING MYOPATHY; CREATINE-KINASE; REDUCTASE ANTIBODIES;
MUSCLE REGENERATION; ANTI-3-HYDROXY-3-METHYLGLUTARYL-COENZYME;
AUTOANTIBODIES; COENZYME; MYOSITIS; OUTCOMES; THERAPY
AB Statins significantly reduce the incidence of cardiovascular disease, are generally safe, and have an acceptable side-effect profile. Indeed, a recent meta-analysis confirmed that mild musculoskeletal problems, such as myalgia, occur in approximately equal numbers of persons treated with statins and those given placebo. 1 Only in rare cases, in approximately 1 of 10,000 treated persons per year, 2 do statins cause serious muscle damage, with weakness and elevated levels of creatine kinase. In the majority of such cases, the patients recover spontaneously after the statin treatment is discontinued. 3,4 It is now recognized, however, that in very rare cases, an autoimmune myopathy develops in patients treated with statins; this disorder is characterized by muscle weakness, evidence of muscle-cell necrosis on biopsy, and the presence of autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. 5-16 In contrast to most patients who have side effects from statin therapy, those with statin-ssociated autoimmune myopathy may have progressive weakness that must be controlled with immunosuppressive therapy. This review describes the clinical characteristics, diagnosis, proposed pathologic mechanisms, and treatment of statin-associated autoimmune myopathy.
C1 [Mammen, Andrew L.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Mammen, Andrew L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Mammen, AL (reprint author), NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, 50 South Dr,Rm 1146,Bldg 50,MSC-8024, Bethesda, MD 20892 USA.
EM andrew.mammen@nih.gov
NR 36
TC 16
Z9 16
U1 5
U2 15
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 18
PY 2016
VL 374
IS 7
BP 664
EP 669
DI 10.1056/NEJMra1515161
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD9ER
UT WOS:000370229000012
PM 26886523
ER
PT J
AU Horne, HN
Sherman, ME
Pfeiffer, RM
Figueroa, JD
Khodr, ZG
Falk, RT
Pollak, M
Patel, DA
Palakal, MM
Linville, L
Papathomas, D
Geller, B
Vacek, PM
Weaver, DL
Chicoine, R
Shepherd, J
Mahmoudzadeh, AP
Wang, J
Fan, B
Malkov, S
Herschorn, S
Hewitt, SM
Brinton, LA
Gierach, GL
AF Horne, Hisani N.
Sherman, Mark E.
Pfeiffer, Ruth M.
Figueroa, Jonine D.
Khodr, Zeina G.
Falk, Roni T.
Pollak, Michael
Patel, Deesha A.
Palakal, Maya M.
Linville, Laura
Papathomas, Daphne
Geller, Berta
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael
Shepherd, John
Mahmoudzadeh, Amir Pasha
Wang, Jeff
Fan, Bo
Malkov, Serghei
Herschorn, Sally
Hewitt, Stephen M.
Brinton, Louise A.
Gierach, Gretchen L.
TI Circulating insulin-like growth factor-I, insulin-like growth factor
binding protein-3 and terminal duct lobular unit involution of the
breast: a cross-sectional study of women with benign breast disease
SO BREAST CANCER RESEARCH
LA English
DT Article
ID CANCER-RISK; MAMMOGRAPHIC DENSITY; IGF-I; POSTMENOPAUSAL WOMEN;
RACIAL-DIFFERENCES; MENSTRUAL-CYCLE; NURSES HEALTH; SEX-HORMONES;
ASSOCIATION; IGFBP-3
AB Background: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease.
Methods: Serum IGF-I, IGFBP-3 and IGF-I: IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density.
Results: Higher IGF-I levels among postmenopausal women and an elevated IGF-I: IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU.
Conclusions: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system.
C1 [Horne, Hisani N.; Khodr, Zeina G.; Falk, Roni T.; Patel, Deesha A.; Palakal, Maya M.; Linville, Laura; Papathomas, Daphne; Gierach, Gretchen L.] NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
[Horne, Hisani N.] US FDA, Silver Spring, MD USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Pollak, Michael] McGill Univ, Montreal, PQ, Canada.
[Patel, Deesha A.] Northwestern Univ, Sch Med, Chicago, IL 60611 USA.
[Geller, Berta; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael] Univ Vermont, Burlington, VT USA.
[Shepherd, John; Mahmoudzadeh, Amir Pasha; Fan, Bo; Malkov, Serghei; Herschorn, Sally] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Wang, Jeff] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Brinton, Louise A.] NCI, Off Director, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Gierach, GL (reprint author), NCI, Metabol Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov
RI Gierach, Gretchen/E-1817-2016;
OI Gierach, Gretchen/0000-0002-0165-5522; Hewitt,
Stephen/0000-0001-8283-1788
FU Intramural Research Program of the NIH, National Cancer Institute;
National Cancer Institute [U01CA70013, 1R21CA157254]; National Center
for Research Resources [M01 RR000109]; Breast Cancer Research Stamp
Funds
FX The authors are indebted to the participants in the BREAST Stamp Project
for their outstanding cooperation and to the physicians, pathologists,
nurses, technologists, and interviewers for their efforts in the field.
The authors thank Claire Bove, Patricia Lutton, Ellen Young and Aileen
Burke for research assistance. We also thank Janet Lawler-Heaver and
Kerry Grace Morrissey from Westat for study management support and Jane
Demuth at Information Management Services for data support and analysis.
The authors would also like to thank Patricia Madigan for her editorial
assistance. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute and Breast Cancer
Research Stamp Funds. Cooperative agreement U01CA70013 (BM Geller, PM
Vacek, DL Weaver, RE Chicoine, SD Herschorn) and 1R21CA157254 (JA
Shepherd, B Fan, AP Mahmoudzadeh, S Malkov) from the National Cancer
Institute funded some of the data collection and image analysis for this
study. Grant number M01 RR000109 from the National Center for Research
Resources funded the blood processing at the University of Vermont
General Clinical Research Center.
NR 49
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Z9 3
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD FEB 18
PY 2016
VL 18
AR 24
DI 10.1186/s13058-016-0678-4
PG 12
WC Oncology
SC Oncology
GA DE0NL
UT WOS:000370321500001
PM 26893016
ER
PT J
AU Wang, CX
Youle, R
AF Wang, Chunxin
Youle, Richard
TI CELL BIOLOGY Form follows function for mitochondria
SO NATURE
LA English
DT Editorial Material
ID MAMMALIAN-CELLS; FISSION; DRP1; MORPHOLOGY; FUSION; PHOSPHORYLATION;
DEGRADATION; SUBSTRATE; AUTOPHAGY; STRESS
C1 [Wang, Chunxin; Youle, Richard] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Wang, CX (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM wangchu@ninds.nih.gov; youler@ninds.nih.gov
NR 16
TC 1
Z9 1
U1 5
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 288
EP 289
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100025
PM 26887490
ER
PT J
AU Fear, J
Oliver, B
AF Fear, Justin
Oliver, Brian
TI DEVELOPMENTAL BIOLOGY Females have a lot of guts
SO NATURE
LA English
DT Editorial Material
ID DROSOPHILA
C1 [Fear, Justin; Oliver, Brian] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Oliver, B (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM briano@helix.nih.gov
NR 11
TC 0
Z9 0
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 289
EP 290
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100026
PM 26887491
ER
PT J
AU Zhao, Z
Martin, C
Fan, R
Bourne, PE
Xie, L
AF Zhao, Zheng
Martin, Che
Fan, Raymond
Bourne, Philip E.
Xie, Lei
TI Drug repurposing to target Ebola virus replication and virulence using
structural systems pharmacology
SO BMC BIOINFORMATICS
LA English
DT Article
DE Drug repositioning; Infectious disease; Indinavir; Sinefungin; Binding
site similarity; RNA-directed RNA polymerase; VP24
ID RESISTANT ACINETOBACTER-BAUMANNII; MOLECULAR-DYNAMICS SIMULATIONS;
HUMAN-IMMUNODEFICIENCY-VIRUS; LIGAND DOCKING; HIV-INTEGRASE; SINEFUNGIN;
BINDING; INHIBITOR; DISCOVERY; PROTEINS
AB Background: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation.
Results: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence of Ebola, and to determine the binding modes with their respective targets. Initial screening has identified a number of promising hits. Notably, Indinavir; an HIV protease inhibitor, may be effective in reducing the virulence of Ebola. Additionally, an antifungal (Sinefungin) and several anti-viral drugs (e.g. Maraviroc, Abacavir, Telbivudine, and Cidofovir) may inhibit Ebola RNA-directed RNA polymerase through targeting the MTase domain.
Conclusions: Identification of safe drug candidates is a crucial first step toward the determination of timely and effective therapeutic approaches to address and mitigate the impact of the Ebola global crisis and future outbreaks of pathogenic diseases. Further in vitro and in vivo testing to evaluate the anti-Ebola activity of these drugs is warranted.
C1 [Zhao, Zheng] Chinese Acad Sci, High Magnet Field Lab, Hefei, Peoples R China.
[Zhao, Zheng] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Martin, Che; Xie, Lei] CUNY, Grad Ctr, New York, NY USA.
[Fan, Raymond] CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA.
[Bourne, Philip E.] NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Xie, Lei] CUNY Hunter Coll, Dept Comp Sci, New York, NY 10021 USA.
RP Xie, L (reprint author), CUNY, Grad Ctr, New York, NY USA.; Xie, L (reprint author), CUNY Hunter Coll, Dept Comp Sci, New York, NY 10021 USA.
EM lxie@iscb.org
FU National Institute of Health [R01-LM011986]; National Science Foundation
[CNS-0958379, CNS-0855217]; City University of New York High Performance
Computing Center at the College of Staten Island
FX We appreciate the constructive suggestions of the anonymous reviewers
and the editor in improving the manuscript. This research was supported,
in part, under National Institute of Health Grant R01-LM011986, National
Science Foundation Grants CNS-0958379 and CNS-0855217, and the City
University of New York High Performance Computing Center at the College
of Staten Island.
NR 75
TC 2
Z9 2
U1 8
U2 37
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 18
PY 2016
VL 17
AR 90
DI 10.1186/s12859-016-0941-9
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA DD9GE
UT WOS:000370232900001
PM 26887654
ER
PT J
AU Vance, TM
Wang, Y
Su, LJ
Fontham, ETH
Steck, SE
Arab, L
Bensen, JT
Mohler, JL
Chen, MH
Chun, OK
AF Vance, Terrence M.
Wang, Ying
Su, L. Joseph
Fontham, Elizabeth T. H.
Steck, Susan E.
Arab, Lenore
Bensen, Jeannette T.
Mohler, James L.
Chen, Ming-Hui
Chun, Ock K.
TI Dietary Total Antioxidant Capacity is Inversely Associated with Prostate
Cancer Aggressiveness in a Population-Based Study
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; VITAMIN-E; BETA-CAROTENE; PLASMA
ANTIOXIDANTS; UNITED-STATES; POSTMENOPAUSAL WOMEN; CAUCASIAN AMERICANS;
OXIDATIVE STRESS; ALPHA-TOCOPHEROL; SERUM LYCOPENE
AB The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.
C1 [Vance, Terrence M.; Wang, Ying; Chun, Ock K.] Univ Connecticut, Dept Nutr Sci, 3624 Horsebarn Rd Extens Unit 4017, Storrs, CT 06269 USA.
[Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA.
[Steck, Susan E.] Univ S Carolina, Dept Epidemiol & Biostat, Canc Prevent & Control Program, Columbia, SC 29208 USA.
[Arab, Lenore] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
RP Chun, OK (reprint author), Univ Connecticut, Dept Nutr Sci, 3624 Horsebarn Rd Extens Unit 4017, Storrs, CT 06269 USA.
EM ock.chun@uconn.edu
FU NIH Cancer Epidemiology Small [1R03CA159421-01A1]; Department of Defense
[DAMD 17-03-2-0052]
FX This research was supported by the NIH Cancer Epidemiology Small Grant
#1R03CA159421-01A1 and Department of Defense contract DAMD 17-03-2-0052.
The authors thank the North Carolina Central Cancer Registry, the
Louisiana Tumor Registry, and the PCaP staff, advisory committees and
participants for their important contributions.
NR 68
TC 0
Z9 0
U1 4
U2 6
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PD FEB 17
PY 2016
VL 68
IS 2
BP 214
EP 224
DI 10.1080/01635581.2016.1134596
PG 11
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA DI1VS
UT WOS:000373285300006
PM 26847416
ER
PT J
AU Kiskowski, M
Chowell, G
AF Kiskowski, Maria
Chowell, Gerardo
TI Modeling household and community transmission of Ebola virus disease:
Epidemic growth, spatial dynamics and insights for epidemic control
SO VIRULENCE
LA English
DT Article
DE waves; dynamical models; Ebola virus (EBOV); agent-based models;
reaction diffusion; emergent dynamics; infectious disease dynamics;
social networks; mathematical epidemiology
ID HEMORRHAGIC-FEVER; TRAVELING-WAVES; WEST-AFRICA; OUTBREAK; CONGO;
NETWORKS; LIBERIA; KIKWIT; EVD
AB The mechanisms behind the sub-exponential growth dynamics of the West Africa Ebola virus disease epidemic could be related to improved control of the epidemic and the result of reduced disease transmission in spatially constrained contact structures. An individual-based, stochastic network model is used to model immediate and delayed epidemic control in the context of social contact networks and investigate the extent to which the relative role of these factors may be determined during an outbreak. We find that in general, epidemics quickly establish a dynamic equilibrium of infections in the form of a wave of fixed size and speed traveling through the contact network. Both greater epidemic control and limited community mixing decrease the size of an infectious wave. However, for a fixed wave size, epidemic control (in contrast with limited community mixing) results in lower community saturation and a wave that moves more quickly through the contact network. We also found that the level of epidemic control has a disproportionately greater reductive effect on larger waves, so that a small wave requires nearly as much epidemic control as a larger wave to end an epidemic.
C1 [Kiskowski, Maria] Univ S Alabama, Dept Math & Stat, Mobile, AL 36688 USA.
[Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Kiskowski, M (reprint author), Univ S Alabama, Dept Math & Stat, Mobile, AL 36688 USA.
EM abyrne@southalabama.edu
FU NSF as part of the joint NSF-NIH-USDA Ecology and Evolution of
Infectious Diseases program [1414374]; United Kingdom Biotechnology and
Biological Sciences Research Council [BB/M008894/1]; National Institute
of General Medical Sciences (NIGMS) at the National Institutes of Health
[1R01GM100471-01]; NSF III: Small: Data Management for Real-Time Data
Driven Epidemic simulation and RAPID NFS [1318788, 1518939, NSF
1518529]; Division of International Epidemiology and Population Studies,
The Fogarty International Center, NIH
FX GC acknowledges support from NSF grant #1414374 as part of the joint
NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program,
United Kingdom Biotechnology and Biological Sciences Research Council
grant BB/M008894/1, grant #1R01GM100471-01 from the National Institute
of General Medical Sciences (NIGMS) at the National Institutes of
Health, NSF grant 1318788 III: Small: Data Management for Real-Time Data
Driven Epidemic simulation and RAPID NFS Grants#1518939 and NSF#1518529,
and the Division of International Epidemiology and Population Studies,
The Fogarty International Center, NIH.
NR 47
TC 1
Z9 1
U1 2
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2150-5594
EI 2150-5608
J9 VIRULENCE
JI Virulence
PD FEB 17
PY 2016
VL 7
IS 2
BP 163
EP 173
DI 10.1080/21505594.2015.1076613
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DH8OP
UT WOS:000373054300013
PM 26399855
ER
PT J
AU Shigehiro, T
Zhai, WJ
Vaidyanath, A
Masuda, J
Mizutani, A
Kasai, T
Murakami, H
Hamada, H
Salomon, DS
Mikuni, K
Seno, Y
Mandai, T
Seno, M
AF Shigehiro, Tsukasa
Zhai, Wenjia
Vaidyanath, Arun
Masuda, Junko
Mizutani, Akifumi
Kasai, Tomonari
Murakami, Hiroshi
Hamada, Hiroki
Salomon, David S.
Mikuni, Katsuhiko
Seno, Yuhki
Mandai, Tadakatsu
Seno, Masaharu
TI Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by
remote loading under solubility gradient
SO JOURNAL OF MICROENCAPSULATION
LA English
DT Article
DE glycosylated docetaxel; solubility gradient; Docetaxel; remote loading
method; liposome
ID TUMOR XENOGRAFTS; IN-VIVO; DELIVERY; PACLITAXEL; CHEMOTHERAPY;
PHARMACOKINETICS; FORMULATIONS; TAXOTERE(R); CANCER
AB Docetaxel comprises one of the most effective anti-cancer drugs despite of serious side effects. Liposomes encapsulation is practically feasible to deliver the drug. However, due to the significant hydrophobicity, docetaxel will be integrated into the lipid bilayer resulting in poor encapsulation capacity. Here, we evaluated a remote loading strategy using a solubility gradient made between the two solvents for 7-glucosyloxyacetyldocetaxel, which has enhanced water solubility of docetaxel with a coupled glucose moiety. Therefore, 7-glucosyloxyacetyldocetaxel was more effectively encapsulated into liposomes with 71.0% of encapsulation efficiency than docetaxel. While 7-glucosyloxyacetyldocetaxel exhibited 90.9% of tubulin stabilisation activity of docetaxel, 7-glucosyloxyacetyldocetaxel encapsulated in liposomes significantly inhibited the growth of tumour in vivo with side effects less than unencapsulated drug. Collectively, the encapsulation of 7-glucosyloxyacetyldocetaxel into liposomes by remote loading under the solubility gradient is considered to be a promising application to prepare practical drug delivery system.
C1 [Shigehiro, Tsukasa; Zhai, Wenjia; Vaidyanath, Arun; Masuda, Junko; Mizutani, Akifumi; Kasai, Tomonari; Murakami, Hiroshi; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn, Kita Ku, Room 460 Bldg ENG-6,3-1-1 Tsushima Naka, Okayama 7008530, Japan.
[Shigehiro, Tsukasa] Japan Soc Promot Sci, Tokyo, Japan.
[Hamada, Hiroki] Okayama Univ Sci, Fac Sci, Okayama, Japan.
[Salomon, David S.] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA.
[Mikuni, Katsuhiko] Ensuiko Sugar Refining Co Ltd, Tokyo, Japan.
[Seno, Yuhki; Mandai, Tadakatsu] Kurashiki Univ Sci & Arts, Fac Life Sci, Kurashiki, Japan.
RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn, Kita Ku, Room 460 Bldg ENG-6,3-1-1 Tsushima Naka, Okayama 7008530, Japan.
EM mseno@okayama-u.ac.jp
FU Ensuiko Sugar Refining Co., Ltd.; Japan Society for the Promotion of
Science [25,2,42045, 26 640079, 15J08264]
FX This study was partly designed and funded by a commercial company
(Ensuiko Sugar Refining Co., Ltd.) and one of the authors, Katsuhiko
Mikuni, is an employee of Ensuiko Sugar Refining Co., Ltd. Okayama
University, Ensuiko Sugar Refining Co., Ltd. and Hiroki Hamada are the
applicants of the Japanese Patent No. 5490326 and the international
patent application No. PCT/JP2013/058242 entitled "Method for producing
liposome encapsulating paclitaxel monoglycoside and/or docetaxel
monoglycoside''. This study was partly supported by Grant-in-Aid for
Scientific Research (A) No. 25,2,42045 (MS), Grant-in-Aid for
Challenging Exploratory Research No. 26 640079 (MS) and Grant-in-Aid for
JSPS Fellows No. 15J08264 (TS) from the Japan Society for the Promotion
of Science.
NR 26
TC 1
Z9 1
U1 5
U2 12
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0265-2048
EI 1464-5246
J9 J MICROENCAPSUL
JI J. Microencapsul.
PD FEB 17
PY 2016
VL 33
IS 2
BP 172
EP 182
DI 10.3109/02652048.2016.1144815
PG 11
WC Chemistry, Applied; Engineering, Chemical; Pharmacology & Pharmacy
SC Chemistry; Engineering; Pharmacology & Pharmacy
GA DI4QH
UT WOS:000373483900008
PM 26885749
ER
PT J
AU Johnson, KL
Williams, JG
Maleki, SJ
Hurlburt, BK
London, RE
Mueller, GA
AF Johnson, Katina L.
Williams, Jason G.
Maleki, Soheila J.
Hurlburt, Barry K.
London, Robert E.
Mueller, Geoffrey A.
TI Enhanced Approaches for Identifying Amadori Products: Application to
Peanut Allergens
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE peanuts (Arachis hypogaea); allergen; advanced glycation end products;
Amadori products; Maillard reactions; Shannon entropy
ID GLYCATION END-PRODUCTS; TANDEM MASS-SPECTROMETRY; PROCESSED PEANUTS;
MAILLARD REACTION; PEPTIDES; PROTEINS; BINDING; FOODS
AB The dry roasting of peanuts is suggested to influence allergic sensitization as a result of the formation of advanced glycation end products (AGEs) on peanut proteins. Identifying AGEs is technically challenging. The AGEs of a peanut allergen were probed with nano-scale liquid chromatography electrospray ionization mass spectrometry (nanoLC-ESI-MS) and tandem mass spectrometry (MS/MS) analyses. Amadori product ions matched to expected peptides and yielded fragments that included a loss of three waters and HCHO. As a result of the paucity of b and y ions in the MS/MS spectrum, standard search algorithms do not perform well. Reactions with isotopically labeled sugars confirmed that the peptides contained Amadori products. An algorithm was developed on the basis of information content (Shannon entropy) and the loss of water and HCHO. Results with test data show that the algorithm finds the correct spectra with high precision, reducing the time needed to manually inspect data. Computational and technical improvements allowed for better identification of the chemical differences between modified and unmodified proteins.
C1 [Johnson, Katina L.; Williams, Jason G.] NIEHS, Epigenet & Stem Cell Biol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
[London, Robert E.; Mueller, Geoffrey A.] NIEHS, Genome Integr & Struct Biol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
[Maleki, Soheila J.; Hurlburt, Barry K.] ARS, USDA, 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA.
RP Mueller, GA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM geoffrey.mueller@nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01-ES102885-01, Z01-ES102488-05]
FX This research was supported in part by Research Projects Z01-ES102885-01
to Robert E. London and Z01-ES102488-05 to Jason G. Williams in the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health.
NR 26
TC 0
Z9 0
U1 9
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
EI 1520-5118
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD FEB 17
PY 2016
VL 64
IS 6
BP 1406
EP 1413
DI 10.1021/acs.jafc.5b05492
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA DE4FF
UT WOS:000370583900023
PM 26811263
ER
PT J
AU Li, JW
Wang, YF
Chen, JF
Liu, ZJ
Bax, A
Yao, LS
AF Li, Jingwen
Wang, Yefei
Chen, Jingfei
Liu, Zhijun
Bax, Ad
Yao, Lishan
TI Observation of alpha-Helical Hydrogen-Bond Cooperativity in an Intact
Protein
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID DENSITY-FUNCTIONAL THEORY; 2D IR SPECTROSCOPY; FRACTIONATION FACTORS;
SCALAR COUPLINGS; 3(10)-HELICAL PEPTIDES; CHEMICAL-SHIFTS; BETA-SHEETS;
DYNAMICS; MODELS; NMR
AB The presence and extent of hydrogen-bonding (H-bonding) cooperativity in proteins remains a fundamental question, which in the past has been studied extensively, mostly by infrared and fluorescence measurements on model peptides. We demonstrate that such cooperativity can be studied in an intact protein by hydrogen/deuterium exchange NMR spectroscopy. The method is based on the fact that substitution of NH by ND in a backbone amide group slightly weakens the N-H center dot center dot center dot O=C hydrogen bond. Our results show that such substitution at position i in an alpha-helix impacts the H-1 and N-15 chemical shifts of the amide sites of residues i-3 to i + 3. Quantum mechanical calculations indicate that the upfield shifts of H-1 and N-15 resonances at site i, observed upon H/D exchanges at sites i-3, i + 1, i + 2, and i + 3, correspond to a decrease of the ith backbone amide electric dipole moment, which weakens its H-bonding and long-range electrostatic interactions with other backbone amides in the alpha-helix. These results provide new quantitative insights into the cooperativity of H-bonding in protein a-helices.
C1 [Li, Jingwen; Wang, Yefei; Chen, Jingfei; Yao, Lishan] Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Shandong Prov Key Lab Synthet Biol, Qingdao 266061, Peoples R China.
[Li, Jingwen; Wang, Yefei; Chen, Jingfei; Yao, Lishan] Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Lab Biofuels, Qingdao 266061, Peoples R China.
[Liu, Zhijun] Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 201210, Peoples R China.
[Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Yao, LS (reprint author), Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Shandong Prov Key Lab Synthet Biol, Qingdao 266061, Peoples R China.; Yao, LS (reprint author), Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Lab Biofuels, Qingdao 266061, Peoples R China.
EM yaols@qibebt.ac.cn
RI yao, lishan/H-3662-2012
OI yao, lishan/0000-0003-1797-922X
FU National Natural Science Foundation of China [21173247, 31270785];
NIDDK, National Institutes of Health (NIH)
FX This work was supported by the National Natural Science Foundation of
China (Grant no. 21173247 and 31270785 to L.Y.). A.B. is supported by
the Intramural Research Program of the NIDDK, National Institutes of
Health (NIH).
NR 45
TC 3
Z9 3
U1 13
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD FEB 17
PY 2016
VL 138
IS 6
BP 1824
EP 1827
DI 10.1021/jacs.5b13140
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DE4EV
UT WOS:000370582900021
PM 26853186
ER
PT J
AU Mo, AX
Colley, DG
AF Mo, Annie X.
Colley, Daniel G.
TI Workshop report: Schistosomiasis vaccine clinical development and
product characteristics
SO VACCINE
LA English
DT Article
DE Schistosomiasis; Vaccine; Clinical development plan (CDP); Preferred
product characteristics (PPC); Target product profile (TPP)
ID THERAPEUTIC VACCINE; HOOKWORM VACCINE; ECONOMIC VALUE; HUMAN IGE;
ELIMINATION; HAEMATOBIUM; CANDIDATE; INFECTION; RESPONSES; EFFICACY
AB A schistosomiasis vaccine meeting was organized to evaluate the utility of a vaccine in public health programs, to discuss clinical development paths, and to define basic product characteristics for desirable vaccines to be used in the context of schistosomiasis control and elimination programs. It was concluded that clinical evaluation of a schistosomiasis vaccine is feasible with appropriate trial design and tools. Some basic Preferred Product Characteristics (PPC) for a human schistosomiasis vaccine and for a veterinary vaccine for bovine use were also proposed.
C1 [Mo, Annie X.] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Colley, Daniel G.] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA.
[Colley, Daniel G.] Univ Georgia, Dept Microbiol, Athens, GA 30602 USA.
RP Mo, AX (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM annie.mo@nih.gov
NR 24
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD FEB 17
PY 2016
VL 34
IS 8
BP 995
EP 1001
DI 10.1016/j.vaccine.2015.12.032
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DF1LK
UT WOS:000371101100001
PM 26721329
ER
PT J
AU Petridis, C
Brook, MN
Shah, V
Kohut, K
Gorman, P
Caneppele, M
Levi, D
Papouli, E
Orr, N
Cox, A
Cross, SS
dos-Santos-Silva, I
Peto, J
Swerdlow, A
Schoemaker, MJ
Bolla, MK
Wang, Q
Dennis, J
Michailidou, K
Benitez, J
Gonzalez-Neira, A
Tessier, DC
Vincent, D
Li, JM
Figueroa, J
Kristensen, V
Borresen-Dale, AL
Soucy, P
Simard, J
Milne, RL
Giles, GG
Margolin, S
Lindblom, A
Bruning, T
Brauch, H
Southey, MC
Hopper, JL
Dork, T
Bogdanova, NV
Kabisch, M
Hamann, U
Schmutzler, RK
Meindl, A
Brenner, H
Arndt, V
Winqvist, R
Pylkas, K
Fasching, PA
Beckmann, MW
Lubinski, J
Jakubowska, A
Mulligan, AM
Andrulis, IL
Tollenaar, RAEM
Devilee, P
Le Marchand, L
Haiman, CA
Mannermaa, A
Kosma, VM
Radice, P
Peterlongo, P
Marme, F
Burwinkel, B
van Deurzen, CHM
Hollestelle, A
Miller, N
Kerin, MJ
Lambrechts, D
Floris, G
Wesseling, J
Flyger, H
Bojesen, SE
Yao, S
Ambrosone, CB
Chenevix-Trench, G
Truong, T
Guenel, P
Rudolph, A
Chang-Claude, J
Nevanlinna, H
Blomqvist, C
Czene, K
Brand, JS
Olson, JE
Couch, FJ
Dunning, AM
Hall, P
Easton, DF
Pharoah, PDP
Pinder, SE
Schmidt, MK
Tomlinson, I
Roylance, R
Garcia-Closas, M
Sawyer, EJ
AF Petridis, Christos
Brook, Mark N.
Shah, Vandna
Kohut, Kelly
Gorman, Patricia
Caneppele, Michele
Levi, Dina
Papouli, Efterpi
Orr, Nick
Cox, Angela
Cross, Simon S.
dos-Santos-Silva, Isabel
Peto, Julian
Swerdlow, Anthony
Schoemaker, Minouk J.
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Michailidou, Kyriaki
Benitez, Javier
Gonzalez-Neira, Anna
Tessier, Daniel C.
Vincent, Daniel
Li, Jingmei
Figueroa, Jonine
Kristensen, Vessela
Borresen-Dale, Anne-Lise
Soucy, Penny
Simard, Jacques
Milne, Roger L.
Giles, Graham G.
Margolin, Sara
Lindblom, Annika
Bruening, Thomas
Brauch, Hiltrud
Southey, Melissa C.
Hopper, John L.
Doerk, Thilo
Bogdanova, Natalia V.
Kabisch, Maria
Hamann, Ute
Schmutzler, Rita K.
Meindl, Alfons
Brenner, Hermann
Arndt, Volker
Winqvist, Robert
Pylkas, Katri
Fasching, Peter A.
Beckmann, Matthias W.
Lubinski, Jan
Jakubowska, Anna
Mulligan, Anna Marie
Andrulis, Irene L.
Tollenaar, Rob A. E. M.
Devilee, Peter
Le Marchand, Loic
Haiman, Christopher A.
Mannermaa, Arto
Kosma, Veli-Matti
Radice, Paolo
Peterlongo, Paolo
Marme, Frederik
Burwinkel, Barbara
van Deurzen, Carolien H. M.
Hollestelle, Antoinette
Miller, Nicola
Kerin, Michael J.
Lambrechts, Diether
Floris, Giuseppe
Wesseling, Jelle
Flyger, Henrik
Bojesen, Stig E.
Yao, Song
Ambrosone, Christine B.
Chenevix-Trench, Georgia
Truong, Therese
Guenel, Pascal
Rudolph, Anja
Chang-Claude, Jenny
Nevanlinna, Heli
Blomqvist, Carl
Czene, Kamila
Brand, Judith S.
Olson, Janet E.
Couch, Fergus J.
Dunning, Alison M.
Hall, Per
Easton, Douglas F.
Pharoah, Paul D. P.
Pinder, Sarah E.
Schmidt, Marjanka K.
Tomlinson, Ian
Roylance, Rebecca
Garcia-Closas, Montserrat
Sawyer, Elinor J.
TI Genetic predisposition to ductal carcinoma in situ of the breast
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Ductal carcinoma in situ; Association study; Genetic predisposition;
Common variants
ID GENOME-WIDE ASSOCIATION; RISK-FACTORS; SUSCEPTIBILITY LOCI; CANCER RISK;
METAANALYSIS; VARIANTS; GRADE; DCIS
AB Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.
Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip.
Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC.
We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8).
Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.
C1 [Petridis, Christos; Shah, Vandna; Levi, Dina; Pinder, Sarah E.; Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London WC2R 2LS, England.
[Petridis, Christos] Kings Coll London, Med & Mol Genet, London WC2R 2LS, England.
[Brook, Mark N.; Swerdlow, Anthony; Schoemaker, Minouk J.; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Roylance, Rebecca] Queen Mary Univ London, Ctr Mol Oncol, Barts Canc Inst, London, England.
[Papouli, Efterpi] Kings Coll London, Guys Hosp, Biomed Res Ctr, London WC2R 2LS, England.
[Orr, Nick] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London SW3 6JB, England.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
[dos-Santos-Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras, Valencia, Spain.
[Tessier, Daniel C.; Vincent, Daniel] Ctr Innovat Genome Quebec, Montreal, PQ, Canada.
[Tessier, Daniel C.; Vincent, Daniel] McGill Univ, Montreal, PQ, Canada.
[Li, Jingmei; Czene, Kamila; Brand, Judith S.; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Figueroa, Jonine; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Oslo Univ Hosp Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Oslo, Norway.
[Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
[Soucy, Penny; Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Genom Ctr, Quebec City, PQ, Canada.
[Milne, Roger L.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Milne, Roger L.; Giles, Graham G.; Hopper, John L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Bruening, Thomas] Ruhr Univ Bochum, Inst Prevent & Occupat Med, German Social Accid Insurance, Univ Str 150, Bochum, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Kabisch, Maria; Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Schmutzler, Rita K.] Univ Cologne, Fac Med, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Cologne, Germany.
[Schmutzler, Rita K.] Univ Cologne, Fac Med, CIO, D-50931 Cologne, Germany.
[Schmutzler, Rita K.] Univ Cologne, Fac Med, CMMC, D-50931 Cologne, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-80290 Munich, Germany.
[Brenner, Hermann; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, Lab Canc Genet & Tumor Biol, Canc & Translat Med Res Unit, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynaecol & Obstet, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Lubinski, Jan; Jakubowska, Anna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland.
[Radice, Paolo] Fdn IRCCS Ist Ricovero & Cura Carattere Sci, INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Peterlongo, Paolo] FFdn Ist FIRC Italian Fdn Canc Res Oncol Mol, IFOM, Milan, Italy.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Marme, Frederik; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[van Deurzen, Carolien H. M.] Erasmus Univ, Med Ctr, Dept Pathol, Rotterdam, Netherlands.
[Hollestelle, Antoinette] Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Miller, Nicola; Kerin, Michael J.] Natl Univ Ireland, Sch Med, Galway, Ireland.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Floris, Giuseppe] Univ Hosp Gashuisberg, Leuven, Belgium.
[Wesseling, Jelle; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Flyger, Henrik] Herlev Hosp, Copenhagen Univ Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Herlev Hosp, Copenhagen Univ Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Herlev Hosp, Copenhagen Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Yao, Song] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Truong, Therese; Guenel, Pascal] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France.
[Truong, Therese; Guenel, Pascal] Univ Paris 11, Villejuif, France.
[Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Nevanlinna, Heli] Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, Helsinki, Finland.
[Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Dunning, Alison M.; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England.
RP Sawyer, EJ (reprint author), Kings Coll London, Guys Hosp, Res Oncol, London WC2R 2LS, England.
EM elinor.sawyer@kcl.ac.uk
RI Li, Jingmei/I-2904-2012; Bruning, Thomas/G-8120-2015; Andrulis,
Irene/E-7267-2013; Dork, Thilo/J-8620-2012; Brenner,
Hermann/B-4627-2017;
OI Giles, Graham/0000-0003-4946-9099; Li, Jingmei/0000-0001-8587-7511;
Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; Schoemaker, Minouk/0000-0001-8403-2234;
Brook, Mark/0000-0002-8969-2378; Dunning, Alison
Margaret/0000-0001-6651-7166
FU Breast Cancer Now
FX ICICLE genotyping was funded by the Breast Cancer Now
(http://breastcancernow.org/), and sample and data collection.
NR 32
TC 7
Z9 7
U1 5
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD FEB 17
PY 2016
VL 18
AR 22
DI 10.1186/s13058-016-0675-7
PG 15
WC Oncology
SC Oncology
GA DD9JQ
UT WOS:000370241900001
PM 26884359
ER
PT J
AU Kite, WA
Melendez-Muniz, VA
Barros, RRM
Wellems, TE
Sa, JM
AF Kite, Whitney A.
Melendez-Muniz, Viviana A.
Barros, Roberto R. Moraes
Wellems, Thomas E.
Sa, Juliana M.
TI Alternative methods for the Plasmodium falciparum artemisinin ring-stage
survival assay with increased simplicity and parasite stage-specificity
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum; Artemisinin; In vitro anti-malarial assays
ID IN-VITRO; WESTERN CAMBODIA; MALARIA; RESISTANCE; CLEARANCE; SENSITIVITY
AB Background: Artemisinin-based combination therapy is recommended to treat Plasmodium falciparum worldwide, but observations of longer artemisinin (ART) parasite clearance times (PCTs) in Southeast Asia are widely interpreted as a sign of potential ART resistance. In search of an in vitro correlate of in vivo PCT after ART treatment, a ring-stage survival assay (RSA) of 0-3 h parasites was developed and linked to polymorphisms in the Kelch propeller protein (K13). However, RSA remains a laborious process, involving heparin, Percoll gradient, and sorbitol treatments to obtain rings in the 0-3 h window. Here two alternative RSA protocols are presented and compared to the standard Percoll-based method, one highly stage-specific and one streamlined for laboratory application.
Methods: For all protocols, P. falciparum cultures were synchronized with 5 % sorbitol treatment twice over two intra-erythrocytic cycles. For a filtration-based RSA, late-stage schizonts were passed through a 1.2 mu m filter to isolate merozoites, which were incubated with uninfected erythrocytes for 45 min. The erythrocytes were then washed to remove lysis products and further incubated until 3 h post-filtration. Parasites were pulsed with either 0.1 % dimethyl sulfoxide (DMSO) or 700 nM dihydroartemisinin in 0.1 % DMSO for 6 h, washed twice in drug-free media, and incubated for 66-90 h, when survival was assessed by microscopy. For a sorbitol-only RSA, synchronized young (0-3 h) rings were treated with 5 % sorbitol once more prior to the assay and adjusted to 1 % parasitaemia. The drug pulse, incubation, and survival assessment were as described above.
Results: Ring-stage survival of P. falciparum parasites containing either the K13 C580 or C580Y polymorphism (associated with low and high RSA survival, respectively) were assessed by the described filtration and sorbitol-only methods and produced comparable results to the reported Percoll gradient RSA. Advantages of both new methods include: fewer reagents, decreased time investment, and fewer procedural steps, with enhanced stage-specificity conferred by the filtration method.
Conclusions: Assessing P. falciparum ART sensitivity in vitro via RSA can be streamlined and accurately evaluated in the laboratory by filtration or sorbitol synchronization methods, thus increasing the accessibility of the assay to research groups.
C1 [Kite, Whitney A.; Melendez-Muniz, Viviana A.; Barros, Roberto R. Moraes; Wellems, Thomas E.; Sa, Juliana M.] NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10, Rockville, MD 20852 USA.
[Melendez-Muniz, Viviana A.] Univ Cent Caribe, Sch Med, Bayamon, PR 00960 USA.
RP Sa, JM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10, Rockville, MD 20852 USA.
EM jsa@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Disease, National Institutes of Health
FX We thank Paul Han, Michael A. Krause, and Anna Liu for providing support
with culturing and setting up experiments, Chanaki Amaratunga for hands
on training in the Percoll gradient RSA, and Jennifer S. Armistead,
Tyler Gibson, and J. Patrick Mershon for providing feedback on the
manuscript. The Intramural Research Program of the National Institute of
Allergy and Infectious Disease, National Institutes of Health supported
this research.
NR 22
TC 0
Z9 0
U1 3
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 17
PY 2016
VL 15
AR 94
DI 10.1186/s12936-016-1148-2
PG 7
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DD9ON
UT WOS:000370255400001
PM 26888201
ER
PT J
AU Luke, T
Wu, H
Zhao, JC
Channappanavar, R
Coleman, CM
Jiao, JA
Matsushita, H
Liu, Y
Postnikova, EN
Ork, BL
Glenn, G
Flyer, D
Defang, G
Raviprakash, K
Kochel, T
Wang, J
Nie, WS
Smith, G
Hensley, LE
Olinger, GG
Kuhn, JH
Holbrook, MR
Johnson, RF
Perlman, S
Sullivan, E
Frieman, MB
AF Luke, Thomas
Wu, Hua
Zhao, Jincun
Channappanavar, Rudragouda
Coleman, Christopher M.
Jiao, Jin-An
Matsushita, Hiroaki
Liu, Ye
Postnikova, Elena N.
Ork, Britini L.
Glenn, Gregory
Flyer, David
Defang, Gabriel
Raviprakash, Kanakatte
Kochel, Tadeusz
Wang, Jonathan
Nie, Wensheng
Smith, Gale
Hensley, Lisa E.
Olinger, Gene G.
Kuhn, Jens H.
Holbrook, Michael R.
Johnson, Reed F.
Perlman, Stanley
Sullivan, Eddie
Frieman, Matthew B.
TI Human polyclonal immunoglobulin G from transchromosomic bovines inhibits
MERS-CoV in vivo
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; RECEPTOR-BINDING DOMAIN; HUMAN
MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; SPIKE PROTEIN; DROMEDARY
CAMELS; SAUDI-ARABIA; SARS-COV; MICE; TRANSMISSION
AB As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A gamma-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody-dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERS-CoV infection and/or other emerging infectious diseases.
C1 [Luke, Thomas] Navy Med Res Ctr, Viral & Rickettsial Dis Dept, Henry Jackson Fdn Adv Mil Med, Silver Spring, MD 20910 USA.
[Wu, Hua; Jiao, Jin-An; Matsushita, Hiroaki; Sullivan, Eddie] SAB Biotherapeut Inc, Sioux Falls, SD 57104 USA.
[Zhao, Jincun; Channappanavar, Rudragouda; Perlman, Stanley] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
[Zhao, Jincun] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou Inst Resp Dis, Guangzhou 510120, Peoples R China.
[Coleman, Christopher M.; Frieman, Matthew B.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Liu, Ye; Glenn, Gregory; Flyer, David; Smith, Gale] Novavax Inc, Gaithersburg, MD 20878 USA.
[Postnikova, Elena N.; Ork, Britini L.; Hensley, Lisa E.; Olinger, Gene G.; Kuhn, Jens H.; Holbrook, Michael R.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Defang, Gabriel] Naval Med Res Unit 3, Dept Virol, Cairo Fpo Ap 09835, Egypt.
[Raviprakash, Kanakatte; Kochel, Tadeusz] Navy Med Res Ctr, Viral & Rickettsial Dis Dept, Silver Spring, MD 20910 USA.
[Wang, Jonathan; Nie, Wensheng] Thermo Fisher Sci, San Francisco, CA 94080 USA.
[Johnson, Reed F.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
[Kochel, Tadeusz] Natl Biodef Anal & Countermeasures Ctr, Forens Virol, Frederick, MD 21702 USA.
RP Luke, T (reprint author), Navy Med Res Ctr, Viral & Rickettsial Dis Dept, Henry Jackson Fdn Adv Mil Med, Silver Spring, MD 20910 USA.
EM thomas.c.luke.ctr@mail.mil
FU Global Emerging Infections Surveillance Response System (GEIS) funds
work unit [847705.82000.25GB.E0018]; NIH [RO1 AI095569, PO1 AI060699,
RO1 AI091322]; Division of Intramural Research of the National Institute
of Allergy and Infectious Diseases (NIAID); Integrated Research Facility
(NIAID, Division of Clinical Research); Battelle Memorial Institute;
NIAID [HHSN272200700016I]; Viral and Rickettsial Diseases Department of
the Naval Medical Research Center; Henry Jackson Foundation for the
Advancement of Military Medicine; U.S. Navy [Omnibus III DO-0005]
FX Funding: This work was supported in part by the Global Emerging
Infections Surveillance Response System (GEIS) funds work unit
#847705.82000.25GB.E0018. This project has been funded in part by a
supplement to NIH RO1 AI095569 (M.B.F.), PO1 AI060699, and RO1 AI091322
(S.P.). The work was supported in part by the Division of Intramural
Research of the National Institute of Allergy and Infectious Diseases
(NIAID), the Integrated Research Facility (NIAID, Division of Clinical
Research), and Battelle Memorial Institute's prime contract with NIAID
(contract HHSN272200700016I). B.L.O. and M.R.H. performed this work as
employees of Battelle Memorial Institute. Subcontractors to Battelle
Memorial Institute who performed this work are as follows: J.H.K. and
E.N.P., as employees of Tunnell Government Services Inc., and G.G.O., as
an employee of MRIGlobal. This project was supported in part by the
Viral and Rickettsial Diseases Department of the Naval Medical Research
Center and The Henry Jackson Foundation for the Advancement of Military
Medicine contract with the U.S. Navy (contract Omnibus III DO-0005).
NR 50
TC 11
Z9 11
U1 0
U2 13
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 17
PY 2016
VL 8
IS 326
AR 326ra21
DI 10.1126/scitranslmed.aaf1061
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DE1KI
UT WOS:000370385500002
PM 26888429
ER
PT J
AU Jin, S
Ji, YT
Wang, Q
Wang, H
Shi, XL
Han, XX
Zhou, TQ
Shang, H
Zhang, LQ
AF Jin, Su
Ji, Yangtao
Wang, Qian
Wang, Hua
Shi, Xuanling
Han, Xiaoxu
Zhou, Tongqing
Shang, Hong
Zhang, Linqi
TI Spatiotemporal hierarchy in antibody recognition against transmitted
HIV-1 envelope glycoprotein during natural infection
SO RETROVIROLOGY
LA English
DT Article
DE HIV; Transmission; Antibody; Vaccine
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BROADLY NEUTRALIZING ANTIBODIES; ANTI-GP41
ANTIBODIES; FOUNDER VIRUS; IN-VIVO; TYPE-1; GP41; IDENTIFICATION;
RESPONSES; PATHWAYS
AB Background: Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine.
Results: We report here antibody profiling of sequential plasma samples against transmitted/founder HIV-1 envelope glycoprotein in an epidemiologically linked transmission pair using our previously reported antigen library approach. We have decomposed the antibody recognition into three major subdomains on the envelope and showed their development in vivo followed a spatiotemporal hierarchy: starting with the ectodomain of gp41 at membrane proximal region, then the V3C3V4 and the V1V2 of gp120 at the membrane distal region. While antibodies to these subdomains appeared to undergo avidity maturation, the early anti-gp41 antibodies failed to translate into detectable autologous neutralization. Instead, it was the much delayed anti-V3C3V4 and anti-V1V2 antibodies constituted the major neutralizing activities.
Conclusions: Our results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120.
C1 [Jin, Su; Wang, Qian; Wang, Hua; Shi, Xuanling; Zhang, Linqi] Tsinghua Univ, Comprehens AIDS Res Ctr, Collaborat Innovat Ctr Diag & Treatment Infect Di, Sch Life Sci, Beijing 100084, Peoples R China.
[Jin, Su; Wang, Qian; Wang, Hua; Shi, Xuanling; Zhang, Linqi] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
[Ji, Yangtao; Han, Xiaoxu; Shang, Hong] China Med Univ, Hosp 1, Key Lab AIDS Immunol, Minist Hlth,Dept Lab Med, Shenyang 110001, Peoples R China.
[Zhou, Tongqing] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhang, LQ (reprint author), Tsinghua Univ, Comprehens AIDS Res Ctr, Collaborat Innovat Ctr Diag & Treatment Infect Di, Sch Life Sci, Beijing 100084, Peoples R China.; Zhang, LQ (reprint author), Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.; Shang, H (reprint author), China Med Univ, Hosp 1, Key Lab AIDS Immunol, Minist Hlth,Dept Lab Med, Shenyang 110001, Peoples R China.
EM hongshang100@hotmail.com; zhanglinqi@tsinghua.edu.cn
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU National Natural Science Foundation Award [81530065]; National Science
and Technology Major Projects [2012ZX10001-006, 2012ZX10001-004,
2012ZX10001-009]; Ministry of Science and Technology of China
[2014CB542500-03]; Tsinghua University Initiative Scientific Research
Program [20124812029]; Janssen Investigator Award
FX This work was supported by the funds from National Natural Science
Foundation Award 81530065, the National Science and Technology Major
Projects (2012ZX10001-006, -004 and -009), Ministry of Science and
Technology of China (2014CB542500-03), also in part by the Tsinghua
University Initiative Scientific Research Program (20124812029) and
Janssen Investigator Award to Linqi Zhang.
NR 56
TC 0
Z9 0
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD FEB 17
PY 2016
VL 13
AR 12
DI 10.1186/s12977-016-0243-3
PG 15
WC Virology
SC Virology
GA DD9FG
UT WOS:000370230500001
PM 26883323
ER
PT J
AU Xu, Y
Orlandi, C
Cao, Y
Yang, SY
Choi, CI
Pagadala, V
Birnbaumer, L
Martemyanov, KA
Vardi, N
AF Xu, Ying
Orlandi, Cesare
Cao, Yan
Yang, Shengyan
Choi, Chan-Il
Pagadala, Vijayakanth
Birnbaumer, Lutz
Martemyanov, Kirill A.
Vardi, Noga
TI The TRPM1 channel in ON-bipolar cells is gated by both the alpha and the
beta gamma subunits of the G-protein G(o)
SO SCIENTIFIC REPORTS
LA English
DT Article
ID METABOTROPIC RECEPTOR MGLUR6; STATIONARY NIGHT BLINDNESS;
HETEROTRIMERIC-G-PROTEINS; ACTIVATED K+ CHANNEL; LIGHT RESPONSE; ROD
BIPOLAR; SPLICE VARIANT; PHOSDUCIN; BINDING; MODULATION
AB Transmission from photoreceptors to ON bipolar cells in mammalian retina is mediated by a sign-inverting cascade. Upon binding glutamate, the metabotropic glutamate receptor mGluR6 activates the heterotrimeric G-protein Ga-o beta 3 gamma 13, and this leads to closure of the TRPM1 channel (melastatin). TRPM1 is thought to be constitutively open, but the mechanism that leads to its closure is unclear. We investigated this question in mouse rod bipolar cells by dialyzing reagents that modify the activity of either G alpha(o) or G beta gamma and then observing their effects on the basal holding current. After opening the TRPM1 channels with light, a constitutively active mutant of G alpha(o) closed the channel, but wild-type G alpha(o) did not. After closing the channels by dark adaptation, phosducin or inactive G alpha(o) (both sequester G beta gamma) opened the channel while the active mutant of G alpha(o) did not. Co-immunoprecipitation showed that TRPM1 interacts with G beta 3 and with the active and inactive forms of G alpha(o). Furthermore, bioluminescent energy transfer assays indicated that while G alpha(o) interacts with both the N- and the C-termini of TRPM1, G beta gamma interacts only with the N-terminus. Our physiological and biochemical results suggest that both Gao and G beta gamma bind TRPM1 channels and cooperate to close them.
C1 [Xu, Ying; Yang, Shengyan] Jinan Univ, GHM Inst CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China.
[Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A.] Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA.
[Choi, Chan-Il; Pagadala, Vijayakanth; Birnbaumer, Lutz] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
[Vardi, Noga] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA.
[Xu, Ying] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Jiangsu, Peoples R China.
RP Xu, Y (reprint author), Jinan Univ, GHM Inst CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China.; Vardi, N (reprint author), Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA.; Xu, Y (reprint author), Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Jiangsu, Peoples R China.
EM xuying@jnu.edu.cn; noga@mail.med.upenn.edu
FU NIH [EY11105]; National Basic Research Program of China (973 Program)
[2011CB707501]; National Natural Science Foundation of China [81470656];
Program of Introducing Talents of Discipline to Universities [B14036,
EY018139]; Intramural Research Program of the NIH [Z01-ES-101643]
FX Supported by NIH grant EY11105 (NV), the National Basic Research Program
of China (973 Program) 2011CB707501 (YX), National Natural Science
Foundation of China 81470656 (YX), Program of Introducing Talents of
Discipline to Universities B14036, EY018139 (KAM), and the Intramural
Research Program of the NIH (project Z01-ES-101643 (LB). We thank Vadim
Arshavsky (Duke University) for providing phosducin, Richard Neubig
(University of Michigan) for providing His6-G alpha o, Nevin Lambert
(Medical College of Georgia, Augusta, GA) for providing BRET sensor.
Edited by Mirotznik Editing Services.
NR 65
TC 0
Z9 0
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 17
PY 2016
VL 6
AR 20940
DI 10.1038/srep20940
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9IQ
UT WOS:000370239300001
PM 26883481
ER
PT J
AU Gaughan, AE
Stevens, FR
Huang, ZJ
Nieves, JJ
Sorichetta, A
Lai, SJ
Ye, XY
Linard, C
Hornby, GM
Hay, SI
Yu, HJ
Tatem, AJ
AF Gaughan, Andrea E.
Stevens, Forrest R.
Huang, Zhuojie
Nieves, Jeremiah J.
Sorichetta, Alessandro
Lai, Shengjie
Ye, Xinyue
Linard, Catherine
Hornby, Graeme M.
Hay, Simon I.
Yu, Hongjie
Tatem, Andrew J.
TI Spatiotemporal patterns of population in mainland China, 1990 to 2010
SO SCIENTIFIC DATA
LA English
DT Article
ID RANDOM FORESTS; 2000 CENSUS; LAND-USE; RISK; LIVE
AB According to UN forecasts, global population will increase to over 8 billion by 2025, with much of this anticipated population growth expected in urban areas. In China, the scale of urbanization has, and continues to be, unprecedented in terms of magnitude and rate of change. Since the late 1970s, the percentage of Chinese living in urban areas increased from similar to 18% to over 50%. To quantify these patterns spatially we use time-invariant or temporally-explicit data, including census data for 1990, 2000, and 2010 in an ensemble prediction model. Resulting multi-temporal, gridded population datasets are unique in terms of granularity and extent, providing fine-scale (similar to 100 m) patterns of population distribution for mainland China. For consistency purposes, the Tibet Autonomous Region, Taiwan, and the islands in the South China Sea were excluded. The statistical model and considerations for temporally comparable maps are described, along with the resulting datasets. Final, mainland China population maps for 1990, 2000, and 2010 are freely available as products from the WorldPop Project website and the WorldPop Dataverse Repository.
C1 [Gaughan, Andrea E.; Stevens, Forrest R.; Nieves, Jeremiah J.] Univ Louisville, Dept Geog & Geosci, Louisville, KY 40292 USA.
[Huang, Zhuojie; Lai, Shengjie; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, 155 Changbai Rd, Beijing 102206, Peoples R China.
[Sorichetta, Alessandro; Lai, Shengjie; Hornby, Graeme M.; Tatem, Andrew J.] Univ Southampton, Geog & Environm, Southampton SO17 1BJ, Hants, England.
[Sorichetta, Alessandro] Univ Southampton, Inst Life Sci, Southampton SO17 1BJ, Hants, England.
[Lai, Shengjie; Tatem, Andrew J.] Stiftelsen Flowminder, Flowminder Fdn, Roslagsgatan 17, SE-11355 Stockholm, Sweden.
[Ye, Xinyue] Kent State Univ, Dept Geog, Kent, OH 44240 USA.
[Linard, Catherine] Univ Libre Bruxelles, Biol Control & Spatial Ecol, B-1050 Brussels, Belgium.
[Linard, Catherine] Univ Namur, Dept Geog, B-5000 Namur, Belgium.
[Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.
[Hay, Simon I.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
RP Gaughan, AE (reprint author), Univ Louisville, Dept Geog & Geosci, Louisville, KY 40292 USA.; Yu, HJ (reprint author), Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, 155 Changbai Rd, Beijing 102206, Peoples R China.
EM ae.gaughan@louisville.edu; yuhj@chinacdc.cn
OI Stevens, Forrest/0000-0002-9328-3753; Lai, Shengjie/0000-0001-9781-8148;
Hay, Simon/0000-0002-0611-7272
FU Google [OICB150153]; Bill & Melinda Gates Foundation [OPP1106427,
1032350, OPP1119467, OPP1106023, OPP1093011]; Belgian Science Policy
[SR/00/304]; NIH/NIAID [U19AI089674]; RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health; Senior Research
Fellowship from Wellcome Trust [095066]; National Science Fund for
Distinguished Young Scholars [81525023]; Ministry of Science and
Technology of China [2012 ZX10004-201, 2014BAI13B05]; NIH [U19 AI51915];
Harvard Center for Communicable Disease Dynamics [U54 GM088558]; Natural
Science Foundation of China [41430637, 41329001]; Chinese Ministry of
Education [13JJD790008]
FX A.E.G., F.R.S., and J.N. are supported by funding from Google
(OICB150153). A.S. is supported by funding from the Bill & Melinda Gates
Foundation (OPP1106427, 1032350). C.L. is supported by funding from the
Belgian Science Policy (SR/00/304). A.J.T. is supported by funding from
NIH/NIAID (U19AI089674), the Bill & Melinda Gates Foundation
(OPP1106427, 1032350), and the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. S.I.H. is funded by
a Senior Research Fellowship from the Wellcome Trust (#095066), and
grants from the Bill & Melinda Gates Foundation (OPP1119467, OPP1106023
and OPP1093011). S.I.H. would also like to acknowledge funding support
from the RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health. H.Y. is supported by the National Science
Fund for Distinguished Young Scholars (No. 81525023), Ministry of
Science and Technology of China (2012 ZX10004-201, 2014BAI13B05), NIH
(U19 AI51915) and the Harvard Center for Communicable Disease Dynamics
(U54 GM088558). X.Y. is supported by the Natural Science Foundation of
China (41430637; 41329001), and Chinese Ministry of Education
(13JJD790008). This work forms part of the WorldPop Project
(www.worldpop.org). We thank Dr Yilan Liao from the Institute of
Geographic Sciences and Natural Resources Research of Chinese Academy of
Sciences and Dr Xiaojuan Jiang from the Gansu Center for Disease Control
and Prevention in data collections. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
TC 3
Z9 3
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2052-4463
J9 SCI DATA
JI Sci. Data
PD FEB 16
PY 2016
VL 3
AR UNSP 160005
DI 10.1038/sdata.2016.5
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EF3GJ
UT WOS:000390212500001
ER
PT J
AU Bezrukov, SM
AF Bezrukov, Sergey M.
TI Smoluchowski Equation Approach in Channel-Facilitated Transport
Problems: Counter-Intuitive Analytical Results and Supporting
Experiments
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Bezrukov, Sergey M.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 57-Subg
BP 9A
EP 9A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500052
ER
PT J
AU Zhu, R
Heilinger, A
Newman, AH
Freissmuth, M
Sitte, HH
Hinterdorfer, P
AF Zhu, Rong
Heilinger, Alexander
Newman, Amy H.
Freissmuth, Michael
Sitte, Harald H.
Hinterdorfer, Peter
TI Nanopharmacological Force Sensing Reveals Two Ligand Binding Sites in
Monoamine Transporters
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zhu, Rong; Heilinger, Alexander; Hinterdorfer, Peter] Johannes Kepler Univ Linz, Biophys, A-4040 Linz, Austria.
[Newman, Amy H.] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Baltimore, MD USA.
[Freissmuth, Michael; Sitte, Harald H.] Med Univ Vienna, Ctr Physiol & Pharmacol, Vienna, Austria.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 58-Subg
BP 9A
EP 9A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500053
ER
PT J
AU Matthies, D
Dalmas, O
Borgnia, MJ
Dominik, PK
Merk, A
Rao, P
Reddy, BG
Islam, S
Bartesaghi, A
Perozo, E
Subramaniam, S
AF Matthies, Doreen
Dalmas, Olivier
Borgnia, Mario J.
Dominik, Pawel K.
Merk, Alan
Rao, Prashant
Reddy, Bharat G.
Islam, Shahidul
Bartesaghi, Alberto
Perozo, Eduardo
Subramaniam, Sriram
TI Single-Particle Cryo-EM Studies of a 200-kDa Magnesium Ion Channel
Reveal Large Structural Changes Upon Gating
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Matthies, Doreen; Borgnia, Mario J.; Merk, Alan; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Dalmas, Olivier; Dominik, Pawel K.; Reddy, Bharat G.; Islam, Shahidul; Perozo, Eduardo] Inst Biophys Dynam, Dept Biochem & Mol Biol, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 62-Subg
BP 10A
EP 10A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500057
ER
PT J
AU Bhattacharya, S
Grisshammer, R
Vaidehi, N
AF Bhattacharya, Supriyo
Grisshammer, Reinhard
Vaidehi, Nagarajan
TI Atomic Level Insights into the Activation Mechanism of Neurotensin
Receptor 1
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Bhattacharya, Supriyo; Vaidehi, Nagarajan] City Hope Natl Med Ctr, Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Grisshammer, Reinhard] NINDS, Membrane Prot Struct & Funct Unit, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 74-Plat
BP 12A
EP 12A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500069
ER
PT J
AU Marston, S
Papadaki, M
Memo, M
Messer, A
Donkervoort, S
Bonneman, C
Nowak, K
Ong, R
McNamara, E
AF Marston, Steven
Papadaki, Maria
Memo, Massimiliano
Messer, Andrew
Donkervoort, Sandra
Bonneman, Carsten
Nowak, Kristen
Ong, Royston
McNamara, Elyshia
TI Molecular Mechanism of Novel Deletions in TPM3 that cause a
Hypercontractile Phenotype with Congenital Muscle Stiffness
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Marston, Steven; Papadaki, Maria; Memo, Massimiliano; Messer, Andrew] Univ London Imperial Coll Sci Technol & Med, London, England.
[Donkervoort, Sandra; Bonneman, Carsten] NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bldg 10, Bethesda, MD 20892 USA.
[Nowak, Kristen; Ong, Royston; McNamara, Elyshia] Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA 6009, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 85-Plat
BP 14A
EP 15A
PG 6
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500080
ER
PT J
AU Jacobs, D
Hoogerheide, DP
Rovini, A
Gurnev, PA
Bezrukov, SM
Rostovtseva, TK
AF Jacobs, Daniel
Hoogerheide, David P.
Rovini, Amandine
Gurnev, Philip A.
Bezrukov, Sergey M.
Rostovtseva, Tatiana K.
TI Membrane Lipid Composition Regulates Alpha-Synuclein Blockage of and
Translocation through the Mitochondrial Voltage-Dependent Anion Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Jacobs, Daniel; Rovini, Amandine; Gurnev, Philip A.; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NICHD, SMT, NIH, Bethesda, MD USA.
[Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 109-Plat
BP 19A
EP 20A
PG 6
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500104
ER
PT J
AU Borgnia, MJ
Banerjee, S
Bartesaghi, A
Matthies, D
Rao, P
Merk, A
Pierson, J
Milne, JL
Subramaniam, S
AF Borgnia, Mario J.
Banerjee, Soojay
Bartesaghi, Alberto
Matthies, Doreen
Rao, Prashant
Merk, Alan
Pierson, Jason
Milne, Jacqueline L.
Subramaniam, Sriram
TI Using cryo-EM to Untangle the Conformational Landscape of a Small
Allosterically-Regulated Complex
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Borgnia, Mario J.; Banerjee, Soojay; Bartesaghi, Alberto; Matthies, Doreen; Rao, Prashant; Merk, Alan; Pierson, Jason; Milne, Jacqueline L.; Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 122-Plat
BP 22A
EP 22A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500117
ER
PT J
AU Kim, LY
Gurel, PS
Omabegho, T
Bryant, Z
Alushin, GM
AF Kim, Laura Y.
Gurel, Pinar S.
Omabegho, Tosan
Bryant, Zev
Alushin, Gregory M.
TI High-Resolution Structural Insight into the Myosin VI-F-Actin Interface
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kim, Laura Y.; Gurel, Pinar S.; Alushin, Gregory M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Omabegho, Tosan; Bryant, Zev] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA.
[Bryant, Zev] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 121-Plat
BP 22A
EP 22A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500116
ER
PT J
AU Montecinos-Franjola, F
Schuck, P
Sackett, DL
AF Montecinos-Franjola, Felipe
Schuck, Peter
Sackett, Dan L.
TI Tubulin Monomer-Monomer Association is Less Influenced by the Solvent
than Dimer-Dimer Association: Structure and Function of Tubulin
Interaction Interfaces
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Montecinos-Franjola, Felipe; Sackett, Dan L.] NICHD, NIH, Bethesda, MD USA.
[Schuck, Peter] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 147-Plat
BP 26A
EP 27A
PG 6
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500142
ER
PT J
AU Perrin, BS
Fu, RQ
Cotten, M
Pastor, RW
AF Perrin, B. Scott, Jr.
Fu, Riqiang
Cotten, Myriam
Pastor, Richard W.
TI The Disruptive State of the Membrane Active Antimicrobial Peptide
Piscidin 1 Investigated by Multi-mS All-Atom Simulations and Solid-State
NMR: Surface Defects are Favored over Stable Pores
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Perrin, B. Scott, Jr.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Rockville, MD USA.
[Fu, Riqiang] Natl High Magnet Field Lab, Tallahassee, FL USA.
[Cotten, Myriam] Hamilton Coll, Dept Chem, Clinton, NY 13323 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 155-Plat
BP 28A
EP 28A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500150
ER
PT J
AU Monfredi, OJ
Ziman, B
Boyett, M
Lakatta, E
Maltsev, VA
AF Monfredi, Oliver J.
Ziman, Bruce
Boyett, Mark
Lakatta, Edward
Maltsev, Victor A.
TI Substantial Cell-To-Cell Heterogeneity of Ion Currents is an Essential
Characteristic of the Sinoatrial Node
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Monfredi, Oliver J.; Boyett, Mark] Univ Manchester, Dept Cardiac Electrophysiol, Manchester, Lancs, England.
[Ziman, Bruce; Lakatta, Edward; Maltsev, Victor A.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 161-Plat
BP 29A
EP 29A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500156
ER
PT J
AU Vaidehi, N
Lee, S
Bhattacharya, S
Sandhu, M
Grisshammer, R
Tate, CG
AF Vaidehi, Nagarajan
Lee, Sangbae
Bhattacharya, Supriyo
Sandhu, Manbir
Grisshammer, Reinhard
Tate, Christopher G.
TI Insights into How Mutations Thermostabilize G-Protein-Coupled Receptors
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Vaidehi, Nagarajan; Lee, Sangbae; Bhattacharya, Supriyo; Sandhu, Manbir] City Hope Natl Med Ctr, Beckman Res Inst, Immunol, Duarte, CA 91010 USA.
[Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, Rockville, MD USA.
[Tate, Christopher G.] MRC Lab Mol Biol, Cambridge Biomed Campus, Cambridge, England.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 212-Plat
BP 39A
EP 40A
PG 8
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500207
ER
PT J
AU Tian, Y
Schwieters, C
Opella, S
Marassi, F
AF Tian, Ye
Schwieters, Charles
Opella, Stanley
Marassi, Francesca
TI NMR Restrained Protein Structure Calculations in Implicit Water/Membrane
Environments
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Tian, Ye; Opella, Stanley] UCSD, Chem & Biochem, La Jolla, CA 92093 USA.
[Tian, Ye; Marassi, Francesca] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA.
[Schwieters, Charles] NIH, Div Computat Biosci, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 302-Pos
BP 57A
EP 58A
PG 4
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500297
ER
PT J
AU Chakraborty, S
Chen, XJ
Slogoff-Sevilla, P
Velmurugu, Y
Steinbach, PJ
Min, JH
Ansari, A
AF Chakraborty, Sagnik
Chen, Xuejing
Slogoff-Sevilla, Phillip
Velmurugu, Yogambigai
Steinbach, Peter J.
Min, Jung-Hyun
Ansari, Anjum
TI DNA Conformational Distribution and Dynamics during Search and
Recognition of Damaged Sites by DNA Repair Protein RAD4/XPC
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Chakraborty, Sagnik; Velmurugu, Yogambigai; Ansari, Anjum] Univ Illinois, Phys, Chicago, IL USA.
[Chen, Xuejing; Slogoff-Sevilla, Phillip; Min, Jung-Hyun] Univ Illinois, Chem, Chicago, IL USA.
[Steinbach, Peter J.] NIH, Ctr Mol Modeling, Bldg 10, Bethesda, MD 20892 USA.
[Ansari, Anjum] Univ Illinois, Bioengn, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 338-Pos
BP 64A
EP 64A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500333
ER
PT J
AU Chereji, RV
Ocampo, J
Burke, T
Clark, DJ
AF Chereji, Razvan V.
Ocampo, Josefina
Burke, Tara
Clark, David J.
TI Major Determinants of Nucleosome Organization
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
ID YEAST
C1 [Chereji, Razvan V.; Ocampo, Josefina; Burke, Tara; Clark, David J.] NICHD, NIH, Bethesda, MD USA.
NR 9
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 356-Pos
BP 68A
EP 68A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500351
ER
PT J
AU Kim, SH
Vlijm, R
de Zwart, P
van der Torre, J
Dalal, Y
Dekker, C
AF Kim, Sung Hyun
Vlijm, Rifka
de Zwart, Paul
van der Torre, Jaco
Dalal, Yamini
Dekker, Cees
TI The Handedness of Nucleosomes is Governed by the Supercoiling of DNA
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kim, Sung Hyun; Vlijm, Rifka; de Zwart, Paul; van der Torre, Jaco; Dekker, Cees] Delft Univ Technol, BioNanoSci, Delft, Netherlands.
[Dalal, Yamini] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 364-Pos
BP 70A
EP 70A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500359
ER
PT J
AU Kraft, ML
Yeager, AN
Weber, PK
Zimmerberg, J
AF Kraft, Mary L.
Yeager, Ashley N.
Weber, Peter K.
Zimmerberg, Joshua
TI Does the Influenza Virus Bud from Cholesterol-and Sphingolipid-Enriched
Plasma membrane domains?
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kraft, Mary L.; Yeager, Ashley N.] Univ Illinois, Chem & Biomol Engn, Urbana, IL 61801 USA.
[Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA USA.
[Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 424-Pos
BP 82A
EP 82A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500419
ER
PT J
AU Lu, Q
Bhat, A
Edwards, L
Harris, Z
Jin, A
AF Lu, Qi
Bhat, Anupama
Edwards, Lance
Harris, Zaki
Jin, Albert
TI How Gold Nanoparticles affect the Lipid Packing in Model Membranes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Lu, Qi; Bhat, Anupama; Edwards, Lance; Harris, Zaki] Delaware State Univ, Dover, DE USA.
[Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 436-Pos
BP 85A
EP 85A
PG 1
WC Biophysics
SC Biophysics
GA DK7GP
UT WOS:000375093500431
ER
PT J
AU Papp, F
Smith, J
Szilagyi, O
Chang, TH
Swartz, KJ
AF Papp, Ferenc
Smith, Jaime
Szilagyi, Orsolya
Chang, Tsg-Hui
Swartz, Kenton J.
TI Characterization of a Fast Voltage-Sensing Protein using Voltage-Clamp
Fluorometry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Papp, Ferenc] Univ Debrecen, Biophys & Cell Biol, Debrecen, Hungary.
[Smith, Jaime; Szilagyi, Orsolya; Chang, Tsg-Hui; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 530-Pos
BP 103A
EP 103A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800018
ER
PT J
AU Arcangeletti, M
Mazzolini, M
Anselmi, C
Grosa, D
Maity, S
Marchesi, A
Napolitano, L
Torre, V
AF Arcangeletti, Manuel
Mazzolini, Monica
Anselmi, Claudio
Grosa, Debora
Maity, Sourav
Marchesi, Arin
Napolitano, Luisa
Torre, Vincent
TI Interactions between the C-Linker and the S4-S5 Linker Mediate Gating in
Cnga1 Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Arcangeletti, Manuel; Mazzolini, Monica; Grosa, Debora; Maity, Sourav; Torre, Vincent] SISSA, I-34014 Trieste, Italy.
[Anselmi, Claudio] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Marchesi, Arin] French Inst Hlth & Med Res Paris, BioAFM Lab, Marseille, France.
[Napolitano, Luisa] Elettra Sincrotrone, Struct Biol Lab, Trieste, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 540-Pos
BP 105A
EP 105A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800028
ER
PT J
AU Singh, H
Ponnalagu, D
Sukur, S
Singh, H
Zhou, YN
Jin, DJ
Rao, SG
AF Singh, Harpreet
Ponnalagu, Devasena
Sukur, Sowmya
Singh, Harkewal
Zhou, Yan Ning
Jin, Ding J.
Rao, Shubha Gururaja
TI A Bacterial Homolog of Chloride Intracellular Channel (CLIC) Protein
Family, Stringent Starvation Protein A (SspA), forms a Non-Selective Ion
Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Singh, Harpreet; Ponnalagu, Devasena; Sukur, Sowmya; Rao, Shubha Gururaja] Drexel Univ, Coll Med, Pharmacol & Physiol, Philadelphia, PA 19104 USA.
[Singh, Harkewal] Univ Missouri, Dept Chem, Columbia, MO 65211 USA.
[Zhou, Yan Ning; Jin, Ding J.] NCI, Frederick, MD 21701 USA.
OI Singh, Harpreet/0000-0002-6135-1897
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 598-Pos
BP 117A
EP 117A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800086
ER
PT J
AU Moen, JM
Ahmet, I
Yavari, A
Matt, MG
Beyman, MG
Ramirez, C
Ashrafian, H
Lakatta, EG
AF Moen, Jack M.
Ahmet, Ismayil
Yavari, Arash
Matt, Michael G.
Beyman, Max G.
Ramirez, Christopher
Ashrafian, Houman
Lakatta, Edward G.
TI AMP Kinase Modulates Heart Rate and Heart Rate Variability through
Autonomic and Intrinsic Mechanisms
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Moen, Jack M.; Ahmet, Ismayil; Matt, Michael G.; Beyman, Max G.; Ramirez, Christopher; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Yavari, Arash; Ashrafian, Houman] Univ Oxford, Cardiovasc Med, Oxford, England.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 619-Pos
BP 121A
EP 122A
PG 7
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800107
ER
PT J
AU Salazar, DT
Poblete, H
Gonzalez, A
Vergara-Jaque, A
Comer, J
Amara, SG
AF Salazar, Delany Torres
Poblete, Horacio
Gonzalez, Aneysis
Vergara-Jaque, Ariela
Comer, Jeffrey
Amara, Susan G.
TI Elucidating the Anion Channel Gating Mechanism in Excitatory Amino Acid
Transporters
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Salazar, Delany Torres; Gonzalez, Aneysis; Amara, Susan G.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Poblete, Horacio; Vergara-Jaque, Ariela; Comer, Jeffrey] Kansas State Univ, Manhattan, KS 66506 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 692-Pos
BP 137A
EP 137A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800180
ER
PT J
AU Amin, A
Weston, M
Mindell, JA
AF Amin, Anowarul
Weston, Mary
Mindell, Joseph A.
TI Role of Counterions in Acidification in Mouse Liver Lysosomes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Amin, Anowarul; Weston, Mary; Mindell, Joseph A.] NINDS, Membrane Transport Biophys Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 699-Pos
BP 138A
EP 138A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800187
ER
PT J
AU Fontana, J
Jurado, KA
Cheng, NQ
Engelman, AN
Steven, AC
AF Fontana, Juan
Jurado, Kellie A.
Cheng, Naiqian
Engelman, Alan N.
Steven, Alasdair C.
TI Cryo-Electron Tomography and Nucleocapsid Protein Labeling by
Tomo-Bubblegram Imaging Reveal a Role for HIV-1 Integrase in Viral
Maturation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Fontana, Juan; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA.
[Jurado, Kellie A.; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 779-Pos
BP 155A
EP 155A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800267
ER
PT J
AU Calco, GN
Kuo, BC
Hoyne, JD
Aronova, MA
Zhang, GF
Leapman, RD
AF Calco, Gina N.
Kuo, Bryan C.
Hoyne, Jake D.
Aronova, Maria A.
Zhang, Guofeng
Leapman, Richard D.
TI Mitochondrial Networks in Beta Cells of Pancreatic Islet of Langerhans
Investigated by Serial Block Face Scanning Electron Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Calco, Gina N.; Kuo, Bryan C.; Hoyne, Jake D.; Aronova, Maria A.; Zhang, Guofeng; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 783-Pos
BP 156A
EP 156A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800271
ER
PT J
AU He, QP
Aronova, MA
Joy, DC
Zhang, GF
Leapman, RD
AF He, Qianping
Aronova, Maria A.
Joy, David C.
Zhang, Guofeng
Leapman, Richard D.
TI Serial Block Face Sem of Biological Structures at Near Isotropic Spatial
Resolution using Multiple Beam Energies and Monte Carlo Simulations
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 NIH, Bldg 10, Bethesda, MD 20892 USA.
Oak Ridge Natl Lab, Oak Ridge, TN USA.
[Joy, David C.] Univ Tennessee, Dept Mat Sci & Engn, Knoxville, TN 37996 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 795-Pos
BP 158A
EP 159A
PG 8
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800283
ER
PT J
AU Liao, HS
Huang, P
Gao, Y
Cai, E
Horkay, F
Chen, XY
Jin, AJ
AF Liao, Hsien-Shun
Huang, Peng
Gao, Yuan
Cai, Edward
Horkay, Ferenc
Chen, Xiaoyuan
Jin, Albert J.
TI Revealing the Self-Assembly Pathways and Nanomechanics of
Enzyme-Triggered Nanofibers from Peptide Amphiphiles for Cancer
Theranostics
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Liao, Hsien-Shun; Huang, Peng; Cai, Edward; Chen, Xiaoyuan; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Liao, Hsien-Shun] Natl Taiwan Univ, Taipei 10764, Taiwan.
[Gao, Yuan; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 4
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 852-Pos
BP 170A
EP 170A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800340
ER
PT J
AU Fu, X
Wang, Z
Bhirde, A
Zhu, J
Liao, HS
Carvajal, N
Niu, G
Eden, H
Chen, XY
Jin, AJ
AF Fu, Xiao
Wang, Zhe
Bhirde, Ashwin
Zhu, Jenny
Liao, Hsien-Shun
Carvajal, Nicole
Niu, Gang
Eden, Henry
Chen, Xiaoyuan
Jin, Albert J.
TI Bio-AFM of Cancer Cells and Multifunctional Theranostics
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Fu, Xiao; Wang, Zhe; Bhirde, Ashwin; Zhu, Jenny; Liao, Hsien-Shun; Carvajal, Nicole; Niu, Gang; Eden, Henry; Chen, Xiaoyuan; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Fu, Xiao] Beijing Inst Technol, Beijing 100081, Peoples R China.
[Bhirde, Ashwin] US FDA, Silver Spring, MD USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 854-Pos
BP 171A
EP 171A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800342
ER
PT J
AU Jin, AJ
Mertz, D
Liao, HS
Johri, A
Torres, L
Wu, YM
Narum, D
AF Jin, Albert J.
Mertz, David
Liao, Hsien-Shun
Johri, Aanchal
Torres, Luis
Wu, Yimin
Narum, David
TI Quantifying Nanoscale Properties of Engineered Virus Capsids for Malaria
Vaccines
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Jin, Albert J.; Mertz, David; Liao, Hsien-Shun; Johri, Aanchal; Torres, Luis] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Mertz, David] Univ Michigan, Biomed Engn, Ann Arbor, MI 48109 USA.
[Wu, Yimin; Narum, David] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 853-Pos
BP 171A
EP 171A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800341
ER
EF