FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Barentsz, JO
Weinreb, JC
Verma, S
Thoeny, HC
Tempany, CM
Shtern, F
Padhani, AR
Margolis, D
Macura, KJ
Haider, MA
Cornud, F
Choyke, PL
AF Barentsz, Jelle O.
Weinreb, Jeffrey C.
Verma, Sadhna
Thoeny, Harriet C.
Tempany, Clare M.
Shtern, Faina
Padhani, Anwar R.
Margolis, Daniel
Macura, Katarzyna J.
Haider, Masoom A.
Cornud, Francois
Choyke, Peter L.
TI Synopsis of the PI-RADS v2 Guidelines for Multiparametric Prostate
Magnetic Resonance Imaging and Recommendations for Use
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID ULTRASOUND-GUIDED BIOPSY; REFERENCE-STANDARD; TARGETED BIOPSIES; CANCER
DETECTION; SCORING SYSTEM; VALIDATION; COHORT; DIAGNOSIS; MEN
C1 [Barentsz, Jelle O.] Dept Radiol & Nucl Med Radboudumc, Nijmegen, Netherlands.
[Weinreb, Jeffrey C.] Yale Univ, Sch Med, New Haven, CT USA.
[Verma, Sadhna] Univ Cincinnati, Cincinnati, OH USA.
[Thoeny, Harriet C.] Harvard Univ, Boston, MA 02115 USA.
[Tempany, Clare M.] Univ Hosp Bern, CH-3010 Bern, Switzerland.
[Shtern, Faina] AdMeTech Fdn, Boston, MA USA.
[Padhani, Anwar R.] Mt Vernon Hosp, Paul Strickland Scanner Ctr, Northwood HA6 2RN, Middx, England.
[Margolis, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA.
[Macura, Katarzyna J.] Johns Hopkins Univ, Baltimore, MD USA.
[Haider, Masoom A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada.
[Cornud, Francois] Univ Paris 05, Paris, France.
[Choyke, Peter L.] NIH, Bethesda, MD 20892 USA.
RP Barentsz, JO (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Radiol, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM jelle.barentsz@radboudumc.nl
NR 23
TC 32
Z9 33
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD JAN
PY 2016
VL 69
IS 1
BP 41
EP 49
DI 10.1016/j.eururo.2015.08.038
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CZ4KX
UT WOS:000367073100012
PM 26361169
ER
PT J
AU O'Brien, TR
Feld, JJ
Kottilil, S
Pfeiffer, RM
AF O'Brien, Thomas R.
Feld, Jordan J.
Kottilil, Shyam
Pfeiffer, Ruth M.
TI No scientific basis to restrict 8 weeks of treatment with
ledipasvir/sofosbuvir to patients with hepatitis C virus RNA < 6,000,000
IU/mL
SO HEPATOLOGY
LA English
DT Editorial Material
C1 [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Feld, Jordan J.] Univ Toronto, Toronto Ctr Liver Dis, Toronto, ON, Canada.
[Kottilil, Shyam] Univ Maryland, Sch Med, Div Clin Care & Res, Inst Human Virol, Baltimore, MD 21201 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP O'Brien, TR (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E108,MSC 9767, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010176-07]
NR 8
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2016
VL 63
IS 1
BP 28
EP 30
DI 10.1002/hep.28292
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3ON
UT WOS:000367014000009
PM 26474163
ER
PT J
AU Zhang, Z
Gao, B
Wang, FS
AF Zhang, Zheng
Gao, Bin
Wang, Fu-Sheng
TI Contribution of Nonignorable Environmental Factor to Impairing Liver
Disease Mortality Reduction Target in China Reply
SO HEPATOLOGY
LA English
DT Letter
C1 [Zhang, Zheng; Wang, Fu-Sheng] Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing, Peoples R China.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Zhang, Z (reprint author), Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing, Peoples R China.
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 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2016
VL 63
IS 1
BP 348
EP 348
DI 10.1002/hep.27879
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3ON
UT WOS:000367014000047
PM 25953045
ER
PT J
AU Schvey, NA
Shomaker, LB
Kelly, NR
Pickworth, CK
Cassidy, O
Galescu, O
Demidowich, AP
Brady, SM
Tanofsky-Kraff, M
Yanovski, JA
AF Schvey, Natasha A.
Shomaker, Lauren B.
Kelly, Nichole R.
Pickworth, Courtney K.
Cassidy, Omni
Galescu, Ovidiu
Demidowich, Andrew P.
Brady, Sheila M.
Tanofsky-Kraff, Marian
Yanovski, Jack A.
TI Pressure To Be Thin and Insulin Sensitivity Among Adolescents
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Adolescents; Pressure to be thin; Insulin; Insulin sensitivity
ID STRESSFUL LIFE EVENTS; DEPRESSIVE SYMPTOMS; BODY DISSATISFACTION;
METABOLIC SYNDROME; RISK-FACTORS; OBESITY; GIRLS; RESISTANCE; CHILDREN;
STIGMA
AB Purpose: Extant research indicates that some of the comorbidities associated with adult obesity may be adversely affected by the stress resulting from negative body image and weight-related stigma. This study examined the association between weight-related pressure and insulin sensitivity in adolescents, who are vulnerable to both weight-based teasing and the onset of metabolic dysregulation.
Methods: Participants were 215 adolescent healthy volunteers (55% female; 59% white; 35% overweight/obese; mean +/- standard deviation age = 15.4 +/- 1.4 year), who completed a self-report measure of pressure to be thin from parents, friends, and romantic partners. Fasting blood samples were obtained to assess serum insulin and glucose, which were used to calculate insulin sensitivity; fat mass (kg) and fat-free mass (%) were measured with air-displacement plethysmography. Pubertal stage was determined by physical examination.
Results: Pressure to be thin was positively associated with fasting insulin (p = .01) and negatively associated with insulin sensitivity (p = .02), after controlling for pubertal stage, sex, race, height, fat-free mass, and adiposity. Pressure to be thin was associated with a greater odds of having hyperinsulinemia (fasting insulin >= 15 mu IU/mL; odds ratio (95% confidence interval): 1.65 [1.08 -2.50], p = .02), adjusting for the same covariates.
Conclusions: Results indicate that adolescents perceiving more pressure to be thin have greater elevations of fasting insulin and poorer insulin sensitivity above and beyond the effect of fat mass. Future research is warranted to elucidate the mechanisms responsible for this relationship. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Schvey, Natasha A.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Schvey, Natasha A.; Shomaker, Lauren B.; Kelly, Nichole R.; Pickworth, Courtney K.; Cassidy, Omni; Galescu, Ovidiu; Demidowich, Andrew P.; Brady, Sheila M.; Tanofsky-Kraff, Marian; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Shomaker, Lauren B.; Kelly, Nichole R.; Cassidy, Omni] Colorado State Univ, Dept Human Dev & Family Studies, Ft Collins, CO 80523 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Div,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637; Galescu, Ovidiu/0000-0003-0948-645X
FU National Research Service Award from the National Institute of Child
Health and Human Development [1F32HD056762]; Intramural Research Program
from the National Institute of Child Health and Human Development
[Z1A-HD-00641]; National Center on Minority Health and Health
Disparities; Office of Behavioral and Social Sciences Research
FX Supported by National Research Service Award 1F32HD056762 from the
National Institute of Child Health and Human Development (to L.B.S.),
and Intramural Research Program grant Z1A-HD-00641 from the National
Institute of Child Health and Human Development with supplemental
funding from the National Center on Minority Health and Health
Disparities and the Office of Behavioral and Social Sciences Research
(to J.A.Y.).
NR 38
TC 0
Z9 0
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
EI 1879-1972
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JAN
PY 2016
VL 58
IS 1
BP 104
EP 110
DI 10.1016/j.jadohealth.2015.09.010
PG 7
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA CZ4GT
UT WOS:000367062200016
PM 26707232
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Response to letter by Berger: The success of masking should be tested
routinely and correctly
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Letter
ID SELECTION BIAS; TRIALS
C1 [Berger, Vance W.] NCI, Biometry Res Grp, Rockville, MD 20850 USA.
[Berger, Vance W.] Univ Maryland Baltimore Cty, Baltimore, MD 20850 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM vb78c@nih.gov
NR 6
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 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD JAN
PY 2016
VL 69
BP 265
EP 266
DI 10.1016/j.jclinepi.2015.02.018
PG 2
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CZ5FJ
UT WOS:000367127600048
PM 26123087
ER
PT J
AU Park, TS
Groh, EM
Patel, K
Kerkar, SP
Lee, CCR
Rosenberg, SA
AF Park, Tristen S.
Groh, Eric M.
Patel, Krishna
Kerkar, Sid P.
Lee, Chyi-Chia Richard
Rosenberg, Steven A.
TI Expression of MAGE-A and NY-ESO-1 in Primary and Metastatic Cancers
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE MAGE-A; NY-ESO-1; melanoma; breast cancer; squamous cell cancer; cancer
testis antigen
ID SQUAMOUS-CELL CARCINOMA; TESTIS ANTIGENS; COLORECTAL-CANCER;
BREAST-CANCER; CLINICAL-SIGNIFICANCE; ESOPHAGEAL CANCER;
GENE-EXPRESSION; MELANOMA; IMMUNOGENICITY; IMMUNOTHERAPY
AB Melanoma-associated antigen-A (MAGE-A) and New York esophageal squamous cell cancer-1 (NY-ESO-1) are 2 cancer testis antigens (CTA) demonstrating potential for use in targeted immunotherapy. Clinical trials in melanoma and synovial sarcomas targeting these antigens in immune-based therapies have demonstrated durable tumor regression. Although protein expression of NY-ESO-1 has been assessed in a variety of cancer types, the expression of MAGE-A has not been studied in depth. In this study we analyzed MAGE-A and NY-ESO-1 expression in 314 melanoma specimens from 301 melanoma patients, 38 patients with squamous cell cancers and 111 patients with adenocarcinomas. Our results demonstrated higher expression of MAGE-A compared with NY-ESO-1 in melanomas (32% vs. 13%) and squamous cell carcinomas (45% vs. 7.9%), and higher expression of both CTAs in metastatic versus primary tumors. CTA expression in adenocarcinomas was low (MAGE-A: 10%, NY-ESO-1: 0.9%). In addition, we looked at concordance of expression among metastatic melanoma lesions within the same patient and found concordant expression in 38 of 47 patients for MAGE-A and 43 of 47 patients for NY-ESO-1. Our study demonstrated that the MAGE-A family may be of greater utility than NY-ESO-1 for targeted immunotherapy in a variety of cancer histologies, in particular metastatic melanomas and squamous cell carcinomas.
C1 [Park, Tristen S.; Groh, Eric M.; Patel, Krishna; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kerkar, Sid P.; Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Park, TS (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM s.tristen.park@gmail.com
RI Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
FU intramural research program of the National Institutes of Health, NCI
FX This research was supported by the intramural research program of the
National Institutes of Health, NCI.
NR 37
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Z9 4
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD JAN
PY 2016
VL 39
IS 1
BP 1
EP 7
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA CZ2MG
UT WOS:000366938700001
PM 26641256
ER
PT J
AU Slaats, GG
Isabella, CR
Kroes, HY
Dempsey, JC
Gremmels, H
Monroe, GR
Phelps, IG
Duran, KJ
Adkins, J
Kumar, SA
Knutzen, DM
Knoers, NV
Mendelsohn, NJ
Neubauer, D
Mastroyianni, SD
Vogt, J
Worgan, L
Karp, N
Bowdin, S
Glass, IA
Parisi, MA
Otto, EA
Johnson, CA
Hildebrandt, F
van Haaften, G
Giles, RH
Doherty, D
AF Slaats, Gisela G.
Isabella, Christine R.
Kroes, Hester Y.
Dempsey, Jennifer C.
Gremmels, Hendrik
Monroe, Glen R.
Phelps, Ian G.
Duran, Karen J.
Adkins, Jonathan
Kumar, Sairam A.
Knutzen, Dana M.
Knoers, Nine V.
Mendelsohn, Nancy J.
Neubauer, David
Mastroyianni, Sotiria D.
Vogt, Julie
Worgan, Lisa
Karp, Natalya
Bowdin, Sarah
Glass, Ian A.
Parisi, Melissa A.
Otto, Edgar A.
Johnson, Colin A.
Hildebrandt, Friedhelm
van Haaften, Gijs
Giles, Rachel H.
Doherty, Dan
TI MKS1 regulates ciliary INPP5E levels in Joubert syndrome
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID MECKEL-GRUBER-SYNDROME; ASPHYXIATING THORACIC DYSTROPHY; PROTEIN
NETWORK; PRIMARY CILIUM; FOLLOW-UP; MUTATIONS; CILIOPATHIES; DISORDERS;
CILIOGENESIS; JEUNE
AB Background Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS.
Methods We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations.
Results We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals with MKS1-related JS carry >= 1 non-truncating mutation. Fibroblasts from individuals with MKS1-related JS make normal or fewer cilia than control fibroblasts, their cilia are more variable in length than controls, and show decreased ciliary ARL13B and INPP5E. Additionally, MKS1 mutant alleles have similar effects in 3D spheroids.
Conclusions MKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content, through an ARL13B-dependent mechanism. Mutations in INPP5E also cause JS, so our findings in patient fibroblasts support the notion that loss of INPP5E function, due to either mutation or mislocalisation, is a key mechanism underlying JS, downstream of MKS1 and ARL13B.
C1 [Slaats, Gisela G.; Gremmels, Hendrik; Giles, Rachel H.] Univ Med Ctr Utrecht, Dept Nephrol & Hypertens, NL-3584 CX Utrecht, Netherlands.
[Isabella, Christine R.; Dempsey, Jennifer C.; Phelps, Ian G.; Adkins, Jonathan; Kumar, Sairam A.; Knutzen, Dana M.; Glass, Ian A.; Doherty, Dan] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Kroes, Hester Y.; Monroe, Glen R.; Duran, Karen J.; Knoers, Nine V.; van Haaften, Gijs] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Adkins, Jonathan] Translat Genom Res Inst, Div Integrated Canc Genom, Phoenix, AZ USA.
[Mendelsohn, Nancy J.] Childrens Hosp & Clin Minnesota, Dept Med Genet, Minneapolis, MN USA.
[Neubauer, David] Univ Childrens Hosp Ljubljana, Dept Child Adolescent & Dev Neurol, Ljubljana, Slovenia.
[Mastroyianni, Sotiria D.] Childrens Hosp Athens P & A Kyriakou, Dept Neurol, Athens, Greece.
[Vogt, Julie] Birmingham Womens Hosp, West Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Worgan, Lisa] Liverpool Hosp, Dept Clin Genet, Liverpool, Merseyside, Australia.
[Karp, Natalya] Univ Western Ontario, Dept Pediat, Med Genet Program, London Hlth Sci Ctr, London, ON N6A 3K7, Canada.
[Bowdin, Sarah] Hosp Sick Children, Dept Paediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada.
[Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Otto, Edgar A.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Johnson, Colin A.] Univ Leeds, Leeds Inst Mol Med, Sect Ophthalmol & Neurosci, Leeds, W Yorkshire, England.
[Hildebrandt, Friedhelm] Boston Childrens Hosp, Div Nephrol, Boston, MA USA.
[Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Doherty, Dan] Seattle Childrens Res Inst, Seattle, WA USA.
RP Giles, RH (reprint author), Univ Med Ctr Utrecht, Dept Nephrol, F03-233,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
EM r.giles@umcutrecht.nl
RI van Haaften, Gijs/G-7832-2012;
OI van Haaften, Gijs/0000-0003-3033-0329; Otto, Edgar/0000-0002-2387-9973;
Gremmels, Hendrik/0000-0002-7818-620X
FU National Institutes of Health [KL2-RR025015, R01NS064077]; University of
Washington Intellectual and Developmental Disabilities Research Center
Genetics Core [P30HD002274, DK068306, RC4-DK090917, DK090917,
K23NS45832, K24HD046712]; European Union 7th Framework Programme
Consortium 'SYSCILIA' [241955]; Dutch Kidney Foundation 'KOUNCIL'
Consortium [CP11.18]; Netherlands Organisation for Scientific Research
(ZonMw-TAS grant) [116001026]; Sir Jules Thorn Award for Biomedical
Research [JTA/09]; Medical 719 Research Council [MR/K011154/1]
FX This research was supported by grants from National Institutes of Health
KL2-RR025015, R01NS064077 to DD, the University of Washington
Intellectual and Developmental Disabilities Research Center Genetics
Core P30HD002274, and DK068306 and RC4-DK090917 to FH and DK090917 to
EAO, K23NS45832 to MAP and K24HD046712 to IAG. DD also received private
donations from families of children with Joubert syndrome. FH is an
investigator of the Howard Hughes Medical Institute. GGS, CAJ, and RHG
were supported by grants from the European Union 7th Framework Programme
Consortium 'SYSCILIA' (241955) and HYK, NVK and RHG receive support from
the Dutch Kidney Foundation 'KOUNCIL' Consortium Grant CP11.18. HG was
supported by the Netherlands Organisation for Scientific Research
(ZonMw-TAS grant 116001026), CAJ was also supported by funding from the
Sir Jules Thorn Award for Biomedical Research (JTA/09) and a Medical 719
Research Council grant (MR/K011154/1).
NR 51
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U1 1
U2 5
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 JAN
PY 2016
VL 53
IS 1
BP 62
EP 72
DI 10.1136/jmedgenet-2015-103250
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA CZ2YK
UT WOS:000366970600007
PM 26490104
ER
PT J
AU Ehlert, A
Schmidt, C
Wolfer, J
Manthei, G
Jacobs, AH
Bruning, R
Heindel, W
Ringelstein, EB
Stummer, W
Pluta, RM
Hesselmann, V
AF Ehlert, Angelika
Schmidt, Christoph
Woelfer, Johannes
Manthei, Gerd
Jacobs, Andreas H.
Bruening, Roland
Heindel, Walter
Ringelstein, E. Bernd
Stummer, Walter
Pluta, Ryszard M.
Hesselmann, Volker
TI Molsidomine for the prevention of vasospasm-related delayed ischemic
neurological deficits and delayed brain infarction and the improvement
of clinical outcome after subarachnoid hemorrhage: a single-center
clinical observational study
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE subarachnoid hemorrhage; molsidomine; CVS; DIND; vasospasm; NO; vascular
disorders
ID CEREBRAL VASOSPASM; NITRIC-OXIDE; ARTERIES; ENDOTHELIUM; CIRCULATION;
DEFINITION; MODEL
AB OBJECTIVE Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible for a poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH.
METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up.
RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p <0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01).
CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.
C1 [Ehlert, Angelika; Manthei, Gerd] Asklepios Hosp St Georg, Dept Neurosurg, Hamburg, Germany.
[Schmidt, Christoph] Univ Hosp Munster, Dept Anasthesiol Intens Care & Pain Med, Munster, Germany.
[Woelfer, Johannes; Stummer, Walter] Univ Hosp Munster, Dept Neurosurg, Munster, Germany.
[Heindel, Walter; Hesselmann, Volker] Univ Hosp Munster, Dept Radiol, Munster, Germany.
[Ringelstein, E. Bernd] Univ Hosp Munster, Dept Neurol, Munster, Germany.
[Jacobs, Andreas H.] European Inst Mol Imaging, Munster, Germany.
[Bruening, Roland] Asklepios Hosp Barmbek, Dept Radiol, Hamburg, Germany.
[Hesselmann, Volker] Asklepios Hosp Hamburg North, Hamburg, Germany.
[Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Hesselmann, V (reprint author), Asklepios Clin Hamburg, Dept Radiol & Neuroradiol, Tangstedter Landstr 400, Hamburg, Germany.
EM v.hesselmann@asklepios.com
NR 33
TC 4
Z9 4
U1 0
U2 2
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD JAN
PY 2016
VL 124
IS 1
BP 51
EP 58
DI 10.3171/2014.12.JNS13846
PG 8
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA CZ3TZ
UT WOS:000367028200012
PM 26162034
ER
PT J
AU Ducharme, LJ
Chandler, RK
Harris, AHS
AF Ducharme, Lori J.
Chandler, Redonna K.
Harris, Alex H. S.
TI Implementing Effective Substance Abuse Treatments in General Medical
Settings: Mapping the Research Terrain
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Integrated care; Implementation science; Alcohol; Substance use
disorders; Evidence-based practices; Primary care
ID RANDOMIZED CLINICAL-TRIAL; PRIMARY-CARE SETTINGS; BRIEF INTERVENTION;
BEHAVIORAL HEALTH; ALCOHOL MISUSE; MENTAL-HEALTH; DRUG-USE; PROGRAM
REGISTERS; STRATEGIES; MANAGEMENT
AB The National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA), and Veterans Health Administration (VHA) share an interest in promoting high quality, rigorous health services research to improve the availability and utilization of evidence-based treatment for substance use disorders (SUD). Recent and continuing changes in the healthcare policy and funding environments prioritize the integration of evidence-based substance abuse treatments into primary care and general medical settings. This area is a prime candidate for implementation research. Recent and ongoing implementation projects funded by these agencies are reviewed. Research in five areas is highlighted: screening and brief intervention for risky drinking; screening and brief intervention for tobacco use; uptake of FDA-approved addiction pharmacotherapies; safe opioid prescribing; and disease management. Gaps in the portfolios, and priorities for future research, are described. Published by Elsevier Inc.
C1 [Ducharme, Lori J.] NIAAA, Bethesda, MD 20892 USA.
[Chandler, Redonna K.] NIDA, Bethesda, MD 20892 USA.
[Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA.
RP Ducharme, LJ (reprint author), NIAAA, 5635 Fishers Lane,Rm 2045, Bethesda, MD 20892 USA.
EM Lori.Ducharme@nih.gov
FU Intramural NIH HHS [Z99 AA999999]
NR 54
TC 4
Z9 4
U1 4
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JAN
PY 2016
VL 60
SI SI
BP 110
EP 118
DI 10.1016/j.jsat.2015.06.020
PG 9
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA CZ1RH
UT WOS:000366882500014
PM 26233697
ER
PT J
AU Bernstein, S
Zambell, K
Amar, MJ
Arango, C
Kelley, RC
Miszewski, SG
Tryon, S
Courville, AB
AF Bernstein, Shanna
Zambell, Kirsten
Amar, Marcelo J.
Arango, Carolina
Kelley, Rachel C.
Miszewski, Susan G.
Tryon, Samantha
Courville, Amber B.
TI Dietary Intake Patterns Are Consistent Across Seasons in a Cohort of
Healthy Adults in a Metropolitan Population
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Seasonal variation in dietary intake; Healthy adults; Macronutrients;
Micronutrients; Food groups
ID NUTRIENT INTAKE; FOOD-INTAKE; PHYSICAL-ACTIVITY; BODY-WEIGHT; WOMEN;
MEN; FREQUENCY; SHANGHAI; CHINA
AB Background Current literature provides conflicting data regarding seasonal variability in dietary intake.
Objective Our aim was to examine seasonal variation in dietary intake in healthy adults from the metropolitan Washington, DC, area.
Design This study utilized an observational cohort design.
Participants/setting Male and female healthy volunteers (n=103) between the ages of 18 and 75 years were recruited from the metropolitan Washington, DC, area to participate in a clinical study at the National Institutes of Health Clinical Center from February 2011 to June 2014.
Main outcome measures Three-to seven-day food records were collected from subjects (n=76) at three time points (12 to 15 weeks apart). Subjects were excluded from analysis (n=27) if they completed less than three time points. Food records were reviewed by nutrition staff, assigned to a season, and coded in Nutrient Data System for Research for energy, macronutrient, micronutrient, and food-group serving analysis.
Statistical analyses Multivariate general linear models were run on energy, macronutrient, micronutrient, and food-group intakes, while being adjusted for age, sex, race, and body mass index (calculated as kg/m(2)).
Results Subjects had a mean +/- standard deviation body mass index of 25 +/- 3.9 and age of 34 +/- 12.4 years. Subject demographics were 71.1% white, 9.2% black/African American, 13.2% Asian, and 6.6% unknown race, with 44.7% males and 55.3% females. Mean intake of energy across seasons was 2,214.6 +/- 623.4 kcal with 17.3%+/- 4.1%, 33.6%+/- 5.5%, 46.6%+/- 8.0%, and 2.7%+/- 3.2% of calories from protein, fat, carbohydrate, and alcohol, respectively. Intakes of energy, macronutrients, micronutrients, and food groups did not differ between seasons.
Conclusions People living in the metropolitan Washington, DC, area did not exhibit seasonal variation in dietary intake. Therefore, when designing studies of nutrient intake in a metropolitan population, these findings suggest that investigators do not need to consider the season during which diet is examined.
C1 [Bernstein, Shanna; Zambell, Kirsten; Arango, Carolina; Kelley, Rachel C.; Miszewski, Susan G.; Tryon, Samantha; Courville, Amber B.] NHLBI, Dept Nutr, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Amar, Marcelo J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
RP Zambell, K (reprint author), NIH, Dept Nutr, Ctr Clin, Bldg 10,Room B2-2426,10 Ctr Dr,MSC 1078, Bethesda, MD 20892 USA.
EM zambellk@cc.nih.gov
FU National Institutes of Health Intramural Research Program
FX This study was funded by the National Institutes of Health Intramural
Research Program.
NR 26
TC 2
Z9 2
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
EI 2212-2680
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD JAN
PY 2016
VL 116
IS 1
BP 38
EP 45
DI 10.1016/j.jand.2015.08.008
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CZ3MV
UT WOS:000367009100006
PM 26376961
ER
PT J
AU Jahns, L
Scheett, AJ
Johnson, LK
Krebs-Smith, SM
Payne, CR
Whigham, LD
Hoverson, BS
Kranz, S
AF Jahns, Lisa
Scheett, Angela J.
Johnson, LuAnn K.
Krebs-Smith, Susan M.
Payne, Collin R.
Whigham, Leah D.
Hoverson, Bonita S.
Kranz, Sibylle
TI Diet Quality of Items Advertised in Supermarket Sales Circulars Compared
to Diets of the US Population, as Assessed by the Healthy Eating
Index-2010
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Diet quality; Healthy Eating Index; Supermarkets; Weekly sales
circulars; Food environment
ID NUTRITION INTERVENTIONS; FOOD; ENERGY; GUIDELINES; DISCOUNTS; AMERICANS;
EDUCATION; PURCHASE; POINT
AB Background Supermarkets use sales circulars to highlight specific foods, usually at reduced prices. Resulting purchases help form the set of available foods within households from which individuals and families make choices about what to eat.
Objective The purposes of this study were to determine how closely foods featured in weekly supermarket sales circulars conform to dietary guidance and how diet quality compares with that of the US population's intakes.
Design Food and beverage items (n=9,149) in 52 weekly sales circulars from a small Midwestern grocery chain in 2009 were coded to obtain food group and nutrient and energy content. Healthy Eating Index-2010 (HEI-2010) total and component scores were calculated using algorithms developed by the National Cancer Institute. HEI-2010 scores for the US population aged 2+ years were estimated using data from the 2009-2010 National Health and Nutrition Examination Survey. HEI-2010 scores of circulars and population intakes were compared using Student's t tests.
Results Mean total (42.8 of 100) HEI-2010 scores of circulars were lower than that of the US population (55.4; P<0.001). Among individual components, Total Protein Foods was the only one for which 100% of the maximum score was met by both circulars and the population. The scores were also similar between the circulars and population for Whole Grains (22%; P=0.81) and Seafood and Plant Proteins (70% to 74%; P=0.33). Circular scores were lower than those of the population for Total and Whole Fruits, Total Vegetables and Greens and Beans, Dairy, Sodium, and Empty Calories (P<0.001); they were higher only for Fatty Acids (P=0.006) and Refined Grains (P<0.001).
Conclusions HEI-2010 total scores for these sales circulars were even lower than US population scores, which have been shown repeatedly to reflect low diet quality. Supermarkets could support improvements in consumer diets by weekly featuring foods that are more in concordance with food and nutrient recommendations.
C1 [Jahns, Lisa; Scheett, Angela J.; Johnson, LuAnn K.; Hoverson, Bonita S.] ARS, USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58203 USA.
[Krebs-Smith, Susan M.] NCI, Risk Factor Assessment Branch, Div Canc Control & Populat Sci, Rockville, MD USA.
[Payne, Collin R.] New Mexico State Univ, Dept Mkt, Mkt, Las Cruces, NM 88003 USA.
[Payne, Collin R.] New Mexico State Univ, Dept Mkt, Consumer Behav Lab, Las Cruces, NM 88003 USA.
[Whigham, Leah D.] Paso del Norte Inst Hlth Living, El Paso, TX USA.
[Kranz, Sibylle] Univ Bristol, Sch Policy Studies, Ctr Exercise Nutr & Hlth Sci, Nutr, Bristol, Avon, England.
RP Jahns, L (reprint author), ARS, USDA, Grand Forks Human Nutr Res Ctr, 2420 2nd Ave N, Grand Forks, ND 58203 USA.
EM lisa.jahns@ars.usda.gov
OI Whigham, Leah/0000-0002-5376-8967
FU USDA, Agricultural Research Service [USDA 3062-51000-51-00D]
FX This study was funded by the USDA, Agricultural Research Service, USDA
3062-51000-51-00D. The contents of this publication do not necessarily
reflect the views or policies of the USDA or the Agricultural Research
Service, nor does mention of trade names, commercial products, or
organizations imply endorsement from the US government.
NR 46
TC 1
Z9 1
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
EI 2212-2680
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD JAN
PY 2016
VL 116
IS 1
BP 115
EP U117
DI 10.1016/j.jand.2015.09.016
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CZ3MV
UT WOS:000367009100011
PM 26508588
ER
PT J
AU Hoffmann, MS
Leibenluft, E
Stringaris, A
Laporte, PP
Pan, PM
Gadelha, A
Manfro, GG
Miguel, EC
Rohde, LA
Salum, GA
AF Hoffmann, Mauricio Scope
Leibenluft, Ellen
Stringaris, Argyris
Laporte, Paola Paganella
Pan, Pedro Mario
Gadelha, Ary
Manfro, Gisele Gus
Miguel, Euripedes Constantino
Rohde, Luis Augusto
Salum, Giovanni Abrahao
TI Positive Attributes Buffer the Negative Associations Between Low
Intelligence and High Psychopathology With Educational Outcomes
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE noncognitive skills; youth strengths inventory; interaction; school
ID PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; SKILL FORMATION; HEALTH; CHILD;
ATTAINMENT; PERSONALITY; TECHNOLOGY; ECONOMICS; STRENGTHS
AB Objective: This study examines the extent to which children's positive attributes are distinct from psychopathology. We also investigate whether positive attributes change or "buffer" the impact of low intelligence and high psychopathology on negative educational outcomes.
Method: In a community sample of 2,240 children (6-14 years of age), we investigated associations among positive attributes, psychopathology, intelligence, and negative educational outcomes. Negative educational outcomes were operationalized as learning problems and poor academic performance. We tested the discriminant validity of psychopathology versus positive attributes using confirmatory factor analysis (CFA) and propensity score matching analysis (PSM), and used generalized estimating equations (GEE) models to test main effects and interactions among predictors of educational outcomes.
Results: According to both CFA and PSM, positive attributes and psychiatric symptoms were distinct constructs. Positive attributes were associated with lower levels of negative educational outcomes, independent of intelligence and psychopathology. Positive attributes buffer the negative effects of lower intelligence on learning problems, and higher psychopathology on poor academic performance.
Conclusion: Children's positive attributes are associated with lower levels of negative school outcomes. Positive attributes act both independently and by modifying the negative effects of low intelligence and high psychiatric symptoms on educational outcomes. Subsequent research should test interventions designed to foster the development of positive attributes in children at high risk for educational problems.
C1 [Hoffmann, Mauricio Scope; Laporte, Paola Paganella] HCPA, Porto Alegre, RS, Brazil.
[Hoffmann, Mauricio Scope; Laporte, Paola Paganella] Univ Fed Rio Grande do Sul, BR-90035003 Porto Alegre, RS, Brazil.
[Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Intramural Res Program, Bethesda, MD 20892 USA.
[Leibenluft, Ellen] NIH, Bethesda, MD 20892 USA.
[Stringaris, Argyris] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
[Pan, Pedro Mario; Gadelha, Ary] Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil.
[Pan, Pedro Mario; Gadelha, Ary] Natl Inst Dev Psychiat Children & Adolescents, INCT CNPq, Sao Paulo, Brazil.
[Hoffmann, Mauricio Scope; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, HCPA, BR-90035003 Porto Alegre, RS, Brazil.
[Manfro, Gisele Gus] INCT CNPq, Brasilia, DF, Brazil.
[Miguel, Euripedes Constantino] Univ Fed Sao Paulo, INCT CNPq, Sao Paulo, Brazil.
[Miguel, Euripedes Constantino] Univ Sao Paulo, Inst Psychiat, Sao Paulo, Brazil.
[Rohde, Luis Augusto] Univ Fed Rio Grande do Sul, HCPA, INCT CNPq, BR-90035003 Porto Alegre, RS, Brazil.
[Salum, Giovanni Abrahao] Univ Fed Rio Grande do Sul, BR-90035003 Porto Alegre, RS, Brazil.
[Salum, Giovanni Abrahao] INCT CNPq, Brasilia, DF, Brazil.
RP Hoffmann, MS (reprint author), Univ Fed Rio Grande do Sul, HCPA, Rua Ramiro Barcelos 2350,Room 2202, BR-90035003 Porto Alegre, RS, Brazil.
EM mauriciodireito@yahoo.com.br
RI Salum, Giovanni/A-7849-2010; Pan, Pedro/I-5167-2013
OI Salum, Giovanni/0000-0002-7537-7289; Pan, Pedro/0000-0002-1943-6520
FU National Institute of Developmental Psychiatry for Children and
Adolescents, a science and technology institute - Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq; National Council for
Scientific and Technological Development) [573974/2008-0]; Fundacao de
Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; Research Support
Foundation of the State of Sao Paulo) [2008/57896-8]
FX This work is supported-by the National Institute of Developmental
Psychiatry for Children and Adolescents, a science and technology
institute funded by Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (CNPq; National Council for Scientific and Technological
Development, grant number 573974/2008-0) and Fundacao de Amparo a
Pesquisa do Estado de Sao Paulo (FAPESP; Research Support Foundation of
the State of Sao Paulo; grant number 2008/57896-8).
NR 37
TC 0
Z9 0
U1 4
U2 7
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 JAN
PY 2016
VL 55
IS 1
BP 47
EP 53
DI 10.1016/j.jaac.2015.10.013
PG 7
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA CZ5DA
UT WOS:000367121500009
PM 26703909
ER
PT J
AU Chia, J
Eroglu, FK
Ozen, S
Orhan, D
Montealegre-Sanchez, G
de Jesus, AA
Goldbach-Mansky, R
Cowen, EW
AF Chia, Justin
Eroglu, Fehime Kara
Ozen, Seza
Orhan, Dicle
Montealegre-Sanchez, Gina
de Jesus, Adriana A.
Goldbach-Mansky, Raphaela
Cowen, Edward W.
TI Failure to thrive, interstitial lung disease, and progressive digital
necrosis with onset in infancy
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Editorial Material
DE autoinflammation; autoinflammatory; gangrene; genodermatosis;
inflammation; interferonopathy; interstitial lung disease; vasculitis
ID VASCULOPATHY
C1 [Chia, Justin] Univ Calgary, Div Dermatol, Dept Med, Calgary, AB T2N 1N4, Canada.
[Eroglu, Fehime Kara; Ozen, Seza] Hacettepe Univ, Dept Pediat Rheumatol, Ankara, Turkey.
[Orhan, Dicle] Hacettepe Univ, Dept Pathol, Ankara, Turkey.
[Montealegre-Sanchez, Gina; de Jesus, Adriana A.; Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), NCI, Dermatol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM cowene@mail.nih.gov
FU Intramural NIH HHS [ZID BC011317-01]
NR 5
TC 3
Z9 3
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD JAN
PY 2016
VL 74
IS 1
BP 186
EP 189
DI 10.1016/j.jaad.2015.10.007
PG 4
WC Dermatology
SC Dermatology
GA CZ4IF
UT WOS:000367066000033
PM 26584874
ER
PT J
AU Doria-Rose, NA
Bhiman, JN
Roark, RS
Schramm, CA
Gorman, J
Chuang, GY
Pancera, M
Cale, EM
Ernandes, MJ
Louder, MK
Asokan, M
Bailer, RT
Druz, A
Fraschilla, IR
Garrett, NJ
Jarosinski, M
Lynch, RM
McKee, K
O'Dell, S
Pegu, A
Schmidt, SD
Staupe, RP
Sutton, MS
Wang, KY
Wibmer, CK
Haynes, BF
Abdool-Karim, S
Shapiro, L
Kwong, PD
Moore, PL
Morris, L
Mascola, JR
AF Doria-Rose, Nicole A.
Bhiman, Jinal N.
Roark, Ryan S.
Schramm, Chaim A.
Gorman, Jason
Chuang, Gwo-Yu
Pancera, Marie
Cale, Evan M.
Ernandes, Michael J.
Louder, Mark K.
Asokan, Mangaiarkarasi
Bailer, Robert T.
Druz, Aliaksandr
Fraschilla, Isabella R.
Garrett, Nigel J.
Jarosinski, Marissa
Lynch, Rebecca M.
McKee, Krisha
O'Dell, Sijy
Pegu, Amarendra
Schmidt, Stephen D.
Staupe, Ryan P.
Sutton, Matthew S.
Wang, Keyun
Wibmer, Constantinos Kurt
Haynes, Barton F.
Abdool-Karim, Salim
Shapiro, Lawrence
Kwong, Peter D.
Moore, Penny L.
Morris, Lynn
Mascola, John R.
TI New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows
Increased Breadth and Exceptional Potency
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; HIV-1
ENVELOPE TRIMER; HUMAN B-CELLS; VACCINE DEVELOPMENT; V1/V2 DOMAIN;
VIRUS; INFECTION; RECOGNITION; SEQUENCE
AB The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al., Nature 509: 55-62, 2014, http://dx.doi.org/10.1038/nature13036). Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight were isolated using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed a 10-fold greater neutralization potency than previously published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among the viruses neutralized, the median 50% inhibitory concentration was 0.001 mu g/ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, the CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.
C1 [Doria-Rose, Nicole A.; Roark, Ryan S.; Gorman, Jason; Chuang, Gwo-Yu; Pancera, Marie; Cale, Evan M.; Ernandes, Michael J.; Louder, Mark K.; Asokan, Mangaiarkarasi; Bailer, Robert T.; Druz, Aliaksandr; Fraschilla, Isabella R.; Jarosinski, Marissa; Lynch, Rebecca M.; McKee, Krisha; O'Dell, Sijy; Pegu, Amarendra; Schmidt, Stephen D.; Staupe, Ryan P.; Sutton, Matthew S.; Wang, Keyun; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bhiman, Jinal N.; Wibmer, Constantinos Kurt; Moore, Penny L.; Morris, Lynn] Natl Hlth Lab Serv, Ctr HIV & STIs, Natl Inst Communicable Dis, Johannesburg, South Africa.
[Bhiman, Jinal N.; Wibmer, Constantinos Kurt; Moore, Penny L.; Morris, Lynn] Univ Witwatersrand, Johannesburg, South Africa.
[Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Syst Biol, New York, NY USA.
[Garrett, Nigel J.; Abdool-Karim, Salim; Moore, Penny L.; Morris, Lynn] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
[Haynes, Barton F.] Duke Univ, Sch Med, Durham, NC USA.
[Haynes, Barton F.] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC USA.
[Abdool-Karim, Salim] Columbia Univ, Dept Epidemiol, New York, NY USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
RI Schmidt, Stephen/B-5398-2012;
OI Moore, Penny/0000-0001-8719-4028; , Lynn/0000-0003-3961-7828; Bhiman,
Jinal/0000-0001-6354-4003; Abdool Karim, Salim/0000-0002-4986-2133;
Wibmer, Constantinos Kurt/0000-0003-2329-2280
FU National Institutes of Health [AI116086-01]; South African Medical
Research Council [D1407250-01]; Wellcome Trust [089933/Z/09/Z]; South
African HIV/AIDS Research and Innovation Platform of the South African
Department of Science and Technology; National Institute of Allergy and
Infectious Diseases, National Institutes of Health, U.S. Department of
Health and Human Services [U19 AI51794]; Columbia University Southern
African Fogarty AIDS International Training and Research Program,
through the Fogarty International Center, National Institutes of Health
[5 D43 TW000231]; University of the Witwatersrand Postgraduate Merit
Award; Poliomyelitis Research Foundation; National Research Foundation
of South Africa; intramural research programs of the Vaccine Research
Center, Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, USA; US
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX National Institutes of Health provided funding to Penny L. Moore, Lynn
Morris, Peter D. Kwong, and John R. Mascola under grant number
AI116086-01. South African Medical Research Council provided funding to
Penny L. Moore under grant number D1407250-01. Wellcome Trust provided
funding to Penny L. Moore under grant number 089933/Z/09/Z.; CAPRISA is
funded by the South African HIV/AIDS Research and Innovation Platform of
the South African Department of Science and Technology and was initially
supported by National Institute of Allergy and Infectious Diseases,
National Institutes of Health, U.S. Department of Health and Human
Services, grant U19 AI51794 (to Salim Abdool-Karim). The Columbia
University Southern African Fogarty AIDS International Training and
Research Program, through the Fogarty International Center, National
Institutes of Health, provided funding to Jinal N. Bhiman, Penny I.
Moore, and Lynn Morris under grant number 5 D43 TW000231. Jinal N.
Bhiman received a University of the Witwatersrand Postgraduate Merit
Award as well as bursaries from the Poliomyelitis Research Foundation
and the National Research Foundation of South Africa. Funding was
provided by the intramural research programs of the Vaccine Research
Center, Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, USA. Use of
sector 22 (Southeast Region Collaborative Access Team) at the Advanced
Photon Source was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science, under contract number W-31-109-Eng-38. The
funders had no role in study design, data collection and interpretation,
or the decision to submit the work for publication.
NR 67
TC 19
Z9 19
U1 2
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 JAN
PY 2016
VL 90
IS 1
BP 76
EP 91
DI 10.1128/JVI.01791-15
PG 16
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000009
PM 26468542
ER
PT J
AU Li, H
Stoddard, MB
Wang, SY
Giorgi, EE
Blair, LM
Learn, GH
Hahn, BH
Alter, HJ
Busch, MP
Fierer, DS
Ribeiro, RM
Perelson, AS
Bhattacharya, T
Shaw, GM
AF Li, Hui
Stoddard, Mark B.
Wang, Shuyi
Giorgi, Elena E.
Blair, Lily M.
Learn, Gerald H.
Hahn, Beatrice H.
Alter, Harvey J.
Busch, Michael P.
Fierer, Daniel S.
Ribeiro, Ruy M.
Perelson, Alan S.
Bhattacharya, Tanmoy
Shaw, George M.
TI Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs
Distinguishes Modes and Models of Virus Transmission and Early
Diversification
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ADAPTIVE IMMUNE-RESPONSES; HIV-1 VACCINE EFFICACY; HCV INFECTION;
TRANSMITTED/FOUNDER VIRUSES; SEXUAL TRANSMISSION; FOUNDER VIRUS;
UNITED-STATES; EVOLUTION; REPLICATION; SELECTION
AB Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between linked donors and recipients. Using single-genome sequencing (SGS) of plasma vRNA, we found that inferred T/F sequences in recipients were identical to viral sequences in their respective donors. Early in infection, HCV genomes generally evolved according to a simple model of random evolution where the coalescent corresponded to the T/F sequence. Closely related sequence lineages could be explained by high multiplicity infection from a donor whose viral sequences had undergone a pretransmission bottleneck due to treatment, immune selection, or recent infection. These findings validate SGS, together with mathematical modeling and phylogenetic analysis, as a novel strategy to infer T/F HCV genome sequences.
C1 [Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Learn, Gerald H.; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Learn, Gerald H.; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Giorgi, Elena E.; Blair, Lily M.; Ribeiro, Ruy M.; Bhattacharya, Tanmoy] Los Alamos Natl Lab, T Div, Los Alamos, NM USA.
[Blair, Lily M.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
[Alter, Harvey J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Busch, Michael P.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
[Fierer, Daniel S.] Icahn Sch Med Mt Sinai, Div Infect Dis, New York, NY 10029 USA.
[Perelson, Alan S.] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA.
[Bhattacharya, Tanmoy] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP Shaw, GM (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
EM shawg@upenn.edu
OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Ribeiro,
Ruy/0000-0002-3988-8241
FU HHS \ National Institutes of Health (NIH) [AI106000, AI02433, OD011095,
AI078881]; University of Pennsylvania (Penn) [P30 AI 045008]
FX HHS vertical bar National Institutes of Health (NIH) provided funding to
George M. Shaw under grant number AI106000. HHS vertical bar National
Institutes of Health (NIH) provided funding to Alan Perelson under grant
number AI02433. HHS vertical bar National Institutes of Health (NIH)
provided funding to Alan Perelson under grant number OD011095. HHS
vertical bar National Institutes of Health (NIH) provided finding to
Alan Perelson under grant number AI078881. University of Pennsylvania
(Penn) provided funding to George M. Shaw under grant number P30 AI
045008.
NR 77
TC 3
Z9 3
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 JAN
PY 2016
VL 90
IS 1
BP 152
EP 166
DI 10.1128/JVI.02156-15
PG 15
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000015
ER
PT J
AU Hu, DS
Wang, V
Yang, M
Abdullah, S
Davis, DA
Uldrick, TS
Polizzotto, MN
Veeranna, RP
Pittaluga, S
Tosato, G
Yarchoan, R
AF Hu, Duosha
Wang, Victoria
Yang, Min
Abdullah, Shahed
Davis, David A.
Uldrick, Thomas S.
Polizzotto, Mark N.
Veeranna, Ravindra P.
Pittaluga, Stefania
Tosato, Giovanna
Yarchoan, Robert
TI Induction of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral
Interleukin-6 by X-Box Binding Protein 1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; PLASMA-CELL
DIFFERENTIATION; TRANSCRIPTION FACTOR; LYTIC CYCLE; GENE-TRANSCRIPTION;
MESSENGER-RNA; DNA-SEQUENCES; FACTOR XBP-1; EXPRESSION
AB Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentric Castleman disease (MCD). The KSHV life cycle has two principal gene repertoires, latent and lytic. KSHV viral interleukin-6 (vIL-6), an analog of human IL-6, is usually lytic; production of vIL-6 by involved plasmablasts is a central feature of KSHV-MCD. vIL-6 also plays a role in PEL and KS. We show that a number of plasmablasts from lymph nodes of patients with KSHV-MCD express vIL-6 but not ORF45, a KSHV lytic gene. We further show that vIL-6 is directly induced by the spliced (active) X-box binding protein-1 (XBP-1s), a transcription factor activated by endoplasmic reticulum (ER) stress and differentiation of B cells in lymph nodes. The promoter region of vIL-6 contains several potential XBP-response elements (XREs), and two of these elements in particular mediate the effect of XBP-1s. Mutation of these elements abrogates the response to XBP-1s but not to the KSHV replication and transcription activator (RTA). Also, XBP-1s binds to the vIL-6 promoter in the region of these XREs. Exposure of PEL cells to a chemical inducer of XBP-1s can induce vIL-6. Patient-derived PEL tumor cells that produce vIL-6 frequently coexpress XBP-1, and immunofluorescence staining of involved KSHV-MCD lymph nodes reveals that most plasmablasts expressing vIL-6 also coexpress XBP-1. These results provide evidence that XBP-1s is a direct activator of KSHV vIL-6 and that this is an important step in the pathogenesis of KSHV-MCD and PEL.
C1 [Hu, Duosha; Wang, Victoria; Yang, Min; Davis, David A.; Uldrick, Thomas S.; Polizzotto, Mark N.; Veeranna, Ravindra P.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abdullah, Shahed; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM Robert.Yarchoan@nih.gov
FU NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute.
NR 54
TC 2
Z9 2
U1 0
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 JAN
PY 2016
VL 90
IS 1
BP 368
EP 378
DI 10.1128/JVI.01192-15
PG 11
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000033
PM 26491160
ER
PT J
AU Wang, KN
Goodman, KN
Li, DY
Raffeld, M
Chavez, M
Cohen, JI
AF Wang, Kening
Goodman, Kyle N.
Li, Daniel Y.
Raffeld, Mark
Chavez, Mayra
Cohen, Jeffrey I.
TI A Herpes Simplex Virus 2 (HSV-2) gD Mutant Impaired for Neural Tropism
Is Superior to an HSV-2 gD Subunit Vaccine To Protect Animals from
Challenge with HSV-2
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RECOMBINANT GLYCOPROTEIN VACCINE; GENITAL HERPES; GUINEA-PIGS; ENTRY
MEDIATOR; CELL ENTRY; T-CELLS; INFECTION; TYPE-2; RECEPTOR; MICE
AB A recent phase 3 trial with soluble herpes simplex virus 2 (HSV-2) glycoprotein D (gD2t) in adjuvant failed to show protection against genital herpes. We postulated that live attenuated HSV-2 would provide more HSV antigens for induction of virus-specific antibodies and cellular immunity than would gD2t. We previously reported an HSV-2 mutant, HSV2-gD27, in which the nectin-1 binding domain of gD2 is altered so that the virus is impaired for infecting neural cells, but not epithelial cells, in vitro and is impaired for infecting dorsal root ganglia in mice (K. Wang, J. D. Kappel, C. Canders, W. F. Davila, D. Sayre, M. Chavez, L. Pesnicak, and J. I. Cohen, J Virol 86: 12891-12902, 2012, doi: 10.1128/JVI.01055-12). Here we report that the mutations in HSV2-gD27 were stable when the virus was passaged in cell culture and during acute infection of mice. HSV2-gD27 was attenuated in mice when it was inoculated onto the cornea, intramuscularly (i.m.), intravaginally, and intracranially. Vaccination of mice i.m. with HSV2-gD27 provided better inhibition of challenge virus replication in the vagina than when the virus was used to vaccinate mice intranasally or subcutaneously. Comparison of i.m. vaccinations with HSV2-gD27 versus gD2t in adjuvant showed that HSV2-gD27 induced larger reductions of challenge virus replication in the vagina and reduced latent viral loads in dorsal root ganglia but induced lower serum neutralizing antibody titers than those obtained with gD2t in adjuvant. Taken together, our data indicate that a live attenuated HSV-2 vaccine impaired for infection of neurons provides better protection from vaginal challenge with HSV-2 than that obtained with a subunit vaccine, despite inducing lower titers of HSV-2 neutralizing antibodies in the serum.
IMPORTANCE
Genital herpes simplex is one of the most prevalent sexually transmitted diseases. Though HSV-2 disease is usually mild, it can be life threatening in neonates and immunocompromised persons. In addition, genital herpes increases the frequency of HIV infection and transmission. HSV-2 maintains a latent infection in sensory neurons and cannot be cleared with antiviral drugs. The virus frequently reactivates, resulting in virus shedding in the genital area, which serves as a source for transmission. A prophylactic vaccine is needed to prevent disease and to control the spread of the virus. Previous human trials of subunit vaccines have been unsuccessful. Here we report the results of vaccinating mice with a new type of live attenuated HSV-2 vaccine that is impaired for infection of neurons and provides better protection of mice than that obtained with a subunit vaccine. The strategy of altering the cell tropism of a virus is a new approach for a live attenuated vaccine.
C1 [Wang, Kening; Goodman, Kyle N.; Li, Daniel Y.; Chavez, Mayra; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, KN (reprint author), NIAID, Med Virol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kwang@niaid.nih.gov; jcohen@niaid.nih.gov
FU Division of Intramural Research, National Cancer Institute; Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases
FX Division of Intramural Research, National Cancer Institute provided
funding to Mark Raffeld. Division of Intramural Research, National
Institute of Allergy and Infectious Diseases provided funding to Kening
Wang, Kyle N. Goodman, Daniel Y. Li, Mayra Chavez, and Jeffrey I. Cohen.
NR 52
TC 0
Z9 0
U1 4
U2 9
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 JAN
PY 2016
VL 90
IS 1
BP 562
EP 574
DI 10.1128/JVI.01845-15
PG 13
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000050
PM 26559846
ER
PT J
AU Batishchev, OV
Shilova, LA
Kachala, MV
Tashkin, VY
Sokolov, VS
Fedorova, NV
Baratova, LA
Knyazev, DG
Zimmerberg, J
Chizmadzhev, YA
AF Batishchev, O. V.
Shilova, L. A.
Kachala, M. V.
Tashkin, V. Y.
Sokolov, V. S.
Fedorova, N. V.
Baratova, L. A.
Knyazev, D. G.
Zimmerberg, J.
Chizmadzhev, Y. A.
TI pH-Dependent Formation and Disintegration of the Influenza A Virus
Protein Scaffold To Provide Tension for Membrane Fusion
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MATRIX PROTEIN; LIPID-MEMBRANES; M1 PROTEIN; POTENTIAL MEASUREMENTS;
BILAYER-MEMBRANES; ADSORPTION; HEMAGGLUTININ; PHOSPHOLIPIDS;
SPECTROSCOPY; ASSOCIATION
AB Influenza virus is taken up from a pH-neutral extracellular milieu into an endosome, whose contents then acidify, causing changes in the viral matrix protein (M1) that coats the inner monolayer of the viral lipid envelope. At a pH of similar to 6, M1 interacts with the viral ribonucleoprotein (RNP) in a putative priming stage; at this stage, the interactions of the M1 scaffold coating the lipid envelope are intact. The M1 coat disintegrates as acidification continues to a pH of similar to 5 to clear a physical path for the viral genome to transit from the viral interior to the cytoplasm. Here we investigated the physicochemical mechanism of M1's pH-dependent disintegration. In neutral media, the adsorption of M1 protein on the lipid bilayer was electrostatic in nature and reversible. The energy of the interaction of M1 molecules with each other in M1 dimers was about 10 times as weak as that of the interaction of M1 molecules with the lipid bilayer. Acidification drives conformational changes in M1 molecules due to changes in the M1 charge, leading to alterations in their electrostatic interactions. Dropping the pH from 7.1 to 6.0 did not disturb the M1 layer; dropping it lower partially desorbed M1 because of increased repulsion between M1 monomers still stuck to the membrane. Lipid vesicles coated with M1 demonstrated pH-dependent rupture of the vesicle membrane, presumably because of the tension generated by this repulsive force. Thus, the disruption of the vesicles coincident with M1 protein scaffold disintegration at pH 5 likely stretches the lipid membrane to the point of rupture, promoting fusion pore widening for RNP release.
IMPORTANCE
Influenza remains a top killer of human beings throughout the world, in part because of the influenza virus's rapid binding to cells and its uptake into compartments hidden from the immune system. To attack the influenza virus during this time of hiding, we need to understand the physical forces that allow the internalized virus to infect the cell. In particular, we need to know how the protective coat of protein inside the viral surface reacts to the changes in acid that come soon after internalization. We found that acid makes the molecules of the protein coat push each other while they are still stuck to the virus, so that they would like to rip the membrane apart. This ripping force is known to promote membrane fusion, the process by which infection actually occurs.
C1 [Batishchev, O. V.; Shilova, L. A.; Kachala, M. V.; Tashkin, V. Y.; Sokolov, V. S.; Chizmadzhev, Y. A.] Russian Acad Sci, AN Frumkin Inst Phys Chem & Electrochem, Moscow, Russia.
[Batishchev, O. V.; Shilova, L. A.] Moscow Inst Phys & Technol, Dolgoprudnyi, Russia.
[Fedorova, N. V.; Baratova, L. A.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia.
[Knyazev, D. G.] Johannes Kepler Univ Linz, Inst Biophys, A-4040 Linz, Austria.
[Zimmerberg, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Membrane Biophys, Program Phys Biol, Bethesda, MD USA.
RP Batishchev, OV (reprint author), Russian Acad Sci, AN Frumkin Inst Phys Chem & Electrochem, Moscow, Russia.
EM olegbati@gmail.com
RI Batishchev, Oleg/L-1976-2013;
OI Batishchev, Oleg/0000-0002-9581-2233; Knyazev, Denis/0000-0003-3197-1849
FU Russian Foundation for Basic Research (RFBR) [15-54-74002]; Division of
Intramural Research of the NICHD; Russian Science Foundation (RSF)
[15-14-00060]
FX Russian Foundation for Basic Research (RFBR) provided funding to Oleg
Batishchev, Liudmila Shilova, and Natalia V. Fedorova under grant number
15-54-74002. Division of Intramural Research of the NICHD provided
funding to Joshua Zimmerberg. Russian Science Foundation (RSF) provided
funding to Oleg Batishchev under grant number 15-14-00060.
NR 61
TC 5
Z9 5
U1 1
U2 22
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 JAN
PY 2016
VL 90
IS 1
BP 575
EP 585
DI 10.1128/JVI.01539-15
PG 11
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000051
PM 26468548
ER
PT J
AU Pastrana, DV
Ray, U
Magaldi, TG
Schowalter, RM
Cuburu, N
Buck, CB
AF Pastrana, Diana V.
Ray, Upasana
Magaldi, Thomas G.
Schowalter, Rachel M.
Cuburu, Nicolas
Buck, Christopher B.
TI BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct
Entry Tropism (vol 87, pg 10105, 2013)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Cuburu, Nicolas; Buck, Christopher B.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pastrana, DV (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
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 JAN
PY 2016
VL 90
IS 1
BP 624
EP 624
DI 10.1128/JVI.02585-15
PG 1
WC Virology
SC Virology
GA CZ1XK
UT WOS:000366899000058
PM 26680468
ER
PT J
AU Brown, P
AF Brown, Patricia
TI A word from OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 3
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 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD JAN
PY 2016
VL 45
IS 1
BP 15
EP 15
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA CZ6MV
UT WOS:000367216300017
PM 26684952
ER
PT J
AU Leifer, ES
Mikus, CR
Karavirta, L
Resnick, BD
Kraus, WE
Hakkinen, K
Earnest, CP
Fleg, JL
AF Leifer, Eric S.
Mikus, Catherine R.
Karavirta, Laura
Resnick, Benjamin D.
Kraus, William E.
Hakkinen, Keijo
Earnest, Conrad P.
Fleg, Jerome L.
TI Adverse Cardiovascular Response to Aerobic Exercise Training: Is This a
Concern?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE PHYSICAL ACTIVITY; BIOMARKER; INDIVIDUAL; RANDOMIZED TRIAL
ID RISK REDUCTION INTERVENTION; DEFINED EXERCISE; BLOOD-PRESSURE;
SEDENTARY; RATIONALE; INFLAME; DESIGN; TRIAL; WOMEN
AB Purpose Aerobic exercise training in sedentary individuals improves physical fitness and various cardiovascular (CV) biomarkers. Nevertheless, there has been controversy as to whether exercise training may adversely affect some biomarkers in a small segment of the population. The purpose of this study was to investigate whether clinically significant worsening of CV biomarkers was more prevalent among individuals randomized to a supervised endurance training program as compared with those randomized to a control condition.
Methods: Baseline and end of study measurements of fasting insulin ( FI), triglycerides ( TG), resting systolic blood pressure ( SBP), and HDL cholesterol ( HDL-C) were obtained on 1188 healthy sedentary subjects from 4 clinical studies. Each study randomized subjects to 4- to 6- month supervised aerobic exercise programs or to a control group of no supervised exercise training. For each of the 4 CV biomarkers, we calculated the respective proportions of control and exercise group subjects whose baseline-to-follow-up changes were greater than or equal to previously reported adverse change ( AC) thresholds. Those thresholdswere increases of 24 pmol center dot L-1 or greater for FI, 0.42 mmol center dot L (-1) or greater for TG, 10 mm Hg or greater for SBP, and a decrease of 0.12 mmol center dot L j1 or greater for HDL-C.
Results The respective proportions of subjects meeting the AC threshold in the control and exercise groups were 15.2% versus 9.6% (P = 0.02) for FI, 14.9% versus 13.1% (P = 0.37) for TG, 16.9% versus 15.8% (P = 0.52) for SBP, and 28.6% versus 22.5% (P = 0.03) for HDL-C. All were nonsignificant at the 0.0125 Bonferroni threshold adjusting for multiple comparisons.
Conclusions These findings do not support the concept that aerobic exercise training increases the risk of adverse changes in the CV biomarkers we studied.
C1 [Leifer, Eric S.; Resnick, Benjamin D.] NHLBI, Off Biostat Res, Bethesda, MD 20817 USA.
[Mikus, Catherine R.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Karavirta, Laura; Hakkinen, Keijo] Univ Jyvaskyla, Dept Biol Phys Act, SF-40100 Jyvaskyla, Finland.
[Kraus, William E.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Earnest, Conrad P.] Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20817 USA.
RP Leifer, ES (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,Room 9206, Bethesda, MD 20817 USA.
EM LeiferE@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute [HL66262, HL57354]; Ministry
of Education, Finland; Juho Vainio Foundation, Finland
FX The DREW and INFLAME studies were supported by grant HL66262 from the
National Heart, Lung, and Blood Institute. The University of Jyvaskyla
study was supported by the Ministry of Education, Finland, and Juho
Vainio Foundation, Finland. The STRRIDE studies were supported by
National Heart, Lung, and Blood Institute grant HL57354. The content of
this manuscript is entirely the responsibility of the authors and should
not be construed as necessarily reflecting the official position or
views of the National Heart, Lung, and Blood Institute or the National
Institutes of Health. The authors have reported that they have no
relationships relevant to the contents of this paper to disclose. The
results of the present study do not constitute endorsement by the
American College of Sports Medicine.
NR 21
TC 1
Z9 1
U1 0
U2 4
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 JAN
PY 2016
VL 48
IS 1
BP 20
EP 25
DI 10.1249/MSS.0000000000000752
PG 6
WC Sport Sciences
SC Sport Sciences
GA CY7LO
UT WOS:000366590100004
PM 26258860
ER
PT J
AU Ahn, K
An, SS
Shugart, YY
Rapoport, JL
AF Ahn, K.
An, S. S.
Shugart, Y. Y.
Rapoport, J. L.
TI Common polygenic variation and risk for childhood-onset schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CONFERRING RISK; DOUBLE-BLIND; VARIANTS;
DISEASE; DISORDER; LINKAGE
AB Childhood-onset schizophrenia (COS) is a rare and severe form of the disorder, with more striking abnormalities with respect to prepsychotic developmental disorders and abnormities in the brain development compared with later-onset schizophrenia. We previously documented that COS patients, compared with their healthy siblings and with adult-onset patients (AOS), carry significantly more rare chromosomal copy number variations, spanning large genomic regions (> 100 kb) (Ahn et al. 2014). Here, we interrogated the contribution of common polygenic variation to the genetic susceptibility for schizophrenia. We examined the association between a direct measure of genetic risk of schizophrenia in 130 COS probands and 103 healthy siblings. Using data from the schizophrenia and autism GWAS of the Psychiatric Genomic Consortia, we selected three risk-related sets of single nucleotide polymorphisms from which we conducted polygenic risk score comparisons for COS probands and their healthy siblings. COS probands had higher genetic risk scores of both schizophrenia and autism than their siblings (P < 0.05). Given the small sample size, these findings suggest that COS patients have more salient genetic risk than do AOS.
C1 [Ahn, K.; Rapoport, J. L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[An, S. S.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Shugart, Y. Y.] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20892 USA.
RP Ahn, K (reprint author), NIMH, Child Psychiat Branch, NIH, 10 Ctr Dr,Room 3N202-MSC 1600, Bethesda, MD 20892 USA.
EM kwangmi.ahn@nih.gov
NR 27
TC 3
Z9 3
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JAN
PY 2016
VL 21
IS 1
BP 94
EP 96
DI 10.1038/mp.2014.158
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CZ4TZ
UT WOS:000367096900012
PM 25510512
ER
PT J
AU Jun, G
Ibrahim-Verbaas, CA
Vronskaya, M
Lambert, JC
Chung, J
Naj, A
Kunkle, BW
Wang, LS
Bis, JC
Bellenguez, C
Harold, D
Lunetta, KL
Destefano, AL
Grenier-Boley, B
Sims, R
Beecham, GW
Smith, AV
Chouraki, V
Hamilton-Nelson, KL
Ikram, MA
Fievet, N
Denning, N
Martin, ER
Schmidt, H
Kamatani, Y
Dunstan, ML
Valladares, O
Laza, AR
Zelenika, D
Ramirez, A
Foroud, TM
Choi, SH
Boland, A
Becker, T
Kukull, WA
van der Lee, SJ
Pasquier, F
Cruchaga, C
Beekly, D
Fitzpatrick, AL
Hanon, O
Gill, M
Barber, R
Gudnason, V
Campion, D
Love, S
Bennett, DA
Amin, N
Berr, C
Tsolaki, M
Buxbaum, JD
Lopez, OL
Deramecourt, V
Fox, NC
Cantwell, LB
Tarraga, L
Dufouil, C
Hardy, J
Crane, PK
Eiriksdottir, G
Hannequin, D
Clarke, R
Evans, D
Mosley, TH
Letenneur, L
Brayne, C
Maier, W
De Jager, P
Emilsson, V
Dartigues, JF
Hampel, H
Kamboh, MI
de Bruijn, RFAG
Tzourio, C
Pastor, P
Larson, EB
Rotter, JI
O'Donovan, MC
Montine, TJ
Nalls, MA
Mead, S
Reiman, EM
Jonsson, PV
Holmes, C
St George-Hyslop, PH
Boada, M
Passmore, P
Wendland, JR
Schmidt, R
Morgan, K
Winslow, AR
Powell, JF
Carasquillo, M
Younkin, SG
Jakobsdottir, J
Kauwe, JSK
Wilhelmsen, KC
Rujescu, D
Nothen, MM
Hofman, A
Jones, L
Haines, JL
Psaty, BM
Van Broeckhoven, C
Holmans, P
Launer, LJ
Mayeux, R
Lathrop, M
Goate, AM
Escott-Price, V
Seshadri, S
Pericak-Vance, MA
Amouyel, P
Williams, J
van Duijn, CM
Schellenberg, GD
Farrer, LA
AF Jun, G.
Ibrahim-Verbaas, C. A.
Vronskaya, M.
Lambert, J-C
Chung, J.
Naj, A. C.
Kunkle, B. W.
Wang, L-S
Bis, J. C.
Bellenguez, C.
Harold, D.
Lunetta, K. L.
Destefano, A. L.
Grenier-Boley, B.
Sims, R.
Beecham, G. W.
Smith, A. V.
Chouraki, V.
Hamilton-Nelson, K. L.
Ikram, M. A.
Fievet, N.
Denning, N.
Martin, E. R.
Schmidt, H.
Kamatani, Y.
Dunstan, M. L.
Valladares, O.
Laza, A. R.
Zelenika, D.
Ramirez, A.
Foroud, T. M.
Choi, S-H
Boland, A.
Becker, T.
Kukull, W. A.
van der Lee, S. J.
Pasquier, F.
Cruchaga, C.
Beekly, D.
Fitzpatrick, A. L.
Hanon, O.
Gill, M.
Barber, R.
Gudnason, V.
Campion, D.
Love, S.
Bennett, D. A.
Amin, N.
Berr, C.
Tsolaki, Magda
Buxbaum, J. D.
Lopez, O. L.
Deramecourt, V.
Fox, N. C.
Cantwell, L. B.
Tarraga, L.
Dufouil, C.
Hardy, J.
Crane, P. K.
Eiriksdottir, G.
Hannequin, D.
Clarke, R.
Evans, D.
Mosley, T. H., Jr.
Letenneur, L.
Brayne, C.
Maier, W.
De Jager, P.
Emilsson, V.
Dartigues, J-F
Hampel, H.
Kamboh, M. I.
de Bruijn, R. F. A. G.
Tzourio, C.
Pastor, P.
Larson, E. B.
Rotter, J. I.
O'Donovan, M. C.
Montine, T. J.
Nalls, M. A.
Mead, S.
Reiman, E. M.
Jonsson, P. V.
Holmes, C.
St George-Hyslop, P. H.
Boada, M.
Passmore, P.
Wendland, J. R.
Schmidt, R.
Morgan, K.
Winslow, A. R.
Powell, J. F.
Carasquillo, M.
Younkin, S. G.
Jakobsdottir, J.
Kauwe, J. S. K.
Wilhelmsen, K. C.
Rujescu, D.
Noethen, M. M.
Hofman, A.
Jones, L.
Haines, J. L.
Psaty, B. M.
Van Broeckhoven, C.
Holmans, P.
Launer, L. J.
Mayeux, R.
Lathrop, M.
Goate, A. M.
Escott-Price, V.
Seshadri, S.
Pericak-Vance, M. A.
Amouyel, P.
Williams, J.
van Duijn, C. M.
Schellenberg, G. D.
Farrer, L. A.
CA IGAP Consortium
TI A novel Alzheimer disease locus located near the gene encoding tau
protein
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID FRONTOTEMPORAL LOBAR DEGENERATION; 17Q21.31 MICRODELETION SYNDROME;
PROGRESSIVE SUPRANUCLEAR PALSY; COMMON VARIANTS; MAPT LOCUS; ASSOCIATION
ANALYSIS; SUSCEPTIBILITY LOCI; KANSL1 CAUSE; RISK-FACTOR; HAPLOTYPE
AB APOE epsilon 4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE epsilon 4+ (10 352 cases and 9207 controls) and APOE epsilon 4 - (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE e4 status. Suggestive associations (P < 1x10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE epsilon 4+: 1250 cases and 536 controls; APOE epsilon 4 -: 718 cases and 1699 controls). Among APOE epsilon 4 - subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P = 5.8 x 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE epsilon 4+ subjects (CR1 and CLU) or APOE epsilon 4 - subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P = 1.6 x 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P <= 1.3 x 10(-8)), frontal cortex (P <= 1.3 x 10(-9)) and temporal cortex (P <= 1.2 x 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P = 9.2 x 10(-6)) and temporal cortex (P = 2.6 x 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE epsilon 4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.
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[Ibrahim-Verbaas, C. A.; De Jager, P.] Erasmus Univ, Erasmus, Med Ctr, Dept Urol, Rotterdam, Netherlands.
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[Lambert, J-C; Bellenguez, C.; Grenier-Boley, B.; Fievet, N.; Amouyel, P.] Inst Pasteur, F-59019 Lille, France.
[Naj, A. C.; Wang, L-S; Valladares, O.; Cantwell, L. B.; Schellenberg, G. D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
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[Ramirez, A.; Maier, W.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.
[Ramirez, A.; Noethen, M. M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Foroud, T. M.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN USA.
[Becker, T.; Maier, W.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
[Becker, T.] Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany.
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[Pasquier, F.; Deramecourt, V.] CHRU Lille, CNR MAJ, F-59037 Lille, France.
[Cruchaga, C.; Goate, A. M.] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA.
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[Hanon, O.] Univ Paris 05, Sorbonne Paris 5, Dept Geriatr, Paris, France.
[Hanon, O.] Broca Hosp, Geriatr Dept, Paris, France.
[Gill, M.] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland.
[Gill, M.] Trinity Coll Dublin, Dublin, Ireland.
[Barber, R.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX USA.
[Campion, D.; Hannequin, D.] CNR MAJ, Inserm U1079, Rouen, France.
[Campion, D.; Hannequin, D.] Univ Hosp, F-76031 Rouen, France.
[Campion, D.; Love, S.] Frenchay Hosp, Sch Clin Sci, Univ Bristol Inst Clin Neurosci, Bristol BS16 1LE, Avon, England.
[Bennett, D. A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
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[Berr, C.] Hop La Colombiere, Inserm U888, Montpellier, France.
[Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol, GR-54006 Thessaloniki, Greece.
[Buxbaum, J. D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
[Buxbaum, J. D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Buxbaum, J. D.] Mt Sinai Sch Med, Dept Genet, New York, NY USA.
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[Dufouil, C.; Hannequin, D.; Letenneur, L.; Dartigues, J-F; Tzourio, C.] Victor Segalen Univ, Inserm U897, F-33076 Bordeaux, France.
[Hardy, J.; Mead, S.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Hardy, J.] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
[Crane, P. K.; Larson, E. B.] Univ Washington, Dept Med, Seattle, WA USA.
[Clarke, R.] Univ Oxford, Clin Trial Serv Unit, OHAP, Oxford, England.
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[Mosley, T. H., Jr.] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA.
[Brayne, C.] Univ Cambridge, Inst Publ Hlth, Cambridge, England.
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[Dartigues, J-F] CHU Bordeaux, Ctr Memoire Ressources & Rech Bordeaux, Bordeaux, France.
[Hampel, H.] Goethe Univ Frankfurt, Dept Psychiat, D-60054 Frankfurt, Germany.
[Hampel, H.] Univ Munich, Dept Psychiat, D-80539 Munich, Germany.
[Kamboh, M. I.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
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[Pastor, P.] Inst Salud Carlos III, CIBERNED, Madrid, Spain.
[Larson, E. B.; Psaty, B. M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
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[Wilhelmsen, K. C.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Rujescu, D.] Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, D-06108 Halle, Germany.
[Noethen, M. M.] Univ Bonn, Inst Human Genet, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Haines, J. L.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
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[Amouyel, P.] CHRU Lille, Univ Hosp, F-59037 Lille, France.
[Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
RP Farrer, LA (reprint author), Boston Univ, Sch Med, Biomed Genet E200, 72 East Concord St, Boston, MA 02118 USA.
EM farrer@bu.edu
RI Gonzalez-Perez, Antonio/A-5247-2010; Deloukas, Panos/B-2922-2013; Hardy,
John/C-2451-2009; Kamatani, Yoichiro/N-5513-2015; Pastor,
Pau/C-9834-2009; Morgan, Grace/C-8098-2013; Powell, John/G-4412-2011;
Schott, Jonathan/A-9065-2011; Fox, Nick/B-1319-2009; Bullido,
Maria/C-8509-2014; Lambert, jean-charles/A-9553-2014; Tsuang,
Debby/L-7234-2016; Reposo, Ramirez-Lorca/D-7907-2014; McQuillin,
Andrew/C-1623-2008; Tzourio, christophe/B-4015-2009; Epelbaum,
Jacques/B-2263-2013; Smith, Albert Vernon/K-5150-2015;
OI Gonzalez-Perez, Antonio/0000-0001-9771-5982; Deloukas,
Panos/0000-0001-9251-070X; Pastor, Pau/0000-0002-7493-8777; Morgan,
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Jonathan/0000-0003-2059-024X; Fox, Nick/0000-0002-6660-657X; Bullido,
Maria/0000-0002-6477-1117; Lambert, jean-charles/0000-0003-0829-7817;
Tsuang, Debby/0000-0002-4716-1894; Holmans, Peter/0000-0003-0870-9412;
Satizabal, Claudia/0000-0002-1115-4430; Panza,
Francesco/0000-0002-7220-0656; Nothen, Markus/0000-0002-8770-2464;
Pickering-Brown, Stuart/0000-0003-1561-6054; Beiser,
Alexa/0000-0001-8551-7778; McQuillin, Andrew/0000-0003-1567-2240;
Tzourio, christophe/0000-0002-6517-2984; Denning,
Nicola/0000-0001-8467-7382; Buxbaum, Joseph/0000-0001-8898-8313; Kamboh,
M. Ilyas/0000-0002-3453-1438; Escott-Price,
Valentina/0000-0003-1784-5483; Smith, Albert Vernon/0000-0003-1942-5845;
Harold, Denise/0000-0001-5195-0143; Lacour, Andre/0000-0003-2692-2583
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Corporacion Tecnologica de Andalucia [08/211]; Agencia IDEA (Consejeria
de Innovacion, Junta de Andalucia) [841318]; Fundacio ACE research
programs; Netherlands Organization for Scientific Research (NWO);
Internationale Stichting Alzheimer Onderzoek (ISAO); Hersenstichting
Nederland (HSN); Centre for Medical Systems Biology (CMSB1 and CMSB2) in
the framework of the Netherlands Genomics Initiative (NGI); Erasmus
Medical Center; Erasmus University, Rotterdam; Netherlands Organization
for Health Research and Development; Research Institute for Diseases in
the Elderly; Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission; Municipality of
Rotterdam; Research Institute for Diseases in the Elderly (RIDE2)
[014-93-015]; Internationale Stichting Alzheimer Onderzoek;
Hersenstichting Nederland; Netherlands Genomics Initiative-Netherlands
Organization for Scientific Research (Center for Medical Systems
Biology); Seventh Framework Program [FP7/2007-2013]; ENGAGE project
[HEALTH-F4-2007-201413]; Netherlands Organization for Health Research
and Development (ZonMW Veni-grant) [916.13.054]; Netherlands Genomics
Initiative-Netherlands Organization for Scientific Research (Netherlands
Consortium for Healthy Aging); National Heart, Lung, and Blood Institute
[U01 HL096917, RC2-HL102419, UC2 HL103010, N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC- 55021, N01-HC-55022,
R01-HL087641, R01-HL093029]; NHGRI [U01-HG004402]; NIH
[HHSN268200625226C]; NIA [R01 AG033193]; National Institutes of Health
[UL1RR025005]; NIH Roadmap for Medical Research; 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 laLongevite; Agence Francaise de Securite
Sanitaire des Produits de Sante; Aquitaine and Bourgogne
RegionalCouncils; Fondation de France; joint French Ministry of
Research/INSERM 'Cohortes et collections de donnees biologiques'
programme; Eisai; Interuniversity Attraction Poles program of the
Belgian Science Policy Office; Foundation for Alzheimer Research
(SAO-FRA); Methusalem Excellence Grant of the Flemish Government;
Research Foundation Flanders (FWO); Special Research Fund of the
University of Antwerp, Belgium; Health Research Council of the Academy
of Finland; Nordic Centre of Excellence in Neurodegeneration; EVO grant
of Kuopio University Hospital [5772708]; Italian Ministry of research
and University; Carimonte Foundation; Italian ministry of Health
[RFPS-2006-7-334858, RF-2010-2319722, RF07-08, RC08-09-10-11-12];
fondazione Monzino; Ministerio de Educacion y Ciencia; Ministerio de
Sanidad y Consumo (Instituto de Salud Carlos III); FundacionRamon
Areces; Swedish Brain Power network; Marianne and Marcus Wallenberg
Foundation; Swedish Research Council [521-2010-3134]; King Gustaf V and
Queen Victoria's Foundation of Freemasons; Stockholm County Council;
Swedish Brain Foundation; Swedish Alzheimer Foundation; Karolinska
Institutet; Medical Research Council (MRC); Alzheimer's Research UK
(ARUK); Welsh Assembly Government; MRC; Alzheimer's Society; Ulster
Garden Villages; N. Ireland RD Office; Royal College of
Physicians/Dunhill Medical Trust; MRC and Mercer's Institute for
Research on Ageing; Bristol Research into Alzheimer's and Care of the
Elderly; Charles Wolfson Charitable Trust; NIH grants; Barnes Jewish
Foundation; Charles and Joanne Knight Alzheimer's Research Initiative;
UCLH/UCL NIHR Biomedical Centre; Queen Square Dementia Biomedical
Research Unit; Lundbeck SA; German Federal Ministry of Education and
Research (BMBF); Competence Network Dementia; Competence Network
Degenerative Dementia; Alfried Krupp von Bohlen und Halbach-Stiftung;
[U01 AG024904]; [RC2 AG036535]; [K01 AG030514]; [DEX-580000-2008-4]
FX The National Institutes of Health, National Institute on Aging (NIH-NIA)
supported this work through the following grants: ADGC, U01 AG032984,
RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIAGADS,
U24-AG041689; NIA LOAD, U24 AG026395, U24 AG026390; MIRAGE: R01
AG025259; Banner Sun Health Research Institute P30 AG019610; Boston
University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01
AG017173, R01AG33193; Columbia University, P50 AG008702, R37 AG015473;
Duke University, P30 AG028377, AG05128; Emory University, AG025688;
Group Health Research Institute, UO1 AG06781, UO1 HG004610; U01
HG006375; Indiana University, P30 AG10133; Johns Hopkins University, P50
AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134;
Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138,
P01 AG002219; New York University, P30 AG08051, MO1RR00096, and UL1
RR029893; Northwestern University, P30 AG013854; Oregon Health & Science
University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161,
R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873;
University of Alabama at Birmingham, P50 AG016582, UL1RR02777;
University of Arizona, R01 AG031581; University of California, Davis,
P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50
AG016575, P50 AG016576, P50 AG016577; University of California, Los
Angeles, P50 AG016570; University of California, San Diego, P50
AG005131; University of California, San Francisco, P50 AG023501, P01
AG019724; University of Kentucky, P30 AG028383; University of Michigan,
P50 AG008671; University of Pennsylvania, P30 AG010124; University of
Pittsburgh, P50 AG005133, AG030653, AG041718; University of Southern
California, P50 AG005142; University of Texas Southwestern, P30
AG012300; University of Miami, R01 AG027944, AG010491, AG027944,
AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt
University, R01 AG019085; and Washington University, P50 AG005681, P01
AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical
Center is funded by NINDS grant no. NS39764, NIMH MH60451 and by Glaxo
Smith Kline. Genotyping of the TGEN2 cohort was supported by Kronos
Science. The TGen series was also funded by NIA grant AG034504 to AJM,
The Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's
Institute, the Medical Research Council, and the state of Arizona and
also includes samples from the following sites: Newcastle Brain Tissue
Resource (funding via the Medical Research Council, local NHS trusts and
Newcastle University), MRC London Brain Bank for Neurodegenerative
Diseases (funding via the Medical Research Council), SouthWest Dementia
Brain Bank (funding via numerous sources, including the Higher Education
Funding Council for England (HEFCE), Alzheimer's Research Trust (ART),
BRACE as well as North Bristol NHS Trust Research and Innovation
Department and DeNDRoN), The Netherlands Brain Bank (funding via
numerous sources, including Stichting MS Research, Brain Net Europe,
Hersenstichting Nederland Breinbrekend Werk, International Parkinson
Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de
Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona.
Marcelle Morrison-Bogorad, PhD, Tony Phelps, PhD and Walter Kukull PhD
are thanked for helping to co-ordinate this collection.; ADNI Funding
for ADNI is through the Northern California Institute for Research and
Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma
AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan
Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics,
Johnson and Johnson, Eli Lilly, Medpace, Merck, Novartis AG, Pfizer, F
Homan-La Roche, Schering-Plough, Synarc, Alzheimer's Association,
Alzheimer's Drug Discovery Foundation, the Dana Foundation, and by the
National Institute of Biomedical Imaging and Bioengineering and NIA
grants U01 AG024904, RC2 AG036535, K01 AG030514. We thank Dr D Stephen
Snyder and Dr Marilyn Miller from NIA who are ex-officio ADGC members.
Support was also from the Alzheimer's Association (LAF, IIRG-08-89720;
MP-V, IIRG-05-14147) and the US Department of Veterans Affairs
Administration, Office of Research and Development, Biomedical
Laboratory Research Program. P.S.G.-H. is supported by the Wellcome
Trust, Howard Hughes Medical Institute, and Canadian Institute of
Health.; AGES: The AGES-Reykjavik Study is funded by NIH contract
N01-AG-12100 (NIA with contributions from the NEI, NIDCD and NHLBI), the
NIA Intramural Research Program, Hjartavernd (the Icelandic Heart
Association) and the Althingi (the Icelandic Parliament).; ASPS/PRODEM:
The Austrian Stroke Prevention Study and The Prospective Dementia
Register of the Austrian Alzheimer Society was supported by The Austrian
Science Fond (FWF) grant number P20545-P05 (H Schmidt) and P13180; The
Austrian Alzheimer Society; The Medical University of Graz.;
Cardiovascular Health Study (CHS): This research was supported by NHLBI
contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and
R01HL120393 with additional contribution from the National Institute of
Neurological Disorders and Stroke (NINDS). Additional support was
provided through R01AG023629, R01AG15928, R01AG20098, R01AG027058 and
R01AG033193 (Seshadri) from the National Institute on Aging (NIA). A
full list of principal CHS investigators and institutions can be found
at CHS-NHLBI.org. The provision of genotyping data was supported in part
by the National Center for Advancing Translational Sciences, CTSI grant
UL1TR000124, and the National Institute of Diabetes and Digestive and
Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the
Southern California Diabetes Endocrinology Research Center.; Framingham
Heart Study (FHS): This work was supported by the National Heart, Lung
and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195)
and its contract with Affymetrix, Inc for genotyping services (Contract
No. N02-HL-64278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGAII) funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. This study as also supported by
grants from the National Institute on Aging: AG08122 and AG033193
(Seshadri). Dr Seshadri and Dr DeStefano were also supported by
additional grants from the National Institute on Aging: (R01 AG16495;
AG031287, AG033040), the National Institute of Neurological Disorders
and Stroke (R01 NS17950), and the National Heart, Lung and Blood
Institute (U01 HL096917, HL093029 and K24HL038444, RC2-HL102419 and UC2
HL103010.; Fundacio ACE: would like to thank patients and controls who
participated in this project. This work has been funded by the Fundacion
Alzheimur (Murcia), the Ministerio de Educacion y Ciencia
(PCT-010000-2007-18), (DEX-580000-2008-4), (Gobierno de Espana),
Corporacion Tecnologica de Andalucia (08/211) and Agencia IDEA (841318)
(Consejeria de Innovacion, Junta de Andalucia). We thank Ms Trinitat
Port-Carbo and her family for their generous support of Fundacio ACE
research programs.; Erasmus Rucphen Family Study: We thank the
participants from the Genetic Research in Isolated Populations in the
Erasmus Rucphen Family Study who made this work possible. This study is
financially supported by the Netherlands Organization for Scientific
Research (NWO), the Internationale Stichting Alzheimer Onderzoek (ISAO),
the Hersenstichting Nederland (HSN) and the Centre for Medical Systems
Biology (CMSB1 and CMSB2) in the framework of the Netherlands Genomics
Initiative (NGI).; The Rotterdam Study: The Rotterdam Study was funded
by Erasmus Medical Center and Erasmus University, Rotterdam; the
Netherlands Organization for Health Research and Development; the
Research Institute for Diseases in the Elderly; the Ministry of
Education, Culture and Science; the Ministry for Health, Welfare and
Sports; the European Commission; and the Municipality of Rotterdam; by
grants from the Research Institute for Diseases in the Elderly
(014-93-015; RIDE2), Internationale Stichting Alzheimer Onderzoek,
Hersenstichting Nederland, the Netherlands Genomics
Initiative-Netherlands Organization for Scientific Research (Center for
Medical Systems Biology and the Netherlands Consortium for Healthy
Aging), the Seventh Framework Program (FP7/2007-2013), the ENGAGE
project (grant agreement HEALTH-F4-2007-201413), MRACE-grant from the
Erasmus Medical Center and the Netherlands Organization for Health
Research and Development (ZonMW Veni-grant no. 916.13.054).; ARIC: The
Atherosclerosis Risk in Communities Study (ARIC) 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, N01-HC-55022 and grants
R01-HL087641, RC2-HL102419 (Boerwinkle, CHARGE-S), UC2 HL103010, U01
HL096917 (Mosley) and R01-HL093029; NHGRI contract U01-HG004402; and NIH
contract HHSN268200625226C and NIA: R01 AG033193 (Seshadri).
Infrastructure was partly supported by Grant Number UL1RR025005, a
component of the National Institutes of Health and NIH Roadmap for
Medical Research.; 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 Study was
performed as part of a collaboration between the Institut National de la
Sante et de la Recherche Medicale (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 laLongevite,
Agence Francaise de Securite Sanitaire des Produits de Sante, the
Aquitaine and Bourgogne RegionalCouncils, 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.; Belgium sample collection: Research at the Antwerp
site is funded in part by the Interuniversity Attraction Poles program
of the Belgian Science Policy Office, the Foundation for Alzheimer
Research (SAO-FRA), a Methusalem Excellence Grant of the Flemish
Government, the Research Foundation Flanders (FWO), the Special Research
Fund of the University of Antwerp, Belgium. KB is a postdoctoral fellow
of the FWO. The Antwerp site authors thank the personnel of the VIB
Genetic Service Facility, the Biobank of the Institute Born-Bunge and
the Departments of Neurology and Memory Clinics at the Hospital Network
Antwerp and the University Hospitals Leuven.; Finish sample collection:
Financial support for this project was provided by the Health Research
Council of the Academy of Finland, EVO grant 5772708 of Kuopio
University Hospital and the Nordic Centre of Excellence in
Neurodegeneration.; Italian sample collections: The Bologna site (FL)
obtained funds from the Italian Ministry of research and University as
well as Carimonte Foundation. The Florence site was supported by a grant
from the Italian ministry of Health (RFPS-2006-7-334858) and grant
RF-2010-2319722. The Milan site was supported by a grant from the
'fondazione Monzino'. We thank the expert contribution of Mr. Carmelo
Romano. The Roma site received financial support from Italian Ministry
of Health, Grant RF07-08 and RC08-09-10-11-12. The Pisa site is grateful
to Dr Annalisa LoGerfo for her technical assistance in the DNA
purification studies.; Spanish sample collection: The Madrid site (MB)
was supported by grants of the Ministerio de Educacion y Ciencia and the
Ministerio de Sanidad y Consumo (Instituto de Salud Carlos III), and an
institutional grant of the FundacionRamon Areces to the CBMSO. We thank
I Sastre and Dr A Martinez-Garcia for the preparation and control of the
DNA collection, and Dr P Gil and Dr P Coria for their cooperation in the
cases/controls recruitment. We are grateful to the Asociacion de
Familiares de Alzheimer de Madrid (AFAL) for continuous encouragement
and help.; Swedish sample collection: Financially supported in part by
the Swedish Brain Power network, the Marianne and Marcus Wallenberg
Foundation, the Swedish Research Council (521-2010-3134), the King
Gustaf V and Queen Victoria's Foundation of Freemasons, the Regional
Agreement on Medical Training and Clinical Research (ALF) between
Stockholm County Council and the Karolinska Institutet, the Swedish
Brain Foundation and the Swedish Alzheimer Foundation.; Cardiff
University was supported by the Wellcome Trust, Medical Research Council
(MRC), Alzheimer's Research UK (ARUK) and the Welsh Assembly Government.
Cambridge University and Kings College London acknowledge support from
the MRC. ARUK supported sample collections at the South West Dementia
Bank and the Universities of Nottingham, Manchester and Belfast. The
Belfast group acknowledges support from the Alzheimer's Society, Ulster
Garden Villages, N. Ireland R&D Office and the Royal College of
Physicians/Dunhill Medical Trust. The MRC and Mercer's Institute for
Research on Ageing supported the Trinity College group. The South West
Dementia Brain Bank acknowledges support from Bristol Research into
Alzheimer's and Care of the Elderly. The Charles Wolfson Charitable
Trust supported the OPTIMA group. Washington University was funded by
NIH grants, Barnes Jewish Foundation and the Charles and Joanne Knight
Alzheimer's Research Initiative. Patient recruitment for the MRC Prion
Unit/UCL NIHR Department of Neurodegenerative Disease collection was
supported by the UCLH/UCL NIHR Biomedical Centre and Queen Square
Dementia Biomedical Research Unit. LASER-AD was funded by Lundbeck SA.
The Bonn group was supported by the German Federal Ministry of Education
and Research (BMBF), Competence Network Dementia and Competence Network
Degenerative Dementia and by the Alfried Krupp von Bohlen und
Halbach-Stiftung. The GERAD1 Consortium also used samples ascertained by
the NIMH AD Genetics Initiative.
NR 46
TC 23
Z9 23
U1 10
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JAN
PY 2016
VL 21
IS 1
BP 108
EP 117
DI 10.1038/mp.2015.23
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CZ4TZ
UT WOS:000367096900014
PM 25778476
ER
PT J
AU Schwartz, DM
Bonelli, M
Gadina, M
O'Shea, JJ
AF Schwartz, Daniella M.
Bonelli, Michael
Gadina, Massimo
O'Shea, John J.
TI Type I/II cytokines, JAKs, and new strategies for treating autoimmune
diseases
SO NATURE REVIEWS RHEUMATOLOGY
LA English
DT Review
AB Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Despite the effectiveness of these drugs, they do not induce complete remission in all patients, prompting the development of alternative strategies - including targeting of intracellular signal transduction pathways downstream of cytokines. Many cytokines that bind type I and type II cytokine receptors are critical regulators of immune-mediated diseases and employ the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway to exert their effect. Pharmacological inhibition of JAKs blocks the actions of type I/II cytokines, and within the past 3 years therapeutic JAK inhibitors, or Jakinibs, have become available to rheumatologists. Jakinibs have proven effective for the treatment of rheumatoid arthritis and other inflammatory diseases. Adverse effects of these agents are largely related to their mode of action and include infections and hyperlipidemia. Jakinibs are currently being investigated for a number of new indications, and second-generation selective Jakinibs are being developed and tested. Targeting STATs could be a future avenue for the treatment of rheumatologic diseases, although substantial challenges remain. Nonetheless, the ability to therapeutically target intracellular signalling pathways has already created a new paradigm for the treatment of rheumatologic disease.
C1 [Schwartz, Daniella M.; Gadina, Massimo; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Schwartz, Daniella M.; Gadina, Massimo; O'Shea, John J.] NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Bonelli, Michael] Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria.
RP Schwartz, DM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM daniella.schwartz@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the NIH
FX The work of D.M.S., M.G. and J.J.O'S. is supported by the Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the NIH.
NR 0
TC 27
Z9 28
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4790
EI 1759-4804
J9 NAT REV RHEUMATOL
JI Nat. Rev. Rheumatol.
PD JAN
PY 2016
VL 12
IS 1
BP 25
EP 36
DI 10.1038/nrrheum.2015.167
PG 12
WC Rheumatology
SC Rheumatology
GA CZ3KE
UT WOS:000367002200004
PM 26633291
ER
PT J
AU Wang, L
Almeida, LEF
Batista, CMD
Khaibullina, A
Xu, N
Albani, S
Guth, KA
Seo, JS
Quezado, M
Quezado, ZMN
AF Wang, Li
Almeida, Luis E. F.
Batista, Celia M. de Souza
Khaibullina, Alfia
Xu, Nuo
Albani, Sarah
Guth, Kira A.
Seo, Ji Sung
Quezado, Martha
Quezado, Zenaide M. N.
TI Cognitive and behavior deficits in sickle cell mice are associated with
profound neuropathologic changes in hippocampus and cerebellum
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Learning; Memory; Hippocampus; Anemia; Cerebellum; Depression; Anxiety;
Pain; Neuronal injury
ID MOUSE MODEL; NEUROIMAGING ABNORMALITIES; EPISODIC MEMORY; PISCES
PROJECT; YOUNG-CHILDREN; PLUS-MAZE; DISEASE; ANEMIA; PAIN; ADULTS
AB Strokes are perhaps the most serious complications of sickle cell disease (SCD) and by the fifth decade occur in approximately 25% of patients. While most patients do not develop strokes, mounting evidence indicates that even without brain abnormalities on imaging studies, SCD patients can present profound neurocognitive dysfunction. We sought to evaluate the neurocognitive behavior profile of humanized SCD mice (Townes, BERK) and to identify hematologic and neuropathologic abnormalities associated with the behavioral alterations observed in these mice. Heterozygous and homozygous Townes mice displayed severe cognitive deficits shown by significant delays in spatial learning compared to controls. Homozygous Townes also had increased depression- and anxiety-like behaviors as well as reduced performance on voluntary wheel running compared to controls. Behavior deficits observed in Townes were also seen in BERKs. Interestingly, most deficits in homozygotes were observed in older mice and were associated with worsening anemia. Further, neuropathologic abnormalities including the presence of large bands of dark/pyknotic (shrunken) neurons in CA1 and CA3 fields of hippocampus and evidence of neuronal dropout in cerebellum were present in homozygotes but not control Townes. These observations suggest that cognitive and behavioral deficits in SCD mice mirror those described in SCD patients and that aging, anemia, and profound neuropathologic changes in hippocampus and cerebellum are possible biologic correlates of those deficits. These findings support using SCD mice for studies of cognitive deficits in SCD and point to vulnerable brain areas with susceptibility to neuronal injury in SCD and to mechanisms that potentially underlie those deficits. (C) 2015 Elsevier Inc. All rights reserved,
C1 [Wang, Li; Almeida, Luis E. F.; Khaibullina, Alfia; Xu, Nuo; Albani, Sarah; Guth, Kira A.; Seo, Ji Sung; Quezado, Zenaide M. N.] Childrens Res Inst, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC USA.
[Batista, Celia M. de Souza] Howard Univ, Dept Nutr Sci, Washington, DC 20059 USA.
[Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Quezado, Zenaide M. N.] Childrens Natl Hlth Syst, Div Anesthesiol & Pain Med, Washington, DC USA.
[Quezado, Zenaide M. N.] George Washington Univ, Childrens Natl Hlth Syst, Childrens Res Inst, Sch Med & Hlth Sci,Ctr Neurosci Res, Washington, DC 20010 USA.
RP Quezado, ZMN (reprint author), George Washington Univ, Sheikh Zayed Inst Pediat Surg Innovat, Div Anesthesiol & Pain Med,Sch Med & Hlth Sci, Ctr Neurosci Res,Childrens Res Inst,Childrens Nat, 111 Michigan Ave, Washington, DC 20010 USA.
EM zquezado@childrensnational.org
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
FU Sheikh Zayed Institute for Pediatric Surgical Innovation [RAC 3000193];
National Institutes of Health Intellectual & Developmental Disabilities
Research Center [P30HD040677]; National Institutes of Health Clinical
Center, NIH
FX This work was supported by the Sheikh Zayed Institute for Pediatric
Surgical Innovation (RAC 3000193), the National Institutes of Health
Intellectual & Developmental Disabilities Research Center Grant
P30HD040677, and the Intramural Program from the National Institutes of
Health Clinical Center, NIH.
NR 67
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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 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JAN
PY 2016
VL 85
BP 60
EP 72
DI 10.1016/j.nbd.2015.10.004
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CZ2SP
UT WOS:000366955200006
PM 26462816
ER
PT J
AU Zaghloul, KA
Chang, EF
AF Zaghloul, Kareem A.
Chang, Edward F.
TI Minimally Invasive Epilepsy Surgery Preface
SO NEUROSURGERY CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 [Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Chang, Edward F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
RP Zaghloul, KA (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kareem.zaghloul@nih.gov; Edward.Chang@ucsf.edu
FU Intramural NIH HHS [Z99 NS999999]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3680
EI 1558-1349
J9 NEUROSURG CLIN N AM
JI Neurosurg. Clin. N. Am.
PD JAN
PY 2016
VL 27
IS 1
BP XIII
EP XIV
DI 10.1016/j.nec.2015.10.001
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA CZ6HH
UT WOS:000367201300001
PM 26615115
ER
PT J
AU Bray, MS
Loos, RJF
McCaffery, JM
Ling, C
Franks, PW
Weinstock, GM
Snyder, MP
Vassy, JL
Agurs-Collins, T
AF Bray, Molly S.
Loos, Ruth J. F.
McCaffery, Jeanne M.
Ling, Charlotte
Franks, Paul W.
Weinstock, George M.
Snyder, Michael P.
Vassy, Jason L.
Agurs-Collins, Tanya
CA Conference Working Grp
TI NIH working group report-using genomic information to guide weight
management: From universal to precision treatment
SO OBESITY
LA English
DT Review
ID BODY-MASS INDEX; DIABETES PREVENTION PROGRAM; PHYSICAL-ACTIVITY LEVELS;
LIFE-STYLE INTERVENTION; GASTRIC BYPASS-SURGERY; OBESITY-RELATED TRAITS;
HUMAN ADIPOSE-TISSUE; LOOK-AHEAD TRIAL; DNA METHYLATION; WIDE
ASSOCIATION
AB ObjectivePrecision medicine utilizes genomic and other data to optimize and personalize treatment. Although more than 2,500 genetic tests are currently available, largely for extreme and/or rare phenotypes, the question remains whether this approach can be used for the treatment of common, complex conditions like obesity, inflammation, and insulin resistance, which underlie a host of metabolic diseases.
MethodsThis review, developed from a Trans-NIH Conference titled Genes, Behaviors, and Response to Weight Loss Interventions, provides an overview of the state of genetic and genomic research in the area of weight change and identifies key areas for future research.
ResultsAlthough many loci have been identified that are associated with cross-sectional measures of obesity/body size, relatively little is known regarding the genes/loci that influence dynamic measures of weight change over time. Although successful short-term weight loss has been achieved using many different strategies, sustainable weight loss has proven elusive for many, and there are important gaps in our understanding of energy balance regulation.
ConclusionsElucidating the molecular basis of variability in weight change has the potential to improve treatment outcomes and inform innovative approaches that can simultaneously take into account information from genomic and other sources in devising individualized treatment plans.
C1 [Bray, Molly S.] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Charles Bronfman Inst Personalized Med, Dept Prevent Med, New York, NY 10029 USA.
[McCaffery, Jeanne M.] Brown Univ, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, Alpert Med Sch,Miriam Hosp, Providence, RI USA.
[Ling, Charlotte; Franks, Paul W.] Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden.
[Weinstock, George M.] Jackson Lab Genom Med, Farmington, CT USA.
[Snyder, Michael P.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Vassy, Jason L.] Harvard Univ, Sch Med, Boston, MA USA.
[Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Bray, MS (reprint author), Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA.
EM mbray@austin.utexas.edu; collinsta@mail.nih.gov
FU National Cancer Institute (NCI), National Institutes of Health (NIH)
FX National Cancer Institute (NCI), National Institutes of Health (NIH).
NR 112
TC 14
Z9 14
U1 4
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD JAN
PY 2016
VL 24
IS 1
BP 14
EP 22
DI 10.1002/oby.21381
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA CZ6CW
UT WOS:000367189800005
PM 26692578
ER
PT J
AU Folgar, FA
Yuan, EL
Sevilla, MB
Chiu, SJ
Farsiu, S
Chew, EY
Toth, CA
AF Folgar, Francisco A.
Yuan, Eric L.
Sevilla, Monica B.
Chiu, Stephanie J.
Farsiu, Sina
Chew, Emily Y.
Toth, Cynthia A.
CA Age Related Eye Disease Stu
TI Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume
Predict 2-Year Progression of Age-Related Macular Degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SD-OCT IMAGES; COLOR FUNDUS PHOTOGRAPHS;
GEOGRAPHIC ATROPHY; EYE DISEASE; SEVERITY SCALE; AUTOMATIC SEGMENTATION;
HYPERREFLECTIVE FOCI; CLINICAL-TRIAL; REPRODUCIBILITY
AB Purpose: To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD).
Design: Prospective, observational study.
Participants: Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study.
Methods: High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semi-automated segmentation of total RPEDC within a 5-mm-diameter macular field.
Main Outcome Measures: Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA).
Results: Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P < 0.001), and RAT volume increased from 8.3 x 10(-4) mm(3) (20.8 x 10(-4) mm(3)) to 18.4 x 10(-4) mm(3) (46.6 x 10(-4) mm(3); P < 0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change.
Conclusions: Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years. These quantitative SD OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials. (C) 2016 by the American Academy of Ophthalmology.
C1 [Folgar, Francisco A.; Yuan, Eric L.; Sevilla, Monica B.; Chiu, Stephanie J.; Farsiu, Sina; Toth, Cynthia A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
[Chiu, Stephanie J.; Farsiu, Sina; Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA.
[Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
RP Toth, CA (reprint author), Duke Univ, Med Ctr 3802, Duke Eye Ctr, Durham, NC 27710 USA.
EM cynthia.toth@dm.duke.edu
FU Alcon (Fort Worth, TX); Genentech (South San Francisco, CA)
FX C.A.T.: Financial support - Alcon (Fort Worth, TX); Genentech (South San
Francisco, CA); Royalties - Alcon (Fort Worth, TX); Patents - image
processing; S.F. and C.A.T. have disclosed separate funding by the
National Institutes of Health, but these grants did not fund this study.
Supported by an unrestricted grant from Genentech (South San Francisco,
CA), which had no role in the design or conduct of this research.
NR 36
TC 10
Z9 10
U1 1
U2 7
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 JAN
PY 2016
VL 123
IS 1
BP 39
EP +
DI 10.1016/j.ophtha.2015.09.016
PG 13
WC Ophthalmology
SC Ophthalmology
GA CZ4GE
UT WOS:000367060700023
PM 26578448
ER
PT J
AU Sen, HN
Abreu, FM
Louis, TA
Sugar, EA
Altaweel, MM
Elner, SG
Holbrook, JT
Jabs, DA
Kim, RY
Kempen, JH
AF Sen, H. Nida
Abreu, Francis M.
Louis, Thomas A.
Sugar, Elizabeth A.
Altaweel, Michael M.
Elner, Susan G.
Holbrook, Janet T.
Jabs, Douglas A.
Kim, Rosa Y.
Kempen, John H.
CA MUST Trial Follow-Up Study Res Grp
TI Cataract Surgery Outcomes in Uveitis The Multicenter Uveitis Steroid
Treatment Trial
SO OPHTHALMOLOGY
LA English
DT Article
ID INTRAOCULAR-LENS IMPLANTATION; VISUAL-ACUITY; PHACOEMULSIFICATION;
COMPLICATIONS; EXTRACTION; POSTERIOR; RISK
AB Purpose: To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial.
Design: Nested prospective cohort study of patients enrolled in a randomized clinical trial.
Participants: Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial.
Methods: Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using logarithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model.
Main Outcome Measures: Best-corrected visual acuity.
Results: After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients underwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from the preoperative visit to the 3-month visit (95% confidence interval [CI], 17-29 letters; P < 0.001) and was stable through 9 months of follow-up. Eyes presumed to have a more severe cataract, as measured by inability to grade vitreous haze, gained an additional 42 letters (95% CI, 34-56 letters; P < 0.001) beyond the 13-letter gain in eyes that had gradable vitreous haze before surgery (95% CI, 9-18 letters; P < 0.001) 3 months after surgery, making up for an initial difference of -45 letters at the preoperative visit (95% CI, -56 to -34 letters; P < 0.001). Black race, longer time from uveitis onset, and hypotony were associated with worse preoperative visual acuity (P < 0.05), but did not affect postsurgical recovery (P > 0.05, test of interaction). After adjusting for other risk factors, there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant vs. systemic therapy, 2 letters; 95% CI, -10 to 15 letters; P = 0.70).
Conclusions: Cataract surgery resulted in substantial, sustained, and similar visual acuity improvement in the eyes of patients with uveitis treated with the fluocinolone acetonide implant or standard systemic therapy. (C) 2016 Published by Elsevier on behalf of the American Academy of Ophthalmology.
C1 [Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Abreu, Francis M.; Louis, Thomas A.; Sugar, Elizabeth A.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Sugar, Elizabeth A.; Holbrook, Janet T.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Altaweel, Michael M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol, Madison, WI USA.
[Elner, Susan G.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol & Med, New York, NY 10029 USA.
[Kim, Rosa Y.] Retina Consultants Houston, Houston, TX USA.
[Kim, Rosa Y.] Houston Methodist Hosp, Blanton Eye Inst, Houston, TX USA.
[Kim, Rosa Y.] Weill Cornell Med Coll, Dept Ophthalmol, New York, NY USA.
[Kempen, John H.] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,10N109, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU National Eye Institute, National Institutes of Health, Bethesda,
Maryland [U10EY014655, U10EY014660, U10EY014656]; National Eye Institute
Intramural Research Program (Bethesda, MD); Research to Prevent
Blindness, Inc., New York, NY; Paul and Evanina Mackall Foundation
(Chicago, IL); Lois Pope Life Foundation (Delray Beach, FL)
FX Supported by the National Eye Institute, National Institutes of Health,
Bethesda, Maryland (Collaborative Agreement nos.: U10EY014655 [D.A.J.],
U10EY014660 [J.T.H.], and U10EY014656 [M.M.A.]); and the National Eye
Institute Intramural Research Program (H.N.S.) (Bethesda, MD). Bausch &
Lomb (Rochester, NY) provided support to the study in the form of
donation of fluocinolone implants for patients randomized to implant
therapy who were uninsured or otherwise unable to pay for implants, or
who were located at a site where implants could not be purchased (e.g.,
the United Kingdom). Additional support was provided by Research to
Prevent Blindness, Inc., New York, NY; the Paul and Evanina Mackall
Foundation (Chicago, IL); and the Lois Pope Life Foundation (Delray
Beach, FL). A representative of the National Eye Institute participated
in the conduct of the study, including the study design; collection,
management, analysis, and interpretation of the data; and review and
approval of this manuscript. The sponsor or funding organization had no
role in the design or conduct of this research.
NR 22
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 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2016
VL 123
IS 1
BP 183
EP 190
DI 10.1016/j.ophtha.2015.09.022
PG 8
WC Ophthalmology
SC Ophthalmology
GA CZ4GE
UT WOS:000367060700042
PM 26499920
ER
PT J
AU Rosellini, AJ
Monahan, J
Street, AE
Heeringa, SG
Hill, ED
Petukhova, M
Reis, BY
Sampson, NA
Bliese, P
Schoenbaum, M
Stein, MB
Ursano, RJ
Kessler, RC
AF Rosellini, A. J.
Monahan, J.
Street, A. E.
Heeringa, S. G.
Hill, E. D.
Petukhova, M.
Reis, B. Y.
Sampson, N. A.
Bliese, P.
Schoenbaum, M.
Stein, M. B.
Ursano, R. J.
Kessler, R. C.
TI Predicting non-familial major physical violent crime perpetration in the
US Army from administrative data
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Actuarial model; crime perpetration; machine learning; military
violence; physical violence; risk model
ID AFGHANISTAN WAR VETERANS; RISK-ASSESSMENT; MILITARY VETERANS; VARIABLE
SELECTION; IRAQ; BEHAVIOR; COMBAT; AGGRESSION; DEPLOYMENT; ANGER
AB Background. Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers.
Method. A consolidated administrative database for all 975 057 soldiers in the US Army in 2004-2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011-2013 sample.
Results. Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80-0.82 in 2004-2009 and 0.77 in the 2011-2013 validation sample. Of all administratively recorded crimes, 36.2-33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004-2009 and an even higher proportion (50.5%) in the 2011-2013 validation sample.
Conclusions. Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.
C1 [Rosellini, A. J.; Hill, E. D.; Petukhova, M.; Sampson, N. A.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Monahan, J.] Univ Virginia, Sch Law, Charlottesville, VA 22903 USA.
[Street, A. E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Street, A. E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Heeringa, S. G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Reis, B. Y.] Boston Childrens Hosp, Predict Med Grp, Boston, MA USA.
[Reis, B. Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Bliese, P.] Univ S Carolina, Darla Moore Sch Business, Columbia, SC 29208 USA.
[Schoenbaum, M.] NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA.
[Stein, M. B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, M. B.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
[Stein, M. B.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Ursano, R. J.] Uniformed Serv Univ Hlth Sci, Sch Med, Ctr Study Traumat Stress, Dept Psychiat, Bethesda, MD USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM Kessler@hcp.med.harvard.edu
FU Department of the Army; US Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
(NIH/NIMH) [U01MH087981]; Department of Defense, Office of the Assistant
Secretary for Defense for Health Affairs, Defense Health Program
(OASD/HA) [W81XWH-12-2-0113]
FX The data analyzed in this report were collected as part of the Army
Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement number U01MH087981 with the US Department of
Health and Human Services, National Institutes of Health, National
Institute of Mental Health (NIH/NIMH). This research was conducted by
Harvard Medical School and is funded by the Department of Defense,
Office of the Assistant Secretary for Defense for Health Affairs,
Defense Health Program (OASD/HA), awarded and administered by the US
Army Medical Research & Materiel Command (USAMRMC), at Fort Detrick, MD,
under Contract Number (Award no. W81XWH-12-2-0113.
NR 61
TC 3
Z9 3
U1 6
U2 18
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 JAN
PY 2016
VL 46
IS 2
BP 303
EP 316
DI 10.1017/S0033291715001774
PG 14
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CZ5VV
UT WOS:000367171300007
PM 26436603
ER
PT J
AU Kim, DH
Saver, JL
Starkman, S
Liebeskind, DS
Ali, LK
Restrepo, L
Kim-Tenser, M
Valdes-Sueiras, M
Eckstein, M
Pratt, F
Stratton, S
Hamilton, S
Conwit, R
Sanossian, N
AF Kim, Dae-Hyun
Saver, Jeffrey L.
Starkman, Sidney
Liebeskind, David S.
Ali, Latisha K.
Restrepo, Lucas
Kim-Tenser, May
Valdes-Sueiras, Miguel
Eckstein, Marc
Pratt, Frank
Stratton, Samuel
Hamilton, Scott
Conwit, Robin
Sanossian, Nerses
CA Field Adm Stroke Therapy-Magnesium
TI Enrollment Yield and Reasons for Screen Failure in a Large Prehospital
Stroke Trial
SO STROKE
LA English
DT Article
DE cell phones; clinical trial; informed consent; physician; stroke
ID THERAPY; METHODOLOGY; SAFETY
AB Background and Purpose The enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated.
Methods The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening processparamedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded.
Results From 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%).
Conclusions In this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider.
C1 [Kim, Dae-Hyun] Dong A Univ, Coll Med, Busan Ulsan Reg Cardiocerebrovasc Ctr, Dept Neurol, Busan, South Korea.
[Saver, Jeffrey L.; Liebeskind, David S.; Ali, Latisha K.; Restrepo, Lucas; Valdes-Sueiras, Miguel] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
[Stratton, Samuel] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Dept Emergency Med & Neurol, Los Angeles, CA 90095 USA.
[Pratt, Frank] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles Cty Fire EMS Agcy, Dept Emergency Med, Los Angeles, CA 90095 USA.
[Kim-Tenser, May; Sanossian, Nerses] Univ So Calif, Keck Sch Med, Dept Neurol, Roxanna Todd Hodges Comprehens Stroke Clin, Los Angeles, CA 90033 USA.
[Eckstein, Marc] Univ So Calif, Keck Sch Med, Los Angeles Fire Dept, Dept Emergency Med, Los Angeles, CA 90033 USA.
[Stratton, Samuel] Harbor Univ Calif Los Angeles Med Ctr, Orange Cty EMS Agcy, Los Angeles EMS Agcy, Dept Emergency Med, Los Angeles, CA USA.
[Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA.
[Conwit, Robin] NINDS, Bethesda, MD 20892 USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, UCLA Comprehens Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@mednet.ucla.edu
RI Emchi, Karma/Q-1952-2016
FU National Institutes of Health [NIH-NINDS U01 NS 44364]
FX This study was supported by an Award from the National Institutes of
Health (NIH-NINDS U01 NS 44364).
NR 12
TC 1
Z9 1
U1 0
U2 1
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 JAN
PY 2016
VL 47
IS 1
BP 232
EP 235
DI 10.1161/STROKEAHA.115.011687
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CZ5IQ
UT WOS:000367136500035
PM 26658446
ER
PT J
AU Keutgen, XM
Nilubol, N
Glanville, J
Sadowski, SM
Liewehr, DJ
Venzon, DJ
Steinberg, SM
Kebebew, E
AF Keutgen, Xavier M.
Nilubol, Naris
Glanville, Joanne
Sadowski, Samira M.
Liewehr, David J.
Venzon, David J.
Steinberg, Seth M.
Kebebew, Electron
TI Resection of primary tumor site is associated with prolonged survival in
metastatic nonfunctioning pancreatic neuroendocrine tumors
SO SURGERY
LA English
DT Article
ID ISLET-CELL CARCINOMA; GUIDELINES; FOREGUT
AB Background. Nonfunctioning pancreatic neuroendocrine tumors (NFpNET) present with distant metastases in up to 50% of patients. It is unknown whether removal of the primary tumor in patients with NFpNET and metastases is beneficial.
Methods. We used the Surveillance, Epidemiology, and End Results database to identify patients with NFpNET and distant metastases. The primary outcome measure in this study was overall survival.
Results. We identified 882 patients with metastatic NFpNET who had survival data; 303 (34%) patients had operative removal of their primary tumor of which 243 (80%) were grade I or II. Median survival of patients undergoing resection of the primary site was 65 (95% confidence interval 60-86) versus 10 (8-12) months for those without resection (P < .0001). Patients diagnosed after 2003 (n = 625, 71%) were more likely to undergo an operation than those diagnosed earlier (P = .001). Multivariable analysis showed that a lesser tumor grade (P < .0001), younger age (P < .0001), diagnosis during or after 2003 (P = .0003), tumor site in the body/tail (P = .009), and operative resection of the primary tumor site (P < .0001) were associated with prolonged survival of patients with NFpNET and distant metastases.
Conclusion. This study suggests that resection of the site of the primary NFpNET is associated with greater survival in patients with distant metastases and could therefore be considered as a additional treatment option in this patient population.
C1 [Keutgen, Xavier M.; Nilubol, Naris; Glanville, Joanne; Sadowski, Samira M.; Kebebew, Electron] NCI, EOB, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liewehr, David J.; Venzon, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, EOB, NIH, 10 Ctr Dr,3W-5840, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Intramural NIH HHS [ZID BC011534-01, Z99 CA999999]
NR 20
TC 8
Z9 8
U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JAN
PY 2016
VL 159
IS 1
BP 311
EP 318
DI 10.1016/j.surg.2015.05.042
PG 8
WC Surgery
SC Surgery
GA CZ3UJ
UT WOS:000367029200067
PM 26453135
ER
PT J
AU Hughes, MS
Azoury, SC
Assadipour, Y
Straughan, DM
Trivedi, AN
Lim, RM
Joy, G
Voellinger, MT
Tang, DM
Venkatesan, AM
Chen, CC
Louie, A
Quezado, MM
Forbes, J
Wank, SA
AF Hughes, Marybeth S.
Azoury, Said C.
Assadipour, Yasmine
Straughan, David M.
Trivedi, Apurva N.
Lim, Ramona M.
Joy, Grishma
Voellinger, Mark T.
Tang, Derek M.
Venkatesan, Aradhana M.
Chen, Clara C.
Louie, Adeline
Quezado, Martha M.
Forbes, Joanne
Wank, Stephen A.
TI Prospective evaluation and treatment of familial carcinoid small
intestine neuroendocrine tumors (SI-NETs)
SO SURGERY
LA English
DT Article
ID GASTROINTESTINAL CARCINOIDS; PROGNOSIS; SURVIVAL; SURGERY; THERAPY;
CANCERS; RISK
AB Background. The aim of this study was to prospectively screen patients with a positive family history of carcinoid small intestine neuroendocrine tumors (SI-NETs) to elucidate the benefits of early detection and operative intervention.
Methods. A single-center, prospective trial was conducted from 2008 to 2014 that evaluated patients with 2 or more blood relatives with carcinoid SI-NETs. All eligible patients were screened with urine/serum biochemistries and various imaging modalities. Operative intervention was elected in patients found to have at least 1 positive diagnostic study.
Results. Twenty-nine patients from 13 families had occult carcinoid SI-NETs (15 female, 14 male). Twenty-four of the 29 patients (83%) had multifocal disease found in either the distal jejunum or ileum. On average, 75.9 cm (range, 13-195) of bowel was resected in 1 segment. Three patients were found to have stage IV disease at operation. All stage I-IIIB patients who had R0 resections have remained disease-free, with a median follow-up of 35 months.
Conclusion. Familial carcinoid SI-IVETs often are asymptomatic and can be diagnosed with aggressive screening. With early detection, there may be a window of opportunity for operative resection to change the natural history of this disease and even prove to be curative.
C1 [Hughes, Marybeth S.; Azoury, Said C.; Assadipour, Yasmine; Straughan, David M.] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
[Trivedi, Apurva N.; Lim, Ramona M.; Joy, Grishma; Voellinger, Mark T.; Tang, Derek M.; Forbes, Joanne; Wank, Stephen A.] NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA.
[Venkatesan, Aradhana M.; Chen, Clara C.; Louie, Adeline] NCI, Radiol & Imaging Sci, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Hughes, MS (reprint author), NCI, Thorac & GI Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1201,RM 4W-5940, Bethesda, MD 20892 USA.
EM hughesm@mail.nih.gov
FU Intramural NIH HHS [ZIA DK071010-07, ZIA DK071010-02, ZIA DK071010-03,
ZIA DK071010-05, ZIA DK071010-06]
NR 26
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JAN
PY 2016
VL 159
IS 1
BP 350
EP 356
DI 10.1016/j.surg.2015.05.041
PG 7
WC Surgery
SC Surgery
GA CZ3UJ
UT WOS:000367029200074
PM 26454678
ER
PT J
AU Gern, L
Aeschlimann, A
Schwan, TG
Lane, RS
AF Gern, L.
Aeschlimann, A.
Schwan, T. G.
Lane, R. S.
TI A tribute to Dr. Willy Burgdorfer, Medical Entomologist Extraordinaire
Obituary
SO TICKS AND TICK-BORNE DISEASES
LA English
DT Biographical-Item
C1 [Gern, L.; Aeschlimann, A.] Univ Neuchatel, Inst Biol, CH-2000 Neuchatel, Switzerland.
[Schwan, T. G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Lane, R. S.] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA.
RP Gern, L (reprint author), Univ Neuchatel, Inst Biol, CH-2000 Neuchatel, Switzerland.
EM lise.gern@unine.ch
NR 4
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 1877-959X
EI 1877-9603
J9 TICKS TICK-BORNE DIS
JI Ticks Tick-Borne Dis.
PY 2016
VL 7
IS 1
BP 66
EP 67
DI 10.1016/j.ttbdis.2015.08.006
PG 2
WC Infectious Diseases; Microbiology; Parasitology
SC Infectious Diseases; Microbiology; Parasitology
GA CZ2RX
UT WOS:000366953400010
PM 26929975
ER
PT J
AU Inker, LA
Tighiouart, H
Coresh, J
Foster, MC
Anderson, AH
Beck, GJ
Contreras, G
Greene, T
Karger, AB
Kusek, JW
Lash, J
Lewis, J
Schelling, JR
Navaneethan, SD
Sondheimer, J
Shafi, T
Levey, AS
AF Inker, Lesley A.
Tighiouart, Hocine
Coresh, Josef
Foster, Meredith C.
Anderson, Amanda H.
Beck, Gerald J.
Contreras, Gabriel
Greene, Tom
Karger, Amy B.
Kusek, John W.
Lash, James
Lewis, Julia
Schelling, Jeffrey R.
Navaneethan, Sankar D.
Sondheimer, James
Shafi, Tariq
Levey, Andrew S.
TI GFR Estimation Using beta-Trace Protein and beta(2)-Microglobulin in CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Beta-trace protein (BTP); beta-2-microglobulin (B2M); filtration marker;
chronic kidney disease (CKD); estimated glomerular filtration rate
(eGFR); measured GFR; estimating equation; kidney function; diagnostic
accuracy
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CYSTATIN-C; SERUM
CREATININE; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; RENAL-FUNCTION;
MORTALITY; MARKERS; BETA-2-MICROGLOBULIN
AB Background: beta-Trace protein (BTP) and beta(2)-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers.
Study Design: Study of diagnostic test accuracy.
Setting & Participants: Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m(2) (N = 3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study).
Index Tests: GFR estimated using creatinine, cystatin C, BTP, or B2M level.
Reference Test: GFR measured as the urinary clearance of iothalamate.
Results: For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation.
Limitations: No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race.
Conclusions: BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use. (C) 2016 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Inker, Lesley A.; Tighiouart, Hocine; Foster, Meredith C.; Levey, Andrew S.] Tufts Med Ctr, Boston, MA 02111 USA.
[Tighiouart, Hocine] Tufts CTSI, Res Design Ctr, Biostat Res Ctr, Boston, MA USA.
[Coresh, Josef; Shafi, Tariq] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Anderson, Amanda H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Beck, Gerald J.] Cleveland Clin, Cleveland, OH 44106 USA.
[Contreras, Gabriel] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
[Karger, Amy B.] Univ Minnesota, Minneapolis, MN USA.
[Kusek, John W.] NIDDK, Bethesda, MD 20892 USA.
[Lash, James] Univ Illinois, Chicago, IL USA.
[Lewis, Julia] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Schelling, Jeffrey R.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
[Sondheimer, James] Wayne State Univ, Detroit, MI USA.
[Tighiouart, Hocine] Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
RP Inker, LA (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA.
EM linker@tuftsmedicalcenter.org
FU NIH, National Kidney Foundation (NKF), Pharmalink AB; Gilead Sciences;
NIH, NKF, Amgen, Pharmalink AB; Nephrogenix; Keryx Biopharmaceuticals;
Genkyotex S.A
FX Dr. Inker reports funding to Tufts Medical Center for research and
contracts with the NIH, National Kidney Foundation (NKF), Pharmalink AB,
and Gilead Sciences; a consulting agreement with Otsuka; and has a
provisional patent (Drs Coresh, Inker, and Levey) filed August 15, 2014
(precise estimation of GFR from multiple biomarkers; licensing under
negotiation). Dr Levey reports funding to Tufts Medical Center for
research and contracts with the NIH, NKF, Amgen, Pharmalink AB, and
Gilead Sciences and has the aforementioned provisional patent. Dr Coresh
has the aforementioned provisional patent. Dr Greene is a consultant for
Jansen Pharmaceuticals and Pfizer and reports grants from Nephrogenix,
Keryx Biopharmaceuticals, and Genkyotex S.A. Dr Kusek works at the
NIDDK. The other authors declare that they have no other relevant
financial interests.
NR 37
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U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JAN
PY 2016
VL 67
IS 1
BP 40
EP 48
DI 10.1053/j.ajkd.2015.07.025
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CZ0ZX
UT WOS:000366836500010
PM 26362696
ER
PT J
AU Ward, MM
Dasgupta, A
Wang, RS
AF Ward, Michael M.
Dasgupta, Abhijit
Wang, Runsheng
TI Response to: 'Heterogeneity, consistency and model fit should be
assessed in Bayesian network meta-analysis' by Wei et al
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Letter
C1 [Ward, Michael M.; Dasgupta, Abhijit; Wang, Runsheng] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041153-12]
NR 5
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 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JAN
PY 2016
VL 75
IS 1
BP E6
EP E6
DI 10.1136/annrheumdis-2015-208670
PG 1
WC Rheumatology
SC Rheumatology
GA CY4TW
UT WOS:000366402400006
PM 26621484
ER
PT J
AU Breyer, BN
Huang, WY
Rabkin, CS
Alderete, JF
Pakpahan, R
Beason, TS
Kenfield, SA
Mabie, J
Ragard, L
Wolin, KY
Grubb, RL
Andriole, GL
Sutcliffe, S
AF Breyer, Benjamin N.
Huang, Wen-Yi
Rabkin, Charles S.
Alderete, John F.
Pakpahan, Ratna
Beason, Tracey S.
Kenfield, Stacey A.
Mabie, Jerome
Ragard, Lawrence
Wolin, Kathleen Y.
Grubb, Robert L., III
Andriole, Gerald L.
Sutcliffe, Siobhan
TI Sexually transmitted infections, benign prostatic hyperplasia and lower
urinary tract symptom-related outcomes: results from the Prostate, Lung,
Colorectal and Ovarian Cancer Screening Trial
SO BJU INTERNATIONAL
LA English
DT Article
DE sexually transmitted infection; benign prostatic hyperplasia; nocturia;
Prostate lung colorectal and ovarian cancer screening trial
ID COMMUNITY-HEALTH SURVEY; TRICHOMONAS-VAGINALIS; RISK-FACTORS; DRUG-USE;
MEN; ASSOCIATION; NOCTURIA; GLAND
AB Objective
To examine whether a history of sexually transmitted infections (STIs) or positive STI serology is associated with prevalent and incident benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS)-related outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
Methods
Self-reported history of STIs (gonorrhoea, syphilis) was ascertained at baseline, and serological evidence of STIs (Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus (HPV)-16, HPV-18, herpes simplex virus type 2, human herpesvirus type 8 and cytomegalovirus) was detected in baseline serum specimens. We used data collected on the baseline questionnaire, as well as results from the baseline prostate-specific antigen (PSA) test and digital rectal examination (DRE), to define prevalent BPH/LUTS-related outcomes as evidence of LUTS (self-reported diagnosis of an enlarged prostate/BPH, BPH surgery or nocturia [waking >= 2 times/night to urinate]) and evidence of prostate enlargement (PSA > 1.4 ng/mL or prostate volume >= 30 mL) in men without prostate cancer. We created a similar definition of incident BPH using data from the follow-up questionnaire completed 5-13 years after enrolment (self-reported diagnosis of an enlarged prostate/BPH or nocturia), data on finasteride use during follow-up, and results from the follow-up PSA tests and DREs. We used Poisson regression with robust variance estimation to calculate prevalence ratios (PRs) in our cross-sectional analysis of self-reported (n = 32 900) and serologically detected STIs (n = 1 143) with prevalent BPH/LUTS, and risk ratios in our prospective analysis of self-reported STIs with incident BPH/LUTS (n = 5 226).
Results Generally null results were observed for associations of a self-reported history of STIs and positive STI serologies with prevalent and incident BPH/LUTS-related outcomes, with the possible exception of T. vaginalis infection. This STI was positively associated with prevalent nocturia (PR 1.36, 95% confidence interval (CI) 1.18-1.65), prevalent large prostate volume (PR 1.21 95% CI 1.02-1.43), and any prevalent BPH/LUTS (PR 1.32 95% CI 1.09-1.61); too few men had information on both STI serologies and incident BPH/LUTS to investigate the associations between T. vaginalis infection and incident BPH/LUTS-related outcomes.
Conclusions Our findings do not support associations of several known STIs with BPH/LUTS-related outcomes, although T. vaginalis infection may warrant further study.
C1 [Breyer, Benjamin N.; Kenfield, Stacey A.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
[Huang, Wen-Yi; Rabkin, Charles S.] Natl Canc Inst, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD USA.
[Alderete, John F.] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Pullman, WA 99164 USA.
[Pakpahan, Ratna; Beason, Tracey S.; Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Mabie, Jerome] Informat Management Serv Inc, Rockville, MD USA.
[Ragard, Lawrence] WESTAT Corp, Rockville, MD 20850 USA.
[Wolin, Kathleen Y.] Coeus Hlth, Chicago, IL USA.
[Grubb, Robert L., III; Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Grubb, Robert L., III; Andriole, Gerald L.; Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
RP Breyer, BN (reprint author), Univ Calif San Francisco, Dept Urol, 400 Parnassus Ave,A610, San Francisco, CA 94143 USA.
EM bbreyer@urology.ucsf.edu
OI Sutcliffe, Siobhan/0000-0002-4613-8107
FU NIDDK [R21DK090595]; NCI [R03CA143949]; Barnes-Jewish Hospital
Foundation; [K12DK083021]
FX This study was funded by NIDDK grant R21DK090595, NCI grant R03CA143949,
and the Barnes-Jewish Hospital Foundation. B.N.B. is supported by
K12DK083021.
NR 28
TC 2
Z9 2
U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD JAN
PY 2016
VL 117
IS 1
BP 145
EP 154
DI 10.1111/bju.13050
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA CZ0WM
UT WOS:000366827000023
PM 25601300
ER
PT J
AU Frank, MG
Adhikary, S
Sobesky, JL
Weber, MD
Watkins, LR
Maier, SF
AF Frank, Matthew G.
Adhikary, Sweta
Sobesky, Julia L.
Weber, Michael D.
Watkins, Linda R.
Maier, Steven F.
TI The danger-associated molecular pattern HMGB1 mediates the
neuroinflammatory effects of methamphetamine
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Methamphetamine; Neuroinflammation; Microglia; HMGB1; DAMP;
Neurotoxicity
ID NECROSIS-FACTOR-ALPHA; MOBILITY GROUP BOX-1; MICROGLIAL ACTIVATION;
INDUCED NEUROTOXICITY; DOPAMINERGIC NEUROTOXICITY; DISCRETE REGIONS;
ALARMIN HMGB1; TNF-ALPHA; BRAIN; PROTEIN
AB Methamphetamine (METH) induces neuroinflammatory effects, which may contribute to the neurotoxicity of METH. However, the mechanism by which METH induces neuroinflammation has yet to be clarified. A considerable body of evidence suggests that METH induces cellular damage and distress, particularly in dopaminergic neurons. Damaged neurons release danger-associated molecular patterns (DAMPs) such as high mobility group box-1 (HMGB1), which induces pro-inflammatory effects. Therefore, we explored the notion here that METH induces neuroinflammation indirectly through the release of HMGB1 from damaged neurons. Adult male Sprague-Dawley rats were injected IP with METH (10 mg/kg) or vehicle (0.9% saline). Neuroinflammatory effects of METH were measured in nucleus accumbens (NAcc), ventral tegmental area (VTA) and prefrontal cortex (PFC) at 2 h, 4 h and 6 h after injection. To assess whether METH directly induces pro-inflammatory effects in microglia, whole brain or striatal microglia were isolated using a Percoll density gradient and exposed to METH (0, 0.1, 1, 10, 100, or 1000 mu M) for 24 h and pro-inflammatory cytokines measured. The effect of METH on HMGB1 and IL-1 beta in striatal tissue was then measured. To determine the role of HMGB1 in the neuroinflammatory effects of METH, animals were injected intra-cisterna magna with the HMGB1 antagonist box A (10 mu g) or vehicle (sterile water). 24 h post-injection, animals were injected IP with METH (10 mg/kg) or vehicle (0.9% saline) and 4 h later neuroinflammatory effects measured in NAcc, VTA, and PFC. METH induced robust pro-inflammatory effects in NAcc, VTA, and PFC as a function of time and pro-inflammatory analyte measured. In particular, METH induced profound effects on IL-1 beta in NAcc (2 h) and PFC (2 h and 4 h). Exposure of microglia to METH in vitro failed to induce a pro-inflammatory response, but rather induced significant cell death as well as a decrease in IL-1 beta. METH treatment increased HMGB1 in parallel with IL-1 beta in striatum. Pre-treatment with the HMGB1 antagonist box A blocked the neuroinflammatory effects (IL-1 beta) of METH in NAcc, VTA and PFC. The present results suggest that HMGB1 mediates, in part, the neuroinflammatory effects of METH and thus may alert CNS innate immune cells to the toxic effects of METH. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Frank, Matthew G.; Sobesky, Julia L.; Weber, Michael D.; Watkins, Linda R.; Maier, Steven F.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Frank, Matthew G.; Sobesky, Julia L.; Weber, Michael D.; Watkins, Linda R.; Maier, Steven F.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
[Adhikary, Sweta] Natl Inst Hlth, Natl Inst Drug Abuse, Bethesda, MD USA.
RP Frank, MG (reprint author), Univ Colorado, Dept Psychol & Neurosci, Campus Box 345, Boulder, CO 80309 USA.
EM matt.frank@colorado.edu
OI Sobesky, Julia/0000-0001-5293-097X
FU DOD Grant [W81XWH-11-1-0637]
FX The present work was supported by a DOD Grant (W81XWH-11-1-0637) to
M.G.F. and S.F.M.
NR 50
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Z9 5
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 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD JAN
PY 2016
VL 51
BP 99
EP 108
DI 10.1016/j.bbi.2015.08.001
PG 10
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA CY7WD
UT WOS:000366619100010
PM 26254235
ER
PT J
AU Kon, AA
Davidson, JE
Morrison, W
Danis, M
White, DB
AF Kon, Alexander A.
Davidson, Judy E.
Morrison, Wynne
Danis, Marion
White, Douglas B.
TI Shared Decision Making in ICUs: An American College of Critical Care
Medicine and American Thoracic Society Policy Statement
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE critical care; decision making; intensive care; intensive care units;
resuscitation orders
ID OF-LIFE CARE; INTERNATIONAL CONSENSUS CONFERENCE; INFORMED NON-DISSENT;
INTENSIVE-CARE; SUBSTITUTED JUDGMENT; SUPPORT DECISIONS;
CLINICAL-PRACTICE; DEFAULT OPTIONS; FAMILY-MEMBERS; ILL PATIENTS
AB Objectives: Shared decision making is endorsed by critical care organizations; however, there remains confusion about what shared decision making is, when it should be used, and approaches to promote partnerships in treatment decisions. The purpose of this statement is to define shared decision making, recommend when shared decision making should be used, identify the range of ethically acceptable decision-making models, and present important communication skills.
Design: The American College of Critical Care Medicine and American Thoracic Society Ethics Committees reviewed empirical research and normative analyses published in peer-reviewed journals to generate recommendations. Recommendations approved by consensus of the full Ethics Committees of American College of Critical Care Medicine and American Thoracic Society were included in the statement.
Main Results: Six recommendations were endorsed: 1) Definition: Shared decision making is a collaborative process that allows patients, or their surrogates, and clinicians to make healthcare decisions together, taking into account the best scientific evidence available, as well as the patient's values, goals, and preferences. 2) Clinicians should engage in a shared decision making process to define overall goals of care (including decisions regarding limiting or withdrawing life-prolonging interventions) and when making major treatment decisions that may be affected by personal values, goals, and preferences. 3) Clinicians should use as their default approach a shared decision making process that includes three main elements: information exchange, deliberation, and making a treatment decision. 4) A wide range of decision-making approaches are ethically supportable, including patient- or surrogate-directed and clinician-directed models. Clinicians should tailor the decision-making process based on the preferences of the patient or surrogate. 5) Clinicians should be trained in communication skills. 6) Research is needed to evaluate decision-making strategies.
Conclusions: Patient and surrogate preferences for decision-making roles regarding value-laden choices range from preferring to exercise significant authority to ceding such authority to providers. Clinicians should adapt the decision-making model to the needs and preferences of the patient or surrogate.
C1 [Kon, Alexander A.] Naval Med Ctr San Diego, Pediat Crit Care Med, San Diego, CA 92134 USA.
[Kon, Alexander A.] Univ Calif San Diego, Dept Pediat, Sch Med, San Diego, CA 92103 USA.
[Davidson, Judy E.] Univ Calif Hlth Syst, San Diego, CA USA.
[Morrison, Wynne] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[White, Douglas B.] Univ Pittsburgh, Sch Med, Program Eth & Decis Making Crit Illness, Pittsburgh, PA USA.
[White, Douglas B.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA.
RP Kon, AA (reprint author), Naval Med Ctr San Diego, Pediat Crit Care Med, San Diego, CA 92134 USA.
EM kon.sandiego@gmail.com
FU Greenwall Foundation's Faculty Scholars in Bioethics program; Greenwall
Foundation; Moore Foundation; Greenwall Foundation Faculty Scholars in
Bioethics; On Data Monitoring Committee for Glaxo-Smith-Klein; National
Institutes of Health (NIH); NIH
FX Dr. Kon is the President-elect of the American Society for Bioethics and
Humanities, an Associate Editor for AJOB Empirical Research Bioethics,
and receives funding from the Greenwall Foundation's Faculty Scholars in
Bioethics program. Dr. Davidson holds a business license for a private
education company; however, she has earned no income related to the
topic presented in this statement. She also provides research-related
volunteer services to American Association of Critical Care Nurses and
Sima Theta Tau International on topics not related to those presented in
this statement. Dr. Morrison is a member of a data monitoring committee
for Glaxo Smith Klein on research not related to the topics covered in
this statement, is a speaker and committee member of the American
Society for Bioethics and Humanities, and is an editorial board member
for the American Academy of Pediatrics. Dr. Danis has professional
relationships with the American Society for Bioethics and Humanities and
the Society of General Internal Medicine not directly related to the
topics covered in this statement. Dr. White receives grant funding from
the Greenwall Foundation and from the Moore Foundation. Potential
conflicts of interest for members of the writing group were reviewed
based on American College of Critical Care Medicine standard operating
procedure. No potential conflicts relating to the content of this
statement were identified.; Dr. Kon received funding from the Greenwall
Foundation Faculty Scholars in Bioethics (The Foundation pays travel
expenses for semiannual scholars' meeting and from American Society for
Bioethics and Humanities. Dr. Kon was a member of the Board of Directors
and was therefore reimbursed for travel expenses to Board meetings) and
he disclosed government work. Dr. Morrison received support from several
grand rounds presentations at other academic institutions with honoraria
and received funding from the On Data Monitoring Committee for
Glaxo-Smith-Klein (paid consultant position, but no payment yet
received). Dr. Danis received support for article research from the
National Institutes of Health (NIH), disclosed government work, and is
an employee of the NIH (Her work on this project has been supported by
the intramural program of the NIH. The views expressed in this paper are
not necessarily a reflection of the policies of the NIH or the US Dept
of Health and Human Service). Dr. White received support for article
research from the NIH. Dr. Davidson disclosed that she does not have any
potential conflicts of interest.
NR 78
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U1 3
U2 7
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 JAN
PY 2016
VL 44
IS 1
BP 188
EP 201
DI 10.1097/CCM.0000000000001396
PG 14
WC Critical Care Medicine
SC General & Internal Medicine
GA CY7QZ
UT WOS:000366605100022
PM 26509317
ER
PT J
AU Cruz, FC
Duarte, JO
Leao, RM
Hummel, LFV
Planeta, CS
Crestani, CC
AF Cruz, Fabio C.
Duarte, Josiane O.
Leao, Rodrigo M.
Hummel, Luiz F. V.
Planeta, Cleopatra S.
Crestani, Carlos C.
TI Adolescent vulnerability to cardiovascular consequences of chronic
social stress: Immediate and long-term effects of social isolation
during adolescence
SO DEVELOPMENTAL NEUROBIOLOGY
LA English
DT Article
DE stress; blood pressure; heart rate; baroreflex; vascular reactivity;
ontogeny
ID FEMALE CYNOMOLGUS MONKEYS; CHRONIC HEART-FAILURE; LOW PULSE PRESSURE;
MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION;
ESSENTIAL-HYPERTENSION; UNANESTHETIZED RATS; ANIMAL-MODELS; NITRIC-OXIDE
AB It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. (c) 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 34-46, 2016
C1 [Cruz, Fabio C.; Duarte, Josiane O.; Leao, Rodrigo M.; Hummel, Luiz F. V.; Planeta, Cleopatra S.; Crestani, Carlos C.] Sao Paulo State Univ, Pharmacol Lab, Dept Nat Act Principles & Toxicol, Sch Pharmaceut Sci,UNESP, Araraquara, SP, Brazil.
[Cruz, Fabio C.; Leao, Rodrigo M.] NIDA, Dept Hlth & Human Serv, Behav Neurosci Branch, Intramural Res Program,US Natl Inst Hlth, Baltimore, MD USA.
[Duarte, Josiane O.; Planeta, Cleopatra S.; Crestani, Carlos C.] Joint UFSCar UNESP, Grad Program Physiol Sci, Sao Carlos, SP, Brazil.
RP Crestani, CC (reprint author), Sao Paulo State Univ, Pharmacol Lab, Dept Nat Act Principles & Toxicol, Sch Pharmaceut Sci,UNESP, Araraquara, SP, Brazil.
EM cccrestani@yahoo.com.br
RI Crestani, Carlos/E-4161-2012
FU Sao Paulo Research Foundation (FAPESP) [2012/14376-0, 2012/50549-6];
PADC/FCF-UNESP
FX Contract grant sponsor: Sao Paulo Research Foundation (FAPESP); contract
grant number: 2012/14376-0 and 2012/50549-6. Contract grant sponsor:
PADC/FCF-UNESP.
NR 60
TC 2
Z9 2
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-8451
EI 1932-846X
J9 DEV NEUROBIOL
JI Dev. Neurobiol.
PD JAN
PY 2016
VL 76
IS 1
BP 34
EP 46
DI 10.1002/dneu.22297
PG 13
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA CY7OG
UT WOS:000366597500003
PM 25914339
ER
PT J
AU Rodriguez, S
Gaunt, TR
Guo, YR
Zheng, J
Barnes, MR
Tang, WH
Danish, F
Johnson, A
Castillo, BA
Li, YR
Hakonarson, H
Buxbaum, SG
Palmer, T
Tsai, MY
Lange, LA
Ebrahim, S
Smith, GD
Lawlor, DA
Folsom, AR
Hoogeveen, R
Reiner, A
Keating, B
Day, INM
AF Rodriguez, Santiago
Gaunt, Tom R.
Guo, Yiran
Zheng, Jie
Barnes, Michael R.
Tang, Weihang
Danish, Fazal
Johnson, Andrew
Castillo, Berta A.
Li, Yun R.
Hakonarson, Hakon
Buxbaum, Sarah G.
Palmer, Tom
Tsai, Michael Y.
Lange, Leslie A.
Ebrahim, Shah
Smith, George Davey
Lawlor, Debbie A.
Folsom, Aaron R.
Hoogeveen, Ron
Reiner, Alex
Keating, Brendan
Day, Ian N. M.
TI Lipids, obesity and gallbladder disease in women: insights from genetic
studies using the cardiovascular gene-centric 50K SNP array
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CHOLESTEROL GALLSTONE FORMATION; GENOME-WIDE ASSOCIATION; RISK-FACTORS;
LOCI; DYSLIPIDEMIA; METAANALYSIS; DESIGN; HEALTH; HEART; MICE
AB Gallbladder disease (GBD) has an overall prevalence of 10-40% depending on factors such as age, gender, population, obesity and diabetes, and represents a major economic burden. Although gallstones are composed of cholesterol by-products and are associated with obesity, presumed causal pathways remain unproven, although BMI reduction is typically recommended. We performed genetic studies to discover candidate genes and define pathways involved in GBD. We genotyped 15 241 women of European ancestry from three cohorts, including 3216 with GBD, using the Human cardiovascular disease (HumanCVD) BeadChip containing up to similar to 53 000 single-nucleotide polymorphisms (SNPs). Effect sizes with P-values for development of GBD were generated. We identify two new loci associated with GBD, GCKR rs1260326: T>C (P=5.88 x 10(-7), beta=-0.146) and TTC39B rs686030:C>A (P=6.95x10(-7), beta=0.271) and detect four independent SNP effects in ABCG8 rs4953023:G>A (P=7.41 x 10(-47), beta= 0.734), ABCG8 rs4299376:G>T (P=2.40 x 10(-18), beta= 0.278), ABCG5 rs6544718:T>C (P=2.08 x 10(-14), beta= 0.044) and ABCG5 rs6720173:G>C (P=3.81 x 10(-12), beta=0.262) in conditional analyses taking genotypes of rs4953023:G>A as a covariate. We also delineate the risk effects among many genotypes known to influence lipids. These data, from the largest GBD genetic study to date, show that specific, mainly hepatocyte-centred, components of lipid metabolism are important to GBD risk in women. We discuss the potential pharmaceutical implications of our findings.
C1 [Rodriguez, Santiago; Gaunt, Tom R.; Zheng, Jie; Danish, Fazal; Day, Ian N. M.] Univ Bristol, Sch Social & Community Med, Bristol Genet Epidemiol Labs, Bristol BS8 2BN, Avon, England.
[Gaunt, Tom R.; Smith, George Davey; Lawlor, Debbie A.] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit IEU, Bristol BS8 2BN, Avon, England.
[Guo, Yiran; Castillo, Berta A.; Li, Yun R.; Hakonarson, Hakon; Keating, Brendan] Univ Penn, Dept Surg, Div Transplantat, Philadelphia, PA 19104 USA.
[Guo, Yiran] BGI Shenzhen, Beishan Ind Zone, Shenzhen, Peoples R China.
[Barnes, Michael R.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Natl Inst Hlth,Biomed Res Unit, London, England.
[Tang, Weihang; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Johnson, Andrew] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Buxbaum, Sarah G.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA.
[Buxbaum, Sarah G.] Jackson State Univ, Dept Epidemiol & Biostat, Sch Hlth Sci, Jackson, MS USA.
[Palmer, Tom] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
[Tsai, Michael Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Lange, Leslie A.] Univ N Carolina, Sch Med Chapel Hill, Dept Genet, Chapel Hill, NC USA.
[Ebrahim, Shah] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Hoogeveen, Ron] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Keating, Brendan] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
RP Day, INM (reprint author), Univ Bristol, Sch Social & Community Med, Bristol Genet Epidemiol Labs, Oakfield House, Bristol BS8 2BN, Avon, England.
EM ian.day@bristol.ac.uk
RI Guo, Yiran/H-4120-2011; Gaunt, Tom/O-3918-2014; Johnson,
Andrew/G-6520-2013; Davey Smith, George/A-7407-2013;
OI Guo, Yiran/0000-0002-6549-8589; Gaunt, Tom/0000-0003-0924-3247; Davey
Smith, George/0000-0002-1407-8314; Li, Yun Rose/0000-0002-8077-4975;
Lawlor, Debbie A/0000-0002-6793-2262
FU National Heart, Lung, and Blood Institute; NHLBI [HHSN268200960009C];
National Heart, Lung and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
[HHSN268200625226C]; component of the National Institutes of Health
[UL1RR025005]; NIH Roadmap for Medical Research; British Heart
Foundation (BHF); Department of Health Policy Research Programme
(England); BHF [PG/07/131/24254]; National Heart, Lung and Blood
Institute, National Institutes of Health, US Department of Health and
Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13,
32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; UK Medical
Research Council (MRC); University of Bristol [G0600705]; MRC project
[MR/K002767/1]
FX The CARe Consortium wishes to acknowledge the support of the National
Heart, Lung, and Blood Institute and the contributions of the research
institutions, study investigators, field staff and study participants in
creating this resource for biomedical research (NHLBI contract number
HHSN268200960009C). The following nine parent studies have contributed
parent study data, ancillary study data and DNA samples through the
Massachusetts Institute of Technology-Broad Institute (N01-HC-65226) to
create this genotype/phenotype database for wide dissemination to the
biomedical research community: the ARIC study, the CHS, the CFS, the
Cooperative Study of Sickle Cell Disease (CSSCD), the CARDIA study, the
FHS, the JHS, the MESA and the SHHS.; ARIC: The ARIC study 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),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. We thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research.; BWHHS: The
BWHHS is supported by funding from the British Heart Foundation (BHF)
and the Department of Health Policy Research Programme (England).
HumanCVD genotyping of the BWHHHS was funded by the BHF
(PG/07/131/24254).; WHI: The WHI program is funded by the National
Heart, Lung and Blood Institute, National Institutes of Health, US
Department of Health and Human Services through contracts N01WH22110,
24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221.; The UK Medical Research Council (MRC)
and the University of Bristol provide core funding for the MRC Centre of
Causal Analyses in Translational Epidemiology (MRC grant G0600705). This
work was also supported by the MRC project grant MR/K002767/1.
NR 33
TC 4
Z9 4
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JAN
PY 2016
VL 24
IS 1
BP 106
EP 112
DI 10.1038/ejhg.2015.63
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CY7UO
UT WOS:000366615000017
PM 25920552
ER
PT J
AU Cuellar-Partida, G
Lu, Y
Kho, PF
Hewitt, AW
Wichmann, HE
Yazar, S
Stambolian, D
Bailey-Wilson, JE
Wojciechowski, R
Wang, JJ
Mitchell, P
Mackey, DA
MacGregor, S
AF Cuellar-Partida, Gabriel
Lu, Yi
Kho, Pik Fang
Hewitt, Alex W.
Wichmann, H. -Erich
Yazar, Seyhan
Stambolian, Dwight
Bailey-Wilson, Joan E.
Wojciechowski, Robert
Wang, Jie Jin
Mitchell, Paul
Mackey, David A.
MacGregor, Stuart
TI Assessing the Genetic Predisposition of Education on Myopia: A Mendelian
Randomization Study
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE Mendelian randomization; myopia; refractive error; education; polygenic
risk scores; instrumental variable
ID UNCORRECTED REFRACTIVE ERROR; BLUE MOUNTAINS EYE; VISUAL IMPAIRMENT;
ASSOCIATION; POPULATION; ATTAINMENT; VARIANTS; EPIDEMIOLOGY; PREVALENCE;
CHILDREN
AB Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 +/- 0.29 diopters (P = 1.04 x 10(-3)). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 +/- 0.03 diopters reduction per education z-score [approximate to 2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. (C) 2015 Wiley Periodicals, Inc.
C1 [Cuellar-Partida, Gabriel; Lu, Yi; MacGregor, Stuart] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia.
[Kho, Pik Fang] QIMR Berghofer Med Res Inst, Dept Epidemiol, Brisbane, Qld, Australia.
[Hewitt, Alex W.] Univ Tasmania, Sch Med, Menzies Res Inst Tasmania, Hobart, Tas, Australia.
[Wichmann, H. -Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H. -Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, D-80290 Munich, Germany.
[Yazar, Seyhan; Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
[Wojciechowski, Robert] Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst Med Res, Ctr Vis Res, Sydney, NSW 2006, Australia.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Dept Ophthalmol, Sydney, NSW 2006, Australia.
RP Cuellar-Partida, G (reprint author), QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia.
EM Gabriel.Cuellar@qimrberghofer.edu.au;
Stuart.MacGregor@qimrberghofer.edu.au
RI Mitchell, Paul/P-1498-2014; Hewitt, Alex/D-1936-2013; Macgregor,
Stuart/C-6442-2009; Wang, Jie Jin/P-1499-2014; Cuellar Partida,
Gabriel/C-6686-2017;
OI Hewitt, Alex/0000-0002-5123-5999; Macgregor, Stuart/0000-0001-6731-8142;
Wang, Jie Jin/0000-0001-9491-4898; Cuellar Partida,
Gabriel/0000-0001-7648-4097; Bailey-Wilson, Joan/0000-0002-9153-2920;
Wojciechowski, Robert/0000-0002-9593-4652; Mackey,
David/0000-0001-7914-4709
FU Intramural NIH HHS [Z01 HG200327-03]; NEI NIH HHS [R01 EY020483, K08
EY022943, K08EY022943, R01 EY024233]
NR 48
TC 7
Z9 7
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2016
VL 40
IS 1
BP 66
EP 72
DI 10.1002/gepi.21936
PG 7
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CY7RF
UT WOS:000366605700006
PM 26497973
ER
PT J
AU Begum, F
Ruczinski, I
Li, SC
Silverman, EK
Cho, MH
Lynch, DA
Curran-Everett, D
Crapo, J
Scharpf, RB
Parker, MM
Hetmanski, JB
Beaty, TH
AF Begum, Ferdouse
Ruczinski, Ingo
Li, Shengchao
Silverman, Edwin K.
Cho, Michael H.
Lynch, David A.
Curran-Everett, Douglas
Crapo, James
Scharpf, Robert B.
Parker, Margaret M.
Hetmanski, Jacqueline B.
Beaty, Terri H.
TI Identifying a Deletion Affecting Total Lung Capacity Among Subjects in
the COPDGene Study Cohort
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE COPD; copy number variant (CNV); total lung capacity (TLCCT); pulmonary
function; lung hyperinflation; genome-wide association study (GWAS)
ID OBSTRUCTIVE PULMONARY-DISEASE; GENOME-WIDE ASSOCIATION; LOCUS;
HYPERINFLATION; EPIDEMIOLOGY; EXPRESSION; EMPHYSEMA; VARIANTS; RISK
AB Chronic obstructive pulmonary disease (COPD) is a progressive disease with both environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified multiple genomic regions influencing risk of COPD. To thoroughly investigate the genetic etiology of COPD, however, it is also important to explore the role of copy number variants (CNVs) because the presence of structural variants can alter gene expression and can be causal for some diseases. Here, we investigated effects of polymorphic CNVs on quantitative measures of pulmonary function and chest computed tomography (CT) phenotypes among subjects enrolled in COPDGene, a multisite study. COPDGene subjects consist of roughly one-third African American (AA) and two-thirds non-Hispanic white adult smokers (with or without COPD). We estimated CNVs using PennCNV on 9,076 COPDGene subjects using Illumina's Omni-Express genome-wide marker array. We tested for association between polymorphic CNV components (defined as disjoint intervals of copy number regions) for several quantitative phenotypes associated with COPD within each racial group. Among the AAs, we identified a polymorphic CNV on chromosome 5q35.2 located between two genes (FAM153B and SIMK1, but also harboring several pseudo-genes) giving genome-wide significance in tests of association with total lung capacity (TLCCT) as measured by chest CT scans. This is the first study of genome-wide association tests of polymorphic CNVs and TLCCT. Although the ARIC cohort did not have the phenotype of TLCCT, we found similar counts of CNV deletions and amplifications among AA and European subjects in this second cohort. (C) 2015 Wiley Periodicals, Inc.
C1 [Begum, Ferdouse; Parker, Margaret M.; Hetmanski, Jacqueline B.; Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Li, Shengchao] NCI, Canc Genom Res Lab CGR, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Silverman, Edwin K.; Cho, Michael H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Lynch, David A.; Crapo, James] Natl Jewish Hlth, Dept Med, Denver, CO USA.
[Curran-Everett, Douglas] Natl Jewish Hlth, Div Biostat & Bioinformat, Denver, CO USA.
[Scharpf, Robert B.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
RP Begum, F (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM fbegum1@jhu.edu
FU NCRR NIH HHS [UL1 RR025005, UL1RR025005]; NHGRI NIH HHS [U01 HG004402];
NHLBI NIH HHS [HHSN268201100005C, HHSN268201100005G, HHSN268201100005I,
HHSN268201100006C, HHSN268201100007C, HHSN268201100007I,
HHSN268201100008C, HHSN268201100008I, HHSN268201100009C,
HHSN268201100009I, HHSN268201100010C, HHSN268201100011C,
HHSN268201100011I, HHSN268201100012C, R01 HL059367, R01 HL086694, R01
HL087641, R01 HL089856, R01 HL089897, R01 HL113264, R01HL087641,
R01HL59367, R01HL086694]; PHS HHS [HHSN268200625226C, HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]
NR 41
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2016
VL 40
IS 1
BP 81
EP 88
DI 10.1002/gepi.21943
PG 8
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CY7RF
UT WOS:000366605700008
PM 26643968
ER
PT J
AU Eke, I
Hehlgans, S
Sandfort, V
Cordes, N
AF Eke, Iris
Hehlgans, Stephanie
Sandfort, Veit
Cordes, Nils
TI 3D matrix-based cell cultures: Automated analysis of tumor cell survival
and proliferation
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE molecular therapeutics; 3D cell culture; extracellular matrix;
clonogenicity; proliferation; therapy testing
ID BREAST-CANCER; 3-DIMENSIONAL CULTURE; EPITHELIAL-CELLS; MAMMALIAN-CELLS;
CARCINOMA-CELLS; STEM-CELLS; IN-VITRO; RESISTANCE; GROWTH; INHIBITION
AB Three-dimensional ex vivo cell cultures mimic physiological in vivo growth conditions thereby significantly contributing to our understanding of tumor cell growth and survival, therapy resistance and identification of novel potent cancer targets. In the present study, we describe advanced three-dimensional cell culture methodology for investigating cellular survival and proliferation in human carcinoma cells after cancer therapy including molecular therapeutics. Single cells are embedded into laminin-rich extracellular matrix and can be treated with cytotoxic drugs, ionizing or UV radiation or any other substance of interest when consolidated and approximating in vivo morphology. Subsequently, cells are allowed to grow for automated determination of clonogenic survival (colony number) or proliferation (colony size). The entire protocol of 3D cell plating takes similar to 1 h working time and pursues for similar to 7 days before evaluation. This newly developed method broadens the spectrum of exploration of malignant tumors and other diseases and enables the obtainment of more reliable data on cancer treatment efficacy.
C1 [Eke, Iris; Hehlgans, Stephanie; Cordes, Nils] Tech Univ Dresden, Med Fac Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany.
[Eke, Iris] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hehlgans, Stephanie] Goethe Univ Frankfurt, Dept Radiotherapy & Oncol, D-60590 Frankfurt, Germany.
[Sandfort, Veit] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Cordes, Nils] Univ Hosp, Dept Radiat Oncol, D-01307 Dresden, Germany.
[Cordes, Nils] Tech Univ Dresden, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany.
[Cordes, Nils] Helmholtz Ctr Dresden Rossendorf, Inst Radiooncol, D-01328 Dresden, Germany.
[Cordes, Nils] German Canc Consortium DKTK, D-01307 Dresden, Germany.
[Cordes, Nils] German Canc Res Ctr, D-69120 Heidelberg, Germany.
RP Cordes, N (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, Fetscherstr 74-PF 41, D-01307 Dresden, Germany.
EM nils.cordes@oncoray.de
OI Cordes, Nils/0000-0001-5684-629X
FU Bundesministerium fur Bildung und Forschung (BMBF) [03ZIK041,
BMBF-02NUK006B]; Deutsche Forschungsgemeinschaft [CO668/4-1]; Deutsche
Krebshilfe [108976]; EFRE Europaische Fonds fur regionale Entwicklung,
Europa fordert Sachsen [100066308]; NIH Intramural Research Program,
National Cancer Institute, Center for Cancer Research
FX The authors were in part supported by a grant from the Bundesministerium
fur Bildung und Forschung (BMBF Contracts 03ZIK041 and BMBF-02NUK006B to
N.C.), the Deutsche Forschungsgemeinschaft (CO668/4-1 to N.C.), the
Deutsche Krebshilfe (108976 to N.C.), the EFRE Europaische Fonds fur
regionale Entwicklung, Europa fordert Sachsen (100066308) and by the NIH
Intramural Research Program, National Cancer Institute, Center for
Cancer Research (to I.E.).
NR 40
TC 7
Z9 7
U1 2
U2 9
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD JAN
PY 2016
VL 48
IS 1
BP 313
EP 321
DI 10.3892/ijo.2015.3230
PG 9
WC Oncology
SC Oncology
GA CZ1WT
UT WOS:000366897300033
PM 26549537
ER
PT J
AU Brown, M
Bernhard, E
Mitchel, J
Stone, H
AF Brown, Martin
Bernhard, Eric
Mitchel, James
Stone, Helen
TI Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma
Multiforme
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID MOTEXAFIN GADOLINIUM; TEXAPHYRIN; TRIALS
C1 [Brown, Martin] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA.
[Bernhard, Eric] NCI, Radiat Res Program, NIH, Rockville, MD USA.
[Mitchel, James] NCI, Radiat Biol Branch, NIH, Rockville, MD USA.
[Stone, Helen] NCI, Radiat Res Program, NIH, Rockville, MD USA.
RP Brown, M (reprint author), Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA.
NR 10
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 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JAN 1
PY 2016
VL 94
IS 1
BP 210
EP 211
DI 10.1016/j.ijrobp.2015.08.047
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CY7FU
UT WOS:000366574700043
PM 26700716
ER
PT J
AU Brown, LK
Kennard, BD
Emslie, GJ
Mayes, TL
Whiteley, LB
Bethel, J
Xu, JH
Thornton, S
Tanney, MR
Hawkins, LA
Garvie, PA
Subramaniam, GA
Worrell, CJ
Stoff, LW
AF Brown, Larry K.
Kennard, Betsy D.
Emslie, Graham J.
Mayes, Taryn L.
Whiteley, Laura B.
Bethel, James
Xu, Jiahong
Thornton, Sarah
Tanney, Mary R.
Hawkins, Linda A.
Garvie, Patricia A.
Subramaniam, Geetha A.
Worrell, Carol J.
Stoff, Laura W.
CA Adolescent Trials Network HIV AIDS
TI Effective Treatment of Depressive Disorders in Medical Clinics for
Adolescents and Young Adults Living With HIV: A Controlled Trial
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE major depressive disorder; cognitive behavioral therapy;
antidepressants; youth; young adults; HIV
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL;
SEROTONIN-REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY;
QUALITY-OF-LIFE; MAJOR DEPRESSION; ANTIRETROVIRAL THERAPY; RESISTANT
DEPRESSION; COLLABORATIVE CARE; QUICK INVENTORY
AB Objective:Preliminary test of a manualized, measurement-guided treatment for depression for adolescents and young adults in care at 4 sites of the Adolescent Trials Network for HIV/AIDS Interventions.Design:The US sites were randomly assigned to either a 24-week, combination cognitive behavioral therapy and medication management algorithm (COMB) tailored for youth living with HIV (YLWH) or to treatment as usual (TAU).Methods:Youth at TAU sites had access to therapists and medication management as needed. COMB-site clinicians were trained in the manualized intervention and participated in supervision calls to monitor intervention fidelity.Results:Over the course of the study with 44 participants, those in COMB, compared with those in TAU, reported fewer depressive symptoms, P < 0.01 (as measured by the Quick Inventory for Depression symptoms) and were more likely to be in remission, P < 0.001 (65% vs. 10% at week 24, end of treatment, and 71% vs. 7% at week 48, final follow-up). A greater proportion of COMB participants received psychotherapy (95% vs. 45%, P < 0.001) and attended more sessions (12.6 vs. 5, P < 0.001) than those in TAU. Viral load decreased in both groups and was associated (P < 0.05) with reduction in depressive symptoms.Conclusions:A 24-week manualized, measurement-guided psychotherapy and medication management algorithm tailored for YLWH was more effective in achieving and sustaining remission from depression than TAU at HIV care clinic sites. Given observed treatment efficacy, this structured combination treatment could be disseminated to medical clinics to successfully treat YLWH, who are at particular risk for depression.
C1 [Brown, Larry K.; Whiteley, Laura B.; Stoff, Laura W.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Psychiat, Providence, RI 02903 USA.
[Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Bethel, James; Xu, Jiahong; Thornton, Sarah] WESTAT Corp, Rockville, MD 20850 USA.
[Tanney, Mary R.; Hawkins, Linda A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Garvie, Patricia A.] Childrens Diagnost & Treatment Ctr, Ft Lauderdale, FL USA.
[Subramaniam, Geetha A.] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[Worrell, Carol J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Brown, LK (reprint author), Brown Univ, Alpert Med Sch, Rhode Isl Hosp, 167 Point St, Providence, RI 02903 USA.
EM larry_brown@brown.edu
FU NIH through the Eunice Kennedy Shriver National Institute of Child
Health and Human Development [U01 HD 040533, U01 HD 040474]; National
Institutes on Drug Abuse and Mental Health; Lifespan Tufts Brown Center
for AIDS Research, a NIH [P30 AI 042853]; National Institute on Drug
Abuse (NIDA) at the National Institutes of Health
FX Research supported by NIH grants U01 HD 040533 and U01 HD 040474 through
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development with supplemental funding from the National Institutes on
Drug Abuse and Mental Health. Support also provided by the Lifespan
Tufts Brown Center for AIDS Research, a NIH-funded program (P30 AI
042853, PI: C. Carpenter).; G.A.S. is an employee of the National
Institute on Drug Abuse (NIDA) at the National Institutes of Health,
which co-funded this research study. She served as scientific
collaborator on the U award but had no role with respect to the P30
grant. The content of this manuscript does not in any way reflect the
official position of NIDA. The remaining authors have no conflicts of
interest to disclose.
NR 50
TC 0
Z9 0
U1 3
U2 8
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 JAN 1
PY 2016
VL 71
IS 1
BP 38
EP 46
DI 10.1097/QAI.0000000000000803
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CY9GL
UT WOS:000366715300006
PM 26761270
ER
PT J
AU Deschamps, MM
Metch, B
Morgan, CA
Zorilla, CD
Donastorg, Y
Swann, E
Taina, D
Patrice, J
Pape, WJ
AF Deschamps, Marie M.
Metch, Barbara
Morgan, Cecilia A.
Zorilla, Carmen D.
Donastorg, Yeycy
Swann, Edith
Taina, Dadaille
Patrice, Joseph
Pape, William J.
CA HVTN 907 Study Team
TI Feasibility of Identifying a Female Sex Worker Cohort at High Risk of
HIV Infection in the Caribbean for HIV Vaccine Efficacy Trials:
Longitudinal Results of HVTN 907
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; vaccine trial; women; female sex workers; Caribbean
ID UNITED-STATES; WOMEN; ACQUISITION
AB Background:Identifying cohorts of Caribbean women with HIV infection rates sufficient for inclusion in HIV vaccine efficacy trials has been challenging. HVTN 907 determined the feasibility of identifying and retaining a cohort of women at high risk for HIV acquisition by focusing recruitment on female sex workers (FSWs).Methods:HIV uninfected FSWs, residing in Haiti, Dominican Republic, and Puerto Rico, who reported unprotected sex and met previously described more stringent site-specific eligibility criteria, were eligible. Behavioral risk assessment, HIV counseling and testing, and pregnancy testing were performed at baseline, 6, 12, and 18 months.Results:Among 799 FSWs (264 from Dominican Republic, 334 from Haiti, and 201 from Puerto Rico), the median age was 26 years, with 54% having less than a high school education and 45% having a monthly household income of less than $US 100. Median number of male partners 6 months before screening was 200. Retention at 18 months was 93%. Twelve women became HIV infected, 9 from Haiti. The annualized HIV incidence was 1.07% (95% confidence interval: 0.55% to 1.87%). Pregnancy incidence was 22.5% (95% confidence interval: 21.9% to 29.5%). Statistically significant declines in risk behaviors occurred between screening and the 18-month visit assessment.Discussion:The HVTN 907 study identified a high-risk cohort of women with excellent retention for all 3 sites, despite major challenges especially in Haiti. These results show that a bridging study of a vaccine shown to be efficacious in other clade settings would be possible among FSWs in the region, particularly in Haiti.
C1 [Deschamps, Marie M.; Taina, Dadaille; Patrice, Joseph; Pape, William J.] GHESKIO, Port Au Prince 6110, Haiti.
[Metch, Barbara; Morgan, Cecilia A.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Zorilla, Carmen D.] Univ Puerto Rico, Sch Med, Maternal & Infant Studies Ctr CEMI, San Juan, PR 00936 USA.
[Donastorg, Yeycy] Unidad Vacunas IDCP COIN DIGECITSS, Santo Domingo, Dominican Rep.
[Swann, Edith] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Deschamps, MM (reprint author), GHESKIO, 33 Blvd Harry Truman, Port Au Prince 6110, Haiti.
EM mariehd@gheskio.org
FU HIV Vaccine Trials Network through Division of AIDS, National Institute
of Allergy and Infectious Disease, National Institutes of Health
[UO1AI068614, UO1AI068635, UO1AI068618, U01AI069415, 5U01AI069421,
5U01AI069486]
FX Supported by the HIV Vaccine Trials Network, which is funded through a
cooperative agreement with the Division of AIDS, National Institute of
Allergy and Infectious Disease, National Institutes of Health, Grants
UO1AI068614, UO1AI068635, UO1AI068618, U01AI069415, 5U01AI069421, and
5U01AI069486.
NR 21
TC 1
Z9 1
U1 0
U2 2
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 JAN 1
PY 2016
VL 71
IS 1
BP 70
EP 77
DI 10.1097/QAI.0000000000000796
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CY9GL
UT WOS:000366715300010
PM 26761272
ER
PT J
AU Hengge, R
Galperin, MY
Ghigo, JM
Gomelsky, M
Green, J
Hughes, KT
Jenal, U
Landini, P
AF Hengge, Regine
Galperin, Michael Y.
Ghigo, Jean-Marc
Gomelsky, Mark
Green, Jeffrey
Hughes, Kelly T.
Jenal, Urs
Landini, Paolo
TI Systematic Nomenclature for GGDEF and EAL Domain-Containing Cyclic
Di-GMP Turnover Proteins of Escherichia coli
SO JOURNAL OF BACTERIOLOGY
LA English
DT Editorial Material
ID SALMONELLA-TYPHIMURIUM; CELLULOSE PRODUCTION; CATALYTIC MECHANISM;
DIGUANYLATE CYCLASE; ALLOSTERIC CONTROL; BIOFILM FORMATION;
PHOSPHODIESTERASE; MOTILITY; IDENTIFICATION; 2ND-MESSENGER
AB In recent years, Escherichia coli has served as one of a few model bacterial species for studying cyclic di-GMP (c-di-GMP) signaling. The widely used E. coli K-12 laboratory strains possess 29 genes encoding proteins with GGDEF and/or EAL domains, which include 12 diguanylate cyclases (DGC), 13 c-di-GMP-specific phosphodiesterases (PDE), and 4 "degenerate" enzymatically inactive proteins. In addition, six new GGDEF and EAL (GGDEF/EAL) domain-encoding genes, which encode two DGCs and four PDEs, have recently been found in genomic analyses of commensal and pathogenic E. coli strains. As a group of researchers who have been studying the molecular mechanisms and the genomic basis of c-di-GMP signaling in E. coli, we now propose a general and systematic dgc and pde nomenclature for the enzymatically active GGDEF/EAL domain-encoding genes of this model species. This nomenclature is intuitive and easy to memorize, and it can also be applied to additional genes and proteins that might be discovered in various strains of E. coli in future studies.
C1 [Hengge, Regine] Humboldt Univ, Inst Biol Mikrobiol, D-10099 Berlin, Germany.
[Galperin, Michael Y.] NIH, NCBI, NLM, Bethesda, MD 20892 USA.
[Ghigo, Jean-Marc] Inst Pasteur, Dept Microbiol, Paris, France.
[Gomelsky, Mark] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
[Green, Jeffrey] Univ Sheffield, Mol Biol & Biotechnol, Sheffield, S Yorkshire, England.
[Hughes, Kelly T.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Jenal, Urs] Univ Basel, Biozentrum, Basel, Switzerland.
[Landini, Paolo] Univ Milan, Dipartimento Biosci, Milan, Italy.
RP Hengge, R (reprint author), Humboldt Univ, Inst Biol Mikrobiol, D-10099 Berlin, Germany.
EM regine.hengge@hu-berlin.de
OI LANDINI, PAOLO/0000-0003-0999-426X
NR 48
TC 10
Z9 10
U1 4
U2 13
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 JAN 1
PY 2016
VL 198
IS 1
BP 7
EP 11
DI 10.1128/JB.00424-15
PG 5
WC Microbiology
SC Microbiology
GA CY7KR
UT WOS:000366587800018
PM 26148715
ER
PT J
AU Chou, SH
Galperin, MY
AF Chou, Shan-Ho
Galperin, Michael Y.
TI Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms
SO JOURNAL OF BACTERIOLOGY
LA English
DT Review
ID PILZ DOMAIN PROTEINS; BACTERIAL CELLULOSE SYNTHASE; REGULATES BIOFILM
FORMATION; PSEUDOMONAS-AERUGINOSA; DIGUANYLATE CYCLASE; VIBRIO-CHOLERAE;
SIGNAL-TRANSDUCTION; STRUCTURAL BASIS; EAL DOMAIN; EXOPOLYSACCHARIDE
PRODUCTION
AB Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub) micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms.
C1 [Chou, Shan-Ho] Natl Chung Hsing Univ, Inst Biochem, Taichung 40227, Taiwan.
[Chou, Shan-Ho] Natl Chung Hsing Univ, NCHU Agr Biotechnol Ctr, Taichung 40227, Taiwan.
[Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Chou, SH (reprint author), Natl Chung Hsing Univ, Inst Biochem, Taichung 40227, Taiwan.
EM shchou@nchu.edu.tw; galperin@ncbi.nlm.nih.gov
OI Galperin, Michael/0000-0002-2265-5572
FU Ministry of Education, Taiwan, ROC; National Science Council, Taiwan,
ROC [102-2113-M005-006-MY3]; NIH Intramural Research Program at the
National Library of Medicine
FX The Ministry of Education, Taiwan, ROC provided funding to Shan-Ho Chou.
The National Science Council, Taiwan, ROC provided funding to Shan-Ho
Chou under grant number 102-2113-M005-006-MY3. The NIH Intramural
Research Program at the National Library of Medicine provided funding to
Michael Y. Galperin.
NR 94
TC 24
Z9 24
U1 5
U2 27
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 JAN 1
PY 2016
VL 198
IS 1
BP 32
EP 46
DI 10.1128/JB.00333-15
PG 15
WC Microbiology
SC Microbiology
GA CY7KR
UT WOS:000366587800013
PM 26055114
ER
PT J
AU Bratzke, LC
Moser, DK
Pelter, MM
Paul, SM
Nesbitt, TS
Cooper, LS
Dracup, KA
AF Bratzke, Lisa C.
Moser, Debra K.
Pelter, Michele M.
Paul, Steven M.
Nesbitt, Thomas S.
Cooper, Lawton S.
Dracup, Kathleen A.
TI Evidence-Based Heart Failure Medications and Cognition
SO JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Article
DE Cognition; drug therapy; heart failure
ID CONVERTING ENZYME-INHIBITORS; OF-THE-LITERATURE; OLDER-ADULTS;
PERFORMANCE-MEASURES; MINI-COG; IMPAIRMENT; DEMENTIA; DYSFUNCTION;
PROGRESSION; PATTERNS
AB Background: The etiology of cognitive impairment in heart failure (HF) is controversial and likely multifactorial. Physicians may hesitate to prescribe evidence-based HF medication because of concerns related to potential negative changes in cognition among a population that is already frequently impaired. We conducted a study to determine if prescription of evidence-based HF medications (specifically, -blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blocking agents, diuretics, and aldosterone inhibitors) was associated with cognition in a large HF sample.
Methods: A total of 612 patients completed baseline data collection for the Rural Education to Improve Outcomes in Heart Failure clinical trial, including information about medications. Global cognition was evaluated using the Mini-Cog.
Results: The sample mean (SD) age was 66 (13) years, 58% were men, and 89% were white. Global cognitive impairment was identified in 206 (34%) of the 612 patients. Prescription of evidence-based HF medications was not related to global cognitive impairment in this sample. This relationship was maintained even after adjusting for potential confounders (eg, age, education, and comorbid burden).
Conclusion: Prescription of evidence-based HF medications is not related to low scores on a measure of global cognitive function in rural patients with HF.
C1 [Bratzke, Lisa C.] Univ Wisconsin, Sch Nursing, Madison, WI 53706 USA.
[Moser, Debra K.] Univ Kentucky, Coll Nursing, Lexington, KY 40506 USA.
[Pelter, Michele M.] Univ Nevada, Orvis Sch Nursing, Reno, NV 89557 USA.
[Paul, Steven M.; Dracup, Kathleen A.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA.
[Nesbitt, Thomas S.] Univ Calif Davis, Sch Med, Strateg Technol & Alliances, Davis, CA 95616 USA.
[Cooper, Lawton S.] NHLBI, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA.
RP Bratzke, LC (reprint author), 701 Highland Ave,Rm 3141, Madison, WI 53705 USA.
EM bratzke@wisc.edu
OI Bratzke, Lisa/0000-0002-0321-4501
FU National Institute of Nursing Research [R00NR012773]; National Heart
Lung and Blood Institute/National Institute for Nursing Research
[R01HL83176]
FX The project described was supported by award numbers R00NR012773 (Brain
Alterations and Cognitive Impairment in Older Adults With Heart Failure)
from the National Institute of Nursing Research and R01HL83176
(Improving Self-care Behaviour in Rural Patients With Heart Failure)
from the National Heart Lung and Blood Institute/National Institute for
Nursing Research. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institute of Nursing Research, the National Heart Lung and
Blood Institute, or the National Institutes of Health.
NR 48
TC 1
Z9 1
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0889-4655
EI 1550-5049
J9 J CARDIOVASC NURS
JI J. Cardiovasc. Nurs.
PD JAN-FEB
PY 2016
VL 31
IS 1
BP 62
EP 68
DI 10.1097/JCN.0000000000000216
PG 7
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA CY9HG
UT WOS:000366717400016
PM 25419943
ER
PT J
AU Sebastian, M
Lopez-Ocasio, M
Metidji, A
Rieder, SA
Shevach, EM
Thornton, AM
AF Sebastian, Mathew
Lopez-Ocasio, Maria
Metidji, Amina
Rieder, Sadiye Amcaoglu
Shevach, Ethan M.
Thornton, Angela M.
TI Helios Controls a Limited Subset of Regulatory T Cell Functions
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FAMILY-MEMBER; BCL6 CONTROLS; FOXP3(+); EXPRESSION; IKAROS;
INFLAMMATION; RESPONSES; DIFFERENTIATION; HOMEOSTASIS; PHENOTYPE
AB A subpopulation (60-70%) of Foxp3(+) regulatory T cells (Tregs) in both mouse and man expresses the transcription factor Helios, but its role in Treg function is still unknown. We generated Treg-specific Helios-deficient mice to examine the function of Helios in Tregs. We show that the selective deletion of Helios in Tregs leads to slow, progressive systemic immune activation, hypergammaglobulinemia, and enhanced germinal center formation in the absence of organ-specific autoimmunity. Helios-deficient Treg suppressor function was normal in vitro, as well as in an in vivo inflammatory bowel disease model. However, Helios-deficient Tregs failed to control the expansion of pathogenic T cells derived from scurfy mice, failed to mediate T follicular regulatory cell function, and failed to control both T follicular helper cell and Th1 effector cell responses. In competitive settings, Helios-deficient Tregs, particularly effector Tregs, were at a disadvantage, indicating that Helios regulates effector Treg fitness. Thus, we demonstrate that Helios controls certain aspects of Treg-suppressive function, differentiation, and survival.
C1 [Sebastian, Mathew; Lopez-Ocasio, Maria; Metidji, Amina; Rieder, Sadiye Amcaoglu; Shevach, Ethan M.; Thornton, Angela M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
OI , Maria/0000-0003-4463-5801
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 46
TC 14
Z9 14
U1 2
U2 10
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 JAN 1
PY 2016
VL 196
IS 1
BP 144
EP 155
DI 10.4049/jimmunol.1501704
PG 12
WC Immunology
SC Immunology
GA CY9OP
UT WOS:000366736500019
PM 26582951
ER
PT J
AU Manifold-Wheeler, BC
Elmore, BO
Triplett, KD
Castleman, MJ
Otto, M
Hall, PR
AF Manifold-Wheeler, Brett C.
Elmore, Bradley O.
Triplett, Kathleen D.
Castleman, Moriah J.
Otto, Michael
Hall, Pamela R.
TI Serum Lipoproteins Are Critical for Pulmonary Innate Defense against
Staphylococcus aureus Quorum Sensing
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-DENSITY LIPOPROTEINS; HOST-DEFENSE;
ALPHA-TOXIN; BACTERIAL PNEUMONIA; LIPOTEICHOIC ACID; APOLIPOPROTEIN-B;
LUNG; SURFACTANT; CHOLESTEROL
AB Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein-deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low-density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). In this article, we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing dependent pathogenesis. Specifically, apolipoprotein B levels in the lung early postinfection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact posttrauma pneumonia susceptibility to both Gram-positive and -negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung.
C1 [Manifold-Wheeler, Brett C.; Elmore, Bradley O.; Triplett, Kathleen D.; Castleman, Moriah J.; Hall, Pamela R.] Univ New Mexico, Coll Pharm, Dept Pharmaceut Sci, Albuquerque, NM 87131 USA.
[Otto, Michael] NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, Bethesda, MD 20892 USA.
RP Hall, PR (reprint author), Univ New Mexico, Coll Pharm, 1 Univ New Mexico,MSC09-5360, Albuquerque, NM 87131 USA.
EM phall@salud.unm.edu
RI Hall, Pamela/O-5402-2016;
OI Hall, Pamela/0000-0003-2367-3382; Castleman, Moriah/0000-0001-7219-5044;
Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [RO1AI091917]; Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by National Institute of Allergy and Infectious
Diseases, National Institutes of Health Grant RO1AI091917 (to P.R.H.)
and the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health (to M.O.).
NR 66
TC 3
Z9 3
U1 0
U2 14
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 JAN 1
PY 2016
VL 196
IS 1
BP 328
EP 335
DI 10.4049/jimmunol.1501835
PG 8
WC Immunology
SC Immunology
GA CY9OP
UT WOS:000366736500035
PM 26608923
ER
PT J
AU Tosh, KW
Mittereder, L
Bonne-Armee, S
Hieny, S
Nutman, TB
Singer, SM
Sher, A
Jankovic, D
AF Tosh, Kevin W.
Mittereder, Lara
Bonne-Armee, Sandra
Hieny, Sara
Nutman, Thomas B.
Singer, Steven M.
Sher, Alan
Jankovic, Dragana
TI The IL-12 Response of Primary Human Dendritic Cells and Monocytes to
Toxoplasma gondii Is Stimulated by Phagocytosis of Live Parasites Rather
Than Host Cell Invasion
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GENE-EXPRESSION PROFILES; TOLL-LIKE RECEPTORS; CROSS-PRESENTATION;
IFN-GAMMA; PHAGOSOME ACIDIFICATION; INFLAMMATORY MONOCYTES; CYTOKINE
PRODUCTION; INTERFERON-GAMMA; ACUTE INFECTION; RESISTANCE
AB As a major natural host for Toxoplasma gondii, the mouse is widely used for the study of the immune response to this medically important protozoan parasite. However, murine innate recognition of toxoplasma depends on the interaction of parasite profilin with TLR11 and TLR12, two receptors that are functionally absent in humans. This raises the question of how human cells detect and respond to T. gondii. In this study, we show that primary monocytes and dendritic cells from peripheral blood of healthy donors produce IL-12 and other proinflammatory cytokines when exposed to toxoplasma tachyzoites. Cell fractionation studies determined that IL-12 and TNF-alpha secretion is limited to CD16(+) monocytes and the CD1c(+) subset of dendritic cells. In direct contrast to their murine counterparts, human myeloid cells fail to respond to soluble tachyzoite extracts and instead require contact with live parasites. Importantly, we found that tachyzoite phagocytosis, but not host cell invasion, is required for cytokine induction. Together these findings identify CD16(+) monocytes and CD1c(+) dendritic cells as the major myeloid subsets in human blood-producing innate cytokines in response to T. gondii and demonstrate an unappreciated requirement for phagocytosis of live parasites in that process. This form of pathogen sensing is distinct from that used by mice, possibly reflecting a direct involvement of rodents and not humans in the parasite life cycle.
C1 [Tosh, Kevin W.; Mittereder, Lara; Hieny, Sara; Sher, Alan; Jankovic, Dragana] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Tosh, Kevin W.; Singer, Steven M.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Bonne-Armee, Sandra; Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Jankovic, D (reprint author), NIH, Bldg 50,Room 6142,50 South Dr,MSC 8003, Bethesda, MD 20892 USA.
EM djankovic@niaid.nih.gov
OI Singer, Steven/0000-0001-5719-7535
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 53
TC 5
Z9 5
U1 0
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 JAN 1
PY 2016
VL 196
IS 1
BP 345
EP 356
DI 10.4049/jimmunol.1501558
PG 12
WC Immunology
SC Immunology
GA CY9OP
UT WOS:000366736500037
PM 26597011
ER
PT J
AU Raizer, JJ
Giglio, P
Hu, J
Groves, M
Merrell, R
Conrad, C
Phuphanich, S
Puduvalli, VK
Loghin, M
Paleologos, N
Yuan, Y
Liu, D
Rademaker, A
Yung, WK
Vaillant, B
Rudnick, J
Chamberlain, M
Vick, N
Grimm, S
Tremont-Lukats, IW
De Groot, J
Aldape, K
Gilbert, MR
AF Raizer, J. J.
Giglio, P.
Hu, J.
Groves, M.
Merrell, R.
Conrad, C.
Phuphanich, S.
Puduvalli, V. K.
Loghin, M.
Paleologos, N.
Yuan, Y.
Liu, D.
Rademaker, A.
Yung, W. K.
Vaillant, B.
Rudnick, J.
Chamberlain, M.
Vick, N.
Grimm, S.
Tremont-Lukats, I. W.
De Groot, J.
Aldape, K.
Gilbert, M. R.
CA Brain Tumor Trials Collaborative
TI A phase II study of bevacizumab and erlotinib after radiation and
temozolomide in MGMT unmethylated GBM patients
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE MGMT; Glioblastoma; Erlotinib; Bevacizumab
ID NEWLY-DIAGNOSED GLIOBLASTOMA; GROWTH-FACTOR RECEPTOR; BRAIN-TUMOR
CONSORTIUM; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; KINASE
INHIBITORS; MALIGNANT GLIOMAS; FACTOR EXPRESSION; MAMMALIAN TARGET;
OPEN-LABEL
AB Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizumab in unmethylated GBM patients after completion of radiation (RT) and TMZ. GBM patients with an unmethylated MGMT promoter were trial eligible. Patient received standard RT (60 Gy) and TMZ (75 mg/m(2) x 6 weeks) after surgical resection of their tumor. After completion of RT they started erlotinib 150 mg daily and bevacizumab 10 mg/kg every 2 weeks until progression. Imaging evaluations occurred every 8 weeks. The primary endpoint was overall survival. Of the 48 unmethylated patients enrolled, 46 were evaluable (29 men and 17 women); median age was 55.5 years (29-75) and median KPS was 90 (70-100). All patients completed RT with TMZ. The median number of cycles (1 cycle was 4 weeks) was 8 (2-47). Forty-one patients either progressed or died with a median progression free survival of 9.2 months. At a follow up of 33 months the median overall survival was 13.2 months. There were no unexpected toxicities and most observed toxicities were categorized as CTC grade 1 or 2. The combination of erlotinib and bevacizumab is tolerable but did not meet our primary endpoint of increasing survival. Importantly, more trials are needed to find better therapies for GBM patients with an unmethylated MGMT promoter.
C1 [Raizer, J. J.; Grimm, S.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
[Giglio, P.; Puduvalli, V. K.] Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA.
[Hu, J.; Phuphanich, S.; Rudnick, J.] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
[Hu, J.; Phuphanich, S.; Rudnick, J.] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA.
[Groves, M.; Conrad, C.] Austin Brain Tumor Ctr, Austin, TX USA.
[Merrell, R.; Vick, N.] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA.
[Loghin, M.; Yung, W. K.; Tremont-Lukats, I. W.; De Groot, J.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Paleologos, N.] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA.
[Yuan, Y.; Liu, D.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Rademaker, A.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Vaillant, B.] Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA.
[Chamberlain, M.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Aldape, K.] Princess Margaret Canc Ctr, Dept Pathol, Toronto, ON, Canada.
[Gilbert, M. R.] NIH, Neurooncol Branch, Bethesda, MD 20892 USA.
RP Raizer, JJ (reprint author), Northwestern Univ, Dept Neurol, 710 North Lake Shore Dr,Abbott Hall,Room 1123, Chicago, IL 60611 USA.
EM jraizer@nm.org
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
FU Genentech; Head for the Cure Foundation
FX Trial was supported by Genentech and "Head for the Cure Foundation".
NR 35
TC 3
Z9 3
U1 0
U2 3
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 JAN
PY 2016
VL 126
IS 1
BP 185
EP 192
DI 10.1007/s11060-015-1958-z
PG 8
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CZ0ZR
UT WOS:000366835900022
PM 26476729
ER
PT J
AU Srivanitchapoom, P
Hallett, M
AF Srivanitchapoom, Prachaya
Hallett, Mark
TI Camptocormia in Parkinson's disease: definition, epidemiology,
pathogenesis and treatment modalities
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Review
ID MULTIPLE-SYSTEM ATROPHY; DEEP BRAIN-STIMULATION; BENT SPINE SYNDROME;
FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; BOTULINUM TOXIN; RESPONSIVE
CAMPTOCORMIA; CLINICAL-MANIFESTATION; DYSTONIC CAMPTOCORMIA; MAGNETIC
STIMULATION; MYASTHENIA-GRAVIS
AB Camptocormia is an axial postural deformity characterised by abnormal thoracolumbar spinal flexion. The symptom usually presents while standing, walking or exercising and is alleviated while sitting, lying in a recumbent position, standing against a wall or using walking support. There is no consensus on the degree of thoracolumbar flexion to define camptocormia. However, most authors usually use an arbitrary number of at least 45 degrees flexion of the thoracolumbar spine when the individual is standing or walking. Aetiologies of camptocormia are heterogeneous, and Parkinson's disease (PD) is one of its many causes. The prevalence of camptocormia in PD ranges from 3% to 18%. Central and peripheral mechanisms might both contribute to its pathogenesis. Although there is no established consensus for treatment of camptocormia in PD, there are non-pharmacological, pharmacological and surgical approaches that can be used.
C1 [Srivanitchapoom, Prachaya] Mahidol Univ, Dept Med, Siriraj Hosp, Fac Med,Div Neurol, Bangkok 10700, Thailand.
[Srivanitchapoom, Prachaya; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr MSC 1428,Bldg 10,Room 7D37, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU NINDS Intramural Programme
FX NINDS Intramural Programme.
NR 101
TC 9
Z9 9
U1 1
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
EI 1468-330X
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD JAN
PY 2016
VL 87
IS 1
BP 75
EP 85
DI 10.1136/jnnp-2014-310049
PG 11
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA CY9ND
UT WOS:000366732700012
PM 25896683
ER
PT J
AU Wu, Y
Liang, J
Horkay, F
Libera, M
AF Wu, Yong
Liang, Jing
Horkay, Ferenc
Libera, Matthew
TI Antimicrobial Loading into and Release from Poly(ethylene
glycol)/Poly(acrylic acid) Semi-interpenetrating Hydrogels
SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS
LA English
DT Article
DE diffusion; hydrogels; poly(ethylene glycol); self-assembly;
semi-interpenetrating network
ID POLY(ACRYLIC ACID); DRUG-DELIVERY; COMPLEX-FORMATION; SOLUTE DIFFUSION;
SURFACES; POLYELECTROLYTES; MECHANISMS; TRANSPORT; MICROGELS; GLYCOL)
AB Electrostatic interactions within a semi-interpenetrating network (semi-IPN) gel can control the postsynthesis loading, long-term retention, and subsequent release of small-molecule cationic antibiotics. Here, electrostatic charge is introduced into an otherwise neutral gel [poly(ethylene glycol) (PEG)] by physically entrapping high-molecular-weight poly(acrylic acid) (PAA). The network structure is characterized by small-angle neutron scattering. PEG/PAA semi-IPN gels absorb over 40 times more antibiotic than PAA-free PEG gels. Subsequent soaking in physiological buffer (pH 7.4; 0.15 M NaCl) releases the loaded antibiotics for periods as long as 30 days. The loaded gels elute antibiotics with diffusivities of 4.46 x 10(-8) cm(2)/s (amikacin) and 2.08 x 10(-8) cm(2)/s (colistin), which are two orders of magnitude less than those in pure PEG gels where diffusion is controlled purely by gel tortuosity. The release and hindered diffusion can be understood based on the partial shielding of the charged groups within the loaded gel, and they have a significant effect on the antimicrobial properties of these gels. (C) 2015 Wiley Periodicals, Inc.
C1 [Wu, Yong; Liang, Jing; Libera, Matthew] Stevens Inst Technol, Dept Chem Engn & Mat Sci, Hoboken, NJ 07030 USA.
[Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
RP Libera, M (reprint author), Stevens Inst Technol, Dept Chem Engn & Mat Sci, Hoboken, NJ 07030 USA.
EM mlibera@stevens.edu
OI Libera, Matthew/0000-0001-5026-802X
FU Army Research Office [W911NF-12-1-0331]; NICHD/NIH; National Science
Foundation [DMR-0944772]
FX This research project has been supported by the Army Research Office
through grant no. W911NF-12-1-0331. F. Horkay acknowledges the support
of the Intramural Research Program of the NICHD/NIH. The authors are
grateful for access to neutron-scattering facilities at the National
Institute of Standards and Technology (U.S. Department of Commerce)
supported in part by the National Science Foundation under Agreement No.
DMR-0944772. The authors thank Boualem Hammouda (NIST) and Yuan Gao
(NIH/NIST) for their help with the SANS experiment.
NR 35
TC 2
Z9 2
U1 10
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-6266
EI 1099-0488
J9 J POLYM SCI POL PHYS
JI J. Polym. Sci. Pt. B-Polym. Phys.
PD JAN 1
PY 2016
VL 54
IS 1
BP 64
EP 72
DI 10.1002/polb.23924
PG 9
WC Polymer Science
SC Polymer Science
GA CY6HI
UT WOS:000366509300007
ER
PT J
AU Kron, IL
Lapar, DJ
Horvath, KA
AF Kron, Irving L.
Lapar, Damien J.
Horvath, Keith A.
CA Govt Relations Committee
Amer Association Thoracic Surg Sci
CTSN Investigators
TI Cardiothoracic Surgical Trials Network: Evidence-based surgery
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
DE Cardiothoracic Surgical Network; clinical trials
ID ISCHEMIC MITRAL REGURGITATION; VALVE REPAIR
C1 [Kron, Irving L.; Lapar, Damien J.] Univ Virginia, Sch Med, Cardiothorac Surg Network, Charlottesville, VA 22908 USA.
[Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
RP Kron, IL (reprint author), Univ Virginia, Dept Surg, POB 800679, Charlottesville, VA 22908 USA.
EM ilk@virginia.edu
FU NHLBI NIH HHS [U01 HL088942, UM1 HL088925]
NR 7
TC 1
Z9 1
U1 0
U2 1
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 JAN
PY 2016
VL 151
IS 1
BP 28
EP 29
DI 10.1016/j.jtcvs.2015.09.122
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CY8MT
UT WOS:000366663500019
PM 26519245
ER
PT J
AU Tapia, MD
Sow, SO
Lyke, KE
Haidara, FC
Diallo, F
Doumbia, M
Traore, A
Coulibaly, F
Kodio, M
Onwuchekwa, U
Sztein, MB
Wahid, R
Campbell, JD
Kieny, MP
Moorthy, V
Imoukhuede, EB
Rampling, T
Roman, F
De Ryck, I
Bellamy, AR
Dally, L
Mbaya, OT
Ploquin, A
Zhou, Y
Stanley, DA
Bailer, R
Koup, RA
Roederer, M
Ledgerwood, J
Hill, AVS
Ballou, WR
Sullivan, N
Graham, B
Levine, MM
AF Tapia, Milagritos D.
Sow, Samba O.
Lyke, Kirsten E.
Haidara, Fadima Cheick
Diallo, Fatoumata
Doumbia, Moussa
Traore, Awa
Coulibaly, Flanon
Kodio, Mamoudou
Onwuchekwa, Uma
Sztein, Marcelo B.
Wahid, Rezwanul
Campbell, James D.
Kieny, Marie-Paule
Moorthy, Vasee
Imoukhuede, Egeruan B.
Rampling, Tommy
Roman, Francois
De Ryck, Iris
Bellamy, Abbie R.
Dally, Len
Mbaya, Olivier Tshiani
Ploquin, Aurelie
Zhou, Yan
Stanley, Daphne A.
Bailer, Robert
Koup, Richard A.
Roederer, Mario
Ledgerwood, Julie
Hill, Adrian V. S.
Ballou, W. Ripley
Sullivan, Nancy
Graham, Barney
Levine, Myron M.
TI Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and
boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind,
randomised trial, a phase 1b, open-label and double-blind,
dose-escalation trial, and a nested, randomised, double-blind,
placebo-controlled trial
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID SMALLPOX ERADICATION; PROTECTIVE IMMUNITY; NONHUMAN-PRIMATES; WEST;
INFECTION; EPIDEMIC; VECTORS; DISEASE; AFRICA
AB Background The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).
Methods In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1: 1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 x 10(10) viral particle units (pu), 2 . 5 x 10(10) pu, 5 x 10(10) pu, or 1 x 10(11) pu; US participants received 1 x 10(10) pu or 1 x 10(11) pu. We randomly allocated Malians in the nested trial (1: 1) to receive a single dose of 2 x 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian).
Findings Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 x 10(10) pu, 35 [38%] to 2 . 5 x 10(10) pu, 35 [38%] to 5 x 10(10) pu, and 11 [12%] to 1 x 10(11) pu) and 20 in the USA (ten [50%] to 1 x 10(10) pu and ten [50%] to 1 x 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 x 10(10) and two [2%] received 1 x 10(11) pu) and four (20%) of 20 in the USA (all received 1 x 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-lo had injection-site pain or tenderness.
Interpretation 1 x 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-lo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers).
C1 [Tapia, Milagritos D.; Lyke, Kirsten E.; Sztein, Marcelo B.; Wahid, Rezwanul; Campbell, James D.; Levine, Myron M.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Tapia, Milagritos D.; Sow, Samba O.; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma] Ctr Dev Vaccins Mali, Bamako, Mali.
[Kieny, Marie-Paule; Moorthy, Vasee] WHO, CH-1211 Geneva, Switzerland.
[Imoukhuede, Egeruan B.; Rampling, Tommy; Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Oxford, England.
[Imoukhuede, Egeruan B.; Rampling, Tommy; Hill, Adrian V. S.] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford, England.
[Imoukhuede, Egeruan B.; Rampling, Tommy; Hill, Adrian V. S.] Natl Inst Hlth Res Oxford Biomed Res Ctr, Oxford, England.
[Roman, Francois; De Ryck, Iris; Ballou, W. Ripley] GlaxoSmithKline Vaccines, Rixensart, Belgium.
[Bellamy, Abbie R.; Dally, Len] EMMES Corp, Rockville, MD USA.
[Mbaya, Olivier Tshiani; Ploquin, Aurelie; Zhou, Yan; Stanley, Daphne A.; Bailer, Robert; Koup, Richard A.; Roederer, Mario; Ledgerwood, Julie; Sullivan, Nancy; Graham, Barney] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Levine, MM (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
EM mlevine@medicine.umaryland.edu
FU Wellcome Trust; Medical Research Council UK; Department for
International Development UK; National Cancer Institute; Frederick
National Laboratory for Cancer Research; Federal Funds from National
Institute of Allergy and Infectious Diseases
FX Wellcome Trust, Medical Research Council UK, Department for
International Development UK, National Cancer Institute, Frederick
National Laboratory for Cancer Research, Federal Funds from National
Institute of Allergy and Infectious Diseases.
NR 25
TC 11
Z9 11
U1 1
U2 11
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 JAN
PY 2016
VL 16
IS 1
BP 31
EP 42
DI 10.1016/S1473-3099(15)00362-X
PG 12
WC Infectious Diseases
SC Infectious Diseases
GA CY8NG
UT WOS:000366664900031
PM 26546548
ER
PT J
AU Makia, NL
Goldstein, JA
AF Makia, Ngome L.
Goldstein, Joyce A.
TI CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor
alpha in Human Liver
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PPAR-ALPHA; HUMAN HEPATOCYTES; TRANSCRIPTIONAL REGULATION;
GENE-EXPRESSION; CYTOCHROME P4502C8; RESPONSE ELEMENT; LIPID-METABOLISM;
PRIMARY CULTURES; MICRORNAS 103; INDUCTION
AB Human cytochrome P450 (CYP) 2C enzymesmetabolize similar to 30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. Previous studies from our laboratory showed that microRNA 107 (miR107) and microRNA 103 downregulate CYP2C8 post-transcriptionally. miR107 is located in intron 5 of the pantothenate kinase 1 (PANK1) gene. p53 has been reported to coregulate the induction of PANK1 and miR107. Here, we examine the possible downregulation of CYP2C8 by drugs capable of inducing miR107. Hypolipidemic drugs, such as bezafibrate, known activators of the peroxisome proliferator-activated receptor alpha (PPAR alpha), induce both the PANK1 gene and miR107 (similar to 2.5-fold) in primary human hepatocytes. Surprisingly, CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPAR alpha in HepG2 cells, with a further increase after bezafibrate (similar to 18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (similar to 10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. Promoter sequence analyses, deletion studies, mutagenesis studies, and electrophoretic mobility shift assays identified a PPAR alpha response element located at position 22109 base pair relative to the translation start site of CYP2C8. Chromatin immunopreciptation assay analysis confirmed recruitment of PPAR alpha to this PPAR alpha response element after bezafibrate treatment of human hepatocytes. Thus, we show for the first time that CYP2C8 is transcriptionally regulated by PPAR alpha, suggesting the potential for drug-drug interactions due to upregulation of CYP2C8 by PPAR activators.
C1 [Makia, Ngome L.; Goldstein, Joyce A.] NIEHS, Human Metab Grp, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Goldstein, JA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM goldste1@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01 ES021024-32]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of
Environmental Health Sciences [Grant Z01 ES021024-32].
NR 52
TC 2
Z9 3
U1 0
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JAN
PY 2016
VL 89
IS 1
BP 154
EP 164
DI 10.1124/mol.115.100255
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY8QA
UT WOS:000366672200015
PM 26467040
ER
PT J
AU Sandtner, W
Stockner, T
Hasenhuetl, PS
Partilla, JS
Seddik, A
Zhang, YW
Cao, JJ
Holy, M
Steinkellner, T
Rudnick, G
Baumann, MH
Ecker, GF
Newman, AH
Sitte, HH
AF Sandtner, Walter
Stockner, Thomas
Hasenhuetl, Peter S.
Partilla, John S.
Seddik, Amir
Zhang, Yuan-Wei
Cao, Jianjing
Holy, Marion
Steinkellner, Thomas
Rudnick, Gary
Baumann, Michael H.
Ecker, Gerhard F.
Newman, Amy Hauck
Sitte, Harald H.
TI Binding Mode Selection Determines the Action of Ecstasy Homologs at
Monoamine Transporters
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID HUMAN SEROTONIN TRANSPORTER; X-RAY STRUCTURES; NEUROTRANSMITTER
TRANSPORTERS; DOPAMINE TRANSPORTER; 3,4-METHYLENEDIOXYMETHAMPHETAMINE
MDMA; BACTERIAL HOMOLOG; AMPHETAMINES; SUBSTRATE; COCAINE;
IDENTIFICATION
AB Determining the structural elements that define substrates and inhibitors at the monoamine transporters is critical to elucidating the mechanisms underlying these disparate functions. In this study, we addressed this question directly by generating a series of N-substituted 3,4-methylenedioxyamphetamine analogs that differ only in the number of methyl substituents on the terminal amine group. Starting with 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N, N-dimethylamphetamine (MDDMA) and 3,4-methylenedioxy-N, N, N-trimethylamphetamine (MDTMA) were prepared. We evaluated the functional activities of the compounds at all three monoamine transporters in native brain tissue and cells expressing the transporters. In addition, we used ligand docking to generate models of the respective protein-ligand complexes, which allowed us to relate the experimental findings to available structural information. Our results suggest that the 3,4-methylenedioxyamphetamine analogs bind at the monoamine transporter orthosteric binding site by adopting one of two mutually exclusive binding modes. 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy-N-methylamphetamine adopt a high-affinity binding mode consistent with a transportable substrate, whereas MDDMA and MDTMA adopt a low-affinity binding mode consistent with an inhibitor, in which the ligand orientation is inverted. Importantly, MDDMA can alternate between both binding modes, whereas MDTMA exclusively binds to the low-affinity mode. Our experimental results are consistent with the idea that the initial orientation of bound ligands is critical for subsequent interactions that lead to transporter conformational changes and substrate translocation.
C1 [Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S.; Holy, Marion; Steinkellner, Thomas; Sitte, Harald H.] Med Univ Vienna, Ctr Physiol & Pharmacol, Inst Pharmacol, A-1090 Vienna, Austria.
[Sitte, Harald H.] Med Univ Vienna, Ctr Addict Res & Sci, A-1090 Vienna, Austria.
[Partilla, John S.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, NIH, Baltimore, MD USA.
[Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, NIH, Baltimore, MD USA.
[Seddik, Amir; Ecker, Gerhard F.] Univ Vienna, Dept Pharmaceut Chem, Vienna, Austria.
[Zhang, Yuan-Wei; Rudnick, Gary] Yale Univ, Dept Pharmacol, New Haven, CT USA.
RP Sitte, HH (reprint author), Med Univ Vienna, Ctr Physiol & Pharmacol, Inst Pharmacol, Waehringerstr 13A, A-1090 Vienna, Austria.
EM harald.sitte@meduniwien.ac.at
RI Stockner, Thomas/A-9509-2014;
OI Stockner, Thomas/0000-0002-7071-8283; Sitte, Harald/0000-0002-1339-7444
FU Austrian Science Fund/FWF (Fonds zur Forderung der Wissenschaft und
Forschung) [W1232, F35]; Medical University of Vienna; National
Institute on Drug Abuse Intramural Research Program [DA000389]
FX This work was supported by the Austrian Science Fund/FWF (Fonds zur
Forderung der Wissenschaft und Forschung) [Grant W1232] to G.F.E. and
H.H.S., Austrian Science Fund/FWF (Fonds zur Forderung der Wissenschaft
und Forschung) [Grant F35] to G.F.E., H.H.S., and T. Sto., and a MDPhD
fellowship by the Medical University of Vienna to P.S.H. M.B.H. and
A.H.N. receive support by the National Institute on Drug Abuse
Intramural Research Program [Grant DA000389].
NR 53
TC 5
Z9 5
U1 2
U2 11
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JAN
PY 2016
VL 89
IS 1
BP 165
EP 175
DI 10.1124/mol.115.101394
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY8QA
UT WOS:000366672200016
PM 26519222
ER
PT J
AU Zhao, ED
Maj, T
Kryczek, I
Li, W
Wu, K
Zhao, LL
Wei, S
Crespo, J
Wan, SS
Vatan, L
Szeliga, W
Shao, I
Wang, Y
Liu, Y
Varambally, S
Chinnaiyan, AM
Welling, TH
Marquez, V
Kotarski, J
Wang, HB
Wang, ZH
Zhang, Y
Liu, R
Wang, GB
Zou, WP
AF Zhao, Ende
Maj, Tomasz
Kryczek, Ilona
Li, Wei
Wu, Ke
Zhao, Lili
Wei, Shuang
Crespo, Joel
Wan, Shanshan
Vatan, Linda
Szeliga, Wojciech
Shao, Irene
Wang, Yin
Liu, Yan
Varambally, Sooryanarayana
Chinnaiyan, Arul M.
Welling, Theodore H.
Marquez, Victor
Kotarski, Jan
Wang, Hongbo
Wang, Zehua
Zhang, Yi
Liu, Rebecca
Wang, Guobin
Zou, Weiping
TI Cancer mediates effector T cell dysfunction by targeting microRNAs and
EZH2 via glycolysis restriction
SO NATURE IMMUNOLOGY
LA English
DT Article
ID HISTONE METHYLTRANSFERASE EZH2; GROUP PROTEIN EZH2; TH17 CELLS;
COLORECTAL-CANCER; OVARIAN-CARCINOMA; DNA METHYLATION; SURVIVAL;
RESPONSES; EXPRESSION; STEMNESS
AB Aerobic glycolysis regulates T cell function. However, whether and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity in cancer patients remains a question. Here we found that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling. Moreover, small hairpin RNA-mediated knockdown of human EZH2 in T cells elicited poor antitumor immunity. EZH2(+)CD8(+) T cells were associated with improved survival in patients. Together, these data unveil a metabolic target and mechanism of cancer immune evasion.
C1 [Zhao, Ende; Maj, Tomasz; Kryczek, Ilona; Li, Wei; Wu, Ke; Wei, Shuang; Crespo, Joel; Wan, Shanshan; Vatan, Linda; Szeliga, Wojciech; Shao, Irene; Wang, Yin; Liu, Yan; Welling, Theodore H.; Zou, Weiping] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA.
[Zhao, Ende; Li, Wei; Wu, Ke] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Surg, Wuhan 430074, Peoples R China.
[Zhao, Lili] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI USA.
[Varambally, Sooryanarayana] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Varambally, Sooryanarayana; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Marquez, Victor] NCI, Ctr Canc Res, Biol Chem Lab, Frederick, MD 21701 USA.
[Kotarski, Jan] Med Univ Lublin, Dept Gynecol Oncol & Gynecol 1, Lublin, Poland.
[Wang, Hongbo; Wang, Zehua] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Obstet & Gynecol, Wuhan 430074, Peoples R China.
[Zhang, Yi] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Liu, Rebecca] Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI USA.
[Zou, Weiping] Univ Michigan, Grad Programs Immunol & Canc Biol, Ann Arbor, MI 48109 USA.
[Zou, Weiping] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Zou, WP (reprint author), Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA.
EM wangguobin1954@126.com; wzou@med.umich.edu
RI Wan, Shanshan/C-3800-2013; Zhao, Ende/B-9851-2013
FU US National Institutes of Health (Intramural Research Program)
[CA123088, CA099985, CA156685, CA171306, 5P30CA46592]; Chinese Ministry
of Science and Technology (973 program) [2015CB554000]; Wuhan Union
Hospital Research Fund; Ovarian Cancer Research Fund; Marsha Rivkin
Center for Ovarian Cancer Research
FX We thank D. Postiff, M. Vinco, R. Craig and J. Barikdar for tissue
procurement core at the University of Michigan; G. Lv, W. Dong and L. Li
for assistance; R. Zhang (Wistar Institute) for shEZH2 plasmids; P. King
for discussions; and B. Leclair and D. Leclair for support. Supported by
the US National Institutes of Health (the Intramural Research Program;
and CA123088, CA099985, CA156685, CA171306 and 5P30CA46592), the Chinese
Ministry of Science and Technology (973 program, 2015CB554000), the
Wuhan Union Hospital Research Fund, the Ovarian Cancer Research Fund,
and Marsha Rivkin Center for Ovarian Cancer Research.
NR 50
TC 30
Z9 30
U1 11
U2 24
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 JAN
PY 2016
VL 17
IS 1
BP 95
EP +
DI 10.1038/ni.3313
PG 11
WC Immunology
SC Immunology
GA CY8RK
UT WOS:000366675800015
PM 26523864
ER
PT J
AU Emmert, K
Kopel, R
Sulzer, J
Bruhl, AB
Berman, BD
Linden, DEJ
Horovitz, SG
Breimhorst, M
Caria, A
Frank, S
Johnston, S
Long, ZY
Paret, C
Robineau, F
Veit, R
Bartsch, A
Beckmann, CF
Van De Ville, D
Haller, S
AF Emmert, Kirsten
Kopel, Rotem
Sulzer, James
Bruehl, Annette B.
Berman, Brian D.
Linden, David E. J.
Horovitz, Silvina G.
Breimhorst, Markus
Caria, Andrea
Frank, Sabine
Johnston, Stephen
Long, Zhiying
Paret, Christian
Robineau, Fabien
Veit, Ralf
Bartsch, Andreas
Beckmann, Christian F.
Van De Ville, Dimitri
Haller, Sven
TI Meta-analysis of real-time fMRI neurofeedback studies using individual
participant data: How is brain regulation mediated?
SO NEUROIMAGE
LA English
DT Article
DE Neurofeedback; Real-time fMRI; Brain regulation
ID CINGULATE CORTEX ACTIVITY; ANTERIOR CINGULATE; SELF-REGULATION;
FUNCTIONAL MRI; INSULAR CORTEX; DEFAULT-MODE; BASAL GANGLIA; MOTOR
IMAGERY; CORTICAL ACTIVITY; RESTING BRAIN
AB An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation.
The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Emmert, Kirsten; Kopel, Rotem; Van De Ville, Dimitri] Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.
[Emmert, Kirsten; Kopel, Rotem; Van De Ville, Dimitri] Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland.
[Sulzer, James] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA.
[Bruehl, Annette B.] Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland.
[Bruehl, Annette B.] Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge, England.
[Berman, Brian D.] Univ Colorado, Dept Neurol, Aurora, CO USA.
[Linden, David E. J.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Horovitz, Silvina G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Breimhorst, Markus] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, D-55122 Mainz, Germany.
[Caria, Andrea; Frank, Sabine; Veit, Ralf] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany.
[Long, Zhiying] Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.
[Long, Zhiying] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
[Long, Zhiying] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
[Paret, Christian] Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Psychosomat Med & Psychotherapy, Mannheim, Germany.
[Paret, Christian] Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Neuroimaging, Mannheim, Germany.
[Robineau, Fabien] Univ Geneva, Dept Neurosci, Lab Neurol & Imaging Cognit, CH-1211 Geneva 4, Switzerland.
[Veit, Ralf] Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany.
[Bartsch, Andreas] Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany.
[Bartsch, Andreas] Univ Wurzburg, Dept Neuroradiol, D-97070 Wurzburg, Germany.
[Bartsch, Andreas] Univ Oxford, FMRIB Ctr, Oxford, England.
[Bartsch, Andreas] Bamberg Hosp, Dept Radiol, Bamberg, Germany.
[Beckmann, Christian F.] Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
[Beckmann, Christian F.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.
[Beckmann, Christian F.] Univ Oxford, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England.
[Haller, Sven] Affidea Ctr Diagnost Radiolog Carouge CDRC, Geneva, Switzerland.
[Haller, Sven] Uppsala Univ, Dept Surg Sci, Radiol, Uppsala, Sweden.
[Haller, Sven] Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
[Haller, Sven] Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland.
RP Emmert, K (reprint author), Univ Hosp Geneva, CIBM, Neuroradiol DISIM, Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland.
EM kirsten.emmert@unige.ch
RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Frank,
Sabine/I-8986-2012; Linden, David/C-7355-2013; Beckmann,
Christian/E-6374-2012;
OI Linden, David/0000-0002-5638-9292; Johnston,
Stephen/0000-0001-9360-8856; Van De Ville, Dimitri/0000-0002-2879-3861;
Haller, Sven/0000-0001-7433-0203
FU Swiss National Science Foundation [320030_147126/1, 320030_127079/1,
PMCDP2_145442, PMCDP2_162223]; Center for Biomedical Imaging (CIBM,
Geneva, Switzerland)
FX This work was supported by the Swiss National Science Foundation
(project 320030_147126/1, 320030_127079/1 and the Marie Heim-Vogtlin
grants PMCDP2_145442 and PMCDP2_162223) and the Center for Biomedical
Imaging (CIBM, Geneva, Switzerland).
NR 77
TC 9
Z9 9
U1 6
U2 21
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 JAN 1
PY 2016
VL 124
BP 806
EP 812
DI 10.1016/j.neuroimage.2015.09.042
PN A
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CY8GL
UT WOS:000366646700075
PM 26419389
ER
PT J
AU Maren, S
Holmes, A
AF Maren, Stephen
Holmes, Andrew
TI Stress and Fear Extinction
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
ID MEDIAL PREFRONTAL CORTEX; SINGLE PROLONGED STRESS; NATIONAL COMORBIDITY
SURVEY; HIPPOCAMPAL ENDOCANNABINOID SYSTEM; ANXIETY-RELATED BEHAVIORS;
NMDA RECEPTOR EXPRESSION; LONG-TERM POTENTIATION; GENETIC MOUSE MODEL;
DSM-IV DISORDERS; POSTTRAUMATIC-STRESS
AB Stress has a critical role in the development and expression of many psychiatric disorders, and is a defining feature of posttraumatic stress disorder (PTSD). Stress also limits the efficacy of behavioral therapies aimed at limiting pathological fear, such as exposure therapy. Here we examine emerging evidence that stress impairs recovery from trauma by impairing fear extinction, a form of learning thought to underlie the suppression of trauma-related fear memories. We describe the major structural and functional abnormalities in brain regions that are particularly vulnerable to stress, including the amygdala, prefrontal cortex, and hippocampus, which may underlie stress-induced impairments in extinction. We also discuss some of the stress-induced neurochemical and molecular alterations in these brain regions that are associated with extinction deficits, and the potential for targeting these changes to prevent or reverse impaired extinction. A better understanding of the neurobiological basis of stress effects on extinction promises to yield novel approaches to improving therapeutic outcomes for PTSD and other anxiety and trauma-related disorders.
C1 [Maren, Stephen] Texas A&M Univ, Dept Psychol, Inst Neurosci, College Stn, TX 77843 USA.
[Holmes, Andrew] NIAAA, NIH, Bethesda, MD USA.
RP Maren, S (reprint author), Texas A&M Univ, Dept Psychol, Inst Neurosci, 301 Old Main Dr, College Stn, TX 77843 USA.
EM maren@tamu.edu
OI Maren, Stephen/0000-0002-9342-7411
FU NIAAA Intramural Research Program; Henry Jackson Foundation for the
Advancement of Military Medicine; Department of Defense in the Center
for Neuroscience and Regenerative Medicine; NIH [R01MH065961]; McKnight
Foundation Memory and Cognitive Disorders Award
FX AH is supported by the NIAAA Intramural Research Program, Henry Jackson
Foundation for the Advancement of Military Medicine, and the Department
of Defense in the Center for Neuroscience and Regenerative Medicine. SM
is supported by grants from the NIH (R01MH065961) and a McKnight
Foundation Memory and Cognitive Disorders Award.
NR 322
TC 22
Z9 22
U1 20
U2 64
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 JAN
PY 2016
VL 41
IS 1
BP 58
EP 79
DI 10.1038/npp.2015.180
PG 22
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OP
UT WOS:000366598400005
PM 26105142
ER
PT J
AU Mantsch, JR
Baker, DA
Funk, D
Le, AD
Shaham, Y
AF Mantsch, John R.
Baker, David A.
Funk, Douglas
Le, Anh D.
Shaham, Yavin
TI Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
ID CORTICOTROPIN-RELEASING-FACTOR; VENTRAL TEGMENTAL AREA; CONDITIONED
PLACE PREFERENCE; KAPPA-OPIOID RECEPTOR; MEDIAL PREFRONTAL CORTEX;
COCAINE-INDUCED REINSTATEMENT; DORSAL RAPHE NUCLEUS; DEPRIVATION-INDUCED
REINSTATEMENT; PALATABLE FOOD SEEKING; MESOLIMBIC DOPAMINE SYSTEM
AB In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse.
C1 [Mantsch, John R.; Baker, David A.] Marquette Univ, Dept Biomed Sci, Milwaukee, WI 53233 USA.
[Funk, Douglas; Le, Anh D.] Univ Toronto, Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Mantsch, JR (reprint author), Marquette Univ, Dept Biomed Sci, Milwaukee, WI 53233 USA.
EM yshaham@intra.nida.nih.gov
FU National Institute on Drug Abuse, NIH
FX The writing of this review was supported by extramural (JRM, DAB, and
AL) and intramural (YS) funds from the National Institute on Drug Abuse,
NIH. Dr David Baker and Dr John Mantsch receive compensation from and
have financial holdings in Promentis Pharmaceuticals.
NR 293
TC 22
Z9 23
U1 13
U2 31
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 JAN
PY 2016
VL 41
IS 1
BP 335
EP 356
DI 10.1038/npp.2015.142
PG 22
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OP
UT WOS:000366598400021
PM 25976297
ER
PT J
AU Chavkin, C
Koob, GF
AF Chavkin, Charles
Koob, George F.
TI Dynorphin, Dysphoria, and Dependence: the Stress of Addiction
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID TOLERABILITY; SAFETY
C1 [Chavkin, Charles] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
[Koob, George F.] NIAAA, Rockville, MD 20852 USA.
RP Chavkin, C (reprint author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
EM cchavkin@u.washington.edu
RI koob, george/P-8791-2016
NR 6
TC 3
Z9 3
U1 1
U2 5
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 JAN
PY 2016
VL 41
IS 1
BP 373
EP 374
DI 10.1038/npp.2015.258
PG 4
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OP
UT WOS:000366598400027
PM 26657953
ER
PT J
AU Marchant, NJ
Whitaker, LR
Bossert, JM
Harvey, BK
Hope, BT
Kaganovsky, K
Adhikary, S
Prisinzano, TE
Vardy, E
Roth, BL
Shaham, Y
AF Marchant, Nathan J.
Whitaker, Leslie R.
Bossert, Jennifer M.
Harvey, Brandon K.
Hope, Bruce T.
Kaganovsky, Konstantin
Adhikary, Sweta
Prisinzano, Thomas E.
Vardy, Eyal
Roth, Bryan L.
Shaham, Yavin
TI Behavioral and Physiological Effects of a Novel Kappa-Opioid
Receptor-Based DREADD in Rats
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID CONTEXT-INDUCED REINSTATEMENT; PROTEIN-COUPLED RECEPTORS;
NUCLEUS-ACCUMBENS; HEROIN SEEKING; DOPAMINE NEURONS; SALVINORIN-A;
REMOTE-CONTROL; PROJECTIONS; SUBICULUM; GLUTAMATE
AB In the past decade, novel methods using engineered receptors have enabled researchers to manipulate neuronal activity with increased spatial and temporal specificity. One widely used chemogenetic method in mice and rats is the DREADD (designer receptors exclusively activated by designer drugs) system in which a mutated muscarinic G protein-coupled receptor is activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). Recently, the Roth laboratory developed a novel inhibitory DREADD in which a mutated kappa-opioid receptor (KORD) is activated by the pharmacologically inert drug salvinorin B (SalB; Vardy et al, 2015). They demonstrated the feasibility of using KORD to study brain circuits involved in motivated behavior in mice. Here, we used behavioral, electrophysiological, and neuroanatomical methods to demonstrate the feasibility of using the novel KORD to study brain circuits involved in motivated behavior in rats. In Exp. 1, we show that SalB dose-dependently decreased spontaneous and cocaine-induced locomotor activity in rats expressing KORD to midbrain (ventral tegmental area/substantia nigra). In Exp. 2, we show that SalB completely inhibited tonic firing in KORD-expressing putative dopamine neurons in midbrain. In Exp. 3, we used a 'retro-DREADD' dual-virus approach to restrict expression of KORD in ventral subiculum neurons that project to nucleus accumbens shell. We show that KORD activation selectively decreased novel context-induced Fos expression in this projection. Our results indicate that the novel KORD is a promising tool to selectively inactivate brain areas and neural circuits in rat studies of motivated behavior.
C1 [Marchant, Nathan J.; Whitaker, Leslie R.; Bossert, Jennifer M.; Hope, Bruce T.; Kaganovsky, Konstantin; Adhikary, Sweta; Shaham, Yavin] NIDA, Behav Neurosci Res Branch, IRP, NIH, Bethesda, MD 20892 USA.
[Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
[Harvey, Brandon K.] NIDA, Optogenet & Transgen Technol Core, IRP, NIH, Bethesda, MD 20892 USA.
[Prisinzano, Thomas E.] Univ Kansas, Sch Pharm, Dept Med Chem, Lawrence, KS 66045 USA.
[Vardy, Eyal] Merck Res Labs, Kenilworth, NJ USA.
[Vardy, Eyal; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
RP Marchant, NJ (reprint author), NIDA, Behav Neurosci Res Branch, IRP, NIH, Bethesda, MD 20892 USA.
EM nathan.marchant@nih.gov; Yshaham@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010;
OI Hope, Bruce/0000-0001-5804-7061; Kaganovsky,
Konstantin/0000-0002-1577-109X
FU NINDS; NIDA-IRP funds; National Health and Medical Research Council
[1053308]; NIH [DA018151]; Asubio Pharmaceuticals; Merck Pharmacology;
NIMH BRAIN Initiative Grant
FX CNO was obtained from the NIH as part of the Rapid Access to
Investigative Drug Program funded by the NINDS. NJM, LRW, JMB, BKH, BTH,
KK, SW, and YS were supported by NIDA-IRP funds to the laboratories of
Yavin Shaham and Bruce Hope. NJM received support from Early Career
Fellowship 1053308 by the National Health and Medical Research Council.
TEP was supported by NIH grant DA018151. EV is currently employed at
Merck. BLR has consulted in the past 18 months with Pfizer, Novartis,
Merck and RuiYi Pharmaceuticals. BLR has received an unrestricted grant
from Asubio Pharmaceuticals and receives compensation as Deputy Editor
of the Journal of Clinical Investigation. BLR has received grant support
for DREADD technology unrelated to this manuscript from Merck
Pharmacology. BLR was supported by an NIMH BRAIN Initiative Grant.
NR 40
TC 12
Z9 12
U1 3
U2 14
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 JAN
PY 2016
VL 41
IS 2
BP 402
EP 409
DI 10.1038/npp.2015.149
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OZ
UT WOS:000366599400003
PM 26019014
ER
PT J
AU Kiyatkin, EA
Ren, S
Wakabayashi, KT
Baumann, MH
Shaham, Y
AF Kiyatkin, Eugene A.
Ren, Suelynn
Wakabayashi, Ken T.
Baumann, Michael H.
Shaham, Yavin
TI Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced
Brain Hyperthermia Potentiated by Social Interaction
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA;
CUTANEOUS VASODILATION; ECSTASY MDMA; HUMANS; TEMPERATURE;
VASOCONSTRICTION; CLOZAPINE; RATS; NEUROTOXICITY
AB MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 degrees C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.
C1 [Kiyatkin, Eugene A.; Ren, Suelynn; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci, IRP, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU National Institute on Drug Abuse-Intramural Research Program, NIH
FX We greatly appreciate the great expertize and valuable assistance of Dr
Charles Spivak in dissolving drugs used in this study. This study is
supported by the National Institute on Drug Abuse-Intramural Research
Program, NIH. EAK and YS designed the research; EAK and SR performed the
research; EAK and SR analyzed the data; EAK, SR, YS, MHB and KTW wrote
the paper. The authors declare no conflict of interest.
NR 44
TC 2
Z9 2
U1 0
U2 5
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 JAN
PY 2016
VL 41
IS 2
BP 549
EP 559
DI 10.1038/npp.2015.182
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OZ
UT WOS:000366599400017
PM 26105141
ER
PT S
AU Ferre-D'Amare, AR
AF Ferre-D'Amare, Adrian R.
BE Ennifar, E
TI Use of the U1A Protein to Facilitate Crystallization and Structure
Determination of Large RNAs
SO NUCLEIC ACID CRYSTALLOGRAPHY: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Crystallization; Crystallizability; Spliceosomal protein; RNA-binding
domain (RBD); Protein purification
ID DELTA VIRUS RIBOZYME; CRYSTAL-STRUCTURE; COMPLEX; RIBOSWITCH; MODULE
AB The preparation of well-ordered crystals of RNAs with complex three-dimensional architecture can be facilitated by engineering a binding site for the spliceosomal protein U1A into a functionally and structurally dispensable stem-loop of the RNA of interest. Once suitable crystals are obtained, the U1A protein, of known structure, can be employed to facilitate preparation of heavy atom or anomalously scattering atom derivatives, or as a source of partial model phases for the molecular replacement method. Here, we describe the methods for making U1A preparations suitable for cocrystallization with RNA. As an example, the cocrystallization of the tetracycline aptamer with U1A is also described.
C1 [Ferre-D'Amare, Adrian R.] NHLBI, Lab RNA Biophys & Cellular Physiol, Bethesda, MD 20892 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, Lab RNA Biophys & Cellular Physiol, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 HL999999, ZIA HL006102-02, ZIA HL006102-01, ]
NR 20
TC 1
Z9 1
U1 2
U2 17
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4939-2763-0; 978-1-4939-2762-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2016
VL 1320
BP 67
EP 76
DI 10.1007/978-1-4939-2763-0_6
D2 10.1007/978-1-4939-2763-0
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Crystallography
SC Biochemistry & Molecular Biology; Crystallography
GA BE0OE
UT WOS:000366483300007
PM 26227038
ER
PT J
AU Hallett, M
AF Hallett, Mark
TI Functional (psychogenic) movement disorders - Clinical presentations
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article; Proceedings Paper
CT 21st World Congress on Parkinson's Disease and Relative Disorders
CY DEC 06-09, 2015
CL Milan, ITALY
DE Functional movement disorder; Psychogehic movement disorder; Conversion;
Tremor; Myoclonus; Dystonia; Gait disorder
ID PERIPHERAL TRAUMA; TREMOR; PARKINSONISM; DIAGNOSIS; SYMPTOMS; DYSTONIA;
GAIT
AB Functional or psychogenic movement disorders are common and disabling, and sometime difficult to diagnose. The history and physical exam can give positive features that will support the diagnosis, which should not be based solely on exclusion. Some clues in the history are sudden onset, intermittent time course, variability of manifestation over time, childhood trauma, history of other somatic symptom and secondary gain. Anxiety and depression are common, but not necessarily more than the general population. On examination, distraction and suggestibility may be present. There are specific signs that should be looked for with different types of movements. For example, with tremor, change in frequency over time and entrainment are common features. With myoclonus, the movements might be complex in type with long latencies to stimulus induced jerks. Gait disorders show good balance despite claims to the contrary. Functional dystonia still remains a challenging diagnosis in many circumstances, although fixed dystonia is one sign more likely to be functional. Published by Elsevier Ltd.
C1 [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
OI Hallett, Mark/0000-0002-3180-6811
FU Intramural NIH HHS [Z01 NS002667-24]
NR 26
TC 3
Z9 3
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JAN
PY 2016
VL 22
SU 1
BP S149
EP S152
DI 10.1016/j.parkreldis.2015.08.036
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA CZ0GA
UT WOS:000366781900032
PM 26365778
ER
PT J
AU Floto, RA
Olivier, KN
Saiman, L
Daley, CL
Herrmann, JL
Nick, JA
Noone, PG
Bilton, D
Corris, P
Gibson, RL
Hempstead, SE
Koetz, K
Sabadosa, KA
Sermet-Gaudelus, I
Smyth, AR
van Ingen, J
Wallace, RJ
Winthrop, KL
Marshall, BC
Haworth, CS
AF Floto, R. Andres
Olivier, Kenneth N.
Saiman, Lisa
Daley, Charles L.
Herrmann, Jean-Louis
Nick, Jerry A.
Noone, Peadar G.
Bilton, Diana
Corris, Paul
Gibson, Ronald L.
Hempstead, Sarah E.
Koetz, Karsten
Sabadosa, Kathryn A.
Sermet-Gaudelus, Isabelle
Smyth, Alan R.
van Ingen, Jakko
Wallace, Richard J.
Winthrop, Kevin L.
Marshall, Bruce C.
Haworth, Charles S.
TI US Cystic Fibrosis Foundation and European Cystic Fibrosis Society
consensus recommendations for the management of non-tuberculous
mycobacteria in individuals with cystic fibrosis: executive summary
SO THORAX
LA English
DT Editorial Material
ID DIAGNOSIS
AB Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with preexisting inflammatory lung disease, such as cystic fibrosis (CF). Pulmonary disease (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition.
C1 [Floto, R. Andres] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Floto, R. Andres; Haworth, Charles S.] Papworth Hosp, Cambridge Ctr Lung Infect, Cambridge CB3 8RE, England.
[Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Saiman, Lisa] Columbia Univ, Dept Pediat, Med Ctr, Pediat Infect Dis, New York, NY 10027 USA.
[Daley, Charles L.] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Denver, CO USA.
[Herrmann, Jean-Louis] Versailles St Quentin Univ, UFR Simone Veil, INSERM U1173, St Quentin En Yvelines, France.
[Herrmann, Jean-Louis] Hop Raymond Poincare, AP HP, Microbiol Serv, Garches, France.
[Nick, Jerry A.] Natl Jewish Hlth, Dept Med, Denver, CO USA.
[Noone, Peadar G.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA.
[Bilton, Diana] Royal Brompton Hosp, Dept Resp Med, London SW3 6LY, England.
[Corris, Paul] Freeman Hosp High Heaton, Dept Resp Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Gibson, Ronald L.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Hempstead, Sarah E.; Sabadosa, Kathryn A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Koetz, Karsten] Sahlgrens Univ Hosp, Dept Pediat, Gothenburg, Sweden.
[Sermet-Gaudelus, Isabelle] Univ Paris 05, Hop Necker Enfants Malad, Serv Pneumopediat, Paris, France.
[Smyth, Alan R.] Univ Nottingham, Div Child Hlth Obstet & Gynaecol, Nottingham NG7 2RD, England.
[van Ingen, Jakko] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
[Wallace, Richard J.] Univ Texas Tyler, Hlth Sci Ctr, Dept Microbiol, Tyler, TX 75799 USA.
[Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA.
[Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Div Publ Hlth, Portland, OR 97201 USA.
[Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Div Prevent Med, Portland, OR 97201 USA.
[Marshall, Bruce C.] Cyst Fibrosis Fdn, Bethesda, MD USA.
RP Floto, RA (reprint author), Univ Cambridge, Cambridge Inst Med Res, Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0XY, England.
EM arf27@cam.ac.uk
RI van Ingen, Jakko/D-5526-2014;
OI van Ingen, Jakko/0000-0002-0581-2003; Andres,
Rodrigo/0000-0002-2188-5659; Herrmann, Jean-Louis/0000-0003-2347-6418;
Smyth, Alan/0000-0001-5494-5438
FU Cystic Fibrosis Foundation; European Cystic Fibrosis Society; Wellcome
Trust; Cambridge NIHR BRC; Intramural programme of the National Heart,
Lung, and Blood Institute, NIH; Vaincre La Mucoviscidose [VLMIC1014,
RF20120600689]; Region Ile-de-France Domaine d'Interet Majeur Maladies
Infectieuses et Emergentes; CF Foundation Clinical Research Award
[NICK13A0]; Imperial College London NIHR Respiratory BRU
FX Cystic Fibrosis Foundation; European Cystic Fibrosis Society, The
Wellcome Trust & Cambridge NIHR BRC (RAF); Intramural programme of the
National Heart, Lung, and Blood Institute, NIH (KNO); Vaincre La
Mucoviscidose (VLMIC1014 and RF20120600689) and the Region Ile-de-France
Domaine d'Interet Majeur Maladies Infectieuses et Emergentes (J-LH); CF
Foundation Clinical Research Award (NICK13A0) (JAN) and Imperial College
London NIHR Respiratory BRU (DB).
NR 5
TC 10
Z9 10
U1 1
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
EI 1468-3296
J9 THORAX
JI Thorax
PD JAN
PY 2016
VL 71
IS 1
BP 88
EP 90
DI 10.1136/thoraxjnl-2015-207983
PG 3
WC Respiratory System
SC Respiratory System
GA CY8TV
UT WOS:000366682100014
PM 26678435
ER
PT J
AU Gupta, T
Robles, MTS
Schowalter, RM
Buck, CB
Pipas, JM
AF Gupta, Tushar
Robles, Maria Teresa Saenz
Schowalter, Rachel M.
Buck, Christopher B.
Pipas, James M.
TI Expression of the small T antigen of Lymphotropic Papovavirus is
sufficient to transform primary mouse embryo fibroblasts
SO VIROLOGY
LA English
DT Article
DE LPV; Transformation; sT; Polyomavirus; SV40
ID AFRICAN-GREEN MONKEY; TRANSGENIC MICE; POLYOMAVIRUS; CELLS; P53;
PROTEINS; VIRUS
AB Polyomaviruses induce cell proliferation and transformation through different oncoproteins encoded within the early region (ER): large T antigen (LT), small T antigen (sT) and, in some cases, additional components. Each virus utilizes different mechanisms to achieve transformation. For instance, the LTs of Simian virus 40 (SV40), BK and/or JC virus can induce transformation; but Merkel Cell Polyomavirus (MCPyV) requires expression of sT. Lymphotropic Papovavirus (LPV) is closely related to Human Polyomavirus 9 (HuPyV9) and, under similar conditions, mice expressing LPV.ER exhibit higher rates of tumor formation than mice expressing SV40.ER. We have investigated the contributions of individual LPV.ER components to cell transformation. In contrast to SV40, LPV.ER transforms mouse embryonic fibroblasts (MEFs), but expression of LPV LT is insufficient to transform MEFs. Furthermore, LPV sT induces immortalization and transformation of MEFs. Thus, in the case of LPV, sT is the main mediator of oncogenesis. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Gupta, Tushar; Robles, Maria Teresa Saenz; Pipas, James M.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Schowalter, Rachel M.; Buck, Christopher B.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pipas, JM (reprint author), Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
EM pipas@pitt.edu
FU NIH [1R21AI109339-01A1]
FX This work was supported by NIH Grant 1R21AI109339-01A1 to JMP.
NR 29
TC 2
Z9 2
U1 0
U2 1
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 JAN
PY 2016
VL 487
BP 112
EP 120
DI 10.1016/j.virol.2015.10.003
PG 9
WC Virology
SC Virology
GA CY5HK
UT WOS:000366438500013
PM 26517398
ER
PT J
AU Eren, E
Zamuda, K
Patton, JT
AF Eren, Elif
Zamuda, Kimberly
Patton, John T.
TI Modeling of the rotavirus group C capsid predicts a surface topology
distinct from other rotavirus species
SO VIROLOGY
LA English
DT Article
DE Rotavirus; Capsid structure; Antigenic topology
ID LINKED GLYCOSYLATION SITE; RAY CRYSTAL-STRUCTURE; VIRUS-LIKE PARTICLES;
ACID-BINDING DOMAIN; S-LAC LECTIN; SIALIC-ACID; RHESUS ROTAVIRUS;
RECEPTOR-BINDING; UNITED-STATES; CELL-SURFACE
AB Rotavirus C (RVC) causes sporadic gastroenteritis in adults and is an established enteric pathogen of swine. Because RVC strains grow poorly in cell culture, which hinders generation of virion-derived RVC triple-layered-particle (TLP) structures, we used the known Rotavirus A (RVA) capsid structure to model the human RVC (Bristol) capsid. Comparative analysis of RVA and RVC capsid proteins showed major differences at the VP7 layer, an important target region for vaccine development due to its antigenic properties. Our model predicted the presence of a surface extended loop in RVC, which could form a major antigenic site on the capsid. We analyzed variations in the glycosylation patterns among RV capsids and identified group specific conserved sites. In addition, our results showed a smaller RVC VP4 foot, which protrudes toward the intermediate VP6 layer, in comparison to that of RVA. Finally, our results showed major structural differences at the VP8* glycan recognition sites. Published by Elsevier Inc.
C1 [Eren, Elif; Zamuda, Kimberly; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Eren, E (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Room 6312, Bethesda, MD 20892 USA.
EM elif.eren@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We would like to thank to the members of the laboratory for critical
review of the manuscript and helpful discussions. This work was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
NR 78
TC 1
Z9 1
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 0042-6822
J9 VIROLOGY
JI Virology
PD JAN
PY 2016
VL 487
BP 150
EP 162
DI 10.1016/j.virol.2015.10.017
PG 13
WC Virology
SC Virology
GA CY5HK
UT WOS:000366438500017
PM 26524514
ER
PT J
AU Arnardottir, NY
Koster, A
Van Domelen, DR
Brychta, RJ
Caserotti, P
Eiriksdottir, G
Sverrisdottir, JE
Sigurdsson, S
Johannsson, E
Chen, KY
Gudnason, V
Harris, TB
Launer, LJ
Sveinsson, T
AF Arnardottir, Nanna Yr
Koster, Annemarie
Van Domelen, Dane R.
Brychta, Robert J.
Caserotti, Paolo
Eiriksdottir, Gudny
Sverrisdottir, Johanna E.
Sigurdsson, Sigurdur
Johannsson, Erlingur
Chen, Kong Y.
Gudnason, Vilmundur
Harris, Tamara B.
Launer, Lenore J.
Sveinsson, Thorarinn
TI Association of change in brain structure to objectively measured
physical activity and sedentary behavior in older adults: Age,
Gene/Environment Susceptibility-Reykjavik Study
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Physical activity; Sedentary behavior; Brain atrophy; Elderly; MRI
ID WHITE-MATTER INTEGRITY; COGNITIVE DECLINE; UNITED-STATES; TISSUE
VOLUMES; AGING HUMANS; RISK-FACTORS; EXERCISE; HEALTH; ATROPHY;
POPULATION
AB Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n = 352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days. More GM (beta = 0.11; p = 0.044) and WM (beta = 0.11; p = 0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (beta = 0.14; p = 0.0037) and WM (beta = 0.11; p = 0.030) was associated with TPA. The 5-year change in WM was associated with SB (p = 0.11; p = 0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Arnardottir, Nanna Yr; Sveinsson, Thorarinn] Univ Iceland, Res Ctr Movement Sci, IS-101 Reykjavik, Iceland.
[Arnardottir, Nanna Yr; Eiriksdottir, Gudny; Sverrisdottir, Johanna E.; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, NL-6200 MD Maastricht, Netherlands.
[Van Domelen, Dane R.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Brychta, Robert J.; Chen, Kong Y.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Caserotti, Paolo] Univ Southern, Dept Sports Sci & Clin Biomech, Odense, Denmark.
[Johannsson, Erlingur] Univ Iceland, Ctr Sport & Hlth Sci, Laugarvatn, Iceland.
[Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
RP Arnardottir, NY (reprint author), Univ Iceland, Res Ctr Movement Sci, IS-101 Reykjavik, Iceland.
EM nya@hi.is
RI Sveinsson, Thorarinn/F-7554-2010; Dey, Kamalesh/E-6568-2017; Koster,
Annemarie/E-7438-2010;
OI Sveinsson, Thorarinn/0000-0001-8989-5514; Chen, Kong/0000-0002-0306-1904
FU NIA [N01-AG-1-2100]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament);
National Science Foundation Graduate Research Fellowship [DGE-0940903];
National Institutes of Health Intramural Research Program [Z01 DK071013,
Z01 DK071014]
FX This study has been funded by NIA contract N01-AG-1-2100, the NIA
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament). This work was
also supported by the National Science Foundation Graduate Research
Fellowship under Grant No. DGE-0940903 and by the National Institutes of
Health Intramural Research Program, grant number: Z01 DK071013 and Z01
DK071014 to RJB and KYC. Thor Aspelund is acknowledged for statistical
consultation. The researchers are indebted to the participants for their
willingness to participate in the study.
NR 66
TC 3
Z9 3
U1 2
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JAN 1
PY 2016
VL 296
BP 118
EP 124
DI 10.1016/j.bbr.2015.09.005
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CY0EL
UT WOS:000366079100016
PM 26363425
ER
PT J
AU Tsutsui-Kimura, I
Ohmura, Y
Izumi, T
Matsushima, T
Amita, H
Yamaguchi, T
Yoshida, T
Yoshioka, M
AF Tsutsui-Kimura, Iku
Ohmura, Yu
Izumi, Takeshi
Matsushima, Toshiya
Amita, Hidetoshi
Yamaguchi, Taku
Yoshida, Takayuki
Yoshioka, Mitsuhiro
TI Neuronal codes for the inhibitory control of impulsive actions in the
rat infralimbic cortex
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Ventromedial prefrontal cortex; Response inhibition; Impulsivity;
Five-choice serial reaction time task; Single-cell recording
ID REACTION-TIME-TASK; MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE;
NUCLEUS-ACCUMBENS; RESPONSE-INHIBITION; RECEPTOR ANTAGONISM; BIPOLAR
DISORDER; PERFORMANCE; BEHAVIORS; ATTENTION
AB Poor impulse control is a debilitating condition observed in various psychiatric disorders and could be a risk factor for drug addiction, criminal involvement, and suicide. The rat infralimbic cortex (IL), located in the ventral portion of the medial prefrontal cortex, has been implicated in impulse control. To elucidate the neurophysiological basis of impulse control, we recorded single unit activity in the IL of a rat performing a 3-choiceserial reaction time task (3-CSRTT) and 2-choice task (2-CT), which are animal models for impulsivity. The inactivation of IL neuronal activity with an injection of muscimol (0.1 mu g/side) disrupted impulse control in the 3-CSRTT. More than 60% (38/56) of isolated IL units were linked to impulse control, while approximately 30% of all units were linked to attentional function in the 3-CSRTT. To avoid confounding motor-related units with the impulse control-related units, we further conducted the 2-CT in which the animals' motor activities were restricted during recording window. More than 30% (14/44) of recorded IL units were linked to impulse control in the 2-CT. Several types of impulse control-related units were identified. Only 16% of all units were compatible with the results of the muscimol experiment, which showed a transient decline in the firing rate immediately before the release of behavioral inhibition. This is the first study to elucidate the neurophysiological basis of impulse control in the IL and to propose that IL neurons control impulsive actions in a more complex manner than previously considered. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Tsutsui-Kimura, Iku; Ohmura, Yu; Izumi, Takeshi; Yoshida, Takayuki; Yoshioka, Mitsuhiro] Hokkaido Univ, Grad Sch Med, Dept Neuropharmacol, Sapporo, Hokkaido 0608638, Japan.
[Matsushima, Toshiya] Hokkaido Univ, Fac Sci, Dept Biol, Sapporo, Hokkaido 0608638, Japan.
[Amita, Hidetoshi] Hokkaido Univ, Grad Sch Life Sci, Sapporo, Hokkaido 0608638, Japan.
[Amita, Hidetoshi] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Yamaguchi, Taku] Nagasaki Int Univ, Dept Pharmacol, Fac Pharmaceut Sci, Sasebo, Japan.
[Tsutsui-Kimura, Iku] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan.
[Tsutsui-Kimura, Iku] Japan Soc Promot Sci, Tokyo, Japan.
RP Izumi, T (reprint author), Hokkaido Univ, Grad Sch Med, Dept Neuropharmacol, N15 W7 Kita Ku, Sapporo, Hokkaido 0608638, Japan.
EM psyizumi@med.hokudai.ac.jp
OI Ohmura, Yu/0000-0002-1537-7332
FU Smoking Research Foundation; Grant for Research Fellow of the Japan
Society for the Promotion of Science [234134]; Japanese Ministry of
Education, Culture, Sports, Science and Technology [06770740]
FX The authors would like to thank Dr. Masaki Tanaka (Hokkaido University,
Japan) and Dr. Takuya Kubo (Hokkaido University, Japan) for their
valuable comments and technical suggestions for this manuscript. This
study was supported by a Grant from the Smoking Research Foundation
(URL: http://www.srf.or.jp/english/index.html) and by Grant for Research
Fellow of the Japan Society for the Promotion of Science 234134 (I.T.K.)
and by the Japanese Ministry of Education, Culture, Sports, Science and
Technology grant No. 06770740 (T. I.).
NR 43
TC 4
Z9 4
U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JAN 1
PY 2016
VL 296
BP 361
EP 372
DI 10.1016/j.bbr.2015.08.025
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CY0EL
UT WOS:000366079100045
PM 26341319
ER
PT J
AU Araki, T
Nishino, M
Gao, W
Dupuis, J
Hunninghake, GM
Murakami, T
Washko, GR
O'Connor, GT
Hatabu, H
AF Araki, Tetsuro
Nishino, Mizuki
Gao, Wei
Dupuis, Josee
Hunninghake, Gary M.
Murakami, Takamichi
Washko, George R.
O'Connor, George T.
Hatabu, Hiroto
TI Normal thymus in adults: appearance on CT and associations with age,
sex, BMI and smoking
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Computed tomography; Thymus gland; Adult; Body mass index; Smoking
ID COMPUTED-TOMOGRAPHY; LUNG-CANCER; HYPERPLASIA; SIZE
AB To investigate CT appearance and size of the thymus in association with participant characteristics.
2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history.
Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04).
Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus.
aEuro cent 74 % of participants (mean age 58.9 years) demonstrated complete fatty thymus.
aEuro cent Women show less fatty thymus compared to men at ages 40-69 years.
aEuro cent Smoking and high BMI are associated with advanced fatty degeneration in thymus.
C1 [Araki, Tetsuro; Nishino, Mizuki; Hatabu, Hiroto] Harvard Univ, Brigham & Womens Hosp, Ctr Pulm Funct Imaging, Dept Radiol,Sch Med, Boston, MA 02215 USA.
[Araki, Tetsuro; Murakami, Takamichi] Kinki Univ, Fac Med, Dept Radiol, Osaka, Japan.
[Gao, Wei; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Dupuis, Josee; O'Connor, George T.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Hunninghake, Gary M.; Washko, George R.] Harvard Univ, Brigham & Womens Hosp, Div Pulm & Crit Care, Sch Med, Boston, MA 02115 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02215 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Araki, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Pulm Funct Imaging, Dept Radiol,Sch Med, 75 Francis St, Boston, MA 02215 USA.
EM taraki@partners.org
FU NCI [1K23CA157631]; NIH [R01 HL116473, R01 HL107246, P01 HL114501, K08
HL092222, U01 HL105371, R01 HL111024, K25 HL104085]; NHLBI [R01
HL111024, N01-HC-25195]
FX Authors acknowledge Alba Cid M.S. for editorial work on the manuscript.
The scientific guarantor of this publication is Tetsuro Araki, MD. The
authors of this manuscript declare no relationships with any companies
whose products or services may be related to the subject matter of the
article. This study has received the following fundings. Dr. Nishino is
supported by NCI Grant Number: 1K23CA157631. Dr. Washko is supported by
NIH Grant Number: R01 HL116473, R01 HL107246 and P01 HL114501. Dr.
Hunninghake is supported by NIH Grant Number: K08 HL092222, U01
HL105371, P01 HL114501, and R01 HL111024. Dr. Hatabu is supported by NIH
Grant Number: K25 HL104085 and R01 HL116473. This work was partially
supported by the NHLBI's Framingham Heart Study contract: N01-HC-25195
and R01 HL111024.
NR 26
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
EI 1432-1084
J9 EUR RADIOL
JI Eur. Radiol.
PD JAN
PY 2016
VL 26
IS 1
BP 15
EP 24
DI 10.1007/s00330-015-3796-y
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CX5EP
UT WOS:000365725200003
PM 25925358
ER
PT J
AU Drozdovitch, V
Kukhta, T
Minenko, V
Trofimik, S
Bouville, A
Potischman, N
AF Drozdovitch, Vladimir
Kukhta, Tatiana
Minenko, Victor
Trofimik, Sergey
Bouville, Andre
Potischman, Nancy
TI RELIABILITYOF QUESTIONNAIRE DATA IN THE DISTANT PAST: RELEVANCE FOR
RADIATION EXPOSURE ASSESSMENT
SO HEALTH PHYSICS
LA English
DT Article
DE Chernobyl; dose assessment; radiation dose; thyroid
ID BELARUSIAN CHILDREN; CHERNOBYL ACCIDENT; DIET; RECALL; REPRODUCIBILITY;
COHORT; FREQUENCY; I-131
AB Interviews with questionnaires are often employed to provide information that may be used for exposure assessment, although the reliability of such information is largely unknown. In this work, the consistency of individual behavior and dietary data collected by means of personal interviews during two study screenings was evaluated. Data were collected for a cohort of about 11,000 persons exposed to I-131 in childhood and adolescence shortly after the Chernobyl accident. The best recollection was found for residential history, milk consumption patterns, and, to a lesser degree, stable iodine administration, while reproducibility of responses about consumption of milk products and leafy vegetables was poor. Consistency of information reported during the personal interviews by the study subjects younger than 10 y at the time of the accident was somewhat lower than for the subjects aged 10-18 y. The authors found slightly better reproducibility of responses for female study subjects than for male subjects and when the time span between two interviews was shorter. In the majority of instances, the best consistency in responses was observed when the mother was interviewed during both screenings rather than the subject. Information that was collected during two personal interviews was used to calculate two sets of thyroid doses due to I-131 intakes. This study shows that, because dose-related measurements are available for all study subjects, the quality of individual behavior and dietary data has, in general, a small influence on the results of the retrospective dose assessment. For studies in which dose-related measurements are not available for all study subjects and only modeling is used for dose reconstruction, high quality individual behavior and dietary data for the study subjects are required to provide realistic and reliable dose estimates.
C1 [Drozdovitch, Vladimir; Potischman, Nancy] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Kukhta, Tatiana] United Inst Informat Problems, Minsk, Byelarus.
[Minenko, Victor; Trofimik, Sergey] Res Inst Nucl Problems, Minsk, Byelarus.
[Bouville, Andre] US Natl Canc Inst, Rockville, MD USA.
RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 9609 Med Ctr Dr,Room 7E548,MSC 9778, Bethesda, MD 20892 USA.
EM drozdovv@mail.nih.gov
FU U.S. National Institutes of Health, National Cancer Institute, Division
of Cancer Epidemiology; National Institute of Allergy and Infectious
Diseases (U.S.); National Cancer Institute, NIAID [DCC-OD-12-900]
FX This work was supported by the U.S. National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
within the framework of Belarus-U.S. Study of Thyroid Cancer and Other
Disease Following the Chernobyl Accident and by the Intra-Agency
Agreement between the National Institute of Allergy and Infectious
Diseases (U.S.) and the National Cancer Institute, NIAID agreement
#DCC-OD-12-900. The authors would like to thank the staff of the
Belarusian Medical Academy of Post-Graduate Education (Minsk, Belarus)
and the Republican Research Center for Radiation Medicine and Human
Ecology (Gomel, Belarus) who conducted personal interviews and processed
and verified the information collected during personal interviews into
the databases.
NR 23
TC 1
Z9 1
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JAN
PY 2016
VL 110
IS 1
BP 74
EP 92
DI 10.1097/HP.0000000000000406
PG 19
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA CY2OX
UT WOS:000366249100009
PM 26606068
ER
PT J
AU Cooper, LL
Woodard, T
Sigurdsson, S
van Buchem, MA
Torjesen, AA
Inker, LA
Aspelund, T
Eiriksdottir, G
Harris, TB
Gudnason, V
Launer, LJ
Mitchell, GF
AF Cooper, Leroy L.
Woodard, Todd
Sigurdsson, Sigurdur
van Buchem, Mark A.
Torjesen, Alyssa A.
Inker, Lesley A.
Aspelund, Thor
Eiriksdottir, Gudny
Harris, Tamara B.
Gudnason, Vilmundur
Launer, Lenore J.
Mitchell, Gary F.
TI Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and
Memory
SO HYPERTENSION
LA English
DT Article
DE cognition; dementia; hemodynamics; memory; vascular stiffness
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; PULSE-WAVE VELOCITY; ARTERIAL
STIFFNESS; COGNITIVE DECLINE; BLOOD-PRESSURE; AGES-REYKJAVIK; ADVANCING
AGE; RISK-FACTORS; HYPERTENSION; HEMODYNAMICS
AB Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment SusceptibilityReykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized : -0.071 +/- 0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained approximate to 41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.
C1 [Cooper, Leroy L.; Woodard, Todd; Torjesen, Alyssa A.; Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA 02062 USA.
[Cooper, Leroy L.] Brown Univ, Rhode Isl Hosp, W Alpert Med Sch, Cardiovasc Res Ctr, Providence, RI 02903 USA.
[Sigurdsson, Sigurdur; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Inker, Lesley A.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Inker, Lesley A.] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 1 Edgewater Dr,Suite 201A, Norwood, MA 02062 USA.
EM GaryFMitchell@mindspring.com
FU National Institutes of Health [N01-AG-12100, 5T32HL094300-05]; National
Institute on Ageing; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); National Institutes of Health,
National Heart, Lung and Blood Institute [HL094898]; UNCF/Merck Science
Initiative
FX This study was supported by National Institutes of Health (contract
N01-AG-12100), National Institute on Ageing Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic
Parliament), and National Institutes of Health, National Heart, Lung and
Blood Institute (HL094898). L.L. Cooper is also supported by National
Institutes of Health grant 5T32HL094300-05 and the UNCF/Merck Science
Initiative.
NR 40
TC 9
Z9 9
U1 4
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JAN
PY 2016
VL 67
IS 1
BP 176
EP 182
DI 10.1161/HYPERTENSIONAHA.115.06398
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CY2RC
UT WOS:000366254800026
PM 26573713
ER
PT J
AU Song, CY
Ghafoor, K
Ghafoor, HU
Khan, NS
Thirunavukkarasu, S
Jennings, BL
Estes, AM
Zaidi, S
Bridges, D
Tso, P
Gonzalez, FJ
Malik, KU
AF Song, Chi Young
Ghafoor, Khuzema
Ghafoor, Hafiz U.
Khan, Nayaab S.
Thirunavukkarasu, Shyamala
Jennings, Brett L.
Estes, Anne M.
Zaidi, Sahar
Bridges, Dave
Tso, Patrick
Gonzalez, Frank J.
Malik, Kafait U.
TI Cytochrome P450 1B1 Contributes to the Development of Atherosclerosis
and Hypertension in Apolipoprotein E-Deficient Mice
SO HYPERTENSION
LA English
DT Article
DE apolipoprotein E; deficiency; cytochrome P450 1B1; diet; atherogenic;
plasma lipids; vascular; remodeling
ID SMOOTH-MUSCLE-CELLS; SALT-INDUCED HYPERTENSION; INDUCIBLE EXPRESSION;
VASCULAR-DISEASE; OXIDATIVE STRESS; CYP1B1; PROMOTES; P4501B1; ACID;
3-METHYLCHOLANTHRENE
AB Cytochrome P450 (CYP) 1B1 contributes to vascular smooth muscle cell growth and hypertension in male mice. This study was conducted to determine the contribution of CYP1B1 to the development of atherosclerosis and hypertension and associated pathogenesis in 8-week-old male apolipoprotein E-deficient (ApoE(-/-)/Cyp1b1(+/+)), and ApoE- and CYP1B1-deficient (ApoE(-/-)/Cyp1b1(-/-)) mice fed a normal or atherogenic diet for 12 weeks. A separate group of ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet was injected every third day with the CYP1B1 inhibitor, 2,3,4,5-tetramethoxystilbene (300 g/kg), or its vehicle, dimethyl sulfoxide (30 L, IP); systolic blood pressure was measured by the tail cuff method. After 12 weeks, mice were euthanized, blood collected for lipid analysis, and aortas harvested for measuring lesions and remodeling, and for infiltration of inflammatory cells by histological and immunohistochemical analysis, respectively, and for reactive oxygen species production. Blood pressure, areas of lipids and collagen deposition, elastin breaks, infiltration of macrophages and T lymphocytes, reactive oxygen species generation in the aorta, and plasma lipid levels were increased in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet; these changes were minimized in mice given 2,3,4,5-tetramethoxystilbene, and in ApoE(-/-)/Cyp1b1(-/-) mice on an atherogenic diet; absorption/production of lipids remained unaltered in these mice. These data suggest that aortic lesions, hypertension, and associated pathogenesis in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet are most likely dependent on CYP1B1-generated oxidative stress and increased plasma lipid levels independent of blood pressure and absorption of lipids. CYP1B1 could serve as a novel target for developing drugs to treat atherosclerosis and hypertension caused by hypercholesterolemia.
C1 [Song, Chi Young; Ghafoor, Khuzema; Ghafoor, Hafiz U.; Khan, Nayaab S.; Thirunavukkarasu, Shyamala; Jennings, Brett L.; Estes, Anne M.; Zaidi, Sahar; Malik, Kafait U.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA.
[Bridges, Dave] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Physiol & Pediat, Memphis, TN 38163 USA.
[Tso, Patrick] Univ Cincinnati, Dept Pathobiol & Mol Med, Cincinnati, OH 45221 USA.
[Gonzalez, Frank J.] NCI, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA.
RP Malik, KU (reprint author), Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA.
EM kmalik@uthsc.edu
OI Bridges, Dave/0000-0002-5334-972X
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[R01HL079109-08]; Memphis Research Consortium; Le Bonheur Children's
Hospital; Mouse Metabolic Phenotyping Center NIH [DK059630]
FX This work was supported by the National Institutes of Health, National
Heart, Lung, and Blood Institute grant R01HL079109-08 (Dr Malik),
Memphis Research Consortium and Le Bonheur Children's Hospital (Dr
Bridges), and Mouse Metabolic Phenotyping Center NIH DK059630 (Dr Tso).
The contents of this article are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Heart, Lung, and Blood Institute.
NR 46
TC 2
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JAN
PY 2016
VL 67
IS 1
BP 206
EP 213
DI 10.1161/HYPERTENSIONAHA.115.06427
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CY2RC
UT WOS:000366254800030
PM 26573711
ER
PT J
AU Williamson, PR
Nash, TE
Williamson, KC
Nath, A
AF Williamson, Peter R.
Nash, Theodore E.
Williamson, Kim C.
Nath, Avindra
TI CNS infections in 2015: emerging catastrophic infections and new
insights into neuroimmunological host damage
SO LANCET NEUROLOGY
LA English
DT Editorial Material
ID CRYPTOCOCCAL MENINGITIS; CEREBROSPINAL-FLUID; ACTIVATION
C1 [Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Nash, Theodore E.] NIAID, Parasit Dis Lab, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Williamson, Kim C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
RP Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tnash@niaid.nih.gov
FU Intramural NIH HHS
NR 11
TC 2
Z9 2
U1 0
U2 3
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 JAN
PY 2016
VL 15
IS 1
BP 17
EP 19
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY3MM
UT WOS:000366313900010
PM 26700901
ER
PT J
AU Gingerich, TJ
Stumpo, DJ
Lai, WS
Randall, TA
Steppan, SJ
Blackshear, PJ
AF Gingerich, Timothy J.
Stumpo, Deborah J.
Lai, Wi S.
Randall, Thomas A.
Steppan, Scott J.
Blackshear, Perry J.
TI Emergence and evolution of Zfp36l3
SO MOLECULAR PHYLOGENETICS AND EVOLUTION
LA English
DT Article
DE Gene evolution; New gene formation; Retrotransposon; Intronization;
Repetitive element expansion; Subcellular localization
ID ZINC-FINGER PROTEINS; TRINUCLEOTIDE REPEAT EXPANSION; MESSENGER-RNA
TURNOVER; AU-RICH ELEMENTS; TRISTETRAPROLIN FAMILY; DUPLICATE GENES;
TANDEM; DIVERSIFICATION; BINDING; DESTABILIZATION
AB In most mammals, the Zfp36 gene family consists of three conserved members, with a fourth member, Zfp36l3, present only in rodents. The ZFP36 proteins regulate post-transcriptional gene expression at the level of mRNA stability in organisms from humans to yeasts, and appear to be expressed in all major groups of eukaryotes. In Mus musculus, Zfp36l3 expression is limited to the placenta and yolk sac, and is important for overall fecundity. We sequenced the Zfp36l3 gene from more than 20 representative species, from members of the Muridae, Cricetidae and Nesomyidae families. Zfp36l3 was not present in Dipodidae, or any families that branched earlier, indicating that this gene is exclusive to the Muroidea superfamily. We provide evidence that Zfp36l3 arose by retrotransposition of an mRNA encoded by a related gene, Zfp36l2 into an ancestral rodent X chromosome. Zfp36l3 has evolved rapidly since its origin, and numerous modifications have developed, including variations in start codon utilization, de nova intron formation by mechanisms including a nested retrotransposition, and the insertion of distinct repetitive regions. One of these repeat regions, a long alanine rich-sequence, is responsible for the full-time cytoplasmic localization of Mus musculus ZFP36L3. In contrast, this repeat sequence is lacking in Peromyscus maniculatus ZFP36L3, and this protein contains a novel nuclear export sequence that controls shuttling between the nucleus and cytosol. Zfp36l3 is an example of a recently acquired, rapidly evolving gene, and its various orthologues illustrate several different mechanisms by which new genes emerge and evolve. Published by Elsevier Inc.
C1 [Gingerich, Timothy J.; Stumpo, Deborah J.; Lai, Wi S.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Randall, Thomas A.] NIEHS, Integrat Bioinformat, Res Triangle Pk, NC 27709 USA.
[Steppan, Scott J.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM Black009@niehs.nih.gov
FU National Institutes of Health, NIEHS; National Science Foundation
[DEB-0841447]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NIEHS, and the National Science
Foundation grant DEB-0841447 to S.J.S. We are grateful to the many
colleagues who provided DNA or tissue samples, as listed in Table S4. We
thank Lori Edwards and Dr. Robert Petrovich for the peptide expression
and purification, Dr. Brian Bennett for help with the Nannospalax galili
sequences, Dr. Agnes Janoshazi and Jeff Tucker for help with the
confocal microscopy, and Drs. David Miller and Ron Cannon for helpful
comments on the manuscript.
NR 47
TC 2
Z9 2
U1 2
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1055-7903
EI 1095-9513
J9 MOL PHYLOGENET EVOL
JI Mol. Phylogenet. Evol.
PD JAN
PY 2016
VL 94
BP 518
EP 530
DI 10.1016/j.ympev.2015.10.016
PN B
PG 13
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA CY5JG
UT WOS:000366443300005
PM 26493225
ER
PT J
AU Ofori, E
Du, GW
Babcock, D
Huang, XM
Vaillancourt, DE
AF Ofori, Edward
Du, Guangwei
Babcock, Debra
Huang, Xuemei
Vaillancourt, David E.
TI Parkinson's disease biomarkers program brain imaging repository
SO NEUROIMAGE
LA English
DT Article
ID MULTIPLE SYSTEM ATROPHY; SUBSTANTIA-NIGRA; CONSENSUS STATEMENT;
FREE-WATER; DIAGNOSIS
AB The Parkinson's Disease Biomarkers Program (PDBP) is a multi-site study designed to identify Parkinson's disease (PD) biomarkers that can be used to improve the understanding of PD pathophysiology and to develop tools that provide novel measures to evaluate PD clinical trials. The PDBP consortium comprises numerous individual projects of which two are specifically geared to the development of brain imaging markers for diagnosis, progression, and prognosis of PD or related disorders. All study data from PD patients, atypical Parkinsonian patients, patients with essential tremor, and healthy controls collected from the sites are integrated in the PDBP database and will be publically available. All subjects are asked to submit blood samples, and undergo a battery of clinical evaluations that cover motor, cognitive, and other background information. In addition, a subset of subjects contributed cerebrospinal fluid samples. A restricted access, web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community. The PDBP consortium is a useful resource for research and collaboration aimed at the discovery of biomarkers and their use in understanding the pathophysiology of PD. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Ofori, Edward; Vaillancourt, David E.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA.
[Du, Guangwei; Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA USA.
[Babcock, Debra] NINDS, NIH, Bethesda, MD 20892 USA.
[Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA.
[Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA USA.
[Huang, Xuemei] Penn State Milton S Hershey Med Ctr, Dept Pharmacol & Kinesiol, Hershey, PA USA.
[Vaillancourt, David E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Vaillancourt, David E.] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA.
RP Vaillancourt, DE (reprint author), Univ Florida, Dept Appl Physiol & Kinesiol, POB 118205, Gainesville, FL 32611 USA.
EM vcourt@ufl.edu
OI Ofori, Edward/0000-0002-5440-1649
FU National Institutes of Health [U01 NS082151, R01 NS075012]
FX This work was supported by the National Institutes of Health (U01
NS082151, R01 NS075012).
NR 16
TC 3
Z9 3
U1 0
U2 4
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 JAN 1
PY 2016
VL 124
SI SI
BP 1120
EP 1124
DI 10.1016/j.neuroimage.2015.05.005
PN B
PG 5
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CY1FB
UT WOS:000366151000012
PM 25976927
ER
PT J
AU Walker, L
Chang, LC
Nayak, A
Irfanoglu, MO
Botteron, KN
McCracken, J
McKinstry, RC
Rivkin, MJ
Wang, DJ
Rumsey, J
Pierpaoli, C
AF Walker, Lindsay
Chang, Lin-Ching
Nayak, Amritha
Irfanoglu, M. Okan
Botteron, Kelly N.
McCracken, James
McKinstry, Robert C.
Rivkin, Michael J.
Wang, Dah-Jyuu
Rumsey, Judith
Pierpaoli, Carlo
CA Brain Dev Cooperative Grp
TI The diffusion tensor imaging (DTI) component of the NIH MRI study of
normal brain development (PedsDTI)
SO NEUROIMAGE
LA English
DT Article
DE Diffusion; DTI; Database; NIH; MRI; Multicenter; Longitudinal; Pediatric
ID ROBUST ESTIMATION; TISSUES; RESTORE; MOTION; NOISE
AB The NIH MM Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools.
This paper focuses on the DTI component of the NIH MM study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov.
This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data. Published by Elsevier Inc.
C1 [Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M. Okan; Pierpaoli, Carlo] NICHD, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD USA.
[Botteron, Kelly N.] Washington Univ, Dept Psychiat, St Louis, MO USA.
[McCracken, James] Univ Calif Los Angeles, Dept Child Psychiat, Los Angeles, CA USA.
[McKinstry, Robert C.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Rivkin, Michael J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
[Rivkin, Michael J.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA.
[Rivkin, Michael J.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA.
[Wang, Dah-Jyuu] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Rumsey, Judith] NIMH, Clin Neurosci Res Branch, Div Translat Res, NIH, Bethesda, MD 20892 USA.
RP Pierpaoli, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Pediat Imaging & Tissue Sci, NIH, 13 South Dr,MSC 5772,Bldg 13,Rm 3W16, Bethesda, MD 20892 USA.
EM cp1a@nih.gov
FU National Institute of Child Health and Human Development; National
Institute on Drug Abuse; National Institute of Mental Health; National
Institute of Neurological Disorders and Stroke [N01-HD02-3343,
N01-MH9-0002, N01-NS-9-2314, N01-NS-9-2315, N01-NS-9-2316,
N01-NS-9-2317, N01-NS-9-2319, N01-NS-9-2320]
FX Data used in the preparation of this article were obtained from the
Pediatric MRI Data Repository created by the NIH MRI Study of normal
brain development. This is a multi-site, longitudinal study of typically
developing children, from ages newborn through young adulthood,
conducted by the Brain Development Cooperative Group and supported by
the National Institute of Child Health and Human Development, the
National Institute on Drug Abuse, the National Institute of Mental
Health, and the National Institute of Neurological Disorders and Stroke
(Contract #s N01-HD02-3343, N01-MH9-0002, and N01-NS-9-2314,
N01-NS-9-2315, N01-NS-9-2316, N01-NS-9-2317, N01-NS-9-2319 and
N01-NS-9-2320).
NR 20
TC 4
Z9 5
U1 3
U2 14
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 JAN 1
PY 2016
VL 124
SI SI
BP 1125
EP 1130
DI 10.1016/j.neuroimage.2015.05.083
PN B
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CY1FB
UT WOS:000366151000013
PM 26048622
ER
PT J
AU Kaufman, AR
Suls, JM
Klein, WMP
AF Kaufman, Annette R.
Suls, Jerry M.
Klein, William M. P.
TI Communicating tobacco product harm: Compared to what?
SO ADDICTIVE BEHAVIORS
LA English
DT Editorial Material
DE Communication; Comparison; Product harm; Harm reduction
ID SMOKELESS TOBACCO; CIGARETTES; PREFERENCES; SIMILARITY; REDUCTION;
MIDDLE; RISK; SNUS
AB With the expansion of tobacco product options, a better understanding is needed of how information about the known and unknown risks of products is communicated to the public. Engaging in comparative processes is an common way for people to understand novel products, but the referent of comparison matters and can influence perceptions and behavior. This paper builds awareness of research from other disciplines, including decision science, marketing, and psychology, which can help inform research and tobacco control efforts. Published by Elsevier Ltd.
C1 [Kaufman, Annette R.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Suls, Jerry M.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
RP Kaufman, AR (reprint author), NCI, 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 Intramural NIH HHS [Z99 CA999999]
NR 26
TC 3
Z9 3
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD JAN
PY 2016
VL 52
BP 123
EP 125
DI 10.1016/j.addbeh.2015.06.039
PG 3
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA CX0HI
UT WOS:000365377100019
PM 26162963
ER
PT J
AU Filler, K
Saligan, LN
AF Filler, Kristin
Saligan, Leorey N.
TI Defining cancer-related fatigue for biomarker discovery
SO SUPPORTIVE CARE IN CANCER
LA English
DT Editorial Material
ID INFLAMMATION; CHEMOTHERAPY; SURVIVORS; INTERLEUKIN-6; SYMPTOMS; ALPHA;
MODEL
C1 [Filler, Kristin; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA.
RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 3,Room 5E, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
FU Intramural NIH HHS [ZIA NR000020-04]
NR 20
TC 4
Z9 4
U1 1
U2 5
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 JAN
PY 2016
VL 24
IS 1
BP 5
EP 7
DI 10.1007/s00520-015-2965-5
PG 3
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA CX6NM
UT WOS:000365817800002
PM 26438143
ER
PT J
AU Belin-Rauscent, A
Fouyssac, M
Bonci, A
Belin, D
AF Belin-Rauscent, Aude
Fouyssac, Maxime
Bonci, Antonello
Belin, David
TI How Preclinical Models Evolved to Resemble the Diagnostic Criteria of
Drug Addiction
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Behavioral models; Cocaine; Compulsive drug seeking; Limbic system;
Substance use disorders
AB Drug addiction is a complex neuropsychiatric disorder that affects a subset of the individuals who take drugs. It is characterized by maladaptive drug-seeking habits that are maintained despite adverse consequences and intense drug craving. The pathophysiology and etiology of addiction is only partially understood despite extensive research because of the gap between current preclinical models of addiction and the clinical criteria of the disorder. This review presents a brief overview, based on selected methodologies, of how behavioral models have evolved over the last 50 years to the development of recent preclinical models of addiction that more closely mimic diagnostic criteria of addiction. It is hoped that these new models will increase our understanding of the complex neurobiological mechanisms whereby some individuals switch from controlled drug use to compulsive drug-seeking habits and relapse to these maladaptive habits. Additionally, by paving the way to bridge the gap that exists between biobehavioral research on addiction and the human situation, these models may provide new perspectives for the development of novel and effective therapeutic strategies for drug addiction.
C1 [Belin-Rauscent, Aude; Fouyssac, Maxime; Belin, David] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England.
[Belin-Rauscent, Aude; Fouyssac, Maxime; Belin, David] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England.
[Bonci, Antonello] NIDA, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Bonci, A (reprint author), NIDA, Intramural Res Program, NIH, US Dept HHS, 251 Bayville Blvd, Baltimore, MD 21224 USA.
EM antonello.bonci@nih.gov
FU Agence Nationale de la Recherche [ANR12 SAMA00201]; University of
Cambridge; Newton Trust; Cambridge Commonwealth; European and
International Trust; National Institute on Drug Abuse
FX This work was supported by the Agence Nationale de la Recherche Grant
No. ANR12 SAMA00201 (DB), the University of Cambridge and the Newton
Trust (DB); the Cambridge Commonwealth, European and International Trust
(MF), and the National Institute on Drug Abuse (AB).
NR 0
TC 11
Z9 12
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 1
PY 2016
VL 79
IS 1
BP 39
EP 46
DI 10.1016/j.biopsych.2015.01.004
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CW9WX
UT WOS:000365350000008
PM 25747744
ER
PT B
AU Grady, PA
McIlvane, JM
AF Grady, Patricia A.
McIlvane, Jessica M.
BE Henly, SJ
TI THE DOMAIN OF NURSING SCIENCE
SO ROUTLEDGE INTERNATIONAL HANDBOOK OF ADVANCED QUANTITATIVE METHODS IN
NURSING RESEARCH
SE Routledge International Handbooks
LA English
DT Article; Book Chapter
ID RANDOMIZED CONTROLLED-TRIAL; IMPLEMENTATION; HEALTH; INTERDISCIPLINARY;
COLLABORATION; INTERVENTION; MEDICINE; CARE
C1 [Grady, Patricia A.] NINR, NIH, Bethesda, MD 20814 USA.
[McIlvane, Jessica M.] Univ S Florida, Tampa, FL 33620 USA.
RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20814 USA.
NR 41
TC 1
Z9 1
U1 0
U2 1
PU ROUTLEDGE
PI ABINGDON
PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND
BN 978-1-315-88230-7; 978-0-415-52180-2
J9 ROUT INT HANDB
PY 2016
BP 3
EP 14
PG 12
WC Social Sciences, Mathematical Methods; Nursing; Social Sciences,
Interdisciplinary; Statistics & Probability
SC Mathematical Methods In Social Sciences; Nursing; Social Sciences -
Other Topics; Mathematics
GA BD7HT
UT WOS:000363111700003
ER
PT J
AU Niknezhad, Z
Hassani, L
Norouzi, D
AF Niknezhad, Zhila
Hassani, Leila
Norouzi, Davood
TI Investigating actinomycin D binding to G-quadruplex, i-motif and
double-stranded DNA in 27-nt segment of c-MYC gene promoter
SO MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
LA English
DT Article
DE Actinomycin D; c-MYC; Quadruplex DNA; Molecular dynamic; Spectroscopy;
Interaction; i-Motif
ID CIRCULAR-DICHROISM; SEQUENCE MOTIFS; HUMAN GENOME; CYCLOPHOSPHAMIDE;
METHOTREXATE; VINCRISTINE; ETOPOSIDE; INSIGHTS; REGION; TUMORS
AB c-MYC DNA is an attractive target for drug design, especially for cancer chemotherapy. Around 90% of c-MYC transcription is controlled by NHE III1, whose 27-nt purine-rich strand has the ability to form G-quadruplex structure. In this investigation, interaction of ActD with 27-nt G-rich strand (G/c-MYC) and its equimolar mixture with the complementary sequence, (GC/c-MYC) as well as related C-rich oligonucleotide (C/c-MYC) was evaluated. Molecular dynamic simulations showed that phenoxazine and lactone rings of ActD come close to the outer G-tetrad nucleotides indicating that ActD binds through end-stacking to the quadruplex DNA. RMSD and RMSF revealed that fluctuation of the quadruplex DNA increases upon interaction with the drug. The results of spectrophotometry and spectrofluorometry indicated that ActD most probably binds to the c-MYC quadruplex and duplex DNA via end-stacking and intercalation, respectively and polarity of ActD environment decreases due to the interaction. It was also found that binding of ActD to the GC-rich DNA is stronger than the two other forms of DNA. Circular dichroism results showed that the type of the three forms of DNA structures doesn't change, but their compactness alters due to their interaction with ActD. Finally, it can be concluded that ActD binds differently to double stranded DNA, quadruplex DNA and i-motif. (c) 2015 Elsevier B.V. All rights reserved.
C1 [Niknezhad, Zhila; Hassani, Leila] Inst Adv Studies Basic Sci, Dept Biol Sci, Zanjan 451951159, Iran.
[Norouzi, Davood] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA.
RP Hassani, L (reprint author), Inst Adv Studies Basic Sci, Dept Biol Sci, Zanjan 451951159, Iran.
EM hasani@iasbs.ac.ir
FU Research Council of Institute for Advanced Studies in Basic Sciences
FX Financial support provided by Research Council of Institute for Advanced
Studies in Basic Sciences is gratefully acknowledged. Also, the author
would like to thank Dr. Laleh Mollazadeh-Beidokhti, Dr. Hamid
Hadi-Alijanvand and Dr. Sara Mohammadi Nejad for their generous
assistance in molecular modeling simulations.
NR 42
TC 0
Z9 0
U1 3
U2 35
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0928-4931
EI 1873-0191
J9 MAT SCI ENG C-MATER
JI Mater. Sci. Eng. C-Mater. Biol. Appl.
PD JAN 1
PY 2016
VL 58
BP 1188
EP 1193
DI 10.1016/j.msec.2015.09.072
PG 6
WC Materials Science, Biomaterials
SC Materials Science
GA CV4OX
UT WOS:000364247500141
PM 26478420
ER
PT J
AU Duran, R
Sharma, K
Dreher, MR
Ashrafi, K
Mirpour, S
Lin, MD
Schernthaner, RE
Schlachter, TR
Tacher, V
Lewis, AL
Willis, S
den Hartog, M
Radaelli, A
Negussie, AH
Wood, BJ
Geschwind, JFH
AF Duran, Rafael
Sharma, Karun
Dreher, Matthew R.
Ashrafi, Koorosh
Mirpour, Sahar
Lin, MingDe
Schernthaner, Ruediger E.
Schlachter, Todd R.
Tacher, Vania
Lewis, Andrew L.
Willis, Sean
den Hartog, Mark
Radaelli, Alessandro
Negussie, Ayele H.
Wood, Bradford J.
Geschwind, Jean-Francois H.
TI A Novel Inherently Radiopaque Bead for Transarterial Embolization to
Treat Liver Cancer - A Pre-clinical Study
SO THERANOSTICS
LA English
DT Article
DE VX2; Embolization; Hepatocellular carcinoma; TACE; radiopaque beads
ID DRUG-ELUTING BEADS; HEPATOCELLULAR-CARCINOMA; ARTERIAL EMBOLIZATION;
PARTICULATE EMBOLI; IMAGEABLE BEADS; BARIUM-SULFATE; MICROSPHERES;
PARTICLES; CONTRAST; CT
AB Purpose: Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent bead's location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model.
Materials and Methods: RO Beads, which are based on LC Bead (R) platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT).
Results: Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the bead's interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads <= 300 mu m were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy.
Conclusion: RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.
C1 [Duran, Rafael; Mirpour, Sahar; Schernthaner, Ruediger E.; Schlachter, Todd R.; Tacher, Vania; Geschwind, Jean-Francois H.] Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Vasc & Intervent Radiol, Baltimore, MD 21287 USA.
[Duran, Rafael; Schernthaner, Ruediger E.; Schlachter, Todd R.; Geschwind, Jean-Francois H.] Yale Univ, Sch Med, Dept Diagnost Radiol & Imaging Sci, New Haven, CT 06520 USA.
[Sharma, Karun] Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA.
[Dreher, Matthew R.] Biocompatibles Inc, Oxford, CT USA.
[Ashrafi, Koorosh; Lewis, Andrew L.; Willis, Sean] Biocompatibles UK Ltd, Farnham, Surrey, England.
[Lin, MingDe] Philips Res North Amer, US Imaging & Intervent UII, Briarcliff Manor, NY USA.
[den Hartog, Mark; Radaelli, Alessandro] Philips Healthcare, IXR, Best, Netherlands.
[Negussie, Ayele H.; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Geschwind, JFH (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, Chairmans Off, 330 Cedar St,TE 2-230, New Haven, CT 06520 USA.
EM jeff.geschwind@yale.edu
OI Schernthaner, Ruediger/0000-0002-1194-1346; Lewis,
Andrew/0000-0001-5779-5631
FU NIH/NCI [R01 CA160771]; Biocompatibles UK Ltd, a BTG International group
company; Biocompatibles/BTG; Bayer HealthCare; Philips Healthcare;
Nordion/BTG; Threshold; Guerbet; DOD; NCI-ECOG; NIH
FX Financial Support: Our study was funded by NIH/NCI R01 CA160771 and by
Biocompatibles UK Ltd, a BTG International group company.; Disclosures:
Jean-Francois H. Geschwind, M.D.: Consultant: Biocompatibles/BTG, Bayer
HealthCare, Guerbet, Nordion/BTG, Philips Healthcare and Jennerex. Grant
Support: Biocompatibles/BTG, Bayer HealthCare, Philips Healthcare,
Nordion/BTG, Threshold, Guerbet, DOD, NCI-ECOG and NIH-R01. Founder and
CEO PreScience Labs, LLC. Koorosh Ashrafi, Matthew R. Dreher, Andrew L.
Lewis and Sean Willis are paid employees of Biocompatibles UK Ltd, a BTG
International group company. MingDe Lin, Alessandro Radaelli and Mark
den Hartog are Philips Employees. Karun Sharma is a consultant to
Biocompatibles/BTG.
NR 29
TC 5
Z9 5
U1 6
U2 17
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2016
VL 6
IS 1
BP 28
EP 39
DI 10.7150/thno.13137
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CU6XN
UT WOS:000363678500003
PM 26722371
ER
PT J
AU Chen, HJ
Niu, G
Wu, H
Chen, XY
AF Chen, Haojun
Niu, Gang
Wu, Hua
Chen, Xiaoyuan
TI Clinical Application of Radiolabeled RGD Peptides for PET Imaging of
Integrin alpha(v)beta(3)
SO THERANOSTICS
LA English
DT Review
DE Angiogenesis; RGD; PET; clinical translation
ID POSITRON-EMISSION-TOMOGRAPHY; BREAST-CANCER PATIENTS; IN-VIVO
EVALUATION; WHOLE-BODY PET/CT; ALPHA-V-BETA-3 EXPRESSION;
MYOCARDIAL-INFARCTION; RADIATION-DOSIMETRY; GA-68-PRGD2 PET/CT;
MOYAMOYA-DISEASE; F-18-ALFATIDE II
AB Molecular imaging for non-invasive assessment of angiogenesisis is of great interest for clinicians because of the wide-spread application of anti-angiogenic cancer therapeutics. Besides, many other interventions that involve the change of blood vessel/tumor microenvironment would also benefit from such imaging strategies. Of the imaging techniques that target angiogenesis, radiolabeled Arg-Gly-Asp (RGD) peptides have been a major focus because of their high affinity and selectivity for integrin alpha(v)beta(3)-one of the most extensively examined target of angiogenesis. Since the level of integrin alpha(v)beta(3) expression has been established as a surrogate marker of angiogenic activity, imaging alpha(v)beta(3) expression can potentially be used as an early indicator of effectiveness of antiangiogenic therapy at the molecular level. In this review, we summarize RGD-based PET tracers that have already been used in clinical trials and intercompared them in terms of radiosynthesis, dosimetry, pharmacokinetics and clinical applications. A perspective of their future use in the clinic is also provided.
C1 [Chen, Haojun; Wu, Hua] Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Ctr, Dept Nucl Med, Xiamen, Peoples R China.
[Chen, Haojun; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Niu, G (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; wuhua1025@163.com; shawn.chen@nih.gov
FU National Natural Science Foundation of China [81471684, 81371596];
Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health; China Scholarship
Council (CSC)
FX The authors gratefully acknowledge the National Natural Science
Foundation of China (81471684 and 81371596) and the Intramural Research
Program, National Institute of Biomedical Imaging and Bioengineering,
National Institutes of Health. Haojun Chen was partially funded by the
China Scholarship Council (CSC).
NR 101
TC 17
Z9 17
U1 22
U2 78
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2016
VL 6
IS 1
BP 78
EP 92
DI 10.7150/thno.13242
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CU6XN
UT WOS:000363678500007
PM 26722375
ER
PT J
AU Rohner, E
Wyss, N
Heg, Z
Faralli, Z
Mbulaiteye, SM
Novak, U
Zwahlen, M
Egger, M
Bohlius, J
AF Rohner, Eliane
Wyss, Natascha
Heg, Zina
Faralli, Zully
Mbulaiteye, Sam M.
Novak, Urban
Zwahlen, Marcel
Egger, Matthias
Bohlius, Julia
TI HIV and human herpesvirus 8 co-infection across the globe: Systematic
review and meta-analysis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HIV; human herpesvirus 8; co-infection; meta-analysis
ID SARCOMA-ASSOCIATED HERPESVIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
KAPOSIS-SARCOMA; RISK-FACTORS; SEXUAL TRANSMISSION; HOMOSEXUAL-MEN;
INFECTION; COHORT; SEROPREVALENCE; SEROPOSITIVITY
AB HIV-infection is an important risk factor for developing Kaposi sarcoma (KS), but it is unclear whether HIV-positive persons are also at increased risk of co-infection with human herpesvirus 8 (HHV-8), the infectious cause of KS. We systematically searched literature up to December 2012 and included studies reporting HHV-8 seroprevalence for HIV-positive and HIV-negative persons. We used random-effects meta-analysis to combine odds ratios (ORs) of the association between HIV and HHV-8 seropositivity and conducted random-effects meta-regression to identify sources of heterogeneity. We included 93 studies with 58,357 participants from 32 countries in sub-Saharan Africa, North and South America, Europe, Asia, and Australia. Overall, HIV-positive persons were more likely to be HHV-8 seropositive than HIV-negative persons (OR 1.99, 95% confidence interval [CI] 1.70-2.34) with considerable heterogeneity among studies (I-2 84%). The association was strongest in men who have sex with men (MSM, OR 3.95, 95% CI 2.92-5.35), patients with hemophilia (OR 3.11, 95% CI 1.19-8.11), and children (OR 2.45, 95% CI 1.58-3.81), but weaker in heterosexuals who engage in low-risk (OR 1.42, 95% CI 1.16-1.74) or high-risk sexual behavior (OR 1.66, 95% CI 1.27-2.17), persons who inject drugs (OR 1.66, 95% CI 1.28-2.14), and pregnant women (OR 1.68, 95% CI 1.15-2.47), p value for interaction <0.001. In conclusion, HIV-infection was associated with an increased HHV-8 seroprevalence in all population groups examined. A better understanding of HHV-8 transmission in different age and behavioral groups is needed to develop strategies to prevent HHV-8 transmission.
What's new? Immunodeficiency sets the stage for human herpesvirus 8 (HHV-8) infection, which can lead to Kaposi sarcoma. Compared with the general population, HHV-8 infection is common in HIV-positive individuals and in men who have sex with men (MSM). Those associations are corroborated by the present meta-analysis, which also shows that HHV-8 seroprevalence is highest in MSM and in children. Sexual transmission of HIV and HHV-8 is likely in MSM. In children, who typically acquire HHV-8 via nonsexual transmission, infection may occur as a result of HHV-8 shedding from HIV-positive family members. Further studies are needed to clarify HHV-8 transmission routes.
C1 [Rohner, Eliane; Wyss, Natascha; Heg, Zina; Faralli, Zully; Zwahlen, Marcel; Egger, Matthias; Bohlius, Julia] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland.
[Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Novak, Urban] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland.
[Egger, Matthias] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa.
RP Bohlius, J (reprint author), Univ Bern, Inst Social & Prevent Med, Finkenhubelweg 11, CH-3012 Bern, Switzerland.
EM julia.bohlius@ispm.unibe.ch
OI Rohner, Eliane/0000-0002-0554-2875
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [U01AI069924]; National Cancer Institute
[5U01A1069924-05]; Swiss Bridge Foundation; Swiss Cancer League [Robert
Wenner Award]; Swiss National Science Foundation [Ambizione-PROSPER]
[PZ00P3_136620_3]; Swiss National Science Foundation [Marie Heim-Vogtlin
grant] [PMCDP3_145489]
FX We thank Sven Trelle for statistical support, and Jingying Wang for her
help with studies published in Chinese. We also thank Kali Tal for her
editorial suggestions. This study was done on behalf of The
International epidemiologic Database to Evaluate AIDS (IeDEA). Research
reported in this publication was supported by the National Institute of
Allergy and Infectious Diseases of the National Institutes of Health
[award number U01AI069924 to M.E.] and also supported by the National
Cancer Institute [grant number 5U01A1069924-05 to M.E.]. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
Additional funding was received from the Swiss Bridge Foundation, the
Swiss Cancer League [Robert Wenner Award to J.B.], and the Swiss
National Science Foundation [Ambizione-PROSPER PZ00P3_136620_3 to J.B.;
Marie Heim-Vogtlin grant PMCDP3_145489 to N.W.]. The authors have no
conflicts of interest to declare.
NR 43
TC 11
Z9 11
U1 0
U2 21
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 JAN 1
PY 2016
VL 138
IS 1
BP 45
EP 54
DI 10.1002/ijc.29687
PG 10
WC Oncology
SC Oncology
GA CU0JY
UT WOS:000363203600009
PM 26175054
ER
PT J
AU Drahos, J
Xiao, Q
Risch, HA
Freedman, ND
Abnet, CC
Anderson, LA
Bernstein, L
Brown, L
Chow, WH
Gammon, MD
Kamangar, F
Liao, LM
Murray, LJ
Ward, MH
Ye, WM
Wu, AH
Vaughan, TL
Whiteman, DC
Cook, MB
AF Drahos, Jennifer
Xiao, Qian
Risch, Harvey A.
Freedman, Neal D.
Abnet, Christian C.
Anderson, Lesley A.
Bernstein, Leslie
Brown, Linda
Chow, Wong-Ho
Gammon, Marilie D.
Kamangar, Farin
Liao, Linda M.
Murray, Liam J.
Ward, Mary H.
Ye, Weimin
Wu, Anna H.
Vaughan, Thomas L.
Whiteman, David C.
Cook, Michael B.
TI Age-specific risk factor profiles of adenocarcinomas of the esophagus: A
pooled analysis from the international BEACON consortium
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE risk factors; esophageal cancer; case-control studies; obesity; age of
onset
ID BODY-MASS INDEX; GASTROESOPHAGEAL-REFLUX DISEASE; SQUAMOUS-CELL
CARCINOMA; GASTRIC CARDIA; UNITED-STATES; ESOPHAGOGASTRIC JUNCTION;
BARRETTS-ESOPHAGUS; SOCIOECONOMIC-FACTORS; METABOLIC SYNDROME;
CIGARETTE-SMOKING
AB Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, 70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR=8.06, 95% CI: 4.52, 14.37; p(effect modification)=0.01) and BMI (ORBMI30vs. <25=4.19, 95% CI: 2.23, 7.87; p(effect modification)=0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers.
What's new? Incidence in esophageal adenocarcinoma has increased sharply among all age groups, with a disconcertingly increasing proportion of advanced-stage tumors occurring at younger (< 50 years) ages. However, the relative rarity of these malignancies has precluded prior studies from assessing risk factors across age groups. Here, by pooling data from 8 case-control studies, the authors find that recurrent heartburn/regurgitation and obesity are appreciably stronger risk factors for early-onset esophageal adenocarcinoma relative to older age-categories. Understanding the mechanisms through which reflux and obesity confer increased risks of esophageal cancer at younger ages might yield important insights for prevention, control, and clinical management.
C1 [Drahos, Jennifer; Xiao, Qian; Freedman, Neal D.; Abnet, Christian C.; Liao, Linda M.; Ward, Mary H.; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Anderson, Lesley A.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Bernstein, Leslie] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Brown, Linda] RTI Int, Rockville, MD USA.
[Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Gammon, Marilie D.] Univ North Carolina Sch, Dept Epidemiol, Chapel Hill, NC USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Whiteman, David C.] QIMR Berghofer Med Res Inst, Populat Hlth, Brisbane, Qld, Australia.
RP Drahos, J (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9774, Bethesda, MD 20892 USA.
EM jennifer.drahos@nih.gov
RI Abnet, Christian/C-4111-2015; Cook, Michael/A-5641-2009; Whiteman,
David/P-2728-2014;
OI Abnet, Christian/0000-0002-3008-7843; Cook, Michael/0000-0002-0533-7302;
Whiteman, David/0000-0003-2563-9559; Liao, Linda/0000-0002-1923-5294;
Anderson, Lesley/0000-0002-1000-3649
FU Public Health Service [U01-CA57983, U01-CA57949, U01-CA57923]; National
Cancer Institute, National Institutes of Health, Department of Health
and Human Services [N02-CP40501, N01-CN05230]; National Cancer Institute
at the National Institutes of Health
FX Grant sponsor: Public Health Service; Grant numbers: U01-CA57983,
U01-CA57949 and U01-CA57923; Grant sponsor: National Cancer Institute,
National Institutes of Health, Department of Health and Human Services;
Grant numbers: N02-CP40501 and N01-CN05230; Grant sponsor: Intramural
Program of the National Cancer Institute at the National Institutes of
Health
NR 51
TC 3
Z9 3
U1 2
U2 21
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 JAN 1
PY 2016
VL 138
IS 1
BP 55
EP 64
DI 10.1002/ijc.29688
PG 10
WC Oncology
SC Oncology
GA CU0JY
UT WOS:000363203600010
PM 26175109
ER
PT J
AU Wangsa, D
Chowdhury, SA
Ryott, M
Gertz, EM
Elmberger, G
Auer, G
Lundqvist, EA
Kuffer, S
Strobel, P
Schaffer, AA
Schwartz, R
Munck-Wikland, E
Ried, T
Heselmeyer-Haddad, K
AF Wangsa, Darawalee
Chowdhury, Salim Akhter
Ryott, Michael
Gertz, E. Michael
Elmberger, Goran
Auer, Gert
Lundqvist, Elisabeth Avall
Kueffer, Stefan
Stroebel, Philipp
Schaeffer, Alejandro A.
Schwartz, Russell
Munck-Wikland, Eva
Ried, Thomas
Heselmeyer-Haddad, Kerstin
TI Phylogenetic analysis of multiple FISH markers in oral tongue squamous
cell carcinoma suggests that a diverse distribution of copy number
changes is associated with poor prognosis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE oral tongue cancer; FISH; genetic markers; phylogenetic modeling; HPV
ID IN-SITU HYBRIDIZATION; CYCLIN D1; GENOMIC IMBALANCES;
HUMAN-PAPILLOMAVIRUS; CIGARETTE-SMOKING; GENETIC-ANALYSIS; EARLY
RECURRENCE; NODE METASTASIS; TREE MODELS; CANCER
AB Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n=15; Stage II, n=30; Stage III, n=7; Stage IV, n=13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress.
What's new? Oral tongue squamous cell carcinoma (OTSCC) is a rare head and neck cancer that typically is asymptomatic in early stages. Hence, in order to improve prognosis in OTSCC, predictive biomarkers that are independent of tumor stage must be identified. Here, using four fluorescence in situ hybridization (FISH) gene probes and the software FISHtrees, phylogenetic tree models of tumor progression in OTSCC patients were constructed. Analyses of the models showed that the more diverse the changes within the four marker genes, the worse the outcome in OTSCC. The markers predicted survival independent of smoking behavior and tumor stage.
C1 [Wangsa, Darawalee; Ried, Thomas; Heselmeyer-Haddad, Kerstin] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wangsa, Darawalee; Auer, Gert; Lundqvist, Elisabeth Avall] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Chowdhury, Salim Akhter] Carnegie Mellon Univ, Joint Carnegie Mellon Univ Pittsburgh PhD Program, Pittsburgh, PA 15213 USA.
[Chowdhury, Salim Akhter; Schwartz, Russell] Carnegie Mellon Univ, Computat Biol Dept, Pittsburgh, PA 15213 USA.
[Ryott, Michael] Sophiahemmet Hosp, Dept Otorhinolaryngol, Stockholm, Sweden.
[Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Elmberger, Goran] Orebro Univ Hosp, Dept Lab Med, Pathol, Orebro, Sweden.
[Lundqvist, Elisabeth Avall] Linkoping Univ, Dept Oncol, Linkoping, Sweden.
[Lundqvist, Elisabeth Avall] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Kueffer, Stefan; Stroebel, Philipp] Univ Med Ctr Gottingen, Inst Pathol, Gottingen, Germany.
[Schwartz, Russell] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
[Munck-Wikland, Eva] Karolinska Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Stockholm, Sweden.
[Munck-Wikland, Eva] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
RP Ried, T (reprint author), NCI, Genet Branch, Ctr Canc Res, 50 South Dr,Bldg 50,Room 1408, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov
RI Schwartz, Russell/A-1998-2016
OI Schwartz, Russell/0000-0002-4970-2252
FU National Institutes of Health (NIH), National Cancer Institute, National
Library of Medicine (Intramural Research Program) NIH Extramural grants
[1R01CA140214, 1R01AI076318]; Swedish Cancer Society (Cancerfonden);
Cancer Society of Stockholm (Cancerforeningen); Laryngfonden; Karolinska
Institutet
FX Grant sponsors: National Institutes of Health (NIH), National Cancer
Institute, National Library of Medicine (Intramural Research Program)
NIH Extramural grants; Grant numbers: 1R01CA140214 and 1R01AI076318;
Grant sponsors: Swedish Cancer Society (Cancerfonden), the Cancer
Society of Stockholm (Cancerforeningen), Laryngfonden and the Karolinska
Institutet
NR 52
TC 2
Z9 2
U1 2
U2 28
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 JAN 1
PY 2016
VL 138
IS 1
BP 98
EP 109
DI 10.1002/ijc.29691
PG 12
WC Oncology
SC Oncology
GA CU0JY
UT WOS:000363203600014
PM 26175310
ER
PT J
AU Sheng, NY
Shi, YS
Lomash, RM
Roche, KW
Nicoll, RA
AF Sheng, Nengyin
Shi, Yun S.
Lomash, Richa Madan
Roche, Katherine W.
Nicoll, Roger A.
TI Neto auxiliary proteins control both the trafficking and biophysical
properties of the kainate receptor GluK1
SO ELIFE
LA English
DT Article
ID SINGLE DENDRITIC SPINES; LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS;
SYNAPTIC PLASTICITY; AMPA RECEPTORS; SUBUNIT; TARPS; ACTIVATION;
PHOSPHORYLATION; INTERNEURONS
AB Kainate receptors (KARs) are a subfamily of glutamate receptors mediating excitatory synaptic transmission and Neto proteins are recently identified auxiliary subunits for KARs. However, the roles of Neto proteins in the synaptic trafficking of KAR GluK1 are poorly understood. Here, using the hippocampal CA1 pyramidal neuron as a null background system we find that surface expression of GluK1 receptor itself is very limited and is not targeted to excitatory synapses. Both Neto1 and Neto2 profoundly increase GluK1 surface expression and also drive GluK1 to synapses. However, the regulation GluK1 synaptic targeting by Neto proteins is independent of their role in promoting surface trafficking. Interestingly, GluK1 is excluded from synapses expressing AMPA receptors and is selectively incorporated into silent synapses. Neto2, but not Neto1, slows GluK1 deactivation, whereas Neto1 speeds GluK1 desensitization and Neto2 slows desensitization. These results establish critical roles for Neto auxiliary subunits controlling KARs properties and synaptic incorporation.
C1 [Sheng, Nengyin; Shi, Yun S.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Shi, Yun S.] Nanjing Univ, Model Anim Res Ctr, Key Lab Model Anim Dis Study, Minist Educ, Nanjing 210008, Jiangsu, Peoples R China.
[Lomash, Richa Madan; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA.
RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
EM roger.nicoll@ucsf.edu
OI Roche, Katherine/0000-0001-7282-6539
FU National Institute of Mental Health [5R01MH080379-09, 5R37MH038256-32,
2R01MH070957-11A1]; National Institute of Neurological Disorders and
Stroke [NS002994-13]; National Natural Science Foundation of China
[31371061, 31571060]; Ministry of Science and Technology of the People's
Republic of China [2014CB942804]
FX National Institute of Mental Health 5R01MH080379-09, 5R37MH038256-32 and
2R01MH070957-11A1 Roger A Nicoll; National Institute of Neurological
Disorders and Stroke NS002994-13 Katherine W Roche; National Natural
Science Foundation of China 31371061 Yun S Shi; Ministry of Science and
Technology of the People's Republic of China 2014CB942804 Yun S Shi;
National Natural Science Foundation of China 31571060 Yun S Shi
NR 29
TC 2
Z9 2
U1 11
U2 26
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 31
PY 2015
VL 4
AR e11682
DI 10.7554/eLife.11682
PG 19
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ1IQ
UT WOS:000373956900001
ER
PT J
AU Iannaccone, A
Giorgianni, F
New, DD
Hollingsworth, TJ
Umfress, A
Alhatem, AH
Neeli, I
Lenchik, NI
Jennings, BJ
Calzada, JI
Satterfield, S
Mathews, D
Diaz, RI
Harris, T
Johnson, KC
Charles, S
Kritchevsky, SB
Gerling, IC
Beranova-Giorgianni, S
Radic, MZ
AF Iannaccone, Alessandro
Giorgianni, Francesco
New, David D.
Hollingsworth, T. J.
Umfress, Allison
Alhatem, Albert H.
Neeli, Indira
Lenchik, Nataliya I.
Jennings, Barbara J.
Calzada, Jorge I.
Satterfield, Suzanne
Mathews, Dennis
Diaz, Rocio I.
Harris, Tamara
Johnson, Karen C.
Charles, Steve
Kritchevsky, Stephen B.
Gerling, Ivan C.
Beranova-Giorgianni, Sarka
Radic, Marko Z.
CA Hlth ABC Study
TI Circulating Autoantibodies in Age-Related Macular Degeneration Recognize
Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation,
and Protection from Oxidative Stress and Apoptosis
SO PLOS ONE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; SUBRETINAL DRUSENOID DEPOSITS;
CANCER-ASSOCIATED RETINOPATHY; ALPHA-ENOLASE AUTOANTIBODIES; FACTOR-H
POLYMORPHISM; HEAT-SHOCK-RESPONSE; BRUCHS MEMBRANE; IN-VIVO; AUTOIMMUNE
RETINOPATHY; OPTICAL-DENSITY
AB Background
We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity.
Methods
Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2 +/- 3.9 years old) included subjects with early to advanced AMD (n = 131) and controls (n = 231). Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR) calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELI-SAs with recombinant proteins to confirm LC-MS/MS results, and quantify autoreactivities.
Results
In AMD, 11 immunoreactive bands were significantly more frequent and 13 were significantly stronger than in controls. Nine of the more frequent bands also showed stronger reactivity. OR estimates ranged between 4.06 and 1.93, and all clearly excluded the null value. Following immunoprecipitation, 2D-GE and LC-MS/MS, five of the possible autoreactivity targets were conclusively identified: two members of the heat shock protein 70 (HSP70) family, HSPA8 and HSPA9; another member of the HSP family, HSPB4, also known as alpha-crystallin A chain (CRYAA); Annexin A5 (ANXA5); and Protein S100-A9, also known as calgranulin B that, when complexed with S100A8, forms calprotectin. ELISA testing with recombinant proteins confirmed, on average, significantly higher reactivities against all targets in AMD samples compared to controls.
Conclusions
Consistent with other evidence supporting the role of inflammation and the immune system in AMD pathogenesis, AAbs were identified in AMD sera, including early-stage disease. Identified targets may be mechanistically linked to AMD pathogenesis because the identified proteins are implicated in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. In particular, a role in autophagy activation is shared by all five autoantigens, raising the possibility that the detected AAbs may play a role in AMD via autophagy compromise and downstream activation of the inflammasome. Thus, we propose that the detected AAbs provide further insight into AMD pathogenesis and have the potential to contribute to disease biogenesis and progression.
C1 [Iannaccone, Alessandro; New, David D.; Hollingsworth, T. J.; Umfress, Allison; Alhatem, Albert H.; Neeli, Indira; Lenchik, Nataliya I.; Jennings, Barbara J.; Calzada, Jorge I.; Diaz, Rocio I.; Charles, Steve] Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Dept Ophthalmol, Memphis, TN 38163 USA.
[Giorgianni, Francesco; Beranova-Giorgianni, Sarka] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA.
[Neeli, Indira; Radic, Marko Z.] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA.
[Lenchik, Nataliya I.; Gerling, Ivan C.] Univ Tennessee, Ctr Hlth Sci, Dept Internal Med Endocrinol, Memphis, TN 38163 USA.
[Calzada, Jorge I.; Diaz, Rocio I.; Charles, Steve] Charles Retina Inst, Memphis, TN USA.
[Satterfield, Suzanne; Johnson, Karen C.; Kritchevsky, Stephen B.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Mathews, Dennis] Eye Specialty Grp, Memphis, TN USA.
[Mathews, Dennis] Southern Coll Optometry, Memphis, TN USA.
[Harris, Tamara] NIA, NIH, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
RP Iannaccone, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Dept Ophthalmol, Memphis, TN 38163 USA.
EM aiannacc@yahoo.com
FU National Institutes of Health/National Eye Institute [K23 EY000409, R21
EY018416, R01 EY022706]; International Retinal Research Foundation;
Research to Prevent Blindness, Inc. New York, NY; University of
Tennessee Health Science Center College of Pharmacy; University of
Tennessee Health Science Center, Neuroscience Undergraduate Merit
Fellowship Award; National Institutes of Health/National Institute on
Aging, Intramural Research Program; National Institutes of
Health/National Institute on AgingH [N01 AG-62101, N01 AG-62103,
N01-AG-62106]
FX This work was funded by: National Institutes of Health/National Eye
Institute grants K23 EY000409 (AI), R21 EY018416 (AI, PI; ICG and MRZ,
co-investigators) and R01 EY022706 (AI, PI; MRZ, FG, ICG, and SBG,
co-investigators) (https://nei.nih.gov); International Retinal Research
Foundation (AI) (http://www.irrfonline.org); Research to Prevent
Blindness, Inc. New York, NY (Career Development Award and Physician
Scientist Award to AI and unrestricted grant to the UTHSC Hamilton Eye
Institute, Memphis, TN, USA) (https://www.rpbusa.org/rpb/?); University
of Tennessee Health Science Center College of Pharmacy, Intramural grant
(FG and SBG) (http://www.uthsc.edu/pharmacy/); University of Tennessee
Health Science Center, Neuroscience Undergraduate Merit Fellowship Award
(AU) (http://www.uthsc.edu/neuroscience/); National Institutes of
Health/National Institute on Aging, Intramural Research Program (TH)
(https://www.nia.nih.gov). The Health ABC study was supported by:
National Institutes of Health/National Institute on AgingH Contracts N01
AG-62101 (SBK, PI: SS and KCJ, co-investigators), N01 AG-62103 (SBK, PI:
SS and KCJ, co-investigators), and N01-AG-62106 (Health ABC Coordinating
Center) (https://www.nia.nih.gov). The Health ABC Publications Committee
and the National Institute on Aging reviewed and approved the manuscript
for publication before submission. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 155
TC 3
Z9 3
U1 2
U2 7
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 DEC 30
PY 2015
VL 10
IS 12
AR e0145323
DI 10.1371/journal.pone.0145323
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA0TN
UT WOS:000367510500028
PM 26717306
ER
PT J
AU Rhee, SY
Jordan, MR
Raizes, E
Chua, A
Parkin, N
Kantor, R
Van Zyl, GU
Mukui, I
Hosseinipour, MC
Frenkel, LM
Ndembi, N
Hamers, RL
de Wit, TFR
Wallis, CL
Gupta, RK
Fokam, J
Zeh, C
Schapiro, JM
Carmona, S
Katzenstein, D
Tang, M
Aghokeng, AF
De Oliveira, T
Wensing, AMJ
Gallant, JE
Wainberg, MA
Richman, DD
Fitzgibbon, JE
Schito, M
Bertagnolio, S
Yang, CF
Shafer, RW
AF Rhee, Soo-Yon
Jordan, Michael R.
Raizes, Elliot
Chua, Arlene
Parkin, Neil
Kantor, Rami
Van Zyl, Gert U.
Mukui, Irene
Hosseinipour, Mina C.
Frenkel, Lisa M.
Ndembi, Nicaise
Hamers, Raph L.
de Wit, Tobias F. Rinke
Wallis, Carole L.
Gupta, Ravindra K.
Fokam, Joseph
Zeh, Clement
Schapiro, Jonathan M.
Carmona, Sergio
Katzenstein, David
Tang, Michele
Aghokeng, Avelin F.
De Oliveira, Tulio
Wensing, Annemarie M. J.
Gallant, Joel E.
Wainberg, Mark A.
Richman, Douglas D.
Fitzgibbon, Joseph E.
Schito, Marco
Bertagnolio, Silvia
Yang, Chunfu
Shafer, Robert W.
TI HIV-1 Drug Resistance Mutations: Potential Applications for
Point-of-Care Genotypic Resistance Testing
SO PLOS ONE
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; ACTIVE ANTIRETROVIRAL THERAPY; SUB-SAHARAN
AFRICA; VIROLOGICAL FAILURE; PROTEASE INHIBITOR; SOUTH-AFRICA;
HIV-1-INFECTED PATIENTS; TREATMENT PROGRAMS; NAIVE INDIVIDUALS;
ATAZANAVIR
AB The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first-or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naive individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naive individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.
C1 [Rhee, Soo-Yon; Katzenstein, David; Tang, Michele; Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Jordan, Michael R.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Raizes, Elliot; Yang, Chunfu] Ctr Dis Control & Prevent, Div Global HIV AIDS, Atlanta, GA USA.
[Chua, Arlene] Access Campaign, Med Sans Frontieres, Geneva, Switzerland.
[Chua, Arlene] Tan Tock Seng Hosp, Inst Infect Dis & Epidemiol, Singapore, Singapore.
[Parkin, Neil] Data First Consulting, Belmont, MA USA.
[Kantor, Rami] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Van Zyl, Gert U.] Natl Hlth Lab Serv, Tygerberg, Coastal Branch, South Africa.
[Van Zyl, Gert U.] Univ Stellenbosch, Div Med Virol, Parow, South Africa.
[Mukui, Irene] Natl AIDS & Sexually Transmitted Infect STI Contr, Minist Hlth, Nairobi, Kenya.
[Hosseinipour, Mina C.] UNC Project, Lilongwe, Malawi.
[Frenkel, Lisa M.] Univ Washington, Seattle, WA 98195 USA.
[Frenkel, Lisa M.] Seattle Childrens Res Inst, Seattle, WA USA.
[Ndembi, Nicaise] Inst Human Virol, Abuja, Nigeria.
[Hamers, Raph L.; de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, AIGHD, Dept Global Hlth, NL-1105 AZ Amsterdam, Netherlands.
[Wallis, Carole L.] Lancet Labs & BARC SA, Johannesburg, South Africa.
[Gupta, Ravindra K.] UCL, Dept Infect, London, England.
[Fokam, Joseph] Chantal BIYA Int Reference Ctr Res HIV AIDS Preve, Yaounde, Cameroon.
[Fokam, Joseph] Univ Yaounde I, FMBS, Yaounde, Cameroon.
[Zeh, Clement] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Schapiro, Jonathan M.] Natl Hemophilia Ctr, Tel Hashomer, Israel.
[Carmona, Sergio] Univ Witwatersrand, Dept Haematol & Mol Med, Johannesburg, South Africa.
[Carmona, Sergio] Natl Hlth Lab Serv, Johannesburg, South Africa.
[Aghokeng, Avelin F.] Virol Lab CREMER IMPM, Yaounde, Cameroon.
[De Oliveira, Tulio] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Sch Lab Med & Med Sci, Durban, South Africa.
[Wensing, Annemarie M. J.] Univ Med Ctr Utrecht, Dept Med Microbiol, Virol, Utrecht, Netherlands.
[Gallant, Joel E.] Southwest CARE Ctr, Santa Fe, NM USA.
[Wainberg, Mark A.] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Montreal, PQ H3T 1E2, Canada.
[Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
[Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Fitzgibbon, Joseph E.] NIAID, NIH, Drug Dev & Clin Sci Branch, Div Aids, Bethesda, MD 20892 USA.
[Schito, Marco] Adv Mil Med Inc, Henry M Jackson Fdn, HJF DAIDS Div, Bethesda, MD USA.
[Bertagnolio, Silvia] WHO, HIV Dept, CH-1211 Geneva, Switzerland.
RP Rhee, SY (reprint author), Stanford Univ, Dept Med, Stanford, CA 94305 USA.
EM syrhee@stanford.edu
OI Chua, Arlene/0000-0001-6428-9083; Mukui, Irene/0000-0002-3699-1841
FU Bill and Melinda Gates Foundation; NIH [AI068581]; CFAR [1P30A142853];
Presidents Emergency Plan for AIDS Relief (PEPFAR) through the Centers
for Disease Control and Prevention (CDC)
FX RWS and SYR were supported in part by a grant from the Bill and Melinda
Gates Foundation and from the NIH (AI068581). NP was supported by a
grant from the Bill and Melinda Gates Foundation. MRJ was supported in
part by CFAR 1P30A142853. This project has been supported in part by the
Presidents Emergency Plan for AIDS Relief (PEPFAR) through the Centers
for Disease Control and Prevention (CDC). Data First Consulting provided
support in the form of salaries for authors NP, but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific
roles of these authors are articulated in the 'author contributions
section. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 60
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Z9 6
U1 2
U2 10
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 DEC 30
PY 2015
VL 10
IS 12
AR e0145772
DI 10.1371/journal.pone.0145772
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA0TN
UT WOS:000367510500068
PM 26717411
ER
PT J
AU Salvador, A
Sandgren, KJ
Liang, F
Thompson, EA
Koup, RA
Pedraz, JL
Hernandez, RM
Lore, K
Igartua, M
AF Salvador, Aiala
Sandgren, Kerrie J.
Liang, Frank
Thompson, Elizabeth A.
Koup, Richard A.
Pedraz, Jose Luis
Maria Hernandez, Rosa
Lore, Karin
Igartua, Manoli
TI Design and evaluation of surface and adjuvant modified PLGA microspheres
for uptake by dendritic cells to improve vaccine responses
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE PLGA; Human primary dendritic cells; Polyethyleneimine; Monophosphoryl
lipid A; Polyinosinic-polycytidilic acid; alpha-galactosylceramide
ID TOLL-LIKE RECEPTOR-3; IMMUNE-RESPONSES; LANGERHANS CELLS; MAST-CELLS;
CROSS-PRESENTATION; NKT CELLS; ANTIGEN; DELIVERY; MICROPARTICLES;
NANOPARTICLES
AB Designing strategies for targeting antigens to dendritic cells is a major goal in vaccinology. Here, PLGA (poly lactic-co-glycolic acid) microspheres and with several surface modifications that affect to their uptake by human blood primary dendritic cells and monocytes have been evaluated. Higher uptake was found by all the cell types when cationic microspheres (PLGA modified with polyethylene imine) were used. These cationic particles were in vivo evaluated in mice. In addition, MPLA(1) or poly(I:C)(2) and alpha-GalCer(3) were also encapsulated to address their adjuvant effect. All the microspheres were able to produce humoral immune responses, albeit they were higher for cationic microspheres. Moreover, surface charge seemed to have a role on biasing the immune response; cationic microspheres induced higher IFN-gamma levels, indicative of Th1 activation, while unmodified ones mainly triggered IL4 and IL17A release, showing Th2 activation. Thus, we have shown here the potential and versatility of these MS, which may be tailored to needs. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Salvador, Aiala; Pedraz, Jose Luis; Maria Hernandez, Rosa; Igartua, Manoli] Univ Basque Country UPV EHU, Sch Pharm, Lab Pharmaceut, NanoBioCel Grp, Vitoria 01006, Spain.
[Salvador, Aiala; Pedraz, Jose Luis; Maria Hernandez, Rosa; Igartua, Manoli] Biomed Res Networking Ctr Bioengn Biomat & Nanome, Vitoria, Spain.
[Sandgren, Kerrie J.; Liang, Frank; Thompson, Elizabeth A.; Lore, Karin] Karolinska Inst, Dept Med Solna, Clin Immunol & Allergy Unit, SE-17176 Stockholm, Sweden.
[Liang, Frank; Thompson, Elizabeth A.; Koup, Richard A.; Lore, Karin] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Lore, K (reprint author), Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med Solna, Clin Immunol & Allergy Unit, L2 04, SE-17176 Stockholm, Sweden.
EM karin.lore@ki.se; manoli.igartua@ehu.es
OI IGARTUA OLAECHEA, MANUELA/0000-0003-0283-7923; PEDRAZ MUNOZ, JOSE
LUIS/0000-0002-3938-2267; Hernandez, Rosa Maria/0000-0002-3947-409X
FU Basque Government (Consolidated Groups) [IT-407-07]; University of the
Basque Country UPV/EHU [UFI11/32]
FX Authors acknowledge the technical support and advice provided by SGIker
(UPV/EHU, MICINN, GV/EJ, ESF) on scanning electron microscopy. This
project was partially supported by the Basque Government (Consolidated
Groups, IT-407-07). Authors gratefully acknowledge the support provided
by the University of the Basque Country UPV/EHU (UFI11/32). Authors also
wish to thank the intellectual and technical assistance from the ICTS
"NANBIOSIS", more specifically by the Drug Formulation Unit (U10) of the
CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the
University of Basque Country (UPV/EHU).
NR 52
TC 1
Z9 1
U1 3
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD DEC 30
PY 2015
VL 496
IS 2
BP 371
EP 381
DI 10.1016/j.ijpharm.2015.10.037
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CZ8YJ
UT WOS:000367384700020
PM 26475970
ER
PT J
AU Kretschmer, F
Sajgo, S
Kretschmer, V
Badea, TC
AF Kretschmer, Friedrich
Sajgo, Szilard
Kretschmer, Viola
Badea, Tudor C.
TI A system to measure the Optokinetic and Optomotor response in mice
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Mouse; Vision; Retina; Behavior; Optomotor response; Head movements;
Optokinetic reflex; Eye movements; Video tracking visual field
ID EYE-MOVEMENTS; CONTRAST SENSITIVITY; SPATIAL VISION; MOUSE; ZEBRAFISH;
REFLEX; STIMULI; ACUITY; ADULT; SPEED
AB Background: Visually evoked compensatory head movements (Optomotor responses) or eye movements (Optokinetic responses) are extensively used in experimental mouse models for developmental defects, pathological conditions, and testing the efficacy of therapeutic manipulations.
New method: We present an automated system to measure Optomotor and Optokinetic responses under identical stimulation conditions, enabling a direct comparison of the two reflexes. A semi-automated calibration procedure and a commercial eye tracker are used to record angular eye velocity in the restrained animal. Novel video tracking algorithms determine the location of the mouse head in real time and allow repositioning of the stimulus relative to the mouse head.
Results: Optomotor and Optokinetic responses yield comparable results with respect to determining visual acuity in mice. Our new head tracking algorithms enable a far more accurate analysis of head angle determination, and reveal individual head retractions, analogous to saccadic eye movements observed during Optokinetic Nystagmus.
Comparison with existing methods: To our knowledge this is the first apparatus allowing the direct comparison of Optomotor and Optokinetic responses in mice. Our tracking algorithms, which allow an objective determination of head movements are a significant increment over existing systems which rely on subjective human observation. The increased accuracy of the novel algorithms increases the robustness of automated Optomotor response determinations and reveals novel aspects of this reflex.
Conclusions: We provide the blueprints for inexpensive hardware, and release open source software for our system, and describe an accurate and accessible method for Optomotor and Optokinetic response determination in mice. Published by Elsevier B.V.
C1 [Kretschmer, Friedrich; Sajgo, Szilard; Kretschmer, Viola; Badea, Tudor C.] NEI, Retinal Circuit Dev & Genet Unit, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Kretschmer, F (reprint author), NEI, Retinal Circuit Dev & Genet Unit, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM friedrich@openetho.com; tudor.badea@nih.gov
FU Intramural Research Program of the National Eye Institute
FX Hugh Cahill has provided guidance with implementing the head surgeries
and designing the head fixation apparatus. Felix Ighovie Onojafe has
provided technical help with head surgery optimization. Haohua Qiang has
helped with calibration and measurement of screen light intensities
under scotopic and photopic conditions. Lance Optican has provided
helpful suggestions and critical reading of the manuscript. Funding for
this work was provided by the Intramural Research Program of the
National Eye Institute.
NR 30
TC 4
Z9 4
U1 5
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
EI 1872-678X
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD DEC 30
PY 2015
VL 256
BP 91
EP 105
DI 10.1016/j.jneumeth.2015.08.007
PG 15
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CY7VW
UT WOS:000366618400010
PM 26279344
ER
PT J
AU Hilbert, K
Pine, DS
Muehlhan, M
Lueken, U
Steudte-Schmiedgen, S
Beesdo-Baum, K
AF Hilbert, Kevin
Pine, Daniel S.
Muehlhan, Markus
Lueken, Ulrike
Steudte-Schmiedgen, Susann
Beesdo-Baum, Katja
TI Gray and white matter volume abnormalities in generalized anxiety
disorder by categorical and dimensional characterization
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Generalized anxiety disorder; Worry; Intolerance of uncertainty;
Neuroimaging; Structural magnetic resonance imaging; Prefrontal cortex;
Putamen; Caudate nucleus; Striatum
ID MAJOR DEPRESSIVE DISORDER; VOXEL-BASED MORPHOMETRY; STATE WORRY
QUESTIONNAIRE; OBSESSIVE-COMPULSIVE DISORDER; IMPLICIT REGULATION;
PEDIATRIC-PATIENTS; METAANALYSIS; BRAIN; CONNECTIVITY; UNCERTAINTY
AB Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Hilbert, Kevin; Muehlhan, Markus; Lueken, Ulrike; Beesdo-Baum, Katja] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany.
[Hilbert, Kevin; Muehlhan, Markus; Lueken, Ulrike; Beesdo-Baum, Katja] Tech Univ Dresden, Neuroimaging Ctr, D-01062 Dresden, Germany.
[Hilbert, Kevin; Beesdo-Baum, Katja] Tech Univ Dresden, Behav Epidemiol, D-01062 Dresden, Germany.
[Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Lueken, Ulrike] Univ Hosp Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany.
[Steudte-Schmiedgen, Susann] Tech Univ Dresden, Biol Psychol, D-01062 Dresden, Germany.
RP Hilbert, K (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany.
EM Kevin.Hilbert@tu-dresden.de
RI Lueken, Ulrike/A-8109-2014;
OI Lueken, Ulrike/0000-0003-1564-4012; Muehlhan, Markus/0000-0002-8855-8724
FU Technische Universitat Dresden (Germany)
FX The research project was partly supported by internal grant funding from
the Technische Universitat Dresden (Germany). All authors report no
financial relationships that might be perceived as conflict of interest.
NR 64
TC 3
Z9 3
U1 9
U2 31
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD DEC 30
PY 2015
VL 234
IS 3
BP 314
EP 320
DI 10.1016/j.pscychresns.2015.10.009
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CX9FU
UT WOS:000366011200005
PM 26490569
ER
PT J
AU Bhatt, S
Weiss, DJ
Mappin, B
Dalrymple, U
Cameron, E
Bisanzio, D
Smith, DL
Moyes, CL
Tatem, AJ
Lynch, M
Fergus, CA
Yukich, J
Bennett, A
Eisele, TP
Kolaczinski, J
Cibulskis, RE
Hay, SI
Gething, PW
AF Bhatt, Samir
Weiss, Daniel J.
Mappin, Bonnie
Dalrymple, Ursula
Cameron, Ewan
Bisanzio, Donal
Smith, David L.
Moyes, Catherine L.
Tatem, Andrew J.
Lynch, Michael
Fergus, Cristin A.
Yukich, Joshua
Bennett, Adam
Eisele, Thomas P.
Kolaczinski, Jan
Cibulskis, Richard E.
Hay, Simon I.
Gething, Peter W.
TI Coverage and system efficiencies of insecticide-treated nets in Africa
from 2000 to 2017
SO ELIFE
LA English
DT Article
ID MALARIA; COUNTRIES; MORTALITY; PROGRESS; CHILDREN; ACCOUNT; EQUITY
AB Insecticide-treated nets (ITNs) for malaria control are widespread but coverage remains inadequate. We developed a Bayesian model using data from 102 national surveys, triangulated against delivery data and distribution reports, to generate year-by-year estimates of four ITN coverage indicators. We explored the impact of two potential 'inefficiencies': uneven net distribution among households and rapid rates of net loss from households. We estimated that, in 2013, 21% (17%-26%) of ITNs were over-allocated and this has worsened over time as overall net provision has increased. We estimated that rates of ITN loss from households are more rapid than previously thought, with 50% lost after 23 (20-28) months. We predict that the current estimate of 920 million additional ITNs required to achieve universal coverage would in reality yield a lower level of coverage (77% population access). By improving efficiency, however, the 920 million ITNs could yield population access as high as 95%.
C1 [Bhatt, Samir; Weiss, Daniel J.; Mappin, Bonnie; Dalrymple, Ursula; Cameron, Ewan; Bisanzio, Donal; Smith, David L.; Moyes, Catherine L.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford, England.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
[Smith, David L.; Tatem, Andrew J.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Lynch, Michael; Fergus, Cristin A.; Cibulskis, Richard E.] World Hlth Org, Global Malaria Programme, Geneva, Switzerland.
[Yukich, Joshua; Eisele, Thomas P.] Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Appl Malaria Res & Evalut, Dept Global Hlth Syst & Dev, New Orleans, LA USA.
[Bennett, Adam] Univ Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA.
[Kolaczinski, Jan] Global Fund Fight AIDS TB & Malaria, Strategy Investment & Impact Div, Geneva, Switzerland.
[Hay, Simon I.] Univ Oxford, Wellcome Trust, Ctr Human Genet, Oxford, England.
[Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford, England.
EM peter.gething@zoo.ox.ac.uk
RI Smith, David/L-8850-2013;
OI Mappin, Bonnie/0000-0002-1205-719X; Smith, David/0000-0003-4367-3849;
Hay, Simon/0000-0002-0611-7272; Gething, Peter/0000-0001-6759-5449;
Moyes, Catherine/0000-0002-8028-4079
FU Medical Research Council [K00669X]; Bill and Melinda Gates Foundation
[OPP1068048, OPP1110495, OPP1106023, OPP1119467, OPP1093011]; Foundation
for the National Institutes of Health [U19AI089674]; Fogarty
International Center; Wellcome Trust [091835, 095066]; World Health
Organization; Global Fund to Fight AIDS, Tuberculosis and Malaria;
Department for International Development
FX Medical Research Council K00669X Samir Bhatt Peter W Gething; Bill and
Melinda Gates Foundation OPP1068048 Daniel J Weiss Bonnie Mappin Ursula
Dalrymple Ewan Cameron Donal Bisanzio Peter W Gething; Foundation for
the National Institutes of Health U19AI089674 David L Smith; Bill and
Melinda Gates Foundation OPP1110495 David L Smith; Fogarty International
Center Simon I Hay David L Smith; Wellcome Trust 091835 Catherine L
Moyes; World Health Organization Michael Lynch Cristin A Fergus Richard
E Cibulskis; Global Fund to Fight AIDS, Tuberculosis and Malaria Jan
Kolaczinski; Bill and Melinda Gates Foundation OPP1106023 Simon I Hay
Peter W Gething; Bill and Melinda Gates Foundation OPP1119467 Simon I
Hay; Wellcome Trust 095066 Simon I Hay; Bill and Melinda Gates
Foundation OPP1093011 Simon I Hay; Department for International
Development Peter W Gething; The funders had no role in study design,
data collection and interpretation, or the decision to submit the work
for publication
NR 36
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Z9 13
U1 2
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 29
PY 2015
VL 4
AR e09672
DI 10.7554/eLife.09672
PG 37
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9HN
UT WOS:000373813400001
ER
PT J
AU Lee, EC
Viboud, C
Simonsen, L
Khan, F
Bansal, S
AF Lee, Elizabeth C.
Viboud, Cecile
Simonsen, Lone
Khan, Farid
Bansal, Shweta
TI Detecting signals of seasonal influenza severity through age dynamics
SO BMC INFECTIOUS DISEASES
LA English
DT Article
DE Influenza; Influenza-like illness; Severity; Metrics; Age patterns;
Epidemiology; Mortality; United States
ID RESPIRATORY SYNCYTIAL VIRUS; CARE-SEEKING BEHAVIOR; TRANSMISSION
PARAMETERS; DECISION-MAKING; UNITED-STATES; MORTALITY; H1N1; INFECTION;
ILLNESS; IMPACT
AB Background: Measures of population-level influenza severity are important for public health planning, but estimates are often based on case-fatality and case-hospitalization risks, which require multiple data sources, are prone to surveillance biases, and are typically unavailable in the early stages of an outbreak. To address the limitations of traditional indicators, we propose a novel severity index based on influenza age dynamics estimated from routine physician diagnosis data that can be used retrospectively and for early warning.
Methods: We developed a quantitative 'ground truth' severity benchmark that synthesizes multiple traditional severity indicators from publicly available influenza surveillance data in the United States. Observing that the age distribution of cases may signal severity early in an epidemic, we constructed novel retrospective and early warning severity indexes based on the relative risk of influenza-like illness (ILI) among working-age adults to that among school-aged children using weekly outpatient medical claims. We compared our relative risk-based indexes to the composite benchmark and estimated seasonal severity for flu seasons from 2001-02 to 2008-09 at the national and state levels.
Results: The severity classifications made by the benchmark were not uniquely captured by any single contributing metric, including pneumonia and influenza mortality; the influenza epidemics of 2003-04 and 2007-08 were correctly identified as the most severe of the study period. The retrospective index was well correlated with the severity benchmark and correctly identified the two most severe seasons. The early warning index performance varied, but it projected 2007-08 as relatively severe 10 weeks prior to the epidemic peak. Influenza severity varied significantly among states within seasons, and four states were identified as possible early warning sentinels for national severity.
Conclusions: Differences in age patterns of ILI may be used to characterize seasonal influenza severity in the United States in real-time and in a spatially resolved way. Future research on antigenic changes among circulating viruses, pre-existing immunity, and changing contact patterns may better elucidate the mechanisms underlying these indexes. Researchers and practitioners should consider the use of composite or ILI-based severity metrics in addition to traditional severity measures to inform epidemiological understanding and situational awareness in future seasonal outbreaks.
C1 [Lee, Elizabeth C.; Bansal, Shweta] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Viboud, Cecile; Bansal, Shweta] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC USA.
[Simonsen, Lone] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Khan, Farid] IMS Hlth, Plymouth Meeting, PA USA.
[Khan, Farid] Pfizer Inc, Collegeville, PA USA.
RP Bansal, S (reprint author), Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
EM shweta.bansal@georgetown.edu
OI Lee, Elizabeth/0000-0002-4156-9637; Simonsen, Lone/0000-0003-1535-8526;
Bansal, Shweta/0000-0002-1740-5421
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, Department of Homeland Security
(DHS); Fogarty International Center, National Institutes of Health (NIH)
FX This work was supported by the Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directorate, Department of Homeland Security (DHS), and the Fogarty
International Center, National Institutes of Health (NIH). The authors
thank Matthew Biggerstaff for providing data on age-specific ILI
care-seeking behavior and comments on our draft, Jason Asher for useful
suggestions in the state-level analyses, and Vittoria Colizza and Anne
Presanis who provided valuable feedback on a previous manuscript
version.
NR 45
TC 3
Z9 3
U1 0
U2 5
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 DEC 29
PY 2015
VL 15
AR 587
DI 10.1186/s12879-015-1318-9
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA CZ8AA
UT WOS:000367320900004
PM 26715193
ER
PT J
AU Okada, M
Wen, L
Miller, TC
Su, D
Shi, YB
AF Okada, Morihiro
Wen, Luan
Miller, Thomas C.
Su, Dan
Shi, Yun-Bo
TI Molecular and cytological analyses reveal distinct transformations of
intestinal epithelial cells during Xenopus metamorphosis
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Thyroid hormone; Metamorphosis; Xenopus laevis; Thyroid hormone
receptor; Stem cells; Intestine
ID MOUSE SMALL-INTESTINE; THYROID-HORMONE RECEPTOR; ACID-BINDING PROTEIN;
ADULT STEM-CELLS; AMPHIBIAN METAMORPHOSIS; LAEVIS TADPOLES; EPIGENETIC
REGULATION; ANURAN METAMORPHOSIS; EXPRESSION PROFILES; CONNECTIVE-TISSUE
AB Background: The thyroid hormone (T3)-induced formation of adult intestine during amphibian metamorphosis resembles the maturation of the mammalian intestine during postembryonic development, the period around birth when plasma T3 level peaks. This process involves de novo formation of adult intestinal stem cells as well as the removal of the larval epithelial cells through apoptosis. Earlier studies have revealed a number of cytological and molecular markers for the epithelial cells undergoing different changes during metamorphosis. However, the lack of established double labeling has made it difficult to ascertain the identities of the metamorphosing epithelial cells.
Results: Here, we carried out different double-staining with a number of cytological and molecular markers during T3-induced and natural metamorphosis in Xenopus laevis. Our studies demonstrated conclusively that the clusters of proliferating cells in the epithelium at the climax of metamorphosis are undifferentiated epithelial cells and express the well-known adult intestinal stem cell marker gene Lgr5. We further show that the adult stem cells and apoptotic larval epithelial cells are distinct epithelial cells during metamorphosis.
Conclusions: Our findings suggest that morphologically identical larval epithelial cells choose two alternative paths: programmed cell death or dedifferentiation to form adult stem cells, in response to T3 during metamorphosis with apoptosis occurring prior to the formation of the proliferating adult stem cell clusters (islets).
C1 [Okada, Morihiro; Wen, Luan; Miller, Thomas C.; Su, Dan; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, 18 Lib Dr, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU intramural Research Program of NICHD, NIH; Japan Society for the
Promotion of Science (NIH) Fellowship
FX This work was supported by the intramural Research Program of NICHD,
NIH. MO was supported in part by Japan Society for the Promotion of
Science (NIH) Fellowship.
NR 50
TC 2
Z9 2
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD DEC 29
PY 2015
VL 5
AR 74
DI 10.1186/s13578-015-0065-3
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ8BF
UT WOS:000367324200001
PM 26719790
ER
PT J
AU Shiroma, EJ
Cook, NR
Manson, JE
Buring, JE
Rimm, EB
Lee, IM
AF Shiroma, Eric J.
Cook, Nancy R.
Manson, Joann E.
Buring, Julie E.
Rimm, Eric B.
Lee, I-Min
TI Comparison of Self-Reported and Accelerometer-Assessed Physical Activity
in Older Women
SO PLOS ONE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; SEDENTARY BEHAVIOR;
ACTIVITY QUESTIONNAIRE; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE;
UNITED-STATES; ADULTS; HEALTH; AGE
AB Background
Self-reported physical activity measures continue to be validated against accelerometers; however, the absence of standardized, accelerometer moderate-to-vigorous physical activity (MVPA) definitions has made comparisons across studies difficult. Furthermore, recent accelerometer models assess accelerations in three axes, instead of only the vertical axis, but validation studies have yet to take incorporate triaxial data.
Methods
Participants (n = 10 115) from the Women's Health Study wore a hip-worn accelerometer (ActiGraph GT3X+) for seven days during waking hours (2011-2014). Women then completed a physical activity questionnaire. We compared self-reported with accelerometer-assessed MVPA, using four established cutpoints for MVPA: three using only vertical axis data (760, 1041 and 1952 counts per minute (cpm)) and one using triaxial data (2690 cpm).
Results
According to self-reported physical activity, 66.6% of women met the US federal physical activity guidelines, engaging in >= 150 minutes per week of MVPA. The percent of women who met guidelines varied widely depending on the accelerometer MVPA definition (760 cpm: 50.0%, 1041 cpm: 33.0%, 1952 cpm: 13.4%, and 2690 cpm: 19.3%).
Conclusions
Triaxial count data do not substantially reduce the difference between self-reported and accelerometer-assessed MVPA.
C1 [Shiroma, Eric J.; Cook, Nancy R.; Manson, Joann E.; Buring, Julie E.; Rimm, Eric B.; Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA.
[Shiroma, Eric J.; Cook, Nancy R.; Manson, Joann E.; Buring, Julie E.; Rimm, Eric B.; Lee, I-Min] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Shiroma, Eric J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Shiroma, EJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA.
EM Eric.shiroma@nih.gov
FU National Institutes of Health [CA154647, CA047988, HL007575]; National
Institute on Aging
FX This research was supported by research grants CA154647 and CA047988
from the National Institutes of Health. EJS was supported in part by and
the Intramural Research Program of the National Institutes of Health,
National Institute on Aging and in part by training grant HL007575 from
the National Institutes of Health. The funders had no role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 64
TC 3
Z9 3
U1 0
U2 7
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 DEC 29
PY 2015
VL 10
IS 12
AR e0145950
DI 10.1371/journal.pone.0145950
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA0IX
UT WOS:000367481900104
PM 26713857
ER
PT J
AU Kalyanasundram, J
Chia, SL
Song, AAL
Raha, AR
Young, HA
Yusoff, K
AF Kalyanasundram, Jeevanathan
Chia, Suet Lin
Song, Adelene Ai-Lian
Raha, Abdul Rahim
Young, Howard A.
Yusoff, Khatijah
TI Surface display of glycosylated Tyrosinase related protein-2 (TRP-2)
tumour antigen on Lactococcus lactis
SO BMC BIOTECHNOLOGY
LA English
DT Article
DE Surface display; Lactococcus lactis; Lysin motif; Tyrosinase related
protein-2
ID ACID BACTERIA; LACTOBACILLUS-PLANTARUM; DOPACHROME TAUTOMERASE;
THERAPEUTIC PROTEINS; PICHIA-PASTORIS; BINDING DOMAIN; EXPRESSION;
MELANOMA; DELIVERY; VACCINE
AB Background: The exploitation of the surface display system of food and commensal lactic acid bacteria (LAB) for bacterial, viral, or protozoan antigen delivery has received strong interest recently. The Generally Regarded as Safe (GRAS) status of the Lactococcus lactis coupled with a non-recombinant strategy of in-trans surface display, provide a safe platform for therapeutic drug and vaccine development. However, production of therapeutic proteins fused with cell-wall anchoring motifs is predominantly limited to prokaryotic expression systems. This presents a major disadvantage in the surface display system particularly when glycosylation has been recently identified to significantly enhance epitope presentation. In this study, the glycosylated murine Tyrosinase related protein-2 (TRP-2) with the ability to anchor onto the L. lactis cell wall was produced in suspension adapted Chinese Hamster Ovary (CHO-S) cells by expressing TRP-2 fused with cell wall anchoring LysM motif (cA) at the C-terminus.
Results: A total amount of 33 mu g of partially purified TRP-2-cA from similar to 6.0 g in wet weight of CHO-S cells was purified by His-tag affinity chromatography. The purified TRP-2-cA protein was shown to be N-glycosylated and successfully anchored to the L. lactis cell wall.
Conclusions: Thus cell surface presentation of glycosylated mammalian antigens may now permit development of novel and inexpensive vaccine platforms.
C1 [Kalyanasundram, Jeevanathan; Song, Adelene Ai-Lian; Raha, Abdul Rahim] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Cell & Mol Biol, Serdang 43400, Selangor Darul, Malaysia.
[Chia, Suet Lin; Yusoff, Khatijah] Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Microbiol, Upm Serdang 43400, Selangor Darul, Malaysia.
[Raha, Abdul Rahim; Yusoff, Khatijah] Univ Putra Malaysia, Inst Biosci, Serdang 43400, Selangor Darul, Malaysia.
[Young, Howard A.] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA.
RP Yusoff, K (reprint author), Univ Putra Malaysia, Fac Biotechnol & Biomol Sci, Dept Microbiol, Upm Serdang 43400, Selangor Darul, Malaysia.
EM kyusoff@upm.edu.my
OI CHIA, SUET LIN/0000-0002-7798-9991
FU Malaysian Ministry of Science, Technology and Innovation
[02-01-04-SF1273]; intramural research program of U. S. National Cancer
Institute
FX The research was funded by Malaysian Ministry of Science, Technology and
Innovation (Grant Number: 02-01-04-SF1273). We would like to thank Dr.
Andrew Hurwitz of US National Cancer Institute for providing TRP-2 cDNA.
A portion of this work was supported by funding to H.A.Y. by the
intramural research program of the U. S. National Cancer Institute.
NR 48
TC 1
Z9 1
U1 3
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6750
J9 BMC BIOTECHNOL
JI BMC Biotechnol.
PD DEC 29
PY 2015
VL 15
AR 113
DI 10.1186/s12896-015-0231-z
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CZ6NW
UT WOS:000367219000001
PM 26715153
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Energetics and population genetics at the root of eukaryotic cellular
and genomic complexity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID EVOLUTION; INTRONS; ORIGIN
C1 [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
NR 18
TC 1
Z9 1
U1 4
U2 22
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 DEC 29
PY 2015
VL 112
IS 52
BP 15777
EP 15778
DI 10.1073/pnas.1520869112
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ6TU
UT WOS:000367234700029
PM 26699503
ER
PT J
AU Ombrello, MJ
Remmers, EF
Tachmazidou, I
Grom, A
Foell, D
Haas, JP
Martini, A
Gattorno, M
Ozen, S
Prahalad, S
Zeft, AS
Bohnsack, JF
Mellins, ED
Ilowite, NT
Russo, R
Len, C
Hilario, MOE
Oliveira, S
Yeung, RSM
Rosenberg, A
Wedderburn, LR
Anton, J
Schwarz, T
Hinks, A
Bilginer, Y
Park, J
Cobb, J
Satorius, CL
Han, B
Baskin, E
Signa, S
Duerr, RH
Achkar, JP
Kamboh, MI
Kaufman, KM
Kottyan, LC
Pinto, D
Scherer, SW
Alarcon-Riquelme, ME
Docampo, E
Estivill, X
Gul, A
de Bakker, PIW
Raychaudhuri, S
Langefeld, CD
Thompson, S
Zeggini, E
Thomson, W
Kastner, DL
Woo, P
AF Ombrello, Michael J.
Remmers, Elaine F.
Tachmazidou, Ioanna
Grom, Alexei
Foell, Dirk
Haas, Johannes-Peter
Martini, Alberto
Gattorno, Marco
Ozen, Seza
Prahalad, Sampath
Zeft, Andrew S.
Bohnsack, John F.
Mellins, Elizabeth D.
Ilowite, Norman T.
Russo, Ricardo
Len, Claudio
Hilario, Maria Odete E.
Oliveira, Sheila
Yeung, Rae S. M.
Rosenberg, Alan
Wedderburn, Lucy R.
Anton, Jordi
Schwarz, Tobias
Hinks, Anne
Bilginer, Yelda
Park, Jane
Cobb, Joanna
Satorius, Colleen L.
Han, Buhm
Baskin, Elizabeth
Signa, Sara
Duerr, Richard H.
Achkar, J. P.
Kamboh, M. Ilyas
Kaufman, Kenneth M.
Kottyan, Leah C.
Pinto, Dalila
Scherer, Stephen W.
Alarcon-Riquelme, Marta E.
Docampo, Elisa
Estivill, Xavier
Guel, Ahmet
de Bakker, Paul I. W.
Raychaudhuri, Soumya
Langefeld, Carl D.
Thompson, Susan
Zeggini, Eleftheria
Thomson, Wendy
Kastner, Daniel L.
Woo, Patricia
CA BSPAR Study Grp
Randomized Placebo Phase Study
CHARMS Grp
BBOP Grp
Int Childhood Arthritis Genetics
TI HLA-DRB1*11 and variants of the MHC class II locus are strong risk
factors for systemic juvenile idiopathic arthritis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE systemic juvenile idiopathic arthritis; Still's disease; human leukocyte
antigen; autoinflammation
ID MACROPHAGE ACTIVATION SYNDROME; RHEUMATOID-ARTHRITIS; CHILDREN;
ASSOCIATIONS; PATHOGENESIS; ABATACEPT; DISEASE; GENES; CELLS
AB Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 x 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 x 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 x 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 x 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.
C1 [Ombrello, Michael J.; Baskin, Elizabeth] NIAMSD, Translat Genet & Genom Unit, NIH, Bethesda, MD 20892 USA.
[Remmers, Elaine F.; Satorius, Colleen L.; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Tachmazidou, Ioanna; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Human Genet, Hinxton CB10 1SA, England.
[Grom, Alexei; Kaufman, Kenneth M.; Kottyan, Leah C.; Thompson, Susan] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA.
[Grom, Alexei; Kaufman, Kenneth M.; Kottyan, Leah C.; Thompson, Susan] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Foell, Dirk] Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, D-48149 Munster, Germany.
[Haas, Johannes-Peter] German Ctr Pediat & Adolescent Rheumatol, D-82467 Garmisch Partenkirchen, Germany.
[Martini, Alberto; Signa, Sara] Univ Genoa, Dept Pediat, I-16145 Genoa, Italy.
[Martini, Alberto; Gattorno, Marco] G Gaslini Inst Children, Pediat Unit 2, I-16147 Genoa, Italy.
[Ozen, Seza; Bilginer, Yelda] Hacettepe Univ, Dept Pediat Rheumatol, TR-06100 Ankara, Turkey.
[Prahalad, Sampath] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
[Prahalad, Sampath] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
[Zeft, Andrew S.] Cleveland Clin, Dept Pediat, Cleveland, OH 44195 USA.
[Bohnsack, John F.] Univ Utah, Dept Pediat, Salt Lake City, UT 84113 USA.
[Mellins, Elizabeth D.; Park, Jane] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Ilowite, Norman T.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
[Ilowite, Norman T.] Childrens Hosp Montefiore, Bronx, NY 10461 USA.
[Russo, Ricardo] Hosp Pediat Garrahan, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina.
[Len, Claudio; Hilario, Maria Odete E.] Univ Fed Sao Paulo, Dept Pediat, BR-04021001 Sao Paulo, Brazil.
[Oliveira, Sheila] Univ Fed Rio de Janeiro, BR-21941901 Rio De Janeiro, Brazil.
[Yeung, Rae S. M.] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A8, Canada.
[Yeung, Rae S. M.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
[Yeung, Rae S. M.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
[Rosenberg, Alan] Univ Saskatchewan, Dept Pediat, Saskatoon, SK S7N 0W8, Canada.
[Wedderburn, Lucy R.] UCL, Inst Child Hlth, London WC1N 1EH, England.
[Wedderburn, Lucy R.; Woo, Patricia] UCL, Ctr Paediat & Adolescent Rheumatol, London WC1N 1EH, England.
[Anton, Jordi] Univ Barcelona, Hosp St Joan de Deu, Pediat Rheumatol Unit, Barcelona 08950, Spain.
[Schwarz, Tobias] Univ Wurzburg, Sect Pediat Rheumatol & Osteol, D-97080 Wurzburg, Germany.
[Hinks, Anne; Cobb, Joanna; Raychaudhuri, Soumya; Thomson, Wendy] Univ Manchester, Manchester Acad Hlth Ctr, Arthritis Res UK Ctr Genet & Genom, Manchester M13 9PT, Lancs, England.
[Cobb, Joanna; Thomson, Wendy] Univ Manchester, Manchester Acad Hlth Ctr, Cent Manchester Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Manchester Musculoskeletal Bio, Manchester M13 9PT, Lancs, England.
[Han, Buhm; Raychaudhuri, Soumya] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA.
[Han, Buhm; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Immunol Allergy & Rheumatol, Boston, MA 02115 USA.
[Han, Buhm] Univ, Coll Med, Asan Med Ctr, Dept Convergence Med, Seoul 138736, South Korea.
[Duerr, Richard H.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA.
[Duerr, Richard H.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Achkar, J. P.] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA.
[Achkar, J. P.] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44195 USA.
[Pinto, Dalila] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 0A4, Canada.
[Alarcon-Riquelme, Marta E.] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Program, Oklahoma City, OK 73104 USA.
[Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Andalusian Govt, Ctr Genom & Oncol Res, Pts Granada 18016, Spain.
[Docampo, Elisa] Univ Liege, Interdisciplinary Cluster Appl Genoprot, B-4000 Cointe Ougree, Belgium.
[Docampo, Elisa; Estivill, Xavier] Barcelona Inst Sci & Technol, CRG, Barcelona 08003, Spain.
[Docampo, Elisa; Estivill, Xavier] UPF, Barcelona 08003, Spain.
[Guel, Ahmet] Istanbul Univ, Istanbul Fac Med, TR-34390 Istanbul, Turkey.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27106 USA.
RP Ombrello, MJ (reprint author), NIAMSD, Translat Genet & Genom Unit, NIH, Bethesda, MD 20892 USA.
EM ombrellomj@mail.nih.gov; kastnerd@mail.nih.gov
RI Scherer, Stephen /B-3785-2013; Estivill, Xavier/A-3125-2013; Oliveira,
Sheila/F-5213-2016; Anton, Jordi/A-9848-2017;
OI Scherer, Stephen /0000-0002-8326-1999; Estivill,
Xavier/0000-0002-0723-2256; Oliveira, Sheila/0000-0002-2426-716X; Anton,
Jordi/0000-0002-8792-4219; Kottyan, Leah/0000-0003-3979-2220; Houghton,
Kristin/0000-0001-7174-1007; Cobb, Joanna/0000-0002-2760-3114; Turvey,
Stuart/0000-0003-1599-1065
FU Intramural Research Programs of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases [Z01-AR041198]; National Human Genome
Research Institute of the NIH [Z01-HG200370]; NIH [R01-AR059049,
R01-AR060893, N1R01-AR062886, AG030653, AG041718, AG005133,
U01-DK062420, R01-DK076025]; Arthritis Research UK [20385, 20542,
20386]; Netherlands Organization for Scientific Research Project
[016.126.354]; Marcus Foundation; Wellcome Trust [098051, 076113,
085475]; Val A. Browning Charitable Foundation; Crohn's & Colitis
Foundation of America Senior Research Award; SPARKS UK [08ICH09,
12ICH08]; Medical Research Council [MR/M004600/1]; UK National Institute
for Health Research Medicines for Children Research Network
FX This work was supported by the Intramural Research Programs of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(Z01-AR041198, to M.J.O.) and the National Human Genome Research
Institute (Z01-HG200370, to D.L.K.) of the NIH. Additional funding was
provided by NIH Grants R01-AR059049 (to A. Grom), R01-AR060893 (to
S.P.), N1R01-AR062886 (to P.I.W.d.B.), AG030653, AG041718, and AG005133
(to M.I.K.), and U01-DK062420 and R01-DK076025 (to R.H.D.); Arthritis
Research UK Grant 20385 (to W.T.); the Netherlands Organization for
Scientific Research Project No. 016.126.354 (to P.I.W.d.B.); the Marcus
Foundation (S.P.); the Wellcome Trust Grant 098051 (to E.Z.); the Val A.
Browning Charitable Foundation (J.F.B.); and a Crohn's & Colitis
Foundation of America Senior Research Award (to R.H.D.). UK patient
cohorts were supported by Arthritis Research UK (Grants 20542 and
20386). Sparks-CHARMS was funded by grants from SPARKS UK (08ICH09 and
12ICH08), the Medical Research Council (MR/M004600/1), and the UK
National Institute for Health Research Medicines for Children Research
Network. This study makes use of data generated by the Wellcome Trust
Case-Control Consortium. A full list of the investigators who
contributed to the generation of data is available at www.wtccc.org.uk.
Funding for the project was provided by the Wellcome Trust under award
076113 and 085475. This study utilized the computational resources of
the NIH high-performance computing Biowulf cluster
(https://hpc.nih.gov).
NR 27
TC 8
Z9 8
U1 3
U2 20
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 DEC 29
PY 2015
VL 112
IS 52
BP 15970
EP 15975
DI 10.1073/pnas.1520779112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ6TU
UT WOS:000367234700064
PM 26598658
ER
PT J
AU Reiner, RC
Le Menach, A
Kunene, S
Ntshalintshali, N
Hsiang, MS
Perkins, TA
Greenhouse, B
Tatem, AJ
Cohen, JM
Smith, DL
AF Reiner, Robert C., Jr.
Le Menach, Arnaud
Kunene, Simon
Ntshalintshali, Nyasatu
Hsiang, Michelle S.
Perkins, T. Alex
Greenhouse, Bryan
Tatem, Andrew J.
Cohen, Justin M.
Smith, David L.
TI Mapping residual transmission for malaria elimination
SO ELIFE
LA English
DT Article
ID SPECIES DISTRIBUTIONS; INFECTIOUS-DISEASE; WETNESS INDEXES; HIGHLANDS;
BURDEN; RISK
AB Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections. In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show 'malariogenic potential', a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination.
C1 [Reiner, Robert C., Jr.; Perkins, T. Alex; Tatem, Andrew J.; Smith, David L.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Reiner, Robert C., Jr.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA.
[Le Menach, Arnaud; Ntshalintshali, Nyasatu; Cohen, Justin M.] Clinton Hlth Access Initiat, Boston, MA USA.
[Kunene, Simon] Natl Malaria Control Program, Manzini, Swaziland.
[Hsiang, Michelle S.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Hsiang, Michelle S.] Univ Calif San Francisco, Malaria Eliminat Initiat, Global Hlth Grp, San Francisco, CA 94143 USA.
[Hsiang, Michelle S.] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA.
[Perkins, T. Alex] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Greenhouse, Bryan] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Smith, David L.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
RP Reiner, RC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM rcreiner@indiana.edu
FU Bill and Melinda Gates Foundation [OPP1110495, OPP1109772, OPP1013170,
OPP1132226, OPP1106427, OPP1032350]; Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; Swaziland Ministry of Health;
National Institute of Allergy and Infectious Diseases [7K23A1101012];
Burroughs Wellcome Fund [SPA0000798]; National Institutes of Health
[ICMER U19 A1089674]; Wellcome Trust
FX Bill and Melinda Gates Foundation OPP1110495 Robert C Reiner Jr T Alex
Perkins David L Smith; The Research and Policy for Infectious Disease
Dynamics (RAPIDD) program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health Robert C Reiner Jr T Alex Perkins Andrew J
Tatem David L Smith; Bill and Melinda Gates Foundation OPP1109772 Arnaud
Le Menach Justin M Cohen; Swaziland Ministry of Health Michelle S
Hsiang; National Institute of Allergy and Infectious Diseases
7K23A1101012 Michelle S Hsiang; Burroughs Wellcome Fund SPA0000798
Michelle S Hsiang; Bill and Melinda Gates Foundation OPP1013170 Michelle
S Hsiang; Bill and Melinda Gates Foundation OPP1132226 T Alex Perkins
Bryan Greenhouse; National Institutes of Health ICMER U19 A1089674 Bryan
Greenhouse David L Smith; Bill and Melinda Gates Foundation OPP1106427
Andrew J Tatem; Bill and Melinda Gates Foundation OPP1032350 Andrew J
Tatem; Wellcome Trust
NR 35
TC 4
Z9 4
U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 29
PY 2015
VL 4
AR e09520
DI 10.7554/eLife.09520
PG 16
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9HC
UT WOS:000373812200001
ER
PT J
AU Reiner, RC
Le Menach, A
Kunene, S
Ntshalintshali, N
Hsiang, MS
Perkins, TA
Greenhouse, B
Tatem, AJ
Cohen, JM
Smith, DL
AF Reiner, Robert C., Jr.
Le Menach, Arnaud
Kunene, Simon
Ntshalintshali, Nyasatu
Hsiang, Michelle S.
Perkins, T. Alex
Greenhouse, Bryan
Tatem, Andrew J.
Cohen, Justin M.
Smith, David L.
TI Mapping residual transmission for malaria elimination
SO ELIFE
LA English
DT Article
ID INFECTIOUS-DISEASE; WETNESS INDEXES; HIGHLANDS; BURDEN; RISK
AB Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections. In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show malariogenic potential, a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination.
C1 [Reiner, Robert C., Jr.; Perkins, T. Alex; Tatem, Andrew J.; Smith, David L.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Reiner, Robert C., Jr.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA.
[Le Menach, Arnaud; Ntshalintshali, Nyasatu; Cohen, Justin M.] Clinton Hlth Access Initiat, Boston, MA USA.
[Kunene, Simon] Natl Malaria Control Program, Manzini, Swaziland.
[Hsiang, Michelle S.] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA.
[Hsiang, Michelle S.] Univ Calif San Francisco, Glbal Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA.
[Hsiang, Michelle S.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA 94143 USA.
[Perkins, T. Alex] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Greenhouse, Bryan] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Smith, David L.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
RP Reiner, RC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.; Reiner, RC (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA.
EM rcreiner@indiana.edu
FU Bill and Melinda Gates Foundation [OPP1110495, OPP1109772, OPP1013170,
OPP1132226, OPP1106427, OPP1032350]; Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health; Swaziland Ministry
of Health; National Institute of Allergy and Infectious Diseases
[7K23AI101012]; Burroughs Wellcome Fund [SPA0000798]; National
Institutes of Health [ICMER U19 AI089674]; Wellcome Trust
FX Funder Grant reference number Author Bill and Melinda Gates Foundation
OPP1110495 Robert C Reiner Jr T Alex Perkins David L Smith; The Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, Department of Homeland Security, and
the Fogarty International Center, National Institutes of Health Robert C
Reiner Jr T Alex Perkins Andrew J Tatem David L Smith; Bill and Melinda
Gates Foundation OPP1109772 Arnaud Le Menach Justin M Cohen; Swaziland
Ministry of Health Michelle S Hsiang; National Institute of Allergy and
Infectious Diseases 7K23AI101012 Michelle S Hsiang; Burroughs Wellcome
Fund SPA0000798 Michelle S Hsiang; Bill and Melinda Gates Foundation
OPP1013170 Michelle S Hsiang; Bill and Melinda Gates Foundation
OPP1132226 T Alex Perkins Bryan Greenhouse; National Institutes of
Health ICMER U19 AI089674 Bryan Greenhouse David L Smith; Bill and
Melinda Gates Foundation OPP1106427 Andrew J Tatem; Bill and Melinda
Gates Foundation OPP1032350 Andrew J Tatem; Wellcome Trust David L
Smith; The funders had no role in study design, data collection and
interpretation, or the decision to submit the work for publication.
NR 35
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U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 29
PY 2015
VL 4
AR e09520
DI 10.7554/eLife.09520
PG 16
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EJ7RG
UT WOS:000393419300001
ER
PT J
AU Camley, BA
Lerner, MG
Pastor, RW
Brown, FLH
AF Camley, Brian A.
Lerner, Michael G.
Pastor, Richard W.
Brown, Frank L. H.
TI Strong influence of periodic boundary conditions on lateral diffusion in
lipid bilayer membranes
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; STOKES-EINSTEIN LAW; BROWNIAN-MOTION;
FORCE-FIELD; TRANSLATIONAL DIFFUSION; CONSTANT-TEMPERATURE; SHEAR
VISCOSITY; PROTEINS; MOBILITY; CHARMM
AB The Saffman-Delbruck hydrodynamic model for lipid-bilayer membranes is modified to account for the periodic boundary conditions commonly imposed in molecular simulations. Predicted lateral diffusion coefficients for membrane-embedded solid bodies are sensitive to box shape and converge slowly to the limit of infinite box size, raising serious doubts for the prospects of using detailed simulations to accurately predict membrane-protein diffusivities and related transport properties. Estimates for the relative error associated with periodic boundary artifacts are 50% and higher for fully atomistic models in currently feasible simulation boxes. MARTINI simulations of LacY membrane protein diffusion and LacY dimer diffusion in DPPC membranes and lipid diffusion in pure DPPC bilayers support the underlying hydrodynamic model. (C) 2015 AIP Publishing LLC.
C1 [Camley, Brian A.] Univ Calif San Diego, Ctr Theoret Biol Phys, San Diego, CA 92093 USA.
[Camley, Brian A.] Univ Calif San Diego, Dept Phys, San Diego, CA 92093 USA.
[Camley, Brian A.; Brown, Frank L. H.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
[Lerner, Michael G.] Earlham Coll, Dept Phys & Astron, Richmond, IN 47374 USA.
[Lerner, Michael G.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Brown, Frank L. H.] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
RP Camley, BA (reprint author), Univ Calif San Diego, Ctr Theoret Biol Phys, San Diego, CA 92093 USA.; Camley, BA (reprint author), Univ Calif San Diego, Dept Phys, San Diego, CA 92093 USA.
OI Lerner, Michael/0000-0003-1222-3212
FU NSF [CHE-1153096, CHE-1465162, CC*IIE-1440689]; Intramural Research
Program of the NIH, National Heart, Lung and Blood Institute; NIH
[F32GM110983]
FX We thank Edward Lyman and Klaus Gawrisch for helpful discussions, and
Antti-Pekka Hynninen for assistance with incorporating the MARTINI
potential into CHARMM. This work was supported in part by the NSF (Grant
Nos. CHE-1153096, CHE-1465162, and CC*IIE-1440689) and by the Intramural
Research Program of the NIH, National Heart, Lung and Blood Institute,
and utilized the high-performance computational capabilities at the
National Institutes of Health, Bethesda, MD (NHLBI LoBoS cluster). BAC
was supported in part by NIH Grant No. F32GM110983.
NR 82
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U1 8
U2 26
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 DEC 28
PY 2015
VL 143
IS 24
AR 243113
DI 10.1063/1.4932980
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DE1UV
UT WOS:000370412900019
PM 26723598
ER
PT J
AU Dobrovolskaia, MA
AF Dobrovolskaia, Marina A.
TI Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs:
Challenges, considerations and strategy
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article; Proceedings Paper
CT 17th International Symposium on Recent Advances in Drug Delivery Systems
CY JUN 14-17, 2015
CL Salt Lake, UT
SP Samyang Biopharmaceuticals, NOF, LSK Biopharma, Univ Utah Vice President Res Off, Coll Pharm, U&I DDS Res Ctr, Univ Utah, Dept Pharmaceut & Pharmaceut Chem
DE Nanoparticles; Endotoxin; Pre-clinical; Immunotoxicity; Thrombosis;
Coagulopathy; Hemolysis; Complement activation; Cytokines; Anaphylaxis;
Phagocytosis; Protein binding
ID LIPOSOME-ENCAPSULATED HEMOGLOBIN; LEUKOCYTE PROCOAGULANT ACTIVITY;
ACID-BASED THERAPEUTICS; RED-BLOOD-CELLS; IN-VITRO; OXIDE NANOPARTICLES;
PAMAM DENDRIMERS; HYPERSENSITIVITY REACTIONS; ENDOTOXIN CONTAMINATION;
COMPLEMENT ACTIVATION
AB Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany pre-clinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly complex. An understanding of both the immune compatibility of nanoformulations and their effects on hematological parameters is now recognized as an important step in the (pre)clinical development of nanomedicines. An evaluation of nanoparticle immunotoxicity is usually performed as a part of a traditional toxicological assessment; however, it often requires additional in vitro and in vivo specialized immuno-and hematotoxicity tests. Herein, I review literature examples and share the experience with the NCI Nanotechnology Characterization Laboratory assay cascade used in the early (discovery-level) phase of pre-clinical development to summarize common challenges in the immunotoxicological assessment of nanomaterials, highlight considerations and discuss solutions to overcome problems that commonly slow or halt the translation of nanoparticle-formulated drugs toward clinical trials. Special attention will be paid to the grand-challenge related to detection, quantification and removal of endotoxin from nanoformulations, and practical considerations related to this challenge. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Canc Res Technol Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
RP Dobrovolskaia, MA (reprint author), NCI, Nanotechnol Characterizat Lab, Canc Res Technol Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
EM marina@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
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. I am grateful to
Allen Kane and Nancy Parrish for the help with manuscript preparation;
to Dr. Serguei Kozlov for the helpful critique; to the NCL technical
staff Barry Neun, Timothy Potter, and Jamie Rodrigues for generating the
data using various in vitro immunoassays; to the NCL's chief
toxicologist, Dr. Stephan Stern, and the former NCL chief chemist, Dr.
Anil Patri, for sharing their expertise and help with establishing the
in vitro-in vivo correlation for immunoassays and with understanding
nanoparticle structure activity relationship; and to the NCL Director,
Dr. Scott McNeil, for helpful suggestions about the information
presented in the manuscript and for providing the opportunity to perform
my research at the NCL.
NR 131
TC 12
Z9 12
U1 3
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD DEC 28
PY 2015
VL 220
BP 571
EP 583
DI 10.1016/j.jconrel.2015.08.056
PN B
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DA7YI
UT WOS:000368021100002
PM 26348388
ER
PT J
AU Skoczen, S
McNeil, SE
Stern, ST
AF Skoczen, Sarah
McNeil, Scott E.
Stern, Stephan T.
TI Stable isotope method to measure drug release from nanomedicines
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Drug release method; Stable isotope dilution; Nanomedicine;
Nanotechnology; Fractionation in biological matrix
ID PLASMA
AB Existing methods to measure nanomedicine drug release in biological matrices are inadequate. A novel drug release method utilizing a stable isotope tracer has been developed. Stable isotope-labeled drug is spiked into plasma containing nanomedicine. The labeled drug equilibrates with plasma components identical to the normoisotopic drug released from the nanomedicine formulation. Therefore, the ultrafilterable fraction of the isotope-labeled drug represents a reliable measure of free normoisotopic drug fraction in plasma, and can be used to calculate nanomedicine encapsulated and unencapsulated drug fractions. To demonstrate the utility of this method, we performed a plasma drug release study with both a fast releasing commercial docetaxel formulation, Taxotere (R), and a delayed releasing nanomicellar formulation of a docetaxel prodrug, Procet 8. The instability of the unencapsulated prodrug in plasma allowed us to compare our calculated prodrug release and docetaxel conversion with the actual docetaxel concentration measured directly without fractionation. Drug release estimates for the fast releasing Taxotere formulation demonstrated accuracy deviation and precision (%CV) of <15%. For the controlled release Procet 8 formulation, we calculated a slow release and conversion of the prodrug in rat plasma that was highly correlated with the direct docetaxel measurement (R-2 = 0.98). We believe that this method will have tremendous utility in the development and regulatory evaluation of nanomedicines, and aid in determination of generic bioequivalence. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Skoczen, Sarah; McNeil, Scott E.; Stern, Stephan T.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Stern, ST (reprint author), Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM sternstephan@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800e001E]
FX The authors thank Celator Pharmaceuticals, Inc. for generously providing
the Procet 8 nanomicellar formulation, and Dr. Rachael M. Crist for
assistance with the preparation of the manuscript. This project has been
funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800e001E. 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 9
TC 3
Z9 3
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD DEC 28
PY 2015
VL 220
BP 169
EP 174
DI 10.1016/j.jconrel.2015.10.042
PN A
PG 6
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CY0TN
UT WOS:000366119100019
PM 26596375
ER
PT J
AU Kim, BW
Cho, H
Choi, CH
Ylaya, K
Chung, JY
Kim, JH
Hewitt, SM
AF Kim, Bo Wook
Cho, Hanbyoul
Choi, Chel Hun
Ylaya, Kris
Chung, Joon-Yong
Kim, Jae-Hoon
Hewitt, Stephen M.
TI Clinical significance of OCT4 and SOX2 protein expression in cervical
cancer
SO BMC CANCER
LA English
DT Article
DE Neoplastic stem cells; OCT4; SOX2; Prognosis; Survival; Uterine cervical
neoplasms
ID SQUAMOUS-CELL CARCINOMA; EMBRYONIC STEM-CELLS; LUNG-CANCER;
TRANSCRIPTIONAL REGULATION; IN-VITRO; NANOG; PROGNOSIS; PREDICTS; GENE;
DIFFERENTIATION
AB Background: Cancer stem cell markers have become a major research focus because of their relationship with radiation or chemotherapy resistance in cancer therapy. Cancer stem cell markers including OCT4 and SOX2 have been found in various solid tumors. Here, we investigate the expression and clinical significance of OCT4 and SOX2 in cervical cancer.
Methods: To define the clinical significance of OCT4 and SOX2 expression, we performed immunohistochemistry for OCT4 and SOX2 on 305 normal cervical epithelium samples, 289 cervical intraepithelial neoplasia samples, and 161 cervical cancer cases and compared the data with clinicopathologic factors, including survival rates of patients with cervical cancer.
Results: OCT4 and SOX2 expression was higher in cervical cancer than normal cervix (both p < 0.001). OCT4 overexpression was associated with lymphovascular space invasion (p = 0.045), whereas loss of SOX2 expression was correlated with large tumor size (p = 0.015). Notably, OCT4 and SOX2 were significantly co-expressed in premalignant cervical lesions, but not in malignant cervical tumor. OCT4 overexpression showed worse 5-year disease-free and overall survival rates (p = 0.012 and p = 0.021, respectively) when compared to the low-expression group, while SOX2 expression showed favorable overall survival (p = 0.025). Cox regression analysis showed that OCT4 was an independent risk factor (hazard ratio = 11.23, 95 % CI, 1.31 - 95.6; p = 0.027) for overall survival while SOX2 overexpression showed low hazard ratio for death (hazard ratio = 0.220, 95 % CI, 0.06-0.72; p = 0.013).
Conclusions: These results suggest that OCT4 overexpression and loss of SOX2 expression are strongly associated with poor prognosis in patients with cervical cancer.
C1 [Kim, Bo Wook; Choi, Chel Hun; Ylaya, Kris; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Choi, Chel Hun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea.
[Kim, Bo Wook] Hallym Univ, Kangdong Sacred Heart Hosp, Dept Obstet & Gynecol, Seoul 135701, South Korea.
RP Kim, JH (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM jaehoonkim@yuhs.ac; genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute, Center for
Cancer Research.
NR 43
TC 0
Z9 0
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD DEC 26
PY 2015
VL 15
AR 1015
DI 10.1186/s12885-015-2015-1
PG 8
WC Oncology
SC Oncology
GA CZ4FG
UT WOS:000367058300002
PM 26706028
ER
PT J
AU Sylvetsky, AC
Nandagopal, R
Nguyen, TT
Abegg, MR
Nagarur, M
Kaplowitz, P
Rother, KI
AF Sylvetsky, Allison C.
Nandagopal, Radha
Nguyen, Tammy T.
Abegg, Marisa R.
Nagarur, Mahathi
Kaplowitz, Paul
Rother, Kristina I.
TI Buddy Study: Partners for better health in adolescents with type 2
diabetes
SO WORLD JOURNAL OF DIABETES
LA English
DT Article
DE Diabetes mellitus type 2; Quality of life; Adolescent; Hemoglobin A1c;
Social support
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; SELF-MANAGEMENT;
CLINICAL-TRIAL; PHYSICAL-ACTIVITY; GLYCEMIC CONTROL; PEER SUPPORT;
YOUNG-ADULTS; YOUTH; EPIDEMIOLOGY
AB AIM: To investigate whether assigning young, healthy and motivated lay volunteer partners ("buddies") to adolescents with type 2 diabetes improves hemoglobin A1c (HbA1c).
METHODS: Adolescents with type 2 diabetes were randomized to partnering with a "buddy" or to conventional treatment. During the initial screening visit, which coincided with a routine outpatient diabetes clinic visit, patients with type 2 diabetes underwent a physical examination, detailed medical history, laboratory measurement of HbA1c, and completed two questionnaires (Pediatric Quality of Life Inventory and Children's Depression Inventory) to assess their overall quality of life and the presence of depressive symptoms. Patients were then randomized to the intervention (the buddy system) or conventional treatment (standard care). All patients were scheduled to return for follow-up at 3- and 6-mo after their initial visit. HbA1c was determined at all visits (i.e., at screening and at the 3- and 6-mo follow-up visits) and quality of life and depressive symptoms were evaluated at the screening visit and were reassessed at the 6-mo visit.
RESULTS: Ten adolescents, recruited from a pool of approximately 200 adolescents, enrolled over a two-year time period, leading to premature termination of the study. In contrast, we easily recruited motivated lay volunteers. We found no change in HbA1c from the initial to the 6-mo visit in either group, yet our small sample size limited systematic assessment of this outcome. Participants repeatedly missed clinic appointments, failed to conduct self-glucose-monitoring and rarely brought their glucometers to clinic visits. Total quality of life scores (72.6 +/- 6.06) at screening were similar to previously reported scores in adolescents with type 2 diabetes (75.7 +/- 15.0) and lower than scores reported in normal-weight (81.2 +/- 0.9), overweight (83.5 +/- 1.8), and obese youths without diabetes (78.5 +/- 1.8) or in adolescents with type 1 diabetes (80.5 +/- 13.1). Among adolescents who returned for their 6-mo visit, there were no differences in total quality of life scores (70.2 +/- 9.18) between screening and follow-up.
CONCLUSION: Our approach, effective in adults with type 2 diabetes, was unsuccessful among adolescents and emphasizes the need for innovative strategies for diabetes treatment in adolescent patients.
C1 [Sylvetsky, Allison C.; Nandagopal, Radha; Nguyen, Tammy T.; Abegg, Marisa R.; Nagarur, Mahathi; Rother, Kristina I.] NIDDK, Sect Pediat Diabet & Metab, NIH, Bethesda, MD 20892 USA.
[Sylvetsky, Allison C.] George Washington Univ, Dept Exercise & Nutr Sci, Washington, DC 20037 USA.
[Nandagopal, Radha; Kaplowitz, Paul] Childrens Natl Med Ctr, Div Endocrinol, Washington, DC 20310 USA.
RP Rother, KI (reprint author), NIDDK, Sect Pediat Diabet & Metab, NIH, 9000 Rockville Pike,Bldg 10,Room 8C432A, Bethesda, MD 20892 USA.
EM kr58q@nih.gov
NR 49
TC 0
Z9 0
U1 6
U2 13
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1948-9358
J9 WORLD J DIABETES
JI World J. Diabetes
PD DEC 25
PY 2015
VL 6
IS 18
BP 1355
EP 1362
DI 10.4239/wjd.v6.i18.1355
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA6CL
UT WOS:000367889400002
PM 26722619
ER
PT J
AU Mattera, R
Guardia, CM
Sidhu, SS
Bonifacino, JS
AF Mattera, Rafael
Guardia, Carlos M.
Sidhu, Sachdev S.
Bonifacino, Juan S.
TI Bivalent Motif-Ear Interactions Mediate the Association of the Accessory
Protein Tepsin with the AP-4 Adaptor Complex
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROGRESSIVE SPASTIC PARAPLEGIA; APPENDAGE DOMAIN; STRUCTURAL BASIS;
SORTING SIGNALS; INTELLECTUAL DISABILITY; DEFICIENCY CAUSES;
ALPHA-APPENDAGE; COATED VESICLES; CLATHRIN; BINDING
AB The heterotetrameric (epsilon-beta 4-mu 4-sigma 4) complex adaptor protein 4 (AP-4) is a component of a non-clathrin coat involved in protein sorting at the trans-Golgi network (TGN). Considerable interest in this complex has arisen from the recent discovery that mutations in each of its four subunits are the cause of a congenital intellectual disability and movement disorder in humans. Despite its physiological importance, the structure and function of this coat remain poorly understood. To investigate the assembly of the AP-4 coat, we dissected the determinants of interaction of AP-4 with its only known accessory protein, the ENTH/VHS-domain-containing protein tepsin. Using a variety of protein interaction assays, we found that tepsin comprises two phylogenetically conserved peptide motifs, [GS] LFXG [ML] X[LV] and S[AV] F[SA] FLN, within its C-terminal unstructured region, which interact with the C-terminal ear (or appendage) domains of the beta 4 and epsilon subunits of AP-4, respectively. Structure-based mutational analyses mapped the binding site for the [GS] LFXG[ML] X[LV] motif to a conserved, hydrophobic surface on the beta 4-ear platform fold. Both peptide-ear interactions are required for efficient association of tepsin with AP-4, and for recruitment of tepsin to the TGN. The bivalency of the interactions increases the avidity of tepsin for AP-4 and may enable cross-linking of multiple AP-4 heterotetramers, thus contributing to the assembly of the AP-4 coat. In addition to revealing critical aspects of this coat, our findings extend the paradigm of peptide-ear interactions, previously established for clathrin-AP-1/AP-2 coats, to a non-clathrin coat.
C1 [Mattera, Rafael; Guardia, Carlos M.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Sidhu, Sachdev S.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bldg 35,Room 2F-226,35A Convent Dr,MSC 3758, Bethesda, MD 20892 USA.
EM bonifacinoj@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU Intramural Program of NICHD, National Institutes of Health [ZIA
HD001607]
FX This work was funded by the Intramural Program of NICHD, National
Institutes of Health (ZIA HD001607). 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 53
TC 1
Z9 1
U1 0
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 DEC 25
PY 2015
VL 290
IS 52
BP 30736
EP 30749
DI 10.1074/jbc.M115.683409
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ6GK
UT WOS:000367199000008
PM 26542808
ER
PT J
AU Matsuo, S
Ogawa, M
Muckenthaler, MU
Mizui, Y
Sasaki, S
Fujimura, T
Takizawa, M
Ariga, N
Ozaki, H
Sakaguchi, M
Gonzalez, FJ
Inoue, Y
AF Matsuo, Shunsuke
Ogawa, Masayuki
Muckenthaler, Martina U.
Mizui, Yumiko
Sasaki, Shota
Fujimura, Takafumi
Takizawa, Masayuki
Ariga, Nagayuki
Ozaki, Hiroaki
Sakaguchi, Masakiyo
Gonzalez, Frank J.
Inoue, Yusuke
TI Hepatocyte Nuclear Factor 4 alpha Controls Iron Metabolism and Regulates
Transferrin Receptor 2 in Mouse Liver
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENRICHED TRANSCRIPTION FACTORS; HEMOCHROMATOSIS PROTEIN HFE;
GENE-EXPRESSION; FACTOR GATA-1; HEPCIDIN; HOMEOSTASIS; MICE; DISRUPTION;
PROMOTER; HYPOTRANSFERRINEMIA
AB Iron is an essential element in biological systems, but excess iron promotes the formation of reactive oxygen species, resulting in cellular toxicity. Several iron-related genes are highly expressed in the liver, a tissue in which hepatocyte nuclear factor 4 alpha (HNF4 alpha) plays a critical role in controlling gene expression. Therefore, the role of hepatic HNF4 alpha in iron homeostasis was examined using liver-specific HNF4 alpha-null mice (Hnf4a(Delta H) mice). Hnf4a(Delta H) mice exhibit hypoferremia and a significant change in hepatic gene expression. Notably, the expression of transferrin receptor 2 (Tfr2) mRNA was markedly decreased in Hnf4a(Delta H) mice. Promoter analysis of the Tfr2 gene showed that the basal promoter was located at a GC-rich region upstream of the transcription start site, a region that can be transactivated in an HNF4 alpha-independent manner. HNF4 alpha-dependent expression of Tfr2 was mediated by a proximal promoter containing two HNF4 alpha-binding sites located between the transcription start site and the translation start site. Both the GC-rich region of the basal promoter and the HNF4 alpha-binding sites were required for maximal transactivation. Moreover, siRNA knockdown of HNF4 alpha suppressed TFR2 expression in human HCC cells. These results suggest that Tfr2 is a novel target gene for HNF4 alpha, and hepatic HNF4 alpha plays a critical role in iron homeostasis.
C1 [Matsuo, Shunsuke; Ogawa, Masayuki; Mizui, Yumiko; Sasaki, Shota; Fujimura, Takafumi; Takizawa, Masayuki; Ariga, Nagayuki; Ozaki, Hiroaki; Inoue, Yusuke] Gunma Univ, Grad Sch Sci & Technol, Div Mol Sci, Kiryu, Gumma 3768515, Japan.
[Muckenthaler, Martina U.] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
[Sakaguchi, Masakiyo] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol, Okayama 7008558, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20852 USA.
RP Inoue, Y (reprint author), Gunma Univ, Grad Sch Sci & Technol, Div Mol Sci, 1-5-1 Tenjin Cho, Kiryu, Gumma 3768515, Japan.
EM yinoue@gunma-u.ac.jp
RI SAKAGUCHI, Masakiyo/B-2280-2011
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan
[25460490]; Kato Memorial Bioscience Foundation
FX This work was supported in part by grants from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan
Grant-in-aid for Scientific Research 25460490 (to Y. I.) and Kato
Memorial Bioscience Foundation (to Y. I.). 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 39
TC 0
Z9 0
U1 1
U2 4
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 DEC 25
PY 2015
VL 290
IS 52
BP 30855
EP 30865
DI 10.1074/jbc.M115.694414
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ6GK
UT WOS:000367199000018
PM 26527688
ER
PT J
AU Barrett, AJ
AF Barrett, Austin J.
TI Tailoring steroid-sensitive virus-specific T cells with TALEN
SO BLOOD
LA English
DT Editorial Material
ID GLUCOCORTICOIDS; CYTOMEGALOVIRUS; MECHANISMS; THERAPY
AB After stem cell transplants, steroid treatment severely damages T-cell responses to cytomegalovirus and abrogates the beneficial effect of adoptively transferred virus-specific T cells. In this issue of Blood, Menger et al describe a clinically applicable technique to inactivate the glucocorticoid receptor with transcription activator-like effector nuclease (TALEN) to render T cells resistant to steroid-induced apoptosis while retaining antiviral functions.(1)
C1 [Barrett, Austin J.] Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 0
U2 3
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 DEC 24
PY 2015
VL 126
IS 26
BP 2767
EP 2768
DI 10.1182/blood-2015-11-679837
PG 2
WC Hematology
SC Hematology
GA DB3RV
UT WOS:000368430000001
PM 26705336
ER
PT J
AU Maric, I
AF Maric, Irina
TI CD30-targeting drugs: cure for mastocytosis?
SO BLOOD
LA English
DT Editorial Material
ID LARGE-CELL LYMPHOMA; BRENTUXIMAB VEDOTIN; HODGKINS LYMPHOMA; PHASE-II;
CONJUGATE; SGN-35
AB New promising targets and targeted drugs for treatment of aggressive forms of systemic mastocytosis are few; in this issue of Blood, Blatt et al(1) provide evidence that aberrant Ki-1 antigen (CD30) expression on neoplastic mast cells may serve as a therapeutic target of brentuximab-vedotin alone or in combination with KIT-targeting drugs.
C1 [Maric, Irina] Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Maric, I (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 10
TC 1
Z9 1
U1 0
U2 0
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 DEC 24
PY 2015
VL 126
IS 26
BP 2771
EP 2773
DI 10.1182/blood-2015-11-678631
PG 5
WC Hematology
SC Hematology
GA DB3RV
UT WOS:000368430000004
PM 26705339
ER
PT J
AU Dai, L
Trillo-Tinoco, J
Cao, YY
Bonstaff, K
Doyle, L
Del Valle, L
Whitby, D
Parsons, C
Reiss, K
Zabaleta, J
Qin, ZQ
AF Dai, Lu
Trillo-Tinoco, Jimena
Cao, Yueyu
Bonstaff, Karlie
Doyle, Lisa
Del Valle, Luis
Whitby, Denise
Parsons, Chris
Reiss, Krzysztof
Zabaleta, Jovanny
Qin, Zhiqiang
TI Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis
for primary effusion lymphoma
SO BLOOD
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; HEPATOCYTE GROWTH-FACTOR;
3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; RECEPTOR
TYROSINE KINASE; C-MET; LUNG-CANCER; SIGNALING PATHWAYS; NSC
NUMBER-663249; ENDOTHELIAL-CELLS; SOMATIC MUTATIONS
AB Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo. The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model. By using microarray analysis, we identify many novel genes that are potentially controlled by HGF/c-MET within PEL cells. One of the downstream candidates, ribonucleoside-diphosphate reductase subunit M2 (RRM2), also displays the promising therapeutic value for PEL treatment. Our findings provide the framework for development of HGF/c-MET-focused therapy and implementation of clinical trials for PEL patients.
C1 [Dai, Lu; Qin, Zhiqiang] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA.
[Dai, Lu; Cao, Yueyu; Qin, Zhiqiang] Tongji Univ, East Hosp, Sch Med, Res Ctr Translat Med, Shanghai 200092, Peoples R China.
[Dai, Lu; Cao, Yueyu; Qin, Zhiqiang] Tongji Univ, East Hosp, Sch Med, Key Lab Arrhythmias, Shanghai 200092, Peoples R China.
[Dai, Lu; Bonstaff, Karlie; Doyle, Lisa; Parsons, Chris; Reiss, Krzysztof] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Med, New Orleans, LA USA.
[Trillo-Tinoco, Jimena; Del Valle, Luis] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Pathol, New Orleans, LA USA.
[Whitby, Denise] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD USA.
[Zabaleta, Jovanny] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Pediat, New Orleans, LA USA.
RP Qin, ZQ (reprint author), Louisiana Canc Res Ctr, 1700 Tulane Ave,Suite 902, New Orleans, LA 70112 USA.
EM zqin@lsuhsc.edu
FU Center for Biomedical Research Excellence subaward [P20-RR021970]; SOM
Research Enhancement Funding; DOD Career Development Award [CA140437];
National Natural Science Foundation of China [81272191, 81472547,
81400164]; National Institutes of Health [UM1-CA181255, R01-CA142362];
federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported by Center for Biomedical Research Excellence
subaward P20-RR021970 (Z.Q.), SOM Research Enhancement Funding (Z.Q.),
DOD Career Development Award CA140437 (Z.Q.), as well as awards from the
National Natural Science Foundation of China (81272191, 81472547 [Z.Q.]
and 81400164 [L. Dai]). HIV+ patient plasma samples were
provided by the HIV Cancer Care Program Biorepository which is supported
by from the National Institutes of Health grants UM1-CA181255 and
R01-CA142362 (C.P.). This work was also funded in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under contract no. HHSN261200800001E (D.W.). Funding sources had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 2
Z9 2
U1 1
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 DEC 24
PY 2015
VL 126
IS 26
BP 2821
EP 2831
DI 10.1182/blood-2015-07-658823
PG 11
WC Hematology
SC Hematology
GA DB3RV
UT WOS:000368430000015
PM 26531163
ER
PT J
AU Naumiec, GR
Jenko, KJ
Zoghbi, SS
Innis, RB
Cai, LS
Pike, VW
AF Naumiec, Gregory R.
Jenko, Kimberley J.
Zoghbi, Sami S.
Innis, Robert B.
Cai, Lisheng
Pike, Victor W.
TI N '-3-(Trifluoromethyl)phenyl Derivatives of N-Aryl-N '-methylguanidines
as Prospective PET Radioligands for the Open Channel of the
N-Methyl-D-aspartate (NMDA) Receptor: Synthesis and Structure-Affinity
Relationships
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IN-VITRO EVALUATION; ION-CHANNEL; PRECLINICAL EVALUATION; SYNAPTIC
PLASTICITY; IODIDES; BINDING; SYSTEM; TRACER; SITE; SPET
AB N-Methyl-D-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain. NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies,: To date, no radioligands have Shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure affinity relationships in N'-3-(trifluoromethyl)phenyl derivatives of N-aryl-N'-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N'-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [H-3](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development.
C1 [Naumiec, Gregory R.; Jenko, Kimberley J.; Zoghbi, Sami S.; Innis, Robert B.; Cai, Lisheng; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU Intramural Research Program of NIH, the National Institute of Mental
Health [ZIA-MH002793]
FX This study was supported by the Intramural Research Program of NIH,
specifically the National Institute of Mental Health (ZIA-MH002793).
NR 40
TC 1
Z9 1
U1 2
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD DEC 24
PY 2015
VL 58
IS 24
BP 9722
EP 9730
DI 10.1021/acs.jmedchem.5b01510
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DA1NS
UT WOS:000367563100022
PM 26588360
ER
PT J
AU de Matos-Neto, EM
Lima, JDCC
de Pereira, WO
Figueredo, RG
Riccardi, DMD
Radloff, K
das Neves, RX
Camargo, RG
Maximiano, LF
Tokeshi, F
Otoch, JP
Goldszmid, R
Camara, NOS
Trinchieri, G
de Alcantara, PSM
Seelaender, M
AF de Matos-Neto, Emidio M.
Lima, Joanna D. C. C.
de Pereira, Welbert O.
Figueredo, Raquel G.
Riccardi, Daniela M. dos R.
Radloff, Katrin
das Neves, Rodrigo X.
Camargo, Rodolfo G.
Maximiano, Linda F.
Tokeshi, Flavio
Otoch, Jose P.
Goldszmid, Romina
Camara, Niels O. S.
Trinchieri, Giorgio
de Alcantara, Paulo S. M.
Seelaender, Marilia
TI Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile
the Culprit?
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE cancer cachexia; inflammatory cells; tumor-adipose tissue crosstalk
macrophages
ID CANCER CACHEXIA; ADIPOSE-TISSUE; SKELETAL-MUSCLE; GENE-EXPRESSION;
MECHANISMS; TIME; INTERLEUKIN-6; INTERVENTION; OBESITY
AB Cachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix (R) system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-I beta expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1 beta. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.
C1 [de Matos-Neto, Emidio M.; Lima, Joanna D. C. C.; Figueredo, Raquel G.; Riccardi, Daniela M. dos R.; Radloff, Katrin; das Neves, Rodrigo X.; Camargo, Rodolfo G.; Seelaender, Marilia] Univ Sao Paulo, Fac Med, Canc Metab Res Grp, Sao Paulo, Brazil.
[de Pereira, Welbert O.] Israelite Albert Einstein Hosp, Israelite Albert Einstein Inst, Sao Paulo, Brazil.
[Maximiano, Linda F.; Tokeshi, Flavio; Otoch, Jose P.; de Alcantara, Paulo S. M.] Univ Sao Paulo, Dept Clin Surg, Sao Paulo, Brazil.
[Goldszmid, Romina; Trinchieri, Giorgio] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Camara, Niels O. S.] Univ Sao Paulo, Dept Immunol, Sao Paulo, Brazil.
RP de Matos-Neto, EM (reprint author), Univ Sao Paulo, Fac Med, Canc Metab Res Grp, Sao Paulo, Brazil.
EM emidiomatos@gmail.com
RI seelaender, marilia/B-9101-2011
OI seelaender, marilia/0000-0002-9999-8020
FU FAPESP [2012/50079-0, 2012/10129-8]; CAPES
FX The authors are grateful to Emilia Ribeiro and hospital staff for
technical support. This work was supported by FAPESP (2012/50079-0;
2012/10129-8) and CAPES.
NR 38
TC 2
Z9 2
U1 0
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD DEC 24
PY 2015
VL 6
AR UNSP 629
DI 10.3389/fimmu.2015.00629
PG 11
WC Immunology
SC Immunology
GA CZ4FR
UT WOS:000367059400001
PM 26732354
ER
PT J
AU Pomrenze, MB
Millan, EZ
Hopf, FW
Keiflin, R
Maiya, R
Blasio, A
Dadgar, J
Kharazia, V
De Guglielmo, G
Crawford, E
Janak, PH
George, O
Rice, KC
Messing, RO
AF Pomrenze, Matthew B.
Millan, E. Zayra
Hopf, F. Woodward
Keiflin, Ronald
Maiya, Rajani
Blasio, Angelo
Dadgar, Jahan
Kharazia, Viktor
De Guglielmo, Giordano
Crawford, Elena
Janak, Patricia H.
George, Olivier
Rice, Kenner C.
Messing, Robert O.
TI A Transgenic Rat for Investigating the Anatomy and Function of
Corticotrophin Releasing Factor Circuits
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE Cre recombinase; CRF; channelrhodopsin-2; designer receptors exclusively
activated by designer drugs; transgenic rat models; central amygdala;
Fos; R121919
ID CENTRAL EXTENDED AMYGDALA; PEPTIDE-IMMUNOREACTIVE NEURONS; STRIA
TERMINALIS; CENTRAL NUCLEUS; BED NUCLEUS; CRF NEURONS; PARAVENTRICULAR
NUCLEUS; NICOTINE WITHDRAWAL; GABAERGIC NEURONS; CONDITIONED FEAR
AB Corticotrophin-releasing factor (CRF) is a 41 amino acid neuropeptide that coordinates adaptive responses to stress. CRF projections from neurons in the central nucleus of the amygdala (CeA) to the brainstem are of particular interest for their role in motivated behavior. To directly examine the anatomy and function of CRF neurons, we generated a BAG transgenic Crh-Cre rat in which bacterial Cre recombinase is expressed from the Crh promoter. Using Cre-dependent reporters, we found that Cre expressing neurons in these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL) and the oval nucleus of the BNST. We detected major projections from CeA CRF neurons to parabrachial nuclei and the locus coeruleus, dorsal and ventral BNST, and more minor projections to lateral portions of the substantia nigra, ventral tegmental area, and lateral hypothalamus. Optogenetic stimulation of CeA CRF neurons evoked GABA-ergic responses in 11% of non-CRF neurons in the medial CeA (CeM) and 44% of non-CRF neurons in the CeL. Chemogenetic stimulation of CeA CRF neurons induced Fos in a similar proportion of non-CRF CeM neurons but a smaller proportion of non-CRF CeL neurons. The CRF1 receptor antagonist R121919 reduced this Fos induction by two-thirds in these regions. These results indicate that CeL CRF neurons provide both local inhibitory GABA and excitatory CRF signals to other CeA neurons, and demonstrate the value of the Crh-Cre rat as a tool for studying circuit function and physiology of CRF neurons.
C1 [Pomrenze, Matthew B.; Maiya, Rajani; Blasio, Angelo; Dadgar, Jahan; Messing, Robert O.] Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX 78712 USA.
[Millan, E. Zayra; Hopf, F. Woodward; Keiflin, Ronald; Dadgar, Jahan; Kharazia, Viktor; Janak, Patricia H.; Messing, Robert O.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[De Guglielmo, Giordano; Crawford, Elena; George, Olivier] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA USA.
[Rice, Kenner C.] NIAAA, Chem Biol Res Branch, Drug Design & Synth Sect, NIDA, Rockville, MD 20852 USA.
RP Messing, RO (reprint author), Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX 78712 USA.
EM romessing@austin.utexas.edu
OI Keiflin, Ronald/0000-0001-5347-7337; george, olivier/0000-0002-3700-5003
FU pilot project funds [U01 AA013517, AA13588, AA017072, AA020608,
AA006420, AA022977]; State of California for medical research for
alcohol and substance abuse [UCSI7]; National Institute on Alcohol Abuse
and Alcoholism; National Institute on Drug Abuse Intramural Research
Programs; Graduate Research Fellowship from the National Science
Foundation
FX This work was supported by pilot project funds through U01 AA013517 to
PH., grants AA13588 and AA017072 to RM, and AA020608, AA006420 and
AA022977 to OG, and funds provided by the State of California for
medical research for alcohol and substance abuse through UCSI7 to PJ and
RM. A portion of this work supported by the National Institute on
Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse
Intramural Research Programs. MP is supported by Graduate Research
Fellowship DGE-1110007 from the National Science Foundation.
NR 69
TC 10
Z9 11
U1 1
U2 13
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 DEC 24
PY 2015
VL 9
AR 487
DI 10.3389/fnins.2015.00487
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CZ4VH
UT WOS:000367100400001
PM 26733798
ER
PT J
AU Quinn, TC
Gaydos, CA
AF Quinn, Thomas C.
Gaydos, Charlotte A.
TI Treatment for Chlamydia Infection - Doxycycline versus Azithromycin
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID NONGONOCOCCAL URETHRITIS; CONTROLLED-TRIAL
C1 [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Quinn, Thomas C.; Gaydos, Charlotte A.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
RP Quinn, TC (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 10
TC 1
Z9 1
U1 1
U2 4
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 DEC 24
PY 2015
VL 373
IS 26
BP 2573
EP 2575
DI 10.1056/NEJMe1513001
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CZ7SG
UT WOS:000367299700014
PM 26699174
ER
PT J
AU Ng, M
Ndungo, E
Kaczmarek, ME
Herbert, AS
Binger, T
Kuehne, AI
Jangra, RK
Hawkins, JA
Gifford, RJ
Biswas, R
Demogines, A
James, RM
Yu, M
Brummelkamp, TR
Drosten, C
Wang, LF
Kuhn, JH
Muller, MA
Dye, JM
Sawyer, SL
Chandran, K
AF Ng, Melinda
Ndungo, Esther
Kaczmarek, Maria E.
Herbert, Andrew S.
Binger, Tabea
Kuehne, Ana I.
Jangra, Rohit K.
Hawkins, John A.
Gifford, Robert J.
Biswas, Rohan
Demogines, Ann
James, Rebekah M.
Yu, Meng
Brummelkamp, Thijn R.
Drosten, Christian
Wang, Lin-Fa
Kuhn, Jens H.
Mueller, Marcel A.
Dye, John M.
Sawyer, Sara L.
Chandran, Kartik
TI Filovirus receptor NPC1 contributes to species-specific patterns of
ebolavirus susceptibility in bats
SO ELIFE
LA English
DT Article
ID NIEMANN-PICK C1; RESPIRATORY SYNDROME CORONAVIRUS; HEMORRHAGIC-FEVER
ARENAVIRUSES; DIPEPTIDYL PEPTIDASE 4; SARS-LIKE CORONAVIRUS; VIRUS ENTRY
REQUIRES; RNA-SEQ DATA; FRUIT BATS; MARBURG VIRUS; TRANSFERRIN
RECEPTOR-1
AB Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature.
C1 [Ng, Melinda; Ndungo, Esther; Jangra, Rohit K.; Biswas, Rohan; Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Kaczmarek, Maria E.] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
[Herbert, Andrew S.; Kuehne, Ana I.; James, Rebekah M.; Dye, John M.] United States Army Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Binger, Tabea; Drosten, Christian; Mueller, Marcel A.] Univ Bonn, Med Ctr, Inst Virol, Bonn, Germany.
[Hawkins, John A.] Univ Texas Austin, Inst Computat Engn & Sci, Austin, TX 78712 USA.
[Gifford, Robert J.] Univ Glasgow, MRC, Virol Unit, Glasgow, Lanark, Scotland.
[Demogines, Ann; Sawyer, Sara L.] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
[Yu, Meng; Wang, Lin-Fa] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Singapore, Singapore.
[Brummelkamp, Thijn R.] Netherlands Canc Inst, Plesmanlaan, Netherlands.
[Drosten, Christian] German Ctr Infect Dis Res, Bonn, Germany.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Ft Detrick, MD USA.
[Sawyer, Sara L.] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
[Sawyer, Sara L.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
RP Dye, JM (reprint author), United States Army Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
EM john.m.dye1.civ@mail.mil; ssawyer@colorado.edu;
kartik.chandran@einstein.yu.edu
OI Mueller, Marcel/0000-0003-2242-5117; Ndungo, Esther/0000-0002-9975-7032
FU National Institutes of Health [AI101436, GM093086]; Defense Threat
Reduction Agency [CB3948, HDTRA1-11-C-0061]; European Commission [EU
FP-7 Antigone]; Bundesministerium fur Bildung und Forschung [EBOKON];
National Research Foundation-Prime Minister's office, Republic of
Singapore [CRP001-056]
FX National Institutes of Health AI101436 Kartik Chandran; Defense Threat
Reduction Agency CB3948 John M Dye; European Commission EU FP-7 Antigone
Thijn R Brummelkamp; Bundesministerium fur Bildung und Forschung EBOKON
Project Christian Drosten Marcel A Muller; National Research
Foundation-Prime Minister's office, Republic of Singapore CRP001-056
Lin-Fa Wang; National Institutes of Health GM093086 Sara L Sawyer;
Defense Threat Reduction Agency HDTRA1-11-C-0061 Sara L Sawyer; The
funders had no role in study design, data collection and interpretation,
or the decision to submit the work for publication.
NR 79
TC 17
Z9 17
U1 9
U2 30
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 23
PY 2015
VL 4
AR e11785
DI 10.7554/eLife.11785
PG 22
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DA0VX
UT WOS:000367516800001
ER
PT J
AU Lin, YJ
Ho, TJ
Yeh, YC
Cheng, CF
Shiao, YT
Wang, CB
Chien, WK
Chen, JH
Liu, X
Tsang, H
Lin, TH
Liao, CC
Huang, SM
Li, JP
Lin, CW
Pang, HY
Lin, JG
Lan, YC
Liu, YH
Chen, SY
Tsai, FJ
Liang, WM
AF Lin, Ying-Ju
Ho, Tsung-Jung
Yeh, Yi-Chun
Cheng, Chi-Fung
Shiao, Yi-Tzone
Wang, Chang-Bi
Chien, Wen-Kuei
Chen, Jin-Hua
Liu, Xiang
Tsang, Hsinyi
Lin, Ting-Hsu
Liao, Chiu-Chu
Huang, Shao-Mei
Li, Ju-Pi
Lin, Cheng-Wen
Pang, Hao-Yu
Lin, Jaung-Geng
Lan, Yu-Ching
Liu, Yu-Huei
Chen, Shih-Yin
Tsai, Fuu-Jen
Liang, Wen-Miin
TI Chinese Herbal Medicine Treatment Improves the Overall Survival Rate of
Individuals with Hypertension among Type 2 Diabetes Patients and
Modulates In Vitro Smooth Muscle Cell Contractility
SO PLOS ONE
LA English
DT Article
ID TANSHINONE IIA SULFONATE; BLOOD-PRESSURE CONTROL; SALVIANOLIC ACID B;
CARDIOVASCULAR EVENTS; DOUBLE-BLIND; BREAST-CANCER; MELLITUS; RISK;
THERAPY; TAIWAN
AB Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.
C1 [Lin, Ying-Ju; Ho, Tsung-Jung; Li, Ju-Pi; Lin, Jaung-Geng; Chen, Shih-Yin; Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung, Taiwan.
[Lin, Ying-Ju; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Liu, Yu-Huei; Chen, Shih-Yin; Tsai, Fuu-Jen] China Med Univ Hosp, Genet Ctr, Dept Med Res, Taichung, Taiwan.
[Ho, Tsung-Jung] China Med Univ, Beigang Hosp, Div Chinese Med, Peikang, Yunlin, Taiwan.
[Ho, Tsung-Jung] China Med Univ, Tainan Municipal An Nan Hosp, Div Chinese Med, Tainan, Taiwan.
[Yeh, Yi-Chun; Cheng, Chi-Fung; Wang, Chang-Bi; Liang, Wen-Miin] China Med Univ, Grad Inst Biostat, Sch Publ Hlth, Taichung, Taiwan.
[Shiao, Yi-Tzone] China Med Univ Hosp, Ctr Heart, Taichung, Taiwan.
[Chien, Wen-Kuei; Chen, Jin-Hua] Taipei Med Univ, Biostat Ctr, Coll Management, Taipei, Taiwan.
[Chen, Jin-Hua] Taipei Med Univ, Sch Hlth Care Adm, Coll Management, Taipei, Taiwan.
[Liu, Xiang; Tsang, Hsinyi] NIAID, NIH, Bethesda, MD 20892 USA.
[Li, Ju-Pi] China Med Univ Hosp, Rheumatism Res Ctr, Taichung, Taiwan.
[Lin, Cheng-Wen; Pang, Hao-Yu] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan.
[Lan, Yu-Ching] China Med Univ, Dept Hlth Risk Management, Taichung, Taiwan.
[Liu, Yu-Huei] China Med Univ, Grad Inst Integrated Med, Taichung, Taiwan.
[Tsai, Fuu-Jen] Asia Univ, Taichung, Taiwan.
RP Tsai, FJ (reprint author), China Med Univ, Sch Chinese Med, Taichung, Taiwan.
EM d0704@mail.cmuh.org.tw; wmliang.cmu@gmail.com
RI Lan, Yu-Ching/F-2449-2017
OI Lan, Yu-Ching/0000-0003-4781-6405
FU Ministry of Science and Technology [MOST 103-2320-B-039 -006 -MY3];
China Medical University [CMU102-PH-01]; China Medical University
Hospital [DMR-104-029, DMR-104-089]; China Medical University Beigang
Hospital [CMUBH R103-008, CMUBH R104-007]
FX This study was funded by Ministry of Science and Technology (MOST
103-2320-B-039 -006 -MY3; YJL), China Medical University (CMU102-PH-01;
YJL and FJT), China Medical University Hospital (DMR-104-029; FJT;
DMR-104-089; YJL), and China Medical University Beigang Hospital (CMUBH
R103-008; TJH; CMUBH R104-007; TJH).
NR 70
TC 2
Z9 2
U1 3
U2 14
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 DEC 23
PY 2015
VL 10
IS 12
AR e0145109
DI 10.1371/journal.pone.0145109
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ4SI
UT WOS:000367092600047
PM 26699542
ER
PT J
AU Pletneva, NV
Pletnev, VZ
Sarkisyan, KS
Gorbachev, DA
Egorov, ES
Mishin, AS
Lukyanov, KA
Dauter, Z
Pletnev, S
AF Pletneva, Nadya V.
Pletnev, Vladimir Z.
Sarkisyan, Karen S.
Gorbachev, Dmitry A.
Egorov, Evgeny S.
Mishin, Alexander S.
Lukyanov, Konstantin A.
Dauter, Zbigniew
Pletnev, Sergei
TI Crystal Structure of Phototoxic Orange Fluorescent Proteins with a
Tryptophan-Based Chromophore
SO PLOS ONE
LA English
DT Article
ID GENETICALLY ENCODED PHOTOSENSITIZER; ASSISTED LIGHT INACTIVATION;
ELECTRON-TRANSFER; RED; OXYGEN
AB Phototoxic fluorescent proteins represent a sparse group of genetically encoded photosensitizers that could be used for precise light-induced inactivation of target proteins, DNA damage, and cell killing. Only two such GFP-based fluorescent proteins (FPs), KillerRed and its monomeric variant SuperNova, were described up to date. Here, we present a crystallographic study of their two orange successors, dimeric KillerOrange and monomeric mKiller-Orange, at 1.81 and 1.57 angstrom resolution, respectively. They are the first orange-emitting protein photosensitizers with a tryptophan-based chromophore (Gln65-Trp66-Gly67). Same as their red progenitors, both orange photosensitizers have a water-filled channel connecting the chromophore to the beta-barrel exterior and enabling transport of ROS. In both proteins, Trp66 of the chromophore adopts an unusual trans-cis conformation stabilized by H- bond with the nearby Gln159. This trans-cis conformation along with the water channel was shown to be a key structural feature providing bright orange emission and phototoxicity of both examined orange photosensitizers.
C1 [Pletneva, Nadya V.; Pletnev, Vladimir Z.; Sarkisyan, Karen S.; Gorbachev, Dmitry A.; Egorov, Evgeny S.; Mishin, Alexander S.; Lukyanov, Konstantin A.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
[Gorbachev, Dmitry A.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow, Russia.
[Mishin, Alexander S.; Lukyanov, Konstantin A.] Nizhny Novgorod State Med Acad, Nizhnii Novgorod, Russia.
[Dauter, Zbigniew; Pletnev, Sergei] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
[Pletnev, Sergei] Leidos Biomed Res Inc, Basic Res Program, Argonne, IL USA.
RP Pletnev, S (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
EM vzpletnev@gmail.com; pletnevs@mail.nih.gov
RI Mishin, Alexander/L-9420-2014; Pletneva, Nadya/F-7839-2014; Pletnev,
Vladimir/Q-6151-2016; Sarkisyan, Karen/M-6821-2015
OI Mishin, Alexander/0000-0002-4935-7030; Sarkisyan,
Karen/0000-0002-5375-6341
FU Russian Science Foundation (RSF) [14-14-00281]; Russian Science
Foundation [14-25-00129]; US Department of Energy, Office of Science,
Office of Basic Energy Sciences [W-31-109-Eng-38]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
FX This project has been supported with a federal grant from the Russian
Science Foundation (RSF) No 14-14-00281. Mutagenesis work has been
supported by Russian Science Foundation grant 14-25-00129. Experiments
were partially carried out using the equipment provided by the IBCH core
facility (CKP IBCH). Diffraction experiments were carried out at
beamline 22-ID of the Southeast Regional Collaborative Access Team
(SER-CAT), located at the Advanced Photon Source, Argonne National
Laboratory, USA. Use of the APS was supported by the US Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
contract no. W-31-109-Eng-38. The project has been supported in part
with federal funds from the National Cancer Institute, National
Institutes of Health under contract no. HHSN261200800001E, 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 US Government. SP is
employed by Leidos Biomedical Research, Inc. The specific contributions
of this author can be found in the Author Contributions section. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 38
TC 2
Z9 3
U1 1
U2 12
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 DEC 23
PY 2015
VL 10
IS 12
AR e0145740
DI 10.1371/journal.pone.0145740
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ4SI
UT WOS:000367092600126
PM 26699366
ER
PT J
AU Davis, SK
Xu, RH
Gebreab, SY
Riestra, P
Gaye, A
Khan, RJ
Wilson, JG
Bidulescu, A
AF Davis, Sharon K.
Xu, Ruihua
Gebreab, Samson Y.
Riestra, Pia
Gaye, Amadou
Khan, Rumana J.
Wilson, James G.
Bidulescu, Aurelian
TI Association of ADIPOQ gene with type 2 diabetes and related phenotypes
in African American men and women: the Jackson Heart Study
SO BMC GENETICS
LA English
DT Article
DE Adiponectin; Type 2 diabetes; ADIPOQ gene; African Americans
ID INSULIN-RESISTANCE SYNDROME; PLASMA ADIPONECTIN; ETHNIC-DIFFERENCES;
RISK; PROMOTER; POLYMORPHISMS; DISEASE; HOMEOSTASIS; POPULATION;
HAPLOTYPES
AB Background: African Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex.
Results: There was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (beta(SE) p = -.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (beta(SE) p = -0.74(0.20), 0.0002).
Conclusions: These findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women.
C1 [Davis, Sharon K.; Xu, Ruihua; Gebreab, Samson Y.; Riestra, Pia; Gaye, Amadou; Khan, Rumana J.] NHGRI, Genom Metab Cardiovasc & Inflammatory Dis Branch, Social Epidemiol Res Unit, Bethesda, MD 20892 USA.
[Wilson, James G.] Univ Mississippi Ctr, Dept Physiol, Jackson, MS 39216 USA.
[Bidulescu, Aurelian] Indiana Univ, Sch Publ Hlth, Bloomington, IN 47405 USA.
RP Davis, SK (reprint author), NHGRI, Genom Metab Cardiovasc & Inflammatory Dis Branch, Social Epidemiol Res Unit, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM sharon.davis@nih.gov
OI Gaye, Amadou/0000-0002-1180-2792
FU National Heart, Lung and Blood Institute [HHSN268201300046C,
HHSN26820130047C, HHSN26820130048C, HHSN268201300049C,
HHSN268201300050C, UH1 HL073461]; National Institute on Minority Health
and Health Disparities; PHS Award from the National Center for Research
Resources [UL1 RR025008]; National Human Genome Research Institute
FX The authors thank the participants in the Jackson Heart Study for their
long-term commitment and important contributions to the study. Funding
for the Jackson Heart Study was supported by contracts
HHSN268201300046C, HHSN26820130047C, HHSN26820130048C,
HHSN268201300049C, HHSN268201300050C from the National Heart, Lung and
Blood Institute and the National Institute on Minority Health and Health
Disparities. The measurement of adiponectin was partially supported by
PHS Award UL1 RR025008 from the National Center for Research Resources
and by UH1 HL073461 from the National Heart, Lung and Blood Institute.
Sharon K. Davis, Samson Y. Gebreab, Ruihua Xu, Pia Riestra, Rumana J.
Khan and Amadou Gaye are supported by the intramural program of the
National Human Genome Research Institute.
NR 45
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD DEC 23
PY 2015
VL 16
AR 147
DI 10.1186/s12863-015-0319-4
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA CZ5HT
UT WOS:000367134000002
PM 26699120
ER
PT J
AU Geeven, G
Zhu, Y
Kim, BJ
Bartholdy, BA
Yang, SM
Macfarlan, TS
Gifford, WD
Pfaff, SL
Verstegen, MJAM
Pinto, H
Vermunt, MW
Creyghton, MP
Wijchers, PJ
Stamatoyannopoulos, JA
Skoultchi, AI
de Laat, W
AF Geeven, Geert
Zhu, Yun
Kim, Byung Ju
Bartholdy, Boris A.
Yang, Seung-Min
Macfarlan, Todd S.
Gifford, Wesley D.
Pfaff, Samuel L.
Verstegen, Marjon J. A. M.
Pinto, Hugo
Vermunt, Marit W.
Creyghton, Menno P.
Wijchers, Patrick J.
Stamatoyannopoulos, John A.
Skoultchi, Arthur I.
de Laat, Wouter
TI Local compartment changes and regulatory landscape alterations in
histone H1-depleted cells
SO GENOME BIOLOGY
LA English
DT Article
DE Histone H1; Chromatin; Chromosome conformation; Hi-C; Epigenomics
ID LINKER HISTONE; CHROMATIN-STRUCTURE; HUMAN GENOME; MOUSE DEVELOPMENT;
MICE LACKING; STEM-CELLS; RNA-SEQ; H1; PRINCIPLES; SPERMATOGENESIS
AB Background: Linker histone H1 is a core chromatin component that binds to nucleosome core particles and the linker DNA between nucleosomes. It has been implicated in chromatin compaction and gene regulation and is anticipated to play a role in higher-order genome structure. Here we have used a combination of genome-wide approaches including DNA methylation, histone modification and DNase I hypersensitivity profiling as well as Hi-C to investigate the impact of reduced cellular levels of histone H1 in embryonic stem cells on chromatin folding and function.
Results: We find that depletion of histone H1 changes the epigenetic signature of thousands of potential regulatory sites across the genome. Many of them show cooperative loss or gain of multiple chromatin marks. Epigenetic alterations cluster to gene-dense topologically associating domains (TADs) that already showed a high density of corresponding chromatin features. Genome organization at the three-dimensional level is largely intact, but we find changes in the structural segmentation of chromosomes specifically for the epigenetically most modified TADs.
Conclusions: Our data show that cells require normal histone H1 levels to expose their proper regulatory landscape. Reducing the levels of histone H1 results in massive epigenetic changes and altered topological organization particularly at the most active chromosomal domains. Changes in TAD configuration coincide with epigenetic landscape changes but not with transcriptional output changes, supporting the emerging concept that transcriptional control and nuclear positioning of TADs are not causally related but independently controlled by the locally associated trans-acting factors.
C1 [Geeven, Geert; Zhu, Yun; Verstegen, Marjon J. A. M.; Vermunt, Marit W.; Creyghton, Menno P.; Wijchers, Patrick J.; de Laat, Wouter] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
[Geeven, Geert; Zhu, Yun; Verstegen, Marjon J. A. M.; Vermunt, Marit W.; Creyghton, Menno P.; Wijchers, Patrick J.; de Laat, Wouter] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
[Kim, Byung Ju; Bartholdy, Boris A.; Yang, Seung-Min; Pinto, Hugo; Skoultchi, Arthur I.] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
[Macfarlan, Todd S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
[Gifford, Wesley D.; Pfaff, Samuel L.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
[Gifford, Wesley D.; Pfaff, Samuel L.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Stamatoyannopoulos, John A.] Univ Washington, Div Oncol, Dept Med, Seattle, WA 98195 USA.
RP Skoultchi, AI (reprint author), Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM arthur.skoultchi@einstein.yu.edu; w.delaat@hubrecht.eu
FU National Institutes of Health [CA079057, GM116143]; NWO/CW TOP grant
[714.012.002]; NWO VICI grant [724.012.003]; EU [2010-259743 (MODHEP)];
European Research Council Starting Grant [209700, 4C]
FX This work was supported by National Institutes of Health Grant CA079057
and GM116143 to A.I.S. and an NWO/CW TOP grant (714.012.002), an NWO
VICI grant 724.012.003, an EU grant 2010-259743 (MODHEP) and a European
Research Council Starting Grant (209700, '4C') to W.d.L.
NR 50
TC 7
Z9 7
U1 6
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD DEC 23
PY 2015
VL 16
AR 289
DI 10.1186/s13059-015-0857-0
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CZ4KU
UT WOS:000367072800001
PM 26700097
ER
PT J
AU Llera, AS
Podhajcer, OL
Breitenbach, MM
Santini, L
Muller, B
Daneri-Navarro, A
Velazquez, CA
Artagaveytia, N
Gomez, J
Frech, MS
Brown, T
Gross, T
AF Llera, A. S.
Podhajcer, O. L.
Breitenbach, M. M.
Santini, L.
Muller, B.
Daneri-Navarro, A.
Velazquez, C. A.
Artagaveytia, N.
Gomez, J.
Frech, M. S.
Brown, T.
Gross, T.
CA Investigators US-Latin Amer Canc R
TI Translational cancer research comes of age in Latin America
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID BREAST-CANCER
AB The U.S.-Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations.
C1 [Llera, A. S.; Podhajcer, O. L.] Fdn Inst Leloir CONICET, Lab Mol & Cellular Therapy, Buenos Aires, DF, Argentina.
[Breitenbach, M. M.; Santini, L.] Minist Saude, Inst Nacl Canc, Rio De Janeiro, Brazil.
[Muller, B.] Inst Nacl Canc, Santiago, Chile.
[Daneri-Navarro, A.] Univ Guadalajara, CUCS, Dept Fisiol, Guadalajara, Jalisco, Mexico.
[Velazquez, C. A.] Univ Sonora, Dept Ciencias Quim Biol, Hermosillo 83000, Sonora, Mexico.
[Artagaveytia, N.] Univ Uruguay, Fac Med, Montevideo, Uruguay.
[Gomez, J.; Frech, M. S.; Brown, T.; Gross, T.] NCI, Ctr Global Hlth, Rockville, MD USA.
RP Podhajcer, OL (reprint author), Fdn Inst Leloir CONICET, Lab Mol & Cellular Therapy, Buenos Aires, DF, Argentina.
EM opodhajcer@leloir.org.ar
RI Daneri-Navarro, Adrian/C-1935-2013
OI Daneri-Navarro, Adrian/0000-0002-8206-749X
NR 9
TC 0
Z9 0
U1 3
U2 8
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 DEC 23
PY 2015
VL 7
IS 319
AR 319fs50
DI 10.1126/scitranslmed.aad5859
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CZ4VY
UT WOS:000367102100001
ER
PT J
AU Lynch, RM
Boritz, E
Coates, EE
DeZure, A
Madden, P
Costner, P
Enama, ME
Plummer, S
Holman, L
Hendel, CS
Gordon, I
Casazza, J
Conan-Cibotti, M
Migueles, SA
Tressler, R
Bailer, RT
McDermott, A
Narpala, S
O'Dell, S
Wolf, G
Lifson, JD
Freemire, BA
Gorelick, RJ
Pandey, JP
Mohan, S
Chomont, N
Fromentin, R
Chun, TW
Fauci, AS
Schwartz, RM
Koup, RA
Douek, DC
Hu, ZH
Capparelli, E
Graham, BS
Mascola, JR
Ledgerwood, JE
AF Lynch, Rebecca M.
Boritz, Eli
Coates, Emily E.
DeZure, Adam
Madden, Patrick
Costner, Pamela
Enama, Mary E.
Plummer, Sarah
Holman, Lasonji
Hendel, Cynthia S.
Gordon, Ingelise
Casazza, Joseph
Conan-Cibotti, Michelle
Migueles, Stephen A.
Tressler, Randall
Bailer, Robert T.
McDermott, Adrian
Narpala, Sandeep
O'Dell, Sijy
Wolf, Gideon
Lifson, Jeffrey D.
Freemire, Brandie A.
Gorelick, Robert J.
Pandey, Janardan P.
Mohan, Sarumathi
Chomont, Nicolas
Fromentin, Remi
Chun, Tae-Wook
Fauci, Anthony S.
Schwartz, Richard M.
Koup, Richard A.
Douek, Daniel C.
Hu, Zonghui
Capparelli, Edmund
Graham, Barney S.
Mascola, John R.
Ledgerwood, Julie E.
CA VRC 601 Study Team
TI Virologic effects of broadly neutralizing antibody VRC01 administration
during chronic HIV-1 infection
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; HUMAN MONOCLONAL-ANTIBODIES;
MUCOSAL SHIV CHALLENGE; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; PASSIVE
TRANSFER; HUMANIZED MICE; IN-VITRO; HIV-1-INFECTED HUMANS; POTENT
NEUTRALIZATION
AB Passive immunization with HIV-1-neutralizing monoclonal antibodies (mAbs) is being considered for prevention and treatment of HIV-1 infection. As therapeutic agents, mAbs could be used to suppress active virus replication, maintain suppression induced by antiretroviral therapy (ART), and/or decrease the size of the persistent virus reservoir. We assessed the impact of VRC01, a potent human mAb targeting the HIV-1 CD4 binding site, on ART-treated and untreated HIV-1-infected subjects. Among six ART-treated individuals with undetectable plasma viremia, two infusions of VRC01 did not reduce the peripheral blood cell-associated virus reservoir measured 4 weeks after the second infusion. In contrast, six of eight ART-untreated, viremic subjects infused with a single dose of VRC01 experienced a 1.1 to 1.8 log(10) reduction in plasma viremia. The two subjects with minimal responses to VRC01 were found to have predominantly VRC01-resistant virus before treatment. Notably, two subjects with plasma virus load <1000 copies/ml demonstrated virus suppression to undetectable levels for over 20 days until VRC01 levels declined. Among the remaining four subjects with baseline virus loads between 3000 and 30,000 copies, viremia was only partially suppressed by mAb infusion, and we observed strong selection pressure for the outgrowth of less neutralization-sensitive viruses. In summary, a single infusion of mAb VRC01 significantly decreased plasma viremia and preferentially suppressed neutralization-sensitive virus strains. These data demonstrate the virological effect of this neutralizing antibody and highlight the need for combination strategies to maintain virus suppression.
C1 [Lynch, Rebecca M.; Boritz, Eli; Coates, Emily E.; DeZure, Adam; Madden, Patrick; Costner, Pamela; Enama, Mary E.; Plummer, Sarah; Holman, Lasonji; Hendel, Cynthia S.; Gordon, Ingelise; Casazza, Joseph; Conan-Cibotti, Michelle; Bailer, Robert T.; McDermott, Adrian; Narpala, Sandeep; O'Dell, Sijy; Wolf, Gideon; Schwartz, Richard M.; Koup, Richard A.; Douek, Daniel C.; Graham, Barney S.; Mascola, John R.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Migueles, Stephen A.; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Tressler, Randall] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Lifson, Jeffrey D.; Freemire, Brandie A.; Gorelick, Robert J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Pandey, Janardan P.; Mohan, Sarumathi] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Chomont, Nicolas; Fromentin, Remi] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2X 0A9, Canada.
[Chomont, Nicolas; Fromentin, Remi] CHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada.
[Hu, Zonghui] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Capparelli, Edmund] Univ Calif San Diego, Sch Med, San Diego, CA 92110 USA.
[Capparelli, Edmund] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92110 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM jmascola@mail.nih.gov; ledgerwood@mail.nih.gov
FU VRC, NIAID, NIH; NIH [1R21AI113096]; Delaney AIDS Research Enterprise to
Find a Cure [1U19AI096109]; National Cancer Institute/NIH
[HHSN261200800001E]; Leidos Biomedical Research Inc.
FX This work was supported by the intramural research program of the VRC,
NIAID, NIH. This work was supported in part by NIH grant 1R21AI113096
(N.C.) and by the Delaney AIDS Research Enterprise to Find a Cure
1U19AI096109. This work was funded in part with Federal funds from the
National Cancer Institute/NIH, under contract no. HHSN261200800001E with
Leidos Biomedical Research Inc. (J.D.L., B.A.F., and R.J.G.).
NR 68
TC 44
Z9 45
U1 6
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 DEC 23
PY 2015
VL 7
IS 319
AR 319ra206
DI 10.1126/scitranslmed.aad5752
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CZ4VY
UT WOS:000367102100005
PM 26702094
ER
PT J
AU Regensteiner, JG
Golden, S
Huebschmann, AG
Barrett-Connor, E
Chang, AY
Chyun, D
Fox, CS
Kim, C
Mehta, N
Reckelhoff, JF
Reusch, JEB
Rexrode, KM
Sumner, AE
Welty, FK
Wenger, NK
Anton, B
AF Regensteiner, Judith G.
Golden, Sherita
Huebschmann, Amy G.
Barrett-Connor, Elizabeth
Chang, Alice Y.
Chyun, Deborah
Fox, Caroline S.
Kim, Catherine
Mehta, Nehal
Reckelhoff, Jane F.
Reusch, Jane E. B.
Rexrode, Kathryn M.
Sumner, Anne E.
Welty, Francine K.
Wenger, Nanette K.
Anton, Blair
CA Council Lifestyle Cardiometab Hlth
Council Epidemiology Prevention
Council Functional Genomics Transl
Council Hypertension
TI Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus
A Scientific Statement From the American Heart Association
SO CIRCULATION
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; PERIPHERAL ARTERIAL-DISEASE; IMPAIRED
GLUCOSE-TOLERANCE; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION;
VISCERAL ADIPOSE-TISSUE; INTIMA-MEDIA THICKNESS; ACUTE
MYOCARDIAL-INFARCTION; EVALUATION PROGRAM KEEP; CENTRAL-NERVOUS-SYSTEM
C1 [Regensteiner, Judith G.; Huebschmann, Amy G.] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Golden, Sherita] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Anton, Blair] Johns Hopkins Med Inst, Baltimore, MD USA.
[Barrett-Connor, Elizabeth] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Chang, Alice Y.] Mayo Clin, Scottsdale, AZ USA.
[Chyun, Deborah] CUNY, New York, NY USA.
[Fox, Caroline S.; Mehta, Nehal] NHLBI, Bethesda, MD USA.
[Kim, Catherine] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Regensteiner, JG (reprint author), Univ Colorado, Sch Med, Boulder, CO 80309 USA.
OI Anton, Blair/0000-0002-7077-6678; Rexrode, Kathryn/0000-0003-3387-8429
FU NHLBI NIH HHS [K23 HL118133]
NR 283
TC 18
Z9 18
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 22
PY 2015
VL 132
IS 25
BP 2424
EP 2447
DI 10.1161/CIR.0000000000000343
PG 24
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DF4DT
UT WOS:000371298400018
PM 26644329
ER
PT J
AU Zhu, GQ
Yan, HH
Pang, YL
Jian, J
Achyut, BR
Liang, XH
Weiss, JM
Wiltrout, RH
Hollander, MC
Yang, L
AF Zhu, Guiquan
Yan, H. Hannah
Pang, Yanli
Jian, Jiang
Achyut, Bhagelu R.
Liang, Xinhua
Weiss, Jonathan M.
Wiltrout, Robert H.
Hollander, M. Christine
Yang, Li
TI CXCR3 as a molecular target in breast cancer metastasis: inhibition of
tumor cell migration and promotion of host anti-tumor immunity
SO ONCOTARGET
LA English
DT Article
DE CXCR3; tumor metastasis; migration; host immunity; drug treatment
ID CHEMOKINE RECEPTOR CXCR3; MURINE MODEL; GROWTH; PLATELET-FACTOR-4;
PROGRESSION; ANTAGONISM; EXPRESSION; SURVIVAL; CARCINOMA; VARIANT
AB Chemokines and chemokine receptors have critical roles in cancer metastasis and have emerged as one of the targeting options in cancer therapy. However, the treatment efficacy on both tumor and host compartments needs to be carefully evaluated. Here we report that targeting CXCR3 decreased tumor cell migration and at the same time improved host anti-tumor immunity. We observed an increased expression of CXCR3 in metastatic tumor cells compared to those from non-metastatic tumor cells. Knockdown (KD) of CXCR3 in metastatic tumor cells suppressed tumor cell migration and metastasis. Importantly, CXCR3 expression in clinical breast cancer samples correlated with progression and metastasis. For the host compartment, deletion of CXCR3 in all host cells in 4T1 mammary tumor model significantly decreased metastasis. The underlying mechanisms involve a decreased expression of IL-4, IL-10, iNOs, and Arg-1 in myeloid cells and an increased T cell response. IFN-gamma neutralization diminished the metastasis inhibition in the CXCR3 knockout (KO) mice bearing 4T1 tumors, suggesting a critical role of host CXCR3 in immune suppression. Consistently, targeting CXCR3 using a small molecular inhibitor (AMG487) significantly suppressed metastasis and improved host anti-tumor immunity. Our findings demonstrate that targeting CXCR3 is effective in both tumor and host compartments, and suggest that CXCR3 inhibition is likely to avoid adverse effects on host cells.
C1 [Zhu, Guiquan; Yan, H. Hannah; Pang, Yanli; Jian, Jiang; Achyut, Bhagelu R.; Hollander, M. Christine; Yang, Li] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Zhu, Guiquan] Sichuan Univ, Sichuan Canc Hosp, Dept Head & Neck Surg, Chengdu 610064, Peoples R China.
[Pang, Yanli] Peking Univ, Dept Obstet & Gynecol, Ctr Reprod Med, Hosp 3, Beijing 100871, Peoples R China.
[Jian, Jiang; Liang, Xinhua] Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Dept Oral & Maxillofacial Surg, Chengdu 610064, Peoples R China.
[Weiss, Jonathan M.; Wiltrout, Robert H.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM yangl3@mail.nih.gov
FU NCI
FX This work was supported by NCI intramural funding to Li Yang.
NR 42
TC 7
Z9 7
U1 1
U2 12
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC 22
PY 2015
VL 6
IS 41
BP 43408
EP 43419
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD4QU
UT WOS:000369908400020
PM 26485767
ER
PT J
AU Pybus, OG
Tatem, AJ
Lemey, P
AF Pybus, Oliver G.
Tatem, Andrew J.
Lemey, Philippe
TI Virus evolution and transmission in an ever more connected world
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE virus; epidemiology; geography; evolution; phylogenetics; transmission
ID CHIKUNGUNYA VIRUS; INFLUENZA-VIRUS; MOLECULAR EVOLUTION;
INFECTIOUS-DISEASES; GLOBAL DISTRIBUTION; EPIDEMIOLOGIC DATA; ANALYSIS
REVEALS; HUMAN MOBILITY; DYNAMICS; SPREAD
AB The frequency and global impact of infectious disease outbreaks, particularly those caused by emerging viruses, demonstrate the need for a better understanding of how spatial ecology and pathogen evolution jointly shape epidemic dynamics. Advances in computational techniques and the increasing availability of genetic and geospatial data are helping to address this problem, particularly when both information sources are combined. Here, we review research at the intersection of evolutionary biology, human geography and epidemiology that is working towards an integrated view of spatial incidence, host mobility and viral genetic diversity. We first discuss how empirical studies have combined viral spatial and genetic data, focusing particularly on the contribution of evolutionary analyses to epidemiology and disease control. Second, we explore the interplay between virus evolution and global dispersal in more depth for two pathogens: human influenza A virus and chikungunya virus. We discuss the opportunities for future research arising from new analyses of human transportation and trade networks, as well as the associated challenges in accessing and sharing relevant spatial and genetic data.
C1 [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton SO17 1BJ, Hants, England.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
[Lemey, Philippe] KU Leuven Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium.
RP Pybus, OG (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM oliver.pybus@zoo.ox.ac.uk
OI Pybus, Oliver/0000-0002-8797-2667
FU European Research Council under the European Union's Seventh Framework
Programme/ERC [614725-PATHPHYLODYN]; NIH/NIAID [U19AI089674]; Bill and
Melinda Gates Foundation [OPP110642749446, 1032350]; RAPIDD program of
the Science and Technology Directorate; Department of Homeland Security;
Wellcome Trust Sustaining Health [106866/Z/15/Z]; Fogarty International
Center, National Institutes of Health; European Union Seventh Framework
Programme [278433-PREDEMICS]; ERC Grant [260864]; Onderzoeksfonds KU
Leuven/Research Fund KU Leuven
FX O.G.P. received funding from the European Research Council under the
European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant
agreement no. 614725-PATHPHYLODYN. A.J.T. is supported by funding from
NIH/NIAID (U19AI089674), the Bill and Melinda Gates Foundation
(OPP110642749446, 1032350), the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, Wellcome Trust
Sustaining Health Grant, 106866/Z/15/Z, and the Fogarty International
Center, National Institutes of Health. P.L. acknowledges funding from
the European Union Seventh Framework Programme (FP7/2007-2013) under
grant agreement no. 278433-PREDEMICS and ERC Grant agreement no. 260864,
as well as funding, the from Onderzoeksfonds KU Leuven/Research Fund KU
Leuven.
NR 86
TC 8
Z9 8
U1 8
U2 36
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD DEC 22
PY 2015
VL 282
IS 1821
AR 20142878
DI 10.1098/rspb.2014.2878
PG 10
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA DA8ZW
UT WOS:000368096900001
PM 26702033
ER
PT J
AU Draper, SJ
Angov, E
Horii, T
Miller, LH
Srinivasan, P
Theisen, M
Biswas, S
AF Draper, Simon J.
Angov, Evelina
Horii, Toshihiro
Miller, Louis H.
Srinivasan, Prakash
Theisen, Michael
Biswas, Sumi
TI Recent advances in recombinant protein-based malaria vaccines
SO VACCINE
LA English
DT Article
DE Malaria; Recombinant protein; Vaccine; Adjuvant; Plasmodium falciparum;
Antibody
ID BLOOD-STAGE MALARIA; APICAL MEMBRANE ANTIGEN-1; TRANSMISSION-BLOCKING
VACCINE; GLUTAMATE-RICH PROTEIN; MEROZOITE SURFACE PROTEIN-3;
PLASMODIUM-FALCIPARUM INVASION; HOST-CELL INVASION; NATURALLY ACQUIRED
ANTIBODIES; MONTANIDE ISA 51; CLINICAL MALARIA
AB Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCeITOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Draper, Simon J.; Biswas, Sumi] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
[Angov, Evelina] Walter Reed Army Inst Res, US Mil Malaria Res Program, Silver Spring, MD 20910 USA.
[Horii, Toshihiro] Osaka Univ, Microbial Dis Res Inst, Dept Mol Protozool, Suita, Osaka 561873, Japan.
[Miller, Louis H.; Srinivasan, Prakash] NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Theisen, Michael] Statens Serum Inst, Dept Congenital Disorders, DK-2300 Copenhagen, Denmark.
[Theisen, Michael] Univ Copenhagen, Rigshosp, Ctr Med Parasitol, Dept Int Hlth Immunol & Microbiol, DK-2100 Copenhagen, Denmark.
[Theisen, Michael] Univ Copenhagen, Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
RP Draper, SJ (reprint author), Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England.
EM simon.draper@ndm.ox.ac.uk
OI Draper, Simon/0000-0002-9415-1357
FU UK Medical Research Council (MRC) [G1000527]; U.S. Military Infectious
Diseases Research Program (MIDRP); U.S. Agency for International
Development (USAID) through an Interagency Agreement (IAA); Ministry of
Education, Culture, Sports, Science and Technology of Japan [24249024];
Global Health Innovative Technology Fund [GHIT RFP 2013-001]; Intramural
Research Program of the Division of Intramtral Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA; USAID; EU FP7 Seventh Framework Program Theme
[Health-2009-2.3.2-5, 242079]; Danish Council for Strategic research
[13127]; European and Developing Countries Clinical Trials Partnership
(EDCTP) [IP.2007.3110.001]
FX SJD is a Jenner Investigator, a Lister Institute Research Prize Fellow
and a UK Medical Research Council (MRC) Career Development Fellow
[G1000527; this Fellowship is jointly funded by the UK MRC and the UK
Department for International Development (DFID) under the MRC/DFID
Concordat agreement]. EA acknowledges funding from the U.S. Military
Infectious Diseases Research Program (MIDRP) and the U.S. Agency for
International Development (USAID) through an Interagency Agreement
(IAA). TH acknowledges funding from Grant-in-Aid for Scientific Research
(A) [grant number 24249024] from the Ministry of Education, Culture,
Sports, Science and Technology of Japan; and Global Health Innovative
Technology Fund [GHIT RFP 2013-001]. LHM and PS are supported by the
Intramural Research Program of the Division of Intramtral Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA; and also acknowledge support from USAID. MT
acknowledges funding from the EU FP7 Seventh Framework Program Theme
Health-2009-2.3.2-5 [grant 242079]; the Danish Council for Strategic
research [grant 13127]; and the European and Developing Countries
Clinical Trials Partnership (EDCTP) [grant IP.2007.3110.001]. SB is a
NDM Leadership Fellow and Junior Research Fellow of St Catherine's
College, Oxford University.
NR 198
TC 11
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U1 8
U2 25
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7433
EP 7443
DI 10.1016/j.vaccine.2015.09.093
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700003
PM 26458807
ER
PT J
AU Ewer, KJ
Sierra-Davidson, K
Salman, AM
Illingworth, JJ
Draper, SJ
Biswas, S
Hill, AVS
AF Ewer, Katie J.
Sierra-Davidson, Kailan
Salman, Ahmed M.
Illingworth, Joseph J.
Draper, Simon J.
Biswas, Sumi
Hill, Adrian V. S.
TI Progress with viral vectored malaria vaccines: A multi-stage approach
involving "unnatural immunity"
SO VACCINE
LA English
DT Article
DE Viral vectors; Malaria; Immunity; Clinical trials
ID LIVER-STAGE MALARIA; PRIME-BOOST IMMUNIZATION; CD8(+) T-CELLS; MVA
ME-TRAP; PLASMODIUM-FALCIPARUM; CIRCUMSPOROZOITE PROTEIN;
MONOCLONAL-ANTIBODIES; STERILE PROTECTION; VIRUS ANKARA; ANTIGEN
AB Viral vectors used in heterologous prime-boost regimens are one of very few vaccination approaches that have yielded significant protection against controlled human malaria infections. Recently, protection induced by chimpanzee adenovirus priming and modified vaccinia Ankara boosting using the ME-TRAP insert has been correlated with the induction of potent CD8(+) T cell responses. This regimen has progressed to field studies where efficacy against infection has now been reported. The same vectors have been used pre-clinically to identify preferred protective antigens for use in vaccines against the pre-erythrocytic, blood-stage and mosquito stages of malaria and this work is reviewed here for the first time. Such antigen screening has led to the prioritization of the PfRH5 blood-stage antigen, which showed efficacy against heterologous strain challenge in non-human primates, and vectors encoding this antigen are in clinical trials. This, along with the high transmission-blocking activity of some sexual-stage antigens, illustrates well the capacity of such vectors to induce high titre protective antibodies in addition to potent T cell responses. All of the protective responses induced by these vectors exceed the levels of the same immune responses induced by natural exposure supporting the view that, for subunit vaccines to achieve even partial efficacy in humans, "unnatural immunity" comprising immune responses of very high magnitude will need to be induced. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Ewer, Katie J.; Sierra-Davidson, Kailan; Salman, Ahmed M.; Illingworth, Joseph J.; Draper, Simon J.; Biswas, Sumi; Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
[Sierra-Davidson, Kailan] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20852 USA.
RP Ewer, KJ (reprint author), Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
EM katie.ewer@ndm.ox.ac.uk
RI Ewer, Katie/B-4328-2011;
OI Ewer, Katie/0000-0001-9827-9836; Draper, Simon/0000-0002-9415-1357
FU Medical Research Council [G1000527]
NR 90
TC 3
Z9 3
U1 3
U2 7
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7444
EP 7451
DI 10.1016/j.vaccine.2015.09.094
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700004
PM 26476366
ER
PT J
AU Richie, TL
Billingsley, PF
Sim, BKL
James, ER
Chakravarty, S
Epstein, JE
Lyke, KE
Mordmuller, B
Alonso, P
Duffy, PE
Doumbo, OK
Sauerwein, RW
Tanner, M
Abdulla, S
Kremsner, PG
Seder, RA
Hoffman, SL
AF Richie, Thomas L.
Billingsley, Peter F.
Sim, B. Kim Lee
James, Eric R.
Chakravarty, Sumana
Epstein, Judith E.
Lyke, Kirsten E.
Mordmueller, Benjamin
Alonso, Pedro
Duffy, Patrick E.
Doumbo, Ogobara K.
Sauerwein, Robert W.
Tanner, Marcel
Abdulla, Salim
Kremsner, Peter G.
Seder, Robert A.
Hoffman, Stephen L.
TI Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria
vaccines
SO VACCINE
LA English
DT Article
DE Malaria vaccine; Plasmodium falciparum; Sporozoite; PfSPZ Vaccine;
PfSPZ-CVac; PfSPZ Challenge
ID DIRECT VENOUS INOCULATION; T-CELL IMMUNITY; IRRADIATED SPOROZOITES;
ATTENUATED SPOROZOITES; INTRADERMAL INJECTION; PROTECTIVE IMMUNITY;
VIVAX MALARIA; IMMUNIZATION; INFECTION; SAFETY
AB Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PESPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. 2015 The Authors. Published by Elsevier Ltd.
C1 [Richie, Thomas L.; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Chakravarty, Sumana; Hoffman, Stephen L.] Sanaria Inc, Rockville, MD 20850 USA.
[Epstein, Judith E.] Naval Med Res Ctr, Silver Spring, MD USA.
[Lyke, Kirsten E.] Univ Maryland, Sch Med, Ctr Malaria Res, Inst Global Hlth, Baltimore, MD 21201 USA.
[Mordmueller, Benjamin; Kremsner, Peter G.] Univ Tubingen, Inst Trop Med, Tubingen, Germany.
[Alonso, Pedro] Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.
[Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
[Sauerwein, Robert W.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Tanner, Marcel] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Abdulla, Salim] Ifakara Hlth Inst, Bagamoyo, Tanzania.
[Seder, Robert A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Richie, TL (reprint author), Sanaria Inc, Rockville, MD 20850 USA.
EM trichie@sanaria.com
FU Division of Microbiology and Infectious Diseases, NIAID, NIH; Vaccine
Research Center, NIAID, NIH; US Navy Advanced Medical Development
Program; Military Infectious Disease Research Program; US Army Medical
Materiel Development Activity; PATH Malaria Vaccine Initiative (Bill &
Melinda Gates Foundation); Institute for OneWorld Health (Bill & Melinda
Gates Foundation); Marathon Oil Corporation (Noble Energy, EG LNG,
AMPCO); German Centre for Infection Research; European Vaccine
Initiative; Swiss State Secretariat for Education, Research and
Innovation; Tanzanian Commission on Science and Technology (COSTECH);
Government of Equatorial Guinea; Ghana Ministry of Health
FX We gratefully acknowledge the past and current support of the following
funding institutions: Division of Microbiology and Infectious Diseases,
NIAID, NIH; Vaccine Research Center, NIAID, NIH; US Navy Advanced
Medical Development Program; Military Infectious Disease Research
Program; US Army Medical Materiel Development Activity; PATH Malaria
Vaccine Initiative (Bill & Melinda Gates Foundation); Institute for
OneWorld Health (Bill & Melinda Gates Foundation); Marathon Oil
Corporation (in partnership with Noble Energy, EG LNG, AMPCO); German
Centre for Infection Research; European Vaccine Initiative; Swiss State
Secretariat for Education, Research and Innovation; Tanzanian Commission
on Science and Technology (COSTECH); Government of Equatorial Guinea;
Ghana Ministry of Health.
NR 50
TC 19
Z9 19
U1 5
U2 9
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7452
EP 7461
DI 10.1016/j.vaccine.2015.09.096
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700005
PM 26469720
ER
PT J
AU Fried, M
Duffy, PE
AF Fried, Michal
Duffy, Patrick E.
TI Designing a VAR2CSA-based vaccine to prevent placental malaria
SO VACCINE
LA English
DT Article
DE Plasmodium falciparum; Placental malaria; Vaccine
ID CHONDROITIN-SULFATE-A; FALCIPARUM-INFECTED ERYTHROCYTES;
PREGNANCY-ASSOCIATED MALARIA; VARIANT SURFACE-ANTIGENS;
LOW-BIRTH-WEIGHT; ADHESION-BLOCKING ANTIBODIES; CROSS-REACTIVE
ANTIBODIES; CSA-BINDING PARASITES; PLASMODIUM-FALCIPARUM; NTS-DBL2X
REGION
AB Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1-2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM. Obstacles to PM vaccine development include the large size (similar to 350 kD), high cysteine content, and sequence variation of VAR2CSA. A number of approaches have been taken to identify the combination of VAR2CSA domains and alleles that can induce broadly active antibodies that block adhesion of heterologous parasite isolates to CSA. This review summarizes these approaches, which have examined VAR2CSA fragments for binding activity, antigenicity with naturally acquired antibodies, and immunogenicity in animals for inducing anti-adhesion or surface-reactive antibodies. Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA, and additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a PM vaccine. (C) 2015 Published by Elsevier Ltd.
C1 [Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20892 USA.
RP Fried, M (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 5640 Fishers Lane,TWB1 Room 1111, Rockville, MD 20892 USA.
EM michal.fried@nih.gov; patrick.duffy@nih.gov
FU NIAID, NIH
FX The authors are supported by the Intramural Research Program, NIAID,
NIH.
NR 69
TC 6
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U1 3
U2 5
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7483
EP 7488
DI 10.1016/j.vaccine.2015.10.011
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700009
PM 26469717
ER
PT J
AU Davies, DH
Duffy, P
Bodmer, JL
Felgner, PL
Doolan, DL
AF Davies, D. Huw
Duffy, Patrick
Bodmer, Jean-Luc
Felgner, Philip L.
Doolan, Denise L.
TI Large screen approaches to identify novel malaria vaccine candidates
SO VACCINE
LA English
DT Article
DE Antigen discovery; Large-scale screen; Immunomics; Reverse vaccinology;
Protein microarrays; T cell antigens
ID HUMORAL IMMUNE-RESPONSES; PLASMODIUM-FALCIPARUM SPOROZOITES; T-CELL
EPITOPES; DIAGNOSTIC ANTIGEN DISCOVERY; PROTEOME MICROARRAYS;
CHONDROITIN SULFATE; ANTIBODY-RESPONSES; LIVER-STAGE; VAR GENE;
HETEROLOGOUS EXPRESSION
AB Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated work by many researchers on different continents spanning more than half a century, a successful malaria vaccine remains elusive. Sequencing of the P. falciparum genome has revealed more than five thousand genes, providing the foundation for systematic approaches to discover candidate vaccine antigens. We are taking advantage of this wealth of information to discover new antigens that may be more effective vaccine targets. Herein, we describe different approaches to large-scale screening of the P. falciparum genome to identify targets of either antibody responses or T cell responses using human specimens collected in Controlled Human Malaria Infections (CHMI) or under conditions of natural exposure in the field. These genome, proteome and transcriptome based approaches offer enormous potential for the development of an efficacious malaria vaccine. (C) 2015 Elsevier Ltd.
C1 [Davies, D. Huw; Felgner, Philip L.] Univ Calif Irvine, Irvine, CA USA.
[Duffy, Patrick] NIAID, Rockville, MD USA.
[Bodmer, Jean-Luc] Genocea Biosci Inc, Cambridge, MA USA.
[Doolan, Denise L.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
RP Doolan, DL (reprint author), Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, QIMR Locked Bag 2000, Brisbane, Qld 4029, Australia.
EM Denise.Doolan@qimrberghofer.edu.au
FU NIAID, NIH; National Health and Medical Research Council (NHMRC),
Australia; NIH
FX We express our gratitude and thanks to the many colleagues central to
the studies reported herein. In particular, we would like to thank
Alessandro Sette, John Sidney and Bjorn Peters for their efforts
developing the T cell algorithm prediction method for antigen discovery;
Bruno Douradinha, Leanne Robinson, Danielle Stansic, Ivo Mueller, Peter
Siba and the staff at Papua New Guinea Institute of Medical Research for
the collection of specimens from Papua New Guinea; and Joanne Roddick,
Lea Lekieffre and Carla Proietti for laboratory assays and analysis. We
wish to thank the numerous collaborators especially, Peter Crompton,
Alyssa Barry, Chris Plowe, Joeseph Vinetz, Bryan Greenhouse, James
Kazura, and Kevin Marsh for the opportunity to analyze sera samples from
many different locations around the world and for their stimulating
discussion. We would also like to thank the many volunteers who
generously donated their specimens for analysis, without who this
research could not have been conducted. PD is supported by the
Intramural Research Program of the NIAID, NIH. DLD is supported by a
Principal Research Fellowship from the National Health and Medical
Research Council (NHMRC), Australia. Funding support from NIH for the
studies reported herein is gratefully acknowledged.
NR 118
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U1 0
U2 5
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7496
EP 7505
DI 10.1016/j.vaccine.2015.09.059
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700011
PM 26428458
ER
PT J
AU Wu, YM
Narum, DL
Fleury, S
Jennings, G
Yadava, A
AF Wu, Yimin
Narum, David L.
Fleury, Sylvain
Jennings, Gary
Yadava, Anjali
TI Particle-based platforms for malaria vaccines
SO VACCINE
LA English
DT Article
DE Malaria; Vaccine; Particle; Delivery; Adjuvant
ID TRANSMISSION-BLOCKING VACCINE; EMULSION-BASED ADJUVANTS; AERUGINOSA
EXOPROTEIN-A; IMMUNE-RESPONSES; ANTIBODY-RESPONSE; THERAPEUTIC VACCINES;
FALCIPARUM-MALARIA; CONJUGATE VACCINES; RHESUS MACAQUES; EPITOPE DENSITY
AB Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of repetitive motifs and missing complementary signal(s) for optimal triggering of the immune response. Therefore, recombinant subunit vaccines require enhancement by vaccine delivery vehicles in order to attain adequate protective immunity. Particle-based delivery platforms, including particulate antigens and particulate adjuvants, are promising delivery vehicles for modifying the way in which immunogens are presented to both the innate and adaptive immune systems. These particle delivery platforms can also co-deliver non-specific immunostimodulators as additional adjuvants. This paper reviews efforts and advances of the Particle-based delivery platforms in development of vaccines against malaria, a disease that claims over 600,000 lives per year, most of them are children under 5 years of age in sub-Sahara Africa. (C) 2015 Elsevier Ltd.
C1 [Wu, Yimin; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, Rockville, MD 20892 USA.
[Fleury, Sylvain] Mymetics Corp, CH-1066 Epalinges, Switzerland.
[Jennings, Gary] Cytos Biotechnol AG, CH-8952 Schlieren, Switzerland.
[Yadava, Anjali] Walter Reed Army Inst Res, Malaria Vaccine Branch, US Mil Malaria Vaccine Program, Silver Spring, MD USA.
RP Wu, YM (reprint author), PATH Malaria Vaccine Initiat, 455 Massachusetts Ave, Washington, DC 20001 USA.
EM ywu@path.org
FU Division of Intramural Research, NIAID, NIH
FX The opinions or assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the
views of either the Department of Health and Human Services, the
Department of the Army, the Department of Defense or the U.S.
Government. YW and DLN are supported by Division of Intramural Research,
NIAID, NIH.
NR 69
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U1 3
U2 7
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 DEC 22
PY 2015
VL 33
IS 52
SI SI
BP 7518
EP 7524
DI 10.1016/j.vaccine.2015.09.097
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DA0MR
UT WOS:000367491700014
PM 26458803
ER
PT J
AU Campbell-Washburn, AE
Rogers, T
Basar, B
Sonmez, M
Kocaturk, O
Lederman, RJ
Hansen, MS
Faranesh, AZ
AF Campbell-Washburn, Adrienne E.
Rogers, Toby
Basar, Burcu
Sonmez, Merdim
Kocaturk, Ozgur
Lederman, Robert J.
Hansen, Michael S.
Faranesh, Anthony Z.
TI Positive contrast spiral imaging for visualization of commercial nitinol
guidewires with reduced heating
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Interventional CMR; Spiral; Non-Cartesian; Positive contrast; White
marker; Guidewire; Real-time
ID STATE FREE PRECESSION; INTERVENTIONAL MRI; PASSIVE DEVICES; WIRES;
CELLS; IRON; CATHETERIZATION; HEART
AB Background: CMR-guidance has the potential to improve tissue visualization during cardiovascular catheterization procedures and to reduce ionizing radiation exposure, but a lack of commercially available CMR guidewires limits widespread adoption. Standard metallic guidewires are considered to be unsafe in CMR due to risks of RF-induced heating. Here, we propose the use of RF-efficient gradient echo (GRE) spiral imaging for reduced guidewire heating (low flip angle, long readout), in combination with positive contrast for guidewire visualization.
Methods: A GRE spiral sequence with 8 interleaves was used for imaging. Positive contrast was achieved using through-slice dephasing such that the guidewire appeared bright and the background signal suppressed. Positive contrast images were interleaved with anatomical images, and real-time image processing was used to produce a color overlay of the guidewire on the anatomy. Temperature was measured with a fiber-optic probe attached to the guidewire in an acrylic gel phantom and in vivo.
Results: Left heart catheterization was performed on swine using the real-time color overlay for procedural guidance with a frame rate of 6.25 frames/second. Using our standard Cartesian real-time imaging (flip angle 60 degrees), temperature increases up to 50 degrees C (phantom) and 4 degrees C (in vivo) were observed. In comparison, spiral GRE images (8 interleaves, flip angle 10 degrees) generated negligible heating measuring 0.37 degrees C (phantom) and 0.06 degrees C (in vivo).
Conclusions: The ability to use commercial metallic guidewires safely during CMR-guided catheterization could potentially expedite clinical translation of these methods.
C1 [Campbell-Washburn, Adrienne E.; Rogers, Toby; Basar, Burcu; Sonmez, Merdim; Kocaturk, Ozgur; Lederman, Robert J.; Hansen, Michael S.; Faranesh, Anthony Z.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Basar, Burcu; Kocaturk, Ozgur] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey.
RP Campbell-Washburn, AE (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM adrienne.campbell@nih.gov
OI Rogers, Toby/0000-0002-6043-3137; lederman, robert/0000-0003-1202-6673
FU National Heart, Lung and Blood Institute Division of Intramural Research
[Z01-HL006039, Z01-HL005062]
FX This work was supported by the National Heart, Lung and Blood Institute
Division of Intramural Research, Z01-HL006039 and Z01-HL005062. RJL is
the principal investigator on a US government Cooperative Research and
Development Agreement (CRADA) with Siemens Medical Solutions.
NR 29
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U1 0
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 DEC 22
PY 2015
VL 17
AR 114
DI 10.1186/s12968-015-0219-9
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DA0UQ
UT WOS:000367513500001
PM 26695490
ER
PT J
AU Matsunaga, K
Kimoto, M
Hanson, C
Sanford, M
Young, HA
Hirao, I
AF Matsunaga, Ken-ichiro
Kimoto, Michiko
Hanson, Charlotte
Sanford, Michael
Young, Howard A.
Hirao, Ichiro
TI Architecture of high-affinity unnatural-base DNA aptamers toward
pharmaceutical applications
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EXPANDED GENETIC ALPHABET; ENDOTHELIAL GROWTH-FACTOR; IN-VITRO
SELECTION; STABLE STRUCTURE; RNA; LIGANDS; D(GCGAAGC); GENERATION;
RESISTANT; FRAGMENT
AB We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-gamma (K-D of 33 pM) survived in human serum at 37 degrees C after 3 days under our experimental conditions, and sustainably inhibited the biological activity of interferon-gamma.
C1 [Matsunaga, Ken-ichiro; Kimoto, Michiko; Hirao, Ichiro] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore.
[Matsunaga, Ken-ichiro; Kimoto, Michiko; Hirao, Ichiro] TagCyx Biotechnol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Matsunaga, Ken-ichiro; Kimoto, Michiko; Hirao, Ichiro] RIKEN Ctr Life Sci Technol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Kimoto, Michiko] JST, PRESTO, Kawaguchi, Saitama 3320012, Japan.
[Hanson, Charlotte; Sanford, Michael; Young, Howard A.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Hirao, I (reprint author), Inst Bioengn & Nanotechnol, 31 Biopolis Way,Nanos 04-01, Singapore 138669, Singapore.
EM YoungHow@mail.nih.gov; ichiro@ibn.a-star.edu.sg
RI Kimoto, Michiko/G-1435-2012; Hirao, Ichiro/G-3041-2012
FU Ministry of Education, Culture, Sports, Science and Technology [KAKENHI
26248043]; Ministry of Economy, Trade, and Industry; Japan Science and
Technology Agency (JST) Precursory Research for Embryonic Science and
Technology (PRESTO); intramural research program of the NIH, National
Cancer Institute
FX This work was supported by a Grant-in-Aid for Scientific Research
[KAKENHI 26248043] from the Ministry of Education, Culture, Sports,
Science and Technology (I.H.), by grants for projects focused on
developing key technologies for discovering and manufacturing drugs for
next-generation treatment and diagnosis from the Ministry of Economy,
Trade, and Industry (I.H.), by the Japan Science and Technology Agency
(JST) Precursory Research for Embryonic Science and Technology (PRESTO)
(M.K.), and by the intramural research program of the NIH, National
Cancer Institute (H.A.Y.).
NR 26
TC 4
Z9 4
U1 10
U2 30
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 DEC 22
PY 2015
VL 5
AR 18478
DI 10.1038/srep18478
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ3XU
UT WOS:000367038100001
PM 26690672
ER
PT J
AU Ahlman, MA
Raman, FS
Penzak, SR
Pang, JN
Fan, ZY
Liu, ST
Gai, N
Li, DB
Bluemke, DA
AF Ahlman, Mark A.
Raman, Fabio S.
Penzak, Scott R.
Pang, Jianing
Fan, Zhaoyang
Liu, Songtao
Gai, Neville
Li, Debiao
Bluemke, David A.
TI Part 1-Coronary angiography with gadofosveset trisodium: a prospective
feasibility study evaluating injection techniques for steady-state
imaging
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
DE Gadofosveset trisodium; MS-325; Gadolinium-based intravascular contrast
agent; Whole-heart coronary magnetic resonance angiography;
Navigator-based angiography; 3.0 Tesla; Image quality; Respiratory
motion correction
ID MAGNETIC-RESONANCE ANGIOGRAPHY; MYOCARDIUM INTRAINDIVIDUAL ASSESSMENT;
EXTRACELLULAR VOLUME FRACTION; MR-ANGIOGRAPHY; CONTRAST AGENT; CORONARY
MRA; 3.0 T; MS-325; TESLA
AB Background: The purpose of this study was to define an optimal injection protocol for 5-10 min duration navigator-based coronary MR angiography using an intravascular gadolinium-based contrast agent (GBCA), which is better suited for steady-state coronary MR angiography than conventional GBCAs.
Methods: Using projections from pharmacokinetic models of the intravascular concentration of gadofosveset, a dual-injection protocol was formulated and tested on 14 healthy human subjects. Modified Look-Locker inversion recovery (MOLLI) sequences were used for T1 mapping at 3 Tesla to evaluate the concentration of tracer in the aorta over the scanning interval.
Results: Pharmacokinetic models for a bolus plus slow infusion technique at a 5, 10, and 15 min steady state intravascular concentration was compared to single bolus curves. The 70 %/30 % bolus/slow infusion technique resulted in the highest intravascular concentration over a 5 min scan duration. Similarly, the 60 %/40 % bolus/slow infusion technique was projected to be ideal for image acquisition duration of 5-10 min. These models were confirmed with T1 maps on normal volunteers. Arterial-venous mixing of contrast was achieved within 90 s of the beginning of the bolus.
Conclusions: Gadofosveset injection is optimized for the lowest intravascular T1 time for 5-10 min duration MR angiography by bolus injection of 60-70 % of the total dose followed by slow infusion of the remainder of the total dose. This protocol achieves rapid and prolonged steady state intravascular concentrations of the GBCA that may be useful for prolonged image acquisition, such as required for navigator-based coronary MR angiography at 3 Tesla.
C1 [Ahlman, Mark A.; Raman, Fabio S.; Liu, Songtao; Gai, Neville; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Penzak, Scott R.] Univ N Texas, Dept Pharmacotherapy, Ft Worth, TX USA.
[Pang, Jianing; Fan, Zhaoyang; Li, Debiao] Cedars Sinai Med Ctr, Bioengn, Los Angeles, CA 90048 USA.
RP Ahlman, MA (reprint author), NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM mark.ahlman@nih.gov
OI Raman, Fabio/0000-0003-2393-9937; Bluemke, David/0000-0002-8323-8086
FU NIH [R01 EB002623]; National Institutes of Health (NIH) intramural
research program; imaging sciences training program
FX J. Pang, Z Fan, and D Li acknowledge support of NIH R01 EB002623.
Otherwise, the National Institutes of Health (NIH) intramural research
program and the imaging sciences training program supported this
research. We thank Jacquin Jones who provided scheduling and recruitment
services for the work herein.
NR 21
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U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD DEC 22
PY 2015
VL 15
AR 177
DI 10.1186/s12872-015-0176-0
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CZ1TP
UT WOS:000366888500001
PM 26695065
ER
PT J
AU Chalamcharla, VR
Folco, HD
Dhakshnamoorthy, J
Grewal, SIS
AF Chalamcharla, Venkata R.
Folco, H. Diego
Dhakshnamoorthy, Jothy
Grewal, Shiv I. S.
TI Conserved factor Dhp1/Rat1/Xrn2 triggers premature transcription
termination and nucleates heterochromatin to promote gene silencing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE heterochromatin; Dhp1/Xrn2; S. pombe; transcription termination
ID RNA-POLYMERASE-II; PRE-MESSENGER-RNA; FISSION YEAST;
SCHIZOSACCHAROMYCES-POMBE; SELECTIVE ELIMINATION; BINDING PROTEIN;
MEIOTIC GENES; DHP1(+) GENE; S. POMBE; POL-II
AB Cotranscriptional RNA processing and surveillance factors mediate heterochromatin formation in diverse eukaryotes. In fission yeast, RNAi machinery and RNA elimination factors including the Mtl1-Red1 core and the exosome are involved in facultative heterochromatin assembly; however, the exact mechanisms remain unclear. Here we show that RNA elimination factors cooperate with the conserved exoribonuclease Dhp1/Rat1/Xrn2, which couples pre-mRNA 3'-end processing to transcription termination, to promote premature termination and facultative heterochromatin formation at meiotic genes. We also find that Dhp1 is critical for RNAi-mediated heterochromatin assembly at retroelements and regulated gene loci and facilitates the formation of constitutive heterochromatin at centromeric and mating-type loci. Remarkably, our results reveal that Dhp1 interacts with the Clr4/Suv39h methyltransferase complex and acts directly to nucleate heterochromatin. Our work uncovers a previously unidentified role for 3'-end processing and transcription termination machinery in gene silencing through premature termination and suggests that noncanonical transcription termination by Dhp1 and RNA elimination factors is linked to heterochromatin assembly. These findings have important implications for understanding silencing mechanisms targeting genes and repeat elements in higher eukaryotes.
C1 [Chalamcharla, Venkata R.; Folco, H. Diego; Dhakshnamoorthy, Jothy; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Grewal, SIS (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan;
National Institutes of Health, National Cancer Institute
FX We are grateful to Dr. Ming Zhou for mass spectrometry analysis. FY13308
was provided by the National Bio-Resource Project of the Ministry of
Education, Culture, Sports, Science, and Technology, Japan. We thank Dr.
Kazuo Tatebayashi for providing the dhp1-1<+ strain
(MP102), Dr. Masayuki Yamamoto for providing CFP-mmi1 allele, and Dr.
Tomoyasu Sugiyama for mtl1-FTP allele. We also thank Jemima Barrowman
for help in preparing and editing the manuscript, and members of the
S.I.S.G. laboratory for helpful suggestions. This work was supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 67
TC 5
Z9 5
U1 2
U2 2
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 DEC 22
PY 2015
VL 112
IS 51
BP 15548
EP 15555
DI 10.1073/pnas.1522127112
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ2DT
UT WOS:000366916000030
PM 26631744
ER
PT J
AU Hu, LH
Vecchiarelli, AG
Mizuuchi, K
Neuman, KC
Liu, J
AF Hu, Longhua
Vecchiarelli, Anthony G.
Mizuuchi, Kiyoshi
Neuman, Keir C.
Liu, Jian
TI Directed and persistent movement arises from mechanochemistry of the
ParA/ParB system
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ParA ATPase; Brownian ratchet; theoretical model; motility
ID BACTERIAL CHROMOSOME SEGREGATION; PROKARYOTIC DNA SEGREGATION; PLASMID
PARTITION; F-PLASMID; PARB; TRANSPORT; COMPLEX; ORGANIZATION; MECHANISM;
BINDING
AB The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos-an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.
C1 [Hu, Longhua; Neuman, Keir C.; Liu, Jian] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Liu, J (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
EM liuj7@mail.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU National Heart, Lung, and Blood Institute intramural research program at
NIH; National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank the reviewers for their constructive suggestions that greatly
improved the quality of the paper. L.H., K.C.N., and J.L. are supported
by National Heart, Lung, and Blood Institute intramural research program
at NIH. A.G.V. and K.M. are supported by National Institute of Diabetes
and Digestive and Kidney Diseases intramural research program.
NR 41
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Z9 4
U1 0
U2 8
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 DEC 22
PY 2015
VL 112
IS 51
BP E7055
EP E7064
DI 10.1073/pnas.1505147112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ2DT
UT WOS:000366916000007
PM 26647183
ER
PT J
AU Wheeler, DS
Underhill, SM
Stolz, DB
Murdoch, GH
Thiels, E
Romero, G
Amara, SG
AF Wheeler, David S.
Underhill, Suzanne M.
Stolz, Donna B.
Murdoch, Geoffrey H.
Thiels, Edda
Romero, Guillermo
Amara, Susan G.
TI Amphetamine activates Rho GTPase signaling to mediate dopamine
transporter internalization and acute behavioral effects of amphetamine
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE dopamine transporter; amphetamine; Rho GTPase; protein kinase A;
endocytosis
ID DEPENDENT MECHANISM; PHOSPHOLIPASE-D; METHAMPHETAMINE; TRAFFICKING;
COCAINE; FAMILY; ENDOCYTOSIS; ADDICTION; RECEPTORS; PROTEINS
AB Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA-and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH's effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action.
C1 [Wheeler, David S.; Romero, Guillermo] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Underhill, Suzanne M.; Amara, Susan G.] NIMH, Lab Mol & Cellular Neurobiol, NIH, Bethesda, MD 20892 USA.
[Stolz, Donna B.] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15261 USA.
[Murdoch, Geoffrey H.] Univ Pittsburgh, Div Neuropathol, Dept Pathol, Pittsburgh, PA 15213 USA.
[Thiels, Edda] Univ Pittsburgh, Ctr Neural Basis Cognit, Ctr Neurosci, Dept Neurobiol, Pittsburgh, PA 15260 USA.
RP Underhill, SM (reprint author), NIMH, Lab Mol & Cellular Neurobiol, NIH, Bethesda, MD 20892 USA.
EM smunderhill@yahoo.com; susan.amara@nih.gov
FU American Recovery and Reinvestment Act (ARRA) [DA07595, F30DK083211];
ARRA [1R56DK079864]; Office of the Senior Vice Chancellor, Health
Sciences, University of Pittsburgh; National Institute of Mental Health
at the NIH; [NCRR-UL1RR024153]
FX We thank S. Watts for his intellectual contributions and M. Miller, M.
Larsen, and P. Hullihen for their technical assistance. The behavioral
data were collected at the Rodent Behavior Analysis Core of the
University of Pittsburgh Schools of the Health Sciences. This work was
supported by American Recovery and Reinvestment Act of 2009
(ARRA)-funded Grants DA07595 (to S.G.A.), F30DK083211 (to D.S.W.),
ARRA-funded 1R56DK079864 (to G.R.), and NCRR-UL1RR024153 (to E.T.) and
by grants from the Office of the Senior Vice Chancellor, Health
Sciences, University of Pittsburgh (to G.R. and E.T.) and the Intramural
Research Program of the National Institute of Mental Health at the NIH
(to S.G.A.).
NR 37
TC 3
Z9 3
U1 1
U2 6
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 DEC 22
PY 2015
VL 112
IS 51
BP E7138
EP E7147
DI 10.1073/pnas.1511670112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ2DT
UT WOS:000366916000016
PM 26553986
ER
PT J
AU Kolf, CM
Song, L
Helm, J
Tuan, RS
AF Kolf, Catherine M.
Song, Lin
Helm, Jeannine
Tuan, Rocky S.
TI Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal
stem cells in vitro
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
DE Mesenchymal stem cells; Osteoblasts; Extracellular matrix; Osteogenesis;
Stem cell niche
ID HUMAN BONE-MARROW; HEMATOPOIETIC PROGENITOR CELLS; EXTRACELLULAR-MATRIX;
STROMAL CELLS; EX-VIVO; DIFFERENTIATION; COLLAGEN; EXPANSION; PROTEIN;
GROWTH
AB Introduction: Adult mesenchymal stem cells (MSCs) are considered promising candidates for cell-based therapies. Their potential utility derives primarily from their immunomodulatory activity, multi-lineage differentiation potential, and likely progenitor cell function in wound healing and repair of connective tissues. However, in vitro, MSCs often senesce and spontaneously differentiate into osteoblasts after prolonged expansion, likely because of lack of regulatory microenvironmental signals. In vivo, osteoblasts that line the endosteal bone marrow surface are in close proximity to MSCs in the marrow stroma and thus may help to regulate MSC fate.
Methods: We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM).
Results: Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis.
Conclusions: These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation.
C1 [Kolf, Catherine M.; Song, Lin; Helm, Jeannine; Tuan, Rocky S.] NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD USA.
[Song, Lin] Johns Hopkins Univ, Dept Biol, Baltimore, MD USA.
[Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, Pittsburgh, PA 15219 USA.
[Kolf, Catherine M.] Johns Hopkins Med Media Relat & Publ Affairs, Baltimore, MD 21231 USA.
[Song, Lin] Stryker Orthoped, Mahwah, NJ 07430 USA.
[Helm, Jeannine] Natl Inst Dent & Craniofacial Res, NIH, Translat Gen Res Branch, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD USA.
EM rst13@pitt.edu
FU NIH Intramural Research Program [Z01 AR41131]; Commonwealth of
Pennsylvania Department of Health [SAP 4100050913]
FX We sincerely thank Dr. Paul Manner (University of Washington) for
providing femoral head tissue samples, and Jim Simone (NIAMS Flow
Cytometry Facility), Dr. Lewis Pannell (Proteomics and Mass Spectrometry
Laboratory, University of South Alabama), and Roberto Diaz (GE) for
countless hours of sample processing and procedural advice. Supported by
the NIH Intramural Research Program (Z01 AR41131) and the Commonwealth
of Pennsylvania Department of Health (SAP 4100050913).
NR 51
TC 3
Z9 3
U1 3
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD DEC 22
PY 2015
VL 6
AR 258
DI 10.1186/s13287-015-0223-x
PG 16
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CZ1VU
UT WOS:000366894600002
PM 26696301
ER
PT J
AU Liu, YJ
He, J
Yang, KK
Yi, CL
Liu, Y
Nie, LM
Khashab, NM
Chen, XY
Nie, ZH
AF Liu, Yijing
He, Jie
Yang, Kuikun
Yi, Chenglin
Liu, Yi
Nie, Liming
Khashab, Niveen M.
Chen, Xiaoyuan
Nie, Zhihong
TI Folding Up of Gold Nanoparticle Strings into Plasmonic Vesicles for
Enhanced Photoacoustic Imaging
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE block copolymers; gold nanoparticles; photoacoustic imaging;
self-assembly; vesicles
ID METAL NANOPARTICLES; DRUG-DELIVERY; THERAPY; ASSEMBLIES; DRIVEN; GROWTH;
CHAINS; THERANOSTICS; BIOMEDICINE; COPOLYMERS
AB The stepwise self-assembly of hollow plasmonic vesicles with vesicular membranes containing strings of gold nanoparticles (NPs) is reported. The formation of chain vesicles can be controlled by tuning the density of the polymer ligands on the surface of the gold NPs. The strong absorption of the chain vesicles in the near-infrared (NIR) region leads to a much higher efficiency in photoacoustic (PA) imaging than for non-chain vesicles. The chain vesicles were further employed for the encapsulation of drugs and the NIR light triggered release of payloads. This work not only offers a new platform for controlling the hierarchical self-assembly of NPs, but also demonstrates that the physical properties of the materials can be tailored by controlling the spatial arrangement of NPs within assemblies to achieve a better performance in biomedical applications.
C1 [Liu, Yijing; He, Jie; Yang, Kuikun; Yi, Chenglin; Liu, Yi; Nie, Zhihong] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Nie, Liming; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
[Khashab, Niveen M.] King Abdullah Univ Sci & Technol, Dept Chem Sci & Engn, Adv Membranes & Porous Mat Ctr, Smart Hybrid Mat SHMs Lab, Thuwal 239556900, Saudi Arabia.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
EM shawn.chen@nih.gov; znie@umd.edu
RI Nie, Zhihong/D-7495-2011; Liu, Yijing/D-6666-2016;
OI Nie, Zhihong/0000-0001-9639-905X; He, Jie/0000-0003-0252-3094
FU National Science Foundation (NSF) [DMR-1255377]; ACS Petroleum Research
Fund [PRF 53461-DNI7]; 3M non-tenured faculty award; Intramural Research
Program of the National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health; Maryland NanoCenter and
its NispLab
FX This work was funded by a National Science Foundation (NSF) CAREER award
(DMR-1255377), the ACS Petroleum Research Fund (PRF 53461-DNI7), a 3M
non-tenured faculty award, and the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health. We acknowledge support by the Maryland NanoCenter
and its NispLab.
NR 41
TC 14
Z9 14
U1 32
U2 120
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 DEC 21
PY 2015
VL 54
IS 52
BP 15809
EP 15812
DI 10.1002/anie.201508616
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA DA8NK
UT WOS:000368061800030
PM 26555318
ER
PT J
AU Ajiro, M
Zheng, ZM
AF Ajiro, Masahiko
Zheng, Zhi-Ming
TI Vemurafenib-resistant BRAF selects alternative branch points different
from its wild-type BRAF in intron 8 for RNA splicing
SO CELL AND BIOSCIENCE
LA English
DT Letter
DE BRAF; RNA splicing; Branch point mapping; Lariat RT-PCR;
Vemurafenib-resistance
ID PRE-MESSENGER-RNA; ACQUIRED-RESISTANCE; IN-VITRO; MELANOMA; SITE;
INHIBITION; EXON; BRAF(V600E); RECOGNITION; SUPPRESSOR
AB One mechanism of resistance of the melanoma-associated BRAF kinase to its small molecule inhibitor vemurafenib is by point mutations in its intron 8 resulting in exons 4-8 skipping. In this report, we carried out in vitro BRAF RNA splicing assays and lariat RT-PCR to map the intron 8 branch points in wild-type and BRAF mutants. We identify multiple branch points (BP) in intron 8 of both wild-type (wt) and vemurafenib-resistant BRAF RNA. In wt BRAF, BPs are located at -29A, -28A and -26A, whereas in a vemurafenib-resistant BRAF splicing mutant, BPs map to -22A, -18A and -15A, proximal to the intron 8 3' splice site. This finding of a distal-to-proximal shift of the branch point sequence in BRAF splicing in response to point-mutations in intron 8 provides insight into the regulation of BRAF alternative splicing upon vemurafenib resistance.
C1 [Ajiro, Masahiko; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
EM zhengt@exchange.nih.gov
NR 53
TC 0
Z9 0
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD DEC 21
PY 2015
VL 5
AR 70
DI 10.1186/s13578-015-0061-7
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ4KK
UT WOS:000367071700002
PM 26697165
ER
PT J
AU Singaravelu, G
Rahimi, S
Krauchunas, A
Rizvi, A
Dharia, S
Shakes, D
Smith, H
Golden, A
Singson, A
AF Singaravelu, Gunasekaran
Rahimi, Sina
Krauchunas, Amber
Rizvi, Anam
Dharia, Sunny
Shakes, Diane
Smith, Harold
Golden, Andy
Singson, Andrew
TI Forward Genetics Identifies a Requirement for the Izumo-like
Immunoglobulin Superfamily spe-45 Gene in Caenorhabditis elegans
Fertilization
SO CURRENT BIOLOGY
LA English
DT Article
ID SPERM; MATURATION; RECEPTOR; PROTEIN
AB Fertilization is a conserved process in all sexually reproducing organisms whereby sperm bind and fuse with oocytes. Despite the importance of sperm-oocyte interactions in fertilization, the molecular underpinnings of this process are still not well understood. The only cognate ligand-receptor pair identified in the context of fertilization is sperm-surface Izumo and egg-surface Juno in the mouse [1]. Here we describe a genetic screening strategy to isolate fertilization mutants in Caenorhabditis elegans in order to generate a more complete inventory of molecules required for gamete interactions. From this screening strategy, we identified, cloned, and characterized spe-45, a gene that encodes an Izumo-like immunoglobulin superfamily protein. Mammalian Izumo is required for male fertility and has the same basic mutant phenotype as spe-45. Worms lacking spe-45 function produce morphologically normal and motile sperm that cannot fuse with oocytes despite direct contact in the reproductive tract. The power of this screen to identify proteins with ancient sperm functions suggests that characterization of additional mutants from our screen may reveal other deeply conserved components in fertility pathways and complement studies in other organisms.
C1 [Singaravelu, Gunasekaran; Rahimi, Sina; Krauchunas, Amber; Rizvi, Anam; Dharia, Sunny; Singson, Andrew] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA.
[Shakes, Diane] Coll William & Mary, Williamsburg, VA 23187 USA.
[Smith, Harold; Golden, Andy] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Singson, A (reprint author), Rutgers State Univ, Waksman Inst Microbiol, 190 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM singson@waksman.rutgers.edu
FU NIH Office of Research Infrastructure Programs [P40 OD010440]; NIH [R01
HD054681]
FX We thank Dr. Steven L'Hernault and Dr. Hitoshi Nishimura for sharing
their unpublished results and for the critical reading of the
manuscript. We would also like to thank members of the A.S. Lab for
assistance with experiments and manuscript preparation. We thank Dr.
Joel Rothman and Dr. Keith Strohmaier for providing the transgenic worms
carrying Pelt-7: gfp. Some strains were provided by the CGC, which is
funded by the NIH Office of Research Infrastructure Programs (P40
OD010440). We thank the Mitani Lab and National Bioresource Project for
the Experimental Animal (Japan) for providing the tm3715 mutant strain.
This work was supported by a grant from the NIH (R01 HD054681) to A.S.
NR 14
TC 1
Z9 1
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD DEC 21
PY 2015
VL 25
IS 24
BP 3220
EP 3224
DI 10.1016/j.cub.2015.10.055
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CZ6TH
UT WOS:000367233400023
PM 26671668
ER
PT J
AU Pitzer, VE
Bilcke, J
Heylen, E
Crawford, FW
Callens, M
De Smet, F
Van Ranst, M
Zeller, M
Matthijnssens, J
AF Pitzer, Virginia E.
Bilcke, Joke
Heylen, Elisabeth
Crawford, Forrest W.
Callens, Michael
De Smet, Frank
Van Ranst, Marc
Zeller, Mark
Matthijnssens, Jelle
TI Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus
Population in Belgium?
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GROUP-A ROTAVIRUS; NATIONAL IMMUNIZATION PROGRAM;
POLYMERASE-CHAIN-REACTION; UNITED-STATES; STRAIN DIVERSITY; GLOBAL
SPREAD; CHILDREN; GENOTYPE; PROTECTION; INFECTION
AB Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural-and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes.
C1 [Pitzer, Virginia E.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06511 USA.
[Pitzer, Virginia E.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bilcke, Joke] Univ Antwerp, Vaccine & Infect Dis Inst VAXINFECTIO, CHERMID, B-2020 Antwerp, Belgium.
[Heylen, Elisabeth; Van Ranst, Marc; Zeller, Mark; Matthijnssens, Jelle] Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol,Rega Inst Med Res, Leuven, Belgium.
[Crawford, Forrest W.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
[Crawford, Forrest W.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA.
[Callens, Michael; De Smet, Frank] Natl Alliance Christian Sickness Funds, Brussels, Belgium.
[De Smet, Frank] Univ Leuven, KU Leuven, Dept Publ Hlth & Primary Care, Environm & Hlth, Leuven, Belgium.
RP Pitzer, VE (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06511 USA.
EM virginia.pitzer@yale.edu; jelle.matthijnssens@uz.kuleuven.ac.be
RI Matthijnssens, Jelle/B-8634-2016; Matthijnssens, Jelle/A-6770-2015;
OI Pitzer, Virginia/0000-0003-1015-2289
FU Bill & Melinda Gates Foundation; RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health; NIH [R01 AI112970,
KL2 TR000140, RR19895, RR029676-01]; Research Foundation - Flanders
(FWO); Institute for the Promotion of Innovation through Science and
Technology in Flanders (IWT Vlaanderen); FWO [K2.003.13N]; Yale High
Performance Computing Cluster
FX V.E.P. was supported by the Bill & Melinda Gates Foundation and the
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health, and NIH grant R01 AI112970. J.B. was supported by
the Research Foundation - Flanders (FWO). F.W.C was supported by NIH
grant KL2 TR000140. M.Z. was supported by the Institute for the
Promotion of Innovation through Science and Technology in Flanders (IWT
Vlaanderen). J.M. was supported by a shore stay abroad FWO travel grant
from FWO (K2.003.13N). V.E.P. would like to acknowledge the support of
the Yale High Performance Computing Cluster and NIH grants RR19895 and
RR029676-01, which support the Louise cluster.
NR 61
TC 5
Z9 5
U1 2
U2 3
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 DEC 21
PY 2015
VL 5
AR 18585
DI 10.1038/srep18585
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ4KS
UT WOS:000367072500001
PM 26687288
ER
PT J
AU Volk, T
Pannicke, U
Reisli, I
Bulashevska, A
Ritter, J
Bjorkman, A
Schaffer, AA
Fliegauf, M
Sayar, EH
Salzer, U
Fisch, P
Pfeifer, D
Di Virgilio, M
Cao, HZ
Yang, F
Zimmermann, K
Keles, S
Caliskaner, Z
Guner, S
Schindler, D
Hammarstrom, L
Rizzi, M
Hummel, M
Pan-Hammarstrom, Q
Schwarz, K
Grimbacher, B
AF Volk, Timo
Pannicke, Ulrich
Reisli, Ismail
Bulashevska, Alla
Ritter, Julia
Bjorkman, Andrea
Schaeffer, Alejandro A.
Fliegauf, Manfred
Sayar, Esra H.
Salzer, Ulrich
Fisch, Paul
Pfeifer, Dietmar
Di Virgilio, Michela
Cao, Hongzhi
Yang, Fang
Zimmermann, Karin
Keles, Sevgi
Caliskaner, Zafer
Guner, Sukru
Schindler, Detlev
Hammarstroem, Lennart
Rizzi, Marta
Hummel, Michael
Pan-Hammarstrom, Qiang
Schwarz, Klaus
Grimbacher, Bodo
TI DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical
severe combined immunodeficiency to mere antibody deficiency
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CLASS SWITCH RECOMBINATION; COMMON VARIABLE IMMUNODEFICIENCY; STEM-CELL
TRANSPLANTATION; NONHOMOLOGOUS END; RAG MUTATIONS; V(D)J RECOMBINATION;
IMMUNE-DEFICIENCY; SEQUENCING DATA; PROTEIN; RECEPTOR
AB Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naive T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients.
C1 [Volk, Timo; Bulashevska, Alla; Fliegauf, Manfred; Salzer, Ulrich; Rizzi, Marta; Grimbacher, Bodo] Univ Med Ctr Freiburg, CCI, Freiburg, Germany.
[Volk, Timo; Bulashevska, Alla; Fliegauf, Manfred; Salzer, Ulrich; Rizzi, Marta; Grimbacher, Bodo] Univ Freiburg, D-79108 Freiburg, Germany.
[Pannicke, Ulrich; Schwarz, Klaus] Univ Ulm, Inst Transfus Med, D-89069 Ulm, Germany.
[Reisli, Ismail; Sayar, Esra H.; Keles, Sevgi; Guner, Sukru] Necmettin Erbakan Univ, Meram Med Fac, Dept Pediat Immunol & Allergy, Konya, Turkey.
[Caliskaner, Zafer] Necmettin Erbakan Univ, Meram Med Fac, Dept Immunol & Allergy, Konya, Turkey.
[Ritter, Julia; Zimmermann, Karin; Hammarstroem, Lennart; Hummel, Michael] Charite, Campus Benjamin Franklin, Inst Pathol, D-13353 Berlin, Germany.
[Bjorkman, Andrea; Pan-Hammarstrom, Qiang] Karolinska Univ, Huddinge Hosp, Dept Lab Med, Div Clin Immunol & Transfus Med, Stockholm, Sweden.
[Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fisch, Paul] Univ Freiburg, Med Ctr, Ctr Pathol, D-79108 Freiburg, Germany.
[Pfeifer, Dietmar] Univ Med Ctr, Dept Hematol Oncol & Stem Cell Transplantat, Freiburg, Germany.
[Di Virgilio, Michela] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Cao, Hongzhi; Yang, Fang] BGI Shenzhen, Sci & Technol Dept, Shenzhen, Peoples R China.
[Schindler, Detlev] Univ Wurzburg, Inst Human Genet, D-97070 Wurzburg, Germany.
[Schwarz, Klaus] German Red Cross Blood Serv Baden Wurttemberg, Inst Clin Transfus Med & Immunogenet Ulm, Hessen, Germany.
[Grimbacher, Bodo] UCL, Inst Immun & Transplantat, London, England.
RP Grimbacher, B (reprint author), Univ Freiburg, Med Ctr, CCI, Engesserstr 4, D-79108 Freiburg, Germany.
EM bodo.grimbacher@uniklinik-freiburg.de
FU German Federal Ministry of Education and Research [BMBF 01EO1303];
Intramural Research Program of the National Institutes of Health,
National Library of Medicine; MOTIVATE program of the medical faculty
Freiburg - Else Kroner Fresenius Foundation; Deutsche Jose Carreras
Leukamie Stiftung [DJCLS R10/34f]; Swedish Research Council; Swedish
Cancer Society; Schroeder-Kurth fund
FX This study was supported by the German Federal Ministry of Education and
Research (BMBF 01EO1303). The authors are responsible for the contents
of this publication. This research was supported in part by the
Intramural Research Program of the National Institutes of Health,
National Library of Medicine. T.V. received funding from the MOTIVATE
program of the medical faculty Freiburg sponsored by the Else Kroner
Fresenius Foundation. M.D.V. is a Helmholtz Young Investigator
(Helmholtz Association, Germany). P.F. received funds from the Deutsche
Jose Carreras Leukamie Stiftung (DJCLS R10/34f). Q.P.H, A.B. and L.H.
received grants from the Swedish Research Council and the Swedish Cancer
Society. D.S.'s group was supported by the Schroeder-Kurth fund.
NR 43
TC 8
Z9 8
U1 4
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD DEC 20
PY 2015
VL 24
IS 25
BP 7361
EP 7372
DI 10.1093/hmg/ddv437
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2XI
UT WOS:000368373600017
PM 26476407
ER
PT J
AU Qian, DC
Byun, JY
Han, YH
Greene, CS
Field, JK
Hung, RJ
Brhane, Y
Mclaughlin, JR
Fehringer, G
Landi, MT
Rosenberger, A
Bickeboller, H
Malhotra, J
Risch, A
Heinrich, J
Hunter, DJ
Henderson, BE
Haiman, CA
Schumacher, FR
Eeles, RA
Easton, DF
Seminara, D
Amos, CI
AF Qian, David C.
Byun, Jinyoung
Han, Younghun
Greene, Casey S.
Field, John K.
Hung, Rayjean J.
Brhane, Yonathan
Mclaughlin, John R.
Fehringer, Gordon
Landi, Maria Teresa
Rosenberger, Albert
Bickeboeller, Heike
Malhotra, Jyoti
Risch, Angela
Heinrich, Joachim
Hunter, David J.
Henderson, Brian E.
Haiman, Christopher A.
Schumacher, Fredrick R.
Eeles, Rosalind A.
Easton, Douglas F.
Seminara, Daniela
Amos, Christopher I.
TI Identification of shared and unique susceptibility pathways among
cancers of the lung, breast, and prostate from genome-wide association
studies and tissue-specific protein interactions
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MOLECULAR INTERACTION DATABASE; BASE-LINE CHARACTERISTICS; TUMOR
MICROENVIRONMENT; ALZHEIMERS-DISEASE; SIGNALING PATHWAYS; GENETIC
INSIGHTS; SYSTEMS-APPROACH; EXPRESSION DATA; RISK-FACTORS; LOCI
AB Results from genome-wide association studies (GWAS) have indicated that strong single-gene effects are the exception, not the rule, for most diseases. We assessed the joint effects of germline genetic variations through a pathway-based approach that considers the tissue-specific contexts of GWAS findings. From GWAS meta-analyses of lung cancer (12 160 cases/16 838 controls), breast cancer (15 748 cases/18 084 controls) and prostate cancer (14 160 cases/12 724 controls) in individuals of European ancestry, we determined the tissue-specific interaction networks of proteins expressed from genes that are likely to be affected by disease-associated variants. Reactome pathways exhibiting enrichment of proteins from each network were compared across the cancers. Our results show that pathways associated with all three cancers tend to be broad cellular processes required for growth and survival. Significant examples include the nerve growth factor (P = 7.86 x 10(-33)), epidermal growth factor (P = 1.18 x 10(-31)) and fibroblast growth factor (P = 2.47 x 10(-31)) signaling pathways. However, within these shared pathways, the genes that influence risk largely differ by cancer. Pathways found to be unique for a single cancer focus on more specific cellular functions, such as interleukin signaling in lung cancer (P = 1.69 x 10(-15)), apoptosis initiation by Bad in breast cancer (P = 3.14 x 10(-9)) and cellular responses to hypoxia in prostate cancer (P = 2.14 x 10(-9)). We present the largest comparative cross-cancer pathway analysis of GWAS to date. Our approach can also be applied to the study of inherited mechanisms underlying risk across multiple diseases in general.
C1 [Qian, David C.; Byun, Jinyoung; Han, Younghun; Amos, Christopher I.] Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Hanover, NH 03755 USA.
[Greene, Casey S.] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Field, John K.] Univ Liverpool, Dept Mol & Clin Canc Med, Canc Res Ctr, Liverpool L69 3GA, Merseyside, England.
[Hung, Rayjean J.; Brhane, Yonathan; Fehringer, Gordon] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Mclaughlin, John R.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[Landi, Maria Teresa; Seminara, Daniela] NCI, NIH, Bethesda, MD 20892 USA.
[Rosenberger, Albert; Bickeboeller, Heike] Univ Med Ctr Groningen, Dept Genet Epidemiol, D-37099 Gottingen, Germany.
[Malhotra, Jyoti] Icahn Sch Med Mt Sinai, Div Hematol & Oncol, New York, NY 10029 USA.
[Risch, Angela] German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-69120 Heidelberg, Germany.
[Heinrich, Joachim] German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
[Hunter, David J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Henderson, Brian E.; Haiman, Christopher A.; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Eeles, Rosalind A.] Inst Canc Res, Dept Canc Genet, London SW7 3RP, England.
[Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
RP Amos, CI (reprint author), Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Hanover, NH 03755 USA.
EM christopher.i.amos@dartmouth.edu
RI Hung, Rayjean/A-7439-2013; Risch, Angela/H-2669-2013
OI Eeles, Rosalind/0000-0002-3698-6241; Risch, Angela/0000-0002-8026-5505
FU National Cancer Institute [U19 CA148127, U19 CA148537, U19 CA148065];
National Science Foundation; Kimball Union Academy [DGE-0947790]
FX This work was supported by the National Cancer Institute (U19 CA148127,
U19 CA148537, U19 CA148065), the National Science Foundation
Graduate-K12 Fellowship in collaboration with Kimball Union Academy
(DGE-0947790 to D.C.Q.), and an anonymous donor to the Geisel School of
Medicine at Dartmouth.
NR 142
TC 4
Z9 4
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD DEC 20
PY 2015
VL 24
IS 25
BP 7406
EP 7420
DI 10.1093/hmg/ddv440
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2XI
UT WOS:000368373600020
PM 26483192
ER
PT J
AU Catenacci, DVT
Junttila, MR
Karrison, T
Bahary, N
Horiba, MN
Nattam, SR
Marsh, R
Wallace, J
Kozloff, M
Rajdev, L
Cohen, D
Wade, J
Sleckman, B
Lenz, HJ
Stiff, P
Kumar, P
Xu, P
Henderson, L
Takebe, N
Salgia, R
Wang, X
Stadler, WM
de Sauvage, FJ
Kindler, HL
AF Catenacci, Daniel V. T.
Junttila, Melissa R.
Karrison, Theodore
Bahary, Nathan
Horiba, Margit N.
Nattam, Sreenivasa R.
Marsh, Robert
Wallace, James
Kozloff, Mark
Rajdev, Lakshmi
Cohen, Deirdre
Wade, James
Sleckman, Bethany
Lenz, Heinz-Josef
Stiff, Patrick
Kumar, Pankaj
Xu, Peng
Henderson, Les
Takebe, Naoko
Salgia, Ravi
Wang, Xi
Stadler, Walter M.
de Sauvage, Frederic J.
Kindler, Hedy L.
TI Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib,
a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SMALL-MOLECULE INHIBITOR; ENGINEERED MOUSE MODELS; DUCTAL
ADENOCARCINOMA; SIGNALING PATHWAY; III TRIAL; CELLS; ANGIOGENESIS;
FIBROBLASTS; GDC-0449; SURVIVAL
AB Purpose
Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in >70% of pancreatic cancers (PCs). We investigated the impact of vismodegib, an SHH antagonist, plus gemcitabine (GV) or gemcitabine plus placebo (GP) in a multicenter phase Ib/randomized phase II trial and preclinical PC models.
Patients and Methods
Patients with PC not amenable to curative therapy who had received no prior therapy for metastatic disease and had Karnofsky performance score >= 80 were enrolled. Patients were randomly assigned in a one-to-one ratio to GV or GP. The primary end point was progression-free-survival (PFS). Exploratory correlative studies included serial SHH serum levels and contrast perfusion computed tomography imaging. To further investigate putative biologic mechanisms of SMO inhibition, two autochthonous pancreatic cancer models (Kras(G12D); p16/p19(fl/fl); Pdx1-Cre and Kras(G12D); p53(R270H/wt); Pdx1-Cre) were studied.
Results
No safety issues were identified in the phase Ib portion (n = 7), and the phase II study enrolled 106 evaluable patients (n = 53 in each arm). Median PFS was 4.0 and 2.5 months for GV and GP arms, respectively (95% CI, 2.5 to 5.3 and 1.9 to 3.8, respectively; adjusted hazard ratio, 0.81; 95% CI, 0.54 to 1.21; P = .30). Median overall survival (OS) was 6.9 and 6.1 months for GV and GP arms, respectively (95% CI, 5.8 to 8.0 and 5.0 to 8.0, respectively; adjusted hazard ratio, 1.04; 95% CI, 0.69 to 1.58; P = .84). Response rates were not significantly different. There were no significant associations between correlative markers and overall response rate, PFS, or OS. Preclinical trials revealed no significant differences with vismodegib in drug delivery, tumor growth rate, or OS in either model.
Conclusion
The addition of vismodegib to gemcitabine in an unselected cohort did not improve overall response rate, PFS, or OS in patients with metastatic PC. Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib. (C) 2015 by American Society of Clinical Oncology.
C1 [Catenacci, Daniel V. T.; Karrison, Theodore; Wallace, James; Kozloff, Mark; Xu, Peng; Henderson, Les; Salgia, Ravi; Stadler, Walter M.; Kindler, Hedy L.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Stiff, Patrick] Loyola Univ, Med Ctr, Chicago, IL 60611 USA.
[Marsh, Robert] Northshore Univ Hlth Syst, Evanston, IL USA.
[Wallace, James; Kozloff, Mark] Ingalls Hosp, Harvey, IL USA.
[Wade, James] Decatur Mem Hosp, Decatur, GA USA.
[Kumar, Pankaj] Oncol Hematol Associates, Peoria, IL USA.
[Junttila, Melissa R.; Wang, Xi; de Sauvage, Frederic J.] Genentech Inc, San Francisco, CA 94080 USA.
[Lenz, Heinz-Josef] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Bahary, Nathan] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Horiba, Margit N.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Nattam, Sreenivasa R.] Ft Wayne Med Oncol Hematol, Ft Wayne, IN USA.
[Rajdev, Lakshmi] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Cohen, Deirdre] NYU, Ctr Canc, New York, NY USA.
[Sleckman, Bethany] St Johns Mercy Med Ctr, St Louis, MO 63141 USA.
[Takebe, Naoko] NCI, NIH, Bethesda, MD 20892 USA.
RP Catenacci, DVT (reprint author), Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 South Maryland Ave,MC 2115, Chicago, IL 60637 USA.
EM dcatenac@medicine.bsd.uchicago.edu
OI Cohen, Deirdre/0000-0002-6178-9266
FU National Cancer Institute under the American Recovery and Reinvestment
Act [N01-CM-62201]
FX Supported by National Cancer Institute Grant No. N01-CM-62201 under the
American Recovery and Reinvestment Act of 2009.
NR 54
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Z9 22
U1 2
U2 8
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 DEC 20
PY 2015
VL 33
IS 36
BP 4284
EP +
DI 10.1200/JCO.2015.62.8719
PG 11
WC Oncology
SC Oncology
GA CY8GX
UT WOS:000366647900007
PM 26527777
ER
PT J
AU Goodfellow, PJ
Billingsley, CC
Lankes, HA
Ali, S
Cohn, DE
Broaddus, RJ
Ramirez, N
Pritchard, CC
Hampel, H
Chassen, AS
Simmons, LV
Schmidt, AP
Gao, F
Brinton, LA
Backes, F
Landrum, LM
Geller, MA
DiSilvestro, PA
Pearl, ML
Lele, SB
Powell, MA
Zaino, RJ
Mutch, D
AF Goodfellow, Paul J.
Billingsley, Caroline C.
Lankes, Heather A.
Ali, Shamshad
Cohn, David E.
Broaddus, Russell J.
Ramirez, Nilsa
Pritchard, Colin C.
Hampel, Heather
Chassen, Alexis S.
Simmons, Luke V.
Schmidt, Amy P.
Gao, Feng
Brinton, Louise A.
Backes, Floor
Landrum, Lisa M.
Geller, Melissa A.
DiSilvestro, Paul A.
Pearl, Michael L.
Lele, Shashikant B.
Powell, Matthew A.
Zaino, Richard J.
Mutch, David
TI Combined Microsatellite Instability, MLH1 Methylation Analysis, and
Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers
From GOG210: An NRG Oncology and Gynecologic Oncology Group Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; GERMLINE MUTATION;
FAMILY-HISTORY; MSH6 MUTATION; RISK; WOMEN; IDENTIFICATION; PMS2;
PERFORMANCE
AB Purpose
The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS.
Patients and Methods
ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women.
Results
Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years.
Conclusion
Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age >60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age <60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease. (C) 2015 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 3.0 License
C1 [Goodfellow, Paul J.; Billingsley, Caroline C.; Cohn, David E.; Hampel, Heather; Chassen, Alexis S.; Simmons, Luke V.; Backes, Floor] Ohio State Univ, Columbus, OH 43210 USA.
[Ramirez, Nilsa] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.
[Ali, Shamshad; Hampel, Heather] NRG Oncol Stat & Data Management Ctr, Columbus, OH USA.
[Lele, Shashikant B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Pearl, Michael L.] Stony Brook Univ Hosp, Stony Brook, NY USA.
[Broaddus, Russell J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Pritchard, Colin C.] Univ Washington, Seattle, WA 98195 USA.
[Schmidt, Amy P.; Gao, Feng; Geller, Melissa A.; Mutch, David] Washington Univ, Sch Med, St Louis, MO USA.
[Brinton, Louise A.] NCI, Washington, DC USA.
[Landrum, Lisa M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Geller, Melissa A.] Univ Minnesota, Minneapolis, MN USA.
[DiSilvestro, Paul A.] Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA.
[Zaino, Richard J.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA.
RP Goodfellow, PJ (reprint author), Ohio State Univ, Ctr Comprehens Canc, Obstet & Gynecol, 460 W 12th Ave,BRT 808, Columbus, OH 43210 USA.
EM paul.goodfellow@osumc.edu
OI Backes, Floor/0000-0002-9225-6913
FU National Institutes of Health/National Cancer Institute [P50 CA134254];
Barnes-Jewish Hospital and Siteman Cancer Center; Ohio State University
James Comprehensive Cancer Center; National Cancer Institute [CA 27469];
GOG Statistical Office [CA37517]; NRG Oncology Group [1 U10 CA180822];
GOG Tissue Bank [U10 CA27469, U24 CA114793, U10 CA180868]
FX Supported by Grant No. P50 CA134254 from the National Institutes of
Health/National Cancer Institute; by Barnes-Jewish Hospital and Siteman
Cancer Center; by Ohio State University James Comprehensive Cancer
Center; and by National Cancer Institute grants to Gynecologic Oncology
Group (GOG) Administrative Office (No. CA 27469), GOG Statistical Office
(No. CA37517), NRG Oncology Group (No. 1 U10 CA180822), and GOG Tissue
Bank (No. U10 CA27469, U24 CA114793, and U10 CA180868).
NR 36
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Z9 20
U1 1
U2 2
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 DEC 20
PY 2015
VL 33
IS 36
BP 4301
EP +
DI 10.1200/JCO.2015.63.9518
PG 13
WC Oncology
SC Oncology
GA CY8GX
UT WOS:000366647900009
PM 26552419
ER
PT J
AU Lauer, MS
Krumholz, HM
Topol, EJ
AF Lauer, Michael S.
Krumholz, Harlan M.
Topol, Eric J.
TI Time for a prepublication culture in clinical research?
SO LANCET
LA English
DT Editorial Material
ID INGELFINGER RULE; SCIENCE
C1 [Lauer, Michael S.] NIH, Off Extramural Res, Bethesda, MD 20892 USA.
[Krumholz, Harlan M.] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Topol, Eric J.] Scripps Translat Sci Inst, La Jolla, CA USA.
RP Lauer, MS (reprint author), NIH, Off Extramural Res, Bldg 10, Bethesda, MD 20892 USA.
EM michael.lauer@nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 12
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 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD DEC 19
PY 2015
VL 386
IS 10012
BP 2447
EP 2449
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CZ1LD
UT WOS:000366866400005
PM 26738703
ER
PT J
AU Khoutorsky, A
Bonin, RP
Sorge, RE
Gkogkas, CG
Pawlowski, SA
Jafarnejad, SM
Pitcher, MH
Alain, T
Perez-Sanchez, J
Salter, EW
Martin, L
Ribeiro-de-Silva, A
De Koninck, Y
Cervero, F
Mogil, JS
Sonenberg, N
AF Khoutorsky, Arkady
Bonin, Robert P.
Sorge, Robert E.
Gkogkas, Christos G.
Pawlowski, Sophie Anne
Jafarnejad, Seyed Mehdi
Pitcher, Mark H.
Alain, Tommy
Perez-Sanchez, Jimena
Salter, Eric W.
Martin, Loren
Ribeiro-de-Silva, Alfredo
De Koninck, Yves
Cervero, Fernando
Mogil, Jeffrey S.
Sonenberg, Nahum
TI Translational control of nociception via 4E-binding protein 1
SO ELIFE
LA English
DT Article
ID MAMMALIAN TARGET; REPRESSOR 4E-BP2; MICE LACKING; SPINAL-CORD; SYNAPTIC
PLASTICITY; NEUROPATHIC PAIN; EIF4F COMPLEX; ACTIVATION; RAPAMYCIN; MTOR
AB Activation of the mechanistic/mammalian target of rapamycin (mTOR) kinase in models of acute and chronic pain is strongly implicated in mediating enhanced translation and hyperalgesia. However, the molecular mechanisms by which mTOR regulates nociception remain unclear. Here we show that deletion of the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a major mTOR downstream effector, which represses elF4E activity and cap-dependent translation, leads to mechanical, but not thermal pain hypersensitivity. Mice lacking 4E-BP1 exhibit enhanced spinal cord expression of neuroligin 1, a cell-adhesion postsynaptic protein regulating excitatory synapse function, and show increased excitatory synaptic input into spinal neurons, and a lowered threshold for induction of synaptic potentiation. Pharmacological inhibition of elF4E or genetic reduction of neuroligin 1 levels normalizes the increased excitatory synaptic activity and reverses mechanical hypersensitivity. Thus, translational control by 4E-BP1 downstream of mTOR effects the expression of neuroligin 1 and excitatory synaptic transmission in the spinal cord, and thereby contributes to enhanced mechanical nociception.
C1 [Khoutorsky, Arkady; Gkogkas, Christos G.; Jafarnejad, Seyed Mehdi; Alain, Tommy; Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ, Canada.
[Khoutorsky, Arkady; Jafarnejad, Seyed Mehdi; Alain, Tommy; Sonenberg, Nahum] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ, Canada.
[Bonin, Robert P.; Perez-Sanchez, Jimena; Salter, Eric W.; De Koninck, Yves] Inst Univ St Mentale Quebec, Unite Neurosci Cellulaires & Mol, Quebec City, PQ, Canada.
[Sorge, Robert E.; Martin, Loren; Mogil, Jeffrey S.] McGill Univ, Dept Psychol, Montreal, PQ, Canada.
[Sorge, Robert E.; Pawlowski, Sophie Anne; Martin, Loren; Ribeiro-de-Silva, Alfredo; De Koninck, Yves; Cervero, Fernando; Mogil, Jeffrey S.] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
[Gkogkas, Christos G.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland.
[Gkogkas, Christos G.] Univ Edinburgh, Patrick Wild Ctr, Edinburgh, Midlothian, Scotland.
[Pawlowski, Sophie Anne; Ribeiro-de-Silva, Alfredo; De Koninck, Yves] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
[Pitcher, Mark H.] NIH, Natl Ctr Complementary & Alternat Med, Porter Neurosci Res Ctr, Bethesda, MD USA.
[De Koninck, Yves] Univ Laval, Dept Psychiat & Neurosci, Quebec City, PQ, Canada.
[Cervero, Fernando] McGill Univ, Anesthesia Res Unit, Montreal, PQ, Canada.
RP Mogil, JS (reprint author), McGill Univ, Dept Psychol, Montreal, PQ, Canada.
EM mogil@mcgill.ca; nahum.sonenberg@mcgill.ca
RI De Koninck, Yves/C-2659-2008;
OI De Koninck, Yves/0000-0002-5779-9330; Bonin, Robert/0000-0002-3287-6803;
Gkogkas, Christos/0000-0001-6281-3419
FU Canadian Institutes of Health Research [MOP-114994]; Louise and Alan
Edwards Foundation
FX Canadian Institutes of Health Research Operating grant to N. Sonenberg
(MOP-114994) Arkady Khoutorsky, Christos Gkogkas, Seyed Mehdi
Jafarnejad, Tommy Alain, Nahum Sonenberg; The Louise and Alan Edwards
Foundation An unrestricted gift to J.S. Mogil Robert E Sorge, Loren
Martin, Jeffrey S Mogil
NR 48
TC 4
Z9 4
U1 0
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 18
PY 2015
VL 4
AR e12002
DI 10.7554/eLife.12002
PG 18
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DA0VT
UT WOS:000367516400001
ER
PT J
AU Wang, HS
Iwasaki, M
Haiman, CA
Kono, S
Wilkens, LR
Keku, TO
Berndt, SI
Tsugane, S
Le Marchand, L
AF Wang, Hansong
Iwasaki, Motoki
Haiman, Christopher A.
Kono, Suminori
Wilkens, Lynne R.
Keku, Temitope O.
Berndt, Sonja I.
Tsugane, Shoichiro
Le Marchand, Loic
TI Interaction between Red Meat Intake and NAT2 Genotype in Increasing the
Risk of Colorectal Cancer in Japanese and African Americans
SO PLOS ONE
LA English
DT Article
ID HETEROCYCLIC AMINE INTAKE; GENOME-WIDE ASSOCIATION; COLON-CANCER;
CYTOCHROME-P450 1A2; CONSUMPTION; SMOKING; POLYMORPHISMS; POPULATIONS;
N-ACETYLTRANSFERASE-2; SUSCEPTIBILITY
AB Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's <= 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; P-trend = 8.0x10(-5)), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; P-trend = 0.05) and null among those with the slow phenotype (P-trend = 0.45). A similar interaction was found for NAT2 and total red meat (P-interaction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.
C1 [Wang, Hansong; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Kono, Suminori] Kyushu Univ, Grad Sch Med Sci, Dept Prevent Med, Fukuoka 812, Japan.
[Keku, Temitope O.] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Le Marchand, L (reprint author), Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
EM loic@cc.hawaii.edu
FU National Institutes of Health [R01 CA126895, CA126895-S01, U01 CA164973,
CA63464, CA54281, CA1326792, CA148085, HG004726, P30 DK 034987, R01
CA66635]; Department of Defense Breast Cancer Research Program Era of
Hope Scholar Award [W81XWH-08-1-0383]; National Cancer Center Research
and Development Fund; Ministry of Health, Labor and Welfare of Japan
FX The colorectal cancer GWAS in Japanese and African Americans was
supported by grants from the National Institutes of Health (R01 CA126895
and CA126895-S01). The Multiethnic Cohort Study is supported by the
National Institutes of Health (U01 CA164973). The genotyping of African
American male and female controls was supported by the National
Institutes of Health (CA63464, CA54281, CA1326792, CA148085 and
HG004726); and a Department of Defense Breast Cancer Research Program
Era of Hope Scholar Award [W81XWH-08-1-0383 to CAH]. JPHC was supported
by the National Cancer Center Research and Development Fund (since 2011)
and a Grant-in-Aid for Cancer Research (from 1989 to 2010) from the
Ministry of Health, Labor and Welfare of Japan. The UNC study was
supported the National Institutes of Health (P30 DK 034987 and R01
CA66635). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 1
Z9 1
U1 3
U2 14
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 DEC 18
PY 2015
VL 10
IS 12
AR e0144955
DI 10.1371/journal.pone.0144955
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9KM
UT WOS:000366725800025
PM 26683305
ER
PT J
AU Li, ZC
Hu, ML
Zong, XF
He, Y
Wang, D
Dai, LL
Dong, M
Zhou, J
Cao, HB
Lv, LX
Chen, XG
Tang, JS
AF Li, Zongchang
Hu, Maolin
Zong, Xiaofen
He, Ying
Wang, Dong
Dai, Lulin
Dong, Min
Zhou, Jun
Cao, Hongbao
Lv, Luxian
Chen, Xiaogang
Tang, Jinsong
TI Association of telomere length and mitochondrial DNA copy number with
risperidone treatment response in first-episode antipsychotic-naive
schizophrenia
SO SCIENTIFIC REPORTS
LA English
DT Article
ID BIPOLAR DISORDER; PSYCHIATRIC-DISORDERS; GENE-EXPRESSION; COMMON
DELETION; COMPLEX-I; STRESS; LONGER; DAMAGE; INHIBITION; STRIATUM
AB Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naive SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (N = 46) and Non-Responders (N = 43) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (beta = -0.108, p = 0.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (beta = -0.178, p = 0.001), and longer telomere length (beta = 0.111, p = 0.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial eta(2) = 0.125, p = 0.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients.
C1 [Li, Zongchang; Hu, Maolin; Zong, Xiaofen; He, Ying; Wang, Dong; Dai, Lulin; Dong, Min; Zhou, Jun; Chen, Xiaogang; Tang, Jinsong] Cent S Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410011, Hunan, Peoples R China.
[Li, Zongchang; Chen, Xiaogang] Cent S Univ, State Key Lab Med Genet, Changsha 410011, Hunan, Peoples R China.
[Cao, Hongbao; Tang, Jinsong] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20892 USA.
[Chen, Xiaogang; Tang, Jinsong] Natl Clin Res Ctr Psychiat & Psychol Dis, Changsha, Hunan, Peoples R China.
[Lv, Luxian] Xinxiang Med Univ, Affiliated Hosp 2, Dept Psychiat, Xinxiang, Henan, Peoples R China.
RP Chen, XG (reprint author), Cent S Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410011, Hunan, Peoples R China.
EM chenxghn@gmail.com; tangjinsonghn@gmail.com
FU National Natural Science Foundation of China [81271484, 81471361,
81371480]; National Key Basic Research and Development Program (973)
[2012CB517904]
FX The study was supported by the National Natural Science Foundation of
China (81271484 and 81471361 to X.C, Grant No. 81371480 to J.T), the
National Key Basic Research and Development Program (973) ( Grant No.
2012CB517904 to X.C). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 2
Z9 2
U1 3
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 DEC 18
PY 2015
VL 5
AR 18553
DI 10.1038/srep18553
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ4GA
UT WOS:000367060300001
PM 26680692
ER
PT J
AU Xie, XQ
Yang, P
Zhang, Y
Zhang, P
Wang, LP
Ding, YH
Yang, M
Tong, Q
Cheng, HZ
Ji, Q
McGuire, T
Yuan, WP
Cheng, T
Gao, YD
AF Xie, Xiang-Qun
Yang, Peng
Zhang, Yu
Zhang, Peng
Wang, Liping
Ding, Yahui
Yang, Ming
Tong, Qin
Cheng, Haizi
Ji, Qing
McGuire, Terence
Yuan, Weiping
Cheng, Tao
Gao, Yingdai
TI Discovery of novel INK4C small-molecule inhibitors to promote human and
murine hematopoietic stem cell ex vivo expansion
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CORD BLOOD TRANSPLANTATION; OSTEOCLAST INHIBITORS; BIOLOGICAL
EVALUATION; INVERSE AGONISTS; CB2 RECEPTOR; SELF-RENEWAL; P18(INK4C);
DIFFERENTIATION; RECONSTITUTION; OPTIMIZATION
AB Hematopoietic stem cells (HSCs) have emerged as promising therapeutic cell sources for high-risk hematological malignancies and immune disorders. However, their clinical use is limited by the inability to expand these cells ex vivo. Therefore, there is an urgent need to identify specific targets and effective probes that can expand HSCs. Here we report a novel class of INK4C (p18(INK4C) or p18) small molecule inhibitors (p18SMIs), which were initially found by in silico 3D screening. We identified a lead p18 inhibitor, XIE18-6, confirmed its p18-targeting specificity and bioactivity of promoting HSCs expansion, and then performed structure-activity relationship (SAR) studies by synthesizing a series of analogs of XIE18-6. Among these, compound 40 showed the most potent bioactivity in HSCs expansion (ED50 = 5.21 nM). We confirmed that compound 40 promoted expansion of both murine and human HSCs, and also confirmed its p18-targeting specificity. Notably, compound 40 did not show significant cytotoxicity toward 32D cells or HSCs, nor did it augment leukemia cell proliferation. Taken together, our newly discovered p18SMIs represent novel chemical agents for murine and human HSCs ex vivo expansion and also can be used as valuable chemical probes for further HSC biology research towards promising utility for therapeutic purposes.
C1 [Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA.
[Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, Sch Pharm, Computat Chem Genom Screening Ctr, Pittsburgh, PA 15260 USA.
[Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, NIH, Natl Ctr Excellence Computat Drug Abuse Res, Pittsburgh, PA 15260 USA.
[Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA 15260 USA.
[Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, Sch Med, Dept Computat Biol, Pittsburgh, PA 15260 USA.
[Xie, Xiang-Qun; Yang, Peng; Zhang, Peng; Wang, Liping; Tong, Qin; Cheng, Haizi; McGuire, Terence] Univ Pittsburgh, Sch Med, Dept Struct Biol, Pittsburgh, PA 15260 USA.
[Zhang, Yu; Ding, Yahui; Yang, Ming; Ji, Qing; Yuan, Weiping; Cheng, Tao; Gao, Yingdai] Chinese Acad Med Sci, Inst Hematol, Key Lab Expt Hematol, Tianjin 300020, Peoples R China.
[Zhang, Yu; Ding, Yahui; Yang, Ming; Ji, Qing; Yuan, Weiping; Cheng, Tao; Gao, Yingdai] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin 300020, Peoples R China.
[Zhang, Yu; Ding, Yahui; Yang, Ming; Ji, Qing; Yuan, Weiping; Cheng, Tao; Gao, Yingdai] Peking Union Med Coll, Tianjin 300020, Peoples R China.
RP Xie, XQ (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA.
EM xix15@pitt.edu; chengtao@ihcams.ac.cn; ydgao@ihcams.ac.cn
FU NIH [R21HL1096541, P30DA035778]; National Basic Research Program of
China [2011CB964800, 2012CB966600]; National Natural Science Foundation
of China [NSFC 81421002, 81170465]; key technologies R & D program of
Tianjin [13RCGFSF19500]
FX Authors would like to acknowledge the funding support to their
laboratories from NIH R21HL1096541 (Xie), P30DA035778 (Xie) and the
National Basic Research Program of China (NO. 2011CB964800,
2012CB966600), the National Natural Science Foundation of China (NSFC
81421002 and 81170465), the key technologies R & D program of Tianjin
(13RCGFSF19500).
NR 40
TC 0
Z9 1
U1 4
U2 14
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 DEC 18
PY 2015
VL 5
AR 18115
DI 10.1038/srep18115
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ4AT
UT WOS:000367046000001
PM 26681454
ER
PT J
AU Keadle, SK
Arem, H
Moore, SC
Sampson, JN
Matthews, CE
AF Keadle, Sarah Kozey
Arem, Hannah
Moore, Steven C.
Sampson, Joshua N.
Matthews, Charles E.
TI Impact of changes in television viewing time and physical activity on
longevity: a prospective cohort study
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Sedentary behavior; Television; Mortality; Prospective cohort
ID ALL-CAUSE MORTALITY; SEDENTARY BEHAVIORS; OLDER-ADULTS; UNITED-STATES;
CARDIOVASCULAR-DISEASE; ACTIVITY QUESTIONNAIRE; SITTING TIME;
LIFE-STYLE; VALIDITY; RISK
AB Background: Television viewing is a highly prevalent sedentary behavior among older adults, yet the mortality risks associated with hours of daily viewing over many years and whether increasing or decreasing viewing time affects mortality is unclear. This study examined: 1) the long-term association between mortality and daily viewing time; 2) the influence of reducing and increasing in television viewing time on longevity and 3) combined effects of television viewing and moderate-to-vigorous physical activity (MVPA) on longevity.
Methods: Participants included 165,087 adults in the NIH-AARP Diet and Health (aged 50-71 yrs) who completed questionnaires at two-time-points (Time 1: 1994-1996, and Time 2: 2004-2006) and were followed until death or December 31, 2011. Multivariable-adjusted Cox proportional hazards regression was used to estimate Hazard Ratios and 95 % confidence intervals (CI) with self-reported television viewing and MVPA and all-cause mortality.
Results: Over 6.6 years of follow-up, there were 20,104 deaths. Compared to adults who watched < 3 h/day of television at both time points, mortality risk was 28 % greater (CI:1.21,1.34) those who watched 5+ h/day at both time-points. Decreasing television viewing from 5+ h/day to 3-4 h/d was associated with a 15 % reduction in mortality risk (CI:0.80, 0.91) and decreasing to <3 h/day resulted in an 12 % lower risk (CI:0.79, 0.97). Conversely, adults who increased their viewing time to 3-4 h/day had an 17 % greater mortality risk (CI:1.10, 1.24) and those who increased to 5+ h/day had a 45 % greater risk (CI:1.32, 1.58), compared to those who consistently watched < 3 h/day. The lowest mortality risk was observed in those who were consistently active and watched < 3 h/day of television.
Conclusions: We confirm that prolonged television viewing time was associated with greater mortality in older adults and demonstrate for the first time that individuals who reduced the amount of time they spent watching television had lower mortality. Our findings provide new evidence to support behavioral interventions that seek to reduce sedentary television viewing in favor of more physically active pursuits, preferably MVPA. Given the high prevalence of physical inactivity and prolonged television viewing in older adults, favorable changes in these two modifiable behaviors could have substantial public health impact.
C1 [Keadle, Sarah Kozey; Arem, Hannah; Moore, Steven C.; Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Keadle, Sarah Kozey] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sampson, Joshua N.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Keadle, SK (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM sarah.keadle@nih.gov
RI Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Keadle, Sarah/0000-0002-9569-9306
FU National Cancer Institute, National Institute of Health
FX This research was supported in part by the Intramural Research Program
at the National Cancer Institute, National Institute of Health.
NR 42
TC 1
Z9 1
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD DEC 18
PY 2015
VL 12
DI 10.1186/s12966-015-0315-0
PG 11
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA CY8UP
UT WOS:000366684200001
PM 26678502
ER
PT J
AU Li, SJ
Liang, YH
Mariano, J
Metzger, MB
Stringer, DK
Hristova, VA
Li, J
Randazzo, PA
Tsai, YC
Ji, XH
Weissman, AM
AF Li, Shengjian
Liang, Yu-He
Mariano, Jennifer
Metzger, Meredith B.
Stringer, Daniel K.
Hristova, Ventzislava A.
Li, Jess
Randazzo, Paul A.
Tsai, Yien Che
Ji, Xinhua
Weissman, Allan M.
TI Insights into Ubiquitination from the Unique Clamp-like Binding of the
RING E3 AO7 to the E2 UbcH5B
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CONJUGATING ENZYME; ALLOSTERIC ACTIVATION; NONCOVALENT UBIQUITIN;
STRUCTURAL BASIS; CHAIN FORMATION; LIGASE COMPLEX; PROTEIN LIGASE; SUMO
CHAIN; DOMAIN; MECHANISM
AB RING proteins constitute the largest class of E3 ubiquitin ligases. Unlike most RINGs, AO7 (RNF25) binds the E2 ubiquitin-conjugating enzyme, UbcH5B (UBE2D2), with strikingly high affinity. We have defined, by co-crystallization, the distinctive means by which AO7 binds UbcH5B. AO7 contains a structurally unique UbcH5B binding region (U5BR) that is connected by an 11-amino acid linker to its RING domain, forming a clamp surrounding the E2. The U5BR interacts extensively with a region of UbcH5B that is distinct from both the active site and the RING-interacting region, referred to as the backside of the E2. An apparent paradox is that the high-affinity binding of the AO7 clamp to UbcH5B, which is dependent on the U5BR, decreases the rate of ubiquitination. We establish that this is a consequence of blocking the stimulatory, non-covalent, binding of ubiquitin to the backside of UbcH5B. Interestingly, when non-covalent backside ubiquitin binding cannot occur, the AO7 clamp now enhances the rate of ubiquitination. The high-affinity binding of the AO7 clamp to UbcH5B has also allowed for the co-crystallization of previously described and functionally important RING mutants at the RING-E2 interface. We show that mutations having marked effects on function only minimally affect the intermolecular interactions between the AO7 RING and UbcH5B, establishing a high degree of complexity in activation through the RING-E2 interface.
C1 [Li, Shengjian; Mariano, Jennifer; Metzger, Meredith B.; Stringer, Daniel K.; Hristova, Ventzislava A.; Tsai, Yien Che; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Liang, Yu-He; Ji, Xinhua] NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Li, Jess] NCI, Struct Biophys Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Randazzo, Paul A.] NCI, Lab Cell & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
EM jix@mail.nih.gov; weissmaa@mail.nih.gov
OI Tsai, Yien Che/0000-0001-9624-1092
FU Werner H. Kristen Student Internship Program
FX We thank Marzena Dyba and Sergey Tarasov of the Biophysics Resource,
Structural Biophysics Laboratory, Center for Cancer Research for
assistance with MST and Mei Yang for providing reagents. Some
experiments were carried out with assistance from Erin Marshall and Alex
Roumeliotis (both supported by the Werner H. Kristen Student Internship
Program). We thank R. Andrew Byrd, Ranabir Das, and Stanley Lipkowitz
for invaluable discussions and critical reading of this manuscript.
Wealso thank Ranabir Das and R. Andrew Byrd for NMR analyses and Gary
Pauly for FlAsH-EDT2.
NR 66
TC 6
Z9 6
U1 0
U2 4
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 DEC 18
PY 2015
VL 290
IS 51
BP 30225
EP 30239
DI 10.1074/jbc.M115.685867
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CY9PG
UT WOS:000366738200003
PM 26475854
ER
PT J
AU Komarow, HD
Sokolic, R
Hershfield, MS
Kohn, DB
Young, M
Metcalfe, DD
Candotti, F
AF Komarow, Hirsh D.
Sokolic, Robert
Hershfield, Michael S.
Kohn, Donald B.
Young, Michael
Metcalfe, Dean D.
Candotti, Fabio
TI Impulse oscillometry identifies peripheral airway dysfunction in
children with adenosine deaminase deficiency
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Article
DE Adenosine deaminase deficiency; SCID; Children; Pulmonary dysfunction;
Impulse oscillometry; Spirometry
ID PULMONARY ALVEOLAR PROTEINOSIS; MICE
AB Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies.
C1 [Komarow, Hirsh D.; Metcalfe, Dean D.] NIAID, LAD, NIH, Bethesda, MD 20892 USA.
[Sokolic, Robert; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
[Hershfield, Michael S.] Duke Univ, Sch Med, Dept Biochem, Durham, NC USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Young, Michael] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Clin Res, Frederick, MD 21702 USA.
[Candotti, Fabio] Univ Lausanne Hosp, Div Immunol & Allergy, CH-1101 Lausanne, Switzerland.
RP Komarow, HD (reprint author), NIAID, LAD, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU Division of Intramural Research, NIAID; NHGRI, NIH; UNIL-CHUV grant
[CGRB 29583]; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This work was supported by the Division of Intramural Research, NIAID
and NHGRI, NIH and by an UNIL-CHUV grant (CGRB 29583 to F.C.). Support
by M.Y. for this project was funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E and [in part] by the National
Institute of Allergy and Infectious Diseases. 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. Authors state no conflict of interest.
NR 10
TC 1
Z9 1
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD DEC 18
PY 2015
VL 10
AR 159
DI 10.1186/s13023-015-0365-z
PG 5
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA CZ0MF
UT WOS:000366798600001
PM 26682746
ER
PT J
AU Murray, EA
Moylan, EJ
Saleem, KS
Basile, BM
Turchi, J
AF Murray, Elisabeth A.
Moylan, Emily J.
Saleem, Kadharbatcha S.
Basile, Benjamin M.
Turchi, Janita
TI Specialized areas for value updating and goal selection in the primate
orbitofrontal cortex
SO ELIFE
LA English
DT Article
ID ORBITAL PREFRONTAL CORTEX; RHESUS-MONKEYS; MACAQUE MONKEY; FRONTAL-LOBE;
REWARD VALUE; REINFORCER DEVALUATION; CONNECTIONAL NETWORKS;
NEURONAL-ACTIVITY; DECISION-MAKING; GUIDED BEHAVIOR
AB The macaque orbitofrontal cortex (OFC) is essential for selecting goals based on current, updated values of expected reward outcomes. As monkeys consume a given type of reward to satiety, its value diminishes, and OFC damage impairs the ability to shift goal choices away from devalued outcomes. To examine the contributions of OFCs components to goal selection, we reversibly inactivated either its anterior (area 11) or posterior (area 13) parts. We found that neurons in area 13 must be active during the selective satiation procedure to enable the updating of outcome valuations. After this updating has occurred, however, area 13 is not needed to select goals based on this knowledge. In contrast, neurons in area 11 do not need to be active during the value-updating process. Instead, inactivation of this area during choices causes an impairment. These findings demonstrate selective and complementary specializations within the OFC.
C1 [Murray, Elisabeth A.; Moylan, Emily J.; Saleem, Kadharbatcha S.; Basile, Benjamin M.; Turchi, Janita] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Murray, EA (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
EM murraye@mail.nih.gov
OI Murray, Elisabeth/0000-0003-1450-1642
FU National Institute of Mental Health [MH002887-10-LN]
FX National Institute of Mental Health MH002887-10-LN Elisabeth A Murray
NR 59
TC 2
Z9 2
U1 2
U2 5
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 17
PY 2015
VL 4
AR e11695
DI 10.7554/eLife.11695
PG 18
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ1HP
UT WOS:000373954200001
ER
PT J
AU Chang, CM
Su, H
Zhang, DH
Wang, YS
Shen, QH
Liu, B
Huang, R
Zhou, TH
Peng, C
Wong, CCL
Shen, HM
Lippincott-Schwartz, J
Liu, W
AF Chang, Chunmei
Su, Hua
Zhang, Danhong
Wang, Yusha
Shen, Qiuhong
Liu, Bo
Huang, Rui
Zhou, Tianhua
Peng, Chao
Wong, Catherine C. L.
Shen, Han-Ming
Lippincott-Schwartz, Jennifer
Liu, Wei
TI AMPK-Dependent Phosphorylation of GAPDH Triggers Sirt1 Activation and Is
Necessary for Autophagy upon Glucose Starvation
SO MOLECULAR CELL
LA English
DT Article
ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; NUCLEAR TRANSLOCATION;
CELL-DEATH; DEACETYLASE SIRT1; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE;
MITOCHONDRIAL AUTOPHAGY; MEDIATED REGULATION; MAMMALIAN-CELLS;
APOPTOSIS; PROTEIN
AB Eukaryotes initiate autophagy to cope with the lack of external nutrients, which requires the activation of the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase Sirtuin 1 (Sirt1). However, the mechanisms underlying the starvation-induced Sirt1 activation for autophagy initiation remain unclear. Here, we demonstrate that glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a conventional glycolytic enzyme, is a critical mediator of AMP-activated protein kinase (AMPK)-driven Sirt1 activation. Under glucose starvation, but not amino acid starvation, cytoplasmic GAPDH is phosphorylated on Ser122 by activated AMPK. This causes GAPDH to redistribute into the nucleus. Inside the nucleus, GAPDH interacts directly with Sirt1, displacing Sirt1's repressor and causing Sirt1 to become activated. Preventing this shift of GAPDH abolishes Sirt1 activation and autophagy, while enhancing it, through overexpression of nuclear-localized GAPDH, increases Sirt1 activation and autophagy. GAPDH is thus a pivotal and central regulator of autophagy under glucose deficiency, undergoing AMPK-dependent phosphorylation and nuclear translocation to activate Sirt1 deacetylase activity.
C1 [Chang, Chunmei; Su, Hua; Zhang, Danhong; Wang, Yusha; Shen, Qiuhong; Liu, Bo; Huang, Rui; Zhou, Tianhua; Liu, Wei] Zhejiang Univ, Sch Med, Program Mol & Cell Biol, Dept Biochem & Mol Biol, Hangzhou 310058, Zhejiang, Peoples R China.
[Liu, Wei] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China.
[Peng, Chao; Wong, Catherine C. L.] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China.
[Shen, Han-Ming] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore.
[Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Liu, W (reprint author), Zhejiang Univ, Sch Med, Program Mol & Cell Biol, Dept Biochem & Mol Biol, Hangzhou 310058, Zhejiang, Peoples R China.
EM liuwei666@zju.edu.cn
OI Shen, Han-Ming/0000-0001-7369-5227
FU National Natural Science Foundation of China [31171288, 31530040,
31271431]; National Basic Research Program of China [2011CB910100,
2013CB910200]
FX We are grateful to the Imaging Center of Zhejiang University School of
Medicine for assistance with confocal microscopy and electron
microscopy. We thank Tao Li for technical support in kinase assay. We
thank Dr. Zongping Xia for providing the AMPK alpha 1/alpha 2
double-knockout MEFs. This study was supported by the National Natural
Science Foundation of China (31171288, 31530040, and 31271431) and the
National Basic Research Program of China (2011CB910100 and
2013CB910200).
NR 51
TC 11
Z9 11
U1 9
U2 30
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 DEC 17
PY 2015
VL 60
IS 6
BP 930
EP 940
DI 10.1016/j.molcel.2015.10.037
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DB1TI
UT WOS:000368291500010
PM 26626483
ER
PT J
AU Mo, M
Arnaoutov, A
Dasso, M
AF Mo, Min
Arnaoutov, Alexei
Dasso, Mary
TI Phosphorylation of Xenopus p31(comet) potentiates mitotic checkpoint
exit
SO CELL CYCLE
LA English
DT Article
DE inhibitor of nuclear factor kappa-B kinase-beta; (IKK-beta); Mad2;
p31(comet); Spindle assembly checkpoint; Xenopus
ID SPINDLE-ASSEMBLY CHECKPOINT; NF-KAPPA-B; CELL-CYCLE; MAD2; ARREST
AB p31(comet) plays an important role in spindle assembly checkpoint (SAC) silencing. However, how p31(comet)'s activity is regulated remains unclear. Here we show that the timing of M-phase exit in Xenopus egg extracts (XEEs) depends upon SAC activity, even under conditions that are permissive for spindle assembly. p31(comet) antagonizes the SAC, promoting XEE progression into anaphase after spindles are fully formed. We further show that mitotic p31(comet) phosphorylation by Inhibitor of nuclear factor -B kinase- (IKK-) enhances this role in SAC silencing. Together, our findings implicate IKK- in the control of anaphase timing in XEE through p31(comet) activation and SAC downregulation.
C1 [Mo, Min; Arnaoutov, Alexei; Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM dassom@mail.nih.gov
OI Dasso, Mary/0000-0002-5410-1371; MO, MIN/0000-0003-1377-143X
FU NICHD [ZIA HD008816]
FX This study was supported by NICHD project number ZIA HD008816.
NR 27
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD DEC 17
PY 2015
VL 14
IS 24
BP 3978
EP 3985
DI 10.1080/15384101.2015.1033590
PG 8
WC Cell Biology
SC Cell Biology
GA CZ4HD
UT WOS:000367063200028
PM 25892037
ER
PT J
AU Paris, RM
Petrovas, C
Ferrando-Martinez, S
Moysi, E
Boswell, KL
Archer, E
Yamamoto, T
Ambrozak, D
Casazza, JP
Haubrich, R
Connors, M
Ake, J
Kim, JH
Koup, RA
AF Paris, Robert M.
Petrovas, Constantinos
Ferrando-Martinez, Sara
Moysi, Eirini
Boswell, Kristin L.
Archer, Eva
Yamamoto, Takuya
Ambrozak, David
Casazza, Joseph P.
Haubrich, Richard
Connors, Mark
Ake, Julie
Kim, Jerome H.
Koup, Richard A.
TI Selective Loss of Early Differentiated, Highly Functional PD1(high) CD4
T Cells with HIV Progression
SO PLOS ONE
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; DISEASE PROGRESSION; SPARING REGIMENS; TELOMERE
LENGTH; IN-VIVO; PD-1; EXHAUSTION; CTLA-4; LYMPHOCYTES; DYSFUNCTION
AB The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127(high) CD4 T cells within the early/intermediate differentiated (EI) (CD27(high)CD45RA(low)) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1(high)CTLA-4(low) CD4 T cells was found specifically in the CD127(high)CD27(high)CD45RA(low) compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1(high) compared to PD-1(low) ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1(low) EI CD4 T cells. In line with our previous findings, PD-1(high) EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.
C1 [Paris, Robert M.; Petrovas, Constantinos; Ferrando-Martinez, Sara; Moysi, Eirini; Boswell, Kristin L.; Archer, Eva; Yamamoto, Takuya; Ambrozak, David; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Moysi, Eirini] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Paris, Robert M.; Ake, Julie] US Mil HIV Res Program, Silver Spring, MD USA.
[Haubrich, Richard] Univ Calif San Diego, Div Infect Dis, Antiviral Res Ctr, San Diego, CA 92103 USA.
[Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea.
RP Petrovas, C (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM petrovasc@mail.nih.gov
OI Yamamoto, Takuya/0000-0003-3753-1211
FU Intramural Research Program of the Vaccine Research Center, National
Institutes of Allergy and Infectious Diseases, National Institutes of
Health [AI064086]; University of California San Diego Center for AIDS
Research [AI36214]; San Diego AIDS Clinical Trial Group [CTU AI69432];
U.S. Army Medical Research and Material Command (USAMRMC)
[Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases
[Y1-AI-2642-12]; Henry M. Jackson Foundation for the Advancement of
Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense
(DOD) [W81XWH-07-2-0067]
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health (AI064086; RH), the University
of California San Diego Center for AIDS Research (AI36214; RH), and the
San Diego AIDS Clinical Trial Group (CTU AI69432; RH). The work was also
supported in part by an Interagency Agreement Y1-AI-2642-12 between the
U.S. Army Medical Research and Material Command (USAMRMC) and the
National Institutes of Allergy and Infectious Diseases and by a
cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson
Foundation for the Advancement of Military Medicine, Inc., and the U.S.
Department of Defense (DOD).
NR 36
TC 1
Z9 2
U1 0
U2 3
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 DEC 17
PY 2015
VL 10
IS 12
AR e0144767
DI 10.1371/journal.pone.0144767
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9JO
UT WOS:000366723400025
PM 26678998
ER
PT J
AU Richards, CL
Lawrence, KA
Su, H
Yang, YY
Yang, XF
Dulebohn, DP
Gherardini, FC
AF Richards, Crystal L.
Lawrence, Kevin A.
Su, Hua
Yang, Youyun
Yang, X. Frank
Dulebohn, Daniel P.
Gherardini, Frank C.
TI Acetyl-Phosphate Is Not a Global Regulatory Bridge between Virulence and
Central Metabolism in Borrelia burgdorferi
SO PLOS ONE
LA English
DT Article
ID RESPONSE REGULATOR; ESCHERICHIA-COLI; LYME-DISEASE; GENE-EXPRESSION;
IN-VITRO; LIPID-II; RPOS; PHOSPHORYLATION; SPIROCHETE; RESISTANCE
AB In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2 (BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway. Previous investigations have attempted to identify the phosphate donor of Rrp2, including the cognate histidine kinase, Hk2 (BB0764), non-cognate histidine kinases such as Hk1, CheA1, and CheA2, and small molecular weight P-donors such as carbamoyl-phosphate and acetyl-phosphate (AcP). In a report by Xu et al., exogenous sodium acetate led to increased expression of RpoS and OspC and it was hypothesized this effect was due to increased levels of AcP via the enzyme AckA (BB0622). Genome analyses identified only one pathway that could generate AcP in B. burgdorferi: the acetate/mevalonate pathway that synthesizes the lipid, undecaprenyl phosphate (C-55-P, lipid I), which is essential for cell wall biogenesis. To assess the role of AcP in Rrp2-dependent regulation of RpoS and OspC, we used a unique selection strategy to generate mutants that lacked ackA (bb0622: acetate to AcP) or pta (bb0589: AcP to acetyl-CoA). These mutants have an absolute requirement for mevalonate and demonstrate that ackA and pta are required for cell viability. When the Delta ackA or Delta pta mutant was exposed to conditions (i.e., increased temperature or cell density) that up-regulate the expression of RpoS and OspC, normal induction of those proteins was observed. In addition, adding 20mM acetate or 20mM benzoate to the growth media of B. burgdorferi strain B31 Delta ackA induced the expression of RpoS and OspC. These data suggest that AcP (generated by AckA) is not directly involved in modulating the Rrp2-RpoN-RpoS regulatory pathway and that exogenous acetate or benzoate are triggering an acid stress response in B. burgdorferi.
C1 [Richards, Crystal L.; Lawrence, Kevin A.; Su, Hua; Dulebohn, Daniel P.; Gherardini, Frank C.] NIH, Lab Zoonot Pathogens, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Yang, Youyun; Yang, X. Frank] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
RP Gherardini, FC (reprint author), NIH, Lab Zoonot Pathogens, Rocky Mt Labs, Hamilton, MT 59840 USA.
EM Fgherardini@niaid.nih.gov
FU Intramural Research Program of the NIAID (National Institute of Allergy
and Infectious Diseases (US)), NIH (National Institutes of Health (US))
FX This research was supported by the Intramural Research Program of the
NIAID (National Institute of Allergy and Infectious Diseases (US)), NIH
(National Institutes of Health (US)). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 0
Z9 0
U1 1
U2 3
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 DEC 17
PY 2015
VL 10
IS 12
AR e0144472
DI 10.1371/journal.pone.0144472
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9JO
UT WOS:000366723400016
PM 26681317
ER
PT J
AU Dennis, A
Thomas, AG
Rawlings, NB
Near, J
Nichols, TE
Clare, S
Johansen-Berg, H
Stagg, CJ
AF Dennis, Andrea
Thomas, Adam G.
Rawlings, Nancy B.
Near, Jamie
Nichols, Thomas E.
Clare, Stuart
Johansen-Berg, Heidi
Stagg, Charlotte J.
TI An Ultra-High Field Magnetic Resonance Spectroscopy Study of Post
Exercise Lactate, Glutamate and Glutamine Change in the Human Brain
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE brain; lactate; glutamate; magnetic resonance spectroscopy; exercise
ID HUMAN VISUAL-CORTEX; CEREBRAL METABOLIC RATIO; BLOOD LACTATE; IN-VIVO;
H-1-NMR SPECTROSCOPY; GLUCOSE-UTILIZATION; ENERGY-METABOLISM;
NEURONAL-ACTIVITY; MAXIMAL EXERCISE; AEROBIC FITNESS
AB During strenuous exercise there is a progressive increase in lactate uptake and metabolism into the brain as workload and plasma lactate levels increase. Although it is now widely accepted that the brain can metabolize lactate, few studies have directly measured brain lactate following vigorous exercise. Here, we used ultra-high field magnetic resonance spectroscopy of the brain to obtain static measures of brain lactate, as well as brain glutamate and glutamine after vigorous exercise. The aims of our experiment were to (a) track the changes in brain lactate following recovery from exercise, and (b) to simultaneously measure the signals from brain glutamate and glutamine. The results of our experiment showed that vigorous exercise resulted in a significant increase in brain lactate. Furthermore, both glutamate and glutamine were successfully resolved, and as expected, although contrary to some previous reports, we did not observe any significant change in either amino acid after exercise. We did however observe a negative correlation between glutamate and a measure of fitness. These results support the hypothesis that peripherally derived lactate is taken up by the brain when available. Our data additionally highlight the potential of ultra-high field MRS as a non-invasive way of measuring multiple brain metabolite changes with exercise.
C1 [Dennis, Andrea; Thomas, Adam G.; Rawlings, Nancy B.; Near, Jamie; Nichols, Thomas E.; Clare, Stuart; Johansen-Berg, Heidi; Stagg, Charlotte J.] Univ Oxford, Nffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain FMRIB, Oxford, England.
[Thomas, Adam G.] NIMH, Sect Funct Imaging Methods, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Near, Jamie] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada.
[Near, Jamie] McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
[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.
[Stagg, Charlotte J.] Univ Oxford, Oxford Ctr Human Brain Act OHBA, Physiol Neuroimaging Grp, Oxford, England.
RP Dennis, A (reprint author), Univ Oxford, Nffield Dept Clin Neurosci, Oxford Ctr Funct MRI Brain FMRIB, Oxford, England.
EM andrea.dennis@ndcn.ox.ac.uk
OI Stagg, Charlotte/0000-0002-5542-5036; Thomas, Adam/0000-0002-2850-1419
FU National Institute for Health Research (NIHR) Oxford Biomedical Research
Center based at Oxford University Hospitals Trust, Oxford University;
NIMH Intramural Research Program based in Bethesda, MD; Wellcome Trust;
Royal Society [102584/Z/13/Z]
FX The work was supported by the National Institute for Health Research
(NIHR) Oxford Biomedical Research Center based at Oxford University
Hospitals Trust, Oxford University. The views expressed are those of the
author(s) and not necessarily those of the NHS, the NIHR, or the
Department of Health. AT is supported by the NIMH Intramural Research
Program based in Bethesda, MD. HJ is a Wellcome Trust Senior Research
Fellow. CS holds a Sir Henry Dale Fellowship jointly funded by the
Wellcome Trust and the Royal Society (Gram Number 102584/Z/13/Z).
NR 69
TC 2
Z9 3
U1 3
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PD DEC 17
PY 2015
VL 6
AR 351
DI 10.3389/fphys.2015.00351
PG 11
WC Physiology
SC Physiology
GA CY9UM
UT WOS:000366751800001
PM 26732236
ER
PT J
AU Mate, SE
Kugelman, JR
Nyenswah, TG
Ladner, JT
Wiley, MR
Cordier-Lassalle, T
Christie, A
Schroth, GP
Gross, SM
Davies-Wayne, GJ
Shinde, SA
Murugan, R
Sieh, SB
Badio, M
Fakoli, L
Taweh, F
de Wit, E
van Doremalen, N
Munster, VJ
Pettitt, J
Prieto, K
Humrighouse, BW
Stroher, U
DiClaro, JW
Hensley, LE
Schoepp, RJ
Safronetz, D
Fair, J
Kuhn, JH
Blackley, DJ
Laney, AS
Williams, DE
Lo, T
Gasasira, A
Nichol, ST
Formenty, P
Kateh, FN
De Cock, KM
Bolay, F
Sanchez-Lockhart, M
Palacios, G
AF Mate, S. E.
Kugelman, J. R.
Nyenswah, T. G.
Ladner, J. T.
Wiley, M. R.
Cordier-Lassalle, T.
Christie, A.
Schroth, G. P.
Gross, S. M.
Davies-Wayne, G. J.
Shinde, S. A.
Murugan, R.
Sieh, S. B.
Badio, M.
Fakoli, L.
Taweh, F.
de Wit, E.
van Doremalen, N.
Munster, V. J.
Pettitt, J.
Prieto, K.
Humrighouse, B. W.
Stroeher, U.
DiClaro, J. W.
Hensley, L. E.
Schoepp, R. J.
Safronetz, D.
Fair, J.
Kuhn, J. H.
Blackley, D. J.
Laney, A. S.
Williams, D. E.
Lo, T.
Gasasira, A.
Nichol, S. T.
Formenty, P.
Kateh, F. N.
De Cock, K. M.
Bolay, F.
Sanchez-Lockhart, M.
Palacios, G.
TI Molecular Evidence of Sexual Transmission of Ebola Virus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SIERRA-LEONE; OUTBREAK; LIBERIA; CONGO; PERSISTENCE; EVOLUTION; DISEASE;
KIKWIT; GUINEA
AB A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD.
C1 [Mate, S. E.; Kugelman, J. R.; Ladner, J. T.; Wiley, M. R.; Prieto, K.; Sanchez-Lockhart, M.; Palacios, G.] US Army Med Res Inst Infect Dis, Ctr Genome Sci, Frederick, MD 21702 USA.
[Schoepp, R. J.] US Army Med Res Inst Infect Dis, Diagnost Syst Div, Frederick, MD 21702 USA.
[Pettitt, J.; Hensley, L. E.; Kuhn, J. H.] NIAID, Div Clin Res, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA.
[Nyenswah, T. G.; Sieh, S. B.; Badio, M.; Kateh, F. N.] Minist Hlth & Social Welf, Monrovia, Liberia.
[Davies-Wayne, G. J.; Murugan, R.] WHO, Monrovia, Liberia.
[Fakoli, L.; Taweh, F.; Bolay, F.] Liberian Inst Biomed Res, Charlesville, Liberia.
[Cordier-Lassalle, T.; Christie, A.; Formenty, P.] WHO, Geneva, Switzerland.
[Christie, A.; Humrighouse, B. W.; Stroeher, U.; Blackley, D. J.; Laney, A. S.; Williams, D. E.; Lo, T.; Nichol, S. T.; De Cock, K. M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Schroth, G. P.; Gross, S. M.] Illumina, San Diego, CA USA.
[Shinde, S. A.] WHO, New Delhi, India.
[de Wit, E.; van Doremalen, N.; Munster, V. J.; Safronetz, D.] NIAID, Rocky Mt Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[DiClaro, J. W.] Naval Med Res Unit 3, Cairo, Egypt.
[Fair, J.] Fdn Merieux, Washington, DC USA.
RP Palacios, G (reprint author), US Army Med Res Inst Infect Dis, 1425 Porter St,Rm 622, Frederick, MD 21702 USA.
EM gustavo.f.palacios.ctr@us.army.mil
RI Palacios, Gustavo/I-7773-2015;
OI Palacios, Gustavo/0000-0001-5062-1938; de Wit,
Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU Defense Threat Reduction Agency
FX Funded by the Defense Threat Reduction Agency and others.
NR 22
TC 74
Z9 75
U1 2
U2 36
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 DEC 17
PY 2015
VL 373
IS 25
BP 2448
EP 2454
DI 10.1056/NEJMoa1509773
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY5QD
UT WOS:000366461400011
PM 26465384
ER
PT J
AU Rochael, NC
Guimaraes-Costa, AB
Nascimento, MTC
DeSouza-Vieira, TS
Oliveira, MP
Souza, LFGE
Oliveira, MF
Saraiva, EM
AF Rochael, Natalia C.
Guimaraes-Costa, Anderson B.
Nascimento, Michelle T. C.
DeSouza-Vieira, Thiago S.
Oliveira, Matheus P.
Garcia e Souza, Luiz F.
Oliveira, Marcus F.
Saraiva, Elvira M.
TI Classical ROS-dependent and early/rapid ROS-independent release of
Neutrophil Extracellular Traps triggered by Leishmania parasites
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; CUTANEOUS LEISHMANIASIS; NADPH OXIDASE; NET
FORMATION; CANDIDA-ALBICANS; INNATE IMMUNITY; MECHANISM;
MYELOPEROXIDASE; GENERATION; PROTEIN
AB Neutrophil extracellular traps (NETs) extruded from neutrophils upon activation are composed of chromatin associated with cytosolic and granular proteins, which ensnare and kill microorganisms. This microbicidal mechanism named classical netosis has been shown to dependent on reactive oxygen species (ROS) generation by NADPH oxidase and also chromatin decondensation dependent upon the enzymes (PAD4), neutrophil elastase (NE) and myeloperoxidase (MPO). NET release also occurs through an early/rapid ROS-independent mechanism, named early/rapid vital netosis. Here we analyze the role of ROS, NE, MPO and PAD4 in the netosis stimulated by Leishmania amazonensis promastigotes in human neutrophils. We demonstrate that promastigotes induce a classical netosis, dependent on the cellular redox imbalance, as well as by a chloroamidine sensitive and elastase activity mechanism. Additionally, Leishmania also induces the early/rapid NET release occurring only 10 minutes after neutrophil-parasite interaction. We demonstrate here, that this early/rapid mechanism is dependent on elastase activity, but independent of ROS generation and chloroamidine. A better understanding of both mechanisms of NET release, and the NETs effects on the host immune system modulation, could support the development of new potential therapeutic strategies for leishmaniasis.
C1 [Rochael, Natalia C.; Guimaraes-Costa, Anderson B.; Nascimento, Michelle T. C.; DeSouza-Vieira, Thiago S.; Saraiva, Elvira M.] Univ Fed Rio de Janeiro, Inst Microbiol Paulo Goes, Lab Imunobiol Leishmanioses, Dept Imunol, BR-21941902 Rio De Janeiro, RJ, Brazil.
[Oliveira, Matheus P.; Garcia e Souza, Luiz F.; Oliveira, Marcus F.] Univ Fed Rio de Janeiro, Programa Biol Mol & Biotecnol, Inst Bioquim Med, Lab Bioquim Resposta Estresse, BR-21941902 Rio De Janeiro, Brazil.
[Oliveira, Matheus P.; Garcia e Souza, Luiz F.] Univ Fed Rio de Janeiro, Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Lab Inflamacao & Metab, BR-21941902 Rio De Janeiro, RJ, Brazil.
[Guimaraes-Costa, Anderson B.] NIAID, Vector Mol Biol Unit, Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Oliveira, MF (reprint author), Univ Fed Rio de Janeiro, Programa Biol Mol & Biotecnol, Inst Bioquim Med, Lab Bioquim Resposta Estresse, Cidade Univ, BR-21941902 Rio De Janeiro, Brazil.
EM maroli@bioqmed.ufrj.br; esaraiva@micro.ufrj.br
FU Ministerio Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq); Fundacao Carlos Chagas Filho de Amparo
a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
FX The authors thank the Hemotherapy Service of Hospital Clementino Fraga
Filho (UFRJ) for buffy coats. This work was supported by Ministerio
Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (CNPq) and Fundacao Carlos Chagas Filho de Amparo a Pesquisa
do Estado do Rio de Janeiro (FAPERJ). We thank the NIH Fellows Editorial
Board for the edition of this manuscript.
NR 51
TC 19
Z9 19
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 DEC 17
PY 2015
VL 5
AR 18302
DI 10.1038/srep18302
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY7EB
UT WOS:000366569900002
PM 26673780
ER
PT J
AU Oldridge, DA
Wood, AC
Weichert-Leahey, N
Crimmins, I
Sussman, R
Winter, C
McDaniel, LD
Diamond, M
Hart, LS
Zhu, SZ
Durbin, AD
Abraham, BJ
Anders, L
Tian, LF
Zhang, SL
Wei, JS
Khan, J
Bramlett, K
Rahman, N
Capasso, M
Iolascon, A
Gerhard, DS
Auvil, JMG
Young, RA
Hakonarson, H
Diskin, SJ
Look, AT
Maris, JM
AF Oldridge, Derek A.
Wood, Andrew C.
Weichert-Leahey, Nina
Crimmins, Ian
Sussman, Robyn
Winter, Cynthia
McDaniel, Lee D.
Diamond, Maura
Hart, Lori S.
Zhu, Shizhen
Durbin, Adam D.
Abraham, Brian J.
Anders, Lars
Tian, Lifeng
Zhang, Shile
Wei, Jun S.
Khan, Javed
Bramlett, Kelli
Rahman, Nazneen
Capasso, Mario
Iolascon, Achille
Gerhard, Daniela S.
Auvil, Jaime M. Guidry
Young, Richard A.
Hakonarson, Hakon
Diskin, Sharon J.
Look, A. Thomas
Maris, John M.
TI Genetic predisposition to neuroblastoma mediated by a LMO1
super-enhancer polymorphism
SO NATURE
LA English
DT Article
ID CELL IDENTITY; HUMAN GENOME; TRANSCRIPTION; INHIBITION; LOCUS;
SUSCEPTIBILITY; ASSOCIATION; DISEASE; CANCER; MYCN
AB Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells(1). Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 x 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P < 0.0001). We demonstrate allelic imbalance favouring the G-containing strand in tumours heterozygous for this SNP, as demonstrated both by RNA sequencing (P < 0.0001) and reporter assays (P = 0.002). These findings indicate that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells.
C1 [Oldridge, Derek A.; Crimmins, Ian; Sussman, Robyn; Winter, Cynthia; McDaniel, Lee D.; Diamond, Maura; Hart, Lori S.; Diskin, Sharon J.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Oldridge, Derek A.; Crimmins, Ian; Sussman, Robyn; Winter, Cynthia; McDaniel, Lee D.; Diamond, Maura; Hart, Lori S.; Diskin, Sharon J.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Oldridge, Derek A.] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA.
[Wood, Andrew C.] Univ Auckland, Dept Mol Med & Pathol, Auckland 1, Auckland Region, New Zealand.
[Weichert-Leahey, Nina; Durbin, Adam D.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Weichert-Leahey, Nina; Durbin, Adam D.; Look, A. Thomas] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Zhu, Shizhen] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Abraham, Brian J.; Anders, Lars; Young, Richard A.] Whitehead Inst Biomed Res, Boston, MA 02142 USA.
[Abraham, Brian J.; Anders, Lars; Young, Richard A.] MIT, Boston, MA 02142 USA.
[Tian, Lifeng; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Zhang, Shile; Wei, Jun S.; Khan, Javed] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Bramlett, Kelli] Thermo Fisher Sci, Austin, TX 78744 USA.
[Rahman, Nazneen] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
[Capasso, Mario; Iolascon, Achille] Univ Naples 2, I-80131 Naples, Italy.
[Capasso, Mario; Iolascon, Achille] CEINGE Biotecnol Avanzate, I-80131 Naples, Italy.
[Gerhard, Daniela S.; Auvil, Jaime M. Guidry] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Hakonarson, Hakon; Diskin, Sharon J.; Maris, John M.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Diskin, Sharon J.; Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
RP Maris, JM (reprint author), Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
EM maris@chop.edu
RI Capasso, Mario/D-1617-2014; Khan, Javed/P-9157-2014; Rahman,
Nazneen/D-2802-2013;
OI Khan, Javed/0000-0002-5858-0488; Rahman, Nazneen/0000-0003-4376-0440;
Capasso, Mario/0000-0003-3306-1259
FU NIH [R01-CA124709, R01-CA180692, R00-CA151869, RC1MD004418,
1K99CA178189, T32-HG000046, R01-CA109901]; Giulio D'Angio Endowed Chair;
PressOn Foundation; Andrew's Army Foundation; Abramson Family Cancer
Research Institute; Brooke Mulford Foundation; University of
Pennsylvania Genome Frontiers Institute; Alex's Lemonade Stand
Foundation Innovation Award; Alex's Lemonade Stand Foundation;
CureSearch for Children's Cancer Foundation; German Cancer Aid 110801;
St Baldrick's Foundation Fellow award; George L. Ohrstrom Jr foundation;
Wellcome Trust [100210/Z/12/Z]; NHS; Fondazione Italiana per la Lotta al
Neuroblastoma; Associazione Oncologia Pediatrica e Neuroblastoma;
Associazione Italiana per la Ricerca sul Cancro
FX This work was supported in part by NIH grants R01-CA124709 (J.M.M.),
R01-CA180692 (J.M.M. and A.T.L.), R00-CA151869 (S.J.D.), RC1MD004418 to
the TARGET consortium, 1K99CA178189 (S.Z.), T32-HG000046 (D.A.O.),
R01-CA109901 (R.A.Y.), the Giulio D'Angio Endowed Chair (J.M.M.), the
PressOn Foundation (J.M.M.), Andrew's Army Foundation (J.M.M.), the
Abramson Family Cancer Research Institute (J.M.M.), the Brooke Mulford
Foundation (J.M.M.), the University of Pennsylvania Genome Frontiers
Institute, an Alex's Lemonade Stand Foundation Innovation Award
(A.T.L.), young investigator awards from Alex's Lemonade Stand
Foundation (S.Z., A.C.W.) and the CureSearch for Children's Cancer
Foundation (S.Z.), grant from the German Cancer Aid 110801 (N.W.-L.), St
Baldrick's Foundation Fellow award (A.C.W.), George L. Ohrstrom Jr
foundation (A.C.W.), Wellcome Trust Senior Investigator Award Ref:
100210/Z/12/Z (N.R.) and NHS funding to the NIHR Biomedical Research
Centre at The Royal Marsden and the ICR (N.R.), Fondazione Italiana per
la Lotta al Neuroblastoma (M.C.), Associazione Oncologia Pediatrica e
Neuroblastoma (M.C.), and Associazione Italiana per la Ricerca sul
Cancro (M.C.). We gratefully acknowledge the Children's Oncology Group
(COG) for providing the specimens and clinical data from neuroblastoma
patients and thank patients and families for participating in the COG,
the UK-based Factors Associated with Childhood Tumors (FACT), and
Italian cooperative group studies. We thank A. Renwick who performed the
Taqman analyses and A. Zachariou for recruiting participants to the FACT
study. We thank G. Blobel for scientific advice and discussion, and
generously providing equipment and reagents for ChIP experiments, N.
Saeki and H. Sasaki for providing the LMO1 cDNA clone, and Y. Nakatan
for providing the lentiviral vector pOZ-FHN.
NR 30
TC 26
Z9 27
U1 7
U2 23
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 DEC 17
PY 2015
VL 528
IS 7582
BP 418
EP +
DI 10.1038/nature15540
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY8SM
UT WOS:000366678600057
PM 26560027
ER
PT J
AU Khositseth, S
Uawithya, P
Somparn, P
Charngkaew, K
Thippamom, N
Hoffert, JD
Saeed, F
Payne, DM
Chen, SH
Fenton, RA
Pisitkun, T
AF Khositseth, Sookkasem
Uawithya, Panapat
Somparn, Poorichaya
Charngkaew, Komgrid
Thippamom, Nattakan
Hoffert, Jason D.
Saeed, Fahad
Payne, D. Michael
Chen, Shu-Hui
Fenton, Robert A.
Pisitkun, Trairak
TI Autophagic degradation of aquaporin-2 is an early event in
hypokalemia-induced nephrogenic diabetes insipidus
SO SCIENTIFIC REPORTS
LA English
DT Article
ID COLLECTING DUCT CELLS; POTASSIUM-DEPLETION NEPHROPATHY; URINARY
CONCENTRATING DEFECT; WATER CHANNEL EXPRESSION; TANDEM MASS-SPECTRA;
RAT-KIDNEY; MODIFIED PEPTIDES; DOWN-REGULATION; K+ HOMEOSTASIS; KNOCKOUT
MICE
AB Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.
C1 [Khositseth, Sookkasem; Thippamom, Nattakan] Thammasat Univ Klong Luang, Dept Pediat, Fac Med, Pathum Thani 12120, Thailand.
[Uawithya, Panapat] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Physiol, Bangkok 10700, Thailand.
[Somparn, Poorichaya; Payne, D. Michael; Pisitkun, Trairak] Chulalongkorn Univ, Fac Med, Res Affairs, Syst Biol Ctr, Bangkok, Thailand.
[Charngkaew, Komgrid] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pathol, Bangkok 10700, Thailand.
[Hoffert, Jason D.] NIDDK, Bethesda, MD 20892 USA.
[Saeed, Fahad] Western Michigan Univ, Dept Elect & Comp Engn, Kalamazoo, MI 49008 USA.
[Saeed, Fahad] Western Michigan Univ, Dept Comp Sci, Kalamazoo, MI 49008 USA.
[Chen, Shu-Hui] Natl Cheng Kung Univ, Dept Chem, Tainan 701, Taiwan.
[Fenton, Robert A.; Pisitkun, Trairak] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark.
[Fenton, Robert A.; Pisitkun, Trairak] Aarhus Univ, Ctr Interact Proteins Epithelial Transport, DK-8000 Aarhus, Denmark.
[Pisitkun, Trairak] NHLBI, Epithelial Syst Biol Lab, Bethesda, MD 20892 USA.
RP Khositseth, S (reprint author), Thammasat Univ Klong Luang, Dept Pediat, Fac Med, Pathum Thani 12120, Thailand.
EM Sookkasem@yahoo.com; pisitkut@nhlbi.nih.gov
FU Thailand Research Fund; Thammasat University; Chulalongkorn Academic
Advancement into Its 2nd Century Project; Danish Medical Research
Council; Lundbeck Foundation; [RMU 5380032]
FX This work was supported by the Research Scholar Grant (RMU 5380032),
Thailand Research Fund, Thammasat University, and the Chulalongkorn
Academic Advancement into Its 2nd Century Project. The immunogold
electron microscopic study is supported by the Danish Medical Research
Council and Lundbeck Foundation. We thank Drs. Mark A. Knepper and
Chung-Lin Chou (NHLBI, NIH, USA) for advice. We thank Nusara Chomanee
and Christina Schmidt for assistance on electron microscopy, and
Chatikorn Boonkrai for assistance on immunofluorescence microscopy. The
authors thank Dr. N. Tony Eissa, Baylor College of Medicine, for very
helpful discussion.
NR 68
TC 2
Z9 3
U1 1
U2 3
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 DEC 17
PY 2015
VL 5
AR 18311
DI 10.1038/srep18311
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY7EG
UT WOS:000366570500002
PM 26674602
ER
PT J
AU Lee, YT
de Vasconcellos, JF
Byrnes, C
Kaushal, M
Rabel, A
Tumburu, L
Allwardt, JM
Miller, JL
AF Lee, Y. Terry
de Vasconcellos, Jaira F.
Byrnes, Colleen
Kaushal, Megha
Rabel, Antoinette
Tumburu, Laxminath
Allwardt, Joshua M.
Miller, Jeffery L.
TI Erythroid-Specific Expression of LIN28A Is Sufficient for Robust
Gamma-Globin Gene and Protein Expression in Adult Erythroblasts
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALPHA-SPECTRIN GENE; STEM-CELLS; MICRORNA;
LIN-28; FETAL; DIFFERENTIATION; ERYTHROPOIESIS; IDENTIFICATION;
HEMOGLOBIN
AB Increasing fetal hemoglobin (HbF) levels in adult humans remains an active area in hematologic research. Here we explored erythroid-specific LIN28A expression for its effect in regulating gamma-globin gene expression and HbF levels in cultured adult erythroblasts. For this purpose, lentiviral transduction vectors were produced with LIN28A expression driven by erythroid-specific gene promoter regions of the human KLF1 or SPTA1 genes. Transgene expression of LIN28A with a linked puromycin resistance marker was restricted to the erythroid lineage as demonstrated by selective survival of erythroid colonies (greater than 95% of all colonies). Erythroblast LIN28A over-expression (LIN28A-OE) did not significantly affect proliferation or inhibit differentiation. Greater than 70% suppression of total let-7 microRNA levels was confirmed in LIN28A-OE cells. Increases in gamma-globin mRNA and protein expression with HbF levels reaching 30-40% were achieved. These data suggest that erythroblast targeting of LIN28A expression is sufficient for increasing fetal hemoglobin expression in adult human erythroblasts.
C1 [Lee, Y. Terry; de Vasconcellos, Jaira F.; Byrnes, Colleen; Kaushal, Megha; Rabel, Antoinette; Tumburu, Laxminath; Allwardt, Joshua M.; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Miller, JL (reprint author), NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
EM jm7f@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX The Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases supported this work.
NR 36
TC 2
Z9 2
U1 4
U2 7
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 DEC 16
PY 2015
VL 10
IS 12
AR e0144977
DI 10.1371/journal.pone.0144977
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9JH
UT WOS:000366722700079
PM 26675483
ER
PT J
AU Cheng, C
Wang, LS
Ko, SY
Kong, WP
Schmidt, SD
Gall, JGD
Colloca, S
Seder, RA
Mascola, JR
Nabel, GJ
AF Cheng, Cheng
Wang, Lingshu
Ko, Sung-Youl
Kong, Wing-Pui
Schmidt, Stephen D.
Gall, Jason G. D.
Colloca, Stefano
Seder, Robert A.
Mascola, John R.
Nabel, Gary J.
TI Combination recombinant simian or chimpanzee adenoviral vectors for
vaccine development
SO VACCINE
LA English
DT Article
DE Adenoviral vectors; Simian adenovirus; Chimpanzee adenovirus; Vaccine
development; Humoral immune response; Cellular immune response
ID T-CELL RESPONSES; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES;
GENE-TRANSFER; ENVELOPE GLYCOPROTEIN; NONHUMAN-PRIMATES; DENDRITIC
CELLS; RHESUS-MONKEYS; V3 LOOP; IMMUNIZATION
AB Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or Sly gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAcI/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development. Published by Elsevier Ltd.
C1 [Cheng, Cheng; Wang, Lingshu; Ko, Sung-Youl; Kong, Wing-Pui; Schmidt, Stephen D.; Seder, Robert A.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
[Colloca, Stefano] Okairos Sri, I-00144 Rome, Italy.
RP Cheng, C (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM chcheng@mail.nih.gov; wangling@niaid.nih.gov; kosungyoul@niaid.nih.gov;
wkong@mail.nih.gov; schmidtst@niaid.nih.gov; jason.gall@nih.gov;
stefano.colloca@reithera.com; rseder@mail.nih.gov;
jmascola@mail.nih.gov; Gary.Nabel@sanofi.com
RI Schmidt, Stephen/B-5398-2012
FU Intramural Research Program of the National Institutes of Health,
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases; Bill and Melinda Gates Foundation
FX We thank Ati Tislerics for assistance with manuscript preparation,
Brenda Hartman for figure preparation, C. Richter King, Alfredo Nicosia,
Riccardo Cortese, Richard M. Schwartz and members of the Nabel lab for
helpful discussions and advice. This work was supported by the
Intramural Research Program of the National Institutes of Health,
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases and by the Bill and Melinda Gates Foundation.
NR 41
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Z9 3
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 DEC 16
PY 2015
VL 33
IS 51
BP 7344
EP 7351
DI 10.1016/j.vaccine.2015.10.023
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0FD
UT WOS:000366779600030
PM 26514419
ER
PT J
AU Kim, S
Shore, DL
Wilson, LE
Sanniez, EI
Kim, JH
Taylor, JA
Sandler, DP
AF Kim, Sangmi
Shore, David L.
Wilson, Lauren E.
Sanniez, Ethel I.
Kim, Jae H.
Taylor, Jack A.
Sandler, Dale P.
TI Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer
risk: results from a prospective study of women with a sister with
breast cancer
SO BMC CANCER
LA English
DT Article
DE Breast cancer; Nonsteroidal anti-inflammatory drugs; Chemoprevention;
Family history; Risk factor heterogeneity
ID HORMONE-RECEPTOR STATUS; LOW-DOSE ASPIRIN; CYCLOOXYGENASE-2 INHIBITORS;
MENOPAUSAL STATUS; FAMILY-HISTORY; TIME-SCALE; NSAID USE; METAANALYSIS;
HEALTH; COHORT
AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit several pathways in experimental models of breast carcinogenesis, but epidemiological evidence remains insufficient to support their use for breast cancer prevention. We examined the association between use of NSAIDs and breast cancer risk in a prospective cohort.
Methods: The Sister Study is a prospective cohort study of women who had a sister(s) with breast cancer. As of December 2013, 2118 incident breast cancers were ascertained from 50,884 women enrolled between 2003 and 2009. Lifetime history of NSAID use was estimated from self-reported data in pill-years, with 1 pill per week for a year equivalent to 1 pill-year. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer in relation to pill-years of use for different NSAIDs, with adjustment for potential confounders.
Results: In the full cohort, although there was some evidence that use of non-aspirin, non-COXib NSAIDs was associated with lower breast cancer risk, there was little evidence of overall association for most categories of NSAID use. Among postmenopausal women NSAID use was not associated with reduced risk of breast cancer. However, among premenopausal women there was significantly reduced risk for any NSAID (HR4vs1 = 0.66, 95 % CI: 0.50-0.87) and specifically for aspirin (HR4vs1 = 0.57, 95 % CI: 0.33-0.98), with small, but non-significant reductions in risk for other drug classes.
Conclusion: Women with a sister with breast cancer are themselves at increased risk and might benefit the most from chemoprevention. Although there was little evidence of protective effect from NSAIDs in the overall cohort of women or among the subset who are postmenopausal, there is intriguing evidence that NSAID use, particularly aspirin, may reduce risk among premenopausal women.
C1 [Kim, Sangmi; Kim, Jae H.] Augusta Univ, Dept Med, Sect Hematol Oncol, Med Coll Georgia,GRU Canc Ctr, Augusta, GA 30912 USA.
[Shore, David L.; Sanniez, Ethel I.] Westat Corp, Durham, NC 27703 USA.
[Wilson, Lauren E.; Taylor, Jack A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27599 USA.
RP Kim, S (reprint author), Augusta Univ, Dept Med, Sect Hematol Oncol, Med Coll Georgia,GRU Canc Ctr, 1410 Laney Walker Blvd, Augusta, GA 30912 USA.
EM sankim@gru.edu
OI taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018;
Wilson, Lauren/0000-0002-5953-2293
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES044005]
FX This work was supported in part by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences (Z01
ES044005).
NR 48
TC 1
Z9 1
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD DEC 16
PY 2015
VL 15
AR 960
DI 10.1186/s12885-015-1979-1
PG 10
WC Oncology
SC Oncology
GA CY6VC
UT WOS:000366545900016
PM 26673874
ER
PT J
AU Kimm, T
Khaliq, ZM
Bean, BP
AF Kimm, Tilia
Khaliq, Zayd M.
Bean, Bruce P.
TI Differential Regulation of Action Potential Shape and Burst-Frequency
Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE action potential clamp; bursting; guangxitoxin-1E; paxilline
ID CA2+-ACTIVATED K+ CHANNELS; NEOCORTICAL PYRAMIDAL NEURONS; ACTIVATED
POTASSIUM CHANNELS; VESTIBULAR NUCLEUS NEURONS; LARGE-CONDUCTANCE;
DEPOLARIZATION BLOCK; MIDBRAIN NEURONS; IN-VIVO; PACEMAKER ACTIVITY;
PURKINJE NEURONS
AB Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting eitherBKor Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell.
C1 [Kimm, Tilia; Bean, Bruce P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Khaliq, Zayd M.] NINDS, Cellular Neurophysiol Unit, NIH, Bethesda, MD 20892 USA.
RP Bean, BP (reprint author), Harvard Univ, Sch Med, 220 Longwood Ave, Boston, MA 02115 USA.
EM bruce_bean@hms.harvard.edu
FU NINDS [R01NS036855, F31NS080323]; NINDS Intramural Program
FX This work was supported by NINDS R01NS036855, F31NS080323, and the NINDS
Intramural Program. We thank to Dr Michelino Puopolo (Stony Brook
University) for sharing preliminary results, and for help and advice,
and to Dr Rachel Wilson for helpful discussion.
NR 75
TC 7
Z9 7
U1 3
U2 10
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 DEC 16
PY 2015
VL 35
IS 50
BP 16404
EP 16417
DI 10.1523/JNEUROSCI.5291-14.2015
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CY6PA
UT WOS:000366530100011
PM 26674866
ER
PT J
AU Lucantonio, F
Gardner, MPH
Mirenzi, A
Newman, LE
Takahashi, YK
Schoenbaum, G
AF Lucantonio, Federica
Gardner, Matthew P. H.
Mirenzi, Aaron
Newman, Laura E.
Takahashi, Yuji K.
Schoenbaum, Geoffrey
TI Neural Estimates of Imagined Outcomes in Basolateral Amygdala Depend on
Orbitofrontal Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE amygdala; extinction; orbitofrontal; over-expectation; rat; single-unit
ID ORBITAL PREFRONTAL CORTEX; REINFORCER DEVALUATION; CENTRAL NUCLEUS;
RHESUS-MONKEYS; REWARD-VALUE; LESIONS; BEHAVIOR; OVEREXPECTATION;
INACTIVATION; MODEL
AB Reciprocal connections between the orbitofrontal cortex (OFC) and the basolateral nucleus of the amygdala (BLA) provide a critical circuit for guiding normal behavior when information about expected outcomes is required. Recently, we reported that outcome signaling by OFC neurons is also necessary for learning in the face of unexpected outcomes during a Pavlovian over-expectation task. Key to learning in this task is the ability to build on prior learning to infer or estimate an amount of reward never previously received. OFC was critical to this process. Notably, in parallel work, we found that BLA was not necessary for learning in this setting. This suggested a dissociation in which the BLA might be critical for acquiring information about the outcomes but not for subsequently using it to make novel predictions. Here we evaluated this hypothesis by recording single-unit activity from BLA in rats during the same Pavlovian over-expectation task used previously. We found that spiking activity recorded in BLA in control rats did reflect novel outcome estimates derived from the integration of prior learning, however consistent with a model in which this process occurs in the OFC, these correlates were entirely abolished by ipsilateral OFC lesions. These data indicate that this information about these novel predictions is represented in the BLA, supported via direct or indirect input from the OFC, even though it does not appear to be necessary for learning.
C1 [Lucantonio, Federica; Gardner, Matthew P. H.; Mirenzi, Aaron; Newman, Laura E.; Takahashi, Yuji K.; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Lucantonio, Federica; Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA.
RP Schoenbaum, G (reprint author), 251 Bayview Dr, Baltimore, MD 21224 USA.
EM geoffrey.schoenbaum@nih.gov
FU NIDA
FX This work was supported by funding from NIDA (G.S.). The opinions
expressed in this article are the authors' own and do not reflect the
view of the National Institutes of Health, the Department of Health and
Human Services, or the United States government.
NR 45
TC 2
Z9 2
U1 2
U2 6
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 DEC 16
PY 2015
VL 35
IS 50
BP 16521
EP 16530
DI 10.1523/JNEUROSCI.3126-15.2015
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CY6PA
UT WOS:000366530100021
PM 26674876
ER
PT J
AU Sedda, L
Qi, QY
Tatem, AJ
AF Sedda, Luigi
Qi, Qiuyin
Tatem, Andrew J.
TI A geostatistical analysis of the association between armed conflicts and
Plasmodium falciparum malaria in Africa, 1997-2010
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum parasite rate 2-10; Conflict density; Violence;
Variogram; Malaria control
ID EMERGING INFECTIOUS-DISEASES; COMPLEX EMERGENCIES; CIVIL CONFLICTS;
PUBLIC-HEALTH; TRANSMISSION; PREVALENCE; MORTALITY; RISK; WARS;
POPULATION
AB Background: The absence of conflict in a country has been cited as a crucial factor affecting the operational feasibility of achieving malaria control and elimination, yet mixed evidence exists on the influence that conflicts have had on malaria transmission. Over the past two decades, Africa has seen substantial numbers of armed conflicts of varying length and scale, creating conditions that can disrupt control efforts and impact malaria transmission. However, very few studies have quantitatively assessed the associations between conflicts and malaria transmission, particularly in a consistent way across multiple countries.
Methods: In this analysis an explicit geostatistical, autoregressive, mixed model is employed to quantitatively assess the association between conflicts and variations in Plasmodium falciparum parasite prevalence across a 13-year period in sub-Saharan Africa.
Results: Analyses of geolocated, malaria prevalence survey variations against armed conflict data in general showed a wide, but short-lived impact of conflict events geographically. The number of countries with decreased P. falciparum parasite prevalence (17) is larger than the number of countries with increased transmission (12), and notably, some of the countries with the highest transmission pre-conflict were still found with lower transmission post-conflict. For four countries, there were no significant changes in parasite prevalence. Finally, distance from conflicts, duration of conflicts, violence of conflict, and number of conflicts were significant components in the model explaining the changes in P. falciparum parasite rate.
Conclusions: The results suggest that the maintenance of intervention coverage and provision of healthcare in conflict situations to protect vulnerable populations can maintain gains in even the most difficult of circumstances, and that conflict does not represent a substantial barrier to elimination goals.
C1 [Sedda, Luigi] Univ Lancaster, Lancaster Med Sch, CHICAS, Lancaster LA1 4YG, England.
[Qi, Qiuyin] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Flowminder Fdn, S-11355 Stockholm, Sweden.
[Tatem, Andrew J.] Univ Southampton, Geog & Environm, Southampton SO17 1BJ, Hants, England.
RP Sedda, L (reprint author), Univ Lancaster, Lancaster Med Sch, CHICAS, Furness Bldg, Lancaster LA1 4YG, England.
EM l.sedda@lancaster.ac.uk
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health; NIH/NIAID [U19AI089674]; Wellcome Trust Sustaining
Health Programme [106866/Z/15/Z]; Bill and Melinda Gates Foundation
[OPP1106427, 1032350]
FX We thank Prof Peter Atkinson (Lancaster University), Prof Simon Hay
(University of Washington) and the two anonymous reviewers for their
constructive comments on the manuscript. We also thank Dr. Catherine
Moyes and Dr. Peter Gething (University of Oxford) for their input and
data sharing. AJT acknowledges funding support from the RAPIDD program
of the Science and Technology Directorate, Department of Homeland
Security, and the Fogarty International Center, National Institutes of
Health, and is also supported by Grants from NIH/NIAID (U19AI089674),
the Wellcome Trust Sustaining Health Programme (106866/Z/15/Z), and the
Bill and Melinda Gates Foundation (OPP1106427 and #1032350).
NR 86
TC 0
Z9 1
U1 1
U2 5
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 DEC 16
PY 2015
VL 14
AR 500
DI 10.1186/s12936-015-1024-5
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CY7BT
UT WOS:000366563700001
PM 26670739
ER
PT J
AU Serra, M
De Pisapia, N
Rigo, P
Papinutto, N
Jager, J
Bornstein, MH
Venuti, P
AF Serra, Mauro
De Pisapia, Nicola
Rigo, Paola
Papinutto, Nico
Jager, Justin
Bornstein, Marc H.
Venuti, Paola
TI Secure attachment status is associated with white matter integrity in
healthy young adults
SO NEUROREPORT
LA English
DT Article
DE attachment; diffusion tensor imaging; maternal relationship; structural
connectivity; white matter
ID SPATIAL STATISTICS; NERVOUS-SYSTEM; DIFFUSION; CHILDHOOD; WATER;
MICROSTRUCTURE; METAANALYSIS; DISORDER; MRI
AB The present study investigates associations between security of attachment in the mother-child relationship and patterns of brain connectivity in young adults. We hypothesized that secure attachment would relate to more efficient connectivity in white matter association fibers due to increased myelination. Attachment security was measured in 53 young adults using the Kerns Security Scale; anatomical information was acquired using diffusion tensor imaging. Higher fractional anisotropy, an index of directionality of diffusion, related to security of attachment in four left-hemisphere white matter association fibers (uncinate fasciculus, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus). As expected, this result was mainly ascribable to increased myelination, which has been independently associated with attachment security. Security of attachment may have an identifiable biological basis. Our research demonstrates the feasibility of coupling neuroimaging tools with clinical investigation.
C1 [Serra, Mauro; De Pisapia, Nicola; Rigo, Paola; Venuti, Paola] Univ Trento, Dept Psychol & Cognit Sci, I-38068 Rovereto, Italy.
[Papinutto, Nico] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Jager, Justin] Arizona State Univ, T Denny Sanford Sch Social & Family Dynam, Phoenix, AZ USA.
[Bornstein, Marc H.] NIH, US Dept HHS, Rockville, MD USA.
RP Serra, M (reprint author), Univ Trento, Dept Psychol & Cognit Sci, I-38068 Rovereto, Italy.
EM mauro.serra@unitn.it
OI De Pisapia, Nicola/0000-0002-1089-8841
FU University of Trento; NIH, NICHD
FX This research was supported by the University of Trento and the
Intramural Research Program of the NIH, NICHD.
NR 31
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 0959-4965
EI 1473-558X
J9 NEUROREPORT
JI Neuroreport
PD DEC 16
PY 2015
VL 26
IS 18
BP 1106
EP 1111
DI 10.1097/WNR.0000000000000479
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA CX2GK
UT WOS:000365514700005
PM 26559724
ER
PT J
AU Lopatina, N
McDannald, MA
Styer, CV
Sadacca, BF
Cheer, JF
Schoenbaum, G
AF Lopatina, Nina
McDannald, Michael A.
Styer, Clay V.
Sadacca, Brian F.
Cheer, Joseph F.
Schoenbaum, Geoffrey
TI Lateral orbitofrontal neurons acquire responses to upshifted,
downshifted, or blocked cues during unblocking
SO ELIFE
LA English
DT Article
ID VENTROMEDIAL PREFRONTAL CORTEX; DECISION-MAKING; BASOLATERAL AMYGDALA;
ECONOMIC VALUE; REWARD VALUE; REINFORCER DEVALUATION; PREDICTION ERRORS;
GOAL VALUES; CHOICE; BRAIN
AB The lateral orbitofrontal cortex (lOFC) has been described as signaling either outcome expectancies or value. Previously, we used unblocking to show that lOFC neurons respond to a predictive cue signaling a valueless change in outcome features (McDannald, 2014). However, many lOFC neurons also fired to a cue that simply signaled more reward. Here, we recorded lOFC neurons in a variant of this task in which rats learned about cues that signaled either more (upshift), less (downshift) or the same (blocked) amount of reward. We found that neurons acquired responses specifically to one of the three cues and did not fire to the other two. These results show that, at least early in learning, lOFC neurons fire to valued cues in a way that is more consistent with signaling of the predicted outcomes features than with signaling of a general, abstract or cached value that is independent of the outcome.
C1 [Lopatina, Nina; Styer, Clay V.; Sadacca, Brian F.; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Baltimore, MD USA.
[Lopatina, Nina] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
[McDannald, Michael A.] Boston Coll, Dept Psychol, Boston, MA USA.
[Cheer, Joseph F.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA.
RP Schoenbaum, G (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA.
EM geoffrey.schoenbaum@nih.gov
OI Sadacca, Brian/0000-0003-1425-6077
FU National Institute on Drug Abuse
FX National Institute on Drug Abuse IRP Geoffrey Schoenbaum
NR 55
TC 4
Z9 4
U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 15
PY 2015
VL 4
AR e11299
DI 10.7554/eLife.11299
PG 17
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ1HB
UT WOS:000373952800001
PM 26670544
ER
PT J
AU Burroughs, AM
Zhang, DP
Schaffer, DE
Iyer, LM
Aravind, L
AF Burroughs, A. Maxwell
Zhang, Dapeng
Schaeffer, Daniel E.
Iyer, Lakshminarayan M.
Aravind, L.
TI Comparative genomic analyses reveal a vast, novel network of
nucleotide-centric systems in biological conflicts, immunity and
signaling
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CYCLIC ADENINE RIBONUCLEOTIDE; MULTIPLE SEQUENCE ALIGNMENT; POTENTIAL
CATION CHANNELS; UBIQUITIN-RELATED DOMAINS; GROUP-II INTRON; C-DI-AMP;
CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SECONDARY HYPOCALCEMIA;
BACILLUS-SUBTILIS
AB Cyclic di- and linear oligo-nucleotide signals activate defenses against invasive nucleic acids in animal immunity; however, their evolutionary antecedents are poorly understood. Using comparative genomics, sequence and structure analysis, we uncovered a vast network of systems defined by conserved prokaryotic gene-neighborhoods, which encode enzymes generating such nucleotides or alternatively processing them to yield potential signaling molecules. The nucleotide-generating enzymes include several clades of the DNA-polymerase beta-like superfamily (including Vibrio cholerae DncV), a minimal version of the CRISPR polymerase and DisA-like cyclicdi- AMP synthetases. Nucleotide-binding/processing domains include TIR domains and members of a superfamily prototyped by Smf/DprA proteins and base (cytokinin)-releasing LOG enzymes. They are combined in conserved gene-neighborhoods with genes for a plethora of protein superfamilies, which we predict to function as nucleotide-sensors and effectors targeting nucleic acids, proteins or membranes (pore-forming agents). These systems are sometimes combined with other biological conflict-systems such as restriction-modification and CRISPR/Cas. Interestingly, several are coupled in mutually exclusive neighborhoods with either a prokaryotic ubiquitin-system or a HORMA domain-PCH2-like AAA+ ATPase dyad. The latter are potential precursors of equivalent proteins in eukaryotic chromosome dynamics. Further, components from these nucleotide-centric systems have been utilized in several other systems including a novel diversity-generating system with a reverse transcriptase. We also found the Smf/DprA/LOG domain from these systems to be recruited as a predicted nucleotide-binding domain in eukaryotic TRPM channels. These findings point to evolutionary and mechanistic links, which bring together CRISPR/Cas, animal interferon-induced immunity, and several other systems that combine nucleic-acid-sensing and nucleotide-dependent signaling.
C1 [Burroughs, A. Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Schaeffer, Daniel E.] Montgomery Blair High Sch, Magnet Program, Silver Spring, MD 20901 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU National Library of Medicine; National Institutes of Health
FX Funding for open access charge: National Library of Medicine, National
Institutes of Health.
NR 161
TC 1
Z9 1
U1 4
U2 8
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 DEC 15
PY 2015
VL 43
IS 22
DI 10.1093/nar/gkv1267
PG 22
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3IN
UT WOS:000371237600016
ER
PT J
AU Carrington, B
Varshney, GK
Burgess, SM
Sood, R
AF Carrington, Blake
Varshney, Gaurav K.
Burgess, Shawn M.
Sood, Raman
TI CRISPR-STAT: an easy and reliable PCR-based method to evaluate
target-specific sgRNA activity
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ZINC-FINGER NUCLEASES; GENE DISRUPTION; ZEBRAFISH; TALENS; SYSTEM; CAS9;
MUTATION; DESIGN; CELLS
AB CRISPR/Cas9 has emerged as a versatile genome-engineering tool that relies on a single guide RNA (sgRNA) and the Cas9 enzyme for genome editing. Simple, fast and economical methods to generate sgRNAs have made targeted mutagenesis routine in cultured cells, mice, zebrafish and other model systems. Pre-screening of sgRNAs for target efficacy is desirable both for successful mutagenesis and minimizing wasted animal husbandry on targets with poor activity. Here, we describe an easy, quick and cost-effective fluorescent polymerase chain reaction (PCR)-based method, CRISPR Somatic Tissue Activity Test (CRISPR-STAT), to determine target-specific efficiency of sgRNA. As a proof of principle, we validated our method using 28 sgRNAs with known and varied levels of germline transmission efficiency in zebrafish by analysis of their somatic activity in injected embryos. Our data revealed a strong positive correlation between the fluorescent PCR profiles of the injected embryos and the germline transmission efficiency. Furthermore, the assay was sensitive enough to evaluate multiplex gene targeting. This method is easy to implement by laboratories with access to a capillary sequencer. Although we validated themethod using CRISPR/Cas9 and zebrafish, it can be applied to other model systems and other genome targeting nucleases.
C1 [Carrington, Blake; Sood, Raman] NHGRI, Zebrafish Core, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Varshney, Gaurav K.; Burgess, Shawn M.] NHGRI, Dev Genom Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Sood, R (reprint author), NHGRI, Zebrafish Core, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
EM rsood@mail.nih.gov
OI Burgess, Shawn/0000-0003-1147-0596; Sood, Raman/0000-0001-5565-662X;
Varshney, Gaurav K./0000-0002-0429-1904
FU Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health
FX Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health. Funding for open access
charge: Intramural Research Program of the National Human Genome
Research Institute; National Institutes of Health.
NR 34
TC 10
Z9 10
U1 6
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 DEC 15
PY 2015
VL 43
IS 22
AR e157
DI 10.1093/nar/gkv802
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3IN
UT WOS:000371237600009
PM 26253739
ER
PT J
AU Hickman, AB
Dyda, F
AF Hickman, Alison B.
Dyda, Fred
TI The casposon-encoded Cas1 protein from Aciduliprofundum boonei is a DNA
integrase that generates target site duplications
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SHORT PALINDROMIC REPEATS; PHAGE MU TRANSPOSASE; ADAPTIVE IMMUNITY;
BINDING DOMAIN; STRUCTURAL BASIS; SPACER ACQUISITION; MUSCA-DOMESTICA;
CRISPR; SYSTEMS; EVOLUTION
AB Many archaea and bacteria have an adaptive immune system known as CRISPR which allows them to recognize and destroy foreign nucleic acid that they have previously encountered. Two CRISPR-associated proteins, Cas1 and Cas2, are required for the acquisition step of adaptation, in which fragments of foreign DNA are incorporated into the host CRISPR locus. Cas1 genes have also been found scattered in several archaeal and bacterial genomes, unassociated with CRISPR loci or other cas proteins. Rather, they are flanked by nearly identical inverted repeats and enclosed within direct repeats, suggesting that these genetic regions might be mobile elements ('casposons'). To investigate this possibility, we have characterized the in vitro activities of the putative Cas1 transposase ('casposase') from Aciduliprofundum boonei. The purified Cas1 casposase can integrate both short oligonucleotides with inverted repeat sequences and a 2.8 kb excised mini-casposon into target DNA. Casposon integration occurs without target specificity and generates 14-15 basepair target site duplications, consistent with those found in casposon host genomes. Thus, Cas1 casposases carry out similar biochemical reactions as the CRISPR Cas1-Cas2 complex but with opposite substrate specificities: casposases integrate specific sequences into random target sites, whereas CRISPR Cas1-Cas2 integrates essentially random sequences into a specific site in the CRISPR locus.
C1 [Hickman, Alison B.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM Fred.Dyda@nih.gov
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, NIH; Intramural Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (NIH), Bethesda MD
FX Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, NIH. Funding for open access charge: The Intramural
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health (NIH), Bethesda MD.
NR 49
TC 0
Z9 0
U1 2
U2 6
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 DEC 15
PY 2015
VL 43
IS 22
DI 10.1093/nar/gkv1180
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3IN
UT WOS:000371237600011
ER
PT J
AU Zhao, HY
Lin, ZH
Lynn, AY
Varnado, B
Beutler, JA
Murelli, RP
Le Grice, SFJ
Tang, L
AF Zhao, Haiyan
Lin, Zihan
Lynn, Anna Y.
Varnado, Brittany
Beutler, John A.
Murelli, Ryan P.
Le Grice, Stuart F. J.
Tang, Liang
TI Two distinct modes of metal ion binding in the nuclease active site of a
viral DNA-packaging terminase: insight into the two-metal-ion catalytic
mechanism
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HIV-1 REVERSE-TRANSCRIPTASE; RIBONUCLEASE-H ACTIVITY; NITROGENASE
MOFE-PROTEIN; B-VIRUS REPLICATION; RNASE-H; SHIGELLA-FLEXNERI;
HYDROXYLATED TROPOLONES; SUBSTRATE-SPECIFICITY; ANGSTROM RESOLUTION;
CRYSTAL-STRUCTURE
AB Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg2+. A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 angstrom. Such proximity of the two metal ions may play an essential role in catalysis by generating a highly positive electrostatic niche to enable formation of the negatively charged pentacovalent phosphate transition state, and provides the structural basis for distinguishing Mg2+ from Ca2+. Using a metal ion chelator beta-thujaplicinol as a molecular probe, we observed a second mode of metal ion binding at the active site, mimicking the DNA binding state. Arrangement of the active site residues differs drastically from those in RNase H-like nucleases, suggesting a drifting of the active site configuration during evolution. The two distinct metal ion binding modes unveiled mechanistic details of the two-metalion catalysis at atomic resolution.
C1 [Zhao, Haiyan; Lin, Zihan; Lynn, Anna Y.; Varnado, Brittany; Tang, Liang] Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Ave, Lawrence, KS 66045 USA.
[Beutler, John A.] Natl Canc Inst, Mol Targets Lab, Frederick, MD 21702 USA.
[Murelli, Ryan P.] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA.
[Le Grice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21702 USA.
RP Tang, L (reprint author), Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Ave, Lawrence, KS 66045 USA.
EM tangl@ku.edu
FU National Institute of General Medical Sciences of the National
Institutes of Health [R01GM090010]; Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services; National Institutes of Health [SC2GM099596]
FX National Institute of General Medical Sciences of the National
Institutes of Health [R01GM090010 to L.T.]; Intramural Research Program
of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services [to S.Le.G and J.A.B]; National
Institutes of Health [SC2GM099596 to R.P.M.]. Funding for open access
charge: NIH.
NR 52
TC 0
Z9 0
U1 5
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 DEC 15
PY 2015
VL 43
IS 22
DI 10.1093/nar/gkv1018
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DF3IN
UT WOS:000371237600043
ER
PT J
AU Bhowmik, SK
Ramirez-Pena, E
Arnold, JM
Putluri, V
Sphyris, N
Michailidis, G
Putluri, N
Ambs, S
Sreekumar, A
Mani, SA
AF Bhowmik, Salil Kumar
Ramirez-Pena, Esmeralda
Arnold, James Michael
Putluri, Vasanta
Sphyris, Nathalie
Michailidis, George
Putluri, Nagireddy
Ambs, Stefan
Sreekumar, Arun
Mani, Sendurai A.
TI EMT-induced metabolite signature identifies poor clinical outcome
SO ONCOTARGET
LA English
DT Article
DE EMT; breast cancer; metabolism; metabolic reprogramming; LC-MS
metabolomics
ID EPITHELIAL-MESENCHYMAL TRANSITION; NEGATIVE BREAST-CANCER;
GENE-EXPRESSION DATA; GLUTAMINE-METABOLISM; STEM-CELLS; ACCUMULATION;
METABOLOMICS; METASTASIS; SURVIVAL; SUBTYPES
AB Metabolic reprogramming is a hallmark of cancer. Epithelial-mesenchymal transition (EMT) induces cancer stem cell (CSC) characteristics and promotes tumor invasiveness; however relatively little is known about the metabolic reprogramming in EMT. Here we show that breast epithelial cells undergo metabolic reprogramming following EMT. Relative to control, cell lines expressing EMT transcription factors show >= 1.5-fold accumulation of glutamine, glutamate, beta-alanine and glycylleucine as well as >= 1.5-fold reduction of phosphoenolpyruvate, urate, and deoxycarnitine. Moreover, these metabolic alterations were found to be predictive of overall survival (hazard ratio = 2.3 (95% confidence interval: 1.31-4.2), logrank p-value = 0.03) and define breast cancer molecular subtypes. EMT-associated metabolites are primarily composed of anapleurotic precursors, suggesting that cells undergoing EMT have a shift in energy production. In summary, we describe a unique panel of metabolites associated with EMT and demonstrate that these metabolites have the potential for predicting clinical and biological characteristics associated with patient survival.
C1 [Bhowmik, Salil Kumar; Arnold, James Michael; Putluri, Vasanta; Putluri, Nagireddy; Sreekumar, Arun] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA.
[Bhowmik, Salil Kumar; Arnold, James Michael; Putluri, Vasanta; Putluri, Nagireddy; Sreekumar, Arun] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA.
[Bhowmik, Salil Kumar; Arnold, James Michael; Putluri, Vasanta; Putluri, Nagireddy; Sreekumar, Arun] Baylor Coll Med, Alkek Ctr Mol Discovery, Houston, TX 77030 USA.
[Ramirez-Pena, Esmeralda; Sphyris, Nathalie; Mani, Sendurai A.] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
[Michailidis, George] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
[Ambs, Stefan] NCI, Human Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Mani, SA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
EM arun.sreekumar@bcm.edu; smani@mdanderson.org
RI Mani, Sendurai/A-7244-2009;
OI Mani, Sendurai/0000-0002-5918-4276; Ramirez-Pena,
Esmeralda/0000-0002-5200-7488
FU Alkek Center for Molecular Discovery (ACMD); [KG110818]; [DMS
1161759]; [RP120092]; [R21-CA185516-01]; [U01CA179674-01A1];
[RP-130485 NIH/NCI CA155243]
FX This study was partially supported by KG110818 (ASK), DMS 1161759 (ASK,
GM), RP120092 (ASK, NP), R21-CA185516-01 (ASK), U01CA179674-01A1 (ASK),
RP-130485 NIH/NCI CA155243 (SAM) and funds from the Alkek Center for
Molecular Discovery (ACMD).
NR 39
TC 5
Z9 6
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC 15
PY 2015
VL 6
IS 40
BP 42651
EP 42660
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD4QP
UT WOS:000369907900021
PM 26315396
ER
PT J
AU Fang, MZ
Guo, WR
Park, Y
Kang, HG
Zarbl, H
AF Fang, Mingzhu
Guo, Wei-Ren
Park, Youngil
Kang, Hwan-Goo
Zarbl, Helmut
TI Enhancement of NAD(+)-dependent SIRT1 deacetylase activity by
methylselenocysteine resets the circadian clock in carcinogen-treated
mammary epithelial cells
SO ONCOTARGET
LA English
DT Article
DE circadian clock; N-methyl-N-nitrosourea; methylselenocysteine; period 2;
SIRT1
ID GENE-EXPRESSION; BREAST-CANCER; DNA-DAMAGE; SELENIUM-COMPOUNDS;
PROSTATE-CANCER; IN-VIVO; MECHANISMS; TRANSCRIPTION; TOXICITY; RISK
AB We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl-N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD(+)/NADH ratio and reduced NAD(+)-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD(+)/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD(+)-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD(+)/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD(+)/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU-treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU-treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD(+)-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis.
C1 [Fang, Mingzhu; Guo, Wei-Ren; Zarbl, Helmut] Rutgers State Univ, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Fang, Mingzhu; Zarbl, Helmut] Rutgers State Univ, Sch Publ Hlth, Piscataway, NJ USA.
[Fang, Mingzhu; Zarbl, Helmut] Rutgers State Univ, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA.
[Fang, Mingzhu; Zarbl, Helmut] Rutgers State Univ, NIEHS Ctr Environm Exposures & Dis, Piscataway, NJ USA.
[Fang, Mingzhu; Zarbl, Helmut] Rutgers State Univ, Canc Inst New Jersey, Piscataway, NJ USA.
[Park, Youngil; Kang, Hwan-Goo] Anim & Plant Quarantine Agcy, Vet Drugs & Biol Div, Anyang 430757, South Korea.
RP Fang, MZ (reprint author), Rutgers State Univ, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
EM fang@eohsi.rutgers.edu
FU National Institutes of Health [U19ES011387, P30ES005022]; V Foundation;
Society of Toxicology - Colgate Palmolive Grant for Alternative Research
FX National Institutes of Health (U19ES011387 and P30ES005022) and V
Foundation Grant for Cancer Research to H.Z. and Society of Toxicology -
Colgate Palmolive Grant for Alternative Research to M.F.
NR 52
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U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC 15
PY 2015
VL 6
IS 40
BP 42879
EP 42891
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD4QP
UT WOS:000369907900039
PM 26544624
ER
PT J
AU Yawn, BP
John-Sowah, J
AF Yawn, Barbara P.
John-Sowah, Joylene
TI Management of Sickle Cell Disease: Recommendations from the, 2014 Expert
Panel Report
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID ACUTE CHEST SYNDROME; RANDOMIZED TRIAL; ORAL PENICILLIN; YOUNG-CHILDREN;
HEALTH-CARE; ANEMIA; HYDROXYUREA; STROKE; PAIN; TRANSFUSIONS
AB Family physicians are the primary and sometimes only health care resource for families affected by sickle cell disease. Recently published guidelines provide important recommendations for health maintenance, acute care, and monitoring of disease-modifying therapy in persons with this condition. This overview highlights some of the most important clinical activities that can and should be carried out in the community care setting. Children with sickle cell anemia should receive prophylactic penicillin from birth through at least five years of age, and all persons with sickle cell disease require vaccination to prevent invasive pneumococcal disease. Annual screening with transcranial Doppler ultrasonography is recommended for all children with sickle cell disease beginning at two years of age and continuing through adolescence to evaluate the risk of stroke and to initiate transfusion therapy in those at high risk. Vasoocclusive crises require immediate and adequate analgesia appropriate to the level of patient-reported pain. Antibiotics, hospitalization, and incentive spirometry are indicated for those with acute chest syndrome. There is strong evidence to support the promotion and use of hydroxyurea therapy in patients nine months and older who have sickle cell anemia because its use can decrease the frequency of vasoocclusive crises and acute chest syndrome with limited adverse effects. Copyright (C) 2015 American Academy of Family Physicians.
C1 [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA.
[John-Sowah, Joylene] NHLBI, Prevent Med Ctr Translat Res & Implementat Sci, Bethesda, MD USA.
RP Yawn, BP (reprint author), Olmsted Med Ctr, 210 9th St SE, Rochester, MN 55904 USA.
EM byawn47@gmail.com
NR 40
TC 0
Z9 0
U1 2
U2 7
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
EI 1532-0650
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD DEC 15
PY 2015
VL 92
IS 12
BP 1069
EP 1076
PG 8
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA DB9XU
UT WOS:000368871800004
PM 26760593
ER
PT J
AU Sviridov, D
Remaley, AT
AF Sviridov, Dmitri
Remaley, Alan T.
TI High-density lipoprotein mimetics: promises and challenges
SO BIOCHEMICAL JOURNAL
LA English
DT Review
DE apolipoproteins; atherosclerosis; cholesterolmetabolism; lipoprotein
metabolism; peptides
ID APOLIPOPROTEIN-A-I; REVERSE CHOLESTEROL TRANSPORT; HERITABLE
HYPERLIPIDEMIC RABBITS; AMPHIPATHIC HELICAL PEPTIDE; RANDOMIZED
CONTROLLED-TRIAL; E-DEFICIENT MICE; E-NULL MICE; APOA-I;
ANTIINFLAMMATORY PROPERTIES; CORONARY ATHEROSCLEROSIS
AB The concept of lipoprotein mimetics was developed and extensively tested in the last three decades. Most lipoprotein mimetics were designed to recreate one or several functions of high-density lipoprotein (HDL) in the context of cardiovascular disease; however, the application of this approach is much broader. Lipoprotein mimetics should not just be seen as a set of compounds aimed at replenishing a deficiency or dysfunctionality of individual elements of lipoprotein metabolism but rather as a designer concept with remarkable flexibility and numerous applications in medicine and biology. In the present review, we discuss the fundamental design principles used to create lipoprotein mimetics, mechanisms of their action, medical indications and efficacy in animal models and human studies.
C1 [Sviridov, Dmitri] Baker IDI Heart & Diabet Inst, Lab Lipoprot & Atherosclerosis, Melbourne, Vic 3004, Australia.
[Remaley, Alan T.] NHLBI, Lipoprot Sect, NIH, Bethesda, MD 20892 USA.
RP Sviridov, D (reprint author), Baker IDI Heart & Diabet Inst, Lab Lipoprot & Atherosclerosis, Melbourne, Vic 3004, Australia.
EM Dmitri.Sviridov@bakeridi.edu.au
FU National Health and Medical Research Council of Australia [GNT1036352];
National Heart, Lung and Blood Institute
FX This work was supported by the National Health and Medical Research
Council of Australia [grant number GNT1036352 (to D.S.)]. D.S. is a
fellow of the NHMRC. Research by A.T.R. is supported by intramural
research funds from the National Heart, Lung and Blood Institute.
NR 105
TC 2
Z9 2
U1 2
U2 10
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD DEC 15
PY 2015
VL 472
BP 249
EP 259
DI 10.1042/BJ20150832
PN 3
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DC4EB
UT WOS:000369172100002
PM 26613945
ER
PT J
AU Costa, PAC
Leoratti, FMS
Figueiredo, MM
Tada, MS
Pereira, DB
Junqueira, C
Soares, IS
Barber, DL
Gazzinelli, RT
Antonelli, LRV
AF Costa, Pedro A. C.
Leoratti, Fabiana M. S.
Figueiredo, Maria M.
Tada, Mauro S.
Pereira, Dhelio B.
Junqueira, Caroline
Soares, Irene S.
Barber, Daniel L.
Gazzinelli, Ricardo T.
Antonelli, Lis R. V.
TI Induction of Inhibitory Receptors on T Cells During Plasmodium vivax
Malaria Impairs Cytokine Production
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE malaria; Plasmodium vivax; regulatory molecules; T cells
ID CHRONIC VIRAL-INFECTION; TUMOR-NECROSIS-FACTOR; FALCIPARUM MALARIA;
PROGRAMMED DEATH-1; TIM-3 EXPRESSION; PD-1 EXPRESSION; HIV-INFECTION;
UP-REGULATION; EXHAUSTION; ACTIVATION
AB The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4(+) and CD8(+) T cells. Higher frequencies of CD4(+) express more than 1 regulatory molecule compared to CD8(+) T cells. Moreover, lower proportions of CD4(+) T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin-3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function.
C1 [Costa, Pedro A. C.; Leoratti, Fabiana M. S.; Figueiredo, Maria M.; Junqueira, Caroline; Gazzinelli, Ricardo T.; Antonelli, Lis R. V.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Immunopatol, Belo Horizonte, MG, Brazil.
[Tada, Mauro S.; Pereira, Dhelio B.] Ctr Pesquisas Med Trop Rondonia, Porto Velho, Brazil.
[Soares, Irene S.] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, BR-05508 Sao Paulo, Brazil.
[Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Gazzinelli, Ricardo T.] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil.
RP Antonelli, LRV (reprint author), CPqRR FIOCRUZ, Fundacao Oswaldo Cruz, Lab Imunopatol, Ave Augusto de Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil.
EM lisantonelli@cpqrr.fiocruz.br
RI Soares, Irene/C-5974-2012;
OI Pereira, Dhelio/0000-0002-7761-5498
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
[483098/2011-6]; Fundacao de Amparo a Pesquisa do Estado de Minas Gerais
[CBB-PPM-00426-13]; National Institute of Science and Technology for
Vaccines [CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ 00077-09]; Oswaldo Cruz
Foundation (FIOCRUZ); National Institutes of Health/National Institute
of Allergy and Infectious Diseases (NIH/NIAID)
FX This work was supported by Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (483098/2011-6), Fundacao de Amparo a Pesquisa
do Estado de Minas Gerais (CBB-PPM-00426-13), the National Institute of
Science and Technology for Vaccines
(CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ 00077-09) and the Oswaldo Cruz
Foundation (FIOCRUZ). L. R. V. A. and R. T. G. are CNPq fellows (PQ). D.
L. B. was supported by the Intramural research program of the National
Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIH/NIAID).
NR 50
TC 7
Z9 7
U1 0
U2 4
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 DEC 15
PY 2015
VL 212
IS 12
BP 1999
EP 2010
DI 10.1093/infdis/jiv306
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DB7CH
UT WOS:000368671500020
PM 26019284
ER
PT J
AU Schiller, JT
Lowy, DR
AF Schiller, John T.
Lowy, Douglas R.
TI Single-Dose Vaccines Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
C1 [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
EM schillej@mail.nih.gov
NR 3
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 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2015
VL 212
IS 12
BP 2022
EP 2023
DI 10.1093/infdis/jiv394
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DB7CH
UT WOS:000368671500023
ER
PT J
AU Zhao, XN
Kumari, D
Gupta, S
Wu, D
Evanitsky, M
Yang, W
Usdin, K
AF Zhao, Xiao-Nan
Kumari, Daman
Gupta, Shikha
Wu, Di
Evanitsky, Maya
Yang, Wei
Usdin, Karen
TI Muts beta generates both expansions and contractions in a mouse model of
the Fragile X-associated disorders
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID TRINUCLEOTIDE REPEAT INSTABILITY; COUPLED REPAIR PROTEIN; KNOCK-IN MICE;
FMR1 GENE; FULL MUTATION; SOMATIC EXPANSION; CGG REPEAT; MISMATCH
RECOGNITION; HAIRPIN STRUCTURES; AGG INTERRUPTIONS
AB Fragile X-associated disorders are Repeat Expansion Diseases that result from expansion of a CGG/CCG-repeat in the FMR1 gene. Contractions of the repeat tract also occur, albeit at lower frequency. However, these contractions can potentially modulate disease symptoms or generate an allele with repeat numbers in the normal range. Little is known about the expansion mechanism and even less about contractions. We have previously demonstrated that the mismatch repair (MMR) protein MSH2 is required for expansions in a mouse model of these disorders. Here, we show that MSH3, the MSH2-binding partner in the MutS beta complex, is required for 98% of germ line expansions and all somatic expansions in this model. In addition, we provide evidence for two different contraction mechanisms that operate in the mouse model, a MutS beta-independent one that generates small contractions and a MutS beta-dependent one that generates larger ones. We also show that MutS beta complexes formed with the repeats have altered kinetics of ATP hydrolysis relative to complexes with bona fide MMR substrates and that MutS beta increases the stability of the CCG-hairpins at physiological temperatures. These data may have important implications for our understanding of the mechanism(s) of repeat instability and for the role of MMR proteins in this process.
C1 [Zhao, Xiao-Nan; Kumari, Daman; Evanitsky, Maya; Usdin, Karen] NIH, Lab Cell & Mol Biol, Sect Gene Struct & Dis, Bethesda, MD 20892 USA.
[Gupta, Shikha; Yang, Wei] NIH, Sect Struct & Mech DNA Repair Replicat & Recombin, Mol Biol Lab, Bethesda, MD 20892 USA.
[Wu, Di] NIH, Sect Phys Biochem, Lab Biochem & Genet, Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD 20892 USA.
RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
RI Zhao, Xiaonan/S-3139-2016
FU Intramural Program of the NIDDK [DK057808-07]
FX The work described in this manuscript was funded by a grant from the
Intramural Program of the NIDDK to K.U. (DK057808-07).
NR 58
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U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD DEC 15
PY 2015
VL 24
IS 24
BP 7087
EP 7096
DI 10.1093/hmg/ddv408
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2WZ
UT WOS:000368372600018
PM 26420841
ER
PT J
AU Rosenberg, SA
AF Rosenberg, Steven A.
TI CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate
Personalized Drug for the Immunotherapy of Human Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; RECOMBINANT
INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; ANTIGENS; REGRESSION; THERAPY
AB The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. (C)2015 AACR.
C1 [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC, Bldg 10,Room 3-3940, Bethesda, MD 20892 USA.
EM sar@nih.gov
FU Intramural NIH HHS [Z01 BC010984-01]
NR 19
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 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2015
VL 21
IS 24
BP 5409
EP 5411
DI 10.1158/1078-0432.CCR-14-3131
PG 3
WC Oncology
SC Oncology
GA DA1HK
UT WOS:000367546700001
PM 26672082
ER
PT J
AU Govindan, R
Mandrekar, SJ
Gerber, DE
Oxnard, GR
Dahlberg, SE
Chaft, J
Malik, S
Mooney, M
Abrams, JS
Janne, PA
Gandara, DR
Ramalingam, SS
Vokes, EE
AF Govindan, Ramaswamy
Mandrekar, Sumithra J.
Gerber, David E.
Oxnard, Geoffrey R.
Dahlberg, Suzanne E.
Chaft, Jamie
Malik, Shakun
Mooney, Margaret
Abrams, Jeffrey S.
Jaenne, Pasi A.
Gandara, David R.
Ramalingam, Suresh S.
Vokes, Everett E.
TI ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in
Early-Stage Non-Small Cell Lung Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID VINORELBINE PLUS CISPLATIN; CHEMOTHERAPY; GEFITINIB; PLACEBO; EGFR;
ADENOCARCINOMA; MULTICENTER; CRIZOTINIB; ERLOTINIB; PHASE-3
AB The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. (C)2015 AACR.
C1 [Govindan, Ramaswamy] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA.
[Mandrekar, Sumithra J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Gerber, David E.] UT Southwestern Med Ctr, Div Hematol & Oncol, Dallas, TX USA.
[Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Chaft, Jamie] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Malik, Shakun; Mooney, Margaret; Abrams, Jeffrey S.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Jaenne, Pasi A.] Harvard Univ, Sch Med, Lowe Ctr Thorac Oncol, Boston, MA USA.
[Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02115 USA.
[Gandara, David R.] Univ Calif Davis, Ctr Comprehens Canc, Div Hematol & Oncol, Sacramento, CA USA.
[Ramalingam, Suresh S.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA.
[Vokes, Everett E.] Univ Chicago, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA.
[Vokes, Everett E.] Univ Chicago, Comprehens Canc Res Ctr, Chicago, IL 60637 USA.
RP Govindan, R (reprint author), Washington Univ, Sch Med, Campus Box 8056, St Louis, MO 63110 USA.
EM rgovinda@dom.wustl.edu
OI Chaft, Jamie/0000-0002-5838-9982
FU NCI of the NIH [U10CA180821, U10CA18088]; [CA180820]; [CA180794];
[CA180870]; [CA180864]; [P30CA008748]
FX This work was supported in part by the NCI of the NIH under award
numbers U10CA180821 and U10CA18088 (to Alliance for Clinical Trials in
Oncology); CA180820, CA180794, CA180870, and CA180864 (to S.E.
Dahlberg); and P30CA008748 (to J. Chaft, through her institution).
NR 23
TC 9
Z9 9
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2015
VL 21
IS 24
BP 5439
EP 5444
DI 10.1158/1078-0432.CCR-15-0354
PG 6
WC Oncology
SC Oncology
GA DA1HK
UT WOS:000367546700008
PM 26672084
ER
PT J
AU Shono, N
Ohzeki, J
Otake, K
Martins, NMC
Nagase, T
Kimura, H
Larionov, V
Earnshaw, WC
Masumoto, H
AF Shono, Nobuaki
Ohzeki, Jun-ichirou
Otake, Koichiro
Martins, Nuno M. C.
Nagase, Takahiro
Kimura, Hiroshi
Larionov, Vladimir
Earnshaw, William C.
Masumoto, Hiroshi
TI CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A
assembly
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE CENP-A; CENP-C; CENP-I; Centromere; Human artificial chromosome; HAC;
Kinetochore
ID CENTROMERIC CHROMATIN; OUTER KINETOCHORE; CELL-CYCLE; EPIGENETIC
REGULATION; VERTEBRATE CELLS; TERMINAL DOMAIN; COMPLEX; DNA; NUCLEOSOME;
HJURP
AB Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoid(teto)). We also obtained cell lines bearing the alphoid(teto) array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly.
C1 [Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Shono, Nobuaki] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan.
[Martins, Nuno M. C.; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
[Nagase, Takahiro] Kazusa DNA Res Inst, Publ Relat Team, Kisarazu, Chiba 2920818, Japan.
[Kimura, Hiroshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan.
[Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Masumoto, H (reprint author), Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 2920818, Japan.
EM masumoto@kazusa.or.jp
RI Shono, Nobuaki/C-4130-2017;
OI Shono, Nobuaki/0000-0002-9060-1074; Martins, Nuno/0000-0003-3953-9313
FU MEXT KAKENHI [23247030, 23114008]; Kazusa DNA Research Institute
Foundation; Wellcome Trust [073915]; Japan Society for the Promotion of
Science (JSPS); Ministry of Education, Culture, Sports, Science and
Technology of Japan; Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research
FX This work was supported by MEXT KAKENHI [grant numbers 23247030 and
23114008]; and the Kazusa DNA Research Institute Foundation (to H.M.).
Work in the W.C.E. laboratory is funded by the Wellcome Trust, of which
W.C.E. is a Principal Research Fellow [grant number 073915]. Additional
experiments were supported by grants-in-aid from the Japan Society for
the Promotion of Science (JSPS) and the Ministry of Education, Culture,
Sports, Science and Technology of Japan (to H.K.); and the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research (to V.L.). Deposited in PMC for
immediate release.
NR 77
TC 8
Z9 8
U1 6
U2 7
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 DEC 15
PY 2015
VL 128
IS 24
BP 4572
EP 4587
DI 10.1242/jcs.180786
PG 16
WC Cell Biology
SC Cell Biology
GA DA1LH
UT WOS:000367556800010
PM 26527398
ER
PT J
AU Hong, JH
Muhammad, E
Zheng, CY
Hershkovitz, E
Alkrinawi, S
Loewenthal, N
Parvari, R
Muallem, S
AF Hong, Jeong Hee
Muhammad, Emad
Zheng, Changyu
Hershkovitz, Eli
Alkrinawi, Soliman
Loewenthal, Neta
Parvari, Ruti
Muallem, Shmuel
TI Essential role of carbonic anhydrase XII in secretory gland fluid and
HCO3- secretion revealed by disease causing human mutation
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID OOCYTE PLASMA-MEMBRANES; SURFACE-PH TRANSIENTS; PIG PANCREATIC-DUCTS;
ENHANCES CO2 FLUXES; CELL LINE CALU-3; SALIVARY-GLANDS; BICARBONATE
TRANSPORTERS; NA+/HCO3-COTRANSPORTER; BASOLATERAL MEMBRANE;
CL-/HCO3-EXCHANGER
AB Aberrant epithelial fluid and HCO3- secretion is associated with many diseases. The activity of HCO3- transporters depends of HCO3- availability that is determined by carbonic anhydrases (CAs). Which CAs are essential for epithelial function is unknown. CA12 stands out since the CA12(E143K) mutation causes salt wasting in sweat and dehydration in humans. Here, we report that expression of CA12 and of CA12(E143K) in mice salivary glands respectively increased and prominently inhibited ductal fluid secretion and salivation in vivo. CA12 markedly increases the activity and is the major HCO3- supplier of ductal Cl--HCO3- exchanger AE2, but not of NBCe1-B. The E143Kmutation alters CA12 glycosylation at N28 and N80, resulting in retention of the basolateral CA12 in the ER. Knockdown of AE2 and of CA12 inhibited pancreatic and salivary gland ductal AE2 activity and fluid secretion. Accordingly, patients homozygous for the CA12(E143K) mutation have a dry mouth, dry tongue phenotype. These findings reveal an unsuspected prominent role of CA12 in epithelial function, explain the disease and call for caution in the use of CA12 inhibitors in cancer treatment.
C1 [Hong, Jeong Hee; Zheng, Changyu; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signalling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Hong, Jeong Hee] Gachon Univ, Coll Med, Dept Physiol, Inchon 406799, South Korea.
[Muhammad, Emad; Parvari, Ruti] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, Beer Sheva, Israel.
[Muhammad, Emad; Parvari, Ruti] Natl Inst Biotechnol Negev, Beer Sheva, Israel.
[Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta] Ben Gurion Univ Negev, Soroka Med Ctr, Pediat Endocrinol Unit, IL-84105 Beer Sheva, Israel.
[Hershkovitz, Eli; Alkrinawi, Soliman; Loewenthal, Neta] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel.
RP Muallem, S (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signalling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA.
EM ruthi@bgu.ac.il; shmuel.muallem@nih.gov
RI Hershkovitz, Eli/F-1922-2012
FU Intramural NIH/NIDCR [DE000735-04]; Ministry of Health, Israel
[3000005152]; Basic Science Research Program through the National
Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future
Planning [2014R1A1A3049477]
FX This work was supported by Intramural NIH/NIDCR grant DE000735-04, grant
3000005152 from the Ministry of Health, Israel and by Basic Science
Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT & Future Planning
(2014R1A1A3049477).
NR 56
TC 2
Z9 2
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
EI 1469-7793
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD DEC 15
PY 2015
VL 593
IS 24
BP 5299
EP 5312
DI 10.1113/JP271378
PG 14
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA DA2JF
UT WOS:000367620400012
PM 26486891
ER
PT J
AU Pilipow, K
Roberto, A
Roederer, M
Waldmann, TA
Mavilio, D
Lugli, E
AF Pilipow, Karolina
Roberto, Alessandra
Roederer, Mario
Waldmann, Thomas A.
Mavilio, Domenico
Lugli, Enrico
TI IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy
SO CANCER RESEARCH
LA English
DT Review
ID IN-VIVO; ANTITUMOR-ACTIVITY; TUMOR MICROENVIRONMENT; INTERLEUKIN-2
THERAPY; METASTATIC MELANOMA; FUSION PROTEIN; CLINICAL-TRIAL; IL-15;
IL-15R-ALPHA; TRANSPLANTATION
AB Preclinical models revealed that the immune system can mediate rejection of established tumors, but direct evidence in humans has been limited to largely immunogenic tumors, such as melanoma. The recent success of immune checkpoint inhibitors and adoptive T-cell transfer immunotherapy in clinical trials has instilled new hope for the use of T-cell immunotherapy in the treatment of cancer. IL15, a potent immunostimulatory cytokine, both potentiates host T-cells and natural killer (NK) cell immune responses and promotes the generation of long-lived memory T cells with superior functional capacity, with potential use in adoptive T-cell transfer protocols. IL15 has been recently tested in the clinic and showed dramatic effects at the level of responding NK and CD8(+) memory T cells. The recent advances in the knowledge of IL15-dependent regulation of T-cell responses, gene expression, and metabolic adaptation have important implications for the use of IL15 in T-cell-based immunotherapy of cancer. (C) 2015 AACR.
C1 [Pilipow, Karolina; Lugli, Enrico] Humanitas Clin & Res Ctr, Lab Translat Immunol, Milan, Italy.
[Roberto, Alessandra; Mavilio, Domenico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Milan, Italy.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Waldmann, Thomas A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Mavilio, Domenico] Univ Milan, Dept Med Biotechnol & Translat Med BioMeTra, Milan, Italy.
RP Lugli, E (reprint author), Humanitas Clin & Res Ctr, Lab Translat Immunol, Via Alessandro Manzoni 113, Milan, Italy.
EM enrico.lugli@humanitasresearch.it
OI Roberto, Alessandra/0000-0001-6615-0026; Mavilio,
Domenico/0000-0001-6147-0952
FU Fondazione Cariplo (Grant Ricerca Biomedica) [2012/0683]; Italian
Ministry of Health (Bando Giovani Ricercatori) [GR-2011-02347324];
Associazione Italiana per la Ricerca sul Cancro [IG 14687]; Intramural
Research Program of the National Institutes of Allergy and Infectious
Diseases; National Cancer Institute; European Union Marie Curie Career
Integration Grant [322093]; Guglielmina Lucatello e Gino Mazzega
Fellowship from the Fondazione Italiana per la Ricerca sul Cancro
FX This work was supported by grants from the Fondazione Cariplo (Grant
Ricerca Biomedica 2012/0683 to E. Lugli), the Italian Ministry of Health
(Bando Giovani Ricercatori GR-2011-02347324 to E. Lugli), the
Associazione Italiana per la Ricerca sul Cancro (IG 14687 to D.
Mavilio), the Intramural Research Program of the National Institutes of
Allergy and Infectious Diseases (M. Roederer), and of the National
Cancer Institute (T.A. Waldmann). E. Lugli is an International Society
for the Advancement of Cytometry (ISAC) scholar and is a recipient of
the European Union Marie Curie Career Integration Grant 322093. A.
Roberto is a recipient of the Guglielmina Lucatello e Gino Mazzega
Fellowship from the Fondazione Italiana per la Ricerca sul Cancro.
NR 43
TC 6
Z9 6
U1 0
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2015
VL 75
IS 24
BP 5187
EP 5193
DI 10.1158/0008-5472.CAN-15-1498
PG 7
WC Oncology
SC Oncology
GA DA1JL
UT WOS:000367552000003
PM 26627006
ER
PT J
AU Feng, YM
Pinkerton, AB
Hulea, L
Zhang, TW
Davies, MA
Grotegut, S
Cheli, Y
Yin, HW
Lau, E
Kim, H
De, SK
Barile, E
Pellecchia, M
Bosenberg, M
Li, JL
James, B
Hassig, CA
Brown, KM
Topisirovic, I
Ronai, ZA
AF Feng, Yongmei
Pinkerton, Anthony B.
Hulea, Laura
Zhang, Tongwu
Davies, Michael A.
Grotegut, Stefan
Cheli, Yann
Yin, Hongwei
Lau, Eric
Kim, Hyungsoo
De, Surya K.
Barile, Elisa
Pellecchia, Maurizio
Bosenberg, Marcus
Li, Jian-Liang
James, Brian
Hassig, Christian A.
Brown, Kevin M.
Topisirovic, Ivan
Ronai, Ze'ev A.
TI SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas
by Disrupting the eIF4F Translation Initiation Complex
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; INHIBITION; RESISTANCE; STRATEGIES; BI-69A11; THERAPY;
LEADS; AKT
AB Disrupting the eukaryotic translation initiation factor 4F (eIF4F) complex offers an appealing strategy to potentiate the effectiveness of existing cancer therapies and to overcome resistance to drugs such as BRAF inhibitors (BRAFi). Here, we identified and characterized the small molecule SBI-0640756 (SBI756), a first-in-class inhibitor that targets eIF4G1 and disrupts the eIF4F complex. SBI-756 impaired the eIF4F complex assembly independently of mTOR and attenuated growth of BRAF-resistant and BRAF-independent melanomas. SBI-756 also suppressed AKT and NF-kappa B signaling, but small-molecule derivatives were identified that only marginally affected these pathways while still inhibiting eIF4F complex formation and melanoma growth, illustrating the potential for further structural and functional manipulation of SBI-756 as a drug lead. In the gene expression signature patterns elicited by SBI-756, DNA damage, and cell-cycle regulatory factors were prominent, with mutations in melanoma cells affecting these pathways conferring drug resistance. SBI-756 inhibited the growth of NRAS, BRAF, and NF1-mutant melanomas in vitro and delayed the onset and reduced the incidence of Nras/Ink4a melanomas in vivo. Furthermore, combining SBI-756 and a BRAFi attenuated the formation of BRAFi-resistant human tumors. Taken together, our findings show how SBI-756 abrogates the growth of BRAF-independent and BRAFi-resistant melanomas, offering a preclinical rationale to evaluate its antitumor effects in other cancers. (C) 2015 AACR.
C1 [Feng, Yongmei; Pinkerton, Anthony B.; Grotegut, Stefan; Cheli, Yann; Lau, Eric; Kim, Hyungsoo; De, Surya K.; Barile, Elisa; Pellecchia, Maurizio; Li, Jian-Liang; James, Brian; Hassig, Christian A.; Ronai, Ze'ev A.] Sanford Burnham Prebys Med Discovery Inst, Ctr Canc, La Jolla, CA 92037 USA.
[Hulea, Laura; Topisirovic, Ivan] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ, Canada.
[Hulea, Laura; Topisirovic, Ivan] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Zhang, Tongwu; Brown, Kevin M.] NCI, Div Canc Epidemiol & Genet, Lab Translat Genom, Bethesda, MD 20892 USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Melanoma Med Oncol, Houston, TX 77030 USA.
[Yin, Hongwei] Translat Genom Res Inst TGen, Canc & Cell Biol Div, Phoenix, AZ USA.
[Bosenberg, Marcus] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Bosenberg, Marcus] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
RP Ronai, ZA (reprint author), Sanford Burnham Prebys Med Discovery Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM zeev@ronailab.net
RI Cheli, Yann/O-5783-2016;
OI Pinkerton, Anthony/0000-0003-4571-152X
FU Melanoma Research Alliance; NCI Cancer Center grant [P30 CA30199,
CA016672]; Assistant Secretary of Defense for Health Affairs through the
Peer-Reviewed Cancer Program [W81XWH-14-1-0127]; CIHR [MOP-115-195]; CRS
[01713]; CIHR new investigator salary award; Intramural Research Program
of the Division of Cancer Epidemiology and Genetics; National Cancer
Institute
FX This work was supported by the Melanoma Research Alliance. Core Services
were supported by NCI Cancer Center grant P30 CA30199 (Z.A. Ronai) and
CA016672 (M.A. Davies). This work was also supported by the Assistant
Secretary of Defense for Health Affairs through the Peer-Reviewed Cancer
Program under Award No. W81XWH-14-1-0127 (Z.A. Ronai), CIHR
(MOP-115-195), CRS (01713), and CIHR new investigator salary award (IT),
and by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics; National Cancer Institute (T. Zhang and K.M.
Brown).
NR 18
TC 2
Z9 2
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2015
VL 75
IS 24
BP 5211
EP 5218
DI 10.1158/0008-5472.CAN-15-0885
PG 8
WC Oncology
SC Oncology
GA DA1JL
UT WOS:000367552000007
PM 26603897
ER
PT J
AU Shanker, A
Pellom, ST
Dudimah, DF
Thounaojam, MC
de Kluyver, RL
Brooks, AD
Yagita, H
McVicar, DW
Murphy, WJ
Longo, DL
Sayers, TJ
AF Shanker, Anil
Pellom, Samuel T., Jr.
Dudimah, Duafalia F.
Thounaojam, Menaka C.
de Kluyver, Rachel L.
Brooks, Alan D.
Yagita, Hideo
McVicar, Daniel W.
Murphy, William J.
Longo, Dan L.
Sayers, Thomas J.
TI Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells
to FasL Cytotoxicity
SO CANCER RESEARCH
LA English
DT Article
ID PROTEASOME INHIBITOR BORTEZOMIB; MULTIPLE-MYELOMA CELLS; IN-VIVO;
INDUCED APOPTOSIS; DENDRITIC CELLS; TUMOR-CELLS; MEDIATED LYSIS;
KAPPA-B; ACTIVATION; EXPRESSION
AB Cancer immunotherapy shows great promise but many patients fail to show objective responses, including in cancers that can respond well, such as melanoma and renal adenocarcinoma. The proteasome inhibitor bortezomib sensitizes solid tumors to apoptosis in response to TNF-family death ligands. Because T cells provide multiple death ligands at the tumor site, we investigated the effects of bortezomib on T-cell responses in immunotherapy models involving low-avidity antigens. Bortezomib did not affect lymphocyte or tissue-resident CD11c(+) CD8(+) dendritic cell counts in tumor-bearing mice, did not inhibit dendritic cell expression of costimulatory molecules, and did not decrease MHC class I/II-associated antigen presentation to cognate T cells. Rather, bortezomib activated NF-kappa B p65 in CD8(+) T cells, stabilizing expression of T-cell receptor CD3 zeta and IL2 receptor-alpha, while maintaining IFN gamma secretion to improve FasL-mediated tumor lysis. Notably, bortezomib increased tumor cell surface expression of Fas in mice as well as human melanoma tissue from a responsive patient. In renal tumor-bearing immunodeficient Rag2(-/-) mice, bortezomib treatment after adoptive T-cell immunotherapy reduced lung metastases and enhanced host survival. Our findings highlight the potential of proteasome inhibitors to enhance antitumor T-cell function in the context of cancer immunotherapy. (C) 2015 AACR.
C1 [Shanker, Anil; Pellom, Samuel T., Jr.; Dudimah, Duafalia F.; Thounaojam, Menaka C.] Meharry Med Coll, Sch Med, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
[Shanker, Anil] Vanderbilt Univ, Host Tumor Interact Res Program, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA.
[Shanker, Anil; Pellom, Samuel T., Jr.] Meharry Med Coll, Sch Grad Studies & Res, Nashville, TN 37208 USA.
[Pellom, Samuel T., Jr.] Meharry Med Coll, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37208 USA.
[de Kluyver, Rachel L.; Brooks, Alan D.; McVicar, Daniel W.; Sayers, Thomas J.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Brooks, Alan D.; Sayers, Thomas J.] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD USA.
[Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan.
[Murphy, William J.] Univ Calif Davis, Sch Med, Div Hematol Oncol, Dept Dermatol, Davis, CA 95616 USA.
[Murphy, William J.] Univ Calif Davis, Sch Med, Div Hematol Oncol, Dept Internal Med, Davis, CA 95616 USA.
[Longo, Dan L.] NIA, Lab Genet & Genom, NIH, Baltimore, MD 21224 USA.
RP Shanker, A (reprint author), Meharry Med Coll, Vanderbilt Ingram Canc Ctr, WBSB 2005,1005 Dr DB Todd Jr Blvd, Nashville, TN 37208 USA.
EM ashanker@mmc.edu; sayerst@mail.nih.gov
FU NCI, NIH [N01-CO-12400, HHSN261200800001E]; NIH [U54 CA163069, SC1
CA182843, U54 MD007593, R01 CA175370, T32 5T32HL007737, R25 GM059994,
G12 MD007586, R24 DA036420, S10 RR0254970]; Intramural Research Program
of NIH, Frederick National Lab, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds to
T.J. Sayers from the NCI, NIH, under contracts N01-CO-12400 and
HHSN261200800001E. This work was also supported by funds to A. Shanker
from the NIH grants U54 CA163069, SC1 CA182843, U54 MD007593, and R01
CA175370. S.T. Pellom was supported by NIH training grants T32
5T32HL007737 and R25 GM059994. The Meharry Morphology and Flow Cytometry
Cores are supported by NIH grants G12 MD007586, R24 DA036420, and S10
RR0254970. This research was also supported (in part) by the Intramural
Research Program of NIH, Frederick National Lab, Center for Cancer
Research.
NR 50
TC 4
Z9 4
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2015
VL 75
IS 24
BP 5260
EP 5272
DI 10.1158/0008-5472.CAN-15-0794
PG 13
WC Oncology
SC Oncology
GA DA1JL
UT WOS:000367552000012
PM 26494122
ER
PT J
AU Yan, HYH
Jiang, J
Pang, YL
Achyut, BR
Lizardo, M
Liang, XH
Hunter, K
Khanna, C
Hollander, C
Yang, L
AF Yan, Hangyi H.
Jiang, Jian
Pang, Yanli
Achyut, B. R.
Lizardo, Michael
Liang, Xinhua
Hunter, Kent
Khanna, Chand
Hollander, Christine
Yang, Li
TI CCL9 Induced by TGF beta Signaling in Myeloid Cells Enhances Tumor Cell
Survival in the Premetastatic Organ
SO CANCER RESEARCH
LA English
DT Article
ID PRE-METASTATIC NICHE; HUMAN-BREAST-CANCER; GROWTH-FACTOR-BETA;
SUPPRESSOR-CELLS; LUNG METASTASIS; MOUSE MODEL;
FUNCTIONAL-CHARACTERIZATION; BONE; MICROENVIRONMENT; INFLAMMATION
AB Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1(+)CD11b(+) immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. Importantly, CCL9 overexpression in myeloid cells lacking TGF beta signaling rescued the tumor metastasis defect observed in mice with myeloid-specific Tgfbr2 deletion. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. In addition, targeting CCL9 may avoid the adverse effects of TGFb-targeted therapy. (C)2015 AACR.
C1 [Yan, Hangyi H.; Jiang, Jian; Achyut, B. R.; Hunter, Kent; Hollander, Christine; Yang, Li] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Jiang, Jian; Liang, Xinhua] Sichuan Univ, West China Coll Stomatol, StateKey Lab Oral Dis, Chengdu 610064, Sichuan, Peoples R China.
[Pang, Yanli] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China.
[Lizardo, Michael; Khanna, Chand] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Yang, L (reprint author), NCI, 37 Convent Dr, Bethesda, MD 20892 USA.
EM yangl3@mail.nih.gov
FU NCI
FX This work was supported by NCI intramural funding to L. Yang.
NR 74
TC 6
Z9 6
U1 3
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2015
VL 75
IS 24
BP 5283
EP 5298
DI 10.1158/0008-5472.CAN-15-2282-T
PG 16
WC Oncology
SC Oncology
GA DA1JL
UT WOS:000367552000014
PM 26483204
ER
PT J
AU Contopoulos-Ioannidis, D
Wheeler, KM
Ramirez, R
Press, C
Mui, E
Zhou, Y
Van Tubbergen, C
Prasad, S
Maldonado, Y
Withers, S
Boyer, KM
Noble, AG
Rabiah, P
Swisher, CN
Heydemann, P
Wroblewski, K
Karrison, T
Grigg, ME
Montoya, JG
McLeod, R
AF Contopoulos-Ioannidis, Despina
Wheeler, Kelsey M.
Ramirez, Raymund
Press, Cindy
Mui, Ernest
Zhou, Ying
Van Tubbergen, Christine
Prasad, Sheela
Maldonado, Yvonne
Withers, Shawn
Boyer, Kenneth M.
Noble, A. Gwendolyn
Rabiah, Peter
Swisher, Charles N.
Heydemann, Peter
Wroblewski, Kristen
Karrison, Theodore
Grigg, Michael E.
Montoya, Jose G.
McLeod, Rima
TI Clustering of Toxoplasma gondii Infections Within Families of
Congenitally Infected Infants
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE clusters; Toxoplasma gondii; toxoplasmosis; congenital infections
ID UNITED-STATES; SEXUAL TRANSMISSION; EYE LESIONS; EPIDEMIC; OUTBREAK;
INGESTION; PREGNANCY; DIAGNOSIS; CHILDREN; EFFICACY
AB Background. Family clusters and epidemics of toxoplasmosis in North, Central, and South America led us to determine whether fathers of congenitally infected infants in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) have a high incidence of Toxoplasma gondii infection.
Methods. We analyzed serum samples collected from NCCCTS families between 1981 and 2013. Paternal serum samples were tested for T. gondii antibodies with immunoglobulin (Ig) G dye test and IgM enzyme-linked immunosorbent assay. Additional testing of paternal serum samples was performed with differential-agglutination and IgG avidity tests when T. gondii IgG and IgM results were positive and serum samples were collected by the 1-year visit of the congenitally infected child. Prevalence of paternal seropositivity and incidence of recent infection were calculated. We analyzed whether certain demographics, maternal parasite serotype, risk factors, or maternal/infant clinical manifestations were associated with paternal T. gondii infection status.
Results. Serologic testing revealed a high prevalence (29 of 81; 36%) of T. gondii infection in fathers, relative to the average seropositivity rate of 9.8% for boys and men aged 12-49 years in the United States between 1994 and 2004 (P < .001). Moreover, there was a higher-than-expected incidence of recent infections among fathers with serum samples collected by the 1-year visit of their child (6 of 45; 13%; P < .001). No demographic patterns or clinical manifestations in mothers or infants were associated with paternal infections, except for sandbox exposure.
Conclusions. The high prevalence of chronic and incidence of recent T. gondii infections in fathers of congenitally infected children indicates that T. gondii infections cluster within families in North America. When a recently infected person is identified, family clustering and community risk factors should be investigated for appropriate clinical management.
C1 [Contopoulos-Ioannidis, Despina; Maldonado, Yvonne] Stanford Univ, Sch Med, Dept Pediat, Div Infect Dis, Stanford, CA 94305 USA.
[Montoya, Jose G.] Stanford Univ, Sch Med, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA.
[Contopoulos-Ioannidis, Despina; Ramirez, Raymund; Press, Cindy; Montoya, Jose G.] Palo Alto Med Fdn, Toxoplasma Serol Lab, Palo Alto, CA USA.
[Wheeler, Kelsey M.; Mui, Ernest; Zhou, Ying; Van Tubbergen, Christine; Prasad, Sheela; Withers, Shawn; Boyer, Kenneth M.; Noble, A. Gwendolyn; Rabiah, Peter; Swisher, Charles N.; Heydemann, Peter; Wroblewski, Kristen; Karrison, Theodore; McLeod, Rima] Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA.
[Wheeler, Kelsey M.; Mui, Ernest; Zhou, Ying; Van Tubbergen, Christine; Prasad, Sheela; Withers, Shawn; Boyer, Kenneth M.; Noble, A. Gwendolyn; Rabiah, Peter; Swisher, Charles N.; Heydemann, Peter; Wroblewski, Kristen; Karrison, Theodore; McLeod, Rima] Univ Chicago, Dept Publ Hlth Sci, Toxoplasmosis Ctr, Dept Pediat Infect Dis, Chicago, IL 60637 USA.
[Boyer, Kenneth M.; Heydemann, Peter] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA.
[Noble, A. Gwendolyn; Swisher, Charles N.] Northwestern Univ, NW Mem Hosp, Lurie Childrens Hosp, Chicago, IL 60611 USA.
[Rabiah, Peter] N Shore Univ Hosp, Evanston, IL USA.
[Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McLeod, R (reprint author), Univ Chicago, 5841 S Maryland Ave N310,MC 2114, Chicago, IL 60637 USA.
EM rmcleod@uchicago.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) [R01
AI27530]; Intramural Research Program of the NIAID; Canadian Institute
for Advanced Research Integrated Microbial Biodiversity program;
Division of Microbiology and Infectious Diseases
FX This work was supported by the Division of Microbiology and Infectious
Diseases, National Institute of Allergy and Infectious Diseases (NIAID)
(grant R01 AI27530); the Intramural Research Program of the NIAID (M. E.
G.); and the Mann Cornwell family, Engel family (and "Taking Out Toxo"),
and Morel and Rooney-Alden families. M. E. G. is a scholar in the
Canadian Institute for Advanced Research Integrated Microbial
Biodiversity program.
NR 40
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U2 10
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 DEC 15
PY 2015
VL 61
IS 12
BP 1815
EP 1824
DI 10.1093/cid/civ721
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CY5RN
UT WOS:000366465100010
PM 26405150
ER
PT J
AU Hutson, SL
Wheeler, KM
McLone, D
Frim, D
Penn, R
Swisher, CN
Heydemann, PT
Boyer, KM
Noble, AG
Rabiah, P
Withers, S
Montoya, JG
Wroblewski, K
Karrison, T
Grigg, ME
McLeod, R
AF Hutson, Samuel L.
Wheeler, Kelsey M.
McLone, David
Frim, David
Penn, Richard
Swisher, Charles N.
Heydemann, Peter T.
Boyer, Kenneth M.
Noble, A. Gwendolyn
Rabiah, Peter
Withers, Shawn
Montoya, Jose G.
Wroblewski, Kristen
Karrison, Theodore
Grigg, Michael E.
McLeod, Rima
TI Patterns of Hydrocephalus Caused by Congenital Toxoplasma gondii
Infection Associate With Parasite Genetics
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE hydrocephalus; Toxoplasma gondii; aqueductal obstruction; foraminal
obstruction
ID ENDOSCOPIC 3RD VENTRICULOSTOMY; INFANTS; MANAGEMENT
AB Four anatomical patterns of hydrocephalus secondary to congenital Toxoplasma gondii infection were identified and characterized for infants enrolled in the National Collaborative Chicago-based Congenital Toxoplasmosis Study. Analysis of parasite serotype revealed that different anatomical patterns associate with Type-II vs Not-Exclusively Type-II strains (NE-II) (P = .035).
C1 [Hutson, Samuel L.; Wheeler, Kelsey M.; Withers, Shawn; McLeod, Rima] Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA.
[McLone, David; Swisher, Charles N.; Noble, A. Gwendolyn] Northwestern Univ, Chicago, IL 60611 USA.
[McLone, David; Swisher, Charles N.; Noble, A. Gwendolyn] Lurie Childrens Hosp & Med Ctr, Chicago, IL USA.
[Frim, David] Univ Chicago, Neurosurg Sect, Chicago, IL 60637 USA.
[Penn, Richard] Univ Illinois, Coll Med, Coll Engn, Dept Bioengn, Chicago, IL USA.
[Heydemann, Peter T.; Boyer, Kenneth M.] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA.
[Rabiah, Peter] N Shore Univ Hosp, Evanston, IL USA.
[Montoya, Jose G.] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA.
[Wroblewski, Kristen; Karrison, Theodore] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA.
[Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McLeod, R (reprint author), Univ Chicago, 5841 S Maryland Ave,Rm N310,MC-2114, Chicago, IL 60637 USA.
EM rmcleod@uchicago.edu
FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR000430]; NIAID NIH HHS [R01
AI027530, R01 AI27530]
NR 16
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U1 2
U2 5
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 DEC 15
PY 2015
VL 61
IS 12
BP 1831
EP 1834
DI 10.1093/cid/civ720
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CY5RN
UT WOS:000366465100012
PM 26405147
ER
PT J
AU Mirani, G
Williams, PL
Chernoff, M
Abzug, MJ
Levin, MJ
Seage, GR
Oleske, JM
Purswani, MU
Hazra, R
Traite, S
Zimmer, B
Van Dyke, RB
AF Mirani, Gayatri
Williams, Paige L.
Chernoff, Miriam
Abzug, Mark J.
Levin, Myron J.
Seage, George R., III
Oleske, James M.
Purswani, Murli U.
Hazra, Rohan
Traite, Shirley
Zimmer, Bonnie
Van Dyke, Russell B.
CA IMPAACT P1074 Study Team
TI Changing Trends in Complications and Mortality Rates Among US Youth and
Young Adults With HIV Infection in the Era of Combination Antiretroviral
Therapy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE pediatric HIV; mortality; opportunistic infections; psychiatric;
pregnancy
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS COLLABORATIVE TRANSMISSION;
PERINATALLY ACQUIRED HIV; OPPORTUNISTIC INFECTIONS; RISK-FACTORS; HAART
ERA; HIV-1-INFECTED CHILDREN; UNITED-KINGDOM; ADOLESCENTS; HEALTH
AB Background. Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur.
Methods. We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed.
Results. Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [ standard deviation] age at last chart review, 20.9 [ 5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions.
Conclusions. Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.
C1 [Mirani, Gayatri; Van Dyke, Russell B.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Williams, Paige L.; Chernoff, Miriam; Traite, Shirley] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Williams, Paige L.; Seage, George R., III] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Abzug, Mark J.; Levin, Myron J.] Univ Colorado, Sch Med, Aurora, CO USA.
[Abzug, Mark J.; Levin, Myron J.] Childrens Hosp Colorado, Aurora, CO USA.
[Oleske, James M.] Rutgers New Jersey Med Sch, Newark, NJ USA.
[Purswani, Murli U.] Bronx Lebanon Hosp Ctr, Albert Einstein Coll Med, Bronx, NY 10456 USA.
[Zimmer, Bonnie] Frontier Sci Technol & Res Fdn, Amherst, NY USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Williams, PL (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA.
EM paige@hsph.harvard.edu
RI Oleske, James/C-1951-2016
OI Oleske, James/0000-0003-2305-5605
FU National Institute of Allergy and Infectious Diseases of NIH [IMPAACT
Leadership and Operations Center] [UM1AI068632]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Institute of Mental Health; National Institute of Allergy and Infectious
Diseases of NIH [IMPAACT Statistical and Data Management Center]
[UM1AI068616]; National Institute of Allergy and Infectious Diseases of
NIH [IMPAACT Laboratory Center] [UM1AI106716]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials (IMPAACT) group was provided by the National Institute
of Allergy and Infectious Diseases of the NIH under (grants UM1AI068632
[IMPAACT Leadership and Operations Center], UM1AI068616 [IMPAACT
Statistical and Data Management Center], and UM1AI106716 [IMPAACT
Laboratory Center]), with cofunding from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development and the
National Institute of Mental Health.
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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 DEC 15
PY 2015
VL 61
IS 12
BP 1850
EP 1861
DI 10.1093/cid/civ687
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CY5RN
UT WOS:000366465100016
PM 26270680
ER
PT J
AU Halford, WP
Geltz, J
Messer, RJ
Hasenkrug, KJ
AF Halford, William P.
Geltz, Joshua
Messer, Ronald J.
Hasenkrug, Kim J.
TI Antibodies Are Required for Complete Vaccine-Induced Protection against
Herpes Simplex Virus 2
SO PLOS ONE
LA English
DT Article
ID CD8(+) T-CELLS; GENITAL HERPES; DEFICIENT MICE; RETROVIRAL INFECTION;
ADENOVIRUS VECTORS; TRIGEMINAL GANGLIA; PEPTIDE LIGANDS; GLYCOPROTEIN-B;
SAFETY PROFILE; NERVOUS-SYSTEM
AB Herpes simplex virus 2 (HSV-2) 0 Delta NLS is a live HSV-2 ICP0(-) mutant vaccine strain that is profoundly attenuated in vivo due to its interferon-hypersensitivity. Recipients of the HSV-2 0.NLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0 Delta NLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0 Delta NLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient mu MT mice. Vaccination with live HSV-2 0 Delta NLS induced equivalent CD8(+) T cell responses in wild-type and mu MT mice. Vaccinated mu MT mice shed similar to 40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell(+)) mice, and most vaccinated mu MT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0 Delta NLS-vaccinated mu MT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2.
C1 [Halford, William P.; Geltz, Joshua] So Illinois Univ, Sch Med, Dept Microbiol & Immunol, Springfield, IL 62702 USA.
[Messer, Ronald J.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Halford, WP (reprint author), So Illinois Univ, Sch Med, Dept Microbiol & Immunol, Springfield, IL 62702 USA.
EM halford@siumed.edu
FU National Institutes of Health [R21 AI081072]; SIU School of Medicine
FX Funding for this study was provided by the National Institutes of Health
grant R21 AI081072 and startup funds to William Halford from the SIU
School of Medicine. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 86
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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 DEC 15
PY 2015
VL 10
IS 12
AR e0145228
DI 10.1371/journal.pone.0145228
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9HZ
UT WOS:000366719300053
PM 26670699
ER
PT J
AU Khoury, MJ
AF Khoury, Muin J.
TI Planning for the Future of Epidemiology in the Era of Big Data and
Precision Medicine
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE big data; epidemiology; funding; genomics; precision medicine; training
ID OMIC TECHNOLOGIES; PRIMER; DESIGN; HEALTH
AB We live in the era of genomics and big data. Evaluating the impact on health of large-scale biological, social, and environmental data is an emerging challenge in the field of epidemiology. In the past 3 years, major discussions and plans for the future of epidemiology, including with several recommendations for actions to transform the field, have been launched by 2 institutes within the National Institutes of Health. In the present commentary, I briefly explore the themes of these recommendations and their effects on leadership, resources, cohort infrastructure, and training. Ongoing engagement within the epidemiology community is needed to determine how to shape the evolution of the field and what truly matters for changing population health. We also need to assess how to leverage existing epidemiology resources and develop new studies to improve human health. Readers are invited to examine these recommendations, consider others that might be important, and join in the conversation about the future of epidemiology.
C1 [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Rockville, MD 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]
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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 DEC 15
PY 2015
VL 182
IS 12
BP 977
EP 979
DI 10.1093/aje/kwv228
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CY8AD
UT WOS:000366629900001
PM 26628513
ER
PT J
AU Loftfield, E
Freedman, ND
Graubard, BI
Guertin, KA
Black, A
Huang, WY
Shebl, FM
Mayne, ST
Sinha, R
AF Loftfield, Erikka
Freedman, Neal D.
Graubard, Barry I.
Guertin, Kristin A.
Black, Amanda
Huang, Wen-Yi
Shebl, Fatma M.
Mayne, Susan T.
Sinha, Rashmi
TI Association of Coffee Consumption With Overall and Cause-Specific
Mortality in a Large US Prospective Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE additives; caffeine; cause-specific mortality; coffee; mortality
ID DOSE-RESPONSE METAANALYSIS; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; DECAFFEINATED COFFEE; CANCER INCIDENCE; CAFFEINE
INTAKE; LIVER-CANCER; RISK; QUESTIONNAIRE; DRINKING
AB Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (< 1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); >= 6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression.
C1 [Loftfield, Erikka; Freedman, Neal D.; Graubard, Barry I.; Guertin, Kristin A.; Black, Amanda; Huang, Wen-Yi; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Loftfield, Erikka; Shebl, Fatma M.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Shebl, Fatma M.; Mayne, Susan T.] Yale Univ, Ctr Canc, New Haven, CT USA.
[Mayne, Susan T.] US Dept HHS, Ctr Food Safety & Appl Nutr, Food & Drug Adm, College Pk, MD USA.
RP Loftfield, E (reprint author), NCI, NCI Shady Grove, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr 6E332, Rockville, MD 20850 USA.
EM erikka.loftfield@nih.gov
FU Yale-National Cancer Institute predoctoral training grant [T32
CA105666]; Intramural Research Program of National Institutes of Health,
National Cancer Institute
FX This study was supported in part by a Yale-National Cancer Institute
predoctoral training grant (grant T32 CA105666) to S.T.M. and by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 42
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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 DEC 15
PY 2015
VL 182
IS 12
BP 1010
EP 1022
DI 10.1093/aje/kwv146
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CY8AD
UT WOS:000366629900005
PM 26614599
ER
PT J
AU Rolland, B
Reid, S
Stelling, D
Warnick, G
Thornquist, M
Feng, ZD
Potter, JD
AF Rolland, Betsy
Reid, Suzanna
Stelling, Deanna
Warnick, Greg
Thornquist, Mark
Feng, Ziding
Potter, John D.
TI Toward Rigorous Data Harmonization in Cancer Epidemiology Research: One
Approach
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cancer epidemiology; data harmonization; data pooling
ID ASIA COHORT CONSORTIUM; BODY-MASS INDEX; DATASHAPER APPROACH; POOLED
ANALYSIS; RISK; ASSOCIATION; DEATH
AB Cancer epidemiologists have a long history of combining data sets in pooled analyses, often harmonizing heterogeneous data from multiple studies into 1 large data set. Although there are useful websites on data harmonization with recommendations and support, there is little research on best practices in data harmonization; each project conducts harmonization according to its own internal standards. The field would be greatly served by charting the process of data harmonization to enhance the quality of the harmonized data. Here, we describe the data harmonization process utilized at the Fred Hutchinson Cancer Research Center (Seattle, Washington) by the coordinating centers of several research projects. We describe a 6-step harmonization process, including: 1) identification of questions the harmonized data set is required to answer; 2) identification of high-level data concepts to answer those questions; 3) assessment of data availability for data concepts; 4) development of common data elements for each data concept; 5) mapping and transformation of individual data points to common data elements; and 6) quality-control procedures. Our aim here is not to claim a "correct" way of doing data harmonization but to encourage others to describe their processes in order that we can begin to create rigorous approaches. We also propose a research agenda around this issue.
C1 [Rolland, Betsy] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Rolland, Betsy; Reid, Suzanna; Stelling, Deanna; Warnick, Greg; Thornquist, Mark; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Potter, John D.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Rolland, B (reprint author), NCI, Canc Prevent Fellowship Program, 9609 Med Ctr Dr,Room 3E460, Rockville, MD 20892 USA.
EM brolland@uw.edu
OI Potter, John/0000-0001-5439-1500
FU Fred Hutchinson Cancer Research Center; National Institutes of Health
[U24-086368]
FX This work was supported by the Fred Hutchinson Cancer Research Center
and National Institutes of Health grant U24-086368 (Z.F.).
NR 12
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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 DEC 15
PY 2015
VL 182
IS 12
BP 1033
EP 1038
DI 10.1093/aje/kwv133
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CY8AD
UT WOS:000366629900007
PM 26589709
ER
PT J
AU Yang, CR
Raghuram, V
Emamian, M
Sandoval, PC
Knepper, MA
AF Yang, Chin-Rang
Raghuram, Viswanathan
Emamian, Milad
Sandoval, Pablo C.
Knepper, Mark A.
TI Deep proteomic profiling of vasopressin-sensitive collecting duct cells.
II. Bioinformatic analysis of vasopressin signaling
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE aquaporin-2; mass spectrometry; ribosome; translation; small GTPase;
protein kinase; phosphorylation
ID PROTEIN-KINASE-A; QUANTITATIVE PHOSPHOPROTEOMICS; AQUAPORIN-2
PHOSPHORYLATION; PLASMA-MEMBRANE; WATER CHANNELS; LC-MS/MS; KIDNEY;
AQP2; EXPRESSION; FRACTIONS
AB Vasopressin controls osmotic water transport in the renal collecting duct through regulation of aquaporin-2 (AQP2). We carried out bioinformatic analysis of quantitative proteomic data from the accompanying article to investigate the mechanisms involved. The experiments used stable isotope labeling by amino acids in cell culture in cultured mpkCCD cells to quantify each protein species in each of five differential-centrifugation (DC) fractions with or without the vasopressin analog 1-desamino-8-D-arginine-vasopressin (dDAVP). The mass spectrometry data and parallel Western blot experiments confirmed that dDAVP addition is associated with an increase in AQP2 abundance in the 17,000-g pellet and a corresponding decrease in the 200,000-g pellet. Remarkably, all subunits of the cytoplasmic ribosome also increased in the 17,000-g pellet in response to dDAVP (P < 10(-34)), with a concomitant decrease in the 200,000-g pellet. Eukaryotic translation initiation complex 3 (eIF3) subunits underwent parallel changes (P < 10(-6)). These findings are consistent with translocation of assembled ribosomes and eIF3 complexes into the rough endoplasmic reticulum in response to dDAVP. Conversely, there was a systematic decrease in small GTPase abundances in the 17,000-g fraction. In contrast, most proteins, including protein kinases, showed no systematic redistribution among DC fractions. Of the 521 protein kinases coded by the mouse genome, 246 were identified, but many fewer were found to colocalize with AQP2 among DC fractions. Bayes' rule was used to integrate the new colocalization data with prior data to identify protein kinases most likely to phosphorylate aquaporin-2 at Ser(256) (Camk2b > Camk2d > Prkaca) and Ser(261) (Mapk1 = Mapk3 > Mapk14).
C1 [Yang, Chin-Rang; Raghuram, Viswanathan; Emamian, Milad; Sandoval, Pablo C.; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NIH, Bldg 10,Rm 6N307,10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA.
EM knepperm@nhlbi.nih.gov
FU [HL-006129]; [HL-001285]
FX This study was carried out in the National Heart, Lung, and Blood
Institute Intramural Program (Projects HL-006129 and HL-001285, M. A.
Knepper). The authors are affiliated with the National, Heart, Lung, and
Blood Institute Division of Intramural Research and receive funding
support through the intramural budget (Projects HL-006129 "Computational
Tools for Proteomics" and HL-001285 "Solute and Water Transport in Renal
Epithelia").
NR 40
TC 9
Z9 9
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD DEC 15
PY 2015
VL 309
IS 12
BP C799
EP C812
DI 10.1152/ajpcell.00214.2015
PG 14
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA CY8BC
UT WOS:000366632400004
PM 26310817
ER
PT J
AU Yang, CR
Tongyoo, P
Emamian, M
Sandoval, PC
Raghuram, V
Knepper, MA
AF Yang, Chin-Rang
Tongyoo, Pumipat
Emamian, Milad
Sandoval, Pablo C.
Raghuram, Viswanathan
Knepper, Mark A.
TI Deep proteomic profiling of vasopressin-sensitive collecting duct cells.
I. Virtual Western blots and molecular weight distributions
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE aquaporin-2; liquid chromatography-tandem mass spectrometry; mass
spectrometry; differential centrifugation; mpkCCD
ID MASS-SPECTROMETRY; PRINCIPAL CELLS; AQUAPORIN 2; PROTEIN; EXPRESSION;
KIDNEY; KAPPA
AB The mouse mpkCCD cell line is a continuous cultured epithelial cell line with characteristics of renal collecting duct principal cells. This line is widely used to study epithelial transport and its regulation. To provide a data resource useful for experimental design and interpretation in studies using mpkCCD cells, we have carried out "deep" proteomic profiling of these cells using three levels of fractionation (differential centrifugation, SDS-PAGE, and HPLC) followed by tandem mass spectrometry to identify and quantify proteins. The analysis of all resulting samples generated 34.6 gigabytes of spectral data. As a result, we identified 6,766 proteins in mpkCCD cells at a high level of stringency. These proteins are expressed over eight orders of magnitude of protein abundance. The data are provided to users as a public data base (https://helixweb.nih.gov/ESBL/Database/mpkFractions/). The mass spectrometry data were mapped back to their gel slices to generate "virtual Western blots" for each protein. For most of the 6,766 proteins, the apparent molecular weight from SDS-PAGE agreed closely with the calculated molecular weight. However, a substantial fraction (>15%) of proteins was found to run aberrantly, with much higher or much lower mobilities than predicted. These proteins were analyzed to identify mechanisms responsible for altered mobility on SDS-PAGE, including high or low isoelectric point, high or low hydrophobicity, physiological cleavage, residence in the lysosome, posttranslational modifications, and expression of alternative isoforms due to alternative exon usage. Additionally, this analysis identified a previously unrecognized isoform of aquaporin-2 with apparent molecular mass <20 kDa.
C1 [Yang, Chin-Rang; Tongyoo, Pumipat; Emamian, Milad; Sandoval, Pablo C.; Raghuram, Viswanathan; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tongyoo, Pumipat] Chulalongkorn Univ, Fac Grad Sch, Interdept Program Biomed Sci, Bangkok, Thailand.
RP Knepper, MA (reprint author), NIH, Bldg 10,Rm 6N307,10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA.
EM knepperm@nhlbi.nih.gov
FU NHLBI Intramural Program [HL-006129, HL-001285]; Thailand Research Fund
under the Royal Golden Jubilee Ph.D. Program; Chulalongkorn University
[PHD/0200/2552]
FX The study was carried out in NHLBI Intramural Program (Projects
HL-006129 and HL-001285, M. A. Knepper). P. Tongyoo was supported by the
Thailand Research Fund under the Royal Golden Jubilee Ph.D. Program and
Chulalongkorn University (PHD/0200/2552). Authors are affiliated with
the NHLBI Division of Intramural Research and receive funding support
through the intramural budget (Projects HL-006129 "Computational Tools
for Proteomics" and HL-001285 "Solute and Water Transport in Renal
Epithelia").
NR 26
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Z9 7
U1 3
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD DEC 15
PY 2015
VL 309
IS 12
BP C785
EP C798
DI 10.1152/ajpcell.00213.2015
PG 14
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA CY8BC
UT WOS:000366632400003
PM 26310816
ER
PT J
AU Nawaz, AA
Chen, YC
Narna, N
Nissly, RH
Ren, LQ
Ozcelik, A
Wang, L
McCoy, JP
Levine, SJ
Huang, TJ
AF Nawaz, Ahmad Ahsan
Chen, Yuchao
Narna, Nitesh
Nissly, Ruth Helmus
Ren, Liqiang
Ozcelik, Adem
Wang, Lin
McCoy, J. Philip
Levine, Stewart J.
Huang, Tony Jun
TI Acoustofluidic Fluorescence Activated Cell Sorter
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID SURFACE ACOUSTIC-WAVES; ON-A-CHIP; FLOW-CYTOMETRY; MICROFLUIDIC CHANNEL;
MAMMALIAN-CELLS; SYSTEM; MICROPARTICLES; SEPARATION; PARTICLES; SSAW
AB Selective isolation of cell subpopulations with defined biological characteristics is crucial for many biological studies and clinical applications. In this work, we present the development of an acoustofluidic fluorescence activated cell sorting (FACS) device that simultaneously performs on-demand, high-throughput, high-resolution cell detection and sorting, integrated onto a single chip. Our acoustofluidic FACS device uses the "microfluidic drifting" technique to precisely focus cells/particles three dimensionally and achieves a flow of single-file particles/cells as they pass through a laser interrogation region. We then utilize short bursts (1.50 mu s) of standing surface acoustic waves (SSAW) triggered by an electronic feedback system to sort fluorescently labeled particles/cells with desired biological properties. We have demonstrated continuous isolation of fluorescently labeled HeLa cells from unlabeled cells at a throughput of similar to 1200 events/s with a purity reaching 92.3 +/- 3.39%. Furthermore, 99.18% postsort cell viability indicates that our acoustofluidic sorting technique maintains a high integrity of cells. Therefore, our integrated acoustofluidic FACS device is demonstrated to achieve two-way cell sorting with high purity, biocompatibility, and biosafety. We believe that our device has significant potential for use as a low-cost, high-performance, portable, and user-friendly FACS instrument.
C1 [Nawaz, Ahmad Ahsan; Chen, Yuchao; Narna, Nitesh; Ren, Liqiang; Ozcelik, Adem; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA.
[Nawaz, Ahmad Ahsan] Natl Univ Sci & Technol, Sch Mech & Mfg Engn, H-12 Islamabad, Pakistan.
[Nissly, Ruth Helmus] Penn State Univ, Huck Inst Life Sci, Microscopy & Cytometry Facil, University Pk, PA 16802 USA.
[Wang, Lin] Ascent Bionano Technol Inc, State Coll, PA 16801 USA.
[McCoy, J. Philip; Levine, Stewart J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.
EM junhuang@psu.edu
RI Huang, Tony/A-1546-2009; Nama, Nitesh/E-9030-2014; Ren,
Liqiang/E-8953-2015
OI Ren, Liqiang/0000-0003-0863-4609
FU National Institutes of Health [1 R01 GM112048-01A1, 1R33EB019785-01];
National Science Foundation [IIP-1534645]; Penn State Center for
Nanoscale Science (MRSEC) [DMR-1420620]; NHLBI Division of Intramural
Research; NSF
FX We thank Dr. Peng Li for helpful discussions and Mark Naivar for his
guidance on the Azurite data acquisition system. This research was
supported by National Institutes of Health (1 R01 GM112048-01A1 and
1R33EB019785-01), National Science Foundation (IIP-1534645), and the
Penn State Center for Nanoscale Science (MRSEC) under Grant DMR-1420620.
J.P.M. and S.J.L. are supported by the NHLBI Division of Intramural
Research. Components of this work were conducted at the Penn State node
of the NSF-funded National Nanotechnology Infrastructure Network (NNIN)
and Microscopy and Cytometry Facility.
NR 61
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U1 5
U2 45
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD DEC 15
PY 2015
VL 87
IS 24
BP 12051
EP 12058
DI 10.1021/acs.analchem.5b02398
PG 8
WC Chemistry, Analytical
SC Chemistry
GA CZ1NC
UT WOS:000366871500017
PM 26331909
ER
PT J
AU Kharebava, G
Rashid, MA
Lee, JW
Sarkar, S
Kevala, K
Kim, HY
AF Kharebava, Giorgi
Rashid, Mohammad A.
Lee, Ji-Won
Sarkar, Sarmila
Kevala, Karl
Kim, Hee-Yong
TI N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes
growth of cortical axons
SO BIOLOGY OPEN
LA English
DT Article
DE Axon; Docosahexaenoic acid; Sonic hedgehog; Synaptamide; Cyclopamine
ID CENTRAL-NERVOUS-SYSTEM; SONIC HEDGEHOG; DOCOSAHEXAENOIC ACID;
NEUROFILAMENT PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; PATHWAY; PROTEIN;
MODULATION; SURVIVAL; BDNF
AB Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3) that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1) transcription and sonic hedgehog (Shh) target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO) agonist (SAG) or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.
C1 [Kharebava, Giorgi; Rashid, Mohammad A.; Lee, Ji-Won; Sarkar, Sarmila; Kevala, Karl; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA.
EM hykim@nih.gov
FU Defense Medical Research and Development Program (DMRDP)
[W81XWH-11-2-0074]; Intramural Research Program of the National
Institute on Alcohol Abuse and Alcoholism, National Institutes of Health
FX This study was supported by the Defense Medical Research and Development
Program (DMRDP) [W81XWH-11-2-0074] and Intramural Research Program of
the National Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health.
NR 61
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PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD DEC 15
PY 2015
VL 4
IS 12
BP 1660
EP 1670
DI 10.1242/bio.013425
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CY8QH
UT WOS:000366672900007
PM 26545965
ER
PT J
AU Herdman, CA
Devkota, L
Lin, CM
Niu, HC
Strecker, TE
Lopez, R
Liu, L
George, CS
Tanpure, RP
Hamel, E
Chaplin, DJ
Mason, RP
Trawick, ML
Pinney, KG
AF Herdman, Christine A.
Devkota, Laxman
Lin, Chen-Ming
Niu, Haichan
Strecker, Tracy E.
Lopez, Ramona
Liu, Li
George, Clinton S.
Tanpure, Rajendra P.
Hamel, Ernest
Chaplin, David J.
Mason, Ralph P.
Trawick, Mary Lynn
Pinney, Kevin G.
TI Structural interrogation of benzosuberene-based inhibitors of tubulin
polymerization
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Inhibitors of tubulin polymerization; Benzosuberene analogues; Vascular
disrupting agents; Small-molecule synthesis
ID VASCULAR DISRUPTING AGENTS; NUCLEOPHILIC AROMATIC-SUBSTITUTION;
COMBRETASTATIN A4 PHOSPHATE; ANTINEOPLASTIC AGENTS; BIOLOGICAL
EVALUATION; TUMOR VASCULATURE; COMBRETUM-CAFFRUM; CELL-GROWTH; A-4
PRODRUG; CANCER
AB The discovery of 3-methoxy-9-(3',4',5'-trimethoxyphenyl)-6,7-dihydro-5H-benzo[ 7] annulen-4-ol (a benzosuberene-based analogue referred to as KGP18) was originally inspired by the natural products colchicine and combretastatin A-4 (CA4). The relative structural simplicity and ease of synthesis of KGP18, coupled with its potent biological activity as an inhibitor of tubulin polymerization and its cytotoxicity (in vitro) against human cancer cell lines, has resulted in studies focused on new analogue design and synthesis. Our goal was to probe the relationship of structure to function in this class of anticancer agents. A series of twenty-two new benzosuberene-based analogues of KGP18 was designed and synthesized. These compounds vary in their methoxylation pattern and separately incorporate trifluoromethyl groups around the pendant aryl ring for the evaluation of the effect of functional group modifications on the fused six-membered aromatic ring. In addition, the 8,9-saturated congener of KGP18 has been synthesized to assess the necessity of unsaturation at the carbon atom bearing the pendant aryl ring. Six of the molecules from this benzosuberene-series of compounds were active (IC50 < 5 mu M) as inhibitors of tubulin polymerization while four analogues were comparable (IC50 approximately 1 mu M) in their tubulin inhibitory activity to CA4 and KGP18. The potency of a bis-trifluoromethyl analogue 74 and the unsaturated KGP18 derivative 73 as inhibitors of tubulin assembly along with their moderate cytotoxicity suggested the potential utility of these compounds as vascular disrupting agents (VDAs) to selectively target microvessels feeding tumors. Accordingly, water-soluble and DMSO-soluble phosphate prodrug salts of each were synthesized for preliminary in vivo studies to assess their potential efficacy as VDAs. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Herdman, Christine A.; Devkota, Laxman; Lin, Chen-Ming; Niu, Haichan; Strecker, Tracy E.; George, Clinton S.; Tanpure, Rajendra P.; Chaplin, David J.; Trawick, Mary Lynn; Pinney, Kevin G.] Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA.
[Lopez, Ramona; Liu, Li; Mason, Ralph P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
[Chaplin, David J.] OXiGENE Inc, San Francisco, CA 94080 USA.
RP Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, One Bear Pl 97348, Waco, TX 76798 USA.
EM Kevin_Pinney@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.; NSF [CHE-0420802]; National
Institutes of Health National Cancer Institute Cancer Center [1P30
CA142543]; [1S10RR024757]
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, and to the NSF for funding the Varian 500 MHz NMR spectrometer
(Grant No. CHE-0420802). 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 would also thank Dr. James
Karban and Dr. Michelle Nemec (Director) for the use of the shared
Molecular Biosciences Center at Baylor University, Dr. Alejandro Ramirez
(Mass Spectrometry Core Facility, Baylor University) and Dr. Kevin
Klausmeyer and Marissa Penney (X-ray analysis). The authors are grateful
to Mr. Tyler Goddard (Baylor University) for his contributions to the
synthesis of certain analogues, and to Jeni Gerberich (UTSW) and Dr. Li
Li (UTSW) for valuable technical assistance. Imaging 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 69
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U1 3
U2 15
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 DEC 15
PY 2015
VL 23
IS 24
BP 7497
EP 7520
DI 10.1016/j.bmc.2015.10.012
PG 24
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA CY8GA
UT WOS:000366645600001
PM 26775540
ER
PT J
AU Bailey, ME
Sackett, DL
Ross, JL
AF Bailey, Megan E.
Sackett, Dan L.
Ross, Jennifer L.
TI Katanin Severing and Binding Microtubules Are Inhibited by Tubulin
Carboxy Tails
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SPASTIC PARAPLEGIA PROTEIN; GAMMA-TUBULIN; IN-VITRO; STABLE
MICROTUBULES; SPINDLE LENGTH; AAA PROTEINS; P60 KATANIN; XENOPUS;
ATPASE; IDENTIFICATION
AB Microtubule dynamics in cells are regulated by associated proteins that can be either stabilizers or destabilizers. A class of destabilizers that is important in a large number of cellular activities is the microtubule-severing enzymes, yet little is known about how they function. Katanin p60 was the first ATPase associated with microtubule severing. Here, we investigate the activity of katanin severing using a GFP-labeled human version. We quantify the effect of katanin concentration on katanin binding and severing activity. We find that free tubulin can inhibit severing activity by interfering with katanin binding to microtubules. The inhibition is mediated by the sequence of the tubulin and specifically depends on the carboxy-terminal tails. We directly investigate the inhibition effect of tubulin carboxy-terminal tails using peptide sequences of alpha-, beta-, or detyrosinated alpha-tubulin tails that have been covalently linked to bovine serum albumin. Our results show that beta-tubulin tails are the most effective at inhibiting severing, and that detyrosinated alpha-tubulin tails are the least effective. These results are distinct from those for other severing enzymes and suggest a scheme for regulation of katanin activity in cells dependent on free tubulin concentration and the modification state of the tubulin.
C1 [Bailey, Megan E.] Univ Massachusetts, Mol & Cellular Biol Grad Program, Amherst, MA 01003 USA.
[Bailey, Megan E.; Ross, Jennifer L.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Ross, JL (reprint author), Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
EM rossj@physics.umass.edu
RI Ross, Jennifer/D-7208-2012
OI Ross, Jennifer/0000-0002-4838-3798
FU National Science Foundation [DMR-1207783]; National Institutes of Health
[R01-GM109909]; Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health
FX Funding for M.E.B. and J.L.R. was provided by National Science
Foundation grant DMR-1207783 to J.L.R. and National Institutes of Health
grant R01-GM109909 to J.L.R. and David Sharp. This work was supported in
part by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 57
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U1 1
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 DEC 15
PY 2015
VL 109
IS 12
BP 2546
EP 2561
DI 10.1016/j.bpj.2015.11.011
PG 16
WC Biophysics
SC Biophysics
GA CY8EC
UT WOS:000366640600013
PM 26682813
ER
PT J
AU Chavan, TS
Jang, H
Khavrutskii, L
Abraham, SJ
Banerjee, A
Freed, BC
Johannessen, L
Tarasov, SG
Gaponenko, V
Nussinov, R
Tarasova, NI
AF Chavan, Tanmay S.
Jang, Hyunbum
Khavrutskii, Lyuba
Abraham, Sherwin J.
Banerjee, Avik
Freed, Benjamin C.
Johannessen, Liv
Tarasov, Sergey G.
Gaponenko, Vadim
Nussinov, Ruth
Tarasova, Nadya I.
TI High-Affinity Interaction of the K-Ras4B Hypervariable Region with the
Ras Active Site
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID K-RAS; MICROSCALE THERMOPHORESIS; SIGNAL-TRANSDUCTION;
MOLECULAR-DYNAMICS; PROTEIN-KINASE; HA-RAS; DOMAIN; ACTIVATION; CANCER;
MEMBRANE
AB Ras proteins are small GTPases that act as signal transducers between cell surface receptors and several intracellular signaling cascades. They contain highly homologous catalytic domains and flexible C-terminal hypervariable regions (HVRs) that differ across Ras isoforms. KRAS is among the most frequently mutated oncogenes in human tumors. Surprisingly, we found that the C-terminal HVR of K-Ras4B, thought to minimally impact the catalytic domain, directly interacts with the active site of the protein. The interaction is almost 100-fold tighter with the GDP-bound than the GTP-bound protein. HVR binding interferes with Ras-Raf interaction, modulates binding to phospholipids, and slightly slows down nucleotide exchange. The data indicate that contrary to previously suggested models of K-Ras4B signaling, HVR plays essential roles in regulation of signaling. High affinity binding of short peptide analogs of HVR to K-Ras active site suggests that targeting this surface with inhibitory synthetic molecules for the therapy of KRAS-dependent tumors is feasible.
C1 [Chavan, Tanmay S.] Univ Illinois, Dept Med Chem, Chicago, IL USA.
[Chavan, Tanmay S.; Abraham, Sherwin J.; Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Banerjee, Avik; Tarasov, Sergey G.] Univ Illinois, Dept Chem, Chicago, IL 60680 USA.
[Jang, Hyunbum; Khavrutskii, Lyuba; Nussinov, Ruth] NCI, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21701 USA.
[Jang, Hyunbum; Khavrutskii, Lyuba; Freed, Benjamin C.; Johannessen, Liv; Nussinov, Ruth; Tarasova, Nadya I.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Banerjee, Avik; Tarasov, Sergey G.] NCI, Struct Biophys Lab, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Gaponenko, V (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM vadimg@uic.edu; nussinor@helix.nih.gov; nadya.tarasova@nih.gov
FU National Cancer Institute [R01CA135341, R01CA188427]; National Heart,
Lung, and Blood Institute [R21HL118588]; National Institute of Allergy
and Infectious Diseases [R01AI058072]; Frederick National Laboratory for
Cancer Research, National Institutes of Health [HHSN261200800001E];
Intramural Research Program of the National Institutes of Health,
Frederick National Lab, Center for Cancer Research
FX We gratefully acknowledge the generous support from the National Cancer
Institute (Awards R01CA135341 and R01CA188427); the National Heart,
Lung, and Blood Institute (Award R21HL118588); and the National
Institute of Allergy and Infectious Diseases (Award R01AI058072) to V.G.
This project 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 National Institutes of Health, Frederick National Lab, Center for
Cancer Research.
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U1 2
U2 13
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 DEC 15
PY 2015
VL 109
IS 12
BP 2602
EP 2613
DI 10.1016/j.bpj.2015.09.034
PG 12
WC Biophysics
SC Biophysics
GA CY8EC
UT WOS:000366640600017
PM 26682817
ER
PT J
AU Qin, LL
Fan, M
Candas, D
Jiang, GC
Papadopoulos, S
Tian, L
Woloschak, G
Grdina, DJ
Li, JJ
AF Qin, Lili
Fan, Ming
Candas, Demet
Jiang, Guochun
Papadopoulos, Stelios
Tian, Lin
Woloschak, Gayle
Grdina, David J.
Li, Jian Jian
TI CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA
Repair
SO CELL REPORTS
LA English
DT Article
ID IONIZING-RADIATION; MITOTIC PHOSPHORYLATION; CELL-DEATH; CYCLIN;
ACTIVATION; PROTECTION; APOPTOSIS; EVENTS; STRESS; CANCER
AB Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy-consuming process. However, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of the cell-cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is reduced significantly in cells harboring CDK1 phosphorylation-deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair are also compromised severely in cells harboring mitochondrially targeted, kinase-deficient CDK1. These results demonstrate a mechanism governing the communication between mitochondria and the nucleus by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress conditions.
C1 [Qin, Lili; Fan, Ming; Candas, Demet; Li, Jian Jian] Univ Calif Davis, Sch Med, Dept Radiat Oncol, Natl Canc Inst,Designated Comprehens Canc Ctr, Sacramento, CA 95817 USA.
[Jiang, Guochun] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Papadopoulos, Stelios; Tian, Lin] Univ Calif Davis, Dept Biochem & Mol Med, Sch Med, Davis, CA 95616 USA.
[Papadopoulos, Stelios; Tian, Lin] Univ Calif Davis, Dept Psychiat & Behav Sci, Sch Med, Davis, CA 95616 USA.
[Woloschak, Gayle] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA.
[Grdina, David J.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
RP Li, JJ (reprint author), Univ Calif Davis, Sch Med, Dept Radiat Oncol, Natl Canc Inst,Designated Comprehens Canc Ctr, Sacramento, CA 95817 USA.
EM jijli@ucdavis.edu
RI Qin, Lili/J-7481-2016; Woloschak, Gayle/A-3799-2017
OI Woloschak, Gayle/0000-0001-9209-8954
FU NIH [CA152313]; Department of Energy Office of Science [DE-SC0001271]
FX The authors are thankful to Dr. Zhenkun Lou at the Mayo Clinic for
providing the DNA-PKcs-pT2609 antibody. This work was partially
supported by grants from the NIH (CA152313 to J.J.L.) and the Department
of Energy Office of Science (DE-SC0001271 to G.W., J.J.L., and D.J.G.).
NR 33
TC 3
Z9 3
U1 3
U2 10
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 DEC 15
PY 2015
VL 13
IS 10
BP 2056
EP 2063
DI 10.1016/j.celrep.2015.11.015
PG 8
WC Cell Biology
SC Cell Biology
GA CY6QQ
UT WOS:000366534300003
PM 26670043
ER
PT J
AU Agarwal, S
Hynes, PG
Tillman, HS
Lake, R
Abou-Kheir, WG
Fang, L
Casey, OM
Ameri, AH
Martin, PL
Yin, JJ
Iaquinta, PJ
Karthaus, WR
Clevers, HC
Sawyers, CL
Kelly, K
AF Agarwal, Supreet
Hynes, Paul G.
Tillman, Heather S.
Lake, Ross
Abou-Kheir, Wassim G.
Fang, Lei
Casey, Orla M.
Ameri, Amir H.
Martin, Philip L.
Yin, Juan Juan
Iaquinta, Phillip J.
Karthaus, Wouter R.
Clevers, Hans C.
Sawyers, Charles L.
Kelly, Kathleen
TI Identification of Different Classes of Luminal Progenitor Cells within
Prostate Tumors
SO CELL REPORTS
LA English
DT Article
ID STEM-CELLS; EPITHELIAL PROGENITORS; MESENCHYMAL TRANSITION; ORGANOID
CULTURES; MAMMARY-GLAND; IN-VITRO; CANCER; HETEROGENEITY; BASAL; ORIGIN
AB Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.
C1 [Agarwal, Supreet; Hynes, Paul G.; Tillman, Heather S.; Lake, Ross; Abou-Kheir, Wassim G.; Fang, Lei; Casey, Orla M.; Ameri, Amir H.; Yin, Juan Juan; Kelly, Kathleen] NCI, Lab Genitourinary Canc Pathogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Martin, Philip L.] Frederick Natl Lab Canc Res, Ctr Adv Preclin Res, Frederick, MD 21702 USA.
[Iaquinta, Phillip J.; Karthaus, Wouter R.; Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Clevers, Hans C.] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
[Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
RP Kelly, K (reprint author), NCI, Lab Genitourinary Canc Pathogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kellyka@mail.nih.gov
RI Sawyers, Charles/G-5327-2016
FU Howard Hughes Medical Institute; Intramural NIH HHS [ZIA BC010802-08];
NCI NIH HHS [P30 CA008748, R01 CA155169, R01 CA193837]
NR 42
TC 2
Z9 2
U1 1
U2 3
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 DEC 15
PY 2015
VL 13
IS 10
BP 2147
EP 2158
DI 10.1016/j.celrep.2015.10.077
PG 12
WC Cell Biology
SC Cell Biology
GA CY6QQ
UT WOS:000366534300013
PM 26628377
ER
PT J
AU Plummer, NW
Evsyukova, IY
Robertson, SD
de Marchena, J
Tucker, CJ
Jensen, P
AF Plummer, Nicholas W.
Evsyukova, Irina Y.
Robertson, Sabrina D.
de Marchena, Jacqueline
Tucker, Charles J.
Jensen, Patricia
TI Expanding the power of recombinase-based labeling to uncover cellular
diversity
SO DEVELOPMENT
LA English
DT Article
DE Cre; Dre; FIp; Intersectional labeling; Norepinephrine
ID SITE-SPECIFIC RECOMBINATION; LOCUS-CERULEUS NEURONS; EMBRYONIC
STEM-CELLS; PREFRONTAL CORTEX; MAMMALIAN-CELLS; FLP-RECOMBINASE; CRE
RECOMBINASE; MICE; PROJECTIONS; MOUSE
AB Investigating the developmental, structural and functional complexity of mammalian tissues and organs depends on identifying and gaining experimental access to diverse cell populations. Here, we describe a set of recombinase-responsive fluorescent indicator alleles in mice that significantly extends our ability to uncover cellular diversity by exploiting the intrinsic genetic signatures that uniquely define cell types. Using a recombinase-based intersectional strategy, these new alleles uniquely permit non-invasive labeling of cells defined by the overlap of up to three distinct gene expression domains. In response to different combinations of Cre, FIp and Dre recombinases, they express eGFP and/or tdTomato to allow the visualization of full cellular morphology. Here, we demonstrate the value of these features through a proof-of-principle analysis of the central noradrenergic system. We label previously inaccessible subpopulations of noradrenergic neurons to reveal details of their three-dimensional architecture and axon projection profiles. These new indicator alleles will provide experimental access to cell populations at unprecedented resolution, facilitating analysis of their developmental origin and anatomical, molecular and physiological properties.
C1 [Plummer, Nicholas W.; Evsyukova, Irina Y.; Robertson, Sabrina D.; de Marchena, Jacqueline; Jensen, Patricia] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Tucker, Charles J.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Jensen, P (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM patricia.jensen@nih.gov
OI Robertson, Sabrina/0000-0003-4598-6929
FU Intramural Research Program of the US National Institutes of Health,
National Institute of Environmental Health Sciences [ZIA-ES-102805]
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health, National Institute of Environmental
Health Sciences (ZIA-ES-102805). Deposited in PMC for release after 12
months.
NR 57
TC 5
Z9 5
U1 1
U2 10
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD DEC 15
PY 2015
VL 142
IS 24
BP 4385
EP 4393
DI 10.1242/dev.129981
PG 9
WC Developmental Biology
SC Developmental Biology
GA CY4GD
UT WOS:000366365700019
PM 26586220
ER
PT J
AU Germain, RN
AF Germain, Ronald N.
TI William E. Paul, MD (1936-2015), President, The American Association of
Immunologists, 1986-1987 In Memoriam
SO JOURNAL OF IMMUNOLOGY
LA English
DT Biographical-Item
C1 [Germain, Ronald N.] NIAID, NIH, Lab Syst Biol, Rockville, MD 20852 USA.
[Germain, Ronald N.] NIAID, NIH, Lymphocyte Biol Sect, Rockville, MD 20852 USA.
[Germain, Ronald N.] NIAID, NIH, Immunol Lab, Rockville, MD 20852 USA.
[Germain, Ronald N.] NIAID, NIH, Trans NIH Ctr Human Immunol, Rockville, MD 20852 USA.
RP Germain, RN (reprint author), NIAID, NIH, Lab Syst Biol, Rockville, MD 20852 USA.
FU Intramural NIH HHS
NR 2
TC 0
Z9 0
U1 0
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 DEC 15
PY 2015
VL 195
IS 12
BP 5519
EP 5521
DI 10.4049/jimmunol.1590025
PG 3
WC Immunology
SC Immunology
GA CY9OB
UT WOS:000366735100001
PM 26637660
ER
PT J
AU Cubas, R
van Grevenynghe, J
Wills, S
Kardava, L
Santich, BH
Buckner, CM
Muir, R
Tardif, V
Nichols, C
Procopio, F
He, Z
Metcalf, T
Ghneim, K
Locci, M
Ancuta, P
Routy, JP
Trautmann, L
Li, YX
McDermott, AB
Koup, RA
Petrovas, C
Migueles, SA
Connors, M
Tomaras, GD
Moir, S
Crotty, S
Haddad, EK
AF Cubas, Rafael
van Grevenynghe, Julien
Wills, Saintedym
Kardava, Lela
Santich, Brian H.
Buckner, Clarisa M.
Muir, Roshell
Tardif, Virginie
Nichols, Carmen
Procopio, Francesco
He, Zhong
Metcalf, Talibah
Ghneim, Khader
Locci, Michela
Ancuta, Petronella
Routy, Jean-Pierre
Trautmann, Lydie
Li, Yuxing
McDermott, Adrian B.
Koup, Rick A.
Petrovas, Constantinos
Migueles, Steven A.
Connors, Mark
Tomaras, Georgia D.
Moir, Susan
Crotty, Shane
Haddad, Elias K.
TI Reversible Reprogramming of Circulating Memory T Follicular Helper Cell
Function during Chronic HIV Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; B-CELLS; INTERFERON-GAMMA; TFH CELLS;
DIFFERENTIATION; INTERLEUKIN-2; ACTIVATION; RESPONSES; REPLICATION;
RESERVOIR
AB Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART.
C1 [Cubas, Rafael; Muir, Roshell; Tardif, Virginie; Nichols, Carmen; He, Zhong; Metcalf, Talibah; Ghneim, Khader; Trautmann, Lydie; Haddad, Elias K.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
[van Grevenynghe, Julien] Inst Armand Frappier, Inst Natl Rech Sci, Laval, PQ H7V 1B7, Canada.
[Wills, Saintedym; Tomaras, Georgia D.] Duke Univ, Dept Immunol, Durham, NC 27710 USA.
[Wills, Saintedym; Tomaras, Georgia D.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Kardava, Lela; Santich, Brian H.; Buckner, Clarisa M.; Moir, Susan] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Procopio, Francesco] CHU Vaudois, Serv Immunol & Allergie, CH-1011 Lausanne, Switzerland.
[Locci, Michela; Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Ancuta, Petronella] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Ancuta, Petronella] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ H3C 3J7, Canada.
[Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ H3H 2R9, Canada.
[Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3H 2R9, Canada.
[Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Div Hematol, Montreal, PQ H3H 2R9, Canada.
[Li, Yuxing] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Li, Yuxing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[McDermott, Adrian B.; Koup, Rick A.; Petrovas, Constantinos] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Migueles, Steven A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Crotty, Shane] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
[Crotty, Shane] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
RP Haddad, EK (reprint author), Drexel Univ, Div Infect Dis & HIV Med, 245 North 15th St, Philadelphia, PA 19102 USA.
EM elias.elhaddad@drexelmed.edu
RI Tomaras, Georgia/J-5041-2016
FU National Institutes of Health Grant [1RO1AI106482-01AI]; American
Foundation for AIDS Research [10867155-RKVA]; Canadian Institutes of
Health Research Grant [103230]; Canadian Institutes of Health Research
Canadian Trials Network/HIV Trial Network [CTN 247]; Fonds de la
Recherche en Sante du Quebec Maladies Infectieuses; Duke Center for AIDS
Research Immunology Core (National Institutes of Health Grant)
[AI064518]; National Institutes of Health/National Institute of Allergy
and Infectious Diseases Grant [R01AI102766]; National Institute of
Allergy and Infectious Diseases Development Grant [P30AI36214]; Center
for AIDS Research; University of California, San Diego
FX This work was supported by National Institutes of Health Grant
1RO1AI106482-01AI (to E.K.H.); the Mathilde Krim Fellowship from the
American Foundation for AIDS Research (Grant 10867155-RKVA) (to R.C.);
and in part by Canadian Institutes of Health Research Grant 103230, the
Canadian Institutes of Health Research Canadian Trials Network/HIV Trial
Network (CTN 247), the Fonds de la Recherche en Sante du Quebec Maladies
Infectieuses, and the Duke Center for AIDS Research Immunology Core
(National Institutes of Health Grant AI064518). Y.L. was funded by
National Institutes of Health/National Institute of Allergy and
Infectious Diseases Grant R01AI102766 and National Institute of Allergy
and Infectious Diseases Development Grant P30AI36214, the Center for
AIDS Research, and the University of California, San Diego. J.-P.R.
holds the Louis Lowenstein Chair in Hematology-Oncology, McGill
University.
NR 42
TC 11
Z9 11
U1 2
U2 12
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 DEC 15
PY 2015
VL 195
IS 12
BP 5625
EP 5636
DI 10.4049/jimmunol.1501524
PG 12
WC Immunology
SC Immunology
GA CY9OB
UT WOS:000366735100013
PM 26546609
ER
PT J
AU Dasgupta, A
Chen, KH
Munk, RB
Sasaki, CY
Curtis, J
Longo, DL
Ghosh, P
AF Dasgupta, Asish
Chen, Kuang-Hueih
Munk, Rachel B.
Sasaki, Carl Y.
Curtis, Jessica
Longo, Dan L.
Ghosh, Paritosh
TI Mechanism of Activation-Induced Downregulation of Mitofusin 2 in Human
Peripheral Blood T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID DIFFERENTIAL REGULATION; RETINOBLASTOMA PROTEIN; PATHWAY;
PHOSPHORYLATION; PROLIFERATION; MITOCHONDRIA; PROGRESSION; INHIBITORS;
MUTATIONS; APOPTOSIS
AB Mitofusin 2 (Mfn2), a mitochondrial protein, was shown to have antiproliferative properties when overexpressed. In this article, we show that activation of resting human peripheral blood T cells caused downregulation of Mfn2 levels. This downregulation of Mfn2 was blocked by different inhibitors (mTOR inhibitor rapamycin, PI3K inhibitor LY294002, and Akt inhibitor A443654), producing cells that were arrested in the G(0)/G(1) stage of the cell cycle. Furthermore, the activation-induced downregulation of Mfn2 preceded the entry of the cells into the cell cycle, suggesting that Mfn2 downregulation is a prerequisite for activated T cell entry into the cell cycle. Accordingly, small interfering RNA-mediated knockdown of Mfn2 resulted in increased T cell proliferation. Overexpression of constitutively active AKT resulted in the downregulation of Mfn2, which can be blocked by a proteasome inhibitor. Akt-mediated downregulation of Mfn2 was via the mTORC1 pathway because this downregulation was blocked by rapamycin, and overexpression of wild-type, but not kinase-dead mTOR, caused Mfn2 downregulation. Our data suggested that activation-induced reactive oxygen species production plays an important role in the downregulation of Mfn2. Collectively, our data suggest that the PI3K-AKT-mTOR pathway plays an important role in activation-induced downregulation of Mfn2 and subsequent proliferation of resting human T cells.
C1 [Dasgupta, Asish; Chen, Kuang-Hueih; Munk, Rachel B.; Sasaki, Carl Y.; Longo, Dan L.; Ghosh, Paritosh] NIA, Lymphocyte Cell Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Curtis, Jessica] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Ghosh, P (reprint author), NIA, Lymphocyte Cell Biol Unit, Genet Lab, Biomed Res Ctr,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM ghoshp@grc.nia.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging.
NR 30
TC 1
Z9 1
U1 0
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 DEC 15
PY 2015
VL 195
IS 12
BP 5780
EP 5786
DI 10.4049/jimmunol.1501023
PG 7
WC Immunology
SC Immunology
GA CY9OB
UT WOS:000366735100028
PM 26566676
ER
PT J
AU Chiu, D
Klucznik, RP
Turan, TN
Lynn, MJ
McCane, CD
Katz, LB
Nizam, A
Derdeyn, CP
Fiorella, D
Lane, BF
Montgomery, J
Janis, S
Chimowitz, MI
AF Chiu, David
Klucznik, Richard P.
Turan, Tanya N.
Lynn, Michael J.
McCane, Charles D.
Katz, Lawrence B.
Nizam, Azhar
Derdeyn, Colin P.
Fiorella, David
Lane, Bethany F.
Montgomery, Jean
Janis, Scott
Chimowitz, Marc I.
TI Enrollment volume effect on risk factor control and outcomes in the
SAMMPRIS trial
SO NEUROLOGY
LA English
DT Article
ID AGGRESSIVE MEDICAL-MANAGEMENT; INTRACRANIAL STENOSIS SAMMPRIS;
PREVENTING RECURRENT STROKE; RANDOMIZED-TRIAL; OPERATOR; EXPERIENCE;
DESIGN
AB Objective:The role of physician experience and patient volumes on the outcome of surgical or endovascular procedures has been well-studied but there are limited data on how these factors affect the outcome of medical therapy.Methods:In the stenting and medical cohorts of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial, we compared Kaplan-Meier (K-M) curves for the primary endpoint (any stroke or death within 30 days of enrollment or ischemic stroke in the territory beyond 30 days) using the log-rank test and the percentages of patients achieving target levels for primary and secondary risk factors during the study using Fisher exact test between patients at high-enrolling (12 patients) vs low-enrolling (<12 patients) sites.Results:In the stenting group, the K-M curves for the primary endpoint were similar at high-enrolling sites and low-enrolling sites (p = 0.93) with rates of 13.5% vs 14.7% at 30 days and 19.0% vs 20.6% at 2 years. In the medical group, the K-M curves differed between high-enrolling sites and low-enrolling sites (p = 0.0005) with rates of 1.8% vs 9.8% at 30 days and 7.3% vs 20.9% at 2 years. The percentages of patients who achieved targets for low-density lipoprotein cholesterol and systolic blood pressure at high- vs low-enrolling sites in both treatment groups combined were 64% vs 49% (p = 0.003) and 70% vs 59% (p = 0.026), respectively.Conclusions:High-enrolling sites in SAMMPRIS achieved better control of primary risk factors and much lower rates of the primary endpoint than low-enrolling sites in the medical group, suggesting that experience with medical management is an important determinant of patient outcome.
C1 [Chiu, David; Klucznik, Richard P.; McCane, Charles D.; Katz, Lawrence B.] Weill Cornell Med Coll, Houston Methodist Hosp, Houston, TX 77030 USA.
[Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Charleston, SC USA.
[Lynn, Michael J.; Nizam, Azhar; Lane, Bethany F.; Montgomery, Jean] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, St Louis, MO USA.
[Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Janis, Scott] NINDS, NIH, Bethesda, MD 20892 USA.
RP Chiu, D (reprint author), Weill Cornell Med Coll, Houston Methodist Hosp, Houston, TX 77030 USA.
EM dchiu@tmhs.org
OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU US Public Health Service National Institute of Neurological Disorders
and Stroke (NINDS) [U01 NS058728]; NIH [UL1RR029882, UL1RR029889,
UL1RR029890, UL1RR024131]; Stryker Neurovascular; AstraZeneca
FX This study was funded by a research grant (U01 NS058728) from the US
Public Health Service National Institute of Neurological Disorders and
Stroke (NINDS). In addition, the following Clinical and Translational
Science Awards, funded by the NIH, provided local support for the
evaluation of patients in the trial: Medical University of South
Carolina (UL1RR029882), University of Florida (UL1RR029889), University
of Cincinnati (UL1RR029890), and University of California, San Francisco
(UL1RR024131). Corporate Support: Stryker Neurovascular (formerly Boston
Scientific Neurovascular) provided study devices and supplemental
funding for third party device distribution, site monitoring, and study
auditing. This research was also supported by the Investigator-Sponsored
Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to
study patients. Vendors: INTERVENT provided the lifestyle modification
program to the study at a discounted rate. The Regulatory and Clinical
Research Institute (RCRI) (Minneapolis, MN) provided assistance in
designing the site monitoring processes and performing the site
monitoring visits. The VA Cooperative Studies Program Clinical Research
Pharmacy Coordinating Center (Albuquerque, NM) handled the procurement,
labeling, distribution, and inventory management of the study devices
and rosuvastatin. Walgreens pharmacies provided study medications except
rosuvastatin to patients at a discounted price (paid for by the study).
NR 12
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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 DEC 15
PY 2015
VL 85
IS 24
BP 2090
EP 2097
DI 10.1212/WNL.0000000000002191
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CY5QI
UT WOS:000366461900003
PM 26561294
ER
PT J
AU Huang, B
Deng, CS
Yang, T
Xue, LL
Wang, Q
Huang, SG
Su, XZ
Liu, YJ
Zheng, SQ
Guan, YZ
Xu, Q
Zhou, JY
Yuan, J
Bacar, A
Abdallah, KS
Attoumane, R
Mliva, AMSA
Zhong, Y
Lu, FL
Song, JP
AF Huang, Bo
Deng, Changsheng
Yang, Tao
Xue, Linlu
Wang, Qi
Huang, Shiguang
Su, Xin-Zhuan
Liu, Yajun
Zheng, Shaoqin
Guan, Yezhi
Xu, Qin
Zhou, Jiuyao
Yuan, Jie
Bacar, Afane
Abdallah, Kamal Said
Attoumane, Rachad
Mliva, Ahamada M. S. A.
Zhong, Yanchun
Lu, Fangli
Song, Jianping
TI Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium
falciparum parasite populations of Grande Comore Island 10 years after
artemisinin combination therapy
SO PARASITES & VECTORS
LA English
DT Article
DE Comoros; Plasmodium falciparum; Artemisinin resistance; K13-propeller;
Polymorphism
ID SUB-SAHARAN AFRICA; IN-VIVO EFFICACY; PROPELLER GENE; MALARIA;
MUTATIONS; ARTESUNATE; AMODIAQUINE; CHLOROQUINE; CHILDREN; PYRIMETHAMINE
AB Background: Plasmodium falciparum malaria is a significant public health problem in Comoros, and artemisinin combination therapy (ACT) remains the first choice for treating acute uncomplicated P. falciparum. The emergence and spread of artemisinin-resistant P. falciparum in Southeast Asia, associated with mutations in K13-propeller gene, poses a potential threat to ACT efficacy. Detection of mutations in the P. falciparum K13-propeller gene may provide the first-hand information on changes in parasite susceptibility to artemisinin. The objective of this study is to determinate the prevalence of mutant K13-propeller gene among the P. falciparum isolates collected from Grande Comore Island, Union of Comoros, where ACT has been in use since 2004.
Methods: A total of 207 P. falciparum clinical isolates were collected from the island during March 2006 and October 2007 (n = 118) and March 2013 and December 2014 (n = 89). All isolates were analysed for single nucleotide polymorphisms (SNPs) and haplotypes in the K13-propeller gene using nested PCR and DNA sequencing.
Results: Only three 2006-2007 samples carried SNPs in the K13-propeller gene, one having a synonymous (G538G) and the other having two non-synonymous (S477Y and D584E) substitutions leading to two mutated haplotypes (2.2 %, 2/95). Three synonymous mutations (R471R, Y500Y, and G538G) (5.9 %, 5/85) and 7 non-synonymous substitutions (21.2 %, 18/85) with nine mutated haplotypes (18.8 %, 16/85) were found in isolates from 2013 to 2014. However, none of the polymorphisms associated with artemisinin-resistance in Southeast Asia was detected from any of the parasites examined.
Conclusion: This study showed increased K13-propeller gene diversity among P. falciparum populations on the Island over the course of 8 years (2006-2014). Nevertheless, none of the polymorphisms known to be associated with artemisinin resistance in Asia was detected in the parasite populations examined. Our data suggest that P. falciparum populations in Grande Comore are still effectively susceptible to artemisinin. Our results provide insights into P. falciparum populations regarding mutations in the gene associated with artemisinin resistance and will be useful for developing and updating anti-malarial guidance in Comoros.
C1 [Huang, Bo; Deng, Changsheng; Yang, Tao; Xue, Linlu; Wang, Qi; Zheng, Shaoqin; Guan, Yezhi; Song, Jianping] Guangzhou Univ Chinese Med, Sci & Technol Pk, Guangzhou 510006, Guangdong, Peoples R China.
[Huang, Shiguang] Jinan Univ, Sch Med, Guangzhou 510632, Guangdong, Peoples R China.
[Su, Xin-Zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Su, Xin-Zhuan] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Peoples R China.
[Liu, Yajun] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510006, Guangdong, Peoples R China.
[Xu, Qin] Guangzhou Univ Chinese Med, Res Inst Trop Med, Guangzhou 510006, Guangdong, Peoples R China.
[Zhou, Jiuyao; Yuan, Jie; Zhong, Yanchun] Guangzhou Univ Chinese Med, Tradit Chinese Med Coll, Guangzhou 510006, Guangdong, Peoples R China.
[Bacar, Afane; Abdallah, Kamal Said; Attoumane, Rachad] Natl Malaria Control Programme, Moroni, Comoros.
[Mliva, Ahamada M. S. A.] Minist Hlth Comoros, Moroni, Comoros.
[Lu, Fangli] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510080, Guangdong, Peoples R China.
RP Song, JP (reprint author), Guangzhou Univ Chinese Med, Sci & Technol Pk, Guangzhou 510006, Guangdong, Peoples R China.
EM songjpgz@sina.com
OI Su, Xinzhuan/0000-0003-3246-3248
FU Natural Science Foundation of China [81273643, 81403295]; International
S&T Cooperation Program of China [2009DFA31180]; China Postdoctoral
Science Foundation [2015M570699]; Guangdong Provincial Science
Foundation [2015A030310107]; Science and Technology Program of Guangzhou
[2014J4500037]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX We thank Cindy Clark of the NIH Library for editing. This work was
supported in part by grants from Natural Science Foundation of China
[grant number 81273643] and International S&T Cooperation Program of
China [grant numbers 2009DFA31180] to JS, China Postdoctoral Science
Foundation [grant number 2015M570699] and Guangdong Provincial Science
Foundation [grant number 2015A030310107] to BH, Natural Science
Foundation of China [grant number 81403295] to CD, Science and
Technology Program of Guangzhou [2014J4500037] to YG, and by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (X-zS). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 45
TC 5
Z9 5
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD DEC 15
PY 2015
VL 8
AR 634
DI 10.1186/s13071-015-1253-z
PG 8
WC Parasitology
SC Parasitology
GA CY7AG
UT WOS:000366559600002
PM 26667053
ER
PT J
AU Chen, XB
Levy, JM
Hou, A
Winters, C
Azzam, R
Sousa, AA
Leapman, RD
Nicoll, RA
Reese, TS
AF Chen, Xiaobing
Levy, Jonathan M.
Hou, Austin
Winters, Christine
Azzam, Rita
Sousa, Alioscka A.
Leapman, Richard D.
Nicoll, Roger A.
Reese, Thomas S.
TI PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor
complexes at the postsynaptic density
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE MAGUKs; knockdown; EM tomography; NMDAR; AMPAR
ID EXCITATORY SYNAPSES; SCAFFOLDING PROTEINS; GLUTAMATE RECEPTORS;
DENDRITIC SPINES; MOLECULAR-ORGANIZATION; NEUROMUSCULAR-JUNCTION;
SYNAPTIC-TRANSMISSION; GUANYLATE KINASES; RAT HIPPOCAMPUS; QUANTAL SIZE
AB The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95 like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membraneassociated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD.
C1 [Chen, Xiaobing; Hou, Austin; Winters, Christine; Azzam, Rita; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Levy, Jonathan M.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Sousa, Alioscka A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Reese, TS (reprint author), NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
EM treese@mbl.edu
FU NINDS; National Institute of Biomedical Imaging and Bioengineering of
the NIH; NIH grants
FX We thank Susan Cheng and Virginia Crocker of the National Institute of
Neurological Disorders and Stroke (NINDS) EM facility for their support
with immunogold EM and EM processing, Carolyn Smith and Paul Gallant of
the NINDS light microscopy imaging facility for their help with confocal
microscopy, Harold Gainer and Ray Fields for providing a facility for
lentivirus-related work, John Chludzinski and Daniel Cox for help with
data analysis, and Andy Jan and Austin Feng for critical reading of the
manuscript. This work was supported by intramural funds from NINDS and
National Institute of Biomedical Imaging and Bioengineering of the NIH
and NIH grants (to RAN.).
NR 86
TC 11
Z9 11
U1 5
U2 14
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 DEC 15
PY 2015
VL 112
IS 50
BP E6983
EP E6992
DI 10.1073/pnas.1517045112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY4UN
UT WOS:000366404200021
PM 26604311
ER
PT J
AU Libich, DS
Tugarinov, V
Clore, GM
AF Libich, David S.
Tugarinov, Vitali
Clore, G. Marius
TI Reply to Marchenko et al.: Flux analysis of GroEL-assisted protein
folding/unfolding
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Libich, David S.; Tugarinov, Vitali; Clore, G. Marius] NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM mariusc@intra.niddk.nih.gov
FU Intramural NIH HHS
NR 6
TC 0
Z9 0
U1 1
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 DEC 15
PY 2015
VL 112
IS 50
BP E6833
EP E6834
DI 10.1073/pnas.1520474112
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY4UN
UT WOS:000366404200004
PM 26604310
ER
PT J
AU Kohli, A
Kattakuzhy, S
Sidharthan, S
Nelson, A
McLaughlin, M
Seamon, C
Wilson, E
Meissner, EG
Sims, Z
Silk, R
Gross, C
Akoth, E
Tang, L
Price, A
Jolley, TA
Emmanuel, B
Proschan, M
Teferi, G
Chavez, J
Abbott, S
Osinusi, A
Mo, HM
Polis, MA
Masur, H
Kottilil, S
AF Kohli, Anita
Kattakuzhy, Sarah
Sidharthan, Sreetha
Nelson, Amy
McLaughlin, Mary
Seamon, Cassie
Wilson, Eleanor
Meissner, Eric G.
Sims, Zayani
Silk, Rachel
Gross, Chloe
Akoth, Elizabeth
Tang, Lydia
Price, Angie
Jolley, Tim A.
Emmanuel, Benjamin
Proschan, Michael
Teferi, Gebeyehu
Chavez, Jose
Abbott, Stephen
Osinusi, Anuoluwapo
Mo, Hongmei
Polis, Michael A.
Masur, Henry
Kottilil, Shyam
TI Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With
Hepatitis C Virus Genotype 1 Infection
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID UNITED-STATES; VIROLOGICAL RESPONSE; SOFOSBUVIR; HCV; LEDIPASVIR;
RIBAVIRIN; COHORT
AB Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) for 6 weeks achieves sustained virologic response (SVR) rates of 95% in some patients. If effective, shorter therapeutic courses could improve adherence and treatment costs.
Objective: To determine factors predictive of SVR to 4 weeks of DAA treatment in patients with stage F0 to F2 liver fibrosis.
Design: Open-label, nonrandomized, phase 2a trial. (Clinical Trials. gov: NCT01805882)
Setting: Single-center.
Patients: 50 treatment-naive and predominantly African American patients with HCV genotype 1 infection and early-stage liver fibrosis were sequentially enrolled into 2 treatment groups.
Intervention: 25 participants received a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks, and 25 received a 4-drug regimen consisting of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks.
Measurements: The primary efficacy end point was SVR12 (HCV RNA level below the lower limit of quantification at post-treatment week 12).
Results: Forty percent (10 of 25) (95% CI, 21% to 61%) of patients in the 3-drug group and 20% (5 of 25) (CI, 7% to 41%) of those in the 4-drug group achieved SVR12. Exploratory analysis suggested that lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12. Ten patients had baseline HCV variants conferring greater than 20-fold resistance in vitro to at least 1 study DAA; all had viral relapse. Forty-eight percent (12 of 25) of patients receiving the 3-drug regimen and 72% (18 of 25) of those receiving the 4-drug regimen had adverse events, most of which were mild. One participant was lost to follow-up.
Limitation: Nonrandomized study design and small sample of patients with early-stage fibrosis.
Conclusion: Combination DAA therapy with 3 or 4 drugs for 4 weeks was well-tolerated but resulted in limited cure rates.
C1 NIAID, NIH, Ctr Clin, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
[Teferi, Gebeyehu; Chavez, Jose; Abbott, Stephen] Unity Hlth Care, Washington, DC 20009 USA.
[Osinusi, Anuoluwapo; Mo, Hongmei] Gilead Sci Inc, Foster City, CA 94404 USA.
RP Kottilil, S (reprint author), Univ Maryland, Div Clin Care & Res, Inst Human Virol, Room S222,725 West Lombard St, Baltimore, MD 21201 USA.
EM SKottilil@ihv.umaryland.edu
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute; Clinical Center Intramural Program; National Institutes of
Health; Gilead Sciences
FX National Institute of Allergy and Infectious Diseases, National Cancer
Institute, and Clinical Center Intramural Program; supported in part by
a cooperative research and development agreement between the National
Institutes of Health and Gilead Sciences.
NR 18
TC 9
Z9 9
U1 1
U2 3
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 DEC 15
PY 2015
VL 163
IS 12
BP 899
EP +
DI 10.7326/M15-0642
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY4BS
UT WOS:000366354200015
PM 26595450
ER
PT J
AU Tashima, KT
Smeaton, LM
Fichtenbaum, CJ
Andrade, A
Eron, JJ
Gandhi, RT
Johnson, VA
Klingman, KL
Ritz, J
Hodder, S
Santana, JL
Wilkin, T
Haubrich, RH
AF Tashima, Karen T.
Smeaton, Laura M.
Fichtenbaum, Carl J.
Andrade, Adriana
Eron, Joseph J.
Gandhi, Rajesh T.
Johnson, Victoria A.
Klingman, Karin L.
Ritz, Justin
Hodder, Sally
Santana, Jorge L.
Wilkin, Timothy
Haubrich, Richard H.
CA A5241 Study Team
TI HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase
Inhibitors A Randomized, Controlled Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID ANTIRETROVIRAL REGIMENS; INFECTION; RITONAVIR; EFFICACY; SAFETY;
MORTALITY; RALTEGRAVIR; 2ND-LINE; ADULTS; NORTH
AB Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials.
Objective: To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents.
Design: Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394)
Setting: Outpatient HIV clinics.
Participants: Treatment-experienced patients with HIV infection and viral resistance.
Intervention: Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs.
Measurements: The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment.
Results: 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group.
Limitation: Unblinded study design, and the study may not be applicable to resource-poor settings.
Conclusion: Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population.
C1 [Tashima, Karen T.] Brown Univ, Alpert Med Sch, Miriam Hosp, Providence, RI 02906 USA.
[Smeaton, Laura M.; Ritz, Justin] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Gandhi, Rajesh T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Fichtenbaum, Carl J.] Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA.
[Andrade, Adriana] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Eron, Joseph J.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA.
[Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
[Klingman, Karin L.] NIAID, Therapeut Res Program, HIV Res Branch, Bethesda, MD 20892 USA.
[Hodder, Sally] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA.
[Santana, Jorge L.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Wilkin, Timothy] Weill Cornell Med Coll, Ctr Special Studies HIV AIDS, New York, NY 10065 USA.
[Haubrich, Richard H.] Gilead Sci Inc, Foster City, CA 94404 USA.
RP Tashima, KT (reprint author), Brown Univ, Alpert Med Sch, Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA.
EM ktashima@lifespan.org
FU National Institute of Allergy and Infectious Diseases; Boehringer
Ingelheim; Janssen; Merck; ViiV Healthcare; Roche; Monogram Biosciences
(LabCorp)
FX National Institute of Allergy and Infectious Diseases, Boehringer
Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram
Biosciences (LabCorp).
NR 21
TC 2
Z9 2
U1 1
U2 1
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 DEC 15
PY 2015
VL 163
IS 12
BP 908
EP +
DI 10.7326/M15-0949
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY4BS
UT WOS:000366354200016
PM 26595748
ER
PT J
AU Jacobson, KA
AF Jacobson, Kenneth A.
TI New paradigms in GPCR drug discovery
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Drug discovery; GPCR; X-ray crystallography; structure-based design;
Signaling; Inhibitors
ID PROTEIN-COUPLED RECEPTOR; ADENOSINE A(2A) RECEPTOR; POSITIVE ALLOSTERIC
MODULATORS; STRUCTURE-BASED DESIGN; HUMAN P2Y(1) RECEPTOR; MU-OPIOID
RECEPTOR; CRYSTAL-STRUCTURE; BIASED-AGONISM; FUNCTIONAL SELECTIVITY;
MOLECULAR PROBES
AB G protein-coupled receptors (GPCRs) remain a major domain of pharmaceutical discovery. The identification of GPCR lead compounds and their optimization are now structure-based, thanks to advances in X-ray crystallography, molecular modeling, protein engineering and biophysical techniques. In silico screening provides useful hit molecules. New pharmacological approaches to tuning the pleotropic action of GPCRs include: allosteric modulators, biased ligands, GPCR heterodimer-targeted compounds, manipulation of polypharmacology, receptor antibodies and tailoring of drug molecules to fit GPCR pharmacogenomics. Measurements of kinetics and drug efficacy are factors influencing clinical success. With the exception of inhibitors of GPCR kinases, targeting of intracellular GPCR signaling or receptor cycling for therapeutic purposes remains a futuristic concept. New assay approaches are more efficient and multidimensional: cell-based, label-free, fluorescence-based assays, and biosensors. Tailoring GPCR drugs to a patient's genetic background is now being considered. Chemoinformatic tools can predict ADME-tox properties. New imaging technology visualizes drug action in vivo. Thus, there is reason to be optimistic that new technology for GPCR ligand discovery will help reverse the current narrowing of the pharmaceutical pipeline. Published by Elsevier Inc.
C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH Intramural Research Grant (NIDDK) [Z01 DK031117]
FX Support from the NIH Intramural Research Grant Z01 DK031117 (NIDDK) is
acknowledged.
NR 161
TC 17
Z9 17
U1 21
U2 58
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD DEC 15
PY 2015
VL 98
IS 4
BP 541
EP 555
DI 10.1016/j.bcp.2015.08.085
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY1EU
UT WOS:000366150300001
PM 26265138
ER
PT J
AU Sharma, RK
Arbab-Zadeh, A
Kishi, S
Chen, MY
Magalhaes, TA
George, RT
Dewey, M
Rybicki, FJ
Kofoed, KF
de Roos, A
Tan, SY
Matheson, M
Vavere, A
Cox, C
Clouse, ME
Miller, JM
Brinker, JA
Arai, AE
Di Carli, MF
Rochitte, CE
Lima, JAC
AF Sharma, Ravi K.
Arbab-Zadeh, Armin
Kishi, Satoru
Chen, Marcus Y.
Magalhaes, Tiago A.
George, Richard T.
Dewey, Marc
Rybicki, Frank J.
Kofoed, Klaus F.
de Roos, Albert
Tan, Swee Yaw
Matheson, Matthew
Vavere, Andrea
Cox, Christopher
Clouse, Melvin E.
Miller, Julie M.
Brinker, Jeffery A.
Arai, Andrew E.
Di Carli, Marcelo F.
Rochitte, Carlos E.
Lima, Joao A. C.
TI Incremental diagnostic accuracy of computed tomography myocardial
perfusion imaging over coronary angiography stratified by pre-test
probability of coronary artery disease and severity of coronary artery
calcification: The CORE320 study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Diagnostic accuracy; Coronary computed tomography angiography;
Myocardial computed tomography perfusion; Coronary calcium score;
Pre-test probability
ID AMERICAN-HEART-ASSOCIATION; NUCLEAR-CARDIOLOGY; CT ANGIOGRAPHY;
MULTICENTER; PERFORMANCE; STENOSIS; SCORE; QUANTIFICATION; RADIOLOGY;
CRITERIA
AB Background: Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis.
Objectives: To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score.
Methods: 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and >= 400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA >= 50% stenosis + corresponding SPECT summed stress score >= 1.
Results: In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p = 0.003) alone. In the same group with CAC score = 400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p = 0.030) and CTP (83, p = 0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p = 0.037) alone. In the high risk/known CAD group with CAC score = 400, AUCs for combined imaging were higher (86) than that for CTA (75, p < 0.001) as well as CTP (78, p = 0.020).
Conclusions: The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score = 400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Sharma, Ravi K.; Arbab-Zadeh, Armin; Kishi, Satoru; Magalhaes, Tiago A.; George, Richard T.; Vavere, Andrea; Miller, Julie M.; Brinker, Jeffery A.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA.
[Chen, Marcus Y.; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Dewey, Marc] Humboldt Univ, Charite Med Sch, D-10099 Berlin, Germany.
[Rybicki, Frank J.; Di Carli, Marcelo F.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kofoed, Klaus F.] Univ Copenhagen, DK-1168 Copenhagen, Denmark.
[de Roos, Albert] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Tan, Swee Yaw] Natl Heart Ctr, Singapore, Singapore.
[Matheson, Matthew; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Clouse, Melvin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Rochitte, Carlos E.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Blalock 5249,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
OI Dewey, Marc/0000-0002-4402-2733; Magalhaes, Tiago/0000-0002-7232-4552
FU Unijules Life Sciences Ltd., India
FX Dr. Ravi K. Sharma is a recipient of a post-doctoral research grant by
Unijules Life Sciences Ltd., India.
NR 26
TC 4
Z9 4
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD DEC 15
PY 2015
VL 201
BP 570
EP 577
DI 10.1016/j.ijcard.2015.05.110
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CY1CL
UT WOS:000366144200158
PM 26334382
ER
PT J
AU Insel, TR
Koroshetz, W
AF Insel, Thomas R.
Koroshetz, Walter
TI What cell biologists should know about the National Institutes of Health
BRAIN Initiative
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
AB The BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is an ambitious project to develop innovative tools for a deeper understanding of how the brain functions in health and disease. Early programs in the National Institutes of Health BRAIN Initiative focus on tools for next-generation imaging and recording, studies of cell diversity and cell census, and integrative approaches to circuit function. In all of these efforts, cell biologists can play a leading role.
C1 [Insel, Thomas R.] NIMH, NIH, Bethesda, MD 20892 USA.
[Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM insel@mail.nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD DEC 15
PY 2015
VL 26
IS 25
BP 4539
EP 4540
DI 10.1091/mbc.E15-06-0348
PG 2
WC Cell Biology
SC Cell Biology
GA CY3RK
UT WOS:000366327200003
PM 26668172
ER
PT J
AU Rahman, MM
Munzig, M
Kaneshiro, K
Lee, B
Strome, S
Muller-Reichert, T
Cohen-Fix, O
AF Rahman, Mohammad M.
Munzig, Mandy
Kaneshiro, Kiyomi
Lee, Brandon
Strome, Susan
Mueller-Reichert, Thomas
Cohen-Fix, Orna
TI Caenorhabditis elegans polo-like kinase PLK-1 is required for merging
parental genomes into a single nucleus
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID ENVELOPE BREAKDOWN; C-ELEGANS; CELL-CYCLE; MITOTIC ENTRY; CHROMOSOME
SEGREGATION; ENDOPLASMIC-RETICULUM; PROTEIN-KINASE; IN-VITRO;
PHOSPHORYLATION; EMBRYOS
AB Before the first zygotic division, the nuclear envelopes of the maternal and paternal pronuclei disassemble, allowing both sets of chromosomes to be incorporated into a single nucleus in daughter cells after mitosis. We found that in Caenorhabditis elegans, partial inactivation of the polo-like kinase PLK-1 causes the formation of two nuclei, containing either the maternal or paternal chromosomes, in each daughter cell. These two nuclei gave rise to paired nuclei in all subsequent cell divisions. The paired-nuclei phenotype was caused by a defect in forming a gap in the nuclear envelopes at the interface between the two pronuclei during the first mitotic division. This was accompanied by defects in chromosome congression and alignment of the maternal and paternal metaphase plates relative to each other. Perturbing chromosome congression by other means also resulted in failure to disassemble the nuclear envelope between the two pronuclei. Our data further show that PLK-1 is needed for nuclear envelope breakdown during early embryogenesis. We propose that during the first zygotic division, PLK-1-dependent chromosome congression and metaphase plate alignment are necessary for the disassembly of the nuclear envelope between the two pronuclei, ultimately allowing intermingling of the maternal and paternal chromosomes.
C1 [Rahman, Mohammad M.; Lee, Brandon; Cohen-Fix, Orna] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Munzig, Mandy; Mueller-Reichert, Thomas] Tech Univ Dresden, Med Fac Carl Gustav Carus, Expt Ctr, Struct Cell Biol Grp, D-01307 Dresden, Germany.
[Kaneshiro, Kiyomi; Strome, Susan] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
RP Cohen-Fix, O (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM ornac@helix.nih.gov
FU Deutsche Forschungsgemeinschaft [DFG SPP1384, MU1423/3-1, MU1423/3-2];
National Institutes of Health R01 Grant [GM34059]; National Institute of
Diabetes and Digestive and Kidney Diseases/National Institutes of Health
FX We thank Kevin O'Connell for alerting us to the plk-1(or683ts) mutant
phenotype and members of the O'Connell, Golden, and Cohen-Fix labs for
advice. We also thank Andy Golden, Ally Walters, Simona Rosu, and Harold
Smith for excellent comments on the manuscript. T.M.-R. was funded by
the Deutsche Forschungsgemeinschaft (DFG SPP1384, Grant MU1423/3-1 and
3-2). K.K. and S.S. were funded by National Institutes of Health R01
Grant GM34059. M.M.R., B.L., and O.C.-F. were funded by an intramural
grant from the National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health.
NR 88
TC 4
Z9 4
U1 2
U2 5
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD DEC 15
PY 2015
VL 26
IS 25
BP 4718
EP 4735
DI 10.1091/mbc.E15-04-0244
PG 18
WC Cell Biology
SC Cell Biology
GA CY3RK
UT WOS:000366327200017
PM 26490119
ER
PT J
AU Helton, SG
Lohoff, FW
AF Helton, Sarah G.
Lohoff, Falk W.
TI Pharmacogenetics of alcohol use disorders and comorbid psychiatric
disorders
SO PSYCHIATRY RESEARCH
LA English
DT Review
DE Pharmacotherapy; Alcohol dependence; Treatment response; Psychiatric
comorbidity; Genetics; Personalized medicine
ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; NATIONAL
EPIDEMIOLOGIC SURVEY; TRANSCRIPTION FACTOR GATA4;
DOPAMINE-BETA-HYDROXYLASE; GENOME-WIDE ASSOCIATION; OPIOID-RECEPTOR
OPRM1; DOUBLE-BLIND; DEPENDENT PATIENTS; MAJOR DEPRESSION
AB Alcohol use disorders (AUDs) represent a significant health burden worldwide. Currently, there are three medications approved by the U.S. Food and Drug Administration for the treatment of AUDs, and other drugs are being prescribed off-label for this purpose. However, response rates for pharmacologic treatment are low, and extant research suggests that treatment effects may partially depend on genetic factors. Personalized medicine, or using a patient's genetics and/or personal history to determine efficacy of treatment prior to prescription, is an emerging tool that will help clinicians treat their patients more effectively and safely. This review systematically discusses current findings from AUD pharmacotherapy trials examining disulfiram, acamprosate, naltrexone, the injectable naltrexone, and topiramate. Furthermore, it presents pharmacogenetics findings associated with these medications in an attempt to further the field of personalized medicine. Research from trials examining AUDs and comorbid major depressive disorder and anxiety disorders is also presented, and pharmacogenetic findings for these treatments are discussed. Lastly, the authors comment on the present and future states of the field of personalized medicine for AUD. Published by Elsevier Ireland Ltd.
C1 [Helton, Sarah G.; Lohoff, Falk W.] NIAAA, Lab Clin Genom & Expt Therapeut, NIH, Bethesda, MD USA.
RP Lohoff, FW (reprint author), NIAAA, Sect Clin Genom & Expt Therapeut CGET, LCTS, NIH, 10 Ctr Dr 10CRC-2-2352, Bethesda, MD 20892 USA.
EM falk.lohoff@nih.gov
RI Lohoff, Falk/M-7951-2016
NR 93
TC 1
Z9 2
U1 10
U2 20
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD DEC 15
PY 2015
VL 230
IS 2
BP 121
EP 129
DI 10.1016/j.psychres.2015.09.019
PG 9
WC Psychiatry
SC Psychiatry
GA CY0DV
UT WOS:000366077400001
PM 26455758
ER
PT J
AU Bertero, T
Cottrill, KA
Annis, S
Bhat, B
Gochuico, BR
Osorio, JC
Rosas, I
Haley, KJ
Corey, KE
Chung, RT
Chau, BN
Chan, SY
AF Bertero, Thomas
Cottrill, Katherine A.
Annis, Sofia
Bhat, Balkrishen
Gochuico, Bernadette R.
Osorio, Juan C.
Rosas, Ivan
Haley, Kathleen J.
Corey, Kathleen E.
Chung, Raymond T.
Chau, B. Nelson
Chan, Stephen Y.
TI A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of
fibrosis in a network of human diseases and physiologic conditions
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MATRIX-METALLOPROTEINASE INHIBITORS; PROMOTES PULMONARY-HYPERTENSION;
HIPPO SIGNALING PATHWAY; GROWTH-FACTOR; CANCER; EXPRESSION; MIR-29; YAP;
PROGRESSION; FIBROBLASTS
AB The molecular origins of fibrosis affecting multiple tissue beds remain incompletely defined. Previously, we delineated the critical role of the control of extracellular matrix (ECM) stiffening by the mechanosensitive microRNA-130/301 family, as activated by the YAP/TAZ co-transcription factors, in promoting pulmonary hypertension (PH). We hypothesized that similar mechanisms may dictate fibrosis in other tissue beds beyond the pulmonary vasculature. Employing an in silico combination of microRNA target prediction, transcriptomic analysis of 137 human diseases and physiologic states, and advanced gene network modeling, we predicted the microRNA-130/301 family as a master regulator of fibrotic pathways across a cohort of seemingly disparate diseases and conditions. In two such diseases (pulmonary fibrosis and liver fibrosis), inhibition of microRNA-130/301 prevented the induction of ECM modification, YAP/TAZ, and downstream tissue fibrosis. Thus, mechanical forces act through a central feedback circuit between microRNA-130/301 and YAP/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states. Such re-conceptualization of interconnections based on shared systems of disease and non-disease gene networks may have broad implications for future convergent diagnostic and therapeutic strategies.
C1 [Bertero, Thomas; Cottrill, Katherine A.; Annis, Sofia; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA.
[Bertero, Thomas; Cottrill, Katherine A.; Annis, Sofia; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Network Med, Boston, MA 02115 USA.
[Bhat, Balkrishen; Chau, B. Nelson] Regulus Therapeut, San Diego, CA USA.
[Gochuico, Bernadette R.] NIH, Bethesda, MD 20892 USA.
[Osorio, Juan C.; Rosas, Ivan; Haley, Kathleen J.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Corey, Kathleen E.; Chung, Raymond T.] Massachusetts Gen Hosp, Liver Ctr & Gastrointestinal Div, Boston, MA 02114 USA.
RP Chan, SY (reprint author), Univ Pittsburgh, Pittsburgh Heart Lung & Blood Vasc Med Inst, Ctr Pulm Vasc Biol & Med, Div Cardiol,Dept Med,Med Ctr, BST1704-2 200 Lothrop St, Pittsburgh, PA 15260 USA.
EM chansy@pitt.edu
OI Osorio, Juan C/0000-0001-8090-1551; BERTERO, Thomas/0000-0002-4801-9902
FU NIH [HL096834, HL124021, DK099422, DK078772]; Pulmonary Hypertension
Association; American Heart Association; Foundation
Bettencourt-Schueller
FX We thank J.W. Snow, S.K. Chan, R. Wang, J. Androsavich, and J. Loscalzo
for manuscript advice. This work was supported by the NIH [grants
HL096834, HL124021 (S.Y.C.); DK099422 (K.E.C.); DK078772 (R.T.C.);
intramural research program (B.R.G.)]; Pulmonary Hypertension
Association; American Heart Association (T.B.); and Foundation
Bettencourt-Schueller (T.B).
NR 63
TC 6
Z9 6
U1 0
U2 9
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 DEC 15
PY 2015
VL 5
AR 18277
DI 10.1038/srep18277
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY4NU
UT WOS:000366385700001
PM 26667495
ER
PT J
AU Ge, ZQ
Bowles, K
Goetz, K
Scholl, HPN
Wang, F
Wang, XJ
Xu, S
Wang, KQ
Wang, H
Chen, R
AF Ge, Zhongqi
Bowles, Kristen
Goetz, Kerry
Scholl, Hendrik P. N.
Wang, Feng
Wang, Xinjing
Xu, Shan
Wang, Keqing
Wang, Hui
Chen, Rui
TI NGS-based Molecular diagnosis of 105 eyeGENE (R) probands with Retinitis
Pigmentosa
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; SYNDROME TYPE-II; RETINAL DEGENERATION; ROD
PHOSPHODIESTERASE; MUTATION SPECTRUM; MACULAR DYSTROPHY; RHODOPSIN GENE;
BETA-SUBUNIT; USH2A GENE; DISEASE
AB The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE (R)) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE (R)'s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE (R).
C1 [Ge, Zhongqi; Wang, Feng; Xu, Shan; Wang, Hui; Chen, Rui] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Ge, Zhongqi; Wang, Feng; Wang, Keqing; Wang, Hui; Chen, Rui] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Goetz, Kerry; Wang, Xinjing] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Bowles, Kristen; Scholl, Hendrik P. N.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Chen, Rui] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
[Chen, Rui] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Chen, Rui] Baylor Coll Med, Struct & Computat Biol & Mol Biophys Grad Program, Houston, TX 77030 USA.
RP Chen, R (reprint author), Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
EM ruichen@bcm.edu
FU Department of Health and Human Services/National Institutes of
Health/National Eye Institute intramural program [06-EI-0236,
10-EI-N164, HHSN-260-2007-00001-C]; Retinal Research Foundation;
Foundation Fighting Blindness [BR-GE-0613-0618-BCM]; National Eye
Institute [R01EY022356]; National Institutes of Health Shared Instrument
Grant [1S10RR026550]; Burroughs Wellcome Trust Fund: The Houston
Laboratory and Population Sciences Training Program in Gene Environment
Interaction; NIH T32 training grant [2T32EY007102-21A1]
FX We would like to thank the patients and families who participated in
this study by participating the eyeGENE (R) network and the eyeGENE (R)
Working Group (https://nei.nih.gov/eyegene/staff_eyegene). The samples
described are available to researchers through request and approval by
the eyeGENE (R) Research Access Subcommittee. Additional information can
be found at the eyeGENE (R) websitenei.nih.gov/eyegene. The eyeGENE (R)
study was supported by the Department of Health and Human
Services/National Institutes of Health/National Eye Institute intramural
program under eyeGENE (R) -Protocol 06-EI-0236 and 10-EI-N164 which has
been funded in part under Contract No. HHSN-260-2007-00001-C. This work
is also supported by grants from the Retinal Research Foundation,
Foundation Fighting Blindness (BR-GE-0613-0618-BCM), and the National
Eye Institute (R01EY022356) (RC). Next-generation sequencing was
conducted at the Functional Genomic Core (FGC) facility at Baylor
College of Medicine supported by National Institutes of Health Shared
Instrument Grant 1S10RR026550 (RC). We thank Ms. Li Zhao and Mr. Evan M.
Jones for reviewing and editing the manuscript. FW was supported by a
predoctoral fellowship funded by the Burroughs Wellcome Trust Fund: The
Houston Laboratory and Population Sciences Training Program in Gene
Environment Interaction. ZG is supported by the NIH T32 training grant
(2T32EY007102-21A1).
NR 54
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U1 0
U2 5
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 DEC 15
PY 2015
VL 5
AR 18287
DI 10.1038/srep18287
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY4NV
UT WOS:000366385800001
PM 26667666
ER
PT J
AU Leikina, E
Defour, A
Melikov, K
Van der Meulen, JH
Nagaraju, K
Bhuvanendran, S
Gebert, C
Pfeifer, K
Chernomordik, LV
Jaiswal, JK
AF Leikina, Evgenia
Defour, Aurelia
Melikov, Kamran
Van der Meulen, Jack H.
Nagaraju, Kanneboyina
Bhuvanendran, Shivaprasad
Gebert, Claudia
Pfeifer, Karl
Chernomordik, Leonid V.
Jaiswal, Jyoti K.
TI Annexin A1 Deficiency does not Affect Myofiber Repair but Delays
Regeneration of Injured Muscles
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CELL-MEMBRANE REPAIR; MYOBLAST FUSION; SKELETAL-MUSCLE;
MUSCULAR-DYSTROPHY; SARCOLEMMAL REPAIR; DYSFERLIN; PROTEINS; MOUSE;
DIFFERENTIATION; DEGENERATION
AB Repair and regeneration of the injured skeletal myofiber involves fusion of intracellular vesicles with sarcolemma and fusion of the muscle progenitor cells respectively. In vitro experiments have identified involvement of Annexin A1 (Anx A1) in both these fusion processes. To determine if Anx A1 contributes to these processes during muscle repair in vivo, we have assessed muscle growth and repair in Anx A1-deficient mouse (AnxA1-/-). We found that the lack of Anx A1 does not affect the muscle size and repair of myofibers following focal sarcolemmal injury and lengthening contraction injury. However, the lack of Anx A1 delayed muscle regeneration after notexin-induced injury. This delay in muscle regeneration was not caused by a slowdown in proliferation and differentiation of satellite cells. Instead, lack of Anx A1 lowered the proportion of differentiating myoblasts that managed to fuse with the injured myofibers by days 5 and 7 after notexin injury as compared to the wild type (w.t.) mice. Despite this early slowdown in fusion of Anx A1-/- myoblasts, regeneration caught up at later times post injury. These results establish in vivo role of Anx A1 in cell fusion required for myofiber regeneration and not in intracellular vesicle fusion needed for repair of myofiber sarcolemma.
C1 [Leikina, Evgenia; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Defour, Aurelia; Van der Meulen, Jack H.; Nagaraju, Kanneboyina; Bhuvanendran, Shivaprasad; Jaiswal, Jyoti K.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Gebert, Claudia; Pfeifer, Karl] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Genome Imprinting, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Nagaraju, Kanneboyina; Jaiswal, Jyoti K.] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA.
RP Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bldg 10 Rm 10D05,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chernoml@mail.nih.gov; jkjaiswal@cnmc.org
RI Jaiswal, Jyoti/M-5891-2013;
OI Jaiswal, Jyoti/0000-0002-5992-5185; defour, aurelia/0000-0002-9114-0054;
Pfeifer, Karl/0000-0002-0254-682X
FU National Institutes of Health / NIAMS [AR055686]; NICHD [HD040677]; MDA
[MDA277389]; AFM; Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health; United States - Israel Binational Science
Foundation (BSF) [2013151]
FX This work was funded by grants from National Institutes of Health /
NIAMS (AR055686), NICHD (HD040677), and MDA (MDA277389) to JKJ, and from
AFM to AD. The research in the LVC laboratory is 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 Grant No 2013151 from the United States - Israel
Binational Science Foundation (BSF).
NR 46
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U1 3
U2 10
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 DEC 15
PY 2015
VL 5
AR 18246
DI 10.1038/srep18246
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY4NB
UT WOS:000366383700001
PM 26667898
ER
PT J
AU Hait, SH
Soares, EA
Sprinz, E
Arthos, J
Machado, ES
Soares, MA
AF Hait, Sabrina H.
Soares, Esmeralda A.
Sprinz, Eduardo
Arthos, James
Machado, Elizabeth S.
Soares, Marcelo A.
TI Worldwide Genetic Features of HIV-1 Env alpha 4 beta 7 Binding Motif:
The Local Dissemination Impact of the LDI Tripeptide
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1; LDI tripeptide; alpha 4 beta 7; virus dissemination; pathogenesis
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MOLECULAR EPIDEMIOLOGY; SOUTHERN BRAZIL;
SUBTYPE-C; INTEGRIN ALPHA(4)BETA(7); HETEROSEXUAL TRANSMISSION; ENVELOPE
GLYCOPROTEIN; MUCOSAL TRANSMISSION; IDENTIFICATION; STRAINS
AB Background:HIV-1 gp120 binds to integrin 47, a homing receptor of lymphocytes to gut-associated lymphoid tissues. This interaction is mediated by the LDI/V tripeptide encoded in the V2-loop. This tripeptide mimics similar motifs in mucosal addressin cellular adhesion molecule (MAdCAM) and vascular CAM (VCAM), the natural ligands of 47. In this study, we explored the association of V2-loop LDI/V mimotopes with transmission routes and patterns of disease progression in HIV-infected adult and pediatric patients. HIV-1 env sequences available in the Los Alamos HIV Sequence database were included in the analyses.Methods:HIV-1 V2-loop sequences generated from infected adults and infants from South and Southeast Brazil, and also retrieved from the Los Alamos database, were assessed for 47 binding tripeptide composition. Chi-Square/Fisher Exact test and Mann Whitney U test were used for tripeptide comparisons. Shannon entropy was assessed for conservancy of the 47 tripeptide mimotope.Results:We observed no association between the tripeptide composition or conservation and virus transmission route or disease progression. However, LDI was linked to successful epidemic dissemination of HIV-1 subtype C in South America, and further to other expanding non-B subtypes in Europe and Asia. In Africa, subtypes showing increased LDV prevalence evidenced an ongoing process of selection toward LDI expansion, an observation also extended to subtype B in the Americas and Western Europe.Conclusions:The V2-loop LDI mimotope was conserved in HIV-1C from South America and other expanding subtypes across the globe, which suggests that LDI may promote successful dissemination of HIV at local geographic levels by means of increased transmission fitness.
C1 [Hait, Sabrina H.; Machado, Elizabeth S.; Soares, Marcelo A.] Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil.
[Hait, Sabrina H.; Soares, Esmeralda A.; Soares, Marcelo A.] Inst Nacl Canc, Programa Oncovirol, BR-20231050 Rio De Janeiro, RJ, Brazil.
[Sprinz, Eduardo] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, BR-90046900 Porto Alegre, RS, Brazil.
[Arthos, James] NIH, Lab Immune Regulat, Bethesda, MD 20892 USA.
[Machado, Elizabeth S.] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil.
RP Soares, MA (reprint author), Inst Nacl Canc, Programa Oncovirol, Rua Andre Cavalcante,37-4 Andar, BR-20231050 Rio De Janeiro, RJ, Brazil.
EM masoares@inca.gov.br
FU Brazilian Ministry of Education (CAPES); Brazilian Ministry of Science
and Technology (CNPq) [304416/2010-0]; Rio de Janeiro State Science
Foundation (FAPERJ) [E226/103.059/2011, E226/112.647/2012]; CNPq
[304169/2013-7]; FAPERJ [E26/111.689/2013]
FX S.H.H. received a PhD scholarship from the Brazilian Ministry of
Education (CAPES). M.A.S. is recipient of grant no. 304416/2010-0 from
the Brazilian Ministry of Science and Technology (CNPq) and grants no.
E226/103.059/2011 and E226/112.647/2012 from the Rio de Janeiro State
Science Foundation (FAPERJ). E.S.M. is recipient of grant 304169/2013-7
from CNPq and grant no. E26/111.689/2013 from FAPERJ. The remaining
authors have no funding or conflicts of interest to disclose.
NR 66
TC 1
Z9 1
U1 0
U2 1
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 DEC 15
PY 2015
VL 70
IS 5
BP 463
EP 471
DI 10.1097/QAI.0000000000000802
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CX3LO
UT WOS:000365600500001
PM 26569174
ER
PT J
AU Barrdahl, M
Canzian, F
Lindstrom, S
Shui, I
Black, A
Hoover, RN
Ziegler, RG
Buring, JE
Chanock, SJ
Diver, WR
Gapstur, SM
Gaudet, MM
Giles, GG
Haiman, C
Henderson, BE
Hankinson, S
Hunter, DJ
Joshi, AD
Kraft, P
Lee, IM
Le Marchand, L
Milne, RL
Southey, MC
Willett, W
Gunter, M
Panico, S
Sund, M
Weiderpass, E
Sanchez, MJ
Overvad, K
Dossus, L
Peeters, PH
Khaw, KT
Trichopoulos, D
Kaaks, R
Campa, D
AF Barrdahl, Myrto
Canzian, Federico
Lindstroem, Sara
Shui, Irene
Black, Amanda
Hoover, Robert N.
Ziegler, Regina G.
Buring, Julie E.
Chanock, Stephen J.
Diver, W. Ryan
Gapstur, Susan M.
Gaudet, Mia M.
Giles, Graham G.
Haiman, Christopher
Henderson, Brian E.
Hankinson, Susan
Hunter, David J.
Joshi, Amit D.
Kraft, Peter
Lee, I-Min
Le Marchand, Loic
Milne, Roger L.
Southey, Melissa C.
Willett, Walter
Gunter, Marc
Panico, Salvatore
Sund, Malin
Weiderpass, Elisabete
Sanchez, Maria-Jose
Overvad, Kim
Dossus, Laure
Peeters, Petra H.
Khaw, Kay-Tee
Trichopoulos, Dimitrios
Kaaks, Rudolf
Campa, Daniele
TI Association of breast cancer risk loci with breast cancer survival
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; SNP; survival; BPC3; meta-analysis
ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; TUMOR-SUPPRESSOR
GENE; SUSCEPTIBILITY LOCI; MAMMOGRAPHIC DENSITY; MULTIETHNIC COHORT;
COMMON VARIANTS; CONFER SUSCEPTIBILITY; IDENTIFIES 2; POLYMORPHISM
AB The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; p(trend)=2.84 x 10(-4); HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p(2DF)=1.45 x 10(-3)). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; p(trend)=6.6 x 10(-4); HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p(2DF)=1.25 x 10(-4)). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.
What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.
C1 [Barrdahl, Myrto; Kaaks, Rudolf; Campa, Daniele] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany.
[Lindstroem, Sara; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Shui, Irene; Hankinson, Susan; Joshi, Amit D.; Kraft, Peter; Lee, I-Min; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA.
[Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Chanock, Stephen J.] Core Genotyping Facil Frederick Natl Lab Canc Res, Gaithersburg, MD USA.
[Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, NW Atlanta, GA USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Haiman, Christopher; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hankinson, Susan] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Epidemiol, Amherst, MA 01003 USA.
[Gapstur, Susan M.] Brigham & Womens Hosp, Canc Res Ctr, Boston, MA 02115 USA.
[Lee, I-Min] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Gunter, Marc] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol Biostat, London, England.
[Panico, Salvatore] Dipartimento Med Clin E Chirurgia, Naples, Italy.
[Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, S-90187 Umea, Sweden.
[Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9001 Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Oslo, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Sanchez, Maria-Jose] Univ Granada, Hosp Univ Granada, Escuela Andaluza Salud Publ, Inst Invest Biosanitaria Ibs Granada, E-18071 Granada, Spain.
[Sanchez, Maria-Jose] CIBERESP, Barcelona, Spain.
[Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark.
[Dossus, Laure] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Nutr Hormones & Womens Hlth Team, U1018, Villejuif, France.
[Dossus, Laure] Univ Paris 11, UMRS 1018, Villejuif, France.
[Dossus, Laure] IGR, Villejuif, France.
[Peeters, Petra H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
[Peeters, Petra H.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
RP Campa, D (reprint author), German Canc Res Ctr, Div Canc Epidemiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM d.campa@dkfz.de
RI Campa, Daniele/K-1617-2016; Panico, Salvatore/K-6506-2016; Weiderpass,
Elisabete/M-4029-2016;
OI Campa, Daniele/0000-0003-3220-9944; Panico,
Salvatore/0000-0002-5498-8312; Weiderpass,
Elisabete/0000-0003-2237-0128; Giles, Graham/0000-0003-4946-9099
FU US National Institutes of Health; National Cancer Institute
[U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07];
Intramural Research Program of National Institutes of Health and
National Cancer Institute, Division of Cancer Epidemiology and Genetics;
Hellenic Health Foundation; Stavros Niarchos Foundation; Department of
Defense Prostate Cancer Research Program Fellowship
FX Grant sponsor: US National Institutes of Health; Grant sponsor: National
Cancer Institute; Grant numbers: U01-CA98233-07, U01-CA98710-06,
U01-CA98216-06 and U01-CA98758-07; Grant sponsor: Intramural Research
Program of National Institutes of Health and National Cancer Institute,
Division of Cancer Epidemiology and Genetics; Grant sponsor: Hellenic
Health Foundation; Grant sponsor: Stavros Niarchos Foundation; Grant
sponsor: Department of Defense Prostate Cancer Research Program
Fellowship
NR 50
TC 1
Z9 1
U1 0
U2 33
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 DEC 15
PY 2015
VL 137
IS 12
BP 2837
EP 2845
DI 10.1002/ijc.29446
PG 9
WC Oncology
SC Oncology
GA CT5IX
UT WOS:000362843300010
PM 25611573
ER
PT J
AU Camargo, MC
Beltran, M
Conde-Glez, CJ
Harris, PR
Michel, A
Waterboer, T
Florez, AC
Torres, J
Ferreccio, C
Sampson, JN
Pawlita, M
Rabkin, CS
AF Camargo, M. Constanza
Beltran, Mauricio
Conde-Glez, Carlos J.
Harris, Paul R.
Michel, Angelika
Waterboer, Tim
Carolina Florez, Astrid
Torres, Javier
Ferreccio, Catterina
Sampson, Joshua N.
Pawlita, Michael
Rabkin, Charles S.
TI Serological response to Helicobacter pylori infection among Latin
American populations with contrasting risks of gastric cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE gastric cancer; H; pylori; Latin America; serology
ID MULTIPLEX SEROLOGY; SERUM ANTIBODIES; PREVALENCE; METAANALYSIS;
CYTOTOXIN; ANTIGENS
AB Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti-H. pylori antibodies among populations with at least twofold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high- and low-risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead-based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high- and low-risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted odds ratio, OR: 1.02, p=0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p<0.05) associated with residence in high-risk areas, but ORs were moderate (1.26, 1.42 and 1.41, respectively) and their discriminatory power was low (area under the curve<0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori-seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified.
What's new? Can antibody patterns reveal a population's gastric cancer risk? These authors tested H. pylori antibodies from individuals in regions of high and low risk in three countries in Latin America. In the largest serological study to date, they measured 15 different anti-H. pylori antibodies to find out whether people in high-risk populations had a different set of antibodies than those in low-risk areas. Persons from high-risk areas had more antibodies to certain proteins, including CagA, suggesting that their infecting strains may be more virulent. However, the difference in immune response was not pronounced enough to reliably assess gastric cancer risk.
C1 [Camargo, M. Constanza; Sampson, Joshua N.; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Beltran, Mauricio] Inst Nacl Salud, Direcc Redes Salud Publ, Bogota, Colombia.
[Conde-Glez, Carlos J.] Inst Nacl Salud Publ, Ctr Invest Salud Poblac, Cuernavaca, Morelos, Mexico.
[Harris, Paul R.] Pontificia Univ Catolica Chile, Dept Gastroenterol & Nutr Pediat, Santiago, Chile.
[Michel, Angelika; Waterboer, Tim; Pawlita, Michael] German Canc Res Ctr DFKZ, Infect & Canc Program, Div Genome Modificat & Carcinogenesis, Heidelberg, Germany.
[Carolina Florez, Astrid] Inst Nacl Salud, Lab Nacl Referencia, Direcc Redes Salud Publ, Lab Parasitol, Bogota, Colombia.
[Torres, Javier] Inst Mexicano Seguro Social, CMN SXXI, UMAE Pediat, Unidad Invest Enfermedades Infecciosas, Mexico City, DF, Mexico.
[Ferreccio, Catterina] Pontificia Univ Catolica Chile, Dept Salud Publ, Cronicas Adv Ctr Chron Dis, Santiago, Chile.
RP Camargo, MC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,BG 9609-6E206, Bethesda, MD 20892 USA.
EM camargomc@mail.nih.gov
RI Camargo, M. Constanza/R-9891-2016; Waterboer, Tim/G-1252-2010;
OI Pawlita, Michael/0000-0002-4720-8306
FU Chilean National Fund for Scientific and Technological Development
(CONICYT); Chilean National Fund for Scientific and Technological
Development (Fondecyt); Chilean National Fund for Scientific and
Technological Development (FONDAP) [1040823, 1130387, 15130011];
Intramural Research Program of the National Cancer Institute, National
Institutes of Health, USA
FX Grant sponsor: Chilean National Fund for Scientific and Technological
Development (CONICYT; Fondecyt and FONDAP Programs); Grant number:
1040823, 1130387, 15130011; Grant sponsor: Intramural Research Program
of the National Cancer Institute, National Institutes of Health, USA
NR 25
TC 3
Z9 4
U1 1
U2 26
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 DEC 15
PY 2015
VL 137
IS 12
BP 3000
EP 3005
DI 10.1002/ijc.29678
PG 6
WC Oncology
SC Oncology
GA CT5IX
UT WOS:000362843300027
PM 26178251
ER
PT J
AU Kelly, PN
Romero, DL
Yang, YB
Shaffer, AL
Chaudhary, D
Robinson, S
Miao, WY
Rui, LX
Westlin, WF
Kapeller, R
Staudt, LM
AF Kelly, Priscilla N.
Romero, Donna L.
Yang, Yibin
Shaffer, Arthur L., III
Chaudhary, Divya
Robinson, Shaughnessy
Miao, Wenyan
Rui, Lixin
Westlin, William F.
Kapeller, Rosana
Staudt, Louis M.
TI Selective interleukin-1 receptor-associated kinase 4 inhibitors for the
treatment of autoimmune disorders and lymphoid malignancy
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID B-CELL LYMPHOMA; SMALL-MOLECULE INHIBITORS; TOLL-LIKE RECEPTORS;
REGULATORY FACTOR-4; CD79B MUTATIONS; ONCOGENIC MYD88; HIGH PREVALENCE;
IRAK-4 KINASE; INFLAMMATION; EXPRESSION
AB Pathological activation of the Toll-like receptor signaling adaptor protein MYD88 underlies many autoimmune and inflammatory disease states. In the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), the oncogenic MYD88 L265P mutation occurs in 29% of cases, making it the most prevalent activating mutation in this malignancy. IRAK4 kinase accounts for almost all of the biological functions of MYD88, highlighting IRAK4 as a therapeutic target for diseases driven by aberrant MYD88 signaling. Using innovative structure-based drug design methodologies, we report the development of highly selective and bioavailable small molecule IRAK4 inhibitors, ND-2158 and ND-2110. These small molecules suppressed LPS-induced TNF production, alleviated collagen-induced arthritis, and blocked gout formation in mouse models. IRAK4 inhibition promoted killing of ABC DLB CL lines harboring MYD88 L265P, by down-modulating survival signals, including NF-kappa B and autocrine IL-6/IL-10 engagement of the JAK-STAT3 pathway. In ABC DLB CL xenograft models, IRAK4 inhibition suppressed tumor growth as a single agent, and in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or the Bcl-2 inhibitor ABT-199. Our findings support pharmacological inhibition of IRAK4 as a therapeutic strategy in autoimmune disorders, in a genetically defined population of ABC DLB CL, and possibly other malignancies dependent on aberrant MYD88 signaling.
C1 [Kelly, Priscilla N.; Yang, Yibin; Shaffer, Arthur L., III; Rui, Lixin; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Romero, Donna L.; Chaudhary, Divya; Miao, Wenyan; Westlin, William F.; Kapeller, Rosana] Nimbus Therapeut, Cambridge, MA 02141 USA.
[Robinson, Shaughnessy] Schrodinger, New York, NY 10036 USA.
RP Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. We thank George Wright for statistical analysis
(Biometric Research Branch, National Cancer Institute/NIH).
NR 44
TC 17
Z9 18
U1 3
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD DEC 14
PY 2015
VL 212
IS 13
BP 2189
EP 2201
DI 10.1084/jem.20151074
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DB1DP
UT WOS:000368248500005
PM 26621451
ER
PT J
AU Skvortsov, AT
Berezhkovskii, AM
Dagdug, L
AF Skvortsov, Alexei T.
Berezhkovskii, Alexander M.
Dagdug, Leonardo
TI Note: Boundary homogenization for a circle with periodic absorbing arcs.
Exact expression for the effective trapping rate
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID CONTROLLED LIGAND-BINDING; DIFFUSION; SURFACES; RECEPTORS; PERMEABILITY;
AUTOCRINE; MEMBRANE; ARRAYS
C1 [Skvortsov, Alexei T.] Def Sci & Technol Org, Maritime Div, Fishermans Bend, Vic 3207, Australia.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico.
RP Skvortsov, AT (reprint author), Def Sci & Technol Org, Maritime Div, Fishermans Bend, Vic 3207, Australia.
FU Consejo Nacional de Ciencia y Tecnologia (CONACyT) [176452]; Intramural
Research Program of the NIH, Center for Information Technology
FX A.S. thanks I. R. MacGillivray for useful discussions and comments. 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.
NR 28
TC 1
Z9 1
U1 0
U2 3
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 DEC 14
PY 2015
VL 143
IS 22
AR 226101
DI 10.1063/1.4936866
PG 2
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CZ6EP
UT WOS:000367194300057
PM 26671405
ER
PT J
AU Faupel-Badger, JM
Nelson, DE
Izmirlian, G
Ross, KH
Raue, K
Tsakraklides, S
Miyaoka, A
Spiegelman, M
AF Faupel-Badger, Jessica M.
Nelson, David E.
Izmirlian, Grant
Ross, Katherine H.
Raue, Kimberley
Tsakraklides, Sophia
Miyaoka, Atsushi
Spiegelman, Maura
TI Independent Association of Postdoctoral Training with Subsequent Careers
in Cancer Prevention
SO PLOS ONE
LA English
DT Article
ID PROGRAM; OUTCOMES; WEB
AB The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP), a structured in-house postdoctoral training program of 3-4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987-2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher's exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio [OR] = 4.99, 95% confidence interval [95% CI): 1.91-13.0) were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38-13.2). In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly.
C1 [Faupel-Badger, Jessica M.] NIGMS, Bethesda, MD 20892 USA.
[Nelson, David E.; Ross, Katherine H.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Izmirlian, Grant] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Raue, Kimberley; Tsakraklides, Sophia; Miyaoka, Atsushi; Spiegelman, Maura] Westat Corp, Rockville, MD USA.
RP Faupel-Badger, JM (reprint author), NIGMS, Bethesda, MD 20892 USA.
EM badgerje@mail.nih.gov
RI User, Test/G-7821-2015
FU National Institutes of Health Evaluation Set-Aside Program
FX This study was funded by the National Institutes of Health Evaluation
Set-Aside Program. NIH Staff provided input on the survey questions but
did not participate in the collection of data. Westat staff analyzed the
data and provided an anonymized dataset to NIH staff for regression
analysis.
NR 22
TC 1
Z9 1
U1 1
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 DEC 14
PY 2015
VL 10
IS 12
AR e0144880
DI 10.1371/journal.pone.0144880
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9GR
UT WOS:000366715900131
PM 26659381
ER
PT J
AU Sigurdsson, S
Forsberg, L
Aspelund, T
van der Geest, RJ
van Buchem, MA
Launer, LJ
Gudnason, V
van Osch, MJ
AF Sigurdsson, Sigurdur
Forsberg, Lars
Aspelund, Thor
van der Geest, Rob J.
van Buchem, Mark A.
Launer, Lenore J.
Gudnason, Vilmundur
van Osch, Matthias J.
TI Feasibility of Using Pseudo-Continuous Arterial Spin Labeling Perfusion
in a Geriatric Population at 1.5 Tesla
SO PLOS ONE
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; ALZHEIMERS-DISEASE; ELDERLY SUBJECTS; 3.0 T; MRI;
REPRODUCIBILITY; BRAIN; RELIABILITY; AGE; LOCALIZATION
AB Objectives
To evaluate the feasibility of using pseudo-continuous arterial spin labeling (pCASL) perfusion in a geriatric population at 1.5-Tesla.
Materials and Methods
In 17 participants (mean age 78.8 +/- 1.63 years) we assessed; 1) inter-session repeatability and reliability of resting state perfusion in 27 brain regions; 2) brain activation using finger-tapping as a means to evaluate the ability to detect flow differences; 3) reliability by comparing cerebral blood flow (CBF) with pCASL to CBF with phase contrast (PC-MR).
Results
The CBF (mean +/- standard deviation (SD)) for the whole brain grey matter (GM) was 40.6 +/- 8.4 and 41.4 +/- 8.7 ml/100g/min for the first and second scan respectively. The within-subject standard deviation (SDw), the repeatability index (RI) and intra-class correlation coefficient (ICC) across the 27 regions ranged from 1.1 to 7.9, 2.2 to 15.5 and 0.35 to 0.98 respectively. For whole brain GM the SDw, RI and ICC were 1.6, 3.2 and 0.96 respectively. The between-subject standard deviation (SDB) was larger than the SDw for all regions. Comparison of CBF at rest and activation on a voxel level showed significantly higher perfusion during finger tapping in the motor-and somatosensory regions. The mean CBF for whole brain GM was 40.6 +/- 8.4 ml/100g/min at rest and 42.6 +/- 8.6 ml/100g/min during activation. Finally the reliability of pCASL against the reference standard of PC-MR was high (ICC = 0.80). The mean CBF for whole brain measured with PC-MRI was 54.3 +/- 10.1 ml/100g/min and 38.3 +/- 7.8 ml/100g/min with pCASL.
Conclusions
The results demonstrate moderate to high levels of repeatability and reliability for most brain regions, comparable to what has been reported for younger populations. The performance of pCASL at 1.5-Tesla shows that region-specific perfusion measurements with this technique are feasible in studies of a geriatric population.
C1 [Sigurdsson, Sigurdur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Forsberg, Lars; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[van der Geest, Rob J.; van Buchem, Mark A.; van Osch, Matthias J.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Sigurdsson, S (reprint author), Iceland Heart Assoc, Kopavogur, Iceland.
EM sigurdur@hjarta.is
NR 42
TC 1
Z9 1
U1 1
U2 3
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 DEC 14
PY 2015
VL 10
IS 12
AR e0144743
DI 10.1371/journal.pone.0144743
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY9GR
UT WOS:000366715900100
PM 26659363
ER
PT J
AU Wang, HF
Fox, CS
Troy, LM
Mckeown, NM
Jacques, PF
AF Wang, Huifen
Fox, Caroline S.
Troy, Lisa M.
Mckeown, Nicola M.
Jacques, Paul F.
TI Longitudinal association of dairy consumption with the changes in blood
pressure and the risk of incident hypertension: the Framingham Heart
Study
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Dairy intake; Blood pressure; Hypertension; Milk products; Yoghurt
ID FOOD FREQUENCY QUESTIONNAIRE; JOINT NATIONAL COMMITTEE; MILK-FAT;
ARTERIAL STIFFNESS; DIETARY PATTERNS; 7TH REPORT; WOMEN; MEN; HEALTH;
REPRODUCIBILITY
AB We aimed to examine the longitudinal association of dairy consumption with the changes in blood pressure (BP) and the risk of incident hypertension (HTN) among adults. This study included 2636 Framingham Heart Study Offspring Cohort members who participated in the 5th through 8th examinations (1991-2008) and were free of HTN at their first examination during the follow-up. Data collected at each examination included dietary intake (by a validated FFQ), BP (following standardised procedures) and anti-hypertensive medication use (by physician-elicited self-report). HTN was defined as systolic BP (SBP)140 mmHg, or diastolic BP (DBP)90 mmHg or anti-hypertensive medication use. We used repeated-measure and discrete-time hazard regressions to examine the associations of dairy consumption with the annualised BP change (n 2075) and incident HTN (n 2340; cases=1026), respectively. Covariates included demographic, lifestyle, overall diet quality, metabolic factors and medication use. Greater intakes of total dairy foods, total low-fat/fat-free dairy foods, low-fat/skimmed milk and yoghurt were associated with smaller annualised increments in SBP and a lower risk of projected HTN incidence. However, with the exception of total dairy foods and yoghurt, these inverse associations with HTN risk were attenuated as the follow-up time increased. For yoghurt, each additional serving was associated with 6 (95 % CI 1, 10) % reduced risk of incident HTN. Total dairy and total low-fat/fat-free dairy intakes were found to be inversely related to changes in DBP. Dairy consumption, as part of a nutritious and energy-balanced diet pattern, may benefit BP control and prevent or delay the onset of HTN.
C1 [Wang, Huifen; Mckeown, Nicola M.; Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Troy, Lisa M.] Univ Massachusetts, Chenoweth Lab, Dept Nutr, Amherst, MA 01003 USA.
RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer US Dept Agr USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM Paul.jacques@tufts.edu
FU NHLBI [NO1-HC-25195]; US Department of Agriculture [58-1950-0-104];
Dannon Company Inc.; General Mills Bell Institute of Health and
Nutrition
FX This work was supported by NHLBI contract no. NO1-HC-25195, US
Department of Agriculture Agreement 58-1950-0-104 and research grants
from The Dannon Company Inc. and General Mills Bell Institute of Health
and Nutrition. Any opinions, findings, conclusions or recommendations
expressed in this paper are those of the authors and do not necessarily
represent those of the NHLBI, the National Institutes of Health, the US
Department of Health and Human Services or the US Department of
Agriculture. The Dannon Company Inc. and General Mills Bell Institute of
Health and Nutrition had no role in the design, analysis or writing of
this article.
NR 51
TC 8
Z9 8
U1 3
U2 18
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD DEC 14
PY 2015
VL 114
IS 11
BP 1887
EP 1899
DI 10.1017/S0007114515003578
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CW7HC
UT WOS:000365167800015
PM 26395861
ER
PT J
AU Geybels, MS
Alumkal, JJ
Luedeke, M
Rinckleb, A
Zhao, SS
Shui, IM
Bibikova, M
Klotzle, B
van den Brandt, PA
Ostrander, EA
Fan, JB
Feng, ZD
Maier, C
Stanford, JL
AF Geybels, Milan S.
Alumkal, Joshi J.
Luedeke, Manuel
Rinckleb, Antje
Zhao, Shanshan
Shui, Irene M.
Bibikova, Marina
Klotzle, Brandy
van den Brandt, Piet A.
Ostrander, Elaine A.
Fan, Jian-Bing
Feng, Ziding
Maier, Christiane
Stanford, Janet L.
TI Epigenomic profiling of prostate cancer identifies differentially
methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative
tumors
SO CLINICAL EPIGENETICS
LA English
DT Article
DE DNA methylation; CpG site; Epigenetics; Epigenomic profiling; Prostate
cancer; Gene fusion; TMPRSS2; ERG; Tumor tissue; Unsupervised
clustering; mRNA expression; C3orf14; CACNA1D; GREM1; KLK10; NT5C;
PDE4D; RAB40C; SEPT9; TRIB2; TCGA
ID IN-SITU HYBRIDIZATION; DNA METHYLATION; BODY METHYLATION;
ERG-EXPRESSION; ST ARRAYS; ASSOCIATION; TARGET; TISSUE;
HYPERMETHYLATION; REARRANGEMENTS
AB Background: About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We therefore investigated epigenome-wide DNA methylation profiles of PCa stratified by T2E status.
Results: The study included 496 patients with clinically localized PCa who had a radical prostatectomy as primary treatment for PCa. Fluorescence in situ hybridization (FISH) "break-apart" assays were used to determine tumor T2E- fusion status, which showed that 266 patients (53.6 %) had T2E-positive PCa. The study showed global DNA methylation differences between tumor subtypes. A large number of differentially methylated CpG sites were identified (false-discovery rate [FDR] Q-value <0.00001; n = 27,876) and DNA methylation profiles accurately distinguished between tumor T2E subgroups. A number of top-ranked differentially methylated CpGs in genes (FDR Q-values = <= 1.53E-29) were identified: C3orf14, CACNA1D, GREM1, KLK10, NT5C, PDE4D, RAB40C, SEPT9, and TRIB2, several of which had a corresponding alteration in mRNA expression. These genes may have various roles in the pathogenesis of PCa, and the calcium-channel gene CACNA1D is a known ERG-target. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings.
Conclusions: This study identified substantial differences in DNA methylation profiles of T2E-positive and T2E-negative tumors, thereby providing further evidence that different underlying oncogenic pathways characterize these molecular subtypes.
C1 [Geybels, Milan S.; Zhao, Shanshan; Shui, Irene M.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Geybels, Milan S.; van den Brandt, Piet A.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands.
[Alumkal, Joshi J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97201 USA.
[Luedeke, Manuel; Rinckleb, Antje; Maier, Christiane] Univ Ulm, Fac Med, Inst Human Genet, D-89069 Ulm, Germany.
[Luedeke, Manuel; Rinckleb, Antje; Maier, Christiane] Univ Ulm, Fac Med, Dept Urol, D-89069 Ulm, Germany.
[Zhao, Shanshan] NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA.
[Bibikova, Marina; Klotzle, Brandy; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA.
[Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Geybels, MS (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
EM mgeybels@fredhutch.org; jstanfor@fredhutch.org
OI Ostrander, Elaine/0000-0001-6075-9738
FU National Cancer Institute [R01 CA056678, R01 CA092579, K05 CA175147, P50
CA097186]; Fred Hutchinson Cancer Research Center; Intramural Program of
the National Human Genome Research Institute; Prostate Cancer
Foundation; Dutch Cancer Society Fellowship (BUIT) [2014-6645]
FX This work was supported by grants from the National Cancer Institute
(R01 CA056678, R01 CA092579, K05 CA175147, and P50 CA097186), with
additional support provided by the Fred Hutchinson Cancer Research
Center, Intramural Program of the National Human Genome Research
Institute, and the Prostate Cancer Foundation. Milan Geybels is the
recipient of a Dutch Cancer Society Fellowship (BUIT 2014-6645).
NR 53
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Z9 5
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1868-7083
J9 CLIN EPIGENETICS
JI Clin. Epigenetics
PD DEC 12
PY 2015
VL 7
AR 128
DI 10.1186/s13148-015-0161-6
PG 12
WC Oncology
SC Oncology
GA CY2NO
UT WOS:000366245600001
PM 26692910
ER
PT J
AU Suzawa, M
Miranda, DA
Ramos, KA
Ang, KKH
Faivre, EJ
Wilson, CG
Caboni, L
Arkin, MR
Kim, YS
Fletterick, RJ
Diaz, A
Schneekloth, JS
Ingraham, HA
AF Suzawa, Miyuki
Miranda, Diego A.
Ramos, Karmela A.
Ang, Kenny K-H
Faivre, Emily J.
Wilson, Christopher G.
Caboni, Laura
Arkin, Michelle R.
Kim, Yeong-Sang
Fletterick, Robert J.
Diaz, Aaron
Schneekloth, John S., Jr.
Ingraham, Holly A.
TI A gene-expression screen identifies a non-toxic sumoylation inhibitor
that mimics SUMO-less human LRH-1 in liver
SO ELIFE
LA English
DT Article
ID PROTEIN SUMOYLATION; EMBRYONIC-DEVELOPMENT; CONJUGATING ENZYMES;
ANDROGEN RECEPTOR; GINKGOLIC ACID; IN-VIVO; CELLS; PATHWAY; HEDGEHOG;
MICE
AB SUMO-modification of nuclear proteins has profound effects on gene expression. However, non-toxic chemical tools that modulate sumoylation in cells are lacking. Here, to identify small molecule sumoylation inhibitors we developed a cell-based screen that focused on the well-sumoylated substrate, human Liver Receptor Homolog-1 (hLRH-1, NR5A2). Our primary gene-expression screen assayed two SUMO-sensitive transcripts, APOC3 and MUC1, that are upregulated by SUMO-less hLRH-1 or by siUBC9 knockdown, respectively. A polyphenol, tannic acid (TA) emerged as a potent sumoylation inhibitor in vitro (IC50 = 12.8 mu M) and in cells. TA also increased hLRH-1 occupancy on SUMO-sensitive transcripts. Most significantly, when tested in humanized mouse primary hepatocytes, TA inhibits hLRH-1 sumoylation and induces SUMO-sensitive genes, thereby recapitulating the effects of expressing SUMO-less hLRH-1 in mouse liver. Our findings underscore the benefits of phenotypic screening for targeting post-translational modifications, and illustrate the potential utility of TA for probing the cellular consequences of sumoylation.
C1 [Suzawa, Miyuki; Miranda, Diego A.; Ramos, Karmela A.; Faivre, Emily J.; Ingraham, Holly A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Ang, Kenny K-H; Wilson, Christopher G.; Arkin, Michelle R.] Univ Calif San Francisco, Dept Pharmaceut Chem, Small Mol Discovery Ctr, San Francisco, CA USA.
[Caboni, Laura; Fletterick, Robert J.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[Kim, Yeong-Sang; Schneekloth, John S., Jr.] NCI, Biol Chem Lab, Frederick, MD 21701 USA.
[Diaz, Aaron] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Ingraham, HA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
EM holly.ingraham@ucsf.edu
FU American Heart Association [14POST2013-0048]; National Institute of
Child Health and Human Development [NIH T32 HD726330]; National
Institute of Diabetes and Digestive and Kidney Diseases [NIH R01
DK063592-S1, NIH P30 DK026743, NIH R01 DK099722]; QB3-Malaysia Program;
National Cancer Institute; University of California, San Francisco;
American Diabetes Association [1-15-MI-08]
FX American Heart Association 14POST2013-0048 Diego A Miranda; National
Institute of Child Health and Human Development NIH T32 HD726330 Diego A
Miranda; National Institute of Diabetes and Digestive and Kidney
Diseases NIH R01 DK063592-S1 Karmela A Ramos Holly A Ingraham;
QB3-Malaysia Program Kenny K-H Ang; National Cancer Institute Intramural
Research Program John S Schneekloth Jr; University of California, San
Francisco UCSF-PBBR/Roche Innovation Grant Holly A Ingraham; National
Institute of Diabetes and Digestive and Kidney Diseases NIH P30 DK026743
Holly A Ingraham; National Institute of Diabetes and Digestive and
Kidney Diseases NIH R01 DK099722 Holly A Ingraham; American Diabetes
Association 1-15-MI-08 Holly A Ingraham; The funders had no role in
study design, data collection and interpretation, or the decision to
submit the work for publication.
NR 65
TC 0
Z9 0
U1 4
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 11
PY 2015
VL 4
AR e09003
DI 10.7554/eLife.09003
PG 22
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9GI
UT WOS:000373809900001
ER
PT J
AU Yu, M
Yang, WJ
Ni, T
Tang, ZY
Nakadai, T
Zhu, J
Roeder, RG
AF Yu, Ming
Yang, Wenjing
Ni, Ting
Tang, Zhanyun
Nakadai, Tomoyoshi
Zhu, Jun
Roeder, Robert G.
TI RNA polymerase II-associated factor 1 regulates the release and
phosphorylation of paused RNA polymerase II
SO SCIENCE
LA English
DT Article
ID PAF1 COMPLEX; TRANSCRIPTION ELONGATION; TERMINAL DOMAIN; P-TEFB;
CHROMATIN; KINASE; CTD; RECRUITMENT; ROLES; SPT5
AB Release of promoter-proximal paused RNA polymerase II (Pol II) during early elongation is a critical step in transcriptional regulation in metazoan cells. Paused Pol II release is thought to require the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity-inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II. We found that Pol II-associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. These findings reveal cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation.
C1 [Yu, Ming; Tang, Zhanyun; Nakadai, Tomoyoshi; Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
[Yang, Wenjing; Zhu, Jun] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Ni, Ting] Fudan Univ, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
[Ni, Ting] Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, Collaborat Innovat Ctr Genet & Dev,Sch Life Sci, Shanghai 200438, Peoples R China.
RP Roeder, RG (reprint author), Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
EM roeder@rockefeller.edu
FU Leukemia and Lymphoma Society SCOR grant; National Heart, Lung, and
Blood Institute; National Science Foundation of China
FX We thank G. Morin for providing the cyclin K cDNA, and S. Malik, S.
Murphy, and M. Guermah for critical reading of the manuscript. Supported
by a Leukemia and Lymphoma Society SCOR grant (R.G.R.), the intramural
research program of the National Heart, Lung, and Blood Institute (W.Y.
and J.Z.), and a National Science Foundation of China grant (T.Ni).
ChIP-seq and RNA-seq data have been submitted to GEO under accession
number GSE62171.
NR 23
TC 17
Z9 17
U1 4
U2 22
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 DEC 11
PY 2015
VL 350
IS 6266
BP 1383
EP 1386
DI 10.1126/science.aad2338
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY1JL
UT WOS:000366162400044
PM 26659056
ER
PT J
AU Tran, E
Ahmadzadeh, M
Lu, YC
Gros, A
Turcotte, S
Robbins, PF
Gartner, JJ
Zheng, ZL
Li, YF
Ray, S
Wunderlich, JR
Somerville, RP
Rosenberg, SA
AF Tran, Eric
Ahmadzadeh, Mojgan
Lu, Yong-Chen
Gros, Alena
Turcotte, Simon
Robbins, Paul F.
Gartner, Jared J.
Zheng, Zhili
Li, Yong F.
Ray, Satyajit
Wunderlich, John R.
Somerville, Robert P.
Rosenberg, Steven A.
TI Immunogenicity of somatic mutations in human gastrointestinal cancers
SO SCIENCE
LA English
DT Article
ID T-CELLS; INTRATUMOR HETEROGENEITY; PD-1 BLOCKADE; MELANOMA; IPILIMUMAB;
PATIENT; IDENTIFICATION; IMMUNOTHERAPY; NIVOLUMAB; ANTI-PD-1
AB It is unknown whether the human immune system frequently mounts a T cell response against mutations expressed by common epithelial cancers. Using a next-generation sequencing approach combined with high-throughput immunologic screening, we demonstrated that tumor-infiltrating lymphocytes (TILs) from 9 out of 10 patients with metastatic gastrointestinal cancers contained CD4(+) and/or CD8(+) T cells that recognized one to three neo-epitopes derived from somatic mutations expressed by the patient's own tumor. There were no immunogenic epitopes shared between these patients. However, we identified in one patient a human leukocyte antigen-C*08:02-restricted T cell receptor from CD8(+) TILs that targeted the KRAS(G12D) hotspot driver mutation found in many human cancers. Thus, a high frequency of patients with common gastrointestinal cancers harbor immunogenic mutations that can potentially be exploited for the development of highly personalized immunotherapies.
C1 [Tran, Eric; Ahmadzadeh, Mojgan; Lu, Yong-Chen; Gros, Alena; Turcotte, Simon; Robbins, Paul F.; Gartner, Jared J.; Zheng, Zhili; Li, Yong F.; Ray, Satyajit; Wunderlich, John R.; Somerville, Robert P.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
EM sar@mail.nih.gov
OI Gros, Alena/0000-0002-1207-1880
FU Milstein Family Foundation; Center for Cancer Research intramural
research program of the National Cancer Institute
FX We thank the Milstein Family Foundation for their generous support, Q.
Wang and U. Rudloff for providing KRAS-genotyped pancreatic cancer cell
lines, A. Mixon and S. Farid for flow cytometry support, M. El-Gamil for
reagents, T. Prickett for RNA-sequencing assistance, and other members
of the Surgery Branch for helpful discussions and technical support. The
data presented in this manuscript are tabulated in the main paper and in
the supplementary materials. The raw whole-exome and genome sequence
data are available through the National Center for Biotechnology
Information Bioproject database, Bioproject PRJNA298330. E.T., Y-C.L.,
and S.A.R. have filed a patent application (U. S. application no.
62/218,688) that relates to the KRASG12D-mutation reactive
TCR. This research was supported by the Center for Cancer Research
intramural research program of the National Cancer Institute.
NR 26
TC 68
Z9 69
U1 8
U2 31
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 DEC 11
PY 2015
VL 350
IS 6266
BP 1387
EP 1390
DI 10.1126/science.aad1253
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY1JL
UT WOS:000366162400045
PM 26516200
ER
PT J
AU Lindhurst, MJ
Yourick, MR
Yu, Y
Savage, RE
Ferrari, D
Biesecker, LG
AF Lindhurst, Marjorie J.
Yourick, Miranda R.
Yu, Yi
Savage, Ronald E.
Ferrari, Dora
Biesecker, Leslie G.
TI Repression of AKT signaling by ARQ 092 in cells and tissues from
patients with Proteus syndrome
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MUTATION; DOMAIN; INHIBITOR; S6
AB A somatic activating mutation in AKT1, c.49G>A, pGlu17Lys, that results in elevated AKT signaling in mutation-positive cells, is responsible for the mosaic overgrowth condition, Proteus syndrome. ARQ 092 is an allosteric pan-AKT inhibitor under development for treatment in cancer. We tested the efficacy of this drug for suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner in as little as two hours. While AKT signaling was suppressed with ARQ 092 treatment, cells retained their ability to respond to growth factor stimulation by increasing pAKT levels proportionally to untreated cells. At concentrations sufficient to decrease AKT signaling, little reduction in cell viability was seen. These results indicate that ARQ 092 can suppress AKT signaling and warrants further development as a therapeutic option for patients with Proteus syndrome.
C1 [Lindhurst, Marjorie J.; Yourick, Miranda R.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Yu, Yi; Savage, Ronald E.; Ferrari, Dora] ArQule Inc, Burlington, MA USA.
RP Lindhurst, MJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM marjr@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute
FX We thank Hannah Kondolf for technical support, Sudharshan Eathiraj for
critical reading of this manuscript, and Julia Fekecs for graphics
support. M.J.L., M.R.Y., and L.G.B. were supported by the Intramural
Research Program of the National Human Genome Research Institute.
NR 25
TC 4
Z9 4
U1 2
U2 2
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 DEC 11
PY 2015
VL 5
AR 17162
DI 10.1038/srep17162
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY1QZ
UT WOS:000366183900001
PM 26657992
ER
PT J
AU Chen, JC
Feng, XM
Desierto, MJ
Keyvanfar, K
Young, NS
AF Chen, Jichun
Feng, Xingmin
Desierto, Marie J.
Keyvanfar, Keyvan
Young, Neal S.
TI IFN-gamma-mediated hematopoietic cell destruction in murine models of
immune-mediated bone marrow failure
SO BLOOD
LA English
DT Article
ID GRAFT-VERSUS-HOST; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA;
INTERFERON-GAMMA; STEM-CELLS; PROGENITOR CELLS; APLASTIC-ANEMIA;
IN-VITRO; MOUSE MODEL; GRANULOCYTE-MACROPHAGE
AB Interferon gamma(IFN-gamma) has been reported to have both negative and positive activity on hematopoietic cells, adding complexity to the interpretation of its pleiotropic functions. We examined the effects of IFN-gamma on murine hematopoietic stem cells (HSCs) and progenitors in vitro and in vivo by using mouse models. IFN-gamma treatment expanded bone marrow (BM) c-Kit(+)Sca1(+)Lin(-)(KSL) cell number but reduced BM KLCD150(+) and KLCD150(+)CD48(-) cells. IFN-gamma-expanded KSL cells engrafted poorly when tested by competitive repopulation in vivo. KSL, KLCD150(+) and KLCD150(+)CD48(-) cells from IFN-gamma-treated animals all showed significant upregulation in Fas expression. When cocultured with activated T cells in vitro, KSL and KLCD150(+) cells from IFN-gamma-treated donors showed increased apoptosis relative to those from untreated animals, and infusion of activated CD8 T cells into IFN-gamma-injected animals in vivo led to partial elimination of KSL cells. Exposure of BM cells or KSL cells to IFN-gamma increased expression of Fas, caspases, and related proapoptotic genes and decreased expression of Ets-1 and other hematopoietic genes. In mouse models of BM failure, mice genetically deficient in IFN-gamma receptor expression showed attenuation of immune-mediated marrow destruction, whereas effector lymphocytes from IFN-gamma-deficient donors were much less potent in initiating BM damage. We conclude that the activity of IFN-gamma on murine hematopoiesis is context dependent. IFN-gamma-augmented apoptotic gene expression facilitates destruction of HSCs and progenitors in the presence of activated cytotoxic T cells, as occurs in human BM failure.
C1 [Chen, Jichun; Feng, Xingmin; Desierto, Marie J.; Keyvanfar, Keyvan; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Clin Res Ctr, NIH Bldg 10,Room 3E-5272,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chenji@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute Intramural Research Program,
National Institutes of Health
FX This study was supported by the National Heart, Lung, and Blood
Institute Intramural Research Program, National Institutes of Health.
NR 74
TC 4
Z9 4
U1 4
U2 13
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 DEC 10
PY 2015
VL 126
IS 24
BP 2621
EP 2631
DI 10.1182/blood-2015-06-652453
PG 11
WC Hematology
SC Hematology
GA DB3RQ
UT WOS:000368429400016
PM 26491068
ER
PT J
AU Donahue, RE
Srinivasula, S
Uchida, N
Kim, I
Claire, AS
Duralde, G
DeGrange, P
Claire, MS
Reba, RC
Bonifacino, AC
Krouse, AE
Metzger, ME
Paik, CH
Lane, HC
Tisdale, JF
Di Mascio, M
AF Donahue, Robert E.
Srinivasula, Sharat
Uchida, Naoya
Kim, Insook
Claire, Alexis St.
Duralde, Gorka
DeGrange, Paula
Claire, Marisa St.
Reba, Richard C.
Bonifacino, Aylin C.
Krouse, Allen E.
Metzger, Mark E.
Paik, Chang H.
Lane, H. Clifford
Tisdale, John F.
Di Mascio, Michele
TI Discordance in lymphoid tissue recovery following stem cell
transplantation in rhesus macaques: an in vivo imaging study
SO BLOOD
LA English
DT Article
ID T-CELLS; IMMUNOLOGICAL-TOLERANCE; NONHUMAN-PRIMATES; CD4; MACROPHAGES;
INFECTION; ANTIBODY; MODEL; VITRO; BODY
AB Ionizing irradiation is used routinely to induce myeloablation and immunosuppression. However, it has not been possible to evaluate the extent of ablation without invasive biopsy. For lymphoid recovery, peripheral blood (PB) lymphocytes (PBLs) have been used for analysis, but they represent <2% of cells in lymphoid tissues (LTs). Using a combination of single-photon emission computed tomography imaging and a radiotracer (Tc-99m-labeled rhesus immunoglobulin G1 anti-CD4R1 (Fab')(2)), we sequentially imaged CD4(+) cell recovery in rhesus macaques following total body irradiation (TBI) and reinfusion of vector-transduced, autologous CD34(+) cells. Our results present for the first time a sequential, real-time, noninvasive method to evaluate CD4(+) cell recovery. Importantly, despite myeloablation of circulating leukocytes following TBI, total depletion of CD4(+) lymphocytes in LTs such as the spleen is not achieved. The impact of TBI on LTs and PBLs is discordant, in which as few as 32.4% of CD4(+) cells were depleted from the spleen. In addition, despite full lymphocyte recovery in the spleen and PB, lymph nodes have suboptimal recovery. This highlights concerns about residual disease, endogenous contributions to recovery, and residual LT damage following ionizing irradiation. Such methodologies also have direct application to immunosuppressive therapy and other immunosuppressive disorders, such as those associated with viral monitoring.
C1 [Donahue, Robert E.; Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Srinivasula, Sharat] Leidos Biomed Res Inc, FNLCR, Biostat Res Branch, Frederick, MD USA.
[Uchida, Naoya; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Kim, Insook] Leidos Biomed Res Inc, FNLCR, Applied Dev Res Directorate, Frederick, MD USA.
[Claire, Alexis St.; Duralde, Gorka; Di Mascio, Michele] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[DeGrange, Paula; Claire, Marisa St.] NIAID, Integrated Res Facil, NIH, Frederick, MD 20892 USA.
[Reba, Richard C.] NIAID, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Paik, Chang H.] NIAID, Radiopharmaceut Lab, Nucl Med Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Donahue, RE (reprint author), NHLBI, Hematol Branch, MSC 4450,49 Convent Dr, Bethesda, MD 20892 USA.
EM donahuer@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI); National Institutes
of Allergy and Infectious Diseases (NIAID); National Institute of
Diabetes, Digestive, and Kidney Diseases (NIDDK) at the National
Institutes of Health (NIH); National Cancer Institute (NCI), NIH
[HHSN261200800001E]
FX This work was supported by the intramural research program of the
National Heart, Lung, and Blood Institute (NHLBI), the National
Institutes of Allergy and Infectious Diseases (NIAID), and the National
Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) at the
National Institutes of Health (NIH). This project has been funded in
part with federal funds from the National Cancer Institute (NCI), NIH,
under contract no. HHSN261200800001E.
NR 18
TC 3
Z9 3
U1 0
U2 8
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 DEC 10
PY 2015
VL 126
IS 24
BP 2632
EP 2641
DI 10.1182/blood-2015-07-657346
PG 10
WC Hematology
SC Hematology
GA DB3RQ
UT WOS:000368429400017
PM 26492933
ER
PT J
AU Scholl, HPN
Moore, AT
Koenekoop, RK
Wen, YQ
Fishman, GA
van den Born, LI
Bittner, A
Bowles, K
Fletcher, EC
Collison, FT
Dagnelie, G
Degli Eposti, S
Michaelides, M
Saperstein, DA
Schuchard, RA
Barnes, C
Zein, W
Zobor, D
Birch, DG
Mendola, JD
Zrenner, E
AF Scholl, Hendrik P. N.
Moore, Anthony T.
Koenekoop, Robert K.
Wen, Yuquan
Fishman, Gerald A.
van den Born, L. Ingeborgh
Bittner, Ava
Bowles, Kristen
Fletcher, Emily C.
Collison, Frederick T.
Dagnelie, Gislin
Degli Eposti, Simona
Michaelides, Michel
Saperstein, David A.
Schuchard, Ronald A.
Barnes, Claire
Zein, Wadih
Zobor, Ditta
Birch, David G.
Mendola, Janine D.
Zrenner, Eberhart
CA RET IRD 01 Study Grp
TI Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis
Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial
65 Protein (RPE65) or Lecithin: Retinol Acyltransferase (LRAT)
SO PLOS ONE
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; OPTICAL COHERENCE TOMOGRAPHY; CELL
INTRAOCULAR IMPLANTS; CHILDHOOD BLINDNESS; VISUAL-FIELDS; GENE-THERAPY;
MOUSE MODEL; MUTATIONS; SENSITIVITY; DYSTROPHY
AB Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m(2)/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a >= 20% increase and 4 of 18 (22%) showed a >= 40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a >= 5 and >= 10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 +/- 4.8 mu m, mean +/- 95% CI) than non-responders (3.5 +/- 1.2 mu m). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.
C1 [Scholl, Hendrik P. N.; Bittner, Ava; Bowles, Kristen; Fletcher, Emily C.; Dagnelie, Gislin] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Moore, Anthony T.; Degli Eposti, Simona; Michaelides, Michel] Moorfields Eye Hosp, London, England.
[Moore, Anthony T.; Degli Eposti, Simona; Michaelides, Michel] UCL, Inst Ophthalmol, London, England.
[Moore, Anthony T.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA.
[Koenekoop, Robert K.; Mendola, Janine D.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Wen, Yuquan; Birch, David G.] Retina Fdn Southwest, Dallas, TX USA.
[Wen, Yuquan] Baylor Univ, Med Ctr, Baylor Visual Funct Ctr, Dallas, TX USA.
[Fishman, Gerald A.; Collison, Frederick T.] Pangere Ctr Inherited Retinal Dis, Chicago Lighthouse, Chicago, IL USA.
[van den Born, L. Ingeborgh] Rotterdam Eye Hosp, Rotterdam, Netherlands.
[van den Born, L. Ingeborgh] Ophthalm Inst, Rotterdam, Netherlands.
[Bittner, Ava] Nova SE Univ, Coll Optometry, Ft Lauderdale, FL 33314 USA.
[Bowles, Kristen] Univ Houston, Coll Optometry, Houston, TX USA.
[Fletcher, Emily C.] Gloucester Royal NHS Fdn Trust, Gloucester Royal Hosp, Gloucester, England.
[Saperstein, David A.] Vitreoretinal Associates Washington, Seattle, WA USA.
[Saperstein, David A.; Schuchard, Ronald A.; Barnes, Claire] QLT Inc, Vancouver, BC, Canada.
[Schuchard, Ronald A.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Barnes, Claire] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Zein, Wadih] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Zobor, Ditta; Zrenner, Eberhart] Univ Tubingen, Inst Ophthalm Res, Ctr Ophthalmol, Tubingen, Germany.
[Birch, David G.] UT Southwestern, Ophthalmol, Dallas, TX USA.
RP Scholl, HPN (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
EM hscholl1@jhmi.edu
FU QLT Inc. [QLT091001]; Wynn-Gund Translational Research Acceleration
Program Enhanced Research and Clinical Training Award, National
Neurovision Research Institute (NNRI) - Foundation Fighting Blindness
(FFB) [NNCD-CL-0310.0049-JHU-WG]; Macular Degeneration Research Award,
American Health Assistance Foundation/BrightFocus Foundation (AHAF)
[M2010042]; Research to Prevent Blindness; Baylor-Johns Hopkins Center
for Mendelian Genetics (National Human Genome Research Institute,
NHGRI/NIH) [1U54HG006542-01]; Canadian Foundation Fighting Blindness;
Canadian Institutes for Health Research; Fonds de la Recherche en Santee
du Quebec; Reseau Vision; NIH; National Institute for Health Research UK
(Moorfields Biomedical Research Centre)
FX Funding: This study was sponsored by QLT Inc., the developer of
QLT091001. Dr. Scholl was supported by the Wynn-Gund Translational
Research Acceleration Program Enhanced Research and Clinical Training
Award, National Neurovision Research Institute (NNRI) - Foundation
Fighting Blindness (FFB; NNCD-CL-0310.0049-JHU-WG); Macular Degeneration
Research Award, American Health Assistance Foundation/BrightFocus
Foundation (AHAF; M2010042); Unrestricted grant to the Wilmer Eye
Institute from Research to Prevent Blindness; and Baylor-Johns Hopkins
Center for Mendelian Genetics (National Human Genome Research Institute,
NHGRI/NIH; 1U54HG006542-01). Dr. Scholl is the Dr. Frieda Derdeyn Bambas
Professor of Ophthalmology. Dr. Koenekoop is supported by the Canadian
Foundation Fighting Blindness, Canadian Institutes for Health Research,
Fonds de la Recherche en Santee du Quebec, Reseau Vision and NIH. Dr
Moore is supported by the National Institute for Health Research UK
(Moorfields Biomedical Research Centre). Drs. Scholl, Moore, Koenekoop,
Fishman, Bittner, Dagnelie, Saperstein, Schuchard, Barnes and Birch
served as paid consultants for QLT Inc. The specific roles of these
authors are articulated in the 'author contributions' section. QLT Inc.
was involved in the study design, data collection and analysis. QLT also
provided technical support for manuscript preparation, reviewed the
manuscript and participated in the decision to publish.
NR 42
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U1 4
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 DEC 10
PY 2015
VL 10
IS 12
AR e0143846
DI 10.1371/journal.pone.0143846
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ1YZ
UT WOS:000366903500007
PM 26656277
ER
PT J
AU Larsen, CP
Whitehead, SS
Durbin, AP
AF Larsen, Christian P.
Whitehead, Stephen S.
Durbin, Anna P.
TI Dengue human infection models to advance dengue vaccine development
SO VACCINE
LA English
DT Article
DE Dengue; Dengue vaccine; Human infection model; Human challenge model
ID HEALTHY ADULT VOLUNTEERS; HEMORRHAGIC-FEVER; VIRUS-REPLICATION; NAIVE
ADULTS; CANDIDATE; ENHANCEMENT; SAFE; ATTENUATION; CHALLENGE; SEVERITY
AB Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LAW) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U.S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2 Delta 30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2 Delta 30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Larsen, Christian P.; Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
[Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA.
RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Room 217, Baltimore, MD 21205 USA.
EM apdurbin@verizon.net
NR 48
TC 3
Z9 3
U1 3
U2 6
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 DEC 10
PY 2015
VL 33
IS 50
SI SI
BP 7075
EP 7082
DI 10.1016/j.vaccine.2015.09.052
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0CA
UT WOS:000366771500005
PM 26424605
ER
PT J
AU Dobrynin, P
Liu, SP
Tamazian, G
Xiong, ZJ
Yurchenko, AA
Krasheninnikova, K
Kliver, S
Schmidt-Kuntzel, A
Koepfli, KP
Johnson, W
Kuderna, LFK
Garcia-Perez, R
de Manuel, M
Godinez, R
Komissarov, A
Makunin, A
Brukhin, V
Qiu, WL
Zhou, L
Li, F
Yi, J
Driscoll, C
Antunes, A
Oleksyk, TK
Eizirik, E
Perelman, P
Roelke, M
Wildt, D
Diekhans, M
Marques-Bonet, T
Marker, L
JunWang, JB
Wang, J
Zhang, GJ
O'Brien, SJ
AF Dobrynin, Pavel
Liu, Shiping
Tamazian, Gaik
Xiong, Zijun
Yurchenko, Andrey A.
Krasheninnikova, Ksenia
Kliver, Sergey
Schmidt-Kuentzel, Anne
Koepfli, Klaus-Peter
Johnson, Warren
Kuderna, Lukas F. K.
Garcia-Perez, Raquel
de Manuel, Marc
Godinez, Ricardo
Komissarov, Aleksey
Makunin, Alexey
Brukhin, Vladimir
Qiu, Weilin
Zhou, Long
Li, Fang
Yi, Jian
Driscoll, Carlos
Antunes, Agostinho
Oleksyk, Taras K.
Eizirik, Eduardo
Perelman, Polina
Roelke, Melody
Wildt, David
Diekhans, Mark
Marques-Bonet, Tomas
Marker, Laurie
Bhak, Jong
Wang, Jun
Zhang, Guojie
O'Brien, Stephen J.
TI Genomic legacy of the African cheetah, Acinonyx jubatus
SO GENOME BIOLOGY
LA English
DT Article
DE Genetic diversity; Conservation biology; Population biology
ID MULTIPLE SEQUENCE ALIGNMENT; DOMESTIC CAT; PHYLOGENETIC ANALYSIS;
GENETIC-VARIATION; MAXIMUM-LIKELIHOOD; POSITIVE SELECTION; SATELLITE
DNA; ASIATIC LIONS; EVOLUTION; DATABASE
AB Background: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations.
Results: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084-12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p < 0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah's extremely high (>80 %) pleiomorphic sperm.
Conclusions: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species' natural history, physiological adaptations and unique reproductive disposition.
C1 [Dobrynin, Pavel; Tamazian, Gaik; Yurchenko, Andrey A.; Krasheninnikova, Ksenia; Kliver, Sergey; Koepfli, Klaus-Peter; Komissarov, Aleksey; Makunin, Alexey; Brukhin, Vladimir; O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199004, Russia.
[Liu, Shiping; Xiong, Zijun; Qiu, Weilin; Zhou, Long; Li, Fang; Yi, Jian; Zhang, Guojie] BGI Shenzhen, Natl Genbank, Shenzhen 518083, Peoples R China.
[Koepfli, Klaus-Peter; Johnson, Warren; Wildt, David] Natl Zool Pk, Smithsonian Conservat Biol Inst, Washington, DC 20007 USA.
[Kuderna, Lukas F. K.; Garcia-Perez, Raquel; de Manuel, Marc; Marques-Bonet, Tomas] Inst Biol Evolut CSIC UPF, Barcelona 08003, Spain.
[Godinez, Ricardo] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
[Godinez, Ricardo] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
[Driscoll, Carlos] Neurogenet Lab, NIAAA, Rockville, MD 20852 USA.
[Antunes, Agostinho] Univ Porto, Interdisciplinary Ctr Marine & Environm Res, CIIMAR CIMAR, P-4050123 Oporto, Portugal.
[Antunes, Agostinho] Univ Porto, Dept Biol, Fac Sci, P-4169007 Oporto, Portugal.
[Oleksyk, Taras K.] Univ Puerto Rico, Dept Biol, Mayaguez, PR USA.
[Eizirik, Eduardo] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Lab Biol Genom & Mol, BR-90619900 Porto Alegre, RS, Brazil.
[Makunin, Alexey; Perelman, Polina] Russian Acad Sci, Inst Mol & Cellular Biol, Novosibirsk 630090, Russia.
[Perelman, Polina] Novosibirsk State Univ, Novosibirsk 630090, Russia.
[Roelke, Melody] Leidos Biomed Res Inc, Lab Anim Sci Progras, Frederick Natl Lab, Frederick, MD 21702 USA.
[Diekhans, Mark] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Schmidt-Kuentzel, Anne] Cheetah Conservat Fund, Life Technol Conservat Genet Lab, Otjiwarongo 9000, Namibia.
[Marker, Laurie] Cheetah Conservat Fund, Otjiwarongo 9000, Namibia.
[Bhak, Jong] UNIST, Dept Biomed Engn, Ulsan, South Korea.
[Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
[Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
[Wang, Jun] King Abdulaziz Univ, Princess Jawhara Ctr Excellence Res Hereditary, Jeddah 21589, Saudi Arabia.
[Wang, Jun] Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China.
[O'Brien, Stephen J.] Nova SE Univ, Oceanog Ctr, Ft Lauderdale, FL 33004 USA.
ICREA, Barcelona, Spain.
[Marques-Bonet, Tomas] CNAG, Barcelona 08013, Spain.
[Marques-Bonet, Tomas] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510006, Guangdong, Peoples R China.
[Zhang, Guojie] Univ Copenhagen, Ctr Social Evolut, Dept Biol, DK-2100 Copenhagen, Denmark.
RP O'Brien, SJ (reprint author), St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, 41A Sredniy Ave, St Petersburg 199004, Russia.
EM lgdchief@gmail.com
RI Yurchenko, Andrey/N-2698-2015; Eizirik, Eduardo/K-8034-2012; Tamazian,
Gaik/P-4723-2015; Perelman, Polina/N-8088-2015; Makunin,
Alexey/N-2055-2015;
OI Yurchenko, Andrey/0000-0002-2239-6902; Eizirik,
Eduardo/0000-0002-9658-0999; Tamazian, Gaik/0000-0002-2931-1123;
Perelman, Polina/0000-0002-0982-5100; Makunin,
Alexey/0000-0002-9555-5097; Kuderna, Lukas/0000-0002-9992-9295; Zhang,
Guojie/0000-0001-6860-1521; Marques-Bonet, Tomas/0000-0002-5597-3075;
Driscoll, Carlos/0000-0003-2392-505X
FU Russian Ministry of Science Mega-grant [11.G34.31.0068]; St. Petersburg
State University grant [1.50.1623.2013]; ICREA grant [BFU2014-55090-P];
EMBO YIP grant [BFU2015-7116- ERC]; MICINN grant [BFU2015-6215-ERC]
FX This work was supported in part by a Russian Ministry of Science
Mega-grant (no 11.G34.31.0068), a St. Petersburg State University grant
(no 1.50.1623.2013), an ICREA grant (no. BFU2014-55090-P), an EMBO YIP
2013 grant (no. BFU2015-7116- ERC) and an MICINN grant (no.
BFU2015-6215-ERC). Sample collection and validation of reproductive
genes were performed under the permit number 1833/2013, granted by the
Namibian Ministry of Environment and Tourism. The authors would like to
express their gratitude to Benedict Paten, Joel Armstrong, Glenn Hickey
and Brian Raney of the UCSC Genomics Institute for their support of the
Progressive Cactus tool and the HAL tools package.
NR 94
TC 12
Z9 12
U1 45
U2 160
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD DEC 10
PY 2015
VL 16
AR 277
DI 10.1186/s13059-015-0837-4
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CY0OP
UT WOS:000366105700001
PM 26653294
ER
PT J
AU Lipkowitz, S
Kohn, EC
AF Lipkowitz, Stanley
Kohn, Elise C.
TI To Treat or Not to Treat: The Use of Hormone Replacement Therapy in
Patients With Ovarian Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; BREAST-CANCER;
POSTMENOPAUSAL WOMEN; SURVIVAL; TAMOXIFEN; OUTCOMES
C1 [Lipkowitz, Stanley; Kohn, Elise C.] Natl Inst Hlth, Natl Canc Inst, Bethesda, MD 20892 USA.
RP Lipkowitz, S (reprint author), Natl Inst Hlth, Natl Canc Inst, Bethesda, MD 20892 USA.
NR 18
TC 0
Z9 0
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 DEC 10
PY 2015
VL 33
IS 35
BP 4127
EP +
DI 10.1200/JCO.2015.63.6670
PG 3
WC Oncology
SC Oncology
GA CX9JG
UT WOS:000366021200002
PM 26438113
ER
PT J
AU Ferrer, RA
Padgett, LS
AF Ferrer, Rebecca A.
Padgett, Lynne S.
TI Leveraging Affective Science to Maximize the Effectiveness of Palliative
Care
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID RANDOMIZED CONTROLLED-TRIAL; EMOTIONS; OUTCOMES
C1 [Ferrer, Rebecca A.; Padgett, Lynne S.] NCI, Rockville, MD 20852 USA.
RP Ferrer, RA (reprint author), NCI, Rockville, MD 20852 USA.
NR 11
TC 1
Z9 1
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 DEC 10
PY 2015
VL 33
IS 35
BP 4229
EP +
DI 10.1200/JCO.2015.62.8883
PG 3
WC Oncology
SC Oncology
GA CX9JG
UT WOS:000366021200018
PM 26460299
ER
PT J
AU Zheng, WW
Best, RB
AF Zheng, Wenwei
Best, Robert B.
TI Reduction of All-Atom Protein Folding Dynamics to One-Dimensional
Diffusion
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID FREE-ENERGY SURFACE; REACTION-COORDINATE; TRANSITION-STATES; NATIVE
TOPOLOGY; DEPENDENT DIFFUSION; GLOBULAR-PROTEINS; KINETICS; SIMULATIONS;
LANDSCAPES; MECHANISMS
AB Theoretical models have often modeled protein folding dynamics as diffusion on a low-dimensional free energy surface, a remarkable simplification. However, the accuracy of such an approximation and the number of dimensions required were not clear. For all-atom folding simulations of ten small proteins in explicit solvent we show that the folding dynamics can indeed be accurately described as diffusion on just a single coordinate, the fraction of native contacts (Q). The diffusion models reproduce both folding rates, and finer details such as transition-path durations and diffusive propagators. The Q-averaged diffusion coefficients decrease with chain length, as anticipated from energy landscape theory. Although the Q-diffusion model does not capture transition-path durations for the protein NuG2, we show that this can be accomplished by designing an improved coordinate Q(opt). Overall, one-dimensional diffusion on a suitable coordinate turns out to be a remarkably faithful model for the dynamics of the proteins considered.
C1 [Zheng, Wenwei; Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health
FX We thank Bill Eaton, Gerhard Hummer, Attila Szabo, and Shoji Takada for
helpful comments. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health. This study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov).
NR 72
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Z9 5
U1 5
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD DEC 10
PY 2015
VL 119
IS 49
BP 15247
EP 15255
DI 10.1021/acs.jpcb.5b09741
PG 9
WC Chemistry, Physical
SC Chemistry
GA CY3WD
UT WOS:000366339700016
PM 26601695
ER
PT J
AU Maraia, RJ
Rijal, E
AF Maraia, Richard J.
Rijal, Eshab
TI STRUCTURAL BIOLOGY A transcriptional specialist resolved
SO NATURE
LA English
DT Editorial Material
ID RNA-POLYMERASE-III; TERMINATION; NETWORK
C1 [Maraia, Richard J.; Rijal, Eshab] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, Bethesda, MD 20892 USA.
RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, Bethesda, MD 20892 USA.
EM maraiar@mail.nih.gov; keshab.rijal@nih.gov
NR 14
TC 3
Z9 3
U1 0
U2 0
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 DEC 10
PY 2015
VL 528
IS 7581
BP 204
EP 205
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX9VH
UT WOS:000366053300028
PM 26605522
ER
PT J
AU Liu, ZD
Gerner, MY
Van Panhuys, N
Levine, AG
Rudensky, AY
Germain, RN
AF Liu, Zhiduo
Gerner, Michael Y.
Van Panhuys, Nicholas
Levine, Andrew G.
Rudensky, Alexander Y.
Germain, Ronald N.
TI Immune homeostasis enforced by co-localized effector and regulatory T
cells
SO NATURE
LA English
DT Article
ID DENDRITIC CELLS; IN-VIVO; LYMPH-NODES; INTERLEUKIN-2; RESPONSES; IL-2;
SUPPRESSION; MECHANISMS; GENERATION; TOLERANCE
AB FOXP3(+) regulatory T cells (T-reg cells) prevent autoimmunity by limiting the effector activity of T cells that have escaped thymic negative selection or peripheral inactivation. Despite the information available about molecular factors mediating the suppressive function of T-reg cells, the relevant cellular events in intact tissues remain largely unexplored, and whether Treg cells prevent activation of self-specific T cells or primarily limit damage from such cells has not been determined. Here we use multiplex, quantitative imaging in mice to show that, within secondary lymphoid tissues, highly suppressive Treg cells expressing phosphorylated STAT5 exist in discrete clusters with rare IL-2-positive T cells that are activated by self-antigens. This local IL-2 induction of STAT5 phosphorylation in T-reg cells is part of a feedback circuit that limits further autoimmune responses. Inducible ablation of T cell receptor expression by T-reg cells reduces their regulatory capacity and disrupts their localization in clusters, resulting in uncontrolled effector T cell responses. Our data thus reveal that autoreactive T cells are activated to cytokine production on a regular basis, with physically co-clustering T cell receptor-stimulated T-reg cells responding in a negative feedback manner to suppress incipient autoimmunity and maintain immune homeostasis.
C1 [Liu, Zhiduo; Gerner, Michael Y.; Van Panhuys, Nicholas; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Levine, Andrew G.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
[Levine, Andrew G.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
RI van Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU NIAID, NIH; US National Institutes of Health [R37AI034206, T32GM007739];
Ludwig Cancer Center at Memorial Sloan-Kettering Cancer Center; Howard
Hughes Medical Institute
FX We thank Y. Belkaid for providing germ-free mice. We also would like to
thank members of the Lymphocyte Biology Section, Laboratory of Systems
Biology for their helpful comments during the course of these studies
and critical input during preparation of this manuscript. This work was
supported by the Intramural Research Program of NIAID, NIH and by the US
National Institutes of Health (R37AI034206 to A.Y.R.; T32GM007739 to
A.G.L.), the Ludwig Cancer Center at Memorial Sloan-Kettering Cancer
Center (A.Y.R.), and the Howard Hughes Medical Institute (A.Y.R.).
NR 36
TC 22
Z9 22
U1 2
U2 32
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 DEC 10
PY 2015
VL 528
IS 7581
BP 225
EP +
DI 10.1038/nature16169
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX9VH
UT WOS:000366053300033
PM 26605524
ER
PT J
AU Hudson, KL
Collins, FS
AF Hudson, Kathy L.
Collins, Francis S.
TI Bringing the Common Rule into the 21st Century
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Hudson, Kathy L.] Natl Inst Hlth, Bethesda, MD 20817 USA.
RP Hudson, KL (reprint author), Natl Inst Hlth, Bethesda, MD 20817 USA.
NR 5
TC 27
Z9 28
U1 1
U2 5
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 DEC 10
PY 2015
VL 373
IS 24
BP 2293
EP 2296
DI 10.1056/NEJMp1512205
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY0QW
UT WOS:000366111600001
PM 26509903
ER
PT J
AU Redfield, MM
Anstrom, KJ
Levine, JA
Koepp, GA
Borlaug, BA
Chen, HH
LeWinter, MM
Joseph, SM
Shah, SJ
Semigran, MJ
Felker, GM
Cole, RT
Reeves, GR
Tedford, RJ
Tang, WHW
McNulty, SE
Velazquez, EJ
Shah, MR
Braunwald, E
AF Redfield, Margaret M.
Anstrom, Kevin J.
Levine, James A.
Koepp, Gabe A.
Borlaug, Barry A.
Chen, Horng H.
LeWinter, Martin M.
Joseph, Susan M.
Shah, Sanjiv J.
Semigran, Marc J.
Felker, G. Michael
Cole, Robert T.
Reeves, Gordon R.
Tedford, Ryan J.
Tang, W. H. Wilson
McNulty, Steven E.
Velazquez, Eric J.
Shah, Monica R.
Braunwald, Eugene
CA NHLBI Heart Failure Clinical Res
TI Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID EXERCISE CAPACITY; PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; SEDENTARY
TIME; DOUBLE-BLIND; TRIAL; THERAPY; ACCELEROMETRY; INTOLERANCE;
INHIBITION
AB BACKGROUND
Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.
METHODS
In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP).
RESULTS
In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P = 0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P = 0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P = 0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels.
CONCLUSIONS
Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo.
C1 [Redfield, Margaret M.; Borlaug, Barry A.; Chen, Horng H.] Mayo Clin, Rochester, MN 55905 USA.
[Anstrom, Kevin J.; McNulty, Steven E.; Velazquez, Eric J.] Duke Clin Res Inst, Durham, NC USA.
[Felker, G. Michael] Duke Univ, Med Ctr, Durham, NC USA.
[Levine, James A.; Koepp, Gabe A.] Mayo Clin, Scottsdale, AZ USA.
[LeWinter, Martin M.] Univ Vermont, Med Ctr, Burlington, VT 05405 USA.
[Joseph, Susan M.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Shah, Sanjiv J.] Northwestern Univ, Chicago, IL 60611 USA.
[Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA.
[Cole, Robert T.] Emory Univ, Atlanta, GA 30322 USA.
[Reeves, Gordon R.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Tedford, Ryan J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA.
[Tang, W. H. Wilson] Cleveland Clin Fdn, Cleveland, OH USA.
RP Redfield, MM (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA.
EM redfield.margaret@mayo.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [U10 HL084904, U01
HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01
HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10
HL110302, U10 HL110309, U10 HL110336, U10 HL110338]
FX Supported by grants from the National Heart, Lung, and Blood Institute
(NHLBI) (coordinating center: U10 HL084904; regional clinical centers:
U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890,
U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297,
U10 HL110302, U10 HL110309, U10 HL110336, and U10 HL110338).
NR 36
TC 42
Z9 44
U1 4
U2 13
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 DEC 10
PY 2015
VL 373
IS 24
BP 2314
EP 2324
DI 10.1056/NEJMoa1510774
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY0QW
UT WOS:000366111600006
PM 26549714
ER
PT J
AU Jiang, Y
Yan, B
Lai, W
Shi, Y
Xiao, D
Jia, J
Liu, S
Li, H
Lu, J
Li, Z
Chen, L
Chen, X
Sun, L
Muegge, K
Cao, Y
Tao, Y
AF Jiang, Y.
Yan, B.
Lai, W.
Shi, Y.
Xiao, D.
Jia, J.
Liu, S.
Li, H.
Lu, J.
Li, Z.
Chen, L.
Chen, X.
Sun, L.
Muegge, K.
Cao, Y.
Tao, Y.
TI Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and
modulation of glycolytic pathway genes by HoxC8
SO ONCOGENE
LA English
DT Article
ID RNA-POLYMERASE-II; SQUAMOUS-CELL CARCINOMA; BASE EXCISION-REPAIR; DNA
METHYLATION; HUMAN GENOME; CANCER; EXPRESSION; DEMETHYLATION;
TRANSCRIPTION; PROGRESSION
AB Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte-specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA polymerase II (RNA Pol II). Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, has a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of tricarboxylic acid (TCA) cycle-related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis.
C1 [Jiang, Y.; Yan, B.; Lai, W.; Shi, Y.; Jia, J.; Li, H.; Lu, J.; Chen, L.; Chen, X.; Cao, Y.; Tao, Y.] Cent S Univ, Canc Res Inst, Changsha 410078, Hunan, Peoples R China.
[Jiang, Y.; Yan, B.; Lai, W.; Shi, Y.; Li, H.; Lu, J.; Chen, L.; Chen, X.; Cao, Y.; Tao, Y.] Cent S Univ, Ctr Mol Imaging, Changsha 410078, Hunan, Peoples R China.
[Xiao, D.] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410078, Hunan, Peoples R China.
[Jia, J.; Liu, S.] Cent S Univ, Xiangya Hosp, Ctr Med Res, Changsha 410078, Hunan, Peoples R China.
[Sun, L.] Cent S Univ, Xiangya Hosp, Ctr Mol Med, Changsha 410078, Hunan, Peoples R China.
[Muegge, K.] NCI, Mouse Canc Genet Program, Basic Sci Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
RP Cao, Y (reprint author), Cent S Univ, Xiangya Sch Med, Xiangya Rd 110, Changsha 410078, Hunan, Peoples R China.
EM ycao98@vip.sina.com; taoyong@csu.edu.cn
FU National Basic Research Program of China [2011CB504300, 2015CB553903];
Hunan Natural Science Foundation of China [12JJ1013]; Fundamental
Research Funds for the Central Universities [2011JQ019, 2013ZZTS074,
2013ZZTS284]; National Natural Science Foundation of China [81171881,
81372427, 81271763, 81302354]; Hunan Provincial Innovation Foundation
For Postgraduate [71380100002]; Frederick National Laboratory for Cancer
Research, National Institutes of Health [HHSN261200800001E]
FX This work was supported by the National Basic Research Program of China
(2011CB504300 (YT); 2015CB553903 (YT)); the Hunan Natural Science
Foundation of China (12JJ1013 (YT)); the Fundamental Research Funds for
the Central Universities (2011JQ019 (YT), 2013ZZTS074 (BY), 2013ZZTS284
(WL)); and the National Natural Science Foundation of China (81171881
and 81372427 (YT), 81271763 (SL), 81302354 (YS)); and the Hunan
Provincial Innovation Foundation For Postgraduate (71380100002 (YJ)).
This project has been funded in part with Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract 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 US
Government.
NR 70
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD DEC 10
PY 2015
VL 34
IS 50
BP 6079
EP 6091
DI 10.1038/onc.2015.53
PG 13
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA CY0RQ
UT WOS:000366113800005
PM 25745994
ER
PT J
AU Cheung, GYC
Yeh, AJ
Kretschmer, D
Duong, AC
Tuffuor, K
Fu, CL
Joo, HS
Diep, BA
Li, M
Nakamura, Y
Nunez, G
Peschel, A
Otto, M
AF Cheung, Gordon Y. C.
Yeh, Anthony J.
Kretschmer, Dorothee
Duong, Anthony C.
Tuffuor, Kwame
Fu, Chih-Lung
Joo, Hwang-Soo
Diep, Binh A.
Li, Min
Nakamura, Yuumi
Nunez, Gabriel
Peschel, Andreas
Otto, Michael
TI Functional characteristics of the Staphylococcus aureus delta-toxin
allelic variant G10S
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PHENOL-SOLUBLE MODULINS; PANTON-VALENTINE LEUKOCIDIN; VIRULENCE
DETERMINANTS; BIOFILM MATURATION; MAST-CELLS; EXPRESSION; HEMOLYSIN;
EPIDERMIDIS; INFECTIONS; EVOLUTION
AB Staphylococcus aureus delta-toxin is a member of the phenol-soluble modulin (PSM) peptide family. PSMs have multiple functions in staphylococcal pathogenesis; for example, they lyse red and white blood cells and trigger inflammatory responses. Compared to other PSMs, delta-toxin is usually more strongly expressed but has only moderate cytolytic capacities. The amino acid sequences of S. aureus PSMs are well conserved with two exceptions, one of which is the delta-toxin allelic variant G10S. This variant is a characteristic of the subspecies S. argenteus and S. aureus sequence types ST1 and ST59, the latter representing the most frequent cause of community-associated infections in Asia. delta-toxin G10S and strains expressing that variant from plasmids or the genome had significantly reduced cytolytic and pro-inflammatory capacities, including in a strain background with pronounced production of other PSMs. However, in murine infection models, isogenic strains expressing the two delta-toxin variants did not cause measurable differences in disease severity. Our findings indicate that the widespread G10S allelic variation of the delta-toxin locus has a significant impact on key pathogenesis mechanisms, but more potent members of the PSM peptide family may overshadow that impact in vivo.
C1 [Cheung, Gordon Y. C.; Yeh, Anthony J.; Duong, Anthony C.; Tuffuor, Kwame; Fu, Chih-Lung; Joo, Hwang-Soo; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, Bethesda, MD 20892 USA.
[Kretschmer, Dorothee; Peschel, Andreas] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Cellular & Mol Microbiol Div, D-72076 Tubingen, Germany.
[Diep, Binh A.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA.
[Li, Min] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Lab Med, Shanghai 200127, Peoples R China.
[Nakamura, Yuumi] Chiba Univ, Grad Sch Med, Dept Dermatol, Chiba 2608670, Japan.
[Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Bacteriol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), NIH; German Research Foundation [SFB685,
TR34]; German Ministry of Education and Research (Menage); Fortune
program of the Medical Faculty, University of Tubingen
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), NIH (to
M.O.) and grants from the German Research Foundation (SFB685 to AP, TR34
to AP and DK), the German Ministry of Education and Research (Menage, to
AP), and the Fortune program of the Medical Faculty, University of
Tubingen to DK.
NR 50
TC 1
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U1 0
U2 3
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 DEC 10
PY 2015
VL 5
AR 18023
DI 10.1038/srep18023
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY0YZ
UT WOS:000366134200003
PM 26658455
ER
PT J
AU Zhang, FQ
Shugart, YY
Yue, WH
Cheng, ZH
Wang, GQ
Zhou, ZH
Jin, CH
Yuan, JM
Liu, S
Xu, Y
AF Zhang, Fuquan
Shugart, Yin Yao
Yue, Weihua
Cheng, Zaohuo
Wang, Guoqiang
Zhou, Zhenhe
Jin, Chunhui
Yuan, Jianmin
Liu, Sha
Xu, Yong
TI Increased Variability of Genomic Transcription in Schizophrenia
SO SCIENTIFIC REPORTS
LA English
DT Article
ID GENE-EXPRESSION
AB Schizophrenia (SZ) is a severe chronic mental disorder with a high heritability. Current microarray analyses typically focus on identifying differentially expressed genes or enriched pathways relevant to phenotypes. Whether there is a variability change of the genomic transcription in diseases has rarely been explored. In this study, we compared coefficient of variation (CV, the ratio of the standard deviation to the mean) of genome transcription of early-onset SZ (EOS) patients with controls in a blood mRNA microarray dataset and a blood microRNA (miRNA) microarray dataset. Furthermore, we compared CV of the expression levels of 17 genes in blood of the 30 patients before and after the 12-week treatment using real-time quantitative PCR (RT-qPCR) analysis. Our results indicated a significant increase of CV of genome transcription in patients compared with controls in both the mRNA and the miRNA datasets. The 30 after-treatment patients showed a significant decrease of CV of gene expression compared with the before-treatment patients. Our study may implicate the blood gene expression variability in SZ, providing further evidence supporting the abnormality of peripheral blood transcriptome in SZ. Given that peripheral blood can be easily collected from patients and followed longitudinally, our results may indicate a new way to facilitate the identification of the signatures of clinical subtypes, their prognosis and treatment response.
C1 [Zhang, Fuquan; Cheng, Zaohuo; Wang, Guoqiang; Zhou, Zhenhe; Jin, Chunhui; Yuan, Jianmin] Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Yue, Weihua] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing 100191, Peoples R China.
[Yue, Weihua] Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing 100191, Peoples R China.
[Yue, Weihua] Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing 100191, Peoples R China.
[Liu, Sha; Xu, Yong] Shanxi Med Univ, Hosp 1, Clin Med Coll 1, Dept Psychiat, Taiyuan, Peoples R China.
RP Zhang, FQ (reprint author), Nanjing Med Univ, Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
EM zhangfq@njmu.edu.cn; xuyongsmu@vip.163.com
FU National Natural Science Foundation of China [81471364, 81271482];
Beijing Natural Science Foundation [7132182]; Program for New Century
Excellent Talents in University [NCET-12-1036]; Construction Plan for
Shanxi Science & Technology Infrastructure Platforms [2015091002-0102];
Intramural Research Program of National Institute of Mental Health,
National Institutes of Health [MH002929-04]
FX We sincerely thank all the subjects for their support and participation
and all the medical staff involved in collecting blood samples. This
work was supported by the National Natural Science Foundation of China
(81471364, 81271482), Beijing Natural Science Foundation (7132182),
Program for New Century Excellent Talents in University (NCET-12-1036),
and Construction Plan for Shanxi Science & Technology Infrastructure
Platforms (2015091002-0102). Shugart was supported by the Intramural
Research Program of National Institute of Mental Health, National
Institutes of Health (MH002929-04).
NR 9
TC 1
Z9 1
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 DEC 10
PY 2015
VL 5
AR 17995
DI 10.1038/srep17995
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY0YU
UT WOS:000366133600002
PM 26657146
ER
PT J
AU Chen, W
Fu, LW
Chen, XY
AF Chen, Wei
Fu, Liwu
Chen, Xiaoyuan
TI Improving cell-based therapies by nanomodification
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Cell-based therapy; Cell functionalization; Nanomodification;
Living-nonliving integration; Material-based biological regulation
ID MESENCHYMAL STEM-CELLS; CANCER VACCINE VECTOR; LIVING CELLS;
DRUG-DELIVERY; MEDIATED DELIVERY; BIOMIMETIC MINERALIZATION;
POLYELECTROLYTE SHELLS; REGENERATIVE MEDICINE; METAL NANOPARTICLES;
PANCREATIC-ISLETS
AB Cell-based therapies are emerging as a promising approach for various diseases. Their therapeutic efficacy depends on rational control and regulation of the functions and behaviors of cells during their treatments. Different from conventional regulatory strategy by chemical adjuvants or genetic engineering, which is restricted by limited synergistic regulatory efficiency or uncertain safety problems, a novel approach based on nanoscale artificial materials can be applied to modify living cells to endow them with novel functions and unique properties. Inspired by natural "nano shell" and "nano compass" structures, cell nanomodification can be developed through both external and internal pathways. In this review, some novel cell surface engineering and intracellular nanoconjugation strategies are summarized. Their potential applications are also discussed, including cell protection, cell labeling, targeted delivery and in situ regulation. It is believed that these novel cell-material complexes can have great potentials for biomedical applications. Published by Elsevier B.V.
C1 [Chen, Wei; Fu, Liwu] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China.
[Chen, Wei; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Fu, LW (reprint author), Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China.
EM Fulw@mail.sysu.edu.cn; shawn.chen@nih.gov
FU National High Technology Research and Development Program of China (863
Program) [2012AA02A303]; Chinese National Nature Sciences Foundation
[81473233]; China Postdoctoral Science Foundation [2015M570745];
Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health [ZIA EB000073]
FX This work was supported in part, by the National High Technology
Research and Development Program of China (863 Program) (No.
2012AA02A303), Chinese National Nature Sciences Foundation (No.
81473233), China Postdoctoral Science Foundation (2015M570745), and the
Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health (ZIA EB000073).
NR 133
TC 4
Z9 4
U1 6
U2 61
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD DEC 10
PY 2015
VL 219
BP 560
EP 575
DI 10.1016/j.jconrel.2015.09.054
PG 16
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CX3HK
UT WOS:000365587800044
PM 26423238
ER
PT J
AU Chen, H
Yang, P
Guo, J
Kwoh, CK
Przytycka, TM
Zheng, J
AF Chen, Hao
Yang, Peng
Guo, Jing
Kwoh, Chee Keong
Przytycka, Teresa M.
Zheng, Jie
TI ARG-walker: inference of individual specific strengths of meiotic
recombination hotspots by population genomics analysis
SO BMC GENOMICS
LA English
DT Article; Proceedings Paper
CT Joint 26th Genome Informatics Workshop /
Asia-Pacific-Bioinformatics-Network (APBioNet) 14th International
Conference on Bioinformatics (GIW/InCoB)
CY SEP 09-11, 2015
CL Tokyo, JAPAN
SP Asia Pacific Bioinformat Network
ID SEQUENCE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; KINASE SUPPRESSOR;
HOT-SPOTS; RAS 2; HUMANS; PRDM9; MOTIF; MAP; ACTIVATION
AB Background: Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable.
Results: In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome.
Conclusions: Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.
C1 [Chen, Hao; Yang, Peng; Guo, Jing; Kwoh, Chee Keong; Zheng, Jie] Nanyang Technol Univ, Sch Comp Engn, Biomed Informat Grad Lab, 50 Nanyang Ave, Singapore 639798, Singapore.
[Chen, Hao] Biopolis, A STAR, Singapore Immunol Network SIgN, Singapore 138648, Singapore.
[Yang, Peng] ASTAR, Inst Infocomm Res, Singapore 138632, Singapore.
[Przytycka, Teresa M.] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Zheng, Jie] Biopolis, A STAR, Genome Inst Singapore, Singapore 138672, Singapore.
RP Zheng, J (reprint author), Nanyang Technol Univ, Sch Comp Engn, Biomed Informat Grad Lab, 50 Nanyang Ave, Singapore 639798, Singapore.
EM zhengjie@ntu.edu.sg
FU MOE AcRF [RG32/11 (M4010977), RGC2/13 (M4011101)]; MOE AcRF, Ministry of
Education, Singapore [ARC6/15 (MOE2014-T2-2-023)]
FX This work was supported by the following funding sources: MOE AcRF Tier
1 Grant RG32/11 (M4010977), MOE AcRF Tier 1 Seed Fund on Complexity
RGC2/13 (M4011101), and MOE AcRF Tier 2 Grant ARC6/15
(MOE2014-T2-2-023), Ministry of Education, Singapore.
NR 38
TC 1
Z9 1
U1 0
U2 1
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 DEC 9
PY 2015
VL 16
SU 12
AR S1
DI 10.1186/1471-2164-16-S12-S1
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DN2ZC
UT WOS:000376930700002
PM 26679564
ER
PT J
AU Pallotto, M
Watkins, PV
Fubara, B
Singer, JH
Briggman, KL
AF Pallotto, Marta
Watkins, Paul V.
Fubara, Boma
Singer, Joshua H.
Briggman, Kevin L.
TI Extracellular space preservation aids the connectomic analysis of neural
circuits
SO ELIFE
LA English
DT Article
ID ELECTRON-MICROSCOPY; DIRECTION-SELECTIVITY; WIRING SPECIFICITY;
HIPPOCAMPAL SLICES; CEREBRAL CORTEX; AMACRINE CELL; RETINA; BRAIN;
SEGMENTATION; SYNAPSES
AB Dense connectomic mapping of neuronal circuits is limited by the time and effort required to analyze 3D electron microscopy (EM) datasets. Algorithms designed to automate image segmentation suffer from substantial error rates and require significant manual error correction. Any improvement in segmentation error rates would therefore directly reduce the time required to analyze 3D EM data. We explored preserving extracellular space (ECS) during chemical tissue fixation to improve the ability to segment neurites and to identify synaptic contacts. ECS preserved tissue is easier to segment using machine learning algorithms, leading to significantly reduced error rates. In addition, we observed that electrical synapses are readily identified in ECS preserved tissue. Finally, we determined that antibodies penetrate deep into ECS preserved tissue with only minimal permeabilization, thereby enabling correlated light microscopy (LM) and EM studies. We conclude that preservation of ECS benefits multiple aspects of the connectomic analysis of neural circuits.
C1 [Pallotto, Marta; Watkins, Paul V.; Fubara, Boma; Briggman, Kevin L.] NINDS, Circuit Dynam & Connect Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Singer, Joshua H.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
[Briggman, Kevin L.] Max Planck Inst Med Res, Dept Biomed Opt, D-69120 Heidelberg 1, Germany.
RP Briggman, KL (reprint author), NINDS, Circuit Dynam & Connect Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM briggmankl@mail.nih.gov
OI Pallotto, Marta/0000-0001-7694-0398
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program [N5003133]; National Eye Institute [EY017836]; Pew
Charitable Trusts Pew Scholars Program in the Biomedical Sciences;
Max-Planck-Gesellschaft
FX National Institute of Neurological Disorders and Stroke Intramural
Research Program (N5003133) Marta Pallotto Paul V Watkins Boma Fubara
Kevin L Briggman; National Eye Institute EY017836 Joshua H Singer; Pew
Charitable Trusts Pew Scholars Program in the Biomedical Sciences Kevin
L Briggman; Max-Planck-Gesellschaft Kevin L Briggman
NR 51
TC 10
Z9 10
U1 0
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 9
PY 2015
VL 4
AR e08206
DI 10.7554/eLife.08206
PG 20
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9FT
UT WOS:000373808200001
ER
PT J
AU Plevock, KM
Galletta, BJ
Slep, KC
Rusan, NM
AF Plevock, Karen M.
Galletta, Brian J.
Slep, Kevin C.
Rusan, Nasser M.
TI Newly Characterized Region of CP190 Associates with Microtubules and
Mediates Proper Spindle Morphology in Drosophila Stem Cells
SO PLOS ONE
LA English
DT Article
ID CENTROSOME-ASSOCIATED PROTEIN; ORDER CHROMATIN ORGANIZATION; INSULATOR
PROTEINS; BINDING; TUBULIN; COMPLEX; LOCALIZATION; MELANOGASTER; EMBRYO;
DOMAIN
AB CP190 is a large, multi-domain protein, first identified as a centrosome protein with oscillatory localization over the course of the cell cycle. During interphase it has a well-established role within the nucleus as a chromatin insulator. Upon nuclear envelope breakdown, there is a striking redistribution of CP190 to centrosomes and the mitotic spindle, in addition to the population at chromosomes. Here, we investigate CP190 in detail by performing domain analysis in cultured Drosophila S2 cells combined with protein structure determination by X-ray crystallography, in vitro biochemical characterization, and in vivo fixed and live imaging of cp190 mutant flies. Our analysis of CP190 identifies a novel N-terminal centrosome and microtubule (MT) targeting region, sufficient for spindle localization. This region consists of a highly conserved BTB domain and a linker region that serves as the MT binding domain. We present the 2.5 resolution structure of the CP190 N-terminal 126 amino acids, which adopts a canonical BTB domain fold and exists as a stable dimer in solution. The ability of the linker region to robustly localize to MTs requires BTB domain-mediated dimerization. Deletion of the linker region using CRISPR significantly alters spindle morphology and leads to DNA segregation errors in the developing Drosophila brain neuroblasts. Collectively, we highlight a multivalent MT-binding architecture in CP190, which confers distinct subcellular cytoskeletal localization and function during mitosis.
C1 [Plevock, Karen M.; Galletta, Brian J.; Rusan, Nasser M.] NIH, Cell Biol & Physiol Ctr, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
[Plevock, Karen M.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Slep, Kevin C.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
RP Slep, KC (reprint author), Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
EM kslep@bio.unc.edu; nasser@nih.gov
RI Rusan, Nasser/P-3511-2016
FU National Institutes of Health [R01GM094415, T32GM008570]; Division of
Intramural Research, National Heart Lung and Blood Institute
[1ZIAHL006104]
FX This work was supported by the National Institutes of Health (grant nos.
R01GM094415, T32GM008570), and the Division of Intramural Research,
National Heart Lung and Blood Institute (grant no. 1ZIAHL006104). Other
than the grants listed above, the authors received no additional funding
for this work.
NR 36
TC 1
Z9 1
U1 1
U2 3
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 DEC 9
PY 2015
VL 10
IS 12
AR e0144174
DI 10.1371/journal.pone.0144174
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ1YX
UT WOS:000366903300039
PM 26649574
ER
PT J
AU Qin, T
Iwata, T
Ransom, TT
Beutler, JA
Porco, JA
AF Qin, Tian
Iwata, Takayuki
Ransom, Tanya T.
Beutler, John A.
Porco, John A., Jr.
TI Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages:
Investigation of "Shapeshifting" Properties
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ENANTIOSELECTIVE TOTAL-SYNTHESIS; FUNGUS PHOMOPSIS-LONGICOLLA;
NATURAL-PRODUCTS; BLENNOLIDE-C; MONOMERIC CHROMANONES;
ORGANIC-MOLECULES; MICHAEL ADDITION; SECALONIC ACIDS; XANTHONE DIMERS;
GONYTRICHUM SP
AB The 2,4'- and 4,4'-linked variants of the cytotoxic agent secalonic acid A and their analogues have been synthesized. Kinetic resolution of an unprotected tetrahydroxanthone scaffold followed by copper-mediated biaryl coupling allowed for efficient access to these compounds. Evaluation of the "shapeshifting" properties of 2,2'-, 2,4'-, and 4,4'-linked variants of the secalonic acids A in a polar solvent in conjunction with assays of the compounds against select cancer cell lines was conducted to study possible correlations between linkage variation and cytotoxicity.
C1 [Qin, Tian; Iwata, Takayuki; Porco, John A., Jr.] Boston Univ, Dept Chem, Boston, MA 02215 USA.
[Qin, Tian; Iwata, Takayuki; Porco, John A., Jr.] Boston Univ, Ctr Mol Discovery BU CMD, Boston, MA 02215 USA.
[Ransom, Tanya T.; Beutler, John A.] NCI, MolecularTargets Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Porco, JA (reprint author), Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA.
EM porco@bu.edu
FU NIH [GM-073855, GM-099920, GM-111625]; NIGMS CMLD Initiative [P50
GM067041]; Vertex Pharmaceuticals, Inc.; Uehara Memorial Foundation;
NIH, National Cancer Institute, Center for Cancer Research;
Developmental Therapeutics Program, Division of Cancer Diagnosis and
Treatment
FX Financial support from the NIH (GM-073855, GM-099920, J.A.P., Jr.) and
the NIGMS CMLD Initiative (P50 GM067041, J.A.P., Jr.) is gratefully
acknowledged. Work at the BU-CMD is supported by NIH R24 grant
GM-111625. We thank Vertex Pharmaceuticals, Inc. for a graduate
fellowship to T.Q, and the Uehara Memorial Foundation for a postdoctoral
fellowship to T.I. This research was also supported in part by the
Intramural Research Program of NIH, National Cancer Institute, Center
for Cancer Research and by the Developmental Therapeutics Program,
Division of Cancer Diagnosis and Treatment. We thank Dr. Jeffrey Bacon
(Boston University) for X-ray crystal structure analysis and Dr. Lauren
Brown (BU-CMD) for experimental assistance.
NR 67
TC 4
Z9 4
U1 3
U2 23
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 DEC 9
PY 2015
VL 137
IS 48
BP 15225
EP 15233
DI 10.1021/jacs.5b09825
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA CY3WF
UT WOS:000366339900025
PM 26544765
ER
PT J
AU Gorjifard, S
Goldszmid, RS
AF Gorjifard, Sayeh
Goldszmid, Romina S.
TI Beating Cancer with a Gut Feeling
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID MICROBIOTA; THERAPY
AB Blockade of immune checkpoint molecules, a group of molecules normally involved in maintaining self-tolerance and limiting T cell responses, has emerged as a breakthrough in cancer therapy. Two recent studies published in Science show that, in mice, gut commensal microbes promote antitumor immunity and may determine therapy efficacy.
C1 [Gorjifard, Sayeh; Goldszmid, Romina S.] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Goldszmid, RS (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM rgoldszmid@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. 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 9
TC 1
Z9 1
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD DEC 9
PY 2015
VL 18
IS 6
BP 646
EP 648
DI 10.1016/j.chom.2015.11.014
PG 3
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CY1AL
UT WOS:000366138400006
PM 26651940
ER
PT J
AU Cliffe, AR
Arbuckle, JH
Vogel, JL
Geden, MJ
Rothbart, SB
Cusack, CL
Strahl, BD
Kristie, TM
Deshmukh, M
AF Cliffe, Anna R.
Arbuckle, Jesse H.
Vogel, Jodi L.
Geden, Matthew J.
Rothbart, Scott B.
Cusack, Corey L.
Strahl, Brian D.
Kristie, Thomas M.
Deshmukh, Mohanish
TI Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is
Required for Herpes Simplex Virus Reactivation
SO CELL HOST & MICROBE
LA English
DT Article
ID LATENCY-ASSOCIATED TRANSCRIPT; PROGRAMMED CELL-DEATH; GANGLIA IN-VIVO;
C-JUN; SYMPATHETIC NEURONS; TYPE-1 DNA; CHROMATIN-STRUCTURE; TRIGEMINAL
GANGLIA; TERMINAL KINASE-1; GENE-EXPRESSION
AB Herpes simplex virus (HSV) reactivation from latent neuronal infection requires stimulation of lytic gene expression from promoters associated with repressive heterochromatin. Various neuronal stresses trigger reactivation, but how these stimuli activate silenced promoters remains unknown. We show that a neuronal pathway involving activation of c-Jun N-terminal kinase (JNK), common to many stress responses, is essential for initial HSV gene expression during reactivation. This JNK activation in neurons is mediated by dual leucine zipper kinase (DLK) and JNK-interacting protein 3 (JIP3), which direct JNK toward stress responses instead of other cellular functions. Surprisingly, JNK-mediated viral gene induction occurs independently of histone demethylases that remove repressive lysine modifications. Rather, JNK signaling results in a histone methyl/phospho switch on HSV lytic promoters, a mechanism permitting gene expression in the presence of repressive lysine methylation. JNK is present on viral promoters during reactivation, thereby linking a neuronal-specific stress pathway and HSV reactivation from latency.
C1 [Cliffe, Anna R.; Geden, Matthew J.; Deshmukh, Mohanish] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
[Cliffe, Anna R.; Geden, Matthew J.; Cusack, Corey L.; Deshmukh, Mohanish] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA.
[Arbuckle, Jesse H.; Vogel, Jodi L.; Kristie, Thomas M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Rothbart, Scott B.; Strahl, Brian D.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Cusack, Corey L.] Univ N Carolina, Neurobiol Curriculum, Chapel Hill, NC 27599 USA.
[Strahl, Brian D.; Deshmukh, Mohanish] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Cliffe, AR (reprint author), Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
EM cliffe@email.unc.edu; mohanish@med.unc.edu
OI Strahl, Brian D/0000-0002-4947-6259
FU NIH [5F32NS078954, F31NS076240, F31CA186654, CA181343, R01GM110058,
NS042197, GM078366]; Laboratory of Viral Diseases, Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, U.S. National Institutes of Health
FX We thank Dr. Steven Triezenberg (Van Andel Research Institute, MI) for
kindly providing the KOS DG1 virus and Pfizer for providing the
WAY-150138. Thank you to members of the Deshmukh lab and Dr. Steve
Bachenheimer (UNC Chapel Hill) for comments on the manuscript. This work
was supported by grants from the NIH (5F32NS078954 to A.R.C.,
F31NS076240 to C.L.C., F31CA186654 to M.J.G., CA181343 to S.B.R.,
R01GM110058 to B.D.S., and NS042197 and GM078366 to M.D.) and funding
from the Laboratory of Viral Diseases, Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of Health to T.M.K.
NR 65
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Z9 7
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD DEC 9
PY 2015
VL 18
IS 6
BP 649
EP 658
DI 10.1016/j.chom.2015.11.007
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CY1AL
UT WOS:000366138400007
PM 26651941
ER
PT J
AU Ladner, JT
Wiley, MR
Mate, S
Dudas, G
Prieto, K
Lovett, S
Nagle, ER
Beitzel, B
Gilbert, ML
Fakoli, L
Diclaro, JW
Schoepp, RJ
Fair, J
Kuhn, JH
Hensley, LE
Park, DJ
Sabeti, PC
Rambaut, A
Sanchez-Lockhart, M
Bolay, FK
Kugelman, JR
Palacios, G
AF Ladner, Jason T.
Wiley, Michael R.
Mate, Suzanne
Dudas, Gytis
Prieto, Karla
Lovett, Sean
Nagle, Elyse R.
Beitzel, Brett
Gilbert, Merle L.
Fakoli, Lawrence
Diclaro, Joseph W., II
Schoepp, Randal J.
Fair, Joseph
Kuhn, Jens H.
Hensley, Lisa E.
Park, Daniel J.
Sabeti, Pardis C.
Rambaut, Andrew
Sanchez-Lockhart, Mariano
Bolay, Fatorma K.
Kugelman, Jeffrey R.
Palacios, Gustavo
TI Evolution and Spread of Ebola Virus in Liberia, 2014-2015
SO CELL HOST & MICROBE
LA English
DT Article
ID RAPID RESPONSE; 2014 OUTBREAK; SIERRA-LEONE; REMOTE AREAS; WEST-AFRICA;
TRANSMISSION; EPIDEMIC; GUINEA
AB The 2013-present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread, and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host.
C1 [Ladner, Jason T.; Wiley, Michael R.; Mate, Suzanne; Prieto, Karla; Lovett, Sean; Nagle, Elyse R.; Beitzel, Brett; Sanchez-Lockhart, Mariano; Kugelman, Jeffrey R.; Palacios, Gustavo] US Army, Ctr Genome Sci, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Dudas, Gytis; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3FL, Midlothian, Scotland.
[Gilbert, Merle L.] US Army, Mol & Translat Sci Div, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Fakoli, Lawrence; Bolay, Fatorma K.] Liberian Inst Biomed Res, Charlesville, Liberia.
[Diclaro, Joseph W., II] Naval Med Res Unit 3, Cairo 11517, Egypt.
[Schoepp, Randal J.] US Army, Diagnost Syst Div, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Fair, Joseph] MRI Global, Rockville, MD 20850 USA.
[Fair, Joseph] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA.
[Kuhn, Jens H.; Hensley, Lisa E.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Park, Daniel J.; Sabeti, Pardis C.] Broad Inst, Cambridge, MA 02142 USA.
[Sabeti, Pardis C.] Harvard Univ, Cambridge, MA 02138 USA.
[Rambaut, Andrew] Univ Edinburgh, Ashworth Labs, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ladner, JT (reprint author), US Army, Ctr Genome Sci, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA.
EM jason.t.ladner.ctr@mail.mil; gustavo.f.palacios.ctr@mail.mil
RI Palacios, Gustavo/I-7773-2015;
OI Palacios, Gustavo/0000-0001-5062-1938; Dudas, Gytis/0000-0002-0227-4158
FU Defense Threat Reduction Agency; S Agency for International Development;
EU [278433-PREDEMICS]; National Institute of Allergy and Infectious
Diseases [HHSN272200700016I]; Global Biosurveillance Technology
Initiative; Global Emerging Infections System
FX This work was supported by the Defense Threat Reduction Agency, Global
Biosurveillance Technology Initiative, Global Emerging Infections System
and US Agency for International Development. A.R. was supported by EU
Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no.
278433-PREDEMICS. The content of this publication does not necessarily
reflect the views or policies of the US Army, the US Dept of Defense,
the US Dept of Health and Human Services or the institutions/companies
affiliated with the authors. J.H.K. performed this work as an employee
of Tunnell Government Services, Inc., a subcontractor to Battelle
Memorial Institute under its prime contract with the National Institute
of Allergy and Infectious Diseases (Contract No. HHSN272200700016I).
NR 44
TC 18
Z9 18
U1 5
U2 42
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD DEC 9
PY 2015
VL 18
IS 6
BP 659
EP 669
DI 10.1016/j.chom.2015.11.008
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CY1AL
UT WOS:000366138400008
PM 26651942
ER
PT J
AU Nunes, NNS
Ferreira, RS
Silva-Lucca, RA
de Sa, LFR
de Oliveira, AEA
Correia, MTD
Paiva, PMG
Wlodawer, A
Oliva, MLV
AF Nunes, Natalia N. S.
Ferreira, Rodrigo S.
Silva-Lucca, Rosemeire A.
de Sa, Leonardo F. R.
de Oliveira, Antonia Elenir A.
Correia, Maria Tereza dos S.
Paiva, Patricia Maria G.
Wlodawer, Alexander
Oliva, Maria Luiza V.
TI Potential of the Lectin/Inhibitor Isolated from Crataeva tapia Bark
(CrataBL) for Controlling Callosobruchus maculatus Larva Development
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE bioinsecticide; C. maculatus; Crataeva tapia; glycosaminoglycan;
inhibitor; lectin
ID VIGNA-UNGUICULATA SEEDS; ANAGASTA-KUEHNIELLA LEPIDOPTERA;
CIRCULAR-DICHROISM SPECTRA; TALISIA-ESCULENTA LECTIN; PLANT-LECTINS;
COWPEA WEEVIL; ZABROTES-SUBFASCIATUS; INSECTICIDAL ACTION;
CARBOHYDRATE-BINDING; BAUHINIA-MONANDRA
AB Callosobruchus maculatus is an important predator of cowpeas. Due to infestation during storage, this insect affects the quality of seed and crop yield. This study aimed to investigate the effects of CrataBL, a multifunction protein isolated from Crataeva tapia bark, on C. maculatus larva development. The protein, which is stable even in extreme pH conditions, showed toxic activity, reducing the larval mass 45 and 70% at concentrations of 0.25 and 1.0% (w/w), respectively. Acting as an inhibitor, CrataBL decreased by 39% the activity of cysteine proteinases from larval gut. Conversely, the activity of serine proteinases was increased about 8-fold. The toxic properties of CrataBL may also be attributed to its capacity of binding to glycoproteins or glycosaminoglycans. Such binding interferes with larval metabolism, because CrataBL FITC was found in the fat body, Malpighian tubules, and feces of larvae. These results demonstrate the potential of this protein for controlling larva development.
C1 [Nunes, Natalia N. S.; Ferreira, Rodrigo S.; Oliva, Maria Luiza V.] Univ Fed Sao Paulo, UNIFESP, Dept Bioquim, EPM, BR-04044020 Sao Paulo, SP, Brazil.
[Silva-Lucca, Rosemeire A.] Univ Estadual Oeste do Parana, Ctr Engn & Ciencias Exatas, Toledo, Parana, Brazil.
[de Sa, Leonardo F. R.; de Oliveira, Antonia Elenir A.] Univ Estadual Norte Fluminense Darcy Ribeiro UENF, CBB, Lab Quim & Funcao Prot & Peptideos, Campos Dos Goytacazes, RJ, Brazil.
[Correia, Maria Tereza dos S.; Paiva, Patricia Maria G.] Univ Fed Pernambuco, Dept Bioquim, Recife, PE, Brazil.
[Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Oliva, MLV (reprint author), Univ Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP, Brazil.
EM olivaml.bioq@epm.br
OI Paiva, Patricia/0000-0003-3467-708X
FU FAPESP [2009/17058-6, 2009/53766-5]; CAPES; CNPq [470275/2012];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This work was supported by FAPESP (2009/17058-6 and 2009/53766-5),
CAPES, and CNPq (470275/2012) and in part by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research,
NR 60
TC 1
Z9 1
U1 6
U2 23
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 DEC 9
PY 2015
VL 63
IS 48
BP 10431
EP 10436
DI 10.1021/acs.jafc.5b03634
PG 6
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA CY3WN
UT WOS:000366340700009
PM 26568149
ER
PT J
AU Yao, PJ
Petralia, RS
Ott, C
Wang, YX
Lippincott-Schwartz, J
Mattson, MP
AF Yao, Pamela J.
Petralia, Ronald S.
Ott, Carolyn
Wang, Ya-Xian
Lippincott-Schwartz, Jennifer
Mattson, Mark P.
TI Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates
Axon Elongation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE axon; hippocampal neuron; primary cilium; profilin 1; Smoothened; Sonic
Hedgehog
ID MICROFLUIDIC CULTURE PLATFORM; PRIMARY CILIA; SMALL-MOLECULE; CEREBELLAR
DEVELOPMENT; MOUSE CEREBELLUM; ACTIN DYNAMICS; OLFACTORY-BULB; RETINAL
AXONS; CELL MOTILITY; LIM-KINASE
AB The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons.
C1 [Yao, Pamela J.; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Petralia, Ronald S.; Wang, Ya-Xian] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
[Ott, Carolyn; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yaopa@grc.nia.nih.gov
FU National Institute on Aging-National Institutes of Health (NIH);
National Institute on Deafness and Other Communication Disorders
(NIDCD)-NIH; National Institute of Child Health and Human
Development-NIH
FX This work was supported by the Intramural Research Programs of the
National Institute on Aging-National Institutes of Health (NIH), the
National Institute on Deafness and Other Communication Disorders
(NIDCD)-NIH, and the National Institute of Child Health and Human
Development-NIH. The facility code for the Advanced Imaging Core of the
NIDCD-NIH is ZIC DC000081-03. We thank Emmette R. Hutchison for
assistance with qRT-PCR; Peisu Zhang and Ryan Wu for lentiviral
production; Fred E. Indig for confocal imaging; James K. Chen for the
Glix8::EGFP construct and Shh-N-expressing HEK 293 cells; James Briscoe
for PAP-A and Gli3N constructs; and John Lander for profilin1
constructs.
NR 80
TC 7
Z9 7
U1 1
U2 5
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 DEC 9
PY 2015
VL 35
IS 49
BP 16126
EP 16141
DI 10.1523/JNEUROSCI.1360-15.2015
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CX9WQ
UT WOS:000366057000011
PM 26658865
ER
PT J
AU Xu, JT
Lin, Y
Connell, JW
Dai, LM
AF Xu, Jiantie
Lin, Yi
Connell, John W.
Dai, Liming
TI Nitrogen-Doped Holey Graphene as an Anode for Lithium-Ion Batteries with
High Volumetric Energy Density and Long Cycle Life
SO SMALL
LA English
DT Article
ID ACTIVE ELECTRODE MATERIAL; RATE CAPABILITY; ELECTROCHEMICAL PROPERTIES;
PERFORMANCE; STORAGE; FABRICATION; CAPACITY; NANOSHEETS; METAL;
ULTRACAPACITORS
C1 [Xu, Jiantie; Dai, Liming] Case Western Reserve Univ, Dept Macromol Sci & Engn, Cleveland, OH 44106 USA.
[Lin, Yi] NIA, Hampton, VA 23666 USA.
[Lin, Yi] Coll William & Mary, Dept Appl Sci, Williamsburg, VA 23185 USA.
[Connell, John W.] NASA, Langley Res Ctr, Adv Mat & Proc Branch, Hampton, VA 23681 USA.
RP Lin, Y (reprint author), NIA, 100 Exploration Way, Hampton, VA 23666 USA.
EM yi.lin@nianet.org; john.w.connell@nasa.gov; liming.dai@case.edu
FU AFOSR [FA9550-12-1-0037]; NSF [CMMI-1400274, DMR-1106160]; Internal
Research and Development (IRAD) program at NASA Langley Research Center;
Leading Edge Aeronautics Research for NASA (LEARN) program [NNX13AB88A]
FX The authors are grateful for financial support from AFOSR
(FA9550-12-1-0037), NSF (CMMI-1400274, DMR-1106160). Y.L. and J.W.C.
acknowledge the financial support from the Internal Research and
Development (IRAD) program at NASA Langley Research Center. Y.L. is also
grateful for the support from the Leading Edge Aeronautics Research for
NASA (LEARN) program (Grant number NNX13AB88A).
NR 45
TC 15
Z9 16
U1 33
U2 150
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1613-6810
EI 1613-6829
J9 SMALL
JI Small
PD DEC 9
PY 2015
VL 11
IS 46
BP 6179
EP 6185
DI 10.1002/smll.201501848
PG 7
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 CX9WP
UT WOS:000366056900005
PM 26485602
ER
PT J
AU Sinha, R
Abnet, CC
White, O
Knight, R
Huttenhower, C
AF Sinha, Rashmi
Abnet, Christian C.
White, Owen
Knight, Rob
Huttenhower, Curtis
TI The microbiome quality control project: baseline study design and future
directions
SO GENOME BIOLOGY
LA English
DT Article
ID SEQUENCE DATA; ILLUMINA; PLATFORM
AB Microbiome research has grown exponentially over the past several years, but studies have been difficult to reproduce across investigations. Relevant variation in measurements between laboratories, from a variety of sources, has not been systematically assessed. This is coupled with a growing concern in the scientific community about the lack of reproducibility in biomedical research. The Microbiome Quality Control project (MBQC) was initiated to identify sources of variation in microbiome studies, to quantify their magnitudes, and to assess the design and utility of different positive and negative control strategies. Here we report on the first MBQC baseline study project and workshop.
C1 [Sinha, Rashmi; Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Knight, Rob] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Knight, Rob] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA.
[Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Sinha, R (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM sinhar@nih.gov
RI Abnet, Christian/C-4111-2015; Knight, Rob/D-1299-2010;
OI Abnet, Christian/0000-0002-3008-7843; Sinha, Rashmi/0000-0002-2466-7462
FU Intramural Research Program of the National Cancer Institute; NIH Common
Fund [U01 HG004866]; Sloan Microbiology of the Built Environment
program; Cohn's and Colitis Foundation of America; NSF CAREER grant
[DBI-1053486]; NIH [U54DE023798]; Crohn's and Colitis Foundation of
America [6109799-01]
FX RS and CCA were supported by the Intramural Research Program of the
National Cancer Institute; OW was supported by the NIH Common Fund U01
HG004866; RK was supported by Sloan Microbiology of the Built
Environment program and by the Cohn's and Colitis Foundation of America;
CH was supported by NSF CAREER grant DBI-1053486, NIH grant U54DE023798,
and by the Crohn's and Colitis Foundation of America grant 6109799-01.
NR 11
TC 19
Z9 19
U1 2
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD DEC 9
PY 2015
VL 16
AR 276
DI 10.1186/s13059-015-0841-8
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CY0OI
UT WOS:000366105000002
PM 26653756
ER
PT J
AU Reperant, LA
Grenfell, BT
Osterhaus, ADME
AF Reperant, Leslie A.
Grenfell, Bryan T.
Osterhaus, Albert D. M. E.
TI Quantifying the risk of pandemic influenza virus evolution by mutation
and re-assortment
SO VACCINE
LA English
DT Article
DE Evolution; Pandemic; Mutation; Reassortment; Latin hypercube sampling;
Probabilistic model
ID RESPIRATORY DROPLET; AIRBORNE TRANSMISSION; SEASONAL INFLUENZA; H5N1
VIRUS; A H5N1; A/H5N1 VIRUS; IN-VITRO; INFECTION; DYNAMICS; HUMANS
AB Large outbreaks of zoonotic influenza A virus (IAV) infections may presage an influenza pandemic. However, the likelihood that an airborne-transmissible variant evolves upon zoonotic infection or co-infection with zoonotic and seasonal IAVs remains poorly understood, as does the relative importance of accumulating mutations versus re-assortment in this process. Using discrete-time probabilistic models, we determined quantitative probability ranges that transmissible variants with 1-5 mutations and transmissible re-assortants evolve after a given number of zoonotic IAV infections. The systematic exploration of a large population of model parameter values was designed to account for uncertainty and variability in influenza virus infection, epidemiological and evolutionary processes. The models suggested that immunocompromised individuals are at high risk of generating IAV variants with pandemic potential by accumulation of mutations. Yet, both immunocompetent and immunocompromised individuals could generate high viral loads of single and double mutants, which may facilitate their onward transmission and the subsequent accumulation of additional 1-2 mutations in newly-infected individuals. This may result in the evolution of a full transmissible genotype along short chains of contact transmission. Although co-infection with zoonotic and seasonal IAVs was shown to be a rare event, it consistently resulted in high viral loads of re-assortants, which may facilitate their onward transmission among humans. The prevention or limitation of zoonotic IAV infection in immunocompromised and contact individuals, including health care workers, as well as vaccination against seasonal IAVs limiting the risk of co-infection should be considered fundamental tools to thwart the evolution of a novel pandemic IAV by accumulation of mutations and re-assortment. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Reperant, Leslie A.; Osterhaus, Albert D. M. E.] Artemis One Hlth Res Fdn, NL-3584 CL Utrecht, Netherlands.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Rockville, MD 20850 USA.
[Osterhaus, Albert D. M. E.] Univ Vet Med, Ctr Infect Med & Zoonosis Res, D-30559 Hannover, Germany.
RP Reperant, LA (reprint author), Artemis One Hlth Res Fdn, Yalelaan 1, NL-3584 CL Utrecht, Netherlands.
EM l.reperant@artemisonehealth.com
FU EU [302060, 223498, 278976]; RAPIDD program of the Science and
Technology Directorate Department of Homeland Security; Fogarty
International Center, NIH, Department of Homeland Security
[HSHQDC-12-C-00058]; Bill and Melinda Gates Foundation
FX The authors thank G. Rimmelzwaan and M.D. Polichtchouk for discussions.
L.A.R. was supported by EU FP7 Marie-Curie International Incoming
Fellowship #302060; B.T.G. by the RAPIDD program of the Science and
Technology Directorate Department of Homeland Security and the Fogarty
International Center, NIH, Department of Homeland Security contract
HSHQDC-12-C-00058 and the Bill and Melinda Gates Foundation; and
A.D.M.E.O. by EU FP7 EMPERIE project #223498 and EU FP7 ANTIGONE project
#278976.
NR 54
TC 2
Z9 2
U1 6
U2 13
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 DEC 8
PY 2015
VL 33
IS 49
SI SI
BP 6955
EP 6966
DI 10.1016/j.vaccine.2015.10.056
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CZ0DS
UT WOS:000366775900003
PM 26603954
ER
PT J
AU Theeler, BJ
Gilbert, MR
AF Theeler, Brett J.
Gilbert, Mark R.
TI Advances in the treatment of newly diagnosed glioblastoma
SO BMC MEDICINE
LA English
DT Review
DE Glioblastoma; High grade glioma; Immunotherapy; Checkpoint inhibitors;
Pseudoprogression
ID MGMT PROMOTER METHYLATION; RANDOMIZED PHASE-III; INTEGRATED GENOMIC
ANALYSIS; HIGH-GRADE GLIOMA; RADIATION-THERAPY; OPEN-LABEL; CONCOMITANT
TEMOZOLOMIDE; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; METASTATIC
MELANOMA
AB Glioblastoma is a refractory malignancy with limited treatment options at tumor recurrence. Only a small proportion of patients survive 2 years or longer with the current standard of care. Gene expression profiling can segregate newly diagnosed patients into groups with different prognoses, and these biomarkers are being incorporated into a new generation of personalized clinical trials. Using the experience from recently completed large scale, multi-faceted, randomized glioblastoma clinical trials, a new clinical trial paradigm is being established to move promising therapies forward into the newly diagnosed treatment setting. Upcoming trials using the immune check-point inhibitors are an example of this changing paradigm and these and other immunotherapies have potential as promising new treatment modalities for newly diagnosed GB patients.
C1 [Theeler, Brett J.] Walter Reed Natl Mil Med Ctr, Dept Neurol, Bethesda, MD 20889 USA.
[Theeler, Brett J.] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD 20889 USA.
[Gilbert, Mark R.] NIH, Bethesda, MD 20892 USA.
RP Theeler, BJ (reprint author), Walter Reed Natl Mil Med Ctr, Dept Neurol, 8901 Wisconsin Ave,Bldg 19, Bethesda, MD 20889 USA.
EM brett.j.theeler.mil@mail.mil
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
NR 92
TC 5
Z9 5
U1 2
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD DEC 8
PY 2015
VL 13
AR 293
DI 10.1186/s12916-015-0536-8
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY1KV
UT WOS:000366166000001
PM 26646075
ER
PT J
AU Margulies, KB
Anstrom, KJ
Redfield, MM
Givertz, MM
Oliveira, GH
Cole, R
Mann, D
Whellan, DJ
Kiernan, MS
Felker, GM
McNulty, SE
Shah, MR
Hernandez, AF
Braunwald, E
Cappola, TP
AF Margulies, Kenneth B.
Anstrom, Kevin J.
Redfield, Margaret M.
Givertz, Michael M.
Oliveira, Guilherme H.
Cole, Robert
Mann, Doug
Whellan, David J.
Kiernan, Michael S.
Felker, G. Michael
McNulty, Steven E.
Shah, Monica R.
Hernandez, Adrian F.
Braunwald, Eugene
Cappola, Thomas P.
TI A Randomized trial of Liraglutide for High-Risk Heart Failure Patients
with Reduced Ejection Fraction
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
C1 [Margulies, Kenneth B.; Cappola, Thomas P.] Univ Penn, Med Cardiol, Philadelphia, PA 19104 USA.
[Anstrom, Kevin J.] Duke Univ, Duke Clin Rsch Inst, Philadelphia, PA USA.
[Redfield, Margaret M.] Mayo Clin, Med Cardiol, Rochester, MN USA.
[Givertz, Michael M.] Brigham & Womens Hosp, Med Cardiol, Boston, MA 02115 USA.
[Oliveira, Guilherme H.] UH Case Med Cntr, Med Cardiovasc Med, Cleveland, OH USA.
[Cole, Robert] Emory Univ, Med Cardiol, Atlanda, GA USA.
[Mann, Doug] Washington Univ, Med Cardiovasc, St Louis, MO USA.
[Whellan, David J.] Thomas Jefferson Univ, Med Cardiol, Philadelphia, PA 19107 USA.
[Kiernan, Michael S.] Tufts Univ, Med Cardiol, Boston, MA 02111 USA.
[Felker, G. Michael; McNulty, Steven E.; Hernandez, Adrian F.] Duke Univ, Duke Clin Rsch Inst, Durham, NC USA.
[Shah, Monica R.] NHLBI, Cardiovasc Sci, Bethesda, MD 20892 USA.
[Braunwald, Eugene] Brigham & Womens Hosp, Cardiovasc Med, Boston, MA 02115 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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
BP 2268
EP 2268
DI 10.1161/CIR.0000000000000334
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100013
ER
PT J
AU Redfield, MM
Anstrom, KJ
Levine, JA
Borlaug, B
Chen, H
LeWinter, MM
Joseph, SM
Shah, SJ
Semigran, MJ
Felker, GM
Cole, RT
Reeves, G
Tedford, RJ
Tang, W
McNulty, SE
Velazquez, EJ
Shah, MR
Braunwald, E
AF Redfield, Margaret M.
Anstrom, Kevin J.
Levine, James A.
Borlaug, Barry
Chen, Horng
LeWinter, Martin M.
Joseph, Susan M.
Shah, Sanjiv J.
Semigran, Marc J.
Felker, G. M.
Cole, Robert T.
Reeves, Gordon
Tedford, Ryan J.
Tang, Wilson
McNulty, Steven E.
Velazquez, Eric J.
Shah, Monica R.
Braunwald, Eugene
CA NHLBI Heart Failure Clinical Rsch
TI Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved
Ejection Fraction (NEAT-HFpEF)
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
C1 [Redfield, Margaret M.; Borlaug, Barry; Chen, Horng] Mayo Clin & Mayo Fdn, Cardiovasc Dis, Rochester, MN USA.
[Anstrom, Kevin J.; McNulty, Steven E.; Velazquez, Eric J.] Duke Clin Rsch Inst, Outcomes, Durham, NC USA.
[Levine, James A.] Mayo Clin & Mayo Fdn, Cardiovasc Dis, Scottsdale, AZ USA.
[LeWinter, Martin M.] Univ Vermont, Med Ctr, Div Cardiol, Burlington, VT USA.
[Joseph, Susan M.] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA.
[Shah, Sanjiv J.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA.
[Semigran, Marc J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Felker, G. M.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Cole, Robert T.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA.
[Reeves, Gordon] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA.
[Tedford, Ryan J.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Tang, Wilson] Cleveland Clin Fdn, Cardiovasc Dis, Cleveland, OH 44195 USA.
[Shah, Monica R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
MA 13362
BP 2268
EP 2268
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100014
ER
PT J
AU Goldstein, D
Ailawadi, G
Moskowitz, A
Perrault, LP
Parides, M
Gelijns, A
Hung, J
Dagenais, F
Goldfarb, AM
Thourani, V
Argenziano, M
Gammie, J
Mack, M
Demers, P
Atluri, P
Rose, EA
O'Sullivan, K
Williams, D
Bagiella, E
Michler, R
Weisel, R
Miller, M
Taddei-Peters, WC
Smith, PK
Moquete, E
O'Gara, P
Overbey, JR
Kron, I
Acker, MA
AF Goldstein, Daniel
Ailawadi, Gorav
Moskowitz, Alan
Perrault, Louis P.
Parides, Michael
Gelijns, Annetine
Hung, Judy
Dagenais, Francois
Goldfarb, A. Marc
Thourani, Vinod
Argenziano, Michael
Gammie, James
Mack, Michael
Demers, Philippe
Atluri, Pavan
Rose, Eric A.
O'Sullivan, Karen
Williams, Deborah
Bagiella, Emilia
Michler, Robert
Weisel, Richard
Miller, Marissa
Taddei-Peters, Wendy C.
Smith, Peter K.
Moquete, Ellen
O'Gara, Patrick
Overbey, Jessica R.
Kron, Irving
Acker, Michael A.
CA CTSN Investigators
TI Two-Year Outcomes following Mitral Valve Repair or Replacement for
Severe Ischemic Mitral Regurgitation
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
DE Cardiac surgery; Mitral regurgitation; Ischemic heart disease
C1 [Goldstein, Daniel] Montefiore Med Ctr, Cardiothorac Surg, Bronx, NY 10467 USA.
[Ailawadi, Gorav; Kron, Irving] Univ Virginia Hlth Syst, Cardiothorac Surg, Charlottesville, VA USA.
[Moskowitz, Alan; Parides, Michael; Gelijns, Annetine; Rose, Eric A.; Williams, Deborah; Moquete, Ellen; Overbey, Jessica R.] Icahn Sch Med Mt Sinai, Populat Hlth Sci & Policy, New York, NY 10029 USA.
[Perrault, Louis P.; Demers, Philippe] Montreal Heart Inst, Surg, Montreal, PQ H1T 1C8, Canada.
[Hung, Judy] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA.
[Dagenais, Francois] Inst Univ Cardiol & Pneumol Quebec, Cardiothorac Surg, Quebec City, PQ, Canada.
[Goldfarb, A. Marc] Cleveland Clin, Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA.
[Thourani, Vinod] Emory Univ, Hosp Midtown, Cardiothorac Surg, Atlanta, GA 30322 USA.
[Argenziano, Michael] Columbia Univ, Med Ctr, NewYork Presbyterian Hosp, Cardiac Surg, New York, NY USA.
[Gammie, James] Univ Maryland, Cardiac Surg, Baltimore, MD 21201 USA.
[Mack, Michael] Baylor Rsch Inst, Cardiovasc Med, Plano, TX USA.
[Atluri, Pavan; Acker, Michael A.] Univ Penns Hlth Syst, Cardiovasc Surg, Philadelphia, PA USA.
[O'Sullivan, Karen; Bagiella, Emilia] Icahn Sch Med Mt Sinai, Hlth Evidence & Policy, New York, NY 10029 USA.
[Michler, Robert] Montefiore Einstein Heart Ctr, Cardiothorac Surg, Bronx, NY USA.
[Weisel, Richard] Toronto Gen Hosp, Cardiovasc Surg, Toronto, ON, Canada.
[Miller, Marissa] NHLBI, Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Taddei-Peters, Wendy C.] NHLBI, Cardiovasc Sci, Bethesda, MD 20892 USA.
[Smith, Peter K.; O'Gara, Patrick] Duke Univ, Surg, Durham, NC USA.
[O'Gara, Patrick] Brigham & Womens Hosp, Cardiovasc Surg, Boston, MA 02115 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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
MA 23690
BP 2276
EP 2276
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100036
ER
PT J
AU Cushman, WC
Evans, GW
Cutler, JA
AF Cushman, William C.
Evans, Gregory W.
Cutler, Jeffrey A.
CA ACCORD ACCORDION Study Grp
TI Long-term Cardiovascular Effects of 4.9 Years of Intensive Blood
Pressure Control in Type 2 Diabetes Mellitus: the Action to Control
Cardiovascular Risk in Diabetes Follow-On Blood Pressure Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
DE Diabetes (Type II); Hypertension; Clinical trials
C1 [Cushman, William C.] VA Med Ctr, Prevent Med Sect 111Q, Memphis, TN USA.
[Evans, Gregory W.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Cutler, Jeffrey A.] NHLBI, Washington, DC USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
MA 20210
BP 2281
EP 2281
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100047
ER
PT J
AU Nichol, G
Schmicker, R
Wang, H
Callaway, C
Weisfeldt, M
Sopko, G
Morrison, L
Cheskes, S
Christenson, J
Straight, R
Idris, A
Isaacs, SM
Stiell, I
Vaillancourt, C
Kudenchuk, P
Rea, T
Aufderheide, T
Colella, MR
Condle, J
Stephens, S
Richardson, J
Leroux, B
Egan, D
May, S
Ornato, J
AF Nichol, Graham
Schmicker, Robter
Wang, Heny
Callaway, Clifton
Weisfeldt, Myron
Sopko, George
Morrison, Laurie
Cheskes, Sheldon
Christenson, Jim
Straight, Ron
Idris, Ahamed
Isaacs, S. Marshal
Stiell, Ian
Vaillancourt, Christian
Kudenchuk, Peter
Rea, Thomas
Aufderheide, Tom
Colella, M. Riccardo
Condle, Joseph
Stephens, Shannon
Richardson, Joseph
Leroux, Brian
Egan, Debra
May, Susanne
Ornato, Joseph
TI Large Randomized Trial of Continuous versus Interrupted Chest
Compressions in Out-of-hospital Cardiac Arrest: Results of the
Resuscitation Outcomes Consortium CCC Trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association / Resuscitation
Science Symposium
CY NOV 15-19, 2015
CL Chicago, IL
SP Amer Heart Assoc
DE Cardiac arrest; Cardiopulmonary resuscitation; Resuscitation
C1 [Nichol, Graham] Univ Washington, Harborview Ctr Prehosp Emergency Care, Prehosp Emergency Care, Seattle, WA 98195 USA.
[Schmicker, Robter] Univ Washington, Clin Trial Ctr, Seattle, WA 98195 USA.
[Wang, Heny] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Callaway, Clifton; Condle, Joseph] Univ Pittsburgh, Pittsburgh, PA USA.
[Weisfeldt, Myron] Johns Hopkins Med, Baltimore, MD USA.
[Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA.
[Morrison, Laurie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Rescu, Toronto, ON M5B 1W8, Canada.
[Morrison, Laurie] UofT, Dept Med, Toronto, ON, Canada.
[Cheskes, Sheldon] Univ Toronto, Toronto, ON, Canada.
[Christenson, Jim] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Straight, Ron] Providence Hlth Care Rsch Inst, Vancouver, BC, Canada.
[Idris, Ahamed] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Isaacs, S. Marshal] UTSW, Dallas, TX USA.
[Stiell, Ian] Univ Ottawa, Ottawa, ON, Canada.
[Vaillancourt, Christian] Univ Ottawa, Ottawa Hosp Rsch Inst, Ottawa, ON, Canada.
[Kudenchuk, Peter; Leroux, Brian; May, Susanne] Univ Washington, Seattle, WA 98195 USA.
[Rea, Thomas; Aufderheide, Tom; Colella, M. Riccardo] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Stephens, Shannon] Univ Alabama Birmingham, Birmingham, AL USA.
[Richardson, Joseph] Birmingham Fire & Rescue Serv, Birmingham, AL USA.
[Egan, Debra] NHLBI, Bethesda, MD 20892 USA.
[Ornato, Joseph] Virginia Commonwealth Univ, Richmond, VA USA.
RI morrison, laurie/A-6325-2012
OI morrison, laurie/0000-0001-8369-9774
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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 8
PY 2015
VL 132
IS 23
MA 23165
BP 2283
EP 2283
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CX7DH
UT WOS:000365861100053
ER
PT J
AU Yu, GT
Bu, LL
Huang, CF
Zhang, WF
Chen, WJ
Gutkind, JS
Kulkarni, AB
Sun, ZJ
AF Yu, Guang-Tao
Bu, Lin-Lin
Huang, Cong-Fa
Zhang, Wen-Feng
Chen, Wan-Jun
Gutkind, J. Silvio
Kulkarni, Ashok B.
Sun, Zhi-Jun
TI PD-1 blockade attenuates immunosuppressive myeloid cells due to
inhibition of CD47/SIRPa axis in HPV negative head and neck squamous
cell carcinoma
SO ONCOTARGET
LA English
DT Article
DE HNSCC; myeloid-derived suppressor cell; tumor associated macrophagy;
PD-1
ID T-CELL; HUMAN-PAPILLOMAVIRUS; SUPPRESSOR-CELLS; OROPHARYNGEAL CANCER;
DENDRITIC CELLS; TUMOR MICROENVIRONMENT; PROGRAMMED DEATH-1; ADVANCED
MELANOMA; IMMUNE-SYSTEM; MOUSE MODEL
AB Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) play key roles in the tumor immune suppressive network and tumor progression. However, precise roles of programmed death-1 (PD-1) in immunological functions of MDSCs and TAMs in head and neck squamous cell carcinoma (HNSCC) have not been clearly elucidated. In the present study, we show that PD-1 and PD-L1 levels were significantly higher in human HNSCC specimen than in normal oral mucosa. MDSCs and TAMs were characterized in mice and human HNSCC specimen, correlated well with PD-1 and PD-L1 expression. aPD-1 treatment was well tolerated and significantly reduced tumor growth in the HNSCC mouse model along with significant reduction in MDSCs and TAMs in immune organs and tumors. Molecular analysis suggests a reduction in the CD47/SIRPa pathway by PD-1 blockade, which regulates MDSCs, TAMs, dendritic cell as well as effector T cells. Hence, these data identify that PD-1/PD-L1 axis is significantly increased in human and mouse HNSCC. Adoptive aPD-1 immunotherapy may provide a novel therapeutic approach to modulate the micro-and macro-environment in HNSCC.
C1 [Yu, Guang-Tao; Bu, Lin-Lin; Huang, Cong-Fa; Sun, Zhi-Jun] Wuhan Univ, Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan 430072, Peoples R China.
[Yu, Guang-Tao; Bu, Lin-Lin; Huang, Cong-Fa; Sun, Zhi-Jun] Wuhan Univ, Minist Educ, Key Lab Oral Biomed, Wuhan 430072, Peoples R China.
[Zhang, Wen-Feng; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Depy Oral Maxillofacial Head Neck Oncol, Wuhan 430072, Peoples R China.
[Chen, Wan-Jun; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
[Kulkarni, Ashok B.; Sun, Zhi-Jun] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Sun, ZJ (reprint author), Wuhan Univ, Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan 430072, Peoples R China.
EM sunzj@whu.edu.cn
FU National Natural Science Foundation of China [81272963, 81472528,
81272964, 81472529, 81402241]; Divison of Intramural Research, NIDCR,
NIH, USA; program for new century excellent talents in university,
Ministry of Education of China [NCET-13-0439]
FX This research was supported by National Natural Science Foundation of
China 81272963, 81472528 (Z.JS.), 81272964, 81472529 (W.F.Z), 81402241
(C.F.H.), and the Divison of Intramural Research, NIDCR, NIH, USA
(A.B.K, W.J.C., and J.S.G). Z.J.S. was supported by program for new
century excellent talents in university (NCET-13-0439), Ministry of
Education of China.
NR 54
TC 12
Z9 12
U1 5
U2 14
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC 8
PY 2015
VL 6
IS 39
BP 42067
EP 42080
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CY0TR
UT WOS:000366119600050
PM 26573233
ER
PT J
AU Whirledge, SD
Oakley, RH
Myers, PH
Lydon, JP
DeMayo, F
Cidlowski, JA
AF Whirledge, Shannon D.
Oakley, Robert H.
Myers, Page H.
Lydon, John P.
DeMayo, Francesco
Cidlowski, John A.
TI Uterine glucocorticoid receptors are critical for fertility in mice
through control of embryo implantation and decidualization
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE glucocorticoid receptor; uterus; decidualization; implantation
ID RAT UTERUS; PREGNANCY; STRESS; CELLS; DEXAMETHASONE; MECHANISMS;
EXPRESSION; MATURATION; INVITRO; BLOCKS
AB In addition to thewell-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic-pituitary-adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions.
C1 [Whirledge, Shannon D.; Oakley, Robert H.; Cidlowski, John A.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Myers, Page H.] NIEHS, Comparat Med Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Lydon, John P.; DeMayo, Francesco] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Cidlowski, JA (reprint author), NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
NR 32
TC 2
Z9 2
U1 4
U2 11
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 DEC 8
PY 2015
VL 112
IS 49
BP 15166
EP 15171
DI 10.1073/pnas.1508056112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX8YA
UT WOS:000365989800052
PM 26598666
ER
PT J
AU Molina-Cruz, A
Canepa, GE
Kamath, N
Pavlovic, NV
Mu, JB
Ramphul, UN
Ramirez, JL
Barillas-Mury, C
AF Molina-Cruz, Alvaro
Canepa, Gaspar E.
Kamath, Nitin
Pavlovic, Noelle V.
Mu, Jianbing
Ramphul, Urvashi N.
Ramirez, Jose Luis
Barillas-Mury, Carolina
TI Plasmodium evasion of mosquito immunity and global malaria transmission:
The lock-and-key theory
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE malaria globalization; immune evasion; anopheles immunity; Plasmodium
selection; Pfs47
ID MYCOBACTERIOPHAGE BXB1 INTEGRASE; ANOPHELES-GAMBIAE; HUMAN ERYTHROCYTES;
SURFACE PROTEIN; FALCIPARUM; PARASITE; COMPLEMENT; SYSTEM; PFS47; DNA
AB Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed.
C1 [Molina-Cruz, Alvaro; Canepa, Gaspar E.; Kamath, Nitin; Pavlovic, Noelle V.; Mu, Jianbing; Ramphul, Urvashi N.; Ramirez, Jose Luis; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Molina-Cruz, A (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM amolina-cruz@niaid.nih.gov; cbarillas@niaid.nih.gov
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (NIAID), NIH
[Z01AI000947]; NIAID Malaria Infection Biology Program; Intramural NIAID
Research Opportunites Program, NIH
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research Z01AI000947, National Institute of
Allergy and Infectious Diseases (NIAID), NIH. We thank Andre
Laughinghouse and Kevin Lee for insectary support, and Jose Ribeiro,
Jesus Valenzuela, and Louis Miller for their comments and insight.
G.E.C. was funded by the NIAID Malaria Infection Biology Program, and
J.L.R. was funded by the Intramural NIAID Research Opportunites Program,
NIH.
NR 41
TC 13
Z9 13
U1 3
U2 16
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 DEC 8
PY 2015
VL 112
IS 49
BP 15178
EP 15183
DI 10.1073/pnas.1520426112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX8YA
UT WOS:000365989800054
PM 26598665
ER
PT J
AU Rossi, M
de Azua, IR
Barella, LF
Sakamoto, W
Zhu, L
Cui, YH
Lu, HY
Rebholz, H
Matschinsky, FM
Doliba, NM
Butcher, AJ
Tobin, AB
Wess, J
AF Rossi, Mario
de Azua, Inigo Ruiz
Barella, Luiz F.
Sakamoto, Wataru
Zhu, Lu
Cui, Yinghong
Lu, Huiyan
Rebholz, Heike
Matschinsky, Franz M.
Doliba, Nicolai M.
Butcher, Adrian J.
Tobin, Andrew B.
Wess, Juergen
TI CK2 acts as a potent negative regulator of receptor-mediated insulin
release in vitro and in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE G protein-coupled receptors; beta-cell function; mouse models; glucose
homeostasis; GPCR regulation
ID PROTEIN-COUPLED RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; KINASE CK2;
TRANSGENIC MICE; PHOSPHORYLATION; MECHANISMS; CELLS; STIMULATION;
ACTIVATION; INHIBITOR
AB G protein-coupled receptors (GPCRs) regulate virtually all physiological functions including the release of insulin from pancreatic beta-cells. beta-Cell M-3 muscarinic receptors (M3Rs) are known to play an essential role in facilitating insulin release and maintaining proper whole-body glucose homeostasis. As is the case with other GPCRs, M3R activity is regulated by phosphorylation by various kinases, including GPCR kinases and casein kinase 2 (CK2). At present, it remains unknown which of these various kinases are physiologically relevant for the regulation of beta-cell activity. In the present study, we demonstrate that inhibition of CK2 in pancreatic beta-cells, knockdown of CK2 alpha expression, or genetic deletion of CK2 alpha in beta-cells of mutant mice selectively augmented M3R-stimulated insulin release in vitro and in vivo. In vitro studies showed that this effect was associated with an M3R-mediated increase in intracellular calcium levels. Treatment of mouse pancreatic islets with CX4945, a highly selective CK2 inhibitor, greatly reduced agonist-induced phosphorylation of beta-cell M3Rs, indicative of CK2-mediated M3R phosphorylation. We also showed that inhibition of CK2 greatly enhanced M3R-stimulated insulin secretion in human islets. Finally, CX4945 treatment protected mice against diet-induced hyperglycemia and glucose intolerance in an M3R-dependent fashion. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on beta-cell GPCRs may represent novel therapeutic targets.
C1 [Rossi, Mario; de Azua, Inigo Ruiz; Barella, Luiz F.; Sakamoto, Wataru; Zhu, Lu; Cui, Yinghong; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Lu, Huiyan] NIDDK, Mouse Transgen Core Facil, NIH, Bethesda, MD 20892 USA.
[Rebholz, Heike] CUNY City Coll, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA.
[Matschinsky, Franz M.; Doliba, Nicolai M.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
[Butcher, Adrian J.; Tobin, Andrew B.] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England.
RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM jurgenw@helix.nih.gov
RI Barella, Luiz/C-1181-2014
OI Barella, Luiz/0000-0003-2211-3842
FU NIDDK, NIH, Department of Health and Human Services; Medical Research
Council Toxicology Unit; American Diabetes Association [7-11-BS-34];
Diabetes Center [NIH DK-19525]; Rapid Response Grant by the Michael J.
Fox Foundation; NIH-Japan Society for Promotion of Science Research
Fellowship Program; NIH-Brazilian National Council for Scientific and
Technological Development Visiting Fellows Program
FX We thank Dr. Weiping Chen [National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) Genomics Core] and Dr. Hans Luecke (NIDDK
Advanced Mass Spectrometry Core) for their help with the analysis of
human beta-cell microarray data and the use of Phos-tag technology,
respectively. This work was supported by the Intramural Research
Program, NIDDK, NIH, Department of Health and Human Services (M.R.,
I.R.d.A., L.F.B., W.S., L.Z., Y.C., and J.W.); the Medical Research
Council Toxicology Unit (A.B.T. and A.J.B.); American Diabetes
Association Grant 7-11-BS-34 (to N.M.D.); Diabetes Center Grant NIH
DK-19525 (to N.M.D. and F.M.M.); and a Rapid Response Grant by the
Michael J. Fox Foundation (to H.R.). W.S. was the recipient of a stipend
from the NIH-Japan Society for Promotion of Science Research Fellowship
Program. L.F.B. received a stipend through the NIH-Brazilian National
Council for Scientific and Technological Development Visiting Fellows
Program.
NR 35
TC 1
Z9 1
U1 1
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 DEC 8
PY 2015
VL 112
IS 49
BP E6818
EP E6824
DI 10.1073/pnas.1519430112
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX8YA
UT WOS:000365989800016
PM 26598688
ER
PT J
AU Sengupta, P
Satpute-Krishnan, P
Seo, AY
Burnette, DT
Patterson, GH
Lippincott-Schwartz, J
AF Sengupta, Prabuddha
Satpute-Krishnan, Prasanna
Seo, Arnold Y.
Burnette, Dylan T.
Patterson, George H.
Lippincott-Schwartz, Jennifer
TI ER trapping reveals Golgi enzymes continually revisit the ER through a
recycling pathway that controls Golgi organization
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Golgi; recycling; mitosis; rapamycin; ER
ID PHOSPHOLIPASE A(2) ANTAGONISTS; ENDOPLASMIC-RETICULUM; BREFELDIN-A;
LIVING CELLS; RETROGRADE TRANSPORT; MAMMALIAN-CELLS; BINDING-PROTEIN;
LIVE CELLS; HELA-CELLS; COMPLEX
AB Whether Golgi enzymes remain localized within the Golgi or constitutively cycle through the endoplasmic reticulum (ER) is unclear, yet is important for understanding Golgi dependence on the ER. Here, we demonstrate that the previously reported inefficient ER trapping of Golgi enzymes in a rapamycin-based assay results from an artifact involving an endogenous ER-localized 13-kD FK506 binding protein (FKBP13) competing with the FKBP12-tagged Golgi enzyme for binding to an FKBP-rapamycin binding domain (FRB)-tagged ER trap. When we express an FKBP12-tagged ER trap and FRB-tagged Golgi enzymes, conditions precluding such competition, the Golgi enzymes completely redistribute to the ER upon rapamycin treatment. A photoactivatable FRB-Golgi enzyme, highlighted only in the Golgi, likewise redistributes to the ER. These data establish Golgi enzymes constitutively cycle through the ER. Using our trapping scheme, we identify roles of rab6a and calcium-independent phospholipase A(2) (iPLA(2)) in Golgi enzyme recycling, and show that retrograde transport of Golgi membrane underlies Golgi dispersal during microtubule depolymerization and mitosis.
C1 [Sengupta, Prabuddha; Satpute-Krishnan, Prasanna; Seo, Arnold Y.; Burnette, Dylan T.; Patterson, George H.; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
FU NIH
FX We thank Juan Bonifacino (US National Institute of Child Health and
Development) for sharing the rab6a plasmids and Mike Davidson (Florida
State University) for sharing the H2B-mCh plasmid. This work was
supported by the Intramural Research Program of the NIH.
NR 56
TC 9
Z9 9
U1 1
U2 8
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 DEC 8
PY 2015
VL 112
IS 49
BP E6752
EP E6761
DI 10.1073/pnas.1520957112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX8YA
UT WOS:000365989800009
PM 26598700
ER
PT J
AU Brennand, KJ
Marchetto, MC
Benvenisty, N
Brustle, O
Ebert, A
Belmonte, JCI
Kaykas, A
Lancaster, MA
Livesey, FJ
McConnell, MJ
Mckay, RD
Morrow, EM
Muotri, AR
Panchision, DM
Rubin, LL
Sawa, A
Soldner, F
Song, HJ
Studer, L
Temple, S
Vaccarino, FM
Wu, J
Vanderhaeghen, P
Gage, FH
Jaenisch, R
AF Brennand, Kristen J.
Marchetto, M. Carol
Benvenisty, Nissim
Bruestle, Oliver
Ebert, Allison
Belmonte, Juan Carlos Izpisua
Kaykas, Ajamete
Lancaster, Madeline A.
Livesey, Frederick J.
McConnell, Michael J.
McKay, Ronald D.
Morrow, Eric M.
Muotri, Alysson R.
Panchision, David M.
Rubin, Lee L.
Sawa, Akira
Soldner, Frank
Song, Hongjun
Studer, Lorenz
Temple, Sally
Vaccarino, Flora M.
Wu, Jun
Vanderhaeghen, Pierre
Gage, Fred H.
Jaenisch, Rudolf
TI Creating Patient-Specific Neural Cells for the In Vitro Study of Brain
Disorders
SO STEM CELL REPORTS
LA English
DT Editorial Material
ID PLURIPOTENT STEM-CELLS; GROUND-STATE PLURIPOTENCY;
SCHIZOPHRENIA-PATIENTS; MAMMALIAN EMBRYOS; SELF-ORGANIZATION;
MOUSE-BRAIN; NEURONS; MODEL; DIFFERENTIATION; INDUCTION
AB As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.
C1 [Brennand, Kristen J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Marchetto, M. Carol; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, San Diego, CA 92037 USA.
[Benvenisty, Nissim] Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel.
[Bruestle, Oliver] Univ Bonn, LIFE & BRAIN Ctr, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany.
[Ebert, Allison] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
[Belmonte, Juan Carlos Izpisua; Wu, Jun] Salk Inst Biol Studies, Gene Express Lab, San Diego, CA 92037 USA.
[Kaykas, Ajamete] Novartis Inst BioMed Res Inc, Dept Neurobiol, Cambridge, MA 02139 USA.
[Lancaster, Madeline A.] Mol Biol Lab, Cambridge CB2 0QH, England.
[Livesey, Frederick J.] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
[McConnell, Michael J.] Univ Virginia, Sch Med, Ctr Brain Immunol & Glia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
[McKay, Ronald D.] Lieber Inst Brain Dev, Brain Dev, Baltimore, MD 21205 USA.
[Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Muotri, Alysson R.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.
[Panchision, David M.] NIMH, Dev Neurobiol Program, Bethesda, MD 20892 USA.
[Rubin, Lee L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Sawa, Akira] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Soldner, Frank; Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Song, Hongjun] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
[Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Stem Cell & Tumor Biol, New York, NY 10021 USA.
[Temple, Sally] Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
[Vaccarino, Flora M.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Vanderhaeghen, Pierre] Univ Brussels ULB, Inst Interdisciplinary Res IRIBHM, B-1070 Brussels, Belgium.
RP Gage, FH (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, San Diego, CA 92037 USA.
EM fgage@salk.edu; jaenisch@wi.mit.edu
RI Brennand, Kristen/J-8704-2012;
OI Brennand, Kristen/0000-0003-0993-5956; Wu, Jun/0000-0001-9863-1668;
Vaccarino, Flora/0000-0003-2167-981X; Lancaster,
Madeline/0000-0003-2324-8853
FU Medical Research Council [MC_UP_1201/9]; NCI NIH HHS [P30 CA014195]; NIA
NIH HHS [RF1 AG042932, RF1AG042932]; NIMH NIH HHS [R01MH095741,
2R01MH104610, P50 MH094268, P50MH094268, R01 MH089176, R01 MH092443, R01
MH094753, R01 MH095741, R01 MH101454, R01 MH102418, R01 MH103134, R01
MH104610, R01 MH105442, R01 MH105660, R01MH089176, R01MH092443,
R01MH094753, R01MH101454, R01MH102418, R01MH103134, R01MH105442,
R01MH105660, R21 MH087879, R21MH087879, R33 MH087874, R33MH087874, U01
MH103365, U01MH1068821, U19 MH107367, U19MH107367]; NINDS NIH HHS [P01
NS066888, P01NS066888, R01 NS047344, R01 NS088538, R01NS047344,
R01NS088538]; Wellcome Trust [, 101052]
NR 62
TC 12
Z9 12
U1 3
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD DEC 8
PY 2015
VL 5
IS 6
BP 933
EP 945
DI 10.1016/j.stemcr.2015.10.011
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CY1BY
UT WOS:000366142900001
PM 26610635
ER
PT J
AU Kanellopoulou, C
Gilpatrick, T
Kilaru, G
Burr, P
Nguyen, CK
Morawski, A
Lenardo, MJ
Muljo, SA
AF Kanellopoulou, Chryssa
Gilpatrick, Timothy
Kilaru, Gokhul
Burr, Patrick
Nguyen, Cuong K.
Morawski, Aaron
Lenardo, Michael J.
Muljo, Stefan A.
TI Reprogramming of Polycomb-Mediated Gene Silencing in Embryonic Stem
Cells by the miR-290 Family and the Methyltransferase Ash1l
SO STEM CELL REPORTS
LA English
DT Article
ID DEVELOPMENTAL REGULATORS; TARGET GENES; GENOME-WIDE; MICRORNAS; MOUSE;
PLURIPOTENCY; DIFFERENTIATION; RECRUITMENT; METHYLATION; TRANSITION
AB Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR-/-ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Poly-comb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family.
C1 [Kanellopoulou, Chryssa; Gilpatrick, Timothy; Morawski, Aaron; Lenardo, Michael J.] NIAID, Immunol Lab, Mol Dev Immune Syst Sect, NIH, Bethesda, MD 20892 USA.
[Kilaru, Gokhul; Burr, Patrick; Nguyen, Cuong K.; Muljo, Stefan A.] NIAID, Immunol Lab, Integrat Immunobiol Unit, NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, Mol Dev Immune Syst Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mlenardo@niaid.nih.gov; stefan.muljo@nih.gov
RI Nguyen, Cuong/D-7567-2013
OI Nguyen, Cuong/0000-0002-1741-669X
FU NIH Intramural Research Program of the NIAID
FX We would like to thank Drs. David Livingston, Ron Germain, Kathrin
Plath, Markus Hafner, and Carrie Lucas for critically reading this
manuscript and Bryan Chim for help with bioinformatics analyses. We also
thank Dr. Livingston for his support during the generation of the
DCR-/-ESCs, anti-Dicer, and anti-Ago2 antibodies and Drs.
Merkenschlager and Graham for sharing the DCRfl/fl;
R26CreERT2 cells. We also thank Dr. Chaigne-Delalande and members of the
Lenardo and Muljo laboratories for helpful discussions, M. Smelkinson
and S. Ganesan at the NIAID Imaging core for assistance with microscopy,
and A. Athman, NIAID Visual and Medical Arts Department, for help with
Figure 4F. This study utilized NIAID high-performance computing and NIH
Biowulf cluster and was supported by the NIH Intramural Research Program
of the NIAID.
NR 32
TC 4
Z9 4
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD DEC 8
PY 2015
VL 5
IS 6
BP 971
EP 978
DI 10.1016/j.stemcr.2015.10.001
PG 8
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CY1BY
UT WOS:000366142900005
PM 26549848
ER
PT J
AU Compton, WM
Blanco, C
Wargo, EM
AF Compton, Wilson M.
Blanco, Carlos
Wargo, Eric M.
TI Integrating Addiction Services Into General Medicine
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Compton, Wilson M.; Blanco, Carlos; Wargo, Eric M.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Compton, WM (reprint author), NIDA, NIH, 6001 Execut Blvd,MSC 9581, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
NR 7
TC 3
Z9 3
U1 2
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 8
PY 2015
VL 314
IS 22
BP 2401
EP 2402
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX8XT
UT WOS:000365989100014
PM 26647261
ER
PT J
AU Taye, MA
Duki, SF
AF Taye, Mesfin Asfaw
Duki, Solomon Fekade
TI The effect of temperature dependence of viscosity on a Brownian heat
engine
SO EUROPEAN PHYSICAL JOURNAL B
LA English
DT Article
ID NONUNIFORM TEMPERATURE; RELATIVE STABILITY; MAXIMUM POWER; EFFICIENCY;
SYSTEMS; MOTORS; ENERGETICS; DRIVEN
AB We modeled a Brownian heat engine as a Brownian particle that hops in a periodic ratchet potential where the ratchet potential is coupled with a spatially varying temperature. The strength for the viscous friction gamma(x) is considered to decrease exponentially when the temperature T(x) of the medium increases (gamma(x) = Be-AT(x)) as proposed originally by Reynolds [O. Reynolds, Phil. Trans. R. Soc. London 177, 157 (1886)]. Our result depicts that the velocity of the motor is considerably higher when the viscous friction is temperature dependent than that of the case where the viscous friction is temperature independent. The dependence of the efficiency eta as well as the coefficient of performance of the refrigerator P-ref on model parameters is also explored. If the motor designed to achieve a high velocity against a frictional drag, in the absence of external load f, we show that Carnot efficiency or Carnot refrigerator is unattainable even at quasistatic limit as long as the viscous friction is temperature dependent A not equal 0. On the contrary, in the limit A -> 0 or in general in the presence of an external load (for any A) f not equal 0, at quasistatic limit, Carnot efficiency or Carnot refrigerator is attainable as long as the heat exchange via kinetic energy is omitted. For all cases, far from quasistatic limit, the efficiency and the coefficient of performance of the refrigerator are higher for constant gamma case than the case where. is temperature dependent. On the other hand, if one includes the heat exchange at the boundary of the heat baths, Carnot efficiency or Carnot refrigerator is unattainable even at quasistatic limit. Moreover, the dependence for the optimized and maximum power efficiencies on the determinant model parameters is explored.
C1 [Taye, Mesfin Asfaw] Calif State Univ Dominguez Hills, Dept Phys, Carson, CA 90747 USA.
[Duki, Solomon Fekade] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Duki, Solomon Fekade] NIH, Bethesda, MD 20894 USA.
RP Taye, MA (reprint author), Calif State Univ Dominguez Hills, Dept Phys, Carson, CA 90747 USA.
EM taye@es.hokudai.ac.jp
OI Duki, Solomon/0000-0003-3042-0252
NR 30
TC 0
Z9 0
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1434-6028
EI 1434-6036
J9 EUR PHYS J B
JI Eur. Phys. J. B
PD DEC 7
PY 2015
VL 88
IS 12
AR 322
DI 10.1140/epjb/e2015-60782-0
PG 12
WC Physics, Condensed Matter
SC Physics
GA DG2JO
UT WOS:000371893400003
ER
PT J
AU Hu, YL
AF Hu, Yinling
TI A feedforward loop of NLRC5 (de)ubiquitination keeps IKK-NF-kappa B in
check
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID T-CELLS; ACQUIRED-IMMUNITY; ALPHA; SKIN; MICE; HOMEOSTASIS; DEFICIENCY;
ACTIVATION; PATHWAYS; INNATE
AB Many receptors signal via adaptors to the IKK-NF-kappa B axis, transducing extracellular cues to transcriptional regulation. In this issue, Meng et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505091) reveal that the IKK regulator NLRC5 shapes NF-kappa B activity through a feedforward loop of NLRC5 ubiquitination and deubiquitination, highlighting a new pathway modulating IKK-NF-kappa B activity.
C1 [Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM huy2@mail.nih.gov
NR 20
TC 1
Z9 2
U1 2
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD DEC 7
PY 2015
VL 211
IS 5
BP 941
EP 943
DI 10.1083/jcb.201511039
PG 3
WC Cell Biology
SC Cell Biology
GA DD0YB
UT WOS:000369646300004
PM 26620908
ER
PT J
AU Schoborg, T
Zajac, AL
Fagerstrom, CJ
Guillen, RX
Rusan, NM
AF Schoborg, Todd
Zajac, Allison L.
Fagerstrom, Carey J.
Guillen, Rodrigo X.
Rusan, Nasser M.
TI An Asp-CaM complex is required for centrosome-pole cohesion and
centrosome inheritance in neural stem cells
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ABNORMAL-SPINDLE PROTEIN; DROSOPHILA S2 CELLS; MITOTIC SPINDLE;
MICROTUBULE MOTOR; MYOSIN-II; DIVISION; NUMA; NEUROBLASTS; ORGANIZATION;
ORIENTATION
AB The interaction between centrosomes and mitotic spindle poles is important for efficient spindle formation, orientation, and cell polarity. However, our understanding of the dynamics of this relationship and implications for tissue homeostasis remains poorly understood. Here we report that Drosophila melanogaster calmodulin (CaM) regulates the ability of the microcephaly-associated protein, abnormal spindle (Asp), to cross-link spindle microtubules. Both proteins colocalize on spindles and move toward spindle poles, suggesting that they form a complex. Our binding and structure-function analysis support this hypothesis. Disruption of the Asp-CaM interaction alone leads to unfocused spindle poles and centrosome detachment. This behavior leads to randomly inherited centrosomes after neuroblast division. We further show that spindle polarity is maintained in neuroblasts despite centrosome detachment, with the poles remaining stably associated with the cell cortex. Finally, we provide evidence that CaM is required for Asp's spindle function; however, it is completely dispensable for Asp's role in microcephaly suppression.
C1 [Schoborg, Todd; Zajac, Allison L.; Fagerstrom, Carey J.; Guillen, Rodrigo X.; Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Rusan, NM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM Nasser@nih.gov
RI Rusan, Nasser/P-3511-2016
FU Division of Intramural Research at the National Institutes of
Health/National Heart, Lung, and Blood Institute [1ZIAHL006126]
FX N.M. Rusan is supported by the Division of Intramural Research at the
National Institutes of Health/National Heart, Lung, and Blood Institute
(1ZIAHL006126).
NR 56
TC 1
Z9 1
U1 1
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD DEC 7
PY 2015
VL 211
IS 5
BP 987
EP 998
DI 10.1083/jcb.201509054
PG 12
WC Cell Biology
SC Cell Biology
GA DD0YB
UT WOS:000369646300009
PM 26620907
ER
PT J
AU Raghunayakula, S
Subramonian, D
Dasso, M
Kumar, R
Zhang, XD
AF Raghunayakula, Sarita
Subramonian, Divya
Dasso, Mary
Kumar, Rita
Zhang, Xiang-Dong
TI Molecular Characterization and Functional Analysis of Annulate Lamellae
Pore Complexes in Nuclear Transport in Mammalian Cells
SO PLOS ONE
LA English
DT Article
ID ACTIVATING PROTEIN RANGAP1; XENOPUS EGG EXTRACT; ARGININE DEPRIVATION;
E3 LIGASE; KB CELLS; IN-VIVO; NUCLEOCYTOPLASMIC TRANSPORT; SUMO-1
MODIFICATION; GTP HYDROLYSIS; RAN
AB Annulate lamellae are cytoplasmic organelles containing stacked sheets of membranes embedded with pore complexes. These cytoplasmic pore complexes at annulate lamellae are morphologically similar to nuclear pore complexes at the nuclear envelope. Although annulate lamellae has been observed in nearly all types of cells, their biological functions are still largely unknown. Here we show that SUMO1-modification of the Ran GTPase-activating protein RanGAP1 not only target RanGAP1 to its known sites at nuclear pore complexes but also to annulate lamellae pore complexes through interactions with the Ran-binding protein RanBP2 and the SUMO-conjugating enzyme Ubc9 in mammalian cells. Furthermore, upregulation of annulate lamellae, which decreases the number of nuclear pore complexes and concurrently increases that of annulate lamellae pore complexes, causes a redistribution of nuclear transport receptors including importin alpha/beta and the exportin CRM1 from nuclear pore complexes to annulate lamellae pore complexes and also reduces the rates of nuclear import and export. Moreover, our results reveal that importin alpha/beta-mediated import complexes initially accumulate at annulate lamellae pore complexes upon the activation of nuclear import and subsequently disassociate for nuclear import through nuclear pore complexes in cells with upregulation of annulate lamellae. Lastly, CRM1-mediated export complexes are concentrated at both nuclear pore complexes and annulate lamellae pore complexes when the disassembly of these export complexes is inhibited by transient expression of a Ran GTPase mutant arrested in its GTP-bound form, suggesting that RanGAP1/RanBP2-activated RanGTP hydrolysis at these pore complexes is required for the dissociation of the export complexes. Hence, our findings provide a foundation for further investigation of how upregulation of annulate lamellae decreases the rates of nuclear transport and also for elucidation of the biological significance of the interaction between annulate lamellae pore complexes and nuclear transport complexes in mammalian cells.
C1 [Raghunayakula, Sarita; Subramonian, Divya; Zhang, Xiang-Dong] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
[Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Kumar, Rita] Wayne State Univ, Dept Emergency Med, Detroit, MI USA.
[Kumar, Rita] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
RP Zhang, XD (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
EM xzhang@wayne.edu
OI Kumar, Rita/0000-0002-9573-7667; Dasso, Mary/0000-0002-5410-1371
NR 82
TC 1
Z9 1
U1 1
U2 3
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 DEC 7
PY 2015
VL 10
IS 12
AR e0144508
DI 10.1371/journal.pone.0144508
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ1YS
UT WOS:000366902700136
PM 26642330
ER
PT J
AU Yao, CX
Behring, JB
Shao, D
Sverdlov, AL
Whelan, SA
Elezaby, A
Yin, XY
Siwik, DA
Seta, F
Costello, CE
Cohen, RA
Matsui, R
Colucci, WS
McComb, ME
Bachschmid, MM
AF Yao, Chunxiang
Behring, Jessica B.
Shao, Di
Sverdlov, Aaron L.
Whelan, Stephen A.
Elezaby, Aly
Yin, Xiaoyan
Siwik, Deborah A.
Seta, Francesca
Costello, Catherine E.
Cohen, Richard A.
Matsui, Reiko
Colucci, Wilson S.
McComb, Mark E.
Bachschmid, Markus M.
TI Overexpression of Catalase Diminishes Oxidative Cysteine Modifications
of Cardiac Proteins
SO PLOS ONE
LA English
DT Article
ID HUMAN CARBONYL REDUCTASE; HYDROGEN-PEROXIDE; SERINE/THREONINE
PHOSPHATASES; CONTRACTILE DYSFUNCTION; MITOCHONDRIAL-MEMBRANE;
TRANSGENIC MICE; CYTOCHROME-C; MOUSE HEART; DNA-DAMAGE; LIM DOMAIN
AB Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2), react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat), an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT) labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg) mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by >= 1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.
C1 [Yao, Chunxiang; Behring, Jessica B.; Shao, Di; Seta, Francesca; Cohen, Richard A.; Matsui, Reiko; Bachschmid, Markus M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect,Dept Med, Boston, MA 02118 USA.
[Sverdlov, Aaron L.; Elezaby, Aly; Siwik, Deborah A.; Colucci, Wilson S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Myocardial Biol Unit,Dept Med, Boston, MA 02118 USA.
[Whelan, Stephen A.; Costello, Catherine E.; McComb, Mark E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Cardiovasc Prote Ctr, Boston, MA 02118 USA.
[Yin, Xiaoyan] Boston Univ, Framingham, MA USA.
[Yin, Xiaoyan] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Yin, Xiaoyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
RP McComb, ME (reprint author), Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Cardiovasc Prote Ctr, Boston, MA 02118 USA.
EM mccomb@bu.edu; bach@bu.edu
RI Shao, Di/F-9758-2016;
OI Sverdlov, Aaron/0000-0003-2539-8038; Bachschmid, Markus
Michael/0000-0002-0748-5528
FU NHLBI, National Institutes of Health, Department of Health and Human
Services [HHSN268201000031C]; NIH [P01 HL 068758, R37 HL104017, R01
HL064750, R01 HL031607, P41 GM104603, R01 DK103750, S10 OD010724];
National Health and Medical Research Council of Australia [APP1037603];
Royal Australasian College of Physicians; AHA Postdoctoral Fellowship
[14POST20490003, 15POST21790006]
FX This work was supported by the NHLBI, National Institutes of Health,
Department of Health and Human Services, under Contract No.
HHSN268201000031C, and by NIH grants P01 HL 068758, R37 HL104017, R01
HL064750, R01 HL031607, P41 GM104603, R01 DK103750 and S10 OD010724. ALS
is funded by a CJ Martin Fellowship from the National Health and Medical
Research Council of Australia (APP1037603), the Marjorie Hooper Overseas
Fellowship from the Royal Australasian College of Physicians and AHA
Postdoctoral Fellowship 14POST20490003. DS is funded from the AHA
Postdoctoral Fellowship 15POST21790006. The contents are solely the
responsibility of the authors and do not represent the official views of
the funders. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 68
TC 4
Z9 4
U1 0
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 DEC 7
PY 2015
VL 10
IS 12
AR e0144025
DI 10.1371/journal.pone.0144025
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CZ1YS
UT WOS:000366902700046
PM 26642319
ER
PT J
AU Kunkel, TA
AF Kunkel, Thomas A.
TI Celebrating DNA's Repair Crew
SO CELL
LA English
DT Editorial Material
ID HUMAN MISMATCH REPAIR; ESCHERICHIA-COLI; EXCISION-REPAIR; PHOTOLYASE;
SYSTEM; DAMAGE
AB This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility.
C1 [Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
NR 15
TC 4
Z9 4
U1 4
U2 18
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 DEC 6
PY 2015
VL 163
IS 6
BP 1301
EP 1303
DI 10.1016/j.cell.2015.11.028
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CX9SE
UT WOS:000366044800008
PM 26638062
ER
PT J
AU Davis, FP
Kanno, Y
O'Shea, JJ
AF Davis, Fred P.
Kanno, Yuka
O'Shea, John J.
TI A Metabolic Switch for Th17 Pathogenicity
SO CELL
LA English
DT Editorial Material
ID T-CELLS; DROPLETS
AB T helper 17 (Th17) cells are critical for host defense but can also drive autoimmunity. This divergent behavior is explored by Gaublomme et al. and Wang et al., who identify inflammation-associated genes by measuring gene expression in nearly 1,000 individual Th17 cells and show that CD5L affects the expression of pro-inflammatory genes by altering lipid synthesis.
C1 [Davis, Fred P.; Kanno, Yuka; O'Shea, John J.] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Davis, FP (reprint author), NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM fred.davis@nih.gov; john.oshea@nih.gov
NR 10
TC 1
Z9 1
U1 4
U2 16
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 DEC 6
PY 2015
VL 163
IS 6
BP 1308
EP U304
DI 10.1016/j.cell.2015.11.033
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CX9SE
UT WOS:000366044800010
PM 26638065
ER
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CA GBD 2013 Risk Factors
TI Global, regional, and national comparative risk assessment of 79
behavioural, environmental and occupational, and metabolic risks or
clusters of risks in 188 countries, 1990-2013: a systematic analysis for
the Global Burden of Disease Study 2013
SO LANCET
LA English
DT Article
ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; CAUSE-SPECIFIC MORTALITY; FINE
PARTICULATE MATTER; OUTDOOR AIR-POLLUTION; MALE BRITISH DOCTORS;
ALL-CAUSE MORTALITY; LONG-TERM EXPOSURE; BLOOD-PRESSURE; TOBACCO SMOKING
AB Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.
Findings All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.
Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
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[Aburto, Tania C.; Avila, Marco A.; Barquera, Simon; Barrientos-Gutierrez, Tonatiuh; Campos-Nonato, Ismael R.; Campuzano, Julio C.; Cantoral, Alejandra J.; Contreras, Alejandra G.; Cuevas-Nasu, Lucia; De la Cruz-Gongora, Vanessa; Garcia-Guerra, Francisco A.; Dantes, Hector Gomez; de Cosio, Teresita Gonzalez; Gonzalez-Castell, Dinorah; Heredia-Pi, Ileana B.; Hernandez, Lucia; Jauregui, Alejandra; Lozano, Rafael; Medina, Catalina; Mejia-Rodriguez, Fabiola; Hernandez, Julio C. Montaez; Pedraza, Lilia S.; Pedroza, Andrea; Quezada, Amado D.; Salvo, Deborah; Sanchez, Luz Maria; Sanchez-Pimienta, Tania G.; Servan-Mori, Edson E.; Levy, Teresa Shamah; Rojo, Martha M. Tellez; Villalpando, Salvador] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
[Adelekan, Ademola] Publ Hlth Promot Alliance, Osogbo, Nigeria.
[Adofo, Koranteng] Kwame Nkrumah Univ Sci, Kumasi, Ghana.
[Adou, Arsene K.] Assoc Ivoirienne Bien Etre Familial, Abidjan, Cote Ivoire.
[Adsuar, Jose C.; Paleo, Urbano Fra] Univ Extremadura, Caceres, Spain.
[Afshin, Ashkan; Micha, Renata; Arian, Dariush Mozaff] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA USA.
[Shahraz, Saeid; Shangguan, Siyi] Tufts Univ, Tufts Med Ctr, Boston, MA USA.
[Agardh, Emilie E.] Inst Publ Hlth Sci, Stockholm, Sweden.
[Al Khabouri, Mazin J.] Minist Hlth, Muscat, Oman.
[Al Lami, Faris H.] Baghdad Coll Med, Baghdad, Iraq.
[Alam, Sayed Saidul; Naheed, Aliya] icddr b, Dhaka, Bangladesh.
[Alasfoor, Deena] Minist Hlth, Al Khuwair, Oman.
[Albittar, Mohammed I.] Independent, Damascus, Syria.
[Alegretti, Miguel A.] Univ Republica, Dept Prevent & Social Med, Montevideo, Uruguay.
[Cavalleri, Fiorella] Univ Republica, Fac Med, Montevideo, Uruguay.
[Alemu, Zewdie A.] Debre Markos Univ, Addis Ababa, Ethiopia.
[Alhabib, Samia] King Abdullah Bin Abdulaziz Univ Hosp, Riyadh, Saudi Arabia.
[Chen, Zhengming] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Gething, Pete] Univ Oxford, Dept Zool, Oxford, England.
[Ali, Raghib; Bennett, Derrick A.; Briggs, Adam D. M.; Hay, Simon I.; Rahimi, Kazem; Scarborough, Peter] Univ Oxford, Oxford, England.
[Singh, Gitanjali M.] Tufts Univ, Boston, MA USA.
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[Simard, Edgar P.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA USA.
[Ali, Mohammed K.; Cunningham, Solveig Argeseanu; Liu, Yang; Narayan, K. M. Venkat; Omer, Saad B.] Emory Univ, Atlanta, GA USA.
[Alla, Francois; Guillemin, Francis] Univ Lorraine, Nancy, France.
[Allebeck, Peter; Roy, Nobhojit] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
[Kivipelto, Miia] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Fereshtehnejad, Seyed-Mohammad] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
[Havmoeller, Rasmus; Sindi, Shireen] Karolinska Inst, Stockholm, Sweden.
[Allen, Peter J.] Minist Hlth, Belmopan, Belize.
[Alsharif, Ubai; Endres, Matthias; Nolte, Sandra; Papachristou, Christina] Charite, Berlin, Germany.
[Alvarez, Elena] Govt, Madrid, Spain.
[Alvis-Guzman, Nelson; Caicedo, Angel J. Paternina] Univ Cartagena, Cartagena De Indias, Colombia.
[Amankwaa, Adansi A.] Albany State Univ, Albany, GA 31705 USA.
[Amare, Azmeraw T.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Hoek, Hans W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Amare, Azmeraw T.] Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia.
[Yenesew, Muluken] Bahir Dar Univ, Bahir Dar, Ethiopia.
[Ameh, Emmanuel A.] Ahmadu Bello Univ, Zaria, Nigeria.
[Ameli, Omid] Boston Univ, Boston, MA USA.
[Amini, Heresh] Kurdistan Univ Med Sci, Kurdistan Environm Hlth Res Ctr, Sanandaj, Iran.
[Amini, Heresh] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
[Tanner, Marcel] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Amini, Heresh] Univ Basel, Basel, Switzerland.
[Ammar, Walid; Harb, Hilda L.] Minist Publ Hlth, Beirut, Lebanon.
[Faraon, Emerito Jose A.] Univ Philippines Manila, Coll Publ Hlth, Manila, Philippines.
[Antonio, Carl Abelardo T.] Univ Philippines Manila, Dept Hlth Policy & Adm, Manila, Philippines.
[Panelo, Carlo Irwin A.] Univ Philippines Manila, Manila, Philippines.
[Arnlov, Johan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Larsson, Anders] Uppsala Univ, Uppsala, Sweden.
[Arnlov, Johan] Dalarna Univ, Falun, Sweden.
[Arsenijevic, Valentina S. Arsic] Univ Belgrade, Inst Microbiol & Immunol, Sch Med, Belgrade, Serbia.
[Arsenijevic, Valentina S. Arsic] Univ Childrens Hosp Belgrade, Belgrade, Serbia.
[Asghar, Rana J.] South Asian Publ Hlth Forum, Islamabad, Pakistan.
[Assadi, Reza] Mashhad Univ Med Sci, Mashhad, Iran.
[Atkins, Lydia S.] Minist Hlth, Wellness Human Serv & Gender Relat, St Lucia, Qld, Australia.
[Awuah, Baffour; Laryea, Dennis O.] Komfo Anokye Teaching Hosp, Kumasi, Ghana.
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[Bahit, Maria C.] INECO Neurociencias, Rosario, Argentina.
[Bakfalouni, Talal] Minist Hlth, Damascus, Syria.
[Balakrishnan, Kalpana] Sri Ramachandra Univ, Madras, Tamil Nadu, India.
[Balalla, Shivanthi; Feigin, Valery L.] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Ao, Braden J. Te] Auckland Univ Technol, Auckland, New Zealand.
[Balu, Ravi Kumar; Dandona, Lalit; Dandona, Rakhi; Goenka, Shifalika; Kumar, G. Anil; Murthy, Kinnari S.; Reddy, K. Srinath] Publ Hlth Fdn India, Delhi, India.
[Banerjee, Amitava] Univ Birmingham, Birmingham, W Midlands, England.
[Barker-Collo, Suzanne L.] Univ Auckland, Sch Psychol, Auckland, New Zealand.
[del Pozo-Cruz, Borja] Univ Auckland, Auckland, New Zealand.
[Barregard, Lars] Univ Gothenburg, Dept Occupat & Environm Hlth, Gothenburg, Sweden.
[Barrero, Lope H.] Pontificia Univ Javeriana, Dept Ind Engn, Bogota, Colombia.
[Basto-Abreu, Ana C.; Ruvalcaba, Carolina Batis; de Castro, E. Filipa; Lopez, Nancy; Texcalac-Sangrador, Jose Luis] Natl Inst Publ Hlth, Mexico City, DF, Mexico.
[Basu, Arindam] Univ Canterbury, Sch Hlth Sci, Christchurch, New Zealand.
[Gaffikin, Lynne] Stanford Univ, Sch Med, Stanford, CA USA.
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[Basulaiman, Mohammed O.; Memish, Ziad A.] Minist Hlth, Riyadh, Saudi Arabia.
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[Bekele, Tolesa] Madawalabu Univ, Bale Robe, Ethiopia.
[Bell, Michelle L.] Yale Univ, New Haven, CT USA.
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[Bernabe, Eduardo; Wolfe, Charles D. A.] Kings Coll London, London, England.
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[Bhala, Neeraj] Queen Elizabeth Hosp, Birmingham, W Midlands, England.
[Bhala, Neeraj] Univ Otago, Capital & Coast District Hlth Board, Wellington, New Zealand.
[Derrett, Sarah] Univ Otago, Dunedin Sch Med, Dept Prevent & Social Med, Wellington, New Zealand.
[Bhalla, Ashish; Jha, Vivekanand] Postgrad Inst Med Educ & Res, Chandigarh, India.
[Bhutta, Zulfi Qar A.] Aga Khan Univ, Med Ctr, Karachi, Pakistan.
[Nisar, Muhammad I.] Aga Khan Univ, Karachi, Pakistan.
[Bikbov, Boris] AI Evdokimov Moscow State Univ Med & Dent, Moscow, Russia.
[Bikbov, Boris] Acad VI Shumakov Fed Res Ctr Transplantol & Artif, Moscow, Russia.
[Bin Abdulhak, Aref A.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Vijayakumar, Lakshmi] Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia.
[Chiang, Peggy P.] Univ Melbourne, Gen Practice & Primary Hlth Care Acad Ctr, Melbourne, Vic, Australia.
[Blore, Jed D.; Brooks, Peter M.; Colquhoun, Samantha M.; Balaji, Arjun Lakshmana; Weintraub, Robert G.; Lopez, Alan D.] Univ Melbourne, Melbourne, Vic, Australia.
[Blyth, Fiona M.] Univ Sydney, Concord, NSW, Australia.
[Meretoja, Atte] Univ Melbourne, Dept Florey, Parkville, Vic, Australia.
[Meretoja, Atte] Univ Melbourne, Dept Med, Parkville, Vic, Australia.
[Bohensky, Megan A.] Univ Melbourne, Parkville, Vic, Australia.
[Basara, Berrak Bora; Yentuer, Goekalp K.] Minist Hlth, Gen Directorate Hlth Res, Ankara, Turkey.
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[Bornstein, Natan M.] Tel Aviv Saurasky Med Ctr, Tel Aviv, Israel.
[Bose, Dipan] World Bank, Washington, DC USA.
[Boufous, Soufiane] Univ New S Wales, Transport & Rd Safety, Sydney, NSW, Australia.
[Degenhardt, Louisa] Univ New S Wales, Sydney, NSW, Australia.
[Bourne, Rupert R.] Anglia Ruskin Univ, Cambridge, England.
[Brainin, Michael] Danube Univ Krems, Krems, Austria.
[Brazinova, Alexandra; Majdan, Marek] Trnava Univ, Fac Hlth Sci & Social Work, Trnava, Slovakia.
[Breitborde, Nicholas J.] Ohio State Univ, Columbus, OH USA.
[Breitborde, Nicholas J.] Univ Arizona, Tucson, AZ USA.
[Schoettker, Ben] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany.
[Broday, David M.] Technion, Haifa, Israel.
[Lunevicius, Raimundas] Univ Liverpool, Sch Med, Liverpool, Merseyside, England.
[Bruce, Nigel G.; Dherani, Mukesh K.; Pope, Daniel] Univ Liverpool, Liverpool, Merseyside, England.
[Brugha, Traolach S.] Univ Leicester, Leicester, Leics, England.
[Brunekreef, Bert; Kromhout, Hans] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Buchbinder, Rachelle] Cabrini Inst, Monash Dept Clin Epidemiol, Melbourne, Vic, Australia.
[Buchbinder, Rachelle] Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
[Gabbe, Belinda; Gibney, Katherine B.; Thrift, Amanda G.] Monash Univ, Melbourne, Vic, Australia.
[Bui, Linh N.; Nguyen, Nhung T.] Hanoi Sch Publ Hlth, Hanoi, Vietnam.
[Bulloch, Andrew G.; Patten, Scott B.; Tonelli, Marcello; Wang, JianLi] Univ Calgary, Calgary, AB, Canada.
[Burch, Michael] Great Ormond St Hosp Sick Children, London, England.
[Burney, Peter G. J.; Foreman, Kyle J.; Jarvis, Deborah L.; Rodriguez, Alina; Rushton, Lesley; Soljak, Michael; Williams, Thomas N.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Caravanos, Jack; Nash, Denis] CUNY, Sch Publ Hlth, New York, NY USA.
[Cardenas, Rosario] Univ Autonoma Metropolitana, Mexico City, DF, Mexico.
[Cardis, Elisabeth; Nieuwenhuijsen, Mark J.; Rojas-Rueda, David] Ctr Res Environm Epidemiol, Barcelona, Spain.
[Carpenter, David O.; Leung, Ricky] SUNY Albany, Rensselaer, NY USA.
[Caso, Valeria] Univ Perugia, Stroke Unit, Perugia, Italy.
[Castaneda-Orjuela, Carlos A.] Colombian Natl Hlth Observ, Inst Nacl Salud, Bogota, Colombia.
[Castaneda-Orjuela, Carlos A.] Univ Nacl Colombia, Dept Publ Hlth, Epidemiol & Publ Hlth Evaluat Grp, Bogota, Colombia.
[Castro, Ruben E.] Univ Diego Portales, Santiago, Chile.
[Catala-Lopez, Ferran] Spanish Med & Healthcare Prod Agcy, Minist Hlth, Div Pharmacoepidemiol & Pharmacovigilance, Madrid, Spain.
[Catala-Lopez, Ferran] Univ Valencia, Dept Med, CIBERSAM, Valencia, Spain.
[Chadha, Vineet K.] Natl TB Inst, Bangalore, Karnataka, India.
[Chang, Jung-chen] Natl Taiwan Univ, Taipei, Taiwan.
[Scott, James G.] Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia.
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[Knibbs, Luke D.] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.
[Charlson, Fiona J.; Erskine, Holly E.; Ferrari, Alize J.; Gouda, Hebe N.; Veerman, Lennert J.; Whiteford, Harvey A.] Univ Queensland, Brisbane, Qld, Australia.
[Chen, Wanqing; Zou, Xiaonong] Chinese Acad Med Sci, Canc Inst, Beijing, Peoples R China.
[Wan, Xia] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing, Peoples R China.
[Chen, Honglei; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Jiang, Ying] Univ Occupat & Environm Hlth, Dept Hlth Dev, Kitakyushu, Fukuoka 807, Japan.
[Takahashi, Ken] Univ Occupat & Environm Hlth, Inst Ind Ecol Sci, Kitakyushu, Fukuoka 807, Japan.
[Chimed-Ochir, Odgerel] Univ Occupat & Environm Hlth, Dept Environm Epidemiol, Kitakyushu, Fukuoka 807, Japan.
[Chowdhury, Rajiv; Powles, John] Univ Cambridge, Cambridge, England.
[Christophi, Costas A.] Cyprus Univ Technol, Limassol, Cyprus.
[Chuang, Ting-Wu] Taipei Med Univ, Taipei, Taiwan.
[Chugh, Sumeet S.] Cedars Sinai Med Ctr, Los Angeles, CA USA.
[Cirillo, Massimo] Univ Salerno, Baronissi, Italy.
[Classen, Thomas K. D.] Univ Bielefeld, Dept Environm & Hlth, Bielefeld, Germany.
[Kraemer, Alexander; Tobollik, Myriam] Univ Bielefeld, Sch Publ Hlth, Bielefeld, Germany.
[Colomar, Mercedes] UNICEM, Montevideo, Uruguay.
[Colquhoun, Samantha M.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Cooper, Leslie T.] Mayo Clin, Rochester, MN USA.
[Coresh, Josef; Matsushita, Kunihiro] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA.
[Tran, Bach X.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Courville, Karen J.] Hosp Dr Gustavo N Collado, Chitre, Panama.
[Criqui, Michael H.; Stein, Murray B.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Damsere-Derry, James] Bldg & Rd Res Inst, Kumasi, Ghana.
[Danawi, Hadi; Refaat, Amany H.] Walden Univ, Minneapolis, MN USA.
[Dargan, Paul I.] Guys & St Thomas NHS Fdn Trust, London, England.
[Davis, Adrian; Fay, Derek F. J.; Schmidt, Juergen C.] Publ Hlth England, London, England.
[Davitoiu, Dragos V.] Univ Med & Pharm Bucharest, Bucharest, Romania.
[Dayama, Anand] Jacobi Med Ctr, Dept Surg, Atlanta, GA USA.
[De Leo, Diego] Griffith Univ, Brisbane, Qld, Australia.
[de Lima, Graca] Local Hlth Unit Matosinhos, Matosinhos, Portugal.
[de Lima, Graca; Machado, Vasco M. P.] Northern Reg Hlth Adm, Dept Publ Hlth, Oporto, Portugal.
[Nogueira, Jose R.; Teixeira, Carolina M.] Northern Reg Hlth Adm, Oporto, Portugal.
[Dellavalle, Robert P.] Eastern Colorado Healthcare Syst, US Dept Vet Affairs, Denver, CO USA.
[Deribe, Kebede] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
[Deribe, Kebede] Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia.
[Mekonnen, Wubegzier] Univ Addis Ababa, Addis Ababa, Ethiopia.
[Derrett, Sarah] Massey Univ, Coll Hlth, Sch Publ Hlth, Palmerston North, New Zealand.
[Jarlais, Don C. Des] Mt Sinai Beth Israel, New York, NY USA.
[Jarlais, Don C. Des] Icahn Sch Med Mt Sinai, New York, NY USA.
[Dessalegn, Muluken] Africa Med & Res Fdn Ethiopia, Addis Ababa, Ethiopia.
[deVeber, Gabrielle A.] Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.
[Lindsay, M. Patrice] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Hu, Howard] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Devries, Karen M.; Larson, Heidi J.; Mckee, Martin; Pearce, Neil; Stoeckl, Heidi; Tillmann, Taavi; Watts, Charlotte H.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
[Dharmaratne, Samath D.] Univ Peradeniya, Peradeniya, Sri Lanka.
[Dokova, Klara] Med Univ Varna, Fac Publ Hlth, Dept Social Med, Varna, Bulgaria.
[Dorsey, E. Ray] Univ Rochester, Med Ctr, Rochester, NY USA.
[Driscoll, Tim R.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW, Australia.
[Marks, Guy B.] Univ Sydney, Woolcock Inst Med Res, Sydney, NSW, Australia.
[Leigh, James] Univ Sydney, Sydney, NSW 2006, Australia.
[Duan, Leilei; Li, Yichong; Liu, Shiwei; Ma, Jixiang; Wang, Linhong; Ye, Pengpeng; Zhou, Maigeng] Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China.
[Durrani, Adnan M.] Natl Inst Hlth, Montgomery Village, MD USA.
[Elshrek, Yousef M.] Univ Tripoli, Fac Agr, Dept Food Sci, Tripoli, Libya.
[Ermakov, Sergey P.] Russian Acad Sci, Inst Social & Econ Studies Populat, Moscow, Russia.
[Ermakov, Sergey P.; Soshnikov, Sergey] Minist Hlth Russian Federat, Fed Res Inst Hlth Org & Informat, Moscow, Russia.
[Liang, Xiaofeng] China CDC, Beijing, Peoples R China.
[Eshrati, Babak] Arak Univ Med Sci & Hlth Affairs, Arak, Iran.
[Farzadfar, Farshad] Univ Tehran Med Sci, NonCommunicable Dis Res Ctr, Tehran, Iran.
[Heydarpour, Pouria; Sahraian, Mohammad Ali] Univ Tehran Med Sci, Multiple Sclerosis Res Ctr, Neurosci Inst, Tehran, Iran.
[Sepanlou, Sadaf G.] Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
[Rahimi-Movaghar, Vafa] Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran.
[Ferri, Cleusa P.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Foigt, Nataliya] Acad Med Sci, Inst Gerontol, Kiev, Ukraine.
[Franklin, Richard C.] James Cook Univ, Townsville, Qld, Australia.
[Gamkrelidze, Amiran; Khonelidze, Irma; Sturua, Lela] Natl Ctr Dis Control & Publ Hlth, Tbilisi, Rep of Georgia.
[Gankpe, Fortune G.] Leras Afrique, Cotonou, Benin.
[Gankpe, Fortune G.] CHU Hassan II, Fes, Morocco.
[Gasana, Evariste] Rwanda Biomed Ctr, TB & Other Respir Dis Div, Kigali, Rwanda.
[Sabin, Nsanzimana] Rwanda Biomed Ctr, Kigali, Rwanda.
[Geleijnse, Johanna M.] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
[Gessner, Bradford D.] Agence Med Prevent, Paris, France.
[Gibney, Katherine B.] Melbourne Hlth, Parkville, Vic, Australia.
[Gillum, Richard F.] Howard Univ, Washington, DC USA.
[Ginawi, Ibrahim A. M.] Univ Hail, Coll Med, Hailsham, E Sussex, England.
[Giroud, Maurice] Univ Hosp Dijon, Dijon, France.
[Giussani, Giorgia] IRCCS Mario Negri Inst Pharmacol Res, Milan, Italy.
[Goginashvili, Ketevan] Minist Labour Hlth & Social Affairs, Tbilisi, Rep of Georgia.
[Esteghamati, Alireza; Hafezi-Nejad, Nima; Sheikhbahaei, Sara] Univ Tehran Med Sci, Endocrinol & Metab Res Inst, Tehran, Iran.
[Gona, Philimon] Univ Massachusetts Boston, Boston, MA USA.
[Goto, Atsushi] Tokyo Womens Med Univ, Dept Publ Hlth, Tokyo, Japan.
[Guerrant, Richard L.] Univ Virginia, Sch Med, Charlottesville, VA USA.
[Terkawi, Abdullah S.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.
[Gugnani, Harish C.] St James Sch Med, Kralendijk, Netherlands.
[Gunnell, David] Univ Bristol, Bristol, Avon, England.
[Gupta, Rahul] West Virginia Bur Publ Hlth, Charleston, WV USA.
[Gupta, Rajeev] Fortis Escorts Hosp, Jaipur, Rajasthan, India.
[Hagstromer, Maria] Karolinska Inst, Huddinge, Sweden.
[Halasa, Yara A.; Idrisov, Bulat T.] Brandeis Univ, Waltham, MA USA.
[Hamadeh, Randah R.] Arabian Gulf Univ, Manama, Bahrain.
[Hammami, Mouhanad] Wayne Cty Dept Hlth & Human Serv, Detroit, MI USA.
[Hankey, Graeme J.] Univ Western Australia, Perth, WA, Australia.
[Hao, Yuantao] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China.
[Zheng, Yingfeng] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China.
[Haregu, Tilahun Nigatu; van de Vijver, Steven] African Populat & Hlth Res Ctr, Nairobi, Kenya.
[Haro, Josep Maria] CIBERSAM, Parc Sanitari St Joan de Deu, Sant Boi De Llobregat, Spain.
[Haro, Josep Maria] Univ Barcelona, Barcelona, Spain.
[Hedayati, Mohammad T.] Mazandaran Univ Med Sci, Sari, Mazandaran, Iran.
[Hijar, Martha] Fdn Entornos AC, Cuernavaca, Morelos, Mexico.
[Hoek, Hans W.] Columbia Univ, Dept Epidemiol, New York, NY USA.
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[Hosgood, H. Dean] Albert Einstein Coll Med, Bronx, NY USA.
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[Hu, Guoqing] Cent S Univ, Changsha, Peoples R China.
[Huang, Cheng] George Washington Univ, Washington, DC USA.
[Hubbell, Bryan J.] US EPA, Res Triangle Pk, NC USA.
[Huiart, Laetitia; Racape, Lionel] CHU La Reunion, Saint Denis, France.
[Husseini, Abdullatif] Qatar Univ, Doha, Qatar.
[Iburg, Kim M.] Aarhus Univ, Aarhus, Denmark.
[Ikeda, Nayu] Natl Inst Hlth Nutr, Tokyo, Japan.
[Innos, Kaire] Natl Inst Hlth Dev, Tallinn, Estonia.
[Inoue, Manami] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Kawakami, Norito] Univ Tokyo, Sch Publ Hlth, Tokyo, Japan.
[Shibuya, Kenji] Univ Tokyo, Tokyo, Japan.
[Islami, Farhad] Amer Canc Soc, New York, NY USA.
[Jacobsen, Kathryn H.] George Mason Univ, Fairfax, VA USA.
[Jansen, Henrica A.] UNFPA Asia & Pacific Reg Off, Bangkok, Thailand.
[Jassal, Simerjot K.] Univ Calif San Diego, San Diego, CA USA.
[Jayaraman, Sudha] Virginia Commonwealth Univ, Richmond, VA USA.
[Jeemon, Panniyammakal; Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India.
[Jiang, Fan] Shanghai Childrens Med Ctr, Tianjin, Peoples R China.
[Jiang, Guohong] Tianjin Ctr Dis Control & Prevent, Tianjin, Peoples R China.
[Phillips, Michael R.] Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China.
[Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
[Juel, Knud] Natl Inst Publ Hlth, Copenhagen, Denmark.
[She, Jun] Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China.
[Kan, Haidong] Fudan Univ, Shanghai, Peoples R China.
[Roseline, Sidibe S. Kany] MARIKANI, Bamako, Mali.
[Karam, Nadim E.] Univ Balamand, Beirut, Lebanon.
[Karch, Andre] Helmholtz Ctr Infect Res, Dept Epidemiol, Braunschweig, Germany.
[Karch, Andre] German Ctr Infect Res, Hannover Braunschweig Site, Braunschweig, Germany.
[Karema, Corine K.] Minist Hlth, Malaria & Other Parasit Dis Div, Kigali City, Rwanda.
[Karthikeyan, Ganesan; Paul, Vinod K.; Satpathy, Maheswar; Tandon, Nikhil] All India Inst Med Sci, New Delhi, India.
[Kaul, Anil] Oklahoma State Univ, Tulsa, OK USA.
[Kazi, Dhruv S.] Univ Calif San Francisco, San Francisco, CA USA.
[Kemp, Andrew H.; Lotufo, Paulo A.; Polanczyk, Guilherme V.; Santos, Itamar S.] Univ Sao Paulo, Sao Paulo, Brazil.
[Kemp, Andrew H.] Univ Sydney, Camperdown, NSW, Australia.
[Kengne, Andre P.; Matzopoulos, Richard; Parry, Charles D.] South African Med Res Council, Cape Town, South Africa.
[Sliwa, Karen] Univ Cape Town, Fac Hlth Sci, Hatter Inst Cardiovasc Res Africa, Cape Town, South Africa.
[Matzopoulos, Richard] Univ Cape Town, Sch Publ Hlth & Family Med, Cape Town, South Africa.
[Kengne, Andre P.; Mayosi, Bongani M.; Stein, Dan J.] Univ Cape Town, Cape Town, South Africa.
[Keren, Andre] Hadassah Kerem Univ Hosp, Cardiol, Jerusalem, Israel.
[Khader, Yousef S.] Jordan Univ Sci & Technol, Irbid, Jordan.
[Khalifa, Shams Eldin Ali Hassan] Supreme Council Hlth, Doha, Qatar.
[Khan, Ejaz A.] Hlth Serv Acad, Islamabad, Pakistan.
[Khan, Ejaz A.] Expanded Programme Immunizat, Islamabad, Pakistan.
[Khang, Young-Ho] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Kieling, Christian] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.
[Kim, Daniel] Northeastern Univ, Boston, MA USA.
[Kim, Sungroul] Soonchunhyang Univ, Seoul, South Korea.
[Kim, Yunjin] Southern Univ Coll, Johor Baharu, Malaysia.
[Kimokoti, Ruth W.] Simmons Coll, Boston, MA USA.
[Kinfu, Yohannes] Univ Canberra, Canberra, ACT, Australia.
[Kissela, Brett M.] Univ Cincinnati, Cincinnati, OH USA.
[Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Suita, Osaka, Japan.
[Kosen, Soewarta] Minist Hlth Indonesia, NIHRD, Ctr Community Empowerment Hlth Policy & Human, Jakarta, Indonesia.
[Warouw, Tati S.] Minist Hlth Indonesia, NIHRD, Jakarta, Indonesia.
[Kravchenko, Michael] Res Ctr Neurol, Moscow, Russia.
[Krishnaswami, Sanjay] Oregon Hlth & Sci Univ, Portland, OR USA.
[Defo, Barthelemy Kuate] Univ Montreal, Montreal, PQ, Canada.
[Kuipers, Ernst J.] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands.
[Kulkarni, Chanda] Rajrajeswari Med Coll & Hosp, Bangalore, Karnataka, India.
[Kulkarni, Veena S.] Arkansas State Univ, State Univ, AR USA.
[Kwan, Gene F.] Boston Med Ctr, Boston, MA USA.
[Lai, Taavi] Fourth View Consulting, Tallinn, Estonia.
[Lalloo, Ratilal] Griffith Univ, Sch Dent & Oral Hlth, Gold Coast, Qld, Australia.
[Lalloo, Ratilal] Univ Adelaide, Sch Dent, Australian Res Ctr Populat Oral Hlth, Adelaide, SA, Australia.
[Lallukka, Tea] Finnish Inst Occupat Hlth, Disabil Prevent Res Ctr, Helsinki, Finland.
[Shiri, Rahman] Finnish Inst Occupat Hlth, Helsinki, Finland.
[Lallukka, Tea] Univ Helsinki, Fac Med, Helsinki, Finland.
[Lam, Hilton] NIH, Inst Hlth Policy & Dev Studies, Manila, Philippines.
[Lan, Qing] NCI, Rockville, MD USA.
[Lansingh, Van C.] Help Me See Inc, New York, NY USA.
[Lansingh, Van C.] Inst Mexicano Oftalmol, Queretaro, Mexico.
[Lavados, Pablo M.] Univ Desarrollo, Serv Neurol, Clin Alemana, Santiago, Chile.
[Lawrynowicz, Alicia E.] Inst Nacl Epidemiol Dr Juan H Jara, Mar Del Plata, Buenos Aires, Argentina.
[Leasher, Janet L.] Nova SE Univ, Coll Optometry, Ft Lauderdale, FL USA.
[Lee, Jong-Tae; Yoon, Seok-Jun] Korea Univ, Seoul, South Korea.
[Levi, Miriam] Tuscany Reg Ctr Occupat Injuries & Dis, Florence, Italy.
[Li, Yichong] Anolinx LLC, Salt Lake City, UT USA.
[Liang, Juan; Wang, Yanping; Zhu, Jun] Sichuan Univ, West China Univ Hosp 2, Natl Off Maternal & Child Hlth Surveillance, Chengdu, Peoples R China.
[Lindsay, M. Patrice] Heart & Stroke Fdn Canada, Ottawa, ON, Canada.
[Lipshultz, Steven E.] Wayne State Univ, Detroit, MI USA.
[Lloyd, Belinda K.] Monash Univ, Eastern Hlth Clin Sch, Fitzroy, Vic, Australia.
[Lloyd, Belinda K.; Room, Robin] Eastern Hlth, Turning Point Alcohol & Drug Ctr, Fitzroy, Vic, Australia.
[Logroscino, Giancarlo] Univ Bari, Bari, Italy.
[Lortet-Tieulent, Joannie] Amer Canc Soc, Atlanta, GA USA.
[Lunevicius, Raimundas] Aintree Univ Hosp NHS Fdn Trust, Liverpool, Merseyside, England.
[Ma, Stefan; Phua, Hwee Pin] Minist Hlth Singapore, Singapore, Singapore.
[Ma, Stefan] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[Magis-Rodriguez, Carlos] Secretaria Salud Mexico, Ctr Nacl Prevenc & Control VIH SIDA, Mexico City, DF, Mexico.
[Mahdi, Abbas A.] King Georges Med Univ, Lucknow, Uttar Pradesh, India.
[Malekzadeh, Reza] Shariati Hosp, Digest Dis Reseach Inst, Tehran, Iran.
[Malekzadeh, Reza] Shiraz Univ Med Sci, Shiraz, Iran.
[Mangalam, Srikanth] Tech Stand & Safety Author, Toronto, ON, Canada.
[Masiye, Felix] Univ Zambia, Lusaka, Zambia.
[Marape, Marape] Botswana Baylor Childrens Clin Ctr Excellence, Gaborone, Botswana.
[Marcenes, Wagner] Queen Mary Univ London, London, England.
[Meaney, Peter A.] Univ Penn, Pereleman Sch Med, Philadelphia, PA USA.
[Martin, Randall V.] Dalhousie Univ, Halifax, NS, Canada.
[Marzan, Melvin B.] Univ East Ramon Magsaysay Memorial, Med Ctr, Quezon City, Philippines.
[Mashal, Mohammad T.] Minist Publ Hlth, Kabul, Afghanistan.
[Mason-Jones, Amanda J.] Univ York, York, N Yorkshire, England.
[Mazorodze, Tasara T.] Automot Ind Dev Ctr Eastern Cape, Port Elizabeth, South Africa.
[Mckay, Abigail C.] EmergentCorp, Belize City, Belize.
[Meaney, Peter A.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Mehndiratta, Man Mohan] Janakpuri Superspecialty Hosp, New Delhi, India.
[Meltzer, Michele] Thomas Jefferson Univ, Philadelphia, PA USA.
[Mendoza, Walter] United Nations Populat Fund, Lima, Peru.
[Meretoja, Atte] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
[Mhimbira, Francis Apolinary] Ifakara Hlth Inst, Bagamoyo, Tanzania.
[Miller, Ted R.] Pacific Inst Res & Evaluat, Calverton, MD USA.
[Miller, Ted R.] Curtin Univ, Ctr Populat Hlth, Perth, WA, Australia.
[Mills, Edward J.] Univ Ottawa, Ottawa, ON, Canada.
[Margolis, David J.; Silberberg, Donald H.] Univ Penn, Philadelphia, PA USA.
[Mishra, Santosh] SNDT Womens Univ, Populat Educ Resource Ctr, Dept Continuing & Adult Educ & Extens, Bombay, Maharashtra, India.
[Ibrahim, Norlinah Mohamed] Univ Kebangsaan Malaysia, Med Ctr, Dept Med, Bandar Tun Razak, Malaysia.
[Mohammad, Karzan A.] Univ Salahaddin, Erbil, Iraq.
[Mola, Glen L.] Univ Papua New Guinea, Boroko, Papua N Guinea.
[Monasta, Lorenzo; Montico, Marcella; Ronfani, Luca] Inst Maternal & Child Hlth, IRCCS Burlo Garofolo, Trieste, Italy.
[Moore, Ami R.] Univ N Texas, Denton, TX USA.
[Morawska, Lidia] Queensland Univ Technol, Int Lab Air Qual & Hlth, Brisbane, Qld, Australia.
[Norman, Rosana E.] Queensland Univ Technol, Inst Hlth Biomed Innovat, Brisbane, Qld, Australia.
[Mori, Rintaro] Natl Ctr Child Hlth & Dev, Setagaya Ku, Tokyo, Japan.
[Tsilimbaris, Miltiadis] Univ Crete, Dept Med, Iraklion, Greece.
[Moschandreas, Joanna] Univ Crete, Iraklion, Greece.
[Moturi, Wilkister N.] Egerton Univ, Egerton, Kenya.
[Werdecker, Andrea] Competence Ctr Mortal Follow Up German Natl Cohor, Heidelberg, Germany.
[Mueller, Ulrich O.; Westerman, Ronny] Fed Inst Populat Res, Wiesbaden, Germany.
[Mukaigawara, Mitsuru] Okinawa Chubu Hosp, Okinawa, Japan.
[Nahas, Ziad] Amer Univ Beirut, Med Ctr, Beirut, Lebanon.
[Naidoo, Kovin S.] Univ KwaZulu Natal, Durban, South Africa.
[Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Bergamo, Italy.
[Nand, Devina] Minist Hlth Fiji, Suva, Fiji.
[Nangia, Vinay] Suraj Eye Inst, Nagpur, Maharashtra, India.
[Neal, Bruce] George Inst Global Hlth, Sydney, NSW, Australia.
[Nejjari, Chakib] Fac Med, Fes, Morocco.
[Neupane, Sudan P.] Univ Oslo, Oslo, Norway.
[Ngalesoni, Frida N.] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania.
[Ngirabega, Jean de Dieu] East African Community Hlth Res Commiss, Kigali, Rwanda.
[Nolla, Joan M.] Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain.
[Nolte, Sandra] Deakin Univ, Melbourne, Vic, Australia.
[Vollset, Stein Emil] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Norheim, Ole F.] Univ Bergen, Bergen, Norway.
[Norrving, Bo] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Nyakarahuka, Luke] Makerere Univ, Kampala, Uganda.
[Oh, In-Hwan] Kyung Hee Univ, Seoul, South Korea.
[Ohkubo, Takayoshi] Teikyo Univ, Sch Med, Tokyo, Japan.
[Olusanya, Bolajoko O.] Ctr Hlth Start Initiat, Ikoyi, Nigeria.
[Opio, John Nelson] Lira Municipal Council, Lira Dist Local Govt, Lira, Uganda.
[Pagcatipunan, Rodolfo S., Jr.] United Lab Inc, Mandaluyong City, Philippines.
[Pandian, Jeyaraj D.] Christian Med Coll Ludhiana, Ludhiana, Punjab, India.
[Park, Eun-Kee] Kosin Univ, Coll Med, Busan, South Korea.
[Stein, Dan J.] South African Med Res Council, Unit Anxiety & Stress Disorders, Cape Town, South Africa.
[Parry, Charles D.] South African Med Res Council, Cape Town, South Africa.
[Parry, Charles D.; Seedat, Soraya] Univ Stellenbosch, Cape Town, South Africa.
[Stokic, Ljiljana Pejin] Econ Inst, Belgrade, Serbia.
[Pereira, David M.] Univ Porto, REQUIMTE, Fac Farm, Dept Quim,Lab Farmacognosia, Oporto, Portugal.
[Perez-Padilla, Rogelio] Natl Inst Resp Dis, Mexico City, DF, Mexico.
[Perez-Ruiz, Fernando] Hosp Univ Cruces, OSI EE Cruces, Baracaldo, Spain.
[Perez-Ruiz, Fernando] Biocruces Hlth Res Inst, Baracaldo, Spain.
[Perico, Norberto; Remuzzi, Giuseppe; Trillini, Matias] IRCCS Mario Negri Inst Pharmacol Res, Bergamo, Italy.
[Perry, Samuel A. L.] Washington State Dept Hlth, Kent, WA USA.
[Pervaiz, Aslam] Postgrad Med Inst, Lahore, Pakistan.
[Pesudovs, Konrad] Flinders Univ S Australia, Adelaide, SA, Australia.
[Peterson, Carrie B.] Aalborg Univ, Aalborg Esst, Denmark.
[Petzold, Max] Hlth Metr Unit, Gothenburg, Sweden.
[Petzold, Max] Univ Witwatersrand, Johannesburg, South Africa.
[Phillips, Michael R.] Emory Univ, Atlanta, GA USA.
[Plass, Dietrich] Fed Environm Agcy, Sect Exposure Assessment & Environm Hlth Indicato, Berlin, Germany.
[Poenaru, Dan] McGill Univ, Montreal Childrens Hosp, Montreal, PQ, Canada.
[Poenaru, Dan] MyungSung Med Coll, Addis Ababa, Ethiopia.
[Pond, Constance D.] Univ Newcastle, Callaghan, NSW 2308, Australia.
[Pope, C. Arden] Brigham Young Univ, Provo, UT USA.
[Popova, Svetlana; Rehm, Juergen] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Prasad, Noela M.] Fred Hollows Fdn, Sydney, NSW, Australia.
[Qato, Dima M.] Univ Illinois, Coll Pharm, Chicago, IL USA.
[Rafay, Anwar; Rana, Saleem M.] Contech Int Hlth Consultants, Lahore, Pakistan.
[Rafay, Anwar; Rana, Saleem M.] Contech Sch Publ Hlth, Lahore, Pakistan.
[Rahman, Sajjad Ur] Hamad Med Corp, Doha, Qatar.
[Raju, Murugesan] Univ Missouri, Columbia, MO USA.
[Rakovac, Ivo] WHO Reg Off Europe, Copenhagen, Denmark.
[Rao, Mayuree] Brown Univ, Warren Alpert Med Sch, Providence, RI USA.
[Razavi, Homie] Ctr Dis Anal, Louisville, CO USA.
[Refaat, Amany H.] Suez Canal Univ, Ismailia, Egypt.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
[Velasquez-Melendez, Gustavo] Univ Fed Minas Gerais, Escola Enfermagem, Belo Horizonte, MG, Brazil.
[Riccio, Patricia M.; Sposato, Luciano A.] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON, Canada.
[Riederer, Anne] George Washington Univ, Washington, DC USA.
[Roca, Anna] MRC Unit, Fajara, Gambia.
[Rodriguez, Alina] Mid Sweden Univ, Stersund, Sweden.
[Romieu, Isabelle; Straif, Kurt] WHO, IARC, Lyon, France.
[Roy, Nobhojit] HBNI Univ, BARC Hosp, Bombay, Maharashtra, India.
[Ruhago, George M.; Sunguya, Bruno F.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Miami, FL USA.
[Saha, Sukanta] Pk Ctr Mental Hlth, Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
[Sahathevan, Ramesh] Univ Kebangsaan Malaysia, Med Ctr, Kuala Lumpur, Malaysia.
[Sahathevan, Ramesh] Calvary Healthcare Bruce, Canberra, ACT, Australia.
[Sanabria, Juan R.] Case Western Reserve Univ, Cleveland, OH USA.
[Sanabria, Juan R.] RFU Chicago Med Sch, Canc Treatment Ctr Amer, N Chicago, IL USA.
[Sanchez-Riera, Lidia] Univ Zurich, Ctr Ageing & Mobil, Zurich, Switzerland.
[Sanchez-Riera, Lidia] City Hosp Waid, Zurich, Switzerland.
[Sapkota, Amir] Univ Maryland, Sch Publ Hlth, College Pk, MD USA.
[Saunders, James E.] Dartmouth Coll, Dartmouth Hitchcock Med Ctr, Lebanon, NH USA.
[Soneji, Samir] Dartmouth Coll, Lebanon, NH USA.
[Sawhney, Monika] Marshall Univ, Huntington, WV USA.
[Saylan, Mete I.] Novartis Turkey, Istanbul, Turkey.
[Schneider, Ione J. C.] Univ Fed Santa Catarina, Florianopolis, SC, Brazil.
[Schwebel, David C.; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Serdar, Berrin] Univ Colorado, Aurora, CO USA.
[Shaddick, Gavin] Univ Bath, Bath BA2 7AY, Avon, England.
[Shangguan, Siyi] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan.
[Shiri, Rahman] Univ Tampere, Sch Hlth Sci, Tampere, Finland.
[Shishani, Kawkab] Washington State Univ, Spokane, WA USA.
[Shiue, Ivy] Northumbria Univ, Hlth & Life Sci, Newcastle Upon Tyne, Tyne & Wear, England.
[Shiue, Ivy] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[Sigfusdottir, Inga D.] Reykjavik Univ, Reykjavik, Iceland.
[Singh, Abhishek] Int Inst Populat Sci, Bombay, Maharashtra, India.
[Soreide, Kjetil] Stavanger Univ Hosp, Stavanger, Norway.
[Sreeramareddy, Chandrashekhar T.] Univ Tunku Abdul Rahman, Fac Med & Hlth Sci, Kajang, Cheras, Malaysia.
[Stapelberg, Nicolas J. C.] Griffith Univ, Southport, Qld, Australia.
[Stathopoulou, Vasiliki] Attikon Univ Hosp, Athens, Greece.
[Steckling, Nadine] Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany.
[Stroumpoulis, Konstantinos] Alexandra Gen Hosp Athens, Athens, Greece.
[Stroumpoulis, Konstantinos] Ctr Hosp Publ Cotentin, Cherbourg, France.
[Swaminathan, Soumya] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Swaroop, Mamta; Yano, Yuichiro] Northwestern Univ, Chicago, IL USA.
[Sykes, Bryan L.] Univ Calif Irvine, Irvine, CA USA.
[Tabb, Karen M.] Univ Illinois, Champaign, IL USA.
[Talongwa, Roberto T.] Minist Hlth, MINSANTE, Yaounde, Cameroon.
[Tanne, David] Chaim Sheba Med Ctr, Tel Hashomer, Israel.
[Tanne, David] Tel Aviv Univ, Tel Hashomer, Israel.
[Tavakkoli, Mohammad] Westchester Med Ctr, Valhalla, NY USA.
[Terkawi, Abdullah S.] Outcomes Res Consortium, Cleveland, OH USA.
[Terkawi, Abdullah S.] King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.
[Thackway, Sarah V.] New South Wales Hlth, Sydney, NSW, Australia.
[Thurston, George D.] NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY USA.
[Topouzis, Fotis] Aristotle Univ Thessaloniki, Thessaloniki, Greece.
[Towbin, Jeff Rey A.] Bonheur Childrens Hosp, Memphis, TN USA.
[Towbin, Jeff Rey A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN USA.
[Toyoshima, Hideaki] Anjo Kosei Hosp, Hlth Care Ctr, Anjo City, Japan.
[Traebert, Jeff Erson] Univ Southern Santa Catarina, Palhoca, Brazil.
[Tran, Bach X.] Hanoi Med Univ, Hanoi, Vietnam.
[Trujillo, Ulises] Serv Canario Salud, Tenerife, Spain.
[Dimbuene, Zacharie Tsala] Univ Kinshasa, Fac Econ & Management, Dept Populat Sci & Dev, Kinshasa, Zaire.
[Tuzcu, Emin Murat] Cleveland Clin, Cleveland, OH USA.
[Uchendu, Uche S.] Dept Vet Affairs, Washington, DC USA.
[Ukwaja, Kingsley N.] Fed Teaching Hosp, Dept Internal Med, Abakaliki, Nigeria.
[Van Dingenen, Rita] European Commiss, Joint Res Ctr, Ispra, Italy.
[Van Gool, Coen H.] Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands.
[Van Os, Jim] Maastricht Univ, Med Ctr, Maastricht, Netherlands.
[Vasankari, Tommi J.] UKK Inst Hlth Promot Res, Tampere, Finland.
[Vasconcelos, Ana Maria N.] Univ Brasilia, Brasilia, DF, Brazil.
[Vijayakumar, Lakshmi] VHS SNEHA, Madras, Tamil Nadu, India.
[Violante, Francesco S.] Univ Bologna, Bologna, Italy.
[Vlassov, Vasiliy Victorovich] Higher Sch Econ, Moscow, Russia.
[Wagner, Gregory R.] Natl Inst Occupat Safety & Hlth, Washington, DC USA.
[Waller, Stephen G.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA.
[Wallin, Mitchell T.] Georgetown Univ, Dept Neurol, Arlington, VA USA.
[Wallin, Mitchell T.] VA Med Ctr, Washington, DC USA.
[Wang, Wenzhi] Beijing Neurosurg Inst, Beijing, Peoples R China.
[Weintraub, Robert G.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Wessells, K. Ryan] Univ Calif Davis, Davis, CA USA.
[Westerman, Ronny] German Natl Cohort Consortium, Heidelberg, Germany.
[Wilkinson, James D.] Wayne State Univ, Detroit, MI USA.
[Williams, Hywel C.] Univ Nottingham, Nottingham, England.
[Woldeyohannes, Solomon M.] Univ Gondar, Inst Publ Hlth, Gondar, Ethiopia.
[Wong, John Q.] Manila Univ, Ateneo Sch Med & Publ Hlth, Pasig, Philippines.
[Woolf, Anthony D.] Royal Cornwall Hosp, Truro, Cornwall, England.
[Xu, Gelin] Nanjing Univ, Sch Med, Jinling Hosp, Nanjing, Peoples R China.
[Yan, Lijing L.] Duke Kunshan Univ, Kunshan, Peoples R China.
[Yang, Gonghuan] Peking Union Med Coll, Beijing, Peoples R China.
[Yano, Yuichiro] Jichi Med Sch, Tochigi, Japan.
[Yip, Paul] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Yonemoto, Naohiro] Natl Ctr Neurol & Psychiat, Kodaira, Tokyo, Japan.
[Younis, Mustafa Z.] Jackson State Univ, Jackson, MS USA.
[Younoussi, Zourkaleini] Univ Niamey, Niamey, Niger.
[Yu, Chuanhua] Sch Publ Hlth, Dept Epidemiol & Biostat, Wuhan, Peoples R China.
[Yu, Chuanhua] Wuhan Univ, Global Hlth Inst, Wuhan, Peoples R China.
[Zaki, Maysaa E.] Mansoura Fac Med, Mansoura, Egypt.
[Zhao, Yong] Chongqing Med Univ, Chongqing, Peoples R China.
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RP Murray, CJ (reprint author), Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
EM cjlm@uw.edu
RI Balakrishnan, Kalpana/B-6653-2015; Davis, Adrian/E-6022-2015;
Nieuwenhuijsen, Mark/C-3914-2017; Alsharif, Ubai/C-6527-2017; Amini,
Heresh/B-3076-2010; Lotufo, Paulo/A-9843-2008; Karch, Andre/D-6973-2017;
Hedayati, Mohammad T./E-2304-2017; Scott, James/D-5900-2012; Franklin,
Richard/H-1731-2012; Giussani, Giorgia/E-8057-2017; Ermakov,
Sergey/G-1709-2016; Pereira, David/M-9286-2013; Parry,
Charles/A-2906-2009; Kravchenko, Michael/B-2596-2012; Nolte,
Sandra/B-7498-2008; Stein, Dan/A-1752-2008; Tonelli,
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Elisabeth/C-3904-2017; Sepanlou, Sadaf/H-9343-2016; Ferri,
Cleusa/B-2922-2010; Devries, Karen/K-1083-2016; Jacobsen,
Kathryn/B-5857-2008; LOGROSCINO, GIANCARLO/K-5148-2016; wang, YA
XING/K-9671-2016; Ribeiro, Antonio/C-2707-2009; Hay, Simon/F-8967-2015;
Naldi, Luigi/K-6343-2016; Thrift, Amanda/I-6251-2012; Weiderpass,
Elisabete/M-4029-2016; Dokova, Klara/N-2448-2016; Montico,
Marcella/B-5290-2013; Fra.Paleo, Urbano/B-8088-2016; Monasta,
Lorenzo/B-1388-2012; Haro, Josep Maria/D-1423-2011; Degenhardt,
Louisa/D-4515-2012; Martin, Randall/C-1205-2014; Hankey, Graeme
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Fiona/F-5290-2011; Patten, Scott/B-4434-2011
OI Catala-Lopez, Ferran/0000-0002-3833-9312; Broday,
David/0000-0002-6525-3979; Bernabe, Eduardo/0000-0002-1858-3713;
Norheim, Ole F./0000-0002-5748-5956; London,
Stephanie/0000-0003-4911-5290; Hoek, Hans/0000-0001-6353-5465;
Moradi-Lakeh, Maziar/0000-0001-7381-5305; Castaneda-Orjuela,
Carlos/0000-0002-8735-6223; Aburto, Tania/0000-0002-6932-9344; Aboyans,
Victor/0000-0002-0322-9818; Gouda, Hebe/0000-0002-5709-4509; Chen,
Honglei/0000-0003-3446-7779; Perez-Ruiz, Fernando/0000-0002-5268-1894;
Kissela, Brett/0000-0002-9773-4013; Sindi, Shireen/0000-0002-3786-0552;
Gething, Peter/0000-0001-6759-5449; Husseini,
Abdullatif/0000-0001-8767-5956; Benjet, Corina/0000-0002-4569-6094;
Gabbe, Belinda/0000-0001-7096-7688; Prabhakaran,
Dorairaj/0000-0002-3172-834X; Neupane, Sudan Prasad/0000-0002-7389-4178;
Khang, Young-Ho/0000-0002-9585-8266; Kemp, Andrew/0000-0003-1146-3791;
Erskine, Holly/0000-0003-3119-9211; Vlassov,
Vasiliy/0000-0001-5203-549X; Soreide, Kjetil/0000-0001-7594-4354;
Santos, Itamar/0000-0003-3212-8466; Villalpando,
Salvador/0000-0001-6429-3816; Borges, Guilherme/0000-0002-3269-0507;
Miller, Ted/0000-0002-0958-2639; Giussani, Giorgia/0000-0003-2460-3095;
Leung, Ricky/0000-0002-2852-6771; Kieling,
Christian/0000-0001-7691-4149; Sreeramareddy,
Chandrashekhar/0000-0002-5693-7631; Xu, Gelin/0000-0002-6194-0341; Goto,
Atsushi/0000-0003-0669-654X; Soshnikov, Sergey/0000-0002-6983-7066;
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Newton, Charles/0000-0002-6999-5507; Mhimbira,
Francis/0000-0001-8989-6832; Olusanya, Bolajoko/0000-0002-3826-0583;
Heredia-Pi, Ileana Beatriz/0000-0002-9998-9239; Goenka,
Shifalika/0000-0001-6993-2883; Stockl, Heidi/0000-0002-0907-8483;
Vlassov, Valentin/0000-0003-2845-2992; Davis,
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Howard/0000-0002-3676-2707; Nieuwenhuijsen, Mark/0000-0001-9461-7981;
Alsharif, Ubai/0000-0002-4024-3950; Amini, Heresh/0000-0002-4825-1322;
Lotufo, Paulo/0000-0002-4856-8450; Karch, Andre/0000-0003-3014-8543;
Hedayati, Mohammad T./0000-0001-6415-4648; Scott,
James/0000-0002-0744-0688; Franklin, Richard/0000-0003-1864-4552;
Ermakov, Sergey/0000-0003-1072-1162; Pereira, David/0000-0003-0384-7592;
Parry, Charles/0000-0001-9787-2785; Kravchenko,
Michael/0000-0001-5187-5518; Nolte, Sandra/0000-0001-6185-9423; Stein,
Dan/0000-0001-7218-7810; Lalloo, Ratilal/0000-0001-5822-1269; Tillmann,
Taavi/0000-0002-8428-3719; Salomon, Joshua/0000-0003-3929-5515; Beyene,
Tariku Jibat/0000-0002-7474-1966; Brenner, Hermann/0000-0002-6129-1572;
Majdan, Marek/0000-0001-8037-742X; Sepanlou, Sadaf/0000-0002-3669-5129;
Ferri, Cleusa/0000-0002-1815-7685; Devries, Karen/0000-0001-8935-2181;
Jacobsen, Kathryn/0000-0002-4198-6246; LOGROSCINO,
GIANCARLO/0000-0003-0423-3242; wang, YA XING/0000-0003-2749-7793;
Ribeiro, Antonio/0000-0002-2740-0042; Hay, Simon/0000-0002-0611-7272;
Naldi, Luigi/0000-0002-3160-2835; Thrift, Amanda/0000-0001-8533-4170;
Weiderpass, Elisabete/0000-0003-2237-0128; Montico,
Marcella/0000-0003-0377-8232; Fra.Paleo, Urbano/0000-0001-6192-7684;
Monasta, Lorenzo/0000-0001-7774-548X; Haro, Josep
Maria/0000-0002-3984-277X; Degenhardt, Louisa/0000-0002-8513-2218;
Martin, Randall/0000-0003-2632-8402; Hankey, Graeme
/0000-0002-6044-7328; Rakovac, Ivo/0000-0003-3462-2636; Banerjee,
Amitava/0000-0001-8741-3411; NORMAN, ROSANA/0000-0002-9742-1957;
Charlson, Fiona/0000-0003-2876-5040; Patten, Scott/0000-0001-9871-4041
FU Bill AMP; Melinda Gates Foundation
FX Funding Bill & Melinda Gates Foundation.
NR 86
TC 238
Z9 252
U1 124
U2 301
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 DEC 5
PY 2015
VL 386
IS 10010
BP 2287
EP 2323
DI 10.1016/S0140-6736(15)00128-2
PG 37
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX8ZB
UT WOS:000365993200031
ER
PT J
AU Islam, MS
Mohanto, NC
Karim, MR
Aktar, S
Hoque, MM
Rahman, A
Jahan, M
Khatun, R
Aziz, A
Salam, KA
Saud, ZA
Hossain, M
Rahman, A
Mandal, A
Haque, A
Miyataka, H
Himeno, S
Hossain, K
AF Islam, Md Shofikul
Mohanto, Nayan Chandra
Karim, Md Rezaul
Aktar, Sharmin
Hoque, Md Mominul
Rahman, Atiqur
Jahan, Momotaj
Khatun, Rabeya
Aziz, Abdul
Salam, Kazi Abdus
Saud, Zahangir Alam
Hossain, Mostaque
Rahman, Aminur
Mandal, Abul
Haque, Azizul
Miyataka, Hideki
Himeno, Seiichiro
Hossain, Khaled
TI Elevated concentrations of serum matrix metalloproteinase-2 and-9 and
their associations with circulating markers of cardiovascular diseases
in chronic arsenic-exposed individuals
SO ENVIRONMENTAL HEALTH
LA English
DT Article
DE Arsenic; MMP-2; MMP-9; Cardiovascular diseases; Cancer; Bangladesh
ID INDUCED MALIGNANT-TRANSFORMATION; CORONARY-ARTERY DISEASE; CELL-ADHESION
MOLECULES; DRINKING-WATER; INCREASED EXPRESSION; DIABETES-MELLITUS;
KIDNEY-DISEASE; IV COLLAGENASE; PLASMA-LEVELS; SKIN-LESIONS
AB Background: Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs.
Methods: A total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits.
Results: Serum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (r(s) = 0.208, p < 0.001 for MMP-2; r(s) = 0.163, p < 0.01 for MMP-9), hair (r(s) = 0.163, p < 0.01 for MMP-2; r(s) = 0.173, p < 0.01 for MMP-9) and nail (r(s) = 0.160, p < 0.01 for MMP-2; r(s) = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (<= 10, 10.1-50 and > 50 mu g/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs.
Conclusions: This study showed the significant positive associations and dose-response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.
C1 [Islam, Md Shofikul; Mohanto, Nayan Chandra; Aktar, Sharmin; Hoque, Md Mominul; Rahman, Atiqur; Jahan, Momotaj; Khatun, Rabeya; Aziz, Abdul; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Khaled] Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh.
[Islam, Md Shofikul; Karim, Md Rezaul] Islamic Univ, Dept Appl Nutr & Food Technol, Kushtia 7003, Bangladesh.
[Salam, Kazi Abdus] NIH, Infectious Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hossain, Mostaque] Kaliganj Upazila Hlth Complex, Gazipur, Bangladesh.
[Rahman, Aminur; Mandal, Abul] Univ Skovde, Sch Biosci, Syst Biol Res Ctr, Skovde, Sweden.
[Haque, Azizul] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Miyataka, Hideki; Himeno, Seiichiro] Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Tokushima 7708514, Japan.
RP Hossain, K (reprint author), Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh.
EM khossainbio@gmail.com
FU Ministry of Science and Technology, Government of the People's Republic
of Bangladesh [39.009.006.01.00.042.2012-2013/ES-21/558]; TWAS
[12-103RG/BIO/AS_I-UNESCO FR: 3240271353]; Rajshahi University
[A-304-5/52/RU/Science (2)/2013]; JSPS KAKENHI [22390127, 24406009];
Heiwa Nakajima Foundation, Japan
FX Ministry of Science and Technology, Government of the People's Republic
of Bangladesh (Grant No. 39.009.006.01.00.042.2012-2013/ES-21/558), TWAS
(Grant No. 12-103RG/BIO/AS_I-UNESCO FR: 3240271353), Rajshahi University
(Grant No. A-304-5/52/RU/Science (2)/2013), JSPS KAKENHI (Grant No.
22390127 and 24406009), and Heiwa Nakajima Foundation, Japan. We thank
M. M. Hasibuzzaman and Tanzina Tanu for their general supports in the
laboratory experiments. We also thank Nurshad Ali for his valuable
suggestions in statistical analysis.
NR 47
TC 2
Z9 2
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD DEC 4
PY 2015
VL 14
AR 92
DI 10.1186/s12940-015-0079-7
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CY0GX
UT WOS:000366085600001
PM 26637202
ER
PT J
AU Genest, O
Hoskins, JR
Kravats, AN
Doyle, SM
Wickner, S
AF Genest, Olivier
Hoskins, Joel R.
Kravats, Andrea N.
Doyle, Shannon M.
Wickner, Sue
TI Hsp70 and Hsp90 of E. coli Directly Interact for Collaboration in
Protein Remodeling
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Hsp40; CbpA; DnaJ; molecular chaperone; protein remodeling
ID HEAT-SHOCK-PROTEIN; DNAK CHAPERONE SYSTEM; ESCHERICHIA-COLI; MOLECULAR
CHAPERONE; CONFORMATIONAL DYNAMICS; TERMINAL DIMERIZATION; SUBSTRATE
TRANSFER; CRYSTAL-STRUCTURE; ATP BINDING; MECHANISM
AB Hsp90 is a highly conserved molecular chaperone that remodels hundreds of client proteins, many involved in the progression of cancer and other diseases. It functions with the Hsp70 chaperone and numerous cochaperones. The bacterial Hsp90 functions with an Hsp70 chaperone, DnaK, but is independent of Hsp90 cochaperones. We explored the collaboration between Escherichia coli Hsp90 and DnaK and found that the two chaperones form a complex that is stabilized by client protein binding. A J-domain protein, CbpA, facilitates assembly of the H5p90(Ec)-DnaK-client complex. We identified E. coli Hsp90 mutants defective in DnaK interaction in vivo and show that the purified mutant proteins are defective in physical and functional interaction with DnaK. Understanding how Hsp90 and Hsp70 collaborate in protein remodeling will provide the groundwork for the development of new therapeutic strategies targeting multiple chaperones and cochaperones. Published by Elsevier Ltd.
C1 [Genest, Olivier; Hoskins, Joel R.; Kravats, Andrea N.; Doyle, Shannon M.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Doyle, SM (reprint author), NIH, 37 Convent Dr,Room 5144, Bethesda, MD 20892 USA.
EM doyles@mail.nih.gov; wickners@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Dan Masison, Michael Reidy and Aurelia Battesti for many
helpful discussions. This research was supported by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research.
NR 55
TC 3
Z9 3
U1 6
U2 31
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 DEC 4
PY 2015
VL 427
IS 24
BP 3877
EP 3889
DI 10.1016/j.jmb.2015.10.010
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CY2KL
UT WOS:000366237400007
PM 26482100
ER
PT J
AU Mazaki-Tovi, S
Vaisbuch, E
Tarca, AL
Kusanovic, JP
Than, NG
Chaiworapongsa, T
Dong, Z
Hassan, SS
Romero, R
AF Mazaki-Tovi, Shali
Vaisbuch, Edi
Tarca, Adi L.
Kusanovic, Juan Pedro
Than, Nandor Gabor
Chaiworapongsa, Tinnakorn
Dong, Zhong
Hassan, Sonia S.
Romero, Roberto
TI Characterization of Visceral and Subcutaneous Adipose Tissue
Transcriptome and Biological Pathways in Pregnant and Non-Pregnant
Women: Evidence for Pregnancy-Related Regional-Specific Differences in
Adipose Tissue
SO PLOS ONE
LA English
DT Article
ID GESTATIONAL DIABETES-MELLITUS; TUMOR-NECROSIS-FACTOR; MATERNAL SERUM
ADIPONECTIN; MESSENGER-RNA EXPRESSION; C-REACTIVE PROTEIN;
COLONY-ENHANCING FACTOR; GLUCOSE-TRANSPORTER EXPRESSION; PLASMA VISFATIN
CONCENTRATIONS; RETINOL-BINDING PROTEIN-4; HORMONE-SENSITIVE LIPASE
AB Objective
The purpose of this study was to compare the transcriptome of visceral and subcutaneous adipose tissues between pregnant and non-pregnant women.
Study Design
The transcriptome of paired visceral and abdominal subcutaneous adipose tissues from pregnant women at term and matched non-pregnant women (n = 11) was profiled with the Affymetrix Human Exon 1.0 ST array. Differential expression of selected genes was validated with the use of quantitative reverse transcription-polymerase chain reaction.
Results
Six hundred forty-four transcripts from 633 known genes were differentially expressed (false discovery rate (FDR) <0.1; fold-change >1.5), while 42 exons from 36 genes showed differential usage (difference in FIRMA scores >2 and FDR<0.1) between the visceral and subcutaneous fat of pregnant women. Fifty-six known genes were differentially expressed between pregnant and non-pregnant subcutaneous fat and three genes in the visceral fat. Enriched biological processes in the subcutaneous adipose tissue of pregnant women were mostly related to inflammation.
Conclusion
The transcriptome of visceral and subcutaneous fat depots reveals pregnancy-related gene expression and splicing differences in both visceral and subcutaneous adipose tissue. Furthermore, for the first time, alternative splicing in adipose tissue has been associated with regional differences and human parturition.
C1 [Mazaki-Tovi, Shali] Chaim Sheba Med Ctr, Dept Obstet & Gynecol, IL-52621 Tel Hashomer, Israel.
[Mazaki-Tovi, Shali] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Vaisbuch, Edi] Kaplan Med Ctr, Dept Obstet & Gynecol, Rehovot, Israel.
[Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
[Tarca, Adi L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
[Kusanovic, Juan Pedro] Pontificia Univ Catolica Chile, Sch Med, Dept Obstet & Gynecol, Santiago, Chile.
[Kusanovic, Juan Pedro] Hosp Dr Sotero del Rio, Ctr Res & Innovat Maternal Fetal Med CIMAF, Dept Obstet & Gynecol, Santiago, Chile.
[Than, Nandor Gabor] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Budapest, Hungary.
[Than, Nandor Gabor] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary.
[Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Mazaki-Tovi, S (reprint author), Chaim Sheba Med Ctr, Dept Obstet & Gynecol, IL-52621 Tel Hashomer, Israel.
EM shalimazaki@gmail.com; romeror@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, U.S. Department of Health and Human Services
FX This project has been funded in whole or in part by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health, U.S.
Department of Health and Human Services.
NR 331
TC 1
Z9 1
U1 0
U2 12
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 DEC 4
PY 2015
VL 10
IS 12
AR e0143779
DI 10.1371/journal.pone.0143779
PG 35
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY1CH
UT WOS:000366143800026
PM 26636677
ER
PT J
AU Vegosen, L
Breysse, PN
Agnew, J
Gray, GC
Nachamkin, I
Sheikh, K
Kamel, F
Silbergeld, E
AF Vegosen, Leora
Breysse, Patrick N.
Agnew, Jacqueline
Gray, Gregory C.
Nachamkin, Irving
Sheikh, Kazim
Kamel, Freya
Silbergeld, Ellen
TI Occupational Exposure to Swine, Poultry, and Cattle and Antibody
Biomarkers of Campylobacter jejuni Exposure and Autoimmune Peripheral
Neuropathy
SO PLOS ONE
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; LINKED-IMMUNOSORBENT-ASSAY; MOLECULAR MIMICRY;
ANTIGANGLIOSIDE ANTIBODIES; AGRICULTURAL HEALTH; NEUROLOGIC SYMPTOMS;
UNITED-STATES; INFECTION; WORKERS; METAANALYSIS
AB Introduction
Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed.
Methods
Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals) and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher's Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies.
Results
Farmers had significantly higher levels of anti-C. jejuni IgA (p < 0.0001) and IgG (p = 0.02) antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21%) tested positive for anti-ganglioside autoantibodies compared to non- farmers (9%), but this difference was not statistically significant (p = 0.11). There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies.
Conclusions
The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to reduce occupational exposure to C. jejuni should be considered.
C1 [Vegosen, Leora; Breysse, Patrick N.; Agnew, Jacqueline; Silbergeld, Ellen] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Gray, Gregory C.] Duke Univ, Div Infect Dis, Sch Med, Durham, NC USA.
[Nachamkin, Irving] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Sheikh, Kazim] Univ Texas Houston, Dept Neurol, Sch Med, Houston, TX USA.
[Kamel, Freya] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Vegosen, L (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
EM lvegosen@jhsph.edu
OI Kamel, Freya/0000-0001-5052-6615
FU intramural research program of the National Institutes of Health;
National Institute of Environmental Health Sciences [Z01-ES049030];
National Institute for Occupational Safety and Health (NIOSH) Education
and Research Center for Occupational Safety and Health at the Johns
Hopkins Bloomberg School of Public Health [T42OH008428, 90035666]; Johns
Hopkins Center for a Livable Future Innovation Grant [1602030070];
Hopkins Sommer Scholarship; Dr. C. W. Kruse Memorial Fund Award
FX This work was supported in part by the intramural research program of
the National Institutes of Health, the National Institute of
Environmental Health Sciences (Z01-ES049030) (https://www.niehs.nih.gov/
and http://aghealth.nih.gov/), the National Institute for Occupational
Safety and Health (NIOSH) Education and Research Center for Occupational
Safety and Health at the Johns Hopkins Bloomberg School of Public Health
#T42OH008428 Pilot Project Research Training Award 90035666
(http://www.jhsph.edu/research/centers-and-institutes/johns-hopkins-educ
ation-and-research-center-for-occupational-safety-and-health/index.
html), the Johns Hopkins Center for a Livable Future Innovation Grant
1602030070
(http://www.jhsph.edu/research/centers-and-institutes/johns-hopkins-cent
er-for-a-livable-future/index.html), Hopkins Sommer Scholarship
(http://www.jhsph.edu/admissions/scholarships/institutional-scholarships
/sommer-scholars/), and the Dr. C. W. Kruse Memorial Fund Award
(http://www.jhsph.edu/). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 0
Z9 0
U1 5
U2 8
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 DEC 4
PY 2015
VL 10
IS 12
AR e0143587
DI 10.1371/journal.pone.0143587
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CY1CH
UT WOS:000366143800019
PM 26636679
ER
PT J
AU Homsy, J
Zaidi, S
Shen, YF
Ware, JS
Samocha, KE
Karczewski, KJ
DePalma, SR
McKean, D
Wakimoto, H
Gorham, J
Jin, SC
Deanfield, J
Giardini, A
Porter, GA
Kim, R
Bilguvar, K
Lopez-Giraldez, F
Tikhonova, I
Mane, S
Romano-Adesman, A
Qi, HJ
Vardarajan, B
Ma, LJ
Daly, M
Roberts, AE
Russell, MW
Mital, S
Newburger, JW
Gaynor, JW
Breitbart, RE
Iossifov, I
Ronemus, M
Sanders, SJ
Kaltman, JR
Seidman, JG
Brueckner, M
Gelb, BD
Goldmuntz, E
Lifton, RP
Seidman, CE
Chung, WK
AF Homsy, Jason
Zaidi, Samir
Shen, Yufeng
Ware, James S.
Samocha, Kaitlin E.
Karczewski, Konrad J.
DePalma, Steven R.
McKean, David
Wakimoto, Hiroko
Gorham, Josh
Jin, Sheng Chih
Deanfield, John
Giardini, Alessandro
Porter, George A., Jr.
Kim, Richard
Bilguvar, Kaya
Lopez-Giraldez, Francesc
Tikhonova, Irina
Mane, Shrikant
Romano-Adesman, Angela
Qi, Hongjian
Vardarajan, Badri
Ma, Lijiang
Daly, Mark
Roberts, Amy E.
Russell, Mark W.
Mital, Seema
Newburger, Jane W.
Gaynor, J. William
Breitbart, Roger E.
Iossifov, Ivan
Ronemus, Michael
Sanders, Stephan J.
Kaltman, Jonathan R.
Seidman, Jonathan G.
Brueckner, Martina
Gelb, Bruce D.
Goldmuntz, Elizabeth
Lifton, Richard P.
Seidman, Christine E.
Chung, Wendy K.
TI De novo mutations in congenital heart disease with neurodevelopmental
and other congenital anomalies
SO SCIENCE
LA English
DT Article
ID INTELLECTUAL DISABILITY; AUTISM; SPECTRUM; GENES; OUTCOMES
AB Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.
C1 [Homsy, Jason; Ware, James S.; Samocha, Kaitlin E.; Karczewski, Konrad J.; DePalma, Steven R.; McKean, David; Wakimoto, Hiroko; Gorham, Josh; Daly, Mark; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Homsy, Jason] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Zaidi, Samir; Jin, Sheng Chih; Bilguvar, Kaya; Brueckner, Martina; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Shen, Yufeng; Qi, Hongjian] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY USA.
[Shen, Yufeng; Qi, Hongjian] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY USA.
[Ware, James S.] Royal Brampton & Harefield NHS Fdn & Trust, NIHR Cardiovasc Biomed Res Unit, London, England.
[Ware, James S.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Ware, James S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Samocha, Kaitlin E.; Karczewski, Konrad J.; Daly, Mark] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Samocha, Kaitlin E.; Karczewski, Konrad J.; Daly, Mark] Harvard Univ, Sch Med, Boston, MA USA.
[DePalma, Steven R.; Seidman, Christine E.] Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Deanfield, John; Giardini, Alessandro] UCL, Dept Cardiol, London, England.
[Deanfield, John; Giardini, Alessandro] Great Ormond St Hosp Sick Children, London, England.
[Porter, George A., Jr.] Univ Rochester, Med Ctr, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Kim, Richard] Univ So Calif, Keck Sch Med, Sect Cardiothorac Surg, Los Angeles, CA 90033 USA.
[Bilguvar, Kaya; Lopez-Giraldez, Francesc; Tikhonova, Irina; Mane, Shrikant] Yale Univ, Yale Ctr Genome Anal, New Haven, CT USA.
[Romano-Adesman, Angela] Steven & Alexandra Cohen Childrens Med Ctr New Yo, New Hyde Pk, NY USA.
[Qi, Hongjian] Columbia Univ, Dept Appl Phys & Appl Math, New York, NY USA.
[Vardarajan, Badri] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Ma, Lijiang; Chung, Wendy K.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA.
[Roberts, Amy E.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Russell, Mark W.] Univ Michigan, Div Pediat Cardiol, Ann Arbor, MI 48109 USA.
[Mital, Seema] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Newburger, Jane W.; Breitbart, Roger E.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Gaynor, J. William] Childrens Hosp Philadelphia, Dept Pediat Cardiac Surg, Philadelphia, PA 19104 USA.
[Iossifov, Ivan; Ronemus, Michael] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Sanders, Stephan J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Kaltman, Jonathan R.] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
[Goldmuntz, Elizabeth] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Goldmuntz, Elizabeth] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA.
[Lifton, Richard P.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06511 USA.
[Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Chung, Wendy K.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
RP Gelb, BD (reprint author), Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
EM martina.brueckner@yale.edu; bruce.gelb@mssm.edu;
goldmuntz@email.chop.edu; richard.lifton@yale.edu;
cseidman@genetics.med.harvard.edu; wkc15@cumc.columbia.edu
RI Lopez-Giraldez, Francesc/A-5251-2011; Porter, George/E-7315-2013;
OI Lopez-Giraldez, Francesc/0000-0001-7476-9822; Porter,
George/0000-0003-0726-9988; Karczewski, Konrad/0000-0003-2878-4671
FU National Heart, Lung, and Blood Institute (PCGC); National Heart, Lung,
and Blood Institute (Pediatric Heart Network); National Heart, Lung, and
Blood Institute (Cardiovascular Development Consortium); National Human
Genome Research Institute of the National Institutes of Health (NIH);
Howard Hughes Medical Institute; Simons Foundation for Autism Research;
John S. LaDue Fellowship at Harvard Medical School; Medical Scientist
Training Program; National Research Science Award; Academy of Medical
Sciences; British Heart Foundation; Wellcome Trust; Arthritis Research
UK; NIHR Cardiovascular Biomedical Research Unit at Royal Brompton and
Harefield NHS Foundation Trust and Imperial College London; Leducq
Foundation; Heart and Stroke Foundation of Ontario; Ted Roger Centre for
Heart Research; Kostin Family Innovation Fund; Aaron Stern Professorship
at the University of Michigan; Braylon's Gift of Hope Fund
FX The authors are grateful to the patients and families who participated
in this research and team members who supported subject recruitment and
sequencing: D. Awad, C. Breton, K. Celia, C. Duarte, D. Etwaru, N.
Fishman, M. Kaspakova, J. Kline, R. Korsin, A. Lanz, E. Marquez, D.
Queen, A. Rodriguez, J. Rose, J. K. Sond, D. Warburton, A. Wilpers, and
R. Yee (Columbia Medical School); B. McDonough, A. Monafo, J. Stryker
(Harvard Medical School); N. Cross (Yale School of Medicine); S. M.
Edman, J. L. Garbarini, J. E. Tusi, S. H. Woyciechowski (Children's
Hospital of Philadelphia); J. Ellashek and N. Tran (Children's Hospital
of Los Angeles); K. Flack L. Panesar, N. Taylor (University College
London); D. Gruber and N. Stellato (Steve and Alexandra Cohen Children's
Medical Center of New York); D. Guevara, A. Julian, M. Mac Neal, C.
Mintz (Icahn School of Medicine at Mount Sinai); and E. Taillie
(University of Rochester School of Medicine and Dentistry). We thank P.
Candrea, E. Mazaika, K. Pavlik, V. Spotlow, and M. Sotiropoulos for
production exome sequences and variant confirmation. This work was
supported by grants from the National Heart, Lung, and Blood Institute
(PCGC, Pediatric Heart Network, and Cardiovascular Development
Consortium) and the National Human Genome Research Institute of the
National Institutes of Health (NIH), Howard Hughes Medical Institute,
Simons Foundation for Autism Research, John S. LaDue Fellowship at
Harvard Medical School, Medical Scientist Training Program and National
Research Science Award, Academy of Medical Sciences, British Heart
Foundation, Wellcome Trust, Arthritis Research UK and the NIHR
Cardiovascular Biomedical Research Unit at Royal Brompton and Harefield
NHS Foundation Trust and Imperial College London, Leducq Foundation,
Heart and Stroke Foundation of Ontario, Ted Roger Centre for Heart
Research, Kostin Family Innovation Fund, Aaron Stern Professorship at
the University of Michigan, and Braylon's Gift of Hope Fund. The views
expressed are those of the authors and do not necessarily reflect those
of the National Heart, Lung, and Blood Institute or NIH. R. P. L. is on
the Board of Directors of Roche. J.G.S. and C. E. S. are founders of and
own shares in Myocardia, a biotechnology company developing small
molecules for the treatment of inherited cardiomyopathy.
NR 22
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U1 1
U2 17
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 DEC 4
PY 2015
VL 350
IS 6265
BP 1262
EP 1266
DI 10.1126/science.aac9396
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX4WG
UT WOS:000365700500080
PM 26785492
ER
PT J
AU Christensen, RP
Bokinsky, A
Santella, A
Wu, YC
Marquina-Solis, J
Guo, M
Kovacevic, I
Kumar, A
Winter, PW
Tashakkori, N
McCreedy, E
Liu, HF
McAuliffe, M
Mohler, W
Colon-Ramos, DA
Bao, ZR
Shroff, H
AF Christensen, Ryan Patrick
Bokinsky, Alexandra
Santella, Anthony
Wu, Yicong
Marquina-Solis, Javier
Guo, Min
Kovacevic, Ismar
Kumar, Abhishek
Winter, Peter W.
Tashakkori, Nicole
McCreedy, Evan
Liu, Huafeng
McAuliffe, Matthew
Mohler, William
Colon-Ramos, Daniel A.
Bao, Zhirong
Shroff, Hari
TI Untwisting the Caenorhabditis elegans embryo
SO ELIFE
LA English
DT Article
ID PLANE ILLUMINATION MICROSCOPY; LIGHT-SHEET MICROSCOPY; C.-ELEGANS;
FLUORESCENCE MICROSCOPY; NERVOUS-SYSTEM; CELL LINEAGE; MORPHOGENESIS;
ELONGATION; EXPRESSION; GUIDANCE
AB The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open-source untwisting and annotation software (http://mipav.cit.nih.gov/plugin_jws/mipav_worm_plugin.php) that allows the investigation of neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. We also provide a tutorial describing how to use the software (Supplementary file 1) and a detailed description of the untwisting algorithm (Appendix). The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of our method provide a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis.
C1 [Christensen, Ryan Patrick; Wu, Yicong; Guo, Min; Kumar, Abhishek; Winter, Peter W.; Tashakkori, Nicole; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA.
[Bokinsky, Alexandra; McCreedy, Evan; McAuliffe, Matthew] NIH, Biomed Imaging Res Serv Sect, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Santella, Anthony; Kovacevic, Ismar; Bao, Zhirong] Sloan Kettering Inst, Dev Biol Program, New York, NY USA.
[Marquina-Solis, Javier; Kumar, Abhishek; Colon-Ramos, Daniel A.] Yale Univ, Sch Med, Dept Cell Biol, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA.
[Guo, Min; Liu, Huafeng] Zhejiang Univ, Coll Opt Sci & Engn, State Key Lab Modern Opt Instrumentat, Hangzhou 310003, Zhejiang, Peoples R China.
[Mohler, William] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA.
RP Christensen, RP (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA.
EM ryan.christensen@nih.gov
RI Zhejiang University, Dep. Optical Eng./G-9022-2011
FU National Institute of Biomedical Imaging and Bioengineering; National
Natural Science Foundation of China [61427807, 61271083, 61525106];
Natural Science Foundation of Zhejiang Province [LR12F03001]; Marine
Biological Laboratory; National Institutes of Health [UO1 HD075602,
R24OD016474]
FX National Institute of Biomedical Imaging and Bioengineering Ryan Patrick
Christensen Yicong Wu Peter W Winter Hari Shroff; National Natural
Science Foundation of China 61427807 Huafeng Liu; National Natural
Science Foundation of China 61271083 Huafeng Liu; National Natural
Science Foundation of China 61525106 Huafeng Liu; Natural Science
Foundation of Zhejiang Province LR12F03001 Huafeng Liu; Marine
Biological Laboratory Whitman Research Award Daniel A Colo'n-Ramos
Zhirong Bao Hari Shroff; National Institutes of Health UO1 HD075602
Daniel AColo'n-Ramos Zhirong Bao Hari Shroff; National Institutes of
Health R24OD016474 Daniel AColo'n-Ramos Zhirong Bao Hari Shroff; The
funders had no role in study design, data collection and interpretation,
or the decision to submit the work for publication.
NR 45
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U1 0
U2 6
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD DEC 3
PY 2015
VL 4
AR e10070
DI 10.7554/eLife.10070
PG 23
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9IP
UT WOS:000373816400001
ER
PT J
AU Ahn, I
Farooqui, M
Lee, YS
Marti, G
Soto, S
Tian, X
Stetler-Stevenson, M
Yuan, CM
Maric, I
Wiestner, A
AF Ahn, Inhye
Farooqui, Mohammed
Lee, Yuh Shan
Marti, Gerald
Soto, Susan
Tian, Xin
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Maric, Irina
Wiestner, Adrian
TI Risk-Adapted Induction and Maintenance with Ofatumumab in Previously
Untreated Patients with Chronic Lymphocytic Leukemia (CLL) / Small
Lymphocytic Lymphoma (SLL)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ahn, Inhye] NCI, NIH, Bethesda, MD 20892 USA.
[Farooqui, Mohammed; Lee, Yuh Shan; Marti, Gerald; Soto, Susan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005228
ER
PT J
AU Albitar, A
Ma, WL
De Dios, I
Estrella, J
Farooqui, M
Wiestner, A
Albitar, M
AF Albitar, Adam
Ma, Wanlong
De Dios, Ivan
Estrella, Jeffrey
Farooqui, Mohammed
Wiestner, Adrian
Albitar, Maher
TI High Sensitivity Testing Shows Multiclonal Mutations in Patients with
CLL Treated with BTK Inhibitor and Lack of Mutations in Ibrutinib-Naive
Patients
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Albitar, Adam; Ma, Wanlong; De Dios, Ivan; Estrella, Jeffrey; Albitar, Maher] NeoGen Labs, Irvine, CA USA.
[Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 3
Z9 3
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002153
ER
PT J
AU Ali, SA
Shi, V
Wang, M
Stroncek, D
Maric, I
Brudno, JN
Stetler-Stevenson, M
Rose, JJ
Feldman, S
Hansen, B
Hakim, FT
Gress, RE
Kochenderfer, JN
AF Ali, Syed Abbas
Shi, Victoria
Wang, Michael
Stroncek, David
Maric, Irina
Brudno, Jennifer N.
Stetler-Stevenson, Maryalice
Rose, Jeremy J.
Feldman, Steven
Hansen, Brenna
Hakim, Frances T.
Gress, Ronald E.
Kochenderfer, James N.
TI Remissions of Multiple Myeloma during a First-in-Humans Clinical Trial
of T Cells Expressing an Anti-B-Cell Maturation Antigen Chimeric Antigen
Receptor
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ali, Syed Abbas] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Shi, Victoria; Hansen, Brenna] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Wang, Michael] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA.
[Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Brudno, Jennifer N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Rose, Jeremy J.; Hakim, Frances T.; Gress, Ronald E.; Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Feldman, Steven] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 4
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000002
ER
PT J
AU Arai, Y
Aoki, K
Takeda, J
Kondo, T
Eto, T
Ota, S
Hashimoto, H
Fukuda, T
Ozawa, Y
Kanda, Y
Kato, C
Kurokawa, M
Iwato, K
Onizuka, M
Ichinohe, T
Atsuta, Y
Takami, A
AF Arai, Yasuyuki
Aoki, Kazunari
Takeda, June
Kondo, Tadakazu
Eto, Tetsuya
Ota, Shuichi
Hashimoto, Hisako
Fukuda, Takahiro
Ozawa, Yukiyasu
Kanda, Yoshinobu
Kato, Chiaki
Kurokawa, Mineo
Iwato, Koji
Onizuka, Makoto
Ichinohe, Tatsuo
Atsuta, Yoshiko
Takami, Akiyoshi
TI Efficacy of High-Dose Cytarabine Added to Cyclophosphamide/Total-Body
Irradiation in the Conditioning Regimen of Allogeneic Hematopoietic Cell
Transplantation for Myeloid Malignancy
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Arai, Yasuyuki; Aoki, Kazunari; Takeda, June; Kondo, Tadakazu] Kyoto Univ, Grad Sch Med, Kyoto, Japan.
[Arai, Yasuyuki] NIAID, NIH, Bethesda, MD 20892 USA.
[Eto, Tetsuya] Hamanomachi Hosp, Dept Hematol, Fukuoka, Japan.
[Ota, Shuichi] Sapporo Hokuyu Hosp, Sapporo, Hokkaido, Japan.
[Hashimoto, Hisako] Inst Biomed Res Innovat, Kobe, Hyogo, Japan.
[Fukuda, Takahiro] Natl Canc Ctr, Dept Hematopoiet Stem Cell Transplantat, Tokyo, Japan.
[Ozawa, Yukiyasu] Japanese Red Cross Nagoya First Hosp, Nagoya, Aichi, Japan.
[Kanda, Yoshinobu] Jichi Med Univ, Saitama Med Ctr, Div Hematol, Saitama, Japan.
[Kato, Chiaki] Meitetsu Hosp, Nagoya, Aichi, Japan.
[Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo, Japan.
[Iwato, Koji] Hiroshima Red Cross Hosp, Dept Transfus, Hiroshima, Japan.
[Onizuka, Makoto] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan.
[Ichinohe, Tatsuo] Hiroshima Univ, Hiroshima, Japan.
[Atsuta, Yoshiko] Nagoya Univ, Grad Sch Med, Dept Healthcare Adm, Nagoya, Aichi 4648601, Japan.
[Atsuta, Yoshiko] Japanese Data Ctr Hematopoiet Cell Transplantat, Nagoya, Aichi, Japan.
[Takami, Akiyoshi] Aichi Med Univ, Nagakute, Aichi 48011, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002171
ER
PT J
AU Breton, A
Sonzogni, L
Theodorou, A
Aktuna, S
Menzel, S
Grosveld, F
Philipsen, S
Thein, SL
AF Breton, Amandine
Sonzogni, Laura
Theodorou, Andria
Aktuna, Suleyman
Menzel, Stephan
Grosveld, Frank
Philipsen, Sjaak
Thein, Swee Lay
TI ASH1L: A Novel Beta-Globin Gene Regulator in Humans?
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Breton, Amandine; Sonzogni, Laura; Theodorou, Andria; Aktuna, Suleyman; Menzel, Stephan] Kings Coll London, Mol Haematol, London WC2R 2LS, England.
[Grosveld, Frank; Philipsen, Sjaak] Erasmus MC, Cell Biol, Rotterdam, Netherlands.
[Thein, Swee Lay] Kings Coll London, Mol Haematol, Div Canc Studies, London WC2R 2LS, England.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002078
ER
PT J
AU Brudno, JN
Somerville, R
Shi, V
Rose, JJ
Halverson, DC
Fowler, DH
Hickstein, DD
Gea-Banacloche, JC
Pavletic, SZ
Goy, A
Lu, TYL
Feldman, S
Iwamoto, A
Kurlander, R
Maric, I
Hansen, B
Wilder, JS
Blacklock-Shuver, B
Hakim, FT
Rosenberg, SA
Gress, RE
Kochenderfer, JN
AF Brudno, Jennifer N.
Somerville, Robert
Shi, Victoria
Rose, Jeremy J.
Halverson, David C.
Fowler, Daniel H.
Hickstein, Dennis D.
Gea-Banacloche, Juan C.
Pavletic, Steven Z.
Goy, Andre
Lu, Tangying L.
Feldman, Steven
Iwamoto, Alex
Kurlander, Roger
Maric, Irina
Hansen, Brenna
Wilder, Jennifer S.
Blacklock-Shuver, Bazetta
Hakim, Frances T.
Rosenberg, Steven A.
Gress, Ronald E.
Kochenderfer, James N.
TI Allogeneic T-Cells Expressing an Anti-CD19 Chimeric Antigen Receptor
Cause Remissions of B-Cell Malignancies after Allogeneic Hematopoietic
Stem Cell Transplantation without Causing Graft-Versus-Host Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Brudno, Jennifer N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Somerville, Robert; Lu, Tangying L.; Feldman, Steven; Iwamoto, Alex; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Shi, Victoria; Hickstein, Dennis D.; Pavletic, Steven Z.; Hansen, Brenna; Blacklock-Shuver, Bazetta; Hakim, Frances T.] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Rose, Jeremy J.; Halverson, David C.; Fowler, Daniel H.; Gea-Banacloche, Juan C.; Gress, Ronald E.; Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Goy, Andre] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Kurlander, Roger; Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wilder, Jennifer S.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Frederick, MD USA.
NR 0
TC 3
Z9 3
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000163
ER
PT J
AU Cantilena, CR
Zhao, X
Kajigaya, S
Dunavin, N
Tian, X
Strickland, SA
Savani, BN
Mohan, SR
Rezvani, K
Feng, XM
Townsley, DM
Battiwalla, M
Ito, S
Barrett, AJ
AF Cantilena, Caroline R.
Zhao, Xin
Kajigaya, Sachiko
Dunavin, Neil
Tian, Xin
Strickland, Stephen A.
Savani, Bipin N.
Mohan, Sanjay R.
Rezvani, Katayoun
Feng, Xingmin
Townsley, Danielle M.
Battiwalla, Minoo
Ito, Sawa
Barrett, Austin John
TI Activity of the Telomerase Inhibitor GRN163L (Imetelstat) on Acute
Myeloblastic Leukemia Blasts Is Enhanced By DNA Methyltransferase
Inhibitors Irrespective of TERT Promoter Methylation Status
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Cantilena, Caroline R.; Zhao, Xin; Kajigaya, Sachiko; Dunavin, Neil; Feng, Xingmin; Townsley, Danielle M.; Battiwalla, Minoo; Ito, Sawa; Barrett, Austin John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Strickland, Stephen A.; Mohan, Sanjay R.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Savani, Bipin N.] Tennessee Valley Healthcare Syst Vet Affairs, Nashville, TN USA.
[Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004067
ER
PT J
AU Chiang, CL
Frissora, FW
Xie, Z
Huang, X
Mani, R
Baskar, S
Rader, C
Chan, KK
Marcucci, G
Byrd, JC
Lee, LJ
Muthusamy, N
AF Chiang, Chi-Ling
Frissora, Frank W.
Xie, Zhiliang
Huang, Xiaomeng
Mani, Rajeswaran
Baskar, Sivasubramanian
Rader, Christoph
Chan, Kenneth K.
Marcucci, Guido
Byrd, John C.
Lee, L. James
Muthusamy, Natarajan
TI Immunoliposomal Delivery of Mir-29b By Targeting Tumor Antigen ROR1
Induces Epigenetic Reprograming in Human-ROR1-Expressed Mouse Model of
Chronic Lymphocytic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chiang, Chi-Ling; Frissora, Frank W.; Xie, Zhiliang] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Huang, Xiaomeng] Univ Utah, Salt Lake City, UT USA.
[Mani, Rajeswaran] Ohio State Univ, Columbus, OH 43210 USA.
[Baskar, Sivasubramanian] NCI, Bethesda, MD 20892 USA.
[Rader, Christoph] Dept Canc Biol, Jupiter, FL USA.
[Rader, Christoph] Dept Mol Therapeut, Jupiter, FL USA.
[Chan, Kenneth K.] Ohio State Univ, Dept Pharmaceut & Pharmaceut Chem, Columbus, OH 43210 USA.
[Marcucci, Guido] Ohio State Univ, Med Ctr, Dept Hematol Oncol, Columbus, OH 43210 USA.
[Byrd, John C.; Muthusamy, Natarajan] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Lee, L. James] Ohio State Univ, Chem & Biomol Engn Dept, Columbus, OH 43210 USA.
RI Chiang, Chi-Ling/O-3038-2016
OI Chiang, Chi-Ling/0000-0002-0275-9673
NR 0
TC 0
Z9 0
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005221
ER
PT J
AU Chien, CD
Nguyen, SM
Qin, HY
Jacoby, E
Fry, TJ
AF Chien, Christopher Daniel
Nguyen, Sang Minh
Qin, Haiying
Jacoby, Elad
Fry, Terry J.
TI CRLF2/Tslpr Overexpressing Acute Lymphoblastic Leukemia Relapse Is
Driven By Chemotherapy-Induced TSLP from Bone Marrow Stromal Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chien, Christopher Daniel; Nguyen, Sang Minh; Qin, Haiying; Jacoby, Elad; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004232
ER
PT J
AU Chin, D
Kutny, MA
Grim, J
Gerbing, RB
Miller, K
Farrar, JE
Auvil, JMG
Smith, MA
Gerhard, DS
Davidsen, TM
Gesuwan, P
Hermida, LC
Marra, MA
Mungall, AJ
Moore, R
Long, W
Ma, Y
Zong, S
Kolb, EA
Gamis, AS
Alonzo, TA
Meshinchi, S
AF Chin, Diana
Kutny, Matthew A.
Grim, Jonathan
Gerbing, Robert B.
Miller, Kristen
Farrar, Jason E.
Auvil, Jaime M. Guidry
Smith, Malcolm A.
Gerhard, Daniela S.
Davidsen, Tanja M.
Gesuwan, Patee
Hermida, Leandro C.
Marra, Marco A.
Mungall, Andrew J.
Moore, Richard
Long, William
Ma, Yussanne
Zong, Stuart
Kolb, E. Anders
Gamis, Alan S.
Alonzo, Todd A.
Meshinchi, Soheil
TI Comprehensive Genomic and Transcript Profiling of CBL Gene in Childhood
AML: A Report from Children's Oncology Group Studies AAML03P1, AAML0531
and COG/NCI Target AML Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chin, Diana; Miller, Kristen; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Kutny, Matthew A.] Univ Alabama Birmingham, Dept Pediat, Div Hematol Oncol, Birmingham, AL USA.
[Grim, Jonathan] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Gerbing, Robert B.] Childrens Oncol Grp, Monrovia, CA USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Davidsen, Tanja M.; Gesuwan, Patee; Hermida, Leandro C.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Marra, Marco A.; Moore, Richard] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Mungall, Andrew J.; Long, William; Ma, Yussanne; Zong, Stuart] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000234
ER
PT J
AU Chou, BK
Bai, H
Gao, YX
Wang, Y
Ye, ZH
Kwon, EM
Liu, PP
Friedman, AD
Wang, ZZ
Cheng, LZ
AF Chou, Bin-Kuan
Bai, Hao
Gao, Yongxing
Wang, Ying
Ye, Zhaohui
Kwon, Erika Mijin
Liu, Pu Paul
Friedman, Alan D.
Wang, Zack Z.
Cheng, Linzhao
TI The Roles of RUNX1 in Human Hematopoiesis and Megakaryopoiesis Revealed
By Genome-Targeted Human iPSCs and an Improved Hematopoietic
Differentiation Model
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chou, Bin-Kuan; Gao, Yongxing; Wang, Ying; Ye, Zhaohui; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Div Hematol, Baltimore, MD USA.
[Chou, Bin-Kuan; Gao, Yongxing; Wang, Ying; Ye, Zhaohui; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD USA.
[Bai, Hao; Wang, Zack Z.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
[Kwon, Erika Mijin] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Pu Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Friedman, Alan D.] Johns Hopkins Univ, Sch Med, Pediat Oncol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003291
ER
PT J
AU Curtis, LM
Pavletic, SZ
Salit, RB
Shaffer, BC
Steinberg, SM
Wilder, JS
Pirsl, F
Blacklock-Schuver, B
Hsu, J
Hughes, TE
Stroncek, D
Adams, S
Hendricks, J
Avila, DN
Mann, J
Halverson, DC
Friedman, TM
Korngold, R
Gea-Banacloche, JC
Fowler, DH
Confer, DL
Hakim, FT
Gress, RE
Bishop, MR
AF Curtis, Lauren M.
Pavletic, Steven Z.
Salit, Rachel B.
Shaffer, Brian C.
Steinberg, Seth M.
Wilder, Jennifer S.
Pirsl, Filip
Blacklock-Schuver, Bazetta
Hsu, Jennifer
Hughes, Thomas E.
Stroncek, David
Adams, Sharon
Hendricks, Jennifer
Avila, Daniele N.
Mann, Jennifer
Halverson, David C.
Friedman, Thea M.
Korngold, Robert
Gea-Banacloche, Juan C.
Fowler, Daniel H.
Confer, Dennis L.
Hakim, Frances T.
Gress, Ronald E.
Bishop, Michael R.
TI Alemtuzumab-Cyclosporine Versus Tacrolimus-Methotrexate-Sirolimus for
Graft-Versus-Host Disease Prophylaxis in Reduced Intensity Allogeneic
Hematopoietic Stem Cell Transplantation from Unrelated Donors: Final
Results of a Randomized Trial
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Curtis, Lauren M.; Pavletic, Steven Z.; Salit, Rachel B.; Shaffer, Brian C.; Wilder, Jennifer S.; Pirsl, Filip; Blacklock-Schuver, Bazetta; Hsu, Jennifer; Avila, Daniele N.; Mann, Jennifer; Halverson, David C.; Gea-Banacloche, Juan C.; Fowler, Daniel H.; Hakim, Frances T.; Gress, Ronald E.; Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Salit, Rachel B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Shaffer, Brian C.] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Serv, Dept Med, New York, NY 10021 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Wilder, Jennifer S.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Monitoring Res Program, Frederick, MD USA.
[Hughes, Thomas E.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Stroncek, David; Adams, Sharon] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hendricks, Jennifer] NIH, Dept Social Work, Ctr Clin, Bethesda, MD 20892 USA.
[Friedman, Thea M.; Korngold, Robert] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Bishop, Michael R.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000129
ER
PT J
AU Davidson-Moncada, JK
Wand, TH
Reger, RN
Wu, CF
Dunbar, CE
Childs, RW
AF Davidson-Moncada, Jan K.
Wand, Taylor Harrison
Reger, Robert N.
Wu, Chuanfeng
Dunbar, Cynthia E.
Childs, Richard W.
TI Identification and Ex Vivo Expansion of a Circulating NK Cell Progenitor
Population That Leads to Sustained Production of CD56+NK Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Davidson-Moncada, Jan K.; Wand, Taylor Harrison] NHLBI, Ctr Human Immunol, Bethesda, MD 20892 USA.
[Reger, Robert N.; Wu, Chuanfeng; Dunbar, Cynthia E.; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002287
ER
PT J
AU De Ravin, SS
Wu, XL
Theobald, N
Lee, JS
Gray, J
Hanson, IC
Notarangelo, L
Sorrentino, BP
Malech, HL
AF De Ravin, Suk See
Wu, Xiaolin
Theobald, Narda
Lee, Janet S.
Gray, John
Hanson, Imelda Celine
Notarangelo, Luigi
Sorrentino, Brian P.
Malech, Harry L.
TI Lentiviral Hematopoietic Stem Cell Gene Therapy for Older Patients with
X-Linked Severe Combined Immunodeficiency
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [De Ravin, Suk See] NIH, LHD, Bethesda, MD 20892 USA.
[Wu, Xiaolin] Leidos Biomed Res Inc, Canc Reserach Technol Program, Frederick, MD USA.
[Theobald, Narda] NIAID, LHD, NIH, Bethesda, MD 20892 USA.
[Lee, Janet S.] NIH, Bethesda, MD 20892 USA.
[Gray, John] Audentes Therapeut, Res & Dev, San Francisco, CA USA.
[Hanson, Imelda Celine] Texas Childrens Hosp, Div Pediat Immunol Allergy & Rheumatol, Houston, TX 77030 USA.
[Notarangelo, Luigi] Harvard Univ, Sch Med, Boston, MA USA.
[Sorrentino, Brian P.] St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 USA.
[Sorrentino, Brian P.] St Jude Childrens Res Hosp, Hematol, Memphis, TN 38105 USA.
[Malech, Harry L.] NIAID, Host Def Lab, Bethesda, MD 20892 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 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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001013
ER
PT J
AU Dunleavy, K
Lai, CE
Roschewski, M
Brudno, JN
Widemann, B
Pittaluga, S
Jaffe, ES
Lucas, AN
Stetler-Stevenson, M
Yuan, CM
Harris, P
Cole, D
Butman, JA
Little, RF
Staudt, LM
Wilson, WH
AF Dunleavy, Kieron
Lai, Catherine E.
Roschewski, Mark
Brudno, Jennifer N.
Widemann, Brigitte
Pittaluga, Stefania
Jaffe, Elaine S.
Lucas, Andrea N.
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Harris, Pamela
Cole, Diane
Butman, John A.
Little, Richard F.
Staudt, Louis M.
Wilson, Wyndham H.
TI Phase I Study of Dose-Adjusted-Teddi-R with Ibrutinib in Untreated and
Relapsed/Refractory Primary CNS Lymphoma
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Dunleavy, Kieron; Roschewski, Mark; Staudt, Louis M.; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
[Lai, Catherine E.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Lucas, Andrea N.; Butman, John A.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Widemann, Brigitte; Cole, Diane] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Harris, Pamela; Little, Richard F.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001218
ER
PT J
AU Dunleavy, K
Noy, A
Abramson, JS
LaCasce, AS
Link, BK
Parekh, S
Jagadeesh, D
Bierman, PJ
Mitsuyasu, RT
Battini, R
Watson, PR
Peace, D
Averbrook, BJ
Naina, HV
Leach, JW
Hanna, WT
Powell, BL
Nagpal, S
Roschewski, M
Lucas, AN
Steinberg, SM
Kahl, BS
Friedberg, JW
Little, RF
Bartlett, NL
Fanale, MA
Wilson, WH
AF Dunleavy, Kieron
Noy, Ariela
Abramson, Jeremy S.
LaCasce, Ann S.
Link, Brian K.
Parekh, Samir
Jagadeesh, Deepa
Bierman, Philip J.
Mitsuyasu, Ronald T.
Battini, Ramakrishna
Watson, Peter R.
Peace, David
Averbrook, Bruce J.
Naina, Harris V.
Leach, Joseph W.
Hanna, Wahid T.
Powell, Bayard L.
Nagpal, Sunil
Roschewski, Mark
Lucas, Andrea N.
Steinberg, Seth M.
Kahl, Brad S.
Friedberg, Jonathan W.
Little, Richard F.
Bartlett, Nancy L.
Fanale, Michelle A.
Wilson, Wyndham H.
TI Risk-Adapted Therapy in Adults with Burkitt Lymphoma: Preliminary Report
of a Multicenter Prospective Phase II Study of DA-EPOCH-R
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Dunleavy, Kieron; Roschewski, Mark; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
[Noy, Ariela] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10021 USA.
[Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA.
[LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Link, Brian K.] Univ Iowa Hosp & Clin, Div Hematol Oncol & Blood & Marrow Transplantat, Iowa City, IA 52242 USA.
[Parekh, Samir] Icahn Sch Med Mt Sinai, Hematol & Med Oncol, New York, NY 10029 USA.
[Jagadeesh, Deepa] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Bierman, Philip J.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Mitsuyasu, Ronald T.] UCLA Med Ctr, Los Angeles, CA USA.
[Battini, Ramakrishna] Montefiore Med Ctr, Dept Oncol, New York, NY USA.
[Watson, Peter R.] Kinston Med Specialists, Kinston, NC USA.
[Peace, David] Univ Illinois, Div Hematol Oncol, Chicago, IL USA.
[Averbrook, Bruce J.] Metrohlth Med Ctr, Cleveland, OH USA.
[Naina, Harris V.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hematol & Oncol, Dallas, TX 75390 USA.
[Leach, Joseph W.] Unity Hosp, Monneapolis, MN USA.
[Hanna, Wahid T.] Univ Tennessee, Inst Canc, Knoxville, TN USA.
[Powell, Bayard L.] Wake Forest Sch Med, Ctr Comprehens Canc, Winston Salem, NC USA.
[Nagpal, Sunil] West Michigan Canc Ctr, Kalamazoo, MI USA.
[Lucas, Andrea N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Kahl, Brad S.] Washington Univ, St Louis, MO USA.
[Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA.
[Little, Richard F.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA.
[Fanale, Michelle A.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001094
ER
PT J
AU Durham, BH
Diamond, EL
Haroche, J
Yao, Z
Ma, J
Parikh, SA
Choi, J
Kim, E
Cohen-Aubart, F
Lee, SCW
Gao, YJ
Micol, JB
Campbell, P
Walsh, MP
Sylvester, B
Dolgalev, I
Olga, A
Heguy, A
Zappile, P
Nakitandwe, J
Dalton, J
Ellison, DW
Estrada-Veras, J
Lacouture, M
Gahl, WA
Stephens, P
Miller, VA
Ross, J
Ali, S
Heritier, S
Donadieu, J
Solit, D
Hyman, DM
Baselga, J
Janku, F
Taylor, BS
Park, CY
Dogan, A
Amoura, Z
Emile, JF
Rampal, RK
Rosen, N
Gruber, TA
Abdel-Wahab, O
AF Durham, Benjamin Heath
Diamond, Eli L.
Haroche, Julien
Yao, Zhan
Ma, Jing
Parikh, Sameer A.
Choi, John
Kim, Eunhee
Cohen-Aubart, Fleur
Lee, Stanley Chun-Wei
Gao, Yijun
Micol, Jean-Baptiste
Campbell, Patrick
Walsh, Michael P.
Sylvester, Brooke
Dolgalev, Igor
Olga, Aminova
Heguy, Adriana
Zappile, Paul
Nakitandwe, Joy
Dalton, James
Ellison, David W.
Estrada-Veras, Juvianee
Lacouture, Mario
Gahl, William A.
Stephens, Phil
Miller, Vincent A.
Ross, Jeffrey
Ali, Siraj
Heritier, Sebastien
Donadieu, Jean
Solit, David
Hyman, David M.
Baselga, Jose
Janku, Filip
Taylor, Barry S.
Park, Christopher Y.
Dogan, Ahmet
Amoura, Zahir
Emile, Jean-Francois
Rampal, Raajit K.
Rosen, Neal
Gruber, Tanja A.
Abdel-Wahab, Omar
TI Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Durham, Benjamin Heath] Sloan Kettering Inst, New York, NY USA.
[Diamond, Eli L.; Yao, Zhan; Kim, Eunhee; Lee, Stanley Chun-Wei; Gao, Yijun; Micol, Jean-Baptiste; Sylvester, Brooke; Lacouture, Mario; Hyman, David M.; Taylor, Barry S.; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Haroche, Julien] Grp Hosp Pitie Salpetriere, Inst E3M, F-75634 Paris, France.
[Ma, Jing; Dalton, James; Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Parikh, Sameer A.] Mayo Clin, Div Hematol, Rochester, MN USA.
[Choi, John] St Jude Childrens Res Hosp, Pathol, Memphis, TN USA.
[Cohen-Aubart, Fleur; Amoura, Zahir] Hop La Pitie Salpetriere, Paris, France.
[Campbell, Patrick; Nakitandwe, Joy] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Walsh, Michael P.] St Jude Childrens Res Hosp, Memphis, TN USA.
[Dolgalev, Igor; Olga, Aminova; Heguy, Adriana; Zappile, Paul] NYU, Langone Med Ctr, New York, NY USA.
[Estrada-Veras, Juvianee; Gahl, William A.] NHGRI, Bethesda, MD 20892 USA.
[Stephens, Phil; Miller, Vincent A.; Ross, Jeffrey; Ali, Siraj] Fdn Med Inc, Cambridge, MA USA.
[Heritier, Sebastien] French Reference Ctr Langerhans Cell Histiocytosi, Paris, France.
[Donadieu, Jean] Hop Trousseau, F-75571 Paris, France.
[Solit, David] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA.
[Baselga, Jose] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Med Serv, New York, NY 10021 USA.
[Janku, Filip] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Park, Christopher Y.] Mem Sloan Kettering Canc Ctr, Pathol & Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Emile, Jean-Francois] Univ Versailles, Boulogne, France.
[Rampal, Raajit K.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Rosen, Neal] Mem Sloan Kettering Canc Ctr, Pharmacol, New York, NY 10021 USA.
[Gruber, Tanja A.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 4
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001227
ER
PT J
AU Feng, XM
Lin, ZH
Desierto, M
Keyvanfar, K
Malide, D
Chen, JC
Young, NS
AF Feng, Xingmin
Lin, Zenghua
Desierto, Marie
Keyvanfar, Keyvan
Malide, Daniela
Chen, Jichun
Young, Neal S.
TI Rapamycin Is Highly Effective in a Mouse Model of Immune-Mediated Bone
Marrow Failure By Mechanisms Distinct from Cyclosporine
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Feng, Xingmin; Lin, Zenghua; Desierto, Marie; Keyvanfar, Keyvan; Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Malide, Daniela] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004002
ER
PT J
AU Fry, TJ
Stetler-Stevenson, M
Shah, NN
Yuan, CM
Yates, B
Delbrook, C
Zhang, L
Lee, DW
Stroncek, D
Mackall, CL
AF Fry, Terry J.
Stetler-Stevenson, Maryalice
Shah, Nirali N.
Yuan, Constance M.
Yates, Bonnie
Delbrook, Cindy
Zhang, Ling
Lee, Daniel W., III
Stroncek, David
Mackall, Crystal L.
TI Clinical Activity and Persistence of Anti-CD22 Chimeric Antigen Receptor
in Children and Young Adults with Relapsed/Refractory Acute
Lymphoblastic Leukemia (ALL)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Fry, Terry J.; Lee, Daniel W., III] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yates, Bonnie; Delbrook, Cindy; Zhang, Ling; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004124
ER
PT J
AU Gardner, K
Douiri, A
Allman, M
Drasar, E
Awogbade, M
Thein, SL
AF Gardner, Kate
Douiri, Abdel
Allman, Marlene
Drasar, Emma
Awogbade, Moji
Thein, Swee Lay
TI Survival in Sickle Cell Disease: Data from a Well-Resourced, National
Health System Setting
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Gardner, Kate; Drasar, Emma; Awogbade, Moji] Kings Coll Hosp London, Dept Haematol, London, England.
[Gardner, Kate; Allman, Marlene; Drasar, Emma; Thein, Swee Lay] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Douiri, Abdel] Kings Coll London, Primary Care & Publ Hlth Sci, London WC2R 2LS, England.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000135
ER
PT J
AU Glynn, SA
Triulzi, DJ
Roback, J
Klein, HG
AF Glynn, Simone A.
Triulzi, Darrell J.
Roback, John
Klein, Harvey G.
TI New Insights in the Potential Effect of Transfusing Red Blood Cells that
Have Been Stored for Different Periods
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Glynn, Simone A.] NHLBI, Div Blood Dis & Resources, Bldg 10, Bethesda, MD 20892 USA.
[Triulzi, Darrell J.] Inst Transfus Med, Pittsburgh, PA USA.
[Roback, John] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Klein, Harvey G.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000040
ER
PT J
AU Gojo, I
Beumer, JH
Pratz, K
Ji, JP
Wang, LH
Rudek, MA
McDevitt, MA
Baer, MR
Blackford, A
Smith, BD
Gore, SD
Carraway, HE
Showel, MM
Levis, MJ
DeZern, AE
Gladstone, D
Jain, T
Greer, J
Pouquet, M
Ismail, AW
Herman, J
Poh, WJ
Karnitz, L
Kaufmann, SH
Chen, A
Karp, JE
AF Gojo, Ivana
Beumer, Jan H.
Pratz, Keith
Ji, Jiuping
Wang, Lihua
Rudek, Michelle A.
McDevitt, Michael A.
Baer, Maria R.
Blackford, Amanda
Smith, B. Douglas
Gore, Steven D.
Carraway, Hetty E.
Showel, Margaret M.
Levis, Mark J.
DeZern, Amy E.
Gladstone, Douglas
Jain, Tania
Greer, Jackie
Pouquet, Marie
Ismail, Ali-Walbi
Herman, James
Poh, Weijie
Karnitz, Larry
Kaufmann, Scott H.
Chen, Alice
Karp, Judith E.
TI A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with
Temozolomide in Acute Leukemias
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Gojo, Ivana; Pratz, Keith; Rudek, Michelle A.; McDevitt, Michael A.; Blackford, Amanda; Smith, B. Douglas; Showel, Margaret M.; Levis, Mark J.; DeZern, Amy E.; Gladstone, Douglas; Jain, Tania; Greer, Jackie; Herman, James; Poh, Weijie; Karp, Judith E.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Beumer, Jan H.; Pouquet, Marie; Ismail, Ali-Walbi] Univ Pittsburgh, Inst Canc, Canc Therapeut Program, Pittsburgh, PA USA.
[Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Ji, Jiuping] NCI, Natl Clin Target Validat Lab, Bethesda, MD 20892 USA.
[Wang, Lihua] NCI, Frederick, MD 21701 USA.
[Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Gore, Steven D.] Yale Canc Ctr, New Haven, CT USA.
[Carraway, Hetty E.] Cleveland Clin, Leukemia Program, Cleveland, OH 44106 USA.
[Karnitz, Larry; Kaufmann, Scott H.] Mayo Clin, Rochester, MN USA.
[Chen, Alice] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004161
ER
PT J
AU Goldberg, L
Pierce, RM
Onozawa, M
Walker, RL
Zhu, YLJ
Meltzer, PS
Aplan, PD
AF Goldberg, Liat
Pierce, Rachel M.
Onozawa, Masahiro
Walker, Robert L.
Zhu, Yeulin J.
Meltzer, Paul S.
Aplan, Peter D.
TI Co-Expression of NUP98-HOXD13 and Mutant IDH2 Triggers an Early T-Cell
Precursor-like Leukemia in Mice
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Goldberg, Liat; Pierce, Rachel M.; Onozawa, Masahiro; Walker, Robert L.; Zhu, Yeulin J.; Meltzer, Paul S.; Aplan, Peter D.] NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 2
Z9 2
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003028
ER
PT J
AU Hakim, FT
Memon, S
Jin, P
Imanguli, MM
Rehman, N
Yan, XY
Rose, JJ
Mays, JW
Dhamala, S
Kapoor, V
Telford, W
Halverson, DC
Baird, K
Fowler, DH
Stroncek, D
Cowen, EW
Pavletic, SZ
Gress, RE
AF Hakim, Frances T.
Memon, Sarfraz
Jin, Ping
Imanguli, Matin M.
Rehman, Najibah
Yan, Xiao-Yi
Rose, Jeremy J.
Mays, Jacqueline W.
Dhamala, Susan
Kapoor, Veena
Telford, William
Halverson, David C.
Baird, Kristin
Fowler, Daniel H.
Stroncek, David
Cowen, Edward W.
Pavletic, Steven Z.
Gress, Ronald E.
TI Upregulation of Interferon-Inducible and Damage Response Receptors in
Chronic Graft-Versus-Host Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hakim, Frances T.; Memon, Sarfraz; Imanguli, Matin M.; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy J.; Dhamala, Susan; Kapoor, Veena; Telford, William; Halverson, David C.; Fowler, Daniel H.; Pavletic, Steven Z.; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Jin, Ping] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Mays, Jacqueline W.] Natl Inst Dent & Craniofacial Res, Clin Res Core, NIH, Bethesda, MD USA.
[Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Baird, Kristin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003046
ER
PT J
AU Hassell, KL
Eckman, JR
Klings, ES
Adams, RJ
Panepinto, JA
Grant, T
Huggins, W
Maiese, DR
Werner, EM
Ramos, EM
Hamilton, CM
AF Hassell, Kathryn L.
Eckman, James R.
Klings, Elizabeth S.
Adams, Robert J.
Panepinto, Julie A.
Grant, Tracey
Huggins, Wayne
Maiese, Deborah R.
Werner, Ellen M.
Ramos, Erin M.
Hamilton, Carol M.
TI Sickle Cell Disease Measures in the Phenx Toolkit
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hassell, Kathryn L.] Univ Colorado Denver, Hlth Sci Ctr, Aurora, CO USA.
[Eckman, James R.] Emory Univ, Hematol & Oncol, Atlanta, GA 30322 USA.
[Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Adams, Robert J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Panepinto, Julie A.] Med Coll Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA.
[Panepinto, Julie A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Grant, Tracey; Huggins, Wayne; Maiese, Deborah R.; Hamilton, Carol M.] RTI Int, Res Triangle Pk, NC USA.
[Werner, Ellen M.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001033
ER
PT J
AU Herman, SEM
McAuley, EM
Wong, DH
Sun, C
Liu, DL
Wiestner, A
AF Herman, Sarah E. M.
McAuley, Erin M.
Wong, Deanna H.
Sun, Clare
Liu, Delong
Wiestner, Adrian
TI Ibrutinib Inhibits Both B-Cell Receptor and Toll-like Receptor Signaling
in Chronic Lymphocytic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Herman, Sarah E. M.; McAuley, Erin M.; Wong, Deanna H.; Sun, Clare; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Delong] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001065
ER
PT J
AU Hickstein, DD
Shah, NN
Freeman, AF
Zerbe, C
Holland, SM
Parta, M
AF Hickstein, Dennis D.
Shah, Nirali N.
Freeman, Alexandra F.
Zerbe, Christa
Holland, Steven M.
Parta, Mark
TI Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Deficiency
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hickstein, Dennis D.] NCI, NIH, Bethesda, MD 20892 USA.
[Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.; Zerbe, Christa] NIAID, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Parta, Mark] Leidos Biomed Res Inc, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004014
ER
PT J
AU Howard, J
Inusa, B
Liossi, C
Rees, DC
Thein, SL
Cheng, E
Sahota, S
Hart, N
Murphy, P
Gavlak, J
Chorozoglou, M
Jacob, E
Nwosu, C
Gwam, M
Wakeford, S
Kirkham, F
AF Howard, Jo
Inusa, Baba
Liossi, Christina
Rees, David C.
Thein, Swee Lay
Cheng, Edith
Sahota, Sati
Hart, Nicholas
Murphy, Patrick
Gavlak, Johanna
Chorozoglou, Maria
Jacob, Eufemia
Nwosu, Carol
Gwam, Maureen
Wakeford, SallyAnn
Kirkham, Fenella
TI Prevention of Morbidity in Sickle Cell Disease ( POMS 2): A Pilot Study
of Nocturnal Respiratory Support Shows That Auto-Adjusting Positive
Airways Pressure Is Safe and Is Preferred to Oxygen Therapy
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Howard, Jo] Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England.
[Inusa, Baba] Guys & St Thomas NHS Fdn Trust, Sky Level 6, Evelina, London, England.
[Liossi, Christina; Cheng, Edith; Gavlak, Johanna; Chorozoglou, Maria; Wakeford, SallyAnn] Southampton Univ Hosp, Southampton, Hants, England.
[Rees, David C.] Kings Coll Hosp London, London, England.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
[Thein, Swee Lay] Kings Coll London, Mol Haematol, Div Canc Studies, London WC2R 2LS, England.
[Sahota, Sati] Unvers Coll London, London, England.
[Hart, Nicholas; Murphy, Patrick] Guys & St Thomas NHS Fdn Trust, London, England.
[Jacob, Eufemia] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
[Gwam, Maureen] Sickle Cell & Young Stroke Survivors, London, England.
[Kirkham, Fenella] UCL Inst Child Hlth, London, England.
RI Kirkham, Fenella/C-2442-2009
OI Kirkham, Fenella/0000-0002-2443-7958
FU National Institute for Health Research [PB-PG-1112-29099]
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003117
ER
PT J
AU Klemen, N
Vizcardo, R
Tran, L
Restifo, NP
AF Klemen, Nicholas
Vizcardo, Raul
Tran, Linda
Restifo, Nicholas P.
TI Precocious Differentiation of Somatic and Pluripotent Stem Cells Bearing
Pre-Arranged TCR
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Klemen, Nicholas; Vizcardo, Raul] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Tran, Linda] NIH, Bethesda, MD 20892 USA.
[Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002284
ER
PT J
AU Klemm, L
Swaminathan, S
Papaemmanuil, E
Ford, AM
Greaves, M
Casellas, R
Schatz, D
Lieber, MR
Muschen, M
AF Klemm, Lars
Swaminathan, Srividya
Papaemmanuil, Elli
Ford, Anthony M.
Greaves, Mel
Casellas, Rafael
Schatz, David
Lieber, Michael R.
Muschen, Markus
TI Exposure to Inflammatory Immune Responses As Driver of Clonal Evolution
in Childhood Acute Lymphoblastic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Klemm, Lars; Swaminathan, Srividya] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Papaemmanuil, Elli] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Ford, Anthony M.] Inst Canc Res, Ctr Evolut & Canc, Div Mol Pathol, London SW3 6JB, England.
[Greaves, Mel] Inst Canc Res, Haematol Oncol, Sutton, Surrey, England.
[Casellas, Rafael] NIAMS, NIH, Bethesda, MD USA.
[Schatz, David] Yale Univ, Sch Med, New Haven, CT USA.
[Lieber, Michael R.] Univ So Calif, Los Angeles, CA USA.
[Muschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000230
ER
PT J
AU Kutny, MA
Alonzo, TA
Wang, YC
Ries, R
Farrar, JE
Auvill, JMG
Smith, MA
Gerhard, DS
Davidsen, TM
Gesuwan, P
Hermida, LC
Marra, MA
Mungall, AJ
Moore, R
Long, W
Ma, Y
Zong, S
Kolb, EA
Gamis, AS
Meshinchi, S
AF Kutny, Matthew A.
Alonzo, Todd A.
Wang, Yi-Cheng
Ries, Rhonda
Farrar, Jason E.
Auvill, Jaime M. Guidry
Smith, Malcolm A.
Gerhard, Daniela S.
Davidsen, Tanja M.
Gesuwan, Patee
Hermida, Leandro C.
Marra, Marco A.
Mungall, Andrew J.
Moore, Richard
Long, William
Ma, Yussanne
Zong, Stuart
Kolb, E. Anders
Gamis, Alan S.
Meshinchi, Soheil
TI TET2 Mutations Are Highly Associated with RUNX1-RUNX1T1 Translocations
and NPMc plus in Childhood AML: a Report from Children's Oncology Group
AAML03P1, AAML0531 and NCI/COG Target AML Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Kutny, Matthew A.] Univ Alabama Birmingham, Dept Pediat, Div Hematol Oncol, Birmingham, AL USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Wang, Yi-Cheng] Childrens Oncol Grp, Monrovia, CA USA.
[Ries, Rhonda; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Auvill, Jaime M. Guidry; Gerhard, Daniela S.; Davidsen, Tanja M.; Gesuwan, Patee; Hermida, Leandro C.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Marra, Marco A.; Moore, Richard] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Mungall, Andrew J.; Long, William; Ma, Yussanne; Zong, Stuart] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004168
ER
PT J
AU Lee, DW
Stetler-Stevenson, M
Yuan, CM
Fry, TJ
Shah, NN
Delbrook, C
Yates, B
Zhang, H
Zhang, L
Kochenderfer, JN
Rosenberg, SA
Stroncek, D
Mackall, CL
AF Lee, Daniel W., III
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Fry, Terry J.
Shah, Nirali N.
Delbrook, Cindy
Yates, Bonnie
Zhang, Hua
Zhang, Ling
Kochenderfer, James N.
Rosenberg, Steven A.
Stroncek, David
Mackall, Crystal L.
TI Safety and Response of Incorporating CD19 Chimeric Antigen Receptor T
Cell Therapy in Typical Salvage Regimens for Children and Young Adults
with Acute Lymphoblastic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Lee, Daniel W., III; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Delbrook, Cindy; Yates, Bonnie; Zhang, Hua; Zhang, Ling; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002121
ER
PT J
AU Lim, EL
Trinh, DL
Ries, RE
Ma, Y
Topham, J
Hughes, MD
Pleasance, E
Mungall, AJ
Moore, R
Zhao, YJ
Gerhard, DS
Oehler, V
Kolb, EA
Gamis, AS
Smith, MA
Alonzo, TA
Arceci, RJ
Meshinchi, S
Marra, MA
AF Lim, Emilia L.
Trinh, Diane L.
Ries, Rhonda E.
Ma, Yussanne
Topham, James
Hughes, Maya D.
Pleasance, Erin
Mungall, Andrew J.
Moore, Richard
Zhao, Yongjun
Gerhard, Daniela S.
Oehler, Vivian
Kolb, E. Anders
Gamis, Alan S.
Smith, Malcolm A.
Alonzo, Todd A.
Arceci, Robert J.
Meshinchi, Soheil
Marra, Marco A.
TI Comprehensive Sequence Analysis of Relapse and Refractory Pediatric
Acute Myeloid Leukemia Identifies miRNA and mRNA Transcripts Associated
with Treatment Resistance - a Report from the COG/NCI-Target AML
Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Lim, Emilia L.; Trinh, Diane L.; Topham, James; Pleasance, Erin; Moore, Richard; Zhao, Yongjun; Marra, Marco A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Ma, Yussanne; Mungall, Andrew J.] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Hughes, Maya D.] Seattle Childrens Hosp, Seattle, WA USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Oehler, Vivian] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Arceci, Robert J.] Phoenix Childrens Hosp, Ronald A Matricaria Inst Mol Med, Phoenix, AZ USA.
[Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002124
ER
PT J
AU Liu, Q
Lopez, L
Pan, C
Velez, D
Corns, JS
Ellenburg, DT
Malech, HL
Murphy, PM
McDermott, DH
AF Liu, Qian
Lopez, Lizbeeth
Pan, Catherina
Velez, Daniel
Corns, John S.
Ellenburg, Donald T.
Malech, Harry L.
Murphy, Philip M.
McDermott, David H.
TI Whim Syndrome Caused By a 5 Base Pair Deletion in the C-Terminus of
Chemokine Receptor CXCR4
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Liu, Qian; Lopez, Lizbeeth; Pan, Catherina; Velez, Daniel; Murphy, Philip M.; McDermott, David H.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Corns, John S.] East Tennessee Childrens Hosp, Pediat Hematol Oncol, Knoxville, TN USA.
[Ellenburg, Donald T.] Allergy & Asthma Affiliates, Knoxville, TN USA.
[Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003127
ER
PT J
AU Liu, Y
Easton, J
Shao, Y
Wilkinson, M
Edmonson, M
Ma, XT
Smith, MA
Rusch, M
Auvil, JG
Gerhard, DS
Relling, MV
Winick, NJ
Raetz, E
Devidas, M
Willman, CL
Harvey, RC
Carroll, WL
Dunsmore, KP
Winter, SS
Wood, BL
Downing, JR
Loh, ML
Hunger, SP
Zhang, JH
Mullighan, CG
AF Liu, Yu
Easton, John
Shao, Ying
Wilkinson, Mark
Edmonson, Michael
Ma, Xiaotu
Smith, Malcolm A.
Rusch, Michael
Auvil, Jaime Guidry
Gerhard, Daniela S.
Relling, Mary V.
Winick, Naomi J.
Raetz, Elizabeth
Devidas, Meenakshi
Willman, Cheryl L.
Harvey, Richard C.
Carroll, William L.
Dunsmore, Kimberly P.
Winter, Stuart S.
Wood, Brent L.
Downing, James R.
Loh, Mignon L.
Hunger, Stephen P.
Zhang, Jinghui
Mullighan, Charles G.
TI The Genomic Landscape of Childhood T-Lineage Acute Lymphoblastic
Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Liu, Yu; Edmonson, Michael] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
[Easton, John; Shao, Ying] St Jude Childrens Res Hosp, Pediat Canc Genome Project Lab, Memphis, TN 38105 USA.
[Wilkinson, Mark; Downing, James R.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Ma, Xiaotu] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Rusch, Michael; Zhang, Jinghui] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
[Auvil, Jaime Guidry] NCI, Bethesda, MD 20892 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Relling, Mary V.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Raetz, Elizabeth] Univ Utah, Huntsman Canc Inst, Dept Pediat, Salt Lake City, UT USA.
[Raetz, Elizabeth] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA.
[Devidas, Meenakshi] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA.
[Willman, Cheryl L.; Harvey, Richard C.] Univ New Mexico, Dept Pathol, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA.
[Carroll, William L.] NYU, Med Ctr, Dept Pediat, Perlmutter Canc Ctr, New York, NY 10016 USA.
[Dunsmore, Kimberly P.] Univ Virginia, Ctr Hlth Sci, Charlottesville, VA USA.
[Winter, Stuart S.] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA.
[Wood, Brent L.] Seattle Canc Care Alliance, Seattle, WA USA.
[Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA USA.
[Hunger, Stephen P.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Hunger, Stephen P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002128
ER
PT J
AU Ma, HS
McCray, ME
Shirley, CM
Duffield, AS
Bruner, JK
Li, L
Nguyen, B
Greenblatt, S
Jung, E
Aplan, PD
Jones, RJ
Small, D
Ghiaur, G
AF Ma, Hayley S.
McCray, Megan E.
Shirley, Courtney M.
Duffield, Amy S.
Bruner, J. Kyle
Li, Li
Bao Nguyen
Greenblatt, Sarah
Jung, Eric
Aplan, Peter D.
Jones, Richard J.
Small, Donald
Ghiaur, Gabriel
TI FLT3 Inhibition and Retinoid Signaling Overcome Stromal Protection to
Target FLT3/ ITD-Expressing Leukemia Stem Cells in the Bone Marrow
Microenvironment
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ma, Hayley S.; Shirley, Courtney M.; Bruner, J. Kyle; Li, Li; Bao Nguyen; Greenblatt, Sarah] Johns Hopkins Univ, Sch Med, Oncol, Baltimore, MD USA.
[McCray, Megan E.; Jones, Richard J.; Ghiaur, Gabriel] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Duffield, Amy S.] Johns Hopkins Univ, Sch Med, Pathol, Baltimore, MD USA.
[Jung, Eric] Penn State Hershey Coll Med, Hummelstown, PA USA.
[Aplan, Peter D.] NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Small, Donald] Johns Hopkins Univ, Sch Med, Oncol & Pediat, Baltimore, MD USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 1
Z9 1
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002227
ER
PT J
AU Mackall, CL
AF Mackall, Crystal L.
TI Latest in Clinical Application of CAR Cell Therapy for B-cell Malignancy
and Transplantation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000026
ER
PT J
AU Matlawska-Wasowska, K
Kang, HN
Devidas, M
Wen, J
Harvey, RC
Nickl, CC
Ness, S
Rusch, M
Li, YJ
Onozawa, M
Martinez, C
Wood, BL
Asselin, B
Chen, IML
Roberts, KG
Baruchel, A
Soulier, J
Dombret, H
Zhang, JH
Larson, RS
Raetz, E
Carroll, WL
Winick, NJ
Aplan, PD
Loh, ML
Mullighan, CG
Hunger, SP
Heerema, NA
Carroll, AJ
Dunsmore, KP
Winter, SS
AF Matlawska-Wasowska, Ksenia
Kang, Huining
Devidas, Meenakshi
Wen, Ji
Harvey, Richard C.
Nickl, Christian C.
Ness, Scott
Rusch, Michael
Li, Yongjin
Onozawa, Masahiro
Martinez, Carmen
Wood, Brent L.
Asselin, Barbara
Chen, I-Ming L.
Roberts, Kathryn G.
Baruchel, Andre
Soulier, Jean
Dombret, Herve
Zhang, Jinghui
Larson, Richard S.
Raetz, Elizabeth
Carroll, William L.
Winick, Naomi J.
Aplan, Peter D.
Loh, Mignon L.
Mullighan, Charles G.
Hunger, Stephen P.
Heerema, Nyla A.
Carroll, Andrew J.
Dunsmore, Kimberly P.
Winter, Stuart S.
TI Mixed Lineage Leukemia Rearrangements (MLL-R) Are Determinants of High
Risk Disease in Homeobox A (HOXA)-deregulated T-Lineage Acute
Lymphoblastic Leukemia: A Children's Oncology Group Study
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Matlawska-Wasowska, Ksenia] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Hematol Oncol, Albuquerque, NM 87131 USA.
[Kang, Huining; Martinez, Carmen] Univ New Mexico, Albuquerque, NM 87131 USA.
[Devidas, Meenakshi] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA.
[Devidas, Meenakshi] Univ Florida, Coll Publ Hlth, Dept Biostat, Gainesville, FL USA.
[Devidas, Meenakshi] Univ Florida, Coll Hlth Profess, Dept Biostat, Gainesville, FL USA.
[Wen, Ji] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Harvey, Richard C.] Univ New Mexico, Ctr Canc, Pathol, Albuquerque, NM 87131 USA.
[Nickl, Christian C.] Univ New Mexico, Pediat, Albuquerque, NM 87131 USA.
[Ness, Scott; Larson, Richard S.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Rusch, Michael; Li, Yongjin; Zhang, Jinghui] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
[Onozawa, Masahiro] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA.
[Wood, Brent L.] Seattle Canc Care Alliance, Seattle, WA USA.
[Asselin, Barbara] Univ Rochester, Pediat Hematol Oncol, Rochester, NY USA.
[Chen, I-Ming L.] Univ New Mexico, Dept Pathol, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA.
[Roberts, Kathryn G.] St Jude Childrens Res Hosp, Pathol, Memphis, TN 38105 USA.
[Baruchel, Andre] Hop St Louis, Dept Pediat Hematol, Paris, France.
[Soulier, Jean] Hop St Louis, Hematol Lab, Paris, France.
[Dombret, Herve] Hop St Louis, Paris, France.
[Raetz, Elizabeth] Univ Utah, Dept Pediat, Huntsman Canc Inst, Salt Lake City, UT USA.
[Raetz, Elizabeth] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA.
[Carroll, William L.] NYU, Med Ctr, Dept Pediat, Perlmutter Canc Ctr, New York, NY 10016 USA.
[Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA USA.
[Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Hunger, Stephen P.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Hunger, Stephen P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Heerema, Nyla A.] Ohio State Univ, Columbus, OH 43210 USA.
[Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
[Dunsmore, Kimberly P.] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA.
[Winter, Stuart S.] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002131
ER
PT J
AU Maxson, JE
Ries, R
Wang, YC
Gerbing, RB
Kolb, EA
Thompson, SL
Auvil, JMG
Marra, MA
Ma, Y
Zong, S
Mungall, AJ
Moore, R
Long, W
Gesuwan, P
Davidsen, TM
Hermida, LC
Farrar, JE
Radich, JP
Smith, MA
Gerhard, DS
Gamis, AS
Alonzo, TA
Meshinchi, S
AF Maxson, Julia Elizabeth
Ries, Rhonda
Wang, Yi-Cheng
Gerbing, Robert B.
Kolb, E. Anders
Thompson, Sarah L.
Auvil, Jaime M. Guidry
Marra, Marco A.
Ma, Yussanne
Zong, Stuart
Mungall, Andrew J.
Moore, Richard
Long, William
Gesuwan, Patee
Davidsen, Tanja M.
Hermida, Leandro C.
Farrar, Jason E.
Radich, Jerald P.
Smith, Malcolm A.
Gerhard, Daniela S.
Gamis, Alan S.
Alonzo, Todd A.
Meshinchi, Soheil
TI CSF3R Mutations Represent a Novel Therapeutic Target in Pediatric AML
with a High Degree of Overlap with CEBPA Mutations: a Report from COG
AAML0531 and COG/NCI Target AML Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Maxson, Julia Elizabeth; Ries, Rhonda; Thompson, Sarah L.; Radich, Jerald P.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Wang, Yi-Cheng; Gerbing, Robert B.; Gamis, Alan S.; Alonzo, Todd A.; Meshinchi, Soheil] Childrens Oncol Grp, Monrovia, CA USA.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Auvil, Jaime M. Guidry; Gesuwan, Patee; Davidsen, Tanja M.; Hermida, Leandro C.; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Marra, Marco A.; Moore, Richard] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Ma, Yussanne; Zong, Stuart; Mungall, Andrew J.; Long, William] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000238
ER
PT J
AU Meyer, SE
Orr, E
Rogers, AM
Doench, JG
Aronow, BJ
Lal, A
McGlinn, E
Grimes, HL
AF Meyer, Sara E.
Orr, Emily
Rogers, Andrew M.
Doench, John G.
Aronow, Bruce J.
Lal, Ashish
McGlinn, Edwina
Grimes, H. Leighton
TI Balancing Proliferation, Differentiation, and Survival: Powerful Genetic
and RNAi Technologies Reveal Essential microRNA Signaling for Leukemic
Progenitor Cell Fitness
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Meyer, Sara E.; Orr, Emily; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
[Rogers, Andrew M.] Cincinnati Childrens Hosp Med Ctr, Div Immunol, Cincinnati, OH 45229 USA.
[Doench, John G.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA.
[Aronow, Bruce J.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
[Lal, Ashish] NCI, Mol Genet Branch, Bethesda, MD 20892 USA.
[McGlinn, Edwina] European Mol Biol Lab, Clayton, Vic, Australia.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001193
ER
PT J
AU Miller, JS
Verneris, MR
Curtsinger, J
DeFor, TE
McKenna, D
Waldmann, TA
Blazar, BR
Weisdorf, DJ
Cooley, S
AF Miller, Jeffrey S.
Verneris, Michael R.
Curtsinger, Julie
DeFor, Todd E.
McKenna, David
Waldmann, Thomas A.
Blazar, Bruce R.
Weisdorf, Daniel J.
Cooley, Sarah
TI A Phase I Study of Intravenous NCI IL-15 to Enhance Adoptively
Transferred NK Cells Uncovers Defects in CD16 Triggered IFN gamma
Production and Competition Between Donor NK and Recipient T Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Miller, Jeffrey S.; Verneris, Michael R.; Curtsinger, Julie; DeFor, Todd E.; McKenna, David; Blazar, Bruce R.; Weisdorf, Daniel J.; Cooley, Sarah] Univ Minnesota, Adult & Pediat Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002003
ER
PT J
AU Montiel-Esparza, R
Knaus, HA
Zeidner, JF
Vulic, A
Prince, GT
Smith, BD
Levis, MJ
Streicher, H
Karp, JE
Luznik, L
Gojo, I
AF Montiel-Esparza, Raul
Knaus, Hanna A.
Zeidner, Joshua F.
Vulic, Ante
Prince, Gabrielle T.
Smith, B. Douglas
Levis, Mark J.
Streicher, Howard
Karp, Judith E.
Luznik, Leo
Gojo, Ivana
TI Immune Modulation with Pomalidomide after Induction Chemotherapy in
Newly Diagnosed Acute Myeloid Leukemia (AML)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Montiel-Esparza, Raul] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Knaus, Hanna A.; Vulic, Ante; Prince, Gabrielle T.; Smith, B. Douglas; Levis, Mark J.; Karp, Judith E.; Luznik, Leo; Gojo, Ivana] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Zeidner, Joshua F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
[Streicher, Howard] NCI, NIH, CTEP, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004151
ER
PT J
AU Morton, LM
Dores, GM
Shiels, MS
Linet, MS
Teepen, JC
Lam, CJK
Tucker, MA
Curtis, RE
AF Morton, Lindsay M.
Dores, Graca M.
Shiels, Meredith S.
Linet, Martha S.
Teepen, Jop C.
Lam, Clara J. K.
Tucker, Margaret A.
Curtis, Rochelle E.
TI Emerging Risks of AML/MDS and Other Myeloid Neoplasms Following
Chemotherapy for First Primary Malignancy, 2000-2012
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Morton, Lindsay M.; Dores, Graca M.; Tucker, Margaret A.] NIH, Div Canc Epidemiol & Genet, NCI, DHHS, Bethesda, MD 20892 USA.
[Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK USA.
[Linet, Martha S.; Curtis, Rochelle E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Teepen, Jop C.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol, NL-6525 ED Nijmegen, Netherlands.
[Lam, Clara J. K.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001308
ER
PT J
AU Mueller, F
Liu, XF
Wayne, AS
Pastan, I
AF Mueller, Fabian
Liu, Xiu-Fen
Wayne, Alan S.
Pastan, Ira
TI Immunotoxin Activity Against B-Lineage Leukemia and Lymphoma Is Exposure
Time Dependent: Implications for Trial Design
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Mueller, Fabian; Liu, Xiu-Fen] NCI, CCR, LMB, NIH, Bethesda, MD 20892 USA.
[Wayne, Alan S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90033 USA.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004132
ER
PT J
AU Naik, RP
Irvin, MR
Judd, S
Gutierrez, O
Zakai, NA
Derebail, VK
Peralta, C
Lewis, M
Zhi, DG
Arnett, D
McClellan, W
Wilson, JG
Reiner, A
Kopp, J
Winkler, C
Cushman, M
AF Naik, Rakhi P.
Irvin, Marguerite R.
Judd, Suzanne
Gutierrez, Orlando
Zakai, Neil A.
Derebail, Vimal K.
Peralta, Carmen
Lewis, Michael
Zhi, Degui
Arnett, Donna
McClellan, William
Wilson, James G.
Reiner, Alexander
Kopp, Jeffrey
Winkler, Cheryl
Cushman, Mary
TI Association of Hemoglobin S and C Traits with Kidney Disease in African
Americans in the Reasons for Geographic and Racial Differences in Stroke
(REGARDS) Study
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Naik, Rakhi P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Irvin, Marguerite R.; Judd, Suzanne; Gutierrez, Orlando; Zhi, Degui; Arnett, Donna] Univ Alabama Birmingham, Birmingham, AL USA.
[Zakai, Neil A.] Univ Vermont, Dept Med, Burlington, VT USA.
[Zakai, Neil A.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Derebail, Vimal K.] Univ N Carolina, UNC Kidney Ctr, Chapel Hill, NC USA.
[Peralta, Carmen] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lewis, Michael; Cushman, Mary] Univ Vermont, Burlington, VT USA.
[McClellan, William] Emory Univ, Atlanta, GA 30322 USA.
[Wilson, James G.] Univ Mississippi, Jackson, MS 39216 USA.
[Reiner, Alexander] Univ Washington, Seattle, WA 98195 USA.
[Kopp, Jeffrey] NIDDK, Bethesda, MD 20892 USA.
[Winkler, Cheryl] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000134
ER
PT J
AU Nayar, U
Sadek, J
Reichel, JB
Bunn, D
Hernandez-Hopkins, D
Barelli, P
Sahai, M
Totonchy, J
Shizuko, S
Shoemaker, R
Warren, D
Elemento, O
Kaye, K
Cesarman, E
AF Nayar, Utthara
Sadek, Jouliana
Reichel, Jonathan B.
Bunn, David
Hernandez-Hopkins, Denise
Barelli, Peter
Sahai, Michelle
Totonchy, Jennifer
Shizuko, Sei
Shoemaker, Robert
Warren, David
Elemento, Olivier
Kaye, Kenneth
Cesarman, Ethel
TI Exquisite Sensitivity of Plasma Cell Malignancies to a Novel Nucleoside
Analog Is Mediated By Overexpressed Adenosine Kinase
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Nayar, Utthara; Sadek, Jouliana; Reichel, Jonathan B.; Hernandez-Hopkins, Denise; Totonchy, Jennifer; Cesarman, Ethel] Weill Cornell Med Coll, Pathol & Lab Med, New York, NY USA.
[Bunn, David] Weill Cornell Med Coll, Gateways Lab Program, New York, NY USA.
[Barelli, Peter; Warren, David] Weill Cornell Med Coll, Dept Biochem, New York, NY USA.
[Sahai, Michelle; Elemento, Olivier] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA.
[Shizuko, Sei] NCI, Viral Vector Toxicol Sect, LHTP, SAIC Frederick, Frederick, MD 21701 USA.
[Shoemaker, Robert] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Kaye, Kenneth] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005290
ER
PT J
AU Ostronoff, F
Ries, RE
Gerbing, RB
Marra, MA
Yussanne, M
Long, W
Zong, S
Mungall, K
Andrew, A
Gerhard, DS
Smith, MA
Patee, G
Davidsen, TM
Hermida, LC
Farrar, JE
Auvil, JG
Raimondi, SC
Hirsch, BA
Kolb, EA
Gamis, AS
Alonzo, TA
Meshinchi, S
AF Ostronoff, Fabiana
Ries, Rhonda E.
Gerbing, Robert B.
Marra, Marco A.
Yussanne, Ma
Long, William
Zong, Stuart
Mungall, Karen
Andrew, Andrew
Gerhard, Daniela S.
Smith, Malcolm A.
Patee, Gesuwan
Davidsen, Tanja M.
Hermida, Leandro C.
Farrar, Jason E.
Auvil, Jaime Guidry
Raimondi, Susana C.
Hirsch, Betsy A.
Kolb, E. Anders
Gamis, Alan S.
Alonzo, Todd A.
Meshinchi, Soheil
TI Rearrangements in Nucleoporin Family of Genes in Childhood Acute Myeloid
Leukemia: A Report from Children Oncology Group and NCI/COG Target AML
Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ostronoff, Fabiana; Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Gerbing, Robert B.; Hirsch, Betsy A.] Childrens Oncol Grp, Monrovia, CA USA.
[Marra, Marco A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Yussanne, Ma; Andrew, Andrew] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Long, William; Zong, Stuart; Mungall, Karen] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Gerhard, Daniela S.; Davidsen, Tanja M.; Hermida, Leandro C.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Patee, Gesuwan; Auvil, Jaime Guidry] NCI, Bethesda, MD 20892 USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Raimondi, Susana C.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000233
ER
PT J
AU Park, SM
Thornton, A
Vu, LP
Chhangawala, S
Minuesa, G
Barlowe, T
Taggart, J
Tivnan, P
Kim, T
Shevach, E
Leslie, CS
Kharas, MG
AF Park, Sun Mi
Thornton, Angela
Vu, Ly P.
Chhangawala, Sagar
Minuesa, Gerard
Barlowe, Trevor
Taggart, James
Tivnan, Patrick
Kim, Theodore
Shevach, Ethan
Leslie, Christina S.
Kharas, Michael G.
TI IKZF2, a Novel Target of MSI2 RNA-Binding Protein Plays an Oncogenic
Role in Myeloid Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Park, Sun Mi; Vu, Ly P.; Minuesa, Gerard; Barlowe, Trevor; Taggart, James; Tivnan, Patrick; Kim, Theodore; Kharas, Michael G.] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10021 USA.
[Thornton, Angela; Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA.
[Chhangawala, Sagar; Leslie, Christina S.] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001192
ER
PT J
AU Philpott, CC
Frey, AG
Ryu, MS
Palenchar, D
Wildemann, J
Vashisht, AA
Wohlschlegel, J
Bullough, K
AF Philpott, Caroline C.
Frey, Avery G.
Ryu, Moon-Suhn
Palenchar, Daniel
Wildemann, Justin
Vashisht, Ajay A.
Wohlschlegel, James
Bullough, Kymberly
TI Special Delivery: The Role of Iron Chaperones in the Distribution of
Iron in Developing Red Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Philpott, Caroline C.; Ryu, Moon-Suhn] NIDDK, Bethesda, MD 20892 USA.
[Frey, Avery G.; Palenchar, Daniel; Wildemann, Justin; Bullough, Kymberly] NIDDK, NIH, Bethesda, MD 20892 USA.
[Vashisht, Ajay A.; Wohlschlegel, James] Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000049
ER
PT J
AU Poe, JC
Jia, W
Li, ZG
Hakim, FT
Pavletic, SZ
Rose, JJ
Rizzieri, DA
Yang, YP
Chen, BJ
Green, M
Anand, S
Siebel, CW
Maillard, I
Chao, NJ
Sarantopoulos, S
AF Poe, Jonathan C.
Jia, Wei
Li, Zhiguo
Hakim, Frances T.
Pavletic, Steven Z.
Rose, Jeremy J.
Rizzieri, David A.
Yang, Yiping
Chen, Benny J.
Green, Michael
Anand, Sarah
Siebel, Christian W.
Maillard, Ivan
Chao, Nelson J.
Sarantopoulos, Stefanie
TI Targeting the Human Notch 2-BCR Axis: A Driver of B-Cell
Hyper-Responsiveness in Active Chronic Graft-Versus Host Disease (cGVHD)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Poe, Jonathan C.; Jia, Wei; Li, Zhiguo; Rizzieri, David A.; Yang, Yiping; Chen, Benny J.; Green, Michael; Anand, Sarah; Chao, Nelson J.; Sarantopoulos, Stefanie] Duke Univ, Med Ctr, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27710 USA.
[Hakim, Frances T.; Pavletic, Steven Z.; Rose, Jeremy J.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Siebel, Christian W.] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
[Maillard, Ivan] Univ Michigan, Ctr Stem Cell Biol, Inst Life Sci, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000209
ER
PT J
AU Rubinstein, PG
Moore, P
Henry, DH
Ratner, L
Sharon, E
Noy, A
AF Rubinstein, Paul G.
Moore, Page
Henry, David H.
Ratner, Lee
Sharon, Elad
Noy, Ariela
TI AMC-085: A Pilot Trial of AVD and Brentuximab Vedotin in the Upfront
Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma. A Trial of the
AIDS Malignancy Consortium
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Rubinstein, Paul G.] John H Stroger Jr Hosp Cook Cty, Dept Med, Chicago, IL USA.
[Moore, Page] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
[Henry, David H.] Penn Onc Hem Associates, Philadelphia, PA USA.
[Ratner, Lee] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA.
[Sharon, Elad] NCI, Bethesda, MD 20892 USA.
[Noy, Ariela] Mem Sloan Kettering Canc Ctr, Med, Lymphoma Serv, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005004
ER
PT J
AU Ryu, MS
Wohlschlegel, J
Philpott, CC
AF Ryu, Moon-Suhn
Wohlschlegel, James
Philpott, Caroline C.
TI Pcbp1 and Ncoa4 Regulate the Flux of Iron through Ferritin in Developing
Erythroid Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ryu, Moon-Suhn; Philpott, Caroline C.] NIDDK, Bethesda, MD 20892 USA.
[Wohlschlegel, James] Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001156
ER
PT J
AU Saleh, LM
Wang, WX
Herman, SEM
Farooqui, M
Sun, C
Barber, E
Corrigan-Cummins, M
Saba, N
Awad, H
Wiestner, A
Calvo, KR
AF Saleh, Layla M.
Wang, Weixin
Herman, Sarah E. M.
Farooqui, Mohammed
Sun, Clare
Barber, Emily
Corrigan-Cummins, Meghan
Saba, Nakhle
Awad, Hasan
Wiestner, Adrian
Calvo, Katherine R.
TI Ibrutinib Responsive Micro-RNAs and Upregulation of Tumor Suppressor
Targets in Chronic Lymphocytic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Saleh, Layla M.; Wang, Weixin; Barber, Emily; Corrigan-Cummins, Meghan; Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Saleh, Layla M.; Awad, Hasan] Mansoura Univ Hosp, Clin Pathol, Mansoura, Egypt.
[Herman, Sarah E. M.; Farooqui, Mohammed; Sun, Clare; Saba, Nakhle; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001233
ER
PT J
AU Scott, BL
Pasquini, MC
Logan, B
Wu, J
Devine, S
Porter, DL
Maziarz, RT
Warlick, E
Fernandez, HF
Alyea, EP
Hamadani, M
Bashey, A
Giralt, SA
Leifer, E
Geller, N
Le-Rademacher, J
Mendizabal, AM
Horowitz, MM
Deeg, HJ
Horwitz, ME
AF Scott, Bart L.
Pasquini, Marcelo C.
Logan, Brent
Wu, Juan
Devine, Steve
Porter, David L.
Maziarz, Richard T.
Warlick, Erica
Fernandez, Hugo F.
Alyea, Edwin P.
Hamadani, Mehdi
Bashey, Asad
Giralt, Sergio A.
Leifer, Eric
Geller, Nancy
Le-Rademacher, Jennifer
Mendizabal, Adam M.
Horowitz, Mary M.
Deeg, H. Joachim
Horwitz, Mitchell E.
TI Results of a Phase III Randomized, Multi-Center Study of Allogeneic Stem
Cell Transplantation after High Versus Reduced Intensity Conditioning in
Patients with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia
(AML): Blood and Marrow Transplant Clinical Trials Network (BMT CTN)
0901
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Scott, Bart L.; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Scott, Bart L.; Deeg, H. Joachim] Univ Washington, Seattle, WA 98195 USA.
[Pasquini, Marcelo C.] Med Coll Wisconsin, Med, Milwaukee, WI 53226 USA.
[Logan, Brent] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Wu, Juan] Emmes Corp, Rockville, MD USA.
[Devine, Steve] Ohio State Univ, Columbus, OH 43210 USA.
[Porter, David L.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Adult Blood & Marrow Stem Cell Transplant Program, Portland, OR 97201 USA.
[Warlick, Erica] Univ Minnesota, Minneapolis, MN USA.
[Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Blood & Marrow Transplantat, Tampa, FL 33682 USA.
[Alyea, Edwin P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Alyea, Edwin P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hamadani, Mehdi] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
[Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA.
[Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, New York, NY 10021 USA.
[Leifer, Eric; Geller, Nancy] NHLBI, Bethesda, MD 20892 USA.
[Le-Rademacher, Jennifer] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Mendizabal, Adam M.] EMMES Corp, Rockville, MD USA.
[Horowitz, Mary M.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Horwitz, Mitchell E.] Duke Univ, Med Ctr, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA.
NR 0
TC 15
Z9 15
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000009
ER
PT J
AU Senkevitch, E
Hixon, J
Andrews, C
Barata, JT
Li, WQ
Durum, S
AF Senkevitch, Emilee
Hixon, Julie
Andrews, Caroline
Barata, Joao T.
Li, Wenqing
Durum, Scott
TI The JAK Inhibitor Ruxolitinib Is Effective in Treating T Cell Acute
Lymphoblastic Leukemia with Gain of Function Mutations in IL-7R Alpha
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Senkevitch, Emilee; Hixon, Julie; Andrews, Caroline; Li, Wenqing; Durum, Scott] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Barata, Joao T.] Univ Lisbon, Inst Mol Med, Fac Med, P-1699 Lisbon, Portugal.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019004130
ER
PT J
AU Shaffer, BC
Ahn, KW
Hu, ZH
Popat, UR
Kalaycio, M
Maziarz, RT
Alyea, E
Sobecks, RM
Pavletic, SZ
Tallman, MS
Saber, W
AF Shaffer, Brian C.
Ahn, Kwang Woo
Hu, Zhen-Huan
Popat, Uday R.
Kalaycio, Matt
Maziarz, Richard T.
Alyea, Edwin
Sobecks, Ron M.
Pavletic, Steven Z.
Tallman, Martin S.
Saber, Wael
TI A Prognostic System Predictive of Outcomes in Persons Undergoing
Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic
Syndrome
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Shaffer, Brian C.] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Serv, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Ahn, Kwang Woo; Saber, Wael] Med Coll Wisconsin, CIBMTR, Dept Med, Milwaukee, WI 53226 USA.
[Hu, Zhen-Huan] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Popat, Uday R.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Kalaycio, Matt] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Adult Blood & Marrow Stem Cell Transplant Program, Portland, OR 97201 USA.
[Alyea, Edwin] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA.
[Sobecks, Ron M.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000128
ER
PT J
AU Smith, F
Brawand, D
Steedman, L
Oakley, M
Wall, C
Rushton, P
Allchurch, M
Sibson, K
Hemmaway, CJ
Thein, SL
Rees, DC
Clark, BE
AF Smith, Frances
Brawand, David
Steedman, Laura
Oakley, Matthew
Wall, Christopher
Rushton, Peter
Allchurch, Margaret
Sibson, Keith
Hemmaway, Claire Jane
Thein, Swee Lay
Rees, David C.
Clark, Barnaby E.
TI A Comprehensive Next Generation Sequencing Gene Panel Focused on
Unexplained Anemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Smith, Frances; Brawand, David; Steedman, Laura; Oakley, Matthew; Wall, Christopher; Rushton, Peter; Clark, Barnaby E.] Viapath Kings Coll Hosp, Dept Mol Pathol, London, England.
[Allchurch, Margaret] Queens Hosp, Haematol, Romford, Essex, England.
[Sibson, Keith] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Hemmaway, Claire Jane] Ba, Romford, Essex, England.
[Thein, Swee Lay] NHLBI, NIH, Bethesda, MD 20892 USA.
[Thein, Swee Lay; Clark, Barnaby E.] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Rees, David C.] Kings Coll Hosp London, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003070
ER
PT J
AU Stroncek, DF
Lee, DW
Ren, JQ
Sabatino, M
Khuu, H
Merchant, MS
Mackall, CL
AF Stroncek, David F.
Lee, Daniel W., III
Ren, Jiaqiang
Sabatino, Marianna
Khuu, Hanh
Merchant, Melinda S.
Mackall, Crystal L.
TI Myeloid Cells in Peripheral Blood Mononuclear Cell (PMBC) Concentrates
Inhibit the Expansion of Chimeric Antigen Receptor (CAR) T Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Stroncek, David F.; Ren, Jiaqiang; Sabatino, Marianna; Khuu, Hanh] NIH, Dept Transfus Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Lee, Daniel W., III] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Merchant, Melinda S.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001135
ER
PT J
AU Sun, L
AF Sun, Lei
TI Id2 Is Required for the Self-Renewal and Proliferation of Hematopoietic
Stem Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Sun, Lei] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003297
ER
PT J
AU Tarlock, K
Hansen, ME
Hylkema, T
Ries, R
Farrar, JE
Auvil, JG
Gerhard, DS
Smith, MA
Davidsen, TM
Gesuwan, P
Hermida, LC
Marra, MA
Mungall, AJ
Mungall, K
Ma, Y
Zong, S
Long, W
Boggon, T
Alonzo, TA
Kolb, EA
Gamis, AS
Meshinchi, S
AF Tarlock, Katherine
Hansen, M. Eva
Hylkema, Tiffany
Ries, Rhonda
Farrar, Jason E.
Auvil, Jaime Guidry
Gerhard, Daniela S.
Smith, Malcolm A.
Davidsen, Tanja M.
Gesuwan, Patee
Hermida, Leandro C.
Marra, Marco A.
Mungall, Andrew J.
Mungall, Karen
Ma, Yussanne
Zong, Stuart
Long, William
Boggon, Titus
Alonzo, Todd A.
Kolb, E. Anders
Gamis, Alan S.
Meshinchi, Soheil
TI Discovery and Functional Validation of Novel Pediatric Specific FLT3
Activating Mutations in Acute Myeloid Leukemia: Results from the COG/NCI
Target Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Tarlock, Katherine; Hansen, M. Eva; Hylkema, Tiffany] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Ries, Rhonda; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Auvil, Jaime Guidry] NCI, Bethesda, MD 20892 USA.
[Gerhard, Daniela S.; Davidsen, Tanja M.; Gesuwan, Patee; Hermida, Leandro C.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Ctep, Cib, NIH, Bethesda, MD 20892 USA.
[Marra, Marco A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Mungall, Andrew J.; Mungall, Karen; Ma, Yussanne; Zong, Stuart; Long, William] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Boggon, Titus] Yale Univ, Sch Med, Pharmacol, New Haven, CT USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000151
ER
PT J
AU Townsley, DM
Dumitriu, B
Scheinberg, P
Desmond, R
Feng, XM
Rios, O
Weinstein, B
Valdez, J
Winkler, T
Desierto, M
Leuva, H
Wu, CL
Calvo, KR
Larochelle, A
Dunbar, CE
Young, NS
AF Townsley, Danielle M.
Dumitriu, Bogdan
Scheinberg, Phillip
Desmond, Ronan
Feng, Xingmin
Rios, Olga
Weinstein, Barbara
Valdez, Janet
Winkler, Thomas
Desierto, Marie
Leuva, Harshraj
Wu, Colin
Calvo, Katherine R.
Larochelle, Andre
Dunbar, Cynthia E.
Young, Neal S.
TI Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia
Accelerates Count Recovery and Increases Response Rates
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Townsley, Danielle M.; Dumitriu, Bogdan; Feng, Xingmin; Rios, Olga; Weinstein, Barbara; Valdez, Janet; Winkler, Thomas; Desierto, Marie; Leuva, Harshraj; Larochelle, Andre; Dunbar, Cynthia E.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Scheinberg, Phillip] Hosp Beneficencia Portuguesa Sao Paulo, Hosp Sao Jose, Sao Paulo, Brazil.
[Desmond, Ronan] Tallaght Hosp, Dept Haematol, Dublin, Ireland.
[Wu, Colin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000003
ER
PT J
AU Tumburu, L
Byrnes, C
Lee, YT
de Vasconcellos, JF
Rabel, A
Miller, JL
AF Tumburu, Laxminath
Byrnes, Colleen
Lee, Y. Terry
de Vasconcellos, Jaira F.
Rabel, Antoinette
Miller, Jeffery L.
TI IGF2BP1 Reverses Hemoglobin Switching in Adult Erythroblasts
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Tumburu, Laxminath; Byrnes, Colleen; Lee, Y. Terry; de Vasconcellos, Jaira F.; Rabel, Antoinette; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019002076
ER
PT J
AU Uchida, N
Atsushi, F
Juan, HMJ
Winkler, T
Tisdale, JF
AF Uchida, Naoya
Atsushi, Fujita
Juan, Haro-Mora J.
Winkler, Thomas
Tisdale, John F.
TI More Efficient Generation of beta-Globin-Expressing Erythroid Cells
Using Stromal Cell-Derived Induced Pluripotent Stem Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Uchida, Naoya; Atsushi, Fujita; Juan, Haro-Mora J.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA.
[Winkler, Thomas] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003274
ER
PT J
AU Voorhees, PM
Mulkey, F
Hassoun, H
Paba-Prada, CE
Efebera, YA
Hoke, E
Aquino, G
Carlisle, D
Suman, V
Richardson, PG
AF Voorhees, Peter M.
Mulkey, Flora
Hassoun, Hani
Paba-Prada, Claudia E.
Efebera, Yvonne A.
Hoke, Eva
Aquino, Guadalupe
Carlisle, Destin
Suman, Vera
Richardson, Paul G.
TI Alliance A061202. a Phase I/II Study of Pomalidomide, Dexamethasone and
Ixazomib Versus Pomalidomide and Dexamethasone for Patients with
Multiple Myeloma Refractory to Lenalidomide and Proteasome Inhibitor
Based Therapy: Phase I Results
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Mulkey, Flora; Hoke, Eva] Alliance Stat & Data Ctr, Durham, NC USA.
[Hassoun, Hani] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, New York, NY 10021 USA.
[Paba-Prada, Claudia E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA.
[Efebera, Yvonne A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Aquino, Guadalupe] NINDS, Off Clin Res, NIH, Bethesda, MD 20892 USA.
[Carlisle, Destin] Univ Chicago, Alliance Protocol Operat Off, Chicago, IL 60637 USA.
[Suman, Vera] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
[Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Hematol Malignancy, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
RI Efebera, Yvonne/E-3012-2011
NR 0
TC 0
Z9 0
U1 0
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001127
ER
PT J
AU Whitehill, G
Amarnath, S
Keyvanfar, K
Muranski, P
Battiwalla, M
Barrett, AJ
Chinnasamy, D
AF Whitehill, Greg
Amarnath, Shoba
Keyvanfar, Keyvan
Muranski, Pawel
Battiwalla, Minoo
Barrett, Austin John
Chinnasamy, Dhana
TI Selective Depletion of Alloreactive Donor T Cells with Adenosine: An
Efficient, Scaleable, GMP-Compliant, Low-Cost Method to Prevent Gvhd
While Preserving Antiviral and Antileukemic Activity in Haploidentical
Stem Cell Transplant
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Whitehill, Greg; Keyvanfar, Keyvan; Muranski, Pawel; Battiwalla, Minoo; Barrett, Austin John; Chinnasamy, Dhana] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Amarnath, Shoba] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019001132
ER
PT J
AU Wilson, WH
Popplewell, LL
Phillips, T
Kimball, AS
Chhabra, S
Ping, J
Neuenburg, J
Cavazos, N
Staudt, LM
de Vos, S
AF Wilson, Wyndham H.
Popplewell, Leslie L.
Phillips, Tycel
Kimball, Amy S.
Chhabra, Saurabh
Ping, Jerry
Neuenburg, Jutta
Cavazos, Nora
Staudt, Louis M.
de Vos, Sven
TI Multicenter Phase 1b Dose-Escalation Study of Ibrutinib and Lenalidomide
Combined with Dose-Adjusted EPOCH-R in Patients with Relapsed/Refractory
DLBCL
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Wilson, Wyndham H.; Staudt, Louis M.] NCI, Bethesda, MD 20892 USA.
[Popplewell, Leslie L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Phillips, Tycel] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kimball, Amy S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Chhabra, Saurabh] Med Univ S Carolina, Charleston, SC 29425 USA.
[Ping, Jerry; Neuenburg, Jutta; Cavazos, Nora] Pharmacyclics LLC, Sunnyvale, CA USA.
[de Vos, Sven] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005005
ER
PT J
AU Wu, CF
Koelle, SJ
Li, B
Espinoza, D
Lu, R
Krouse, AE
Metzger, M
Donahue, R
Dunbar, CE
AF Wu, Chuanfeng
Koelle, Samson J.
Li, Brian
Espinoza, Diego
Lu, Rong
Krouse, Allen E.
Metzger, Mark
Donahue, Robert
Dunbar, Cynthia E.
TI Clonal Tracking of the Geographic Distribution of Hematopoiesis in
Nonhuman Primates Provides New Insights into HSPC Migration and
Differentiation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Wu, Chuanfeng; Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Koelle, Samson J.; Li, Brian; Espinoza, Diego; Krouse, Allen E.; Metzger, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Lu, Rong] Univ So Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000305
ER
PT J
AU Yang, YM
Lin, TS
Jacoby, E
Qin, HY
Gardner, EG
Chien, CD
Lee, DW
Fry, TJ
AF Yang, Yinmeng
Lin, Tasha
Jacoby, Elad
Qin, Haiying
Gardner, Elizabeth Grier
Chien, Christopher Daniel
Lee, Daniel W., III
Fry, Terry J.
TI CD4 CAR T Cells Mediate CD8-like Cytotoxic Anti-Leukemic Effects
Resulting in Leukemic Clearance and Are Less Susceptible to Attenuation
By Endogenous TCR Activation Than CD8 CAR T Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Yang, Yinmeng; Lin, Tasha; Jacoby, Elad; Qin, Haiying; Gardner, Elizabeth Grier; Chien, Christopher Daniel; Lee, Daniel W., III; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yang, Yinmeng] Georgetown Univ, Dept Tumor Biol, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019000164
ER
PT J
AU Yu, KR
Wu, CF
Espinoza, D
Yabe, I
Panch, SR
Hong, SG
Koelle, SJ
Lu, R
Bonifacino, A
Krouse, A
Metzger, M
Donahue, R
Dunbar, CE
AF Yu, Kyung-Rok
Wu, Chuanfeng
Espinoza, Diego
Yabe, Idalia
Panch, Sandhya R.
Hong, So Gun
Koelle, Samson Jonathan
Lu, Rong
Bonifacino, Aylin
Krouse, Alan
Metzger, Mark
Donahue, Robert
Dunbar, Cynthia E.
TI The Impact of Aging of Hematopoietic Stem and Progenitor Cells (HSPCs)
in Non-Human Primates As Interrogated By Genetic Barcode Clonal Tracking
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Yu, Kyung-Rok; Espinoza, Diego; Yabe, Idalia; Panch, Sandhya R.; Hong, So Gun; Koelle, Samson Jonathan; Bonifacino, Aylin; Krouse, Alan; Metzger, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Chuanfeng; Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Lu, Rong] Univ So Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019003275
ER
PT J
AU Zeidan, AM
Zeidner, JF
Duffield, A
Knaus, HA
Ferguson, A
Sheldon, K
DeZern, AE
Gojo, I
Gore, SD
Streicher, H
Luznik, L
Smith, BD
AF Zeidan, Amer M.
Zeidner, Joshua F.
Duffield, Amy
Knaus, Hanna A.
Ferguson, Anna
Sheldon, Katherine
DeZern, Amy E.
Gojo, Ivana
Gore, Steven D.
Streicher, Howard
Luznik, Leo
Smith, B. Douglas
TI Stabilization of Myelodysplastic Syndromes (MDS) Following
Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint
Inhibitor Ipilimumab: A Phase I Trial
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Zeidan, Amer M.] Yale Univ, Sch Med, New Haven, CT USA.
[Zeidner, Joshua F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Duffield, Amy; Knaus, Hanna A.; Ferguson, Anna; Sheldon, Katherine; Luznik, Leo; Smith, B. Douglas] Johns Hopkins Univ, Baltimore, MD USA.
[Knaus, Hanna A.; Gojo, Ivana] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[DeZern, Amy E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Gore, Steven D.] Yale Canc Ctr, New Haven, CT USA.
[Streicher, Howard] NCI, NIH, CTEP, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XN
UT WOS:000368019005144
ER
PT J
AU Aerbajinai, W
Joo, J
Yan, M
Kumkhaek, C
Rodgers, GP
AF Aerbajinai, Wulin
Joo, Jungsoo
Yan, Ming
Kumkhaek, Chutima
Rodgers, Griffin P.
TI Glia Maturation Factor-Gamma Regulates the Intracellular Growth of
Salmonella Via Modulation of Ferroportin in Murine Macrophages
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Aerbajinai, Wulin; Kumkhaek, Chutima; Rodgers, Griffin P.] NHLBI, NIH, Mol & Clin Hematol Branch, Bethesda, MD USA.
[Joo, Jungsoo; Yan, Ming] NHLBI, NIH, Lab Biochem & Genet, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101046
ER
PT J
AU Alter, BP
Ballew, BJ
Giri, N
Chandrasekharappa, S
Ameziane, N
de Winter, J
Savage, SA
AF Alter, Blanche P.
Ballew, Bari J.
Giri, Neelam
Chandrasekharappa, Settara
Ameziane, Najim
de Winter, Johan
Savage, Sharon A.
TI Novel Fanci Mutations in Fanconi Anemia with Vacterl Association
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Alter, Blanche P.; Ballew, Bari J.; Giri, Neelam; Savage, Sharon A.] NCI, Clin Genet Branch, DCEG, Bethesda, MD 20892 USA.
[Chandrasekharappa, Settara] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ameziane, Najim] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[de Winter, Johan] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021803083
ER
PT J
AU Anandi, P
Tian, X
Chokshi, PD
Watters, N
Ito, S
Battiwalla, M
Barrett, AJ
AF Anandi, Prathima
Tian, Xin
Chokshi, Puja D.
Watters, Noelle
Ito, Sawa
Battiwalla, Minoo
Barrett, Austin John
TI T Cell Depleted Allogeneic Stem Cell Transplants for Hematological
Malignancies: A 20 Year Experience Shows No Relationship Between Choice
of Transplanted T Cell Dose or Delayed T Cell Add-Back on Major Outcomes
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Anandi, Prathima; Chokshi, Puja D.; Ito, Sawa; Battiwalla, Minoo; Barrett, Austin John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, Xin; Watters, Noelle] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100178
ER
PT J
AU Arons, E
Davies, S
Still, K
Chai, N
Potocka, K
Zhou, H
Kreitman, RJ
AF Arons, Evgeny
Davies, Sarah
Still, Katherine
Chai, Nathan
Potocka, Katherine
Zhou, Hong
Kreitman, Robert J.
TI Molecular Evidence of Ongoing Antigen Driven Somatic Hypermutation in
the Natural History of Classic and Variant Hairy Cell Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Arons, Evgeny; Davies, Sarah; Still, Katherine; Chai, Nathan; Potocka, Katherine; Zhou, Hong; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102160
ER
PT J
AU Bot, A
Rossi, JM
Jiang, YZ
Navale, L
Shen, YW
Sherman, M
Mardiros, A
Yoder, SC
Go, WY
Rosenberg, SA
Wiezorek, J
Chang, DD
Kochenderfer, JN
Roberts, MR
AF Bot, Adrian
Rossi, John M.
Jiang, Yizhou
Navale, Lynn
Shen, Yueh-wei
Sherman, Marika
Mardiros, Armen
Yoder, Sean C.
Go, William Y.
Rosenberg, Steven A.
Wiezorek, Jeff
Chang, David D.
Kochenderfer, James N.
Roberts, Margo R.
TI Cyclophosphamide and Fludarabine Conditioning Chemotherapy Induces a Key
Homeostatic Cytokine Profile in Patients Prior to CAR T Cell Therapy
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Bot, Adrian; Rossi, John M.; Jiang, Yizhou; Navale, Lynn; Shen, Yueh-wei; Sherman, Marika; Mardiros, Armen; Yoder, Sean C.; Go, William Y.; Wiezorek, Jeff; Chang, David D.; Roberts, Margo R.] Kite Pharma, Santa Monica, CA USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021802051
ER
PT J
AU Bresciani, E
Carrington, B
Kwon, EM
Jones, M
Wincovitch, S
Sood, RB
Liu, PP
AF Bresciani, Erica
Carrington, Blake
Kwon, Erika Mijin
Jones, Marypat
Wincovitch, Stephen
Sood, Raman B.
Liu, Paul P.
TI Development of Multi-Lineage Hematopoiesis in Two Novel Zebrafish runx1
mutants
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Bresciani, Erica; Kwon, Erika Mijin; Sood, Raman B.; Liu, Paul P.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Carrington, Blake; Jones, Marypat; Wincovitch, Stephen] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101211
ER
PT J
AU Carlsten, M
Namazi, A
Reger, RN
Berg, M
Childs, RW
AF Carlsten, Mattias
Namazi, Ali
Reger, Robert N.
Berg, Maria
Childs, Richard W.
TI ER-Stress-Induced Suppression of HLA-E on Bortezomib-Evading Malignant
Plasma Cells Dramatically Enhances Their Susceptibility to NK Cell
Killing: Identification of an Achilles Heel in Myeloma Cells That Can be
Utilized to Prevent Disease Relapse Following Bortezomib Treatment
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Carlsten, Mattias; Namazi, Ali; Reger, Robert N.; Berg, Maria; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801238
ER
PT J
AU Cherkasova, E
Espinoza, L
Kotecha, R
Reger, RN
Berg, M
Aue, G
Attar, RM
Sasser, AK
Carlsten, M
Childs, RW
AF Cherkasova, Elena
Espinoza, Luis
Kotecha, Ritesh
Reger, Robert N.
Berg, Maria
Aue, Georg
Attar, Ricardo M.
Sasser, A. Kate
Carlsten, Mattias
Childs, Richard W.
TI Treatment of Ex Vivo Expanded NK Cells with Daratumumab F(ab ')2
Fragments Protects Adoptively Transferred NK Cells from
Daratumumab-Mediated Killing and Augments Daratumumab-Induced Antibody
Dependent Cellular Toxicity (ADCC) of Myeloma
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Cherkasova, Elena; Kotecha, Ritesh; Reger, Robert N.; Berg, Maria; Aue, Georg; Carlsten, Mattias; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Espinoza, Luis] Kanazawa Univ, Kanazawa, Ishikawa, Japan.
[Attar, Ricardo M.; Sasser, A. Kate] Janssen Res & Dev LLC, Spring House, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801186
ER
PT J
AU Cheruku, PS
Cash, A
Dunbar, CE
Young, NS
Larochelle, A
AF Cheruku, Patali S.
Cash, Ayla
Dunbar, Cynthia E.
Young, Neal S.
Larochelle, Andre
TI The Thrombopoietin Receptor Agonist Eltrombopag Has DNA Repair Activity
in Human Hematopoietic Stem and Progenitor Cells
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Cheruku, Patali S.; Cash, Ayla; Dunbar, Cynthia E.; Young, Neal S.; Larochelle, Andre] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101245
ER
PT J
AU Chinnasamy, D
Whitehill, G
Keyvanfar, K
Brownell, I
Buck, C
Muranski, P
Barrett, AJ
AF Chinnasamy, Dhana
Whitehill, Greg
Keyvanfar, Keyvan
Brownell, Isaac
Buck, Christopher
Muranski, Pawel
Barrett, Austin John
TI Adoptive T Cell Therapy for Polyomaviral Infections and Related Diseases
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chinnasamy, Dhana; Whitehill, Greg; Keyvanfar, Keyvan; Muranski, Pawel; Barrett, Austin John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Brownell, Isaac] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Buck, Christopher] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801236
ER
PT J
AU Choi, U
Theobald, N
Robert, TE
Gray, J
Rawlings, DJ
Sorrentino, BP
Malech, H
De Ravin, SS
AF Choi, Uimook
Theobald, Narda
Robert, Throm E.
Gray, John
Rawlings, David J.
Sorrentino, Brian P.
Malech, Harry
De Ravin, Suk See
TI High Titer Lentivector from a Stable Lenti-Producer Efficiently Corrects
CD34+Hematopoietic Stem Cells from Patients with p47phox-Deficient
Chronic Granulomatous Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Choi, Uimook; Theobald, Narda; Malech, Harry; De Ravin, Suk See] NIAID, LHD, NIH, Bethesda, MD 20892 USA.
[Robert, Throm E.] St Jude Childrens Res Hosp, Div Expt Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Gray, John] Audentes Therapeut, Res & Developement, San Francisco, CA USA.
[Rawlings, David J.] Seattle Childrens Res Inst, Seattle, WA USA.
[Sorrentino, Brian P.] St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100201
ER
PT J
AU Chung, YJ
Kim, S
Zhang, ZH
Aplan, PD
AF Chung, Yang Jo
Kim, Suntae
Zhang, Zhenhua
Aplan, Peter D.
TI Plasticity of Stromal and Hematopoietic Bone Marrow Cells in a Murine
Model of Myelodysplastic Syndrome
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Chung, Yang Jo] NCI, Genet Branch, NIH, CCR, Bethesda, MD 20892 USA.
[Kim, Suntae; Zhang, Zhenhua] NCI, NIH, CCR, Bethesda, MD 20892 USA.
[Aplan, Peter D.] NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103039
ER
PT J
AU Churchman, ML
Jones, L
Evans, K
Richmond, J
Shapiro, IM
Pachter, JA
Weaver, DT
Houghton, PJ
Smith, MA
Lock, RB
Mullighan, CG
AF Churchman, Michelle L.
Jones, Luke
Evans, Kathryn
Richmond, Jennifer
Shapiro, Irina M.
Pachter, Jonathan A.
Weaver, David T.
Houghton, Peter J.
Smith, Malcolm A.
Lock, Richard B.
Mullighan, Charles G.
TI Efficacy of Focal Adhesion Kinase Inhibition in Combination with
Dasatinib in BCR-ABL1 Acute Lymphoblastic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Churchman, Michelle L.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Jones, Luke; Evans, Kathryn; Richmond, Jennifer; Lock, Richard B.] Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst, Sydney, NSW, Australia.
[Shapiro, Irina M.; Pachter, Jonathan A.; Weaver, David T.] Verastem Inc, Needham, MA USA.
[Houghton, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021800023
ER
PT J
AU Clark, BE
Shooter, CC
Smith, F
Brawand, D
Steedman, L
Oakley, M
Rushton, P
Rooks, H
Wang, XD
Drousiotou, A
Kyrri, A
Felekis, X
Petrou, M
Will, AM
Fisher, C
Higgs, DR
Harteveld, C
Phylipsen, M
Kleanthous, M
Thein, SL
AF Clark, Barnaby E.
Shooter, Claire C.
Smith, Frances
Brawand, David
Steedman, Laura
Oakley, Matthew
Rushton, Peter
Rooks, Helen
Wang, Xunde
Drousiotou, Anthi
Kyrri, Andriani
Felekis, Xenia
Petrou, Miranda
Will, Andrew M.
Fisher, Chris
Higgs, Douglas R.
Harteveld, Cornelius
Phylipsen, Marion
Kleanthous, Marina
Thein, Swee Lay
TI Characterisation of Three Unique Head-to-Tail Alpha Globin Cluster
Duplications Contributing to Beta Thalassemia Intermedia in 3 Families
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Clark, Barnaby E.; Smith, Frances; Brawand, David; Steedman, Laura; Oakley, Matthew; Rushton, Peter] Kings Coll Hosp London, Dept Mol Pathol, Viapath, London, England.
[Clark, Barnaby E.; Shooter, Claire C.; Thein, Swee Lay] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Rooks, Helen] Kings Coll London, Mol Haematol, London WC2R 2LS, England.
[Wang, Xunde] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA.
[Drousiotou, Anthi; Felekis, Xenia; Petrou, Miranda; Kleanthous, Marina] Cyprus Inst Neurol & Genet, Nicosia, Cyprus.
[Kyrri, Andriani] Thalassaemia Ctr, Nicosia, Cyprus.
[Will, Andrew M.] Royal Manchester Childrens Hosp, Paediat Haematol, Manchester M27 1HA, Lancs, England.
[Fisher, Chris; Higgs, Douglas R.] Univ Oxford, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.
[Harteveld, Cornelius; Phylipsen, Marion] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104257
ER
PT J
AU Desnica, L
Pulanic, D
Seiwerth, RS
Matic, N
Stipetic, MM
Bilic, E
Ceovic, R
Kelecic, DL
Rajic, L
Bilic, E
Durakovic, N
Peric, Z
Pulanic, TK
Vukic, T
Petricek, I
Dusek, D
Bojanic, I
Prenc, E
Prah, ID
Grce, M
Zadro, R
Batinic, D
Vrhovac, R
Pavletic, SZ
Nemet, D
AF Desnica, Lana
Pulanic, Drazen
Seiwerth, Ranka Serventi
Matic, Nikolina
Stipetic, Marinka Mravak
Bilic, Ervina
Ceovic, Romana
Kelecic, Dina Ljubas
Rajic, Ljubica
Bilic, Ernest
Durakovic, Nadira
Peric, Zinaida
Pulanic, Tajana Klepac
Vukic, Tamara
Petricek, Igor
Dusek, Davorka
Bojanic, Ines
Prenc, Ema
Prah, Iva Diana
Grce, Magdalena
Zadro, Renata
Batinic, Drago
Vrhovac, Radovan
Pavletic, Steven Z.
Nemet, Damir
TI Implementation of NIH Criteria for Standardization of Chronic
Graft-Versus-Host Disease in Croatia: Two-Year Experience
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Desnica, Lana; Pulanic, Drazen; Seiwerth, Ranka Serventi; Matic, Nikolina; Peric, Zinaida; Vrhovac, Radovan] Univ Hosp Ctr Zagreb, Dept Hematol, Zagreb 10000, Croatia.
[Stipetic, Marinka Mravak] Univ Hosp Ctr Zagreb, Dept Dent Med, Zagreb 10000, Croatia.
[Bilic, Ervina] Univ Hosp Ctr Zagreb, Dept Neurol, Zagreb 10000, Croatia.
[Ceovic, Romana] Univ Hosp Ctr Zagreb, Dept Dermatol, Zagreb 10000, Croatia.
[Kelecic, Dina Ljubas] Univ Hosp Ctr Zagreb, Dept Gastroenterol, Zagreb 10000, Croatia.
[Rajic, Ljubica; Bilic, Ernest] Univ Hosp Ctr Zagreb, Dept Pediat, Zagreb 10000, Croatia.
[Durakovic, Nadira] Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb, Croatia.
[Pulanic, Tajana Klepac] Community Hlth Ctr East, Zagreb 10000, Croatia.
[Vukic, Tamara] Univ Hosp Ctr Zagreb, Dept Phys Therapy, Zagreb 10000, Croatia.
[Petricek, Igor] Univ Hosp Ctr Zagreb, Dept Ophthalmol, Zagreb 10000, Croatia.
[Dusek, Davorka] Univ Hosp Infect Dis, Zagreb 10000, Croatia.
[Bojanic, Ines] Univ Hosp Ctr Zagreb, Dept Transfusiol, Zagreb 10000, Croatia.
[Prenc, Ema; Prah, Iva Diana] Sch Med, Zagreb 10000, Croatia.
[Grce, Magdalena] Rudjer Boskovic Inst, Zagreb 10000, Croatia.
[Zadro, Renata; Batinic, Drago] Univ Hosp Ctr Zagreb, Dept Lab Diagnost, Zagreb 10000, Croatia.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Nemet, Damir] Clin Hosp Ctr Zagreb, Internal Med, Zagreb, Croatia.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021805233
ER
PT J
AU Drasar, E
Fitzpatrick, E
Gardner, K
Awogbade, M
Dhawan, A
Bomford, A
Suddle, A
Thein, SL
AF Drasar, Emma
Fitzpatrick, Emer
Gardner, Kate
Awogbade, Moji
Dhawan, Anil
Bomford, Adrian
Suddle, Abid
Thein, Swee Lay
TI Noninvasive Assessment of Liver Fibrosis in Patients with Sickle Cell
Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Drasar, Emma; Awogbade, Moji] Kings Coll Hosp London, Dept Haematol, London, England.
[Fitzpatrick, Emer; Dhawan, Anil] Kings Coll Hosp London, Dept Paediat Hepatol, London, England.
[Gardner, Kate] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Bomford, Adrian; Suddle, Abid] Kings Coll Hosp London, Dept Hepatol, London, England.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104288
ER
PT J
AU Fanale, MA
Wang, ZQ
Ma, WC
Oki, Y
Hagemeister, FB
Fayad, LE
Fowler, N
Romaguera, JE
Shah, N
Chuang, HH
Lei, F
Horowitz, SB
Chihara, D
Wesson, E
Hutto, TY
Ruben, C
Samaniego, F
Muzzafar, T
Piekarz, R
Davis, RE
AF Fanale, Michelle A.
Wang, Zhiqiang
Ma, Wencai
Oki, Yasuhiro
Hagemeister, Fredrick B.
Fayad, Luis E.
Fowler, Nathan
Romaguera, Jorge E.
Shah, Nina
Chuang, Hubert H.
Lei, Feng
Horowitz, Sandra B.
Chihara, Dai
Wesson, Emily
Hutto, Toni Y.
Ruben, Charnelle
Samaniego, Felipe
Muzzafar, Tariq
Piekarz, Richard
Davis, R. Eric
TI Gene Expression Profiling for Molecular Features of Response in a Phase
I Trial of Alisertib Plus Romidepsin for Relapsed/Refractory Aggressive
B- and T-Cell Lymphomas
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Fanale, Michelle A.; Wang, Zhiqiang; Ma, Wencai; Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E.; Fowler, Nathan; Romaguera, Jorge E.; Chihara, Dai; Wesson, Emily; Hutto, Toni Y.; Ruben, Charnelle; Samaniego, Felipe; Davis, R. Eric] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
[Shah, Nina] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Chuang, Hubert H.] Univ Texas MD Anderson Canc Ctr, Dept Nucl Med, Houston, TX 77030 USA.
[Lei, Feng] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Horowitz, Sandra B.] Univ Texas MD Anderson Canc Ctr, Dept Pharm, Houston, TX 77030 USA.
[Muzzafar, Tariq] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA.
[Piekarz, Richard] NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102217
ER
PT J
AU Farooqui, M
Valdez, J
Soto, S
Stetler-Stevenson, M
Yuan, CM
Thomas, F
Tian, X
Maric, I
Wiestner, A
AF Farooqui, Mohammed
Valdez, Janet
Soto, Susan
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Thomas, Francine
Tian, Xin
Maric, Irina
Wiestner, Adrian
TI Single Agent Ibrutinib in CLL/SLL Patients with and without Deletion 17p
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Farooqui, Mohammed; Valdez, Janet; Soto, Susan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Thomas, Francine] NIH, Serv Radiol, Clin Res Ctr, Bethesda, MD 20892 USA.
[Thomas, Francine] NIH, Imaging Serv, Clin Res Ctr, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Hematol Sect, Dept Lab Med, CCR, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103132
ER
PT J
AU Farooqui, M
Valdez, J
Soto, S
Bray, A
Tian, X
Wiestner, A
AF Farooqui, Mohammed
Valdez, Janet
Soto, Susan
Bray, Amanda
Tian, Xin
Wiestner, Adrian
TI Atrial Fibrillation in CLL/SLL Patients on Ibrutinib
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Farooqui, Mohammed; Valdez, Janet; Soto, Susan; Bray, Amanda; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103128
ER
PT J
AU Farrar, JE
Alonzo, TA
Ries, RE
Gerbing, RB
Auvil, JMG
Davidsen, TM
Gesuwan, P
Hermida, LC
Marra, MA
Mungall, AJ
Mungall, K
Ma, Y
Long, W
Zong, S
Kolb, EA
Smith, MA
Gerhard, DS
Gamis, AS
Meshinchi, S
AF Farrar, Jason E.
Alonzo, Todd A.
Ries, Rhonda E.
Gerbing, Robert B.
Auvil, Jaime M. Guidry
Davidsen, Tanja M.
Gesuwan, Patee
Hermida, Leandro C.
Marra, Marco A.
Mungall, Andrew J.
Mungall, Karen
Ma, Yussanne
Long, William
Zong, Stuart
Kolb, E. Anders
Smith, Malcolm A.
Gerhard, Daniela S.
Gamis, Alan S.
Meshinchi, Soheil
TI ASXL1 and ASXL2 Mutations in Childhood AML Are Strongly Associated with
t(8;21) but Do Not Independently Impact on Prognosis: A Report from the
Children's Oncology Group and NCI/COG Target Initiative
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Alonzo, Todd A.; Gerbing, Robert B.] Childrens Oncol Grp, Monrovia, CA USA.
[Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Auvil, Jaime M. Guidry; Davidsen, Tanja M.; Gesuwan, Patee; Hermida, Leandro C.; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Marra, Marco A.; Mungall, Andrew J.; Mungall, Karen; Ma, Yussanne; Long, William; Zong, Stuart] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Kolb, E. Anders] Alfred I duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol Bone Marrow Transplantat, Kansas City, MO USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102099
ER
PT J
AU Fishman, NS
Kim, J
Lichy, D
Vaughan, K
Yoon, S
Sheth, N
Ahad, J
Darbari, D
Chadwick, K
Ackerman, H
Gorbach, AM
Taylor, JG
AF Fishman, Nathan S.
Kim, Joseph
Lichy, Daniel
Vaughan, Kathleen
Yoon, Stephen
Sheth, Niral
Ahad, James
Darbari, Deepika
Chadwick, Katherine
Ackerman, Hans
Gorbach, Alexander M.
Taylor, James G.
TI Altered Oxygenation, Vascular and Ischemic Pain Responses in Adults with
Sickle Cell Anemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Fishman, Nathan S.; Vaughan, Kathleen; Darbari, Deepika; Chadwick, Katherine; Taylor, James G.] NHLBI, Genom Med Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Kim, Joseph; Lichy, Daniel; Yoon, Stephen; Sheth, Niral; Ahad, James; Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry, NIH, Bethesda, MD USA.
[Darbari, Deepika] NHLBI, Pediat Hematol & Oncol, NHLBI Pulm & Vasc Med, Childrens Natl Med Ctr, Washington, DC USA.
[Ackerman, Hans] NHLBI, Physiol Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104281
ER
PT J
AU Galanina, N
Smith, SM
Liao, CH
Petrich, AM
Libao, B
Gartenhaus, R
Westin, JR
Cohen, KS
Knost, J
Stadler, W
Doyle, A
Karrison, T
Gordon, LI
Evens, AM
AF Galanina, Natalie
Smith, Sonali M.
Liao, Chuanhong
Petrich, Adam M.
Libao, Bernadette
Gartenhaus, Ron
Westin, Jason R.
Cohen, Kenneth S.
Knost, James
Stadler, Walter
Doyle, Austin
Karrison, Theodore
Gordon, Leo I.
Evens, Andrew M.
TI Selective MEK Inhibition with AZD-6244 (selumetinib) in Patients with
Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL): A University
of Chicago Phase II Consortium Trial
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Galanina, Natalie; Smith, Sonali M.; Cohen, Kenneth S.; Stadler, Walter] Univ Chicago, Div Hematol Oncol, Chicago, IL 60637 USA.
[Liao, Chuanhong; Libao, Bernadette; Karrison, Theodore] Univ Chicago, Chicago, IL 60637 USA.
[Petrich, Adam M.; Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA.
[Gartenhaus, Ron] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Westin, Jason R.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
[Knost, James] Illinois Canc Care, Peoria, IL USA.
[Doyle, Austin] NCI, Bethesda, MD 20892 USA.
[Evens, Andrew M.] Univ Massachusetts, Sch Med, Univ Hosp, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021800247
ER
PT J
AU Gooptu, M
Florea, AED
Leiby, BE
Pro, B
Sprandio, JD
Whittaker-Menezes, D
Cotzia, P
Uppal, G
Caro, J
Gong, J
Martinez-Outschoorn, U
AF Gooptu, Mahasweta
Florea, Alina E. Dulau
Leiby, Benjamin E.
Pro, Barbara
Sprandio, John David, Jr.
Whittaker-Menezes, Diana
Cotzia, Paolo
Uppal, Guldeep
Caro, Jaime
Gong, Jerald
Martinez-Outschoorn, Ubaldo
TI Metabolic Patterns in Cancer Cells and Tumor Microenvironment in Diffuse
Large B-Cell Lymphoma: Tumor-Stromal Metabolic Coupling
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Gooptu, Mahasweta] Thomas Jefferson Univ, Med Oncol, Philadelphia, PA 19107 USA.
[Florea, Alina E. Dulau] NIH, Bethesda, MD 20892 USA.
[Leiby, Benjamin E.] Thomas Jefferson Univ, Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA.
[Pro, Barbara] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Sprandio, John David, Jr.] Consultants Med Oncol & Hematol INC, Mainline Hlth Bryn Mawr Hosp, Drexel Hill, PA USA.
[Whittaker-Menezes, Diana; Martinez-Outschoorn, Ubaldo] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Cotzia, Paolo] Thomas Jefferson Univ, Pathol, Philadelphia, PA 19107 USA.
[Uppal, Guldeep; Gong, Jerald] Thomas Jefferson Univ, Hematopathol, Philadelphia, PA 19107 USA.
[Caro, Jaime] Cooper Univ Healthcare, Hematol & Med Oncol, Camden, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
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 DEC 3
PY 2015
VL 126
IS 23
PG 4
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021800149
ER
PT J
AU Goswami, M
Prince, GT
Biancotto, A
Moir, S
Cheung, F
Kutliarov, Y
Dunham, K
Chen, JG
Shi, RY
Zhou, HZ
Golding, H
Tang, JR
Tsang, JS
Dickler, HB
Noonan, K
Smith, BD
Burrello, IM
Hourigan, CS
AF Goswami, Meghali
Prince, Gabrielle T.
Biancotto, Angelique
Moir, Susan
Cheung, Foo
Kutliarov, Yuri
Dunham, Kimberly
Chen, Jinguo
Shi, Rongye
Zhou, Huizhi
Golding, Hana
Tang, Jingrong
Tsang, John S.
Dickler, Howard B.
Noonan, Kimberly
Smith, B. Douglas
Burrello, Ivan M.
Hourigan, Christopher S.
TI Impaired Response to Influenza Vaccination in AML Patients
Post-Chemotherapy Associated with a Highly Atypical B-Cell Profile
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Goswami, Meghali; Hourigan, Christopher S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Goswami, Meghali] George Washington Univ, Inst Biomed Sci, Washington, DC USA.
[Prince, Gabrielle T.; Noonan, Kimberly] Johns Hopkins Sch Med, Baltimore, MD USA.
[Biancotto, Angelique; Cheung, Foo; Kutliarov, Yuri; Chen, Jinguo; Shi, Rongye; Zhou, Huizhi; Tsang, John S.; Dickler, Howard B.; Hourigan, Christopher S.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Moir, Susan] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Dunham, Kimberly] NCI, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Golding, Hana] US FDA, Silver Spring, MD USA.
[Tang, Jingrong] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Smith, B. Douglas] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Burrello, Ivan M.] Johns Hopkins Sch Med, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104309
ER
PT J
AU Hardy, NM
Citrin, D
Hakim, FT
Avila, DN
Blacklock-Schuver, B
Cotton, S
Cho, M
Fowler, DH
Gea-Banacloche, JC
Holtzman, NG
Kurdziel, KA
Memon, S
Pavletic, SZ
Pittaluga, S
Rose, JJ
Sportes, C
Wilder, JS
Gress, RE
Bishop, MR
AF Hardy, Nancy M.
Citrin, Deborah
Hakim, Frances T.
Avila, Daniele N.
Blacklock-Schuver, Bazetta
Cotton, Stephanie
Cho, Monica
Fowler, Daniel H.
Gea-Banacloche, Juan C.
Holtzman, Noa G.
Kurdziel, Karen A.
Memon, Sarfraz
Pavletic, Steven Z.
Pittaluga, Stefania
Rose, Jeremy J.
Sportes, Claude
Wilder, Jennifer S.
Gress, Ronald E.
Bishop, Michael R.
TI Pilot Study of Radiation-Targeted Donor Lymphocyte Infusion for Cancer
Progression after Allogeneic Hematopoietic Stem Cell Transplantation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hardy, Nancy M.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Hardy, Nancy M.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Hardy, Nancy M.; Hakim, Frances T.; Cotton, Stephanie; Cho, Monica; Sportes, Claude; Gress, Ronald E.; Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Avila, Daniele N.; Blacklock-Schuver, Bazetta; Fowler, Daniel H.; Gea-Banacloche, Juan C.; Memon, Sarfraz; Pavletic, Steven Z.; Rose, Jeremy J.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Holtzman, Noa G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Kurdziel, Karen A.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Sportes, Claude] Georgia Regents Univ, GRU Canc Ctr, Augusta, GA USA.
[Wilder, Jennifer S.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Bishop, Michael R.] Univ Chicago, Sch Med, Hematopoiet Stem Cell Transplantat Program, Chicago, IL 60637 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100127
ER
PT J
AU Hasegawa, A
Kaneko, H
Ishihara, D
Nakamura, M
Watanabe, A
Trainor, CD
Masayuki, Y
Shimizu, R
AF Hasegawa, Atsushi
Kaneko, Hiroshi
Ishihara, Daishi
Nakamura, Masahiro
Watanabe, Akira
Trainor, Cecelia D.
Masayuki, Yamamoto
Shimizu, Ritsuko
TI GATA1 Changes DNA-Binding Fashion in a Binding-Site-Specific Manner and
Alters Transcriptional Activity during Erythropoiesis
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hasegawa, Atsushi; Kaneko, Hiroshi; Ishihara, Daishi; Shimizu, Ritsuko] Tohoku Univ, Grad Sch Med, Dept Mol Hematol, Sendai, Miyagi 980, Japan.
[Nakamura, Masahiro; Watanabe, Akira] Kyoto Univ, Dept Life Sci Frontiers, Ctr iPS Cell Res & Applicat CiRA, Kyoto, Japan.
[Trainor, Cecelia D.] NIH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Masayuki, Yamamoto] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Sendai, Miyagi 980, Japan.
[Masayuki, Yamamoto] Tohoku Univ, Med Mega Bank Org, Sendai, Miyagi 980, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105150
ER
PT J
AU Helene, S
Goris, K
Van Durm, R
Van Hoof, J
Greinix, HT
Wolff, D
Pavletic, SZ
Lee, SJ
Maertens, J
De Geest, S
Dobbels, F
Duarte, RF
AF Helene, Schoemans
Goris, Kathy
Van Durm, Raf
Van Hoof, Jasper
Greinix, Hildegard T.
Wolff, Daniel
Pavletic, Steven Z.
Lee, Stephanie J.
Maertens, Johan
De Geest, Sabina
Dobbels, Fabienne
Duarte, Rafael F.
TI Development and Preliminary Usability and Accuracy Testing of the EBMT
Gvhd App to Support Graft Versus Host Disease Diagnosis and Scoring
According to NIH Criteria, By the EBMT Complications and Quality of Life
Working Party
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Helene, Schoemans; Goris, Kathy; Van Durm, Raf; Van Hoof, Jasper; Dobbels, Fabienne] Univ Hosp Leuven, Leuven, Belgium.
[Greinix, Hildegard T.] Med Univ Graz, Hematol, Graz, Austria.
[Wolff, Daniel] Univ Regensburg, D-93053 Regensburg, Germany.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Maertens, Johan] Univ Hosp Gasthuisberg Leuven, Dept Hematol, Leuven, Belgium.
[De Geest, Sabina] Katholieke Univ Leuven, Hlth Serv Res, Leuven, Belgium.
[Duarte, Rafael F.] Hosp Univ Puerta de Hierro, Dept Hematol, Madrid, Spain.
NR 0
TC 0
Z9 0
U1 2
U2 4
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104033
ER
PT J
AU Herman, SEM
Montraveta, A
Niemann, CU
Mora-Jensen, H
Gulrajani, M
Krantz, F
Harrington, BK
Covey, T
Lannutti, BJ
Izumi, R
Ulrich, RG
Byrd, JC
Wiestner, A
Johnson, AJ
Woyach, JA
AF Herman, Sarah E. M.
Montraveta, Arnau
Niemann, Carsten U.
Mora-Jensen, Helena
Gulrajani, Michael
Krantz, Fanny
Harrington, Bonnie K.
Covey, Todd
Lannutti, Brian J.
Izumi, Raquel
Ulrich, Roger G.
Byrd, John C.
Wiestner, Adrian
Johnson, Amy J.
Woyach, Jennifer A.
TI The Bruton Tyrosine Kinase (BTK) Inhibitor ACP-196 Demonstrates Clinical
Activity in Two Mouse Models of Chronic Lymphocytic Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Herman, Sarah E. M.; Niemann, Carsten U.; Mora-Jensen, Helena; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Montraveta, Arnau] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
[Gulrajani, Michael; Krantz, Fanny; Covey, Todd; Lannutti, Brian J.; Izumi, Raquel; Ulrich, Roger G.] Acerta Pharma, Redwood City, CA USA.
[Harrington, Bonnie K.] Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA.
[Byrd, John C.; Woyach, Jennifer A.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Johnson, Amy J.] Ohio State Univ, Dept Med, Div Hematol, Columbus, OH 43210 USA.
RI Woyach, Jennifer/F-1087-2015
NR 0
TC 0
Z9 0
U1 1
U2 3
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103115
ER
PT J
AU Heuston, EF
Keller, CA
Anderson, SM
Hardison, RC
Bodine, DM
AF Heuston, Elisabeth F.
Keller, Cheryl A.
Anderson, Stacie M.
Hardison, Ross C.
Bodine, David M.
CA NIH Intramural Sequencing Ctr
TI Enhancer Accessibility during Erythropoiesis and Megakaryopoiesis
Correlates with Lineage-Specific Gene Expression
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Heuston, Elisabeth F.; Anderson, Stacie M.; Bodine, David M.] NHGRI, Bethesda, MD 20892 USA.
[Keller, Cheryl A.; Hardison, Ross C.] Penn State Univ, State Coll, PA USA.
[NIH Intramural Sequencing Ctr] NHGRI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105142
ER
PT J
AU Hosokawa, K
Muranski, P
Feng, XM
Townsley, DM
Liu, BY
Knickelbein, J
Keyvanfar, K
Dumitriu, B
Ito, S
Kajigaya, S
Taylor, JG
Kaplan, MJ
Nussenblatt, RB
Barrett, AJ
O'Shea, J
Young, NS
AF Hosokawa, Kohei
Muranski, Pawel
Feng, Xingmin
Townsley, Danielle M.
Liu, Baoying
Knickelbein, Jared
Keyvanfar, Keyvan
Dumitriu, Bogdan
Ito, Sawa
Kajigaya, Sachiko
Taylor, James G.
Kaplan, Mariana J.
Nussenblatt, Robert B.
Barrett, Austin John
O'Shea, John
Young, Neal S.
TI High Frequency of Circulating CD8(+) Memory Stem T Cells in Acquired
Aplastic Anemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M.; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G.; Barrett, Austin John; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Baoying; Knickelbein, Jared; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Kaplan, Mariana J.; O'Shea, John] NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105179
ER
PT J
AU Hosokawa, K
Kajigaya, S
Keyvanfar, K
Townsley, DM
Dumitriu, B
Desierto, M
Rios, O
Weinstein, B
Feng, XM
Young, NS
AF Hosokawa, Kohei
Kajigaya, Sachiko
Keyvanfar, Keyvan
Townsley, Danielle M.
Dumitriu, Bogdan
Desierto, Marie
Rios, Olga
Weinstein, Barbara
Feng, Xingmin
Young, Neal S.
TI Whole Transcriptome Sequencing Identifies Novel Pathways Associated with
Paroxysmal Nocturnal Hemoglobinuria-Increased CXCR2 Expression in PNH
Granulocytes
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Hosokawa, Kohei; Kajigaya, Sachiko; Keyvanfar, Keyvan; Townsley, Danielle M.; Dumitriu, Bogdan; Desierto, Marie; Rios, Olga; Weinstein, Barbara; Feng, Xingmin; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105174
ER
PT J
AU Im, A
Hakim, FT
Pirsl, F
Steinberg, SM
Curtis, LM
Mitchell, SA
Cowen, EW
Hsu, J
Baruffaldi, J
Masuch, L
Gea-Banacloche, JC
Halverson, DC
Fowler, DH
Gress, RE
Pavletic, SZ
AF Im, Annie
Hakim, Frances T.
Pirsl, Filip
Steinberg, Seth M.
Curtis, Lauren M.
Mitchell, Sandra A.
Cowen, Edward W.
Hsu, Jennifer
Baruffaldi, Judy
Masuch, Licia
Gea-Banacloche, Juan C.
Halverson, David C.
Fowler, Daniel H.
Gress, Ronald E.
Pavletic, Steven Z.
TI Clinical and Immunologic Characteristics of Patients with Chronic
Graft-Versus-Host Disease Persisting Seven or More Years after Diagnosis
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Im, Annie] Univ Pittsburgh, Med Ctr, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA.
[Im, Annie; Pirsl, Filip; Curtis, Lauren M.; Hsu, Jennifer; Baruffaldi, Judy; Masuch, Licia; Gea-Banacloche, Juan C.; Fowler, Daniel H.; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Hakim, Frances T.; Halverson, David C.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100102
ER
PT J
AU Jacoby, E
Nguyen, SM
Welp, KM
Qin, HY
Yang, YM
Chien, CD
Shern, J
Fry, TJ
AF Jacoby, Elad
Nguyen, Sang Minh
Welp, Kathryn M.
Qin, Haiying
Yang, Yinmeng
Chien, Christopher Daniel
Shern, John
Fry, Terry J.
TI Lineage Switch As a Relapse Mechanism of Pre-B Acute Lymphoblastic
Leukemia Following CD19 CAR
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Jacoby, Elad; Nguyen, Sang Minh; Welp, Kathryn M.; Qin, Haiying; Yang, Yinmeng; Chien, Christopher Daniel; Shern, John; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102036
ER
PT J
AU Kang, EM
Wright, NA
Nicholls, K
Hilligoss, D
Kelly, C
Kuhns, DB
Malech, HL
AF Kang, Elizabeth M.
Wright, Nicola A.
Nicholls, Katherine
Hilligoss, Dianne
Kelly, Corin
Kuhns, Douglas B.
Malech, Harry L.
TI Allogeneic Transplantation for P40 CGD Is Curative of Inflammatory
Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Kang, Elizabeth M.; Hilligoss, Dianne; Kelly, Corin; Malech, Harry L.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[Wright, Nicola A.] Alberta Childrens Prov Gen Hosp, Pediat Hematol Oncol BMT, Calgary, AB, Canada.
[Nicholls, Katherine] Royal Melbourne Hosp, Dept Immunol & Allergy, Melbourne, Vic, Australia.
[Kuhns, Douglas B.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021805168
ER
PT J
AU Kanter, J
Walters, MC
Hsieh, M
Thompson, AA
Krishnamurti, L
Kwiatkowski, J
Kamble, RT
von Kalle, C
Kuypers, FA
Cavazzana, M
Leboulch, P
Sandler, L
Soni, S
Tisdale, JF
AF Kanter, Julie
Walters, Mark C.
Hsieh, Matthew
Thompson, Alexis A.
Krishnamurti, Lakshmanan
Kwiatkowski, Janet
Kamble, Rammurti T.
von Kalle, Christof
Kuypers, Frans A.
Cavazzana, Marina
Leboulch, Philippe
Sandler, Laura
Soni, Sandeep
Tisdale, John F.
TI Initial Results from Study Hgb-206: A Phase 1 Study Evaluating Gene
Therapy By Transplantation of Autologous CD34+Stem Cells Transduced Ex
Vivo with the Lentiglobin BB305 Lentiviral Vector in Subjects with
Severe Sickle Cell Disease
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Kanter, Julie] Med Univ S Carolina, Charleston, SC 29425 USA.
[Walters, Mark C.] UCSF Benioff Childrens Hosp, Oakland, CA USA.
[Hsieh, Matthew; Tisdale, John F.] NIH, Bethesda, MD 20892 USA.
[Thompson, Alexis A.] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Krishnamurti, Lakshmanan] Emory Univ, Atlanta, GA 30322 USA.
[Kwiatkowski, Janet] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Kamble, Rammurti T.] Houston Methodist Hosp, Houston, TX USA.
[von Kalle, Christof] German Canc Res Ctr, Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Kuypers, Frans A.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Cavazzana, Marina] Hop Univ Necker Enfants Malades, Biotherapy Dept, Paris, France.
[Leboulch, Philippe] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Leboulch, Philippe] Harvard Univ, Sch Med, Boston, MA USA.
[Leboulch, Philippe] Mahidol Univ, Ramathibodi Hosp, Bangkok 10700, Thailand.
[Leboulch, Philippe] CEA iMETI, Fontenay Aux Roses, France.
[Leboulch, Philippe] Univ Paris 11, Fontenay Aux Roses, France.
[Sandler, Laura; Soni, Sandeep] Bluebird Bio Inc, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104115
ER
PT J
AU Karambelkar, AD
Reger, RN
Carlsten, M
Childs, RW
AF Karambelkar, Amrita D.
Reger, Robert N.
Carlsten, Mattias
Childs, Richard W.
TI Ex Vivo Expanded NK Cells Mediate Highly Efficient and Rapid Killing of
Ewing Sarcoma Cells Through Degranulation with Tumor Cytotoxicity
Controlled by the NKG2D, DNAM-1, and NKp30 NK Receptors
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Karambelkar, Amrita D.; Reger, Robert N.; Carlsten, Mattias; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Karambelkar, Amrita D.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100059
ER
PT J
AU Khan, NE
Rosenberg, PS
Alter, BP
AF Khan, Nicholas Economou
Rosenberg, Philip S.
Alter, Blanche P.
TI Preemptive Bone Marrow Transplantation and Event- Free Survival in
Fanconi Anemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Khan, Nicholas Economou; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105190
ER
PT J
AU Kreitman, RJ
Arons, E
Tallman, MS
Tadeusz, R
Coutre, S
Wilson, WH
Stetler-Stevenson, M
Yuan, CM
Lanasa, M
FitzGerald, DJP
Pastan, I
AF Kreitman, Robert J.
Arons, Evgeny
Tallman, Martin S.
Tadeusz, Robak
Coutre, Steven
Wilson, Wyndham H.
Stetler-Stevenson, Maryalice
Yuan, Constance M.
Lanasa, Mark
FitzGerald, David J. P.
Pastan, Ira
TI High Response Rate of Moxetumomab Pasudotox in Relapsed/Refractory Hairy
Cell Leukemia Includes Eradication of Minimal Residual Disease:
Potential Importance for Outcome
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Kreitman, Robert J.; Arons, Evgeny] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Tadeusz, Robak] Med Univ Lodz, Dept Hematol, Lodz, Poland.
[Coutre, Steven] Stanford Univ, Stanford Canc Ctr, Stanford, CA 94305 USA.
[Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Lanasa, Mark] MedImmune, Clin Dev, Oncol, Gaithersburg, MD USA.
[FitzGerald, David J. P.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801103
ER
PT J
AU Kurotaki, D
Nakabayashi, J
Nishiyama, A
Sasaki, H
Kaneko, N
Koizumi, S
Ozato, K
Suzuki, Y
Tamura, T
AF Kurotaki, Daisuke
Nakabayashi, Jun
Nishiyama, Akira
Sasaki, Haruka
Kaneko, Naofumi
Koizumi, Shin-ichi
Ozato, Keiko
Suzuki, Yutaka
Tamura, Tomohiko
TI Enhancer Landscape Dynamics and the Role of IRF8 in Mononuclear
Phagocyte Development
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Kurotaki, Daisuke; Nishiyama, Akira; Sasaki, Haruka; Kaneko, Naofumi; Koizumi, Shin-ichi; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan.
[Nakabayashi, Jun] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 232, Japan.
[Ozato, Keiko] NICHD, NIH, Bethesda, MD USA.
[Suzuki, Yutaka] Univ Tokyo, Grad Sch Frontier Sci, Dept Comput Biol, Chiba, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101222
ER
PT J
AU Le, RQ
Anandi, P
Tian, X
Ito, S
Jain, NA
Goswami, M
Lai, CE
Hourigan, CS
Adams, S
Hensel, NF
Barrett, AJ
Battiwalla, M
AF Le, Robert Q.
Anandi, Prathima
Tian, Xin
Ito, Sawa
Jain, Natasha A.
Goswami, Meghali
Lai, Catherine E.
Hourigan, Christopher S.
Adams, Sharon
Hensel, Nancy F.
Barrett, Austin John
Battiwalla, Minoo
TI Comparison of Donor KIR Genotype, Recipient CMV Reactivation and
Pretransplant MRD in Predicting Relapse after Ex Vivo T-Deplete Allohsct
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Le, Robert Q.; Anandi, Prathima; Ito, Sawa; Jain, Natasha A.; Hensel, Nancy F.; Barrett, Austin John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Goswami, Meghali; Lai, Catherine E.; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Adams, Sharon] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104094
ER
PT J
AU Levy, ER
Reger, RN
Carlsten, M
Childs, RW
AF Levy, Emily R.
Reger, Robert N.
Carlsten, Mattias
Childs, Richard W.
TI mRNA Transfection of NK Cells with Gain-of-Function CXCR4 As a Novel
Method to Enhance the Homing of Adoptively Transferred NK Cells to the
Bone Marrow for the Treatment of Hematological Malignancies
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Levy, Emily R.; Reger, Robert N.; Carlsten, Mattias; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Levy, Emily R.] George Washington Univ, Inst Biomed Sci, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103284
ER
PT J
AU Li, LQ
Layer, JH
Warzecha, C
Tripathi, R
Love, P
Dave, UP
AF Li, Liqi
Layer, Justin H.
Warzecha, Claude
Tripathi, Rati
Love, Paul
Dave, Utpal P.
TI Lmo2 ' s Oncogenic Function in T-Cell Leukemia Requires Ldb1
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Li, Liqi; Warzecha, Claude; Love, Paul] NICHD, Sect Cellular & Dev Biol, NIH, Bethesda, MD USA.
[Layer, Justin H.; Tripathi, Rati] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA.
[Dave, Utpal P.] Tennessee Valley Healthcare Syst, Nashville VA, Nashville, TN USA.
[Dave, Utpal P.] Vanderbilt Univ, Med Ctr, Med & Canc Biol, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105229
ER
PT J
AU Lichtenberg, J
Heuston, EF
Keller, CA
Hardison, RC
Bodine, DM
AF Lichtenberg, Jens
Heuston, Elisabeth F.
Keller, Cheryl A.
Hardison, Ross C.
Bodine, David M.
TI Comparison of Expression and Epigenetic Profiles in Human and Mouse
Erythropoiesis and Megakaryopoiesis Using a Systems Biology Model
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Lichtenberg, Jens; Heuston, Elisabeth F.; Bodine, David M.] NHGRI, Bethesda, MD 20892 USA.
[Keller, Cheryl A.; Hardison, Ross C.] Penn State Univ, State Coll, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101221
ER
PT J
AU Lindqvist, EK
Lund, SH
Costello, R
Burton, D
Korde, NS
Mailankody, S
Gudnason, V
Eiriksdottir, G
Launer, L
Harris, TB
Hultcrantz, M
Landgren, O
Kristinsson, SY
Bjorkholm, M
AF Lindqvist, Ebba K.
Lund, Sigrun H.
Costello, Rene
Burton, Debra
Korde, Neha S.
Mailankody, Sham
Gudnason, Vilmundur
Eiriksdottir, Gudny
Launer, Leonore
Harris, Tamara B.
Hultcrantz, Malin
Landgren, Ola
Kristinsson, Sigurdur Y.
Bjorkholm, Magnus
TI No Risk of Arterial or Venous Thrombosis in Monoclonal Gammopathy of
Undetermined Significance: Results from a Population-Based Study
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Lindqvist, Ebba K.; Hultcrantz, Malin; Landgren, Ola; Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden.
[Lindqvist, Ebba K.; Hultcrantz, Malin; Landgren, Ola; Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden.
[Lund, Sigrun H.] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
[Costello, Rene; Burton, Debra; Mailankody, Sham] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Korde, Neha S.] NCI, Dept Med, Myeloma Serv, NIH, Bethesda, MD 20892 USA.
[Korde, Neha S.; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, New York, NY 10021 USA.
[Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Gudnason, Vilmundur; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland.
[Launer, Leonore; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Kristinsson, Sigurdur Y.] Univ Iceland, Fac Med, Reykjavik, Iceland.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801194
ER
PT J
AU McDermott, DH
Jacobs, P
Liu, Q
Gao, JL
Murphy, PM
AF McDermott, David H.
Jacobs, Paejonette
Liu, Qian
Gao, Jiliang
Murphy, Philip M.
TI CXCR4 Gene Dosage Is Critical for HSC Engraftment
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [McDermott, David H.; Jacobs, Paejonette; Liu, Qian; Gao, Jiliang; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103261
ER
PT J
AU McReynolds, LJ
Aplan, PD
Small, D
Ding, L
Johnson, KD
Bresnick, EH
Holland, SM
AF McReynolds, Lisa J.
Aplan, Peter D.
Small, Donald
Ding, Li
Johnson, Kirby D.
Bresnick, Emery H.
Holland, Steven M.
TI Mouse Modeling of GATA2 Related MDS/AML
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [McReynolds, Lisa J.; Ding, Li; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Aplan, Peter D.] NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Small, Donald] Johns Hopkins Univ, Dept Oncol & Pediat, Baltimore, MD USA.
[Johnson, Kirby D.; Bresnick, Emery H.] Univ Wisconsin, Sch Med & Publ Hlth, UW Madison Blood Res Program, Carbon Canc Ctr,Dept Cell & Regenerat Biol, Madison, WI USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103050
ER
PT J
AU Meier, ER
Byrnes, C
Martin, B
Tumburu, L
Lee, YT
Luban, NLC
Miller, JL
AF Meier, Emily Riehm
Byrnes, Colleen
Martin, Brenda
Tumburu, Laxminath
Lee, Y. Terry
Luban, Naomi L. C.
Miller, Jeffery L.
TI Early Pathogenesis of Sickle Cell Anemia: Absolute Reticulocyte Counts
Are Correlated with Increased Detection of CD36+Reticulocytes during the
First Two Years of Postnatal Life
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Meier, Emily Riehm; Martin, Brenda; Luban, Naomi L. C.] Childrens Natl Med Ctr, Div Hematol, Washington, DC 20010 USA.
[Byrnes, Colleen; Tumburu, Laxminath; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101019
ER
PT J
AU Melgar, K
Walker, M
Jiang, JK
Wilson, K
Mulloy, JC
Thomas, CJ
Starczynowski, DT
AF Melgar, Katelyn
Walker, MacKenzie
Jiang, Jian-kang
Wilson, Kelli
Mulloy, James C.
Thomas, Craig J.
Starczynowski, Daniel T.
TI Novel Small Molecule FLT3 Inhibitors for the Treatment of FLT3-ITD AML
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Melgar, Katelyn; Mulloy, James C.; Starczynowski, Daniel T.] Cincinnati Childrens Hosp Med Ctr, Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Walker, MacKenzie; Jiang, Jian-kang; Wilson, Kelli; Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Starczynowski, Daniel T.] Univ Cincinnati, Canc & Cell Biol, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105256
ER
PT J
AU Mule, MP
Mannis, GN
Radich, JP
Wood, BL
Ramos, NR
Lai, CE
Flanders, M
Andreadis, C
Damon, LE
Logan, AC
Martin, TC
Hourigan, CS
AF Mule, Matthew P.
Mannis, Gabriel N.
Radich, Jerald P.
Wood, Brent L.
Ramos, Nestor R.
Lai, Catherine E.
Flanders, Michael
Andreadis, Charalambos
Damon, Lloyd E.
Logan, Aaron C.
Martin, Thomas C.
Hourigan, Christopher S.
TI leMultigene MRD Assessment Improves AML Relapse Risk Stratification in
Autologous Hematopoietic Cell Transplantation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Mule, Matthew P.; Ramos, Nestor R.; Lai, Catherine E.; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Mannis, Gabriel N.; Flanders, Michael; Andreadis, Charalambos; Damon, Lloyd E.; Logan, Aaron C.; Martin, Thomas C.] Univ Calif San Francisco, Dept Med, Div Hematol & Blood & Marrow Transplantat, San Francisco, CA USA.
[Radich, Jerald P.; Wood, Brent L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801292
ER
PT J
AU Muranski, P
Stegemann, S
Whitehill, G
Barrett, AJ
AF Muranski, Pawel
Stegemann, Scott
Whitehill, Greg
Barrett, A. John
TI In Vitro Generation of Multi-Epitope Specific CD4(+) T Helper Cells for
Adoptive Immunotherapy of Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Muranski, Pawel; Stegemann, Scott; Whitehill, Greg; Barrett, A. John] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100055
ER
PT J
AU Mwirigi, AN
Muzah, C
Odeh, L
Suddle, A
Thein, SL
Awogbade, M
AF Mwirigi, Anne Nkirote
Muzah, Chengetai
Odeh, Liz
Suddle, Abid
Thein, Swee Lay
Awogbade, Moji
TI A Five Year Experience of Acute Intrahepatic Cholestasis in Patients
with Sickle Cell Disease at a Large Teaching Hospital in London
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Mwirigi, Anne Nkirote; Awogbade, Moji] Kings Coll Hosp London, Dept Haematol, London, England.
[Muzah, Chengetai; Odeh, Liz] Kings Coll Hosp London, London, England.
[Suddle, Abid] Kings Coll Hosp London, Dept Hepatol, London, England.
[Thein, Swee Lay] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104298
ER
PT J
AU Navarro, A
Clot, G
Martinez-Trillos, A
Salaverria, I
Martin-Garcia, D
Trim, N
Fernandez, V
Villamor, N
Colomer, D
Pinyol, M
Jares, P
Erber, WN
Wiestner, A
Wilson, WH
Siebert, R
Aymerich, M
Lopez-Guillermo, A
Sanchez, A
Campo, E
Matutes, E
Bea, S
AF Navarro, Alba
Clot, Guillem
Martinez-Trillos, Alejandra
Salaverria, Itziar
Martin-Garcia, David
Trim, Nicola
Fernandez, Veronica
Villamor, Neus
Colomer, Dolors
Pinyol, Magda
Jares, Pedro
Erber, Wendy N.
Wiestner, Adrian
Wilson, Wyndham H.
Siebert, Reiner
Aymerich, Marta
Lopez-Guillermo, Armando
Sanchez, Alex
Campo, Elias
Matutes, Estella
Bea, Silvia
TI Gene Expression Profiling Signatures Allow the Identification of
Unclassifiable Leukemic B-Cell Lymphoid Neoplasms
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Navarro, Alba; Salaverria, Itziar; Martin-Garcia, David; Bea, Silvia] IDIBAPS, Barcelona, Spain.
[Clot, Guillem; Fernandez, Veronica] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain.
[Martinez-Trillos, Alejandra; Matutes, Estella] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain.
[Trim, Nicola] West Midlands Reg Genet Lab, Birmingham, W Midlands, England.
[Villamor, Neus; Colomer, Dolors; Aymerich, Marta] Hosp Clin Barcelona, Barcelona, Spain.
[Pinyol, Magda; Jares, Pedro] IDIBAPS, Genom Unit, Barcelona, Spain.
[Erber, Wendy N.] Univ Western Australia, Pathol, Crawley, Australia.
[Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA.
[Siebert, Reiner] Univ Kiel, Inst Human Genet, Kiel, Germany.
[Lopez-Guillermo, Armando] Hosp Clin Barcelona, Hematol, Barcelona, Spain.
[Sanchez, Alex] Univ Barcelona, Dept Stat, Barcelona, Spain.
[Campo, Elias] Hosp Clin Barcelona, Hematophatol Unit, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 3
U2 3
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021800159
ER
PT J
AU O'Brien, K
Vlachos, A
Anderson, SM
Tsujiura, C
Blanc, L
Atsidaftos, E
Farrar, JE
Ellis, SR
Lipton, JM
Bodine, DM
AF O'Brien, Kelly
Vlachos, Adrianna
Anderson, Stacie M.
Tsujiura, Crystiana
Blanc, Lionel
Atsidaftos, Eva
Farrar, Jason E.
Ellis, Steven R.
Lipton, Jeffrey Michael
Bodine, David M.
CA NIH Intramural Sequencing Ctr
TI Transcriptome Analysis of Erythroid Cells Cultured from Diamond Blackfan
Anemia Patients with Ribosomal and GATA1 Mutations Reveals Dysregulation
of Inflammatory Response Genes
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [O'Brien, Kelly; Anderson, Stacie M.; Tsujiura, Crystiana; Bodine, David M.] NHGRI, Bethesda, MD 20892 USA.
[Vlachos, Adrianna; Blanc, Lionel; Atsidaftos, Eva; Lipton, Jeffrey Michael] Schneider Childrens Hosp, Feinstein Inst Med Res, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY USA.
[NIH Intramural Sequencing Ctr] NHGRI, Rockville, MD USA.
[Farrar, Jason E.] Univ Arkansas Med Sci, Dept Pediat, Hematol Oncol Sect, Little Rock, AR 72205 USA.
[Ellis, Steven R.] Univ Louisville, Louisville, KY 40292 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105171
ER
PT J
AU Ondrejka, SL
Jaffe, ES
Gong, SY
Rajagopalan, D
Love, C
Dave, S
AF Ondrejka, Sarah Lynn
Jaffe, Elaine S.
Gong, Shunyou
Rajagopalan, Deepthi
Love, Cassandra
Dave, Sandeep
TI Whole Exome Sequencing Defines the Genetic Differences Between Pediatric
and Adult Follicular Lymphoma
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Ondrejka, Sarah Lynn] Cleveland Clin, Cleveland, OH 44106 USA.
[Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Gong, Shunyou] Northwestern Univ, Chicago, IL 60611 USA.
[Rajagopalan, Deepthi; Love, Cassandra] Duke Univ, Durham, NC USA.
[Dave, Sandeep] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105202
ER
PT J
AU Patel, MI
Johnson, N
Altekruse, S
Rhoads, K
AF Patel, Manali I.
Johnson, Norman
Altekruse, Sean
Rhoads, Kim
TI Are Racial and Ethnic Disparities in Mortality from Acute Leukemia Due
to Socioeconomic Status Factors? Data from the Surveillance Epidemiology
and End Results Database Linked to the National Longitudinal Mortality
Study
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Patel, Manali I.] Stanford Univ, Dept Med, Sch Med, Hematol, Stanford, CA 94305 USA.
[Johnson, Norman] US Bur Census, Natl Longitudinal Mortal Study, Bethesda, MD USA.
[Altekruse, Sean] NIH, Bethesda, MD 20892 USA.
[Rhoads, Kim] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100266
ER
PT J
AU Perez, A
Navale, L
Rossi, JM
Shen, YW
Jiang, YZ
Sherman, M
Mardiros, A
Yoder, SC
Go, WY
Rosenberg, SA
Wiezorek, J
Roberts, MR
Chang, DD
Kochenderfer, JN
Bot, A
AF Perez, Arianne
Navale, Lynn
Rossi, John M.
Shen, Yueh-wei
Jiang, Yizhou
Sherman, Marika
Mardiros, Armen
Yoder, Sean C.
Go, William Y.
Rosenberg, Steven A.
Wiezorek, Jeff
Roberts, Margo R.
Chang, David D.
Kochenderfer, James N.
Bot, Adrian
TI Pharmacodynamic Profile and Clinical Response in Patients with B-Cell
Malignancies of Anti-CD19 CAR T-Cell Therapy
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Perez, Arianne; Navale, Lynn; Rossi, John M.; Shen, Yueh-wei; Jiang, Yizhou; Sherman, Marika; Mardiros, Armen; Yoder, Sean C.; Go, William Y.; Wiezorek, Jeff; Roberts, Margo R.; Chang, David D.; Bot, Adrian] Kite Pharma, Santa Monica, CA USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100207
ER
PT J
AU Plowden, TC
Millan, NM
Owen, CM
Healy, MW
Banks, NK
Hsieh, M
Fitzhugh, CD
Witmyer, J
Peak, D
Frankfurter, D
DeCherney, AH
Tisdale, JF
Wolff, EF
AF Plowden, Torie C.
Millan, Nicole M.
Owen, Carter M.
Healy, Mae W.
Banks, Nicole K.
Hsieh, Matthew
Fitzhugh, Courtney D.
Witmyer, Jeannine
Peak, Doug
Frankfurter, David
DeCherney, Alan H.
Tisdale, John F.
Wolff, Erin F.
TI Fertility Preservation for Women with Sickle Cell Disease (SCD)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Plowden, Torie C.; Millan, Nicole M.; Owen, Carter M.; Healy, Mae W.; Banks, Nicole K.; DeCherney, Alan H.; Wolff, Erin F.] NICHD, NIH, PRAE, Bethesda, MD USA.
[Hsieh, Matthew; Tisdale, John F.; Wolff, Erin F.] NHLBI, NIH, MCHB, Bethesda, MD 20892 USA.
[Fitzhugh, Courtney D.] NHLBI, NIH, SCB, Bethesda, MD 20892 USA.
[Witmyer, Jeannine; Peak, Doug; Frankfurter, David] GWU, Washington, DC USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104290
ER
PT J
AU Pratz, KW
Gojo, I
Karp, JE
Luznik, L
Smith, BD
Jones, RJ
Greer, J
Gocke, C
Baer, MR
Duong, VH
Wright, JJ
Rudek, MA
Emadi, A
Levis, MJ
AF Pratz, Keith W.
Gojo, Ivana
Karp, Judith E.
Luznik, Leo
Smith, B. Douglas
Jones, Richard J.
Greer, Jackie
Gocke, Christopher
Baer, Maria R.
Duong, Vu H.
Wright, John J.
Rudek, Michelle A.
Emadi, Ashkan
Levis, Mark J.
TI Prospective Study of Peri-Transplant Use of Sorafenib As Remission
Maintenance for FLT3-ITD Patients Undergoing Allogeneic Transplantation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Pratz, Keith W.; Gojo, Ivana; Karp, Judith E.; Luznik, Leo; Smith, B. Douglas; Greer, Jackie; Rudek, Michelle A.; Levis, Mark J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Jones, Richard J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Gocke, Christopher] Johns Hopkins, Baltimore, MD USA.
[Baer, Maria R.; Duong, Vu H.; Emadi, Ashkan] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Wright, John J.] NCI, CTEP, DCTD, NIH,Invest Drug Branch, Bethesda, MD 20892 USA.
NR 0
TC 7
Z9 7
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 4
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104046
ER
PT J
AU Purev, E
Aue, G
Kotecha, R
Wilder, J
Khuu, HM
Stroncek, DF
Kurlanders, R
Reger, RN
Flegel, WA
Adams, S
Cook, L
Ramos, C
Cho, E
Childs, RW
AF Purev, Enkhtsetseg
Aue, Georg
Kotecha, Ritesh
Wilder, Jennifer
Khuu, Hahn M.
Stroncek, David F.
Kurlanders, Roger
Reger, Robert N.
Flegel, Willy A.
Adams, Sharon
Cook, Lisa
Ramos, Catalina
Cho, Elena
Childs, Richard W.
TI Excellent Engraftment and Long-Term Survival in Patients with Severe
Aplastic Anemia (SAA) Undergoing Allogeneic Hematopoietic Stem Cell
Transplantation (HSCT) with Haplo-Identical CD34+Cells Combined with a
Single Umbilical Cord Blood Unit
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Purev, Enkhtsetseg; Aue, Georg; Kotecha, Ritesh; Cook, Lisa; Ramos, Catalina; Cho, Elena] NHLBI, NIH, Bethesda, MD 20892 USA.
[Wilder, Jennifer] NIH, Unrealted Donor Hematopoiet Stem Cell Transplant, Bethesda, MD 20892 USA.
[Khuu, Hahn M.; Flegel, Willy A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Stroncek, David F.; Adams, Sharon] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kurlanders, Roger] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Reger, Robert N.; Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021805169
ER
PT J
AU Qin, HY
Haso, W
Nguyen, SM
Fry, TJ
AF Qin, Haiying
Haso, Waleed
Sang Minh Nguyen
Fry, Terry J.
TI Preclinical Development of Bispecific Chimeric Antigen Receptor
Targeting Both CD19 and CD22
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Qin, Haiying; Sang Minh Nguyen] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Haso, Waleed] NCI, NIH, Bethesda, MD 20892 USA.
[Fry, Terry J.] Childrens Natl Med Ctr, Pediat Oncol Branch, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 2
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021802052
ER
PT J
AU Reading, NS
Clark, BE
Song, JH
Shooter, CC
Miller, RE
Agarwal, AM
Thein, SL
Divoky, V
Prchal, JT
AF Reading, N. Scott
Clark, Barnaby E.
Song, Jihyun
Shooter, Claire C.
Miller, Robin E.
Agarwal, Archana M.
Thein, Swee Lay
Divoky, Vladimir
Prchal, Josef T.
TI Sickle Cell Anemia in a Child with Three beta-Globin Clusters
(beta-S/beta-S, beta-A): Loss of LCR and 3 ' HS1 in the Duplicated
Wild-Type beta-Globin Cluster Does Not Fully Abrogate Its Transcript
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Reading, N. Scott; Prchal, Josef T.] ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA.
[Reading, N. Scott; Song, Jihyun] Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT USA.
[Reading, N. Scott; Agarwal, Archana M.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Clark, Barnaby E.] Kings Coll Hosp London, Dept Mol Pathol, Viapath, London, England.
[Shooter, Claire C.; Thein, Swee Lay] Kings Coll London, Div Canc Studies, Mol Haematol, London WC2R 2LS, England.
[Miller, Robin E.] Nemours AI duPont Hosp Children, Nemours Ctr Canc & Blood Disorders, Wilmington, DE USA.
[Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bethesda, MD 20892 USA.
[Divoky, Vladimir] Palacky Univ, Fac Med & Dent, Dept Biol, CR-77147 Olomouc, Czech Republic.
[Prchal, Josef T.] Univ Utah, Div Hematol, Salt Lake City, UT USA.
[Prchal, Josef T.] George E Wahlen Dept Vet Affairs Med Ctr, Dept Med, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 4
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104253
ER
PT J
AU Shah, NN
Freeman, AF
Parta, M
Su, H
Uzel, G
Gea-Banacloche, JC
Holland, SM
Hickstein, DD
AF Shah, Nirali N.
Freeman, Alexandra F.
Parta, Mark
Su, Helen
Uzel, Gulbu
Gea-Banacloche, Juan C.
Holland, Steven M.
Hickstein, Dennis D.
TI Haploidentical Transplantation for DOCK8 Deficiency
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Shah, Nirali N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Parta, Mark] Leidos Biomed Res Inc, Bethesda, MD USA.
[Su, Helen] NIAID, NIH, Host Def Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Gea-Banacloche, Juan C.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Hickstein, Dennis D.] NCI, ETIB, NCI, Bethesda, MD USA.
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101067
ER
PT J
AU Shanis, DL
Anandi, P
Grant, C
Pophali, PA
Koklanaris, E
Savani, BN
Barrett, AJ
Battiwalla, M
Stratton, P
AF Shanis, Dana L.
Anandi, Prathima
Grant, Caitlin
Pophali, Priyanka A.
Koklanaris, Eleftheria
Savani, Bipin N.
Barrett, Austin John
Battiwalla, Minoo
Stratton, Pamela
TI Extensive Chronic Graft-Versus-Host-Disease Significantly Increases the
Risk of Severe and Multifocal Genital Tract HPV Disease in Long-Term
Survivors of Allogeneic Stem Cell Transplantation
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Shanis, Dana L.; Grant, Caitlin; Stratton, Pamela] NICHD, NIH, Bethesda, MD USA.
[Anandi, Prathima; Barrett, Austin John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Pophali, Priyanka A.] Cleveland Clin, Dept Hematol & Med Oncol, Cleveland, OH 44106 USA.
[Koklanaris, Eleftheria] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
RI Pophali, Priyanka/P-8646-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020100121
ER
PT J
AU Sharma, KR
Rattila, S
Kiesler, P
Ballesteros, A
Luo, J
Koontz, S
Warren, J
Malech, HL
Dveksler, G
Kang, EM
AF Sharma, Karlie R.
Rattila, Shemona
Kiesler, Patricia
Ballesteros, Angela
Luo, Jian
Koontz, Sherry
Warren, James
Malech, Harry L.
Dveksler, Gabriela
Kang, Elizabeth M.
TI Graft Versus Host Disease (GvHD) Is Attenuated By Administration of
Pregnancy Specific Glycoproteins through Induction of Immune Tolerance
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Sharma, Karlie R.; Koontz, Sherry; Malech, Harry L.; Kang, Elizabeth M.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Rattila, Shemona; Warren, James; Dveksler, Gabriela] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA.
[Kiesler, Patricia] NIAID, NIH, Bethesda, MD 20892 USA.
[Ballesteros, Angela] NIH, Bethesda, MD 20892 USA.
[Luo, Jian] Stanford Univ, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021801220
ER
PT J
AU Shirasugi, Y
Noji, H
Shichishima, T
Sugimori, C
Obara, N
Chiba, S
Ninomiya, H
Nakamura, Y
Ando, K
Yonemura, Y
Kawaguchi, T
Hosokawa, K
Ueda, Y
Nishimura, JI
Kanakura, Y
Nakao, S
AF Shirasugi, Yukari
Noji, Hideyoshi
Shichishima, Tsutomu
Sugimori, Chiharu
Obara, Naoshi
Chiba, Shigeru
Ninomiya, Haruhiko
Nakamura, Yoshihiko
Ando, Kiyoshi
Yonemura, Yuji
Kawaguchi, Tatsuya
Hosokawa, Kohei
Ueda, Yasutaka
Nishimura, Jun-Ichi
Kanakura, Yuzuru
Nakao, Shinji
TI An Interim 4-Year Analysis of Prospective Multicenter Observational
Study of PNH-Type Cells in Japanese Patients with Bone Marrow Failure
Syndrome (OPTIMA study)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Shirasugi, Yukari; Nakamura, Yoshihiko; Ando, Kiyoshi] Tokai Univ, Sch Med, Dept Hematol & Oncol, Isehara, Kanagawa 25911, Japan.
[Shirasugi, Yukari; Noji, Hideyoshi; Shichishima, Tsutomu; Sugimori, Chiharu; Obara, Naoshi; Chiba, Shigeru; Ninomiya, Haruhiko; Nakamura, Yoshihiko; Ando, Kiyoshi; Yonemura, Yuji; Kawaguchi, Tatsuya; Hosokawa, Kohei; Ueda, Yasutaka; Nishimura, Jun-Ichi; Kanakura, Yuzuru; Nakao, Shinji] Japan PNH Study Grp, Tokyo, Japan.
[Noji, Hideyoshi] Fukushima Med Univ, Dept Internal Med 1, Fukushima, Japan.
[Shichishima, Tsutomu] Fukushima Med Univ, Fukushima, Japan.
[Sugimori, Chiharu] Ishikawa Prefectural Cent Hosp, Dept Hematol, Kanazawa, Ishikawa, Japan.
[Obara, Naoshi] Univ Tsukuba, Dept Hematol, Tsukuba, Ibaraki, Japan.
[Chiba, Shigeru] Univ Tsukuba, Inst Clin Med, Dept Clin & Expt Hematol, Tsukuba, Ibaraki 305, Japan.
[Ninomiya, Haruhiko] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
[Yonemura, Yuji] Kumamoto Univ Hosp, Dept Transfus Med & Cell Therapy, Kumamoto, Japan.
[Kawaguchi, Tatsuya] Kumamoto Univ, Grad Sch Mecical Sci, Dept Hematol & Infect Dis, Kumamoto, Japan.
[Hosokawa, Kohei] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hosokawa, Kohei; Nakao, Shinji] Kanazawa Univ, Grad Sch Med Sci, Cellular Transplantat Biol, Kanazawa, Ishikawa, Japan.
[Ueda, Yasutaka; Nishimura, Jun-Ichi; Kanakura, Yuzuru] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Suita, Osaka, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021803084
ER
PT J
AU Siddiqi, T
Scuto, A
Beumer, JH
Song, JY
Frankel, P
Ruel, C
Cobb, J
Kiesel, BF
Weisenburger, DD
Kelly, KR
Tuscano, J
Popplewell, L
Forman, SJ
Piekarz, R
Newman, EM
AF Siddiqi, Tanya
Scuto, Anna
Beumer, Jan H.
Song, Joo Y.
Frankel, Paul
Ruel, Chris
Cobb, Jacob
Kiesel, Brian F.
Weisenburger, Dennis D.
Kelly, Kevin R.
Tuscano, Joseph
Popplewell, Leslie
Forman, Stephen J.
Piekarz, Richard
Newman, Edward M.
TI Results from a Phase 1 Study and Expanded Cohort of an Interrupted
Dosing Schedule of the Aurora Kinase a Inhibitor MLN8237 Combined with
Vorinostat in Lymphoid Malignancies
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Siddiqi, Tanya] City Hope Natl Med Ctr, Natl Med Ctr, Duarte, CA USA.
[Scuto, Anna] City Hope Natl Med Ctr, Ctr Comprehens Canc, Beckman Res Inst, Duarte, CA USA.
[Beumer, Jan H.; Kiesel, Brian F.] Univ Pittsburgh, Inst Canc, Canc Therapeut Program, Pittsburgh, PA USA.
[Song, Joo Y.; Weisenburger, Dennis D.] City Hope Natl Med Ctr, Natl Med Ctr, Dept Pathol, Duarte, CA USA.
[Frankel, Paul; Ruel, Chris] City Hope Natl Med Ctr, Natl Med Ctr, Biostat, Duarte, CA USA.
[Cobb, Jacob] City Hope Natl Med Ctr, Natl Med Ctr, Pathol, Duarte, CA USA.
[Kelly, Kevin R.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Tuscano, Joseph] Univ Calif Davis, Sacramento, CA 95817 USA.
[Popplewell, Leslie] City Hope Natl Med Ctr, Natl Med Ctr, Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA.
[Forman, Stephen J.] City Hope Natl Med Ctr, Dept Hematol, Duarte, CA USA.
[Forman, Stephen J.] City Hope Natl Med Ctr, HCT, Duarte, CA USA.
[Piekarz, Richard] NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
[Newman, Edward M.] City Hope Natl Med Ctr, Duarte, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102243
ER
PT J
AU Soumerai, JD
Zelenetz, AD
Moskowitz, CH
Younes, A
Palomba, ML
Hamlin, PA
Noy, A
Horwitz, SM
Matasar, MJ
Moskowitz, AJ
Portlock, CS
Straus, DJ
Chen, A
Little, RF
France, F
Whang, J
Mishra, N
Jarjies, C
Gerecitano, JF
AF Soumerai, Jacob D.
Zelenetz, Andrew D.
Moskowitz, Craig H.
Younes, Anas
Palomba, Maria Lia
Hamlin, Paul A., Jr.
Noy, Ariela
Horwitz, Steven M.
Matasar, Matthew J.
Moskowitz, Alison J.
Portlock, Carol S.
Straus, David J.
Chen, Alice
Little, Richard F.
France, Fallon
Whang, Juho
Mishra, Nishant
Jarjies, Christine
Gerecitano, John F.
TI Veliparib (ABT-888), Bendamustine, and Rituximab (VBR) Is Well Tolerated
and Efficacious in Patients with Lymphoma: Final Analysis of a Phase 1b
Clinical Trial of VB and a Cohort Expansion of Vbr in Patients with
B-Cell Lymphoma
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Soumerai, Jacob D.; Zelenetz, Andrew D.; Moskowitz, Craig H.; Younes, Anas; Palomba, Maria Lia; Hamlin, Paul A., Jr.; Noy, Ariela; Horwitz, Steven M.; Matasar, Matthew J.; Moskowitz, Alison J.; Portlock, Carol S.; Straus, David J.; Gerecitano, John F.] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10021 USA.
[Moskowitz, Craig H.; Matasar, Matthew J.] Mem Sloan Kettering Canc Ctr, Dept Med, Adult BMT Serv, New York, NY 10021 USA.
[Chen, Alice; Little, Richard F.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[France, Fallon; Whang, Juho; Mishra, Nishant; Jarjies, Christine] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102203
ER
PT J
AU Spornick, N
Almeida, LE
Speller-Brown, B
Darbari, D
Jackson, K
Finkel, J
Quezado, Z
AF Spornick, Nicholas
Almeida, Luis E.
Speller-Brown, Barbara
Darbari, Deepika
Jackson, Kevin
Finkel, Julie
Quezado, Zena
TI Sickle Cell Disease Patients Show Sensitization of Myelinated Sensory
Nerve Fibers
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Spornick, Nicholas] Quinnipiac Univ, Frank H Netter Sch Med, Hamden, CT USA.
[Spornick, Nicholas; Almeida, Luis E.; Jackson, Kevin; Finkel, Julie; Quezado, Zena] Childrens Natl Hlth Syst, Childrens Res Inst, Washington, DC USA.
[Speller-Brown, Barbara] Childrens Natl Hlth Syst, Washington, DC USA.
[Darbari, Deepika] NHLBI, Pediat Hematol & Oncol, NHLBI Pulm & Vasc Med, Childrens Natl Med Ctr, Washington, DC USA.
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020104274
ER
PT J
AU Srour, SA
Devesa, SS
Morton, LM
Check, DP
Curtis, RE
Linet, MS
Dores, GM
AF Srour, Samer A.
Devesa, Susan S.
Morton, Lindsay M.
Check, David P.
Curtis, Rochelle E.
Linet, Martha S.
Dores, Graca M.
TI Incidence and Patient Survival of Myeloproliferative Neoplasms (MPNs)
and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs) in the
United States: A Population-Based View of the Modern Diagnostic Era
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Srour, Samer A.; Devesa, Susan S.; Dores, Graca M.] Oklahoma City VA Hlth Care Syst, Oklahoma City, OK USA.
[Srour, Samer A.] Univ Oklahoma, Hlth Sci Ctr, Grad Coll, Oklahoma City, OK USA.
[Srour, Samer A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Devesa, Susan S.; Morton, Lindsay M.; Check, David P.; Curtis, Rochelle E.; Linet, Martha S.; Dores, Graca M.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020103001
ER
PT J
AU Su, R
Li, ZJ
Chen, P
Li, YY
Chao, H
Wang, YG
Arnovitz, S
He, M
Gurbuxani, S
Zuo, ZX
Elkahloun, AG
Li, SL
Weng, HY
Huang, H
Neilly, MB
Wang, SS
Larson, RA
Zhang, JW
Jiang, X
Wei, MJ
Jin, J
Liu, PP
Chen, JJ
AF Su, Rui
Li, Zejuan
Chen, Ping
Li, Yuanyuan
Chao, Hu
Wang, Yungui
Arnovitz, Stephen
He, Miao
Gurbuxani, Sandeep
Zuo, Zhixiang
Elkahloun, Abdel G.
Li, Shenglai
Weng, Hengyou
Huang, Hao
Neilly, Mary Beth
Wang, Shusheng
Larson, Richard A.
Zhang, Jiwang
Jiang, Xi
Wei, Minjie
Jin, Jie
Liu, Paul P.
Chen, Jianjun
TI Overexpression and Knockout of Mir-126 Both Promote Leukemogenesis
through Targeting Distinct Gene Signaling
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Su, Rui; Wang, Yungui; Weng, Hengyou; Jiang, Xi; Chen, Jianjun] Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA.
[Li, Zejuan; Chen, Ping; Wang, Yungui; Arnovitz, Stephen; Weng, Hengyou; Neilly, Mary Beth; Jiang, Xi; Chen, Jianjun] Univ Chicago, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA.
[Li, Zejuan] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Li, Yuanyuan; Chao, Hu; He, Miao; Li, Shenglai; Huang, Hao; Larson, Richard A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Zuo, Zhixiang] Univ Cincinnati, Cincinnati, OH USA.
[Elkahloun, Abdel G.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Wang, Shusheng] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
[Zhang, Jiwang] Loyola Univ, Med Ctr, Inst Oncol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA.
[Wei, Minjie] China Med Univ, Dept Pharmacol, Shenyang 110001, Peoples R China.
[Jin, Jie] Zhejiang Univ, Dept Hematol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China.
[Jin, Jie] Zhejiang Univ, Inst Hematol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China.
[Liu, Paul P.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Paul P.] NHGRI, Microarray Core, NIH, Bethesda, MD 20892 USA.
RI Zuo, Zhixiang/M-4441-2016
OI Zuo, Zhixiang/0000-0002-2492-2689
NR 0
TC 0
Z9 0
U1 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105233
ER
PT J
AU Wang, XH
Wang, HQ
Bi, CF
Zhang, XY
Huang, X
Zhang, X
Iqbal, J
Wright, GW
Staudt, LM
Chan, WC
McKeithan, TW
Wang, P
Zhang, HL
Fu, K
AF Wang, Xianhuo
Wang, Huaqing
Bi, Chengfeng
Zhang, Xiaoyan
Huang, Xin
Zhang, Xuan
Iqbal, Javeed
Wright, George W.
Staudt, Louis M.
Chan, Wing C.
McKeithan, Timothy W.
Wang, Ping
Zhang, Huilai
Fu, Kai
TI Microrna-17 similar to 92 Cluster Upregulates NF-KB Activity Via
Suppressing Multiple NF-KB Negative Regulators Mediating Ubiquitination
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Wang, Xianhuo; Wang, Huaqing; Wang, Ping; Zhang, Huilai; Fu, Kai] Tianjin Med Univ Canc Inst & Hosp, Sino US Ctr Lymphoma & Leukemia, Natl Clin Res Ctr Canc, Dept Lymphoma,Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China.
[Wang, Xianhuo; Bi, Chengfeng; Zhang, Xiaoyan; Huang, Xin; Zhang, Xuan; Iqbal, Javeed; Fu, Kai] Univ Nebraska Med Ctr, Dept Pathol & Microbiol & Internal Med, Omaha, NE USA.
[Zhang, Xiaoyan] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Dept Pediat, Tianjin, Peoples R China.
[Zhang, Xiaoyan] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.
[Zhang, Xiaoyan] Peking Union Med Coll, Tianjin, Peoples R China.
[Wright, George W.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chan, Wing C.; McKeithan, Timothy W.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105204
ER
PT J
AU Webster, JA
Tibes, R
Blackford, A
Morris, L
Patnaik, MM
Wang, LH
Rebechi, M
Greer, J
Litzow, MR
Karnitz, L
Rosner, GL
Doyle, A
Kaufmann, SH
Karp, JE
Smith, BD
AF Webster, Jonathan Allen
Tibes, Raoul
Blackford, Amanda
Morris, Lawrence
Patnaik, Mrinal M.
Wang, Lihua
Rebechi, Melanie
Greer, Jacqueline
Litzow, Mark R.
Karnitz, Larry
Rosner, Gary L.
Doyle, Austin
Kaufmann, Scott H.
Karp, Judith E.
Smith, B. Douglas
TI Randomized Phase II Trial of Timed Sequential Cytosine Arabinoside with
and without the CHK1 Inhibitor MK-8876 in Adults with Relapsed and
Refractory Acute Myelogenous Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Webster, Jonathan Allen; Rebechi, Melanie; Greer, Jacqueline; Karp, Judith E.; Smith, B. Douglas] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Tibes, Raoul] Mayo Clin, Scottsdale, AZ USA.
[Blackford, Amanda; Rosner, Gary L.] Johns Hopkins Univ, Baltimore, MD USA.
[Morris, Lawrence] BMT Grp Georgia, Atlanta, GA USA.
[Patnaik, Mrinal M.; Litzow, Mark R.] Mayo Clin, Div Hematol, Rochester, MN USA.
[Wang, Lihua] NCI, Frederick, MD 21701 USA.
[Karnitz, Larry] Mayo Clin, Rochester, MN USA.
[Doyle, Austin] NCI, Bethesda, MD 20892 USA.
[Kaufmann, Scott H.] Mayo Clin, Oncol Res, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102075
ER
PT J
AU Weinacht, KG
Charbonnier, LM
Plant, A
Torgerson, T
Rosenzweig, S
Fleisher, T
Notarangelo, LD
AF Weinacht, Katja G.
Charbonnier, Louis M.
Plant, Ashley
Torgerson, Troy
Rosenzweig, Serge
Fleisher, Thomas
Notarangelo, Luigi Daniele
TI Successful Therapy of a Patient with a Novel STAT1 Gain of Function
Mutation and Life-Threatening Cytopenias with Janus Kinase Inhibitor
Ruxolitinib
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Weinacht, Katja G.] Childrens Hosp Boston, Dana Farber Canc Inst, Hematol Oncol, Boston, MA USA.
[Charbonnier, Louis M.] Boston Childrens Hosp, Dept Pediat Immunol, Boston, MA USA.
[Plant, Ashley] Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA USA.
[Torgerson, Troy] Univ Washington, Seattle, WA 98195 USA.
[Torgerson, Troy] Seattle Childrens Res Inst, Seattle, WA USA.
[Rosenzweig, Serge] NIAID, NIH, Bethesda, MD 20892 USA.
[Fleisher, Thomas] NIAID, NCI, Lab Med, NIH, Bethesda, MD 20892 USA.
[Notarangelo, Luigi Daniele] Boston Childrens Hosp, Div Immunol, Boston, MA USA.
RI Notarangelo, Luigi/F-9718-2016
OI Notarangelo, Luigi/0000-0002-8335-0262
NR 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105001
ER
PT J
AU Winkler, T
Corat, MAF
Liu, DL
Jung, MJ
Townsley, DM
Wu, CF
Young, NS
Dunbar, CE
AF Winkler, Thomas
Corat, Marcus A. F.
Liu, Delong
Jung, Moonjung
Townsley, Danielle M.
Wu, Chuanfeng
Young, Neal S.
Dunbar, Cynthia E.
TI Insights into Clonal Relationships of Putative Adaptive Natural Killer
Cells (NK) in Humans, Via Mapping of Somatic Piga Mutations in Patients
with Paroxysmal Nocturna Hemoglobinuria (PNH)
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Winkler, Thomas; Corat, Marcus A. F.; Liu, Delong; Jung, Moonjung; Townsley, Danielle M.; Wu, Chuanfeng; Young, Neal S.; Dunbar, Cynthia E.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020101061
ER
PT J
AU Xao, WB
Chen, W
Sorbara, L
Davies-Hill, T
Pittaluga, S
Raffeld, M
Jaffe, ES
AF Xao, Wenbin
Chen, Wayne
Sorbara, Lynn
Davies-Hill, Theresa
Pittaluga, Stefania
Raffeld, Mark
Jaffe, Elaine S.
TI Hodgkin Lymphoma Variant of Richter Transformation: Morphology, EBV
Status, Clonality and Survival Analysis a Retrospective Study of 77
Patients
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Xao, Wenbin; Chen, Wayne; Sorbara, Lynn; Davies-Hill, Theresa] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020102149
ER
PT J
AU Yang, YG
Zhang, YB
Zhu, J
Lai, CE
Tang, JR
McReynolds, LJ
Hsu, AP
Hickstein, DD
Townsley, DM
Holland, SM
Calvo, KR
Hourigan, CS
AF Yang, Yangin
Zhang, Yubo
Zhu, Jun
Lai, Catherine E.
Tang, Jingrong
McReynolds, Lisa J.
Hsu, Amy P.
Hickstein, Dennis D.
Townsley, Danielle M.
Holland, Steven M.
Calvo, Katherine R.
Hourigan, Christopher S.
TI Development of Somatic NRAS Mutation Associated with Rapid Transition
from Germline GATA2 Mutation Associated Myelodysplastic Syndrome to
Acute Myeloid Leukemia
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Yang, Yangin; Zhang, Yubo; Zhu, Jun] NHLBI, DNA Sequencing & Genom Core, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Lai, Catherine E.; Tang, Jingrong; Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[McReynolds, Lisa J.; Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hickstein, Dennis D.] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Townsley, Danielle M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105182
ER
PT J
AU Zhao, L
Alemu, L
Cheng, J
Zhen, T
Friedman, AD
Liu, PP
AF Zhao, Ling
Alemu, Lemlem
Cheng, Jun
Zhen, Tao
Friedman, Alan D.
Liu, Pu Paul
TI The Multimerization Domain of Cbf beta-SMMHC Is Required for
Leukemogenesis
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Zhao, Ling; Alemu, Lemlem; Zhen, Tao; Liu, Pu Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Cheng, Jun] NHGRI, Transgen Mouse Core, NIH, Bethesda, MD 20892 USA.
[Friedman, Alan D.] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105232
ER
PT J
AU Zhao, X
Feng, XM
Townsley, DM
Winkler, T
Desmond, R
Olnes, MJ
Leuva, H
Dumitriu, B
Dunbar, CE
Young, NS
AF Zhao, Xin
Feng, Xingmin
Townsley, Danielle M.
Winkler, Thomas
Desmond, Ronan
Olnes, Matthew J.
Leuva, Harshraj
Dumitriu, Bogdan
Dunbar, Cynthia E.
Young, Neal S.
TI Persistent Elevation of Plasma Thrombopoietin Levels in Severe Aplastic
Anemia, Even with Hematologic Recovery
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Zhao, Xin; Feng, Xingmin; Townsley, Danielle M.; Winkler, Thomas; Desmond, Ronan; Olnes, Matthew J.; Leuva, Harshraj; Dumitriu, Bogdan; Dunbar, Cynthia E.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105175
ER
PT J
AU Zhen, T
Zhao, L
Hyde, RK
Alemu, L
Liu, PP
AF Zhen, Tao
Zhao, Ling
Hyde, R. Katherine
Alemu, Lemlem
Liu, Pu Paul
TI CHD7 Deficiency Inhibits CBFB-MYH11-Induced Leukemogenesis
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Zhen, Tao; Zhao, Ling; Alemu, Lemlem; Liu, Pu Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Hyde, R. Katherine] Univ Nebraska Med Ctr, Omaha, NE USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 2
WC Hematology
SC Hematology
GA DA7XY
UT WOS:000368020105228
ER
PT J
AU Zhu, JQ
Chin, K
Aerbajinai, W
Li, HZ
Kumkhaek, C
Hsieh, M
Rodgers, GP
AF Zhu, Jianqiong
Chin, Kyung
Aerbajinai, Wulin
Li, Hongzhen
Kumkhaek, Chutima
Hsieh, Matthew
Rodgers, Griffin P.
TI A Novel Recombinant Eklf-GATA1 Fusion Protein Reduces Erythrocytes
Sickling in Human Erythroid Culture Model
SO BLOOD
LA English
DT Meeting Abstract
CT 57th Annual Meeting of the American-Society-of-Hematology
CY DEC 05-08, 2015
CL Orlando, FL
SP Amer Soc Hematol
C1 [Zhu, Jianqiong; Chin, Kyung; Aerbajinai, Wulin; Li, Hongzhen; Kumkhaek, Chutima; Hsieh, Matthew; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 DEC 3
PY 2015
VL 126
IS 23
PG 3
WC Hematology
SC Hematology
GA DA7YP
UT WOS:000368021802038
ER
PT J
AU Costa, GNO
Dudbridge, F
Fiaccone, RL
da Silva, TM
Conceicao, JS
Strina, A
Figueiredo, CA
Magalhaes, WCS
Rodrigues, MR
Gouveia, MH
Kehdy, FSG
Horimoto, ARVR
Horta, B
Burchard, EG
Pino-Yanes, M
Navarro, BD
Romieu, I
Hancock, DB
London, S
Lima-Costa, MF
Pereira, AC
Tarazona, E
Rodrigues, LC
Barreto, ML
AF Costa, Gustavo N. O.
Dudbridge, Frank
Fiaccone, Rosemeire L.
da Silva, Thiago M.
Conceicao, Jackson S.
Strina, Agostino
Figueiredo, Camila A.
Magalhaes, Wagner C. S.
Rodrigues, Maira R.
Gouveia, Mateus H.
Kehdy, Fernanda S. G.
Horimoto, Andrea R. V. R.
Horta, Bernardo
Burchard, Esteban G.
Pino-Yanes, Maria
Navarro, Blanca Del Rio
Romieu, Isabelle
Hancock, Dana B.
London, Stephanie
Lima-Costa, Maria Fernanda
Pereira, Alexandre C.
Tarazona, Eduardo
Rodrigues, Laura C.
Barreto, Mauricio L.
TI A genome-wide association study of asthma symptoms in Latin American
children
SO BMC GENETICS
LA English
DT Article
DE Asthma symptoms; Genome-wide association; Latin America; Children
ID HERITABILITY; GENES; BIOGENESIS; PHENOTYPES; ANCESTRY; LEUKEMIA; HEIGHT;
FAMILY; LOCUS; SCALE
AB Background: Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.
Methods: 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples.
Results: Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45-2.18, p-value 2.83 x 10(-8)) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02-4.49, p-value 6.68 x 10(-8) and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76-3.53, p-value 2.45 x 10(-7)). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.
Conclusions: We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.
C1 [Costa, Gustavo N. O.; da Silva, Thiago M.; Strina, Agostino; Barreto, Mauricio L.] Univ Fed Bahia, Inst Saude Colet, Salvador, BA, Brazil.
[Fiaccone, Rosemeire L.; Conceicao, Jackson S.] Univ Fed Bahia, Inst Matemat, Salvador, BA, Brazil.
[Figueiredo, Camila A.] Univ Fed Bahia, Inst Ciencias Saude, Salvador, BA, Brazil.
[Magalhaes, Wagner C. S.; Rodrigues, Maira R.; Gouveia, Mateus H.; Kehdy, Fernanda S. G.; Tarazona, Eduardo] Univ Fed Minas Gerais, Inst Ciencias Biol, Belo Horizonte, MG, Brazil.
[Horimoto, Andrea R. V. R.] Univ Sao Paulo, Inst Coracao, Sao Paulo, Brazil.
[Horta, Bernardo] Univ Fed Pelotas, Programa Pos Grad Epidemiol, Pelotas, Brazil.
[Burchard, Esteban G.; Pino-Yanes, Maria] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Navarro, Blanca Del Rio; London, Stephanie] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Romieu, Isabelle] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Hancock, Dana B.] RTI Int, Behav & Urban Hlth Program, Res Triangle Pk, NC USA.
[Lima-Costa, Maria Fernanda; Pereira, Alexandre C.] Fundacao Oswaldo Cruz, Inst Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil.
[Dudbridge, Frank] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Rodrigues, Laura C.] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London WC1, England.
[Barreto, Mauricio L.] Fundacao Osvaldo Cruz, Ctr Pesquisa Goncalo Muniz, Salvador, BA, Brazil.
RP Costa, GNO (reprint author), Univ Fed Bahia, Inst Saude Colet, Salvador, BA, Brazil.
EM gustavokosta@gmail.com
RI Figueiredo, Camila/H-3525-2015; Magalhaes, Wagner/D-8822-2015; Horta,
Bernardo/A-7604-2008; Pino-Yanes, Maria/C-8498-2017;
OI Figueiredo, Camila/0000-0003-1356-6188; Pino-Yanes,
Maria/0000-0003-0332-437X; Hancock, Dana/0000-0003-2240-3604; Nunes de
Oliveira Costa, Gustavo/0000-0003-3445-0192; London,
Stephanie/0000-0003-4911-5290
FU Department of Science and Technology (DECIT, Ministry of Health);
National Fund for Scientific and Technological Development (FNDCT,
Ministry of Science and Technology); Funding of Studies and Projects
(FINEP, Ministry of Science and Technology, Brazil); Brazilian National
Research Council (CNPq); Wellcome Trust UK [072405/Z/03/Z]; National
Institutes of Health [HL088133, HL078885, HL004464, HL104608, HL117004,
ES015794, MD006902]; American Asthma Foundation; Sandler Foundation;
RWJF Amos Medical Faculty Development Award; Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences, USA
FX This work was supported by the Department of Science and Technology
(DECIT, Ministry of Health), National Fund for Scientific and
Technological Development (FNDCT, Ministry of Science and Technology),
Funding of Studies and Projects (FINEP, Ministry of Science and
Technology, Brazil), the Brazilian National Research Council (CNPq) and
the Wellcome Trust UK, Ref 072405/Z/03/Z.; E.G.B. was funded by grants
from National Institutes of Health (HL088133, HL078885, HL004464,
HL104608, HL117004, ES015794 and MD006902) and by the American Asthma
Foundation, the Sandler Foundation and the RWJF Amos Medical Faculty
Development Award.; Supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences, USA.
NR 50
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Z9 3
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD DEC 3
PY 2015
VL 16
AR 141
DI 10.1186/s12863-015-0296-7
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA CX8IX
UT WOS:000365947200005
PM 26635092
ER
PT J
AU Robey, PG
Riminucci, M
Boyde, A
Sipp, D
AF Robey, Pamela Gehron
Riminucci, Mara
Boyde, Alan
Sipp, Douglas
TI Paolo Bianco (1955-2015) Obituary
SO CELL STEM CELL
LA English
DT Biographical-Item
C1 [Robey, Pamela Gehron] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Riminucci, Mara] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy.
[Boyde, Alan] Queen Mary Univ London, Dent Phys Sci, London E1 4NS, England.
[Sipp, Douglas] RIKEN, Ctr Dev Biol, Wako, Saitama 3510198, Japan.
RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA.
EM probey@dir.nidcr.nih.gov
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 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD DEC 3
PY 2015
VL 17
IS 6
BP 649
EP 650
DI 10.1016/j.stem.2015.11.013
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CY1AS
UT WOS:000366139100007
PM 27010035
ER
PT J
AU Ryall, JG
Cliff, T
Dalton, S
Sartorelli, V
AF Ryall, James G.
Cliff, Tim
Dalton, Stephen
Sartorelli, Vittorio
TI Metabolic Reprogramming of Stem Cell Epigenetics
SO CELL STEM CELL
LA English
DT Review
ID ACETYLGLUCOSAMINE TRANSFERASE OGT; MUSCLE SATELLITE CELLS; HEMATOPOIETIC
STEM; SKELETAL-MUSCLE; SELF-RENEWAL; VITAMIN-C; GLYCOLYTIC METABOLISM;
HISTONE DEMETHYLATION; SOMATIC-CELLS; BONE-MARROW
AB For many years, stem cell metabolism was viewed as a byproduct of cell fate status rather than an active regulatory mechanism; however, there is now a growing appreciation that metabolic pathways influence epigenetic changes associated with lineage commitment, specification, and self-renewal. Here we review how metabolites generated during glycolytic and oxidative processes are utilized in enzymatic reactions leading to epigenetic modifications and transcriptional regulation. We discuss how "metabolic reprogramming" contributes to global epigenetic changes in the context of naive and primed pluripotent states, somatic reprogramming, and hematopoietic and skeletal muscle tissue stem cells, and we discuss the implications for regenerative medicine.
C1 [Ryall, James G.] Univ Melbourne, Dept Physiol, Basic & Clin Myol Lab, Stem Cell Metab & Regenerat Med Grp, Melbourne, Vic 3010, Australia.
[Cliff, Tim; Dalton, Stephen] Univ Georgia, Paul D Coverdell Ctr Biomed & Hlth Sci, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
[Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20829 USA.
RP Ryall, JG (reprint author), Univ Melbourne, Dept Physiol, Basic & Clin Myol Lab, Stem Cell Metab & Regenerat Med Grp, Melbourne, Vic 3010, Australia.
EM jgryall@gmail.com; sartorev@mail.nih.gov
OI Ryall, James/0000-0003-4702-1143
FU Intramural Research Program of NIAMS; National Institute for General
Medical Sciences [P01 GM085354]; Australian Research Council (ARC)
[DP150100206]
FX This work was supported in part by the Intramural Research Program of
NIAMS, a grant to S.D. from the National Institute for General Medical
Sciences (P01 GM085354), and a grant to J.G.R. from the Australian
Research Council (ARC, DP150100206). We thank Stefania Dell'Orso, John
J. O'Shea, and Richard M. Siegel (NIAMS); Thomas Rando (Stanford
University); and Eytan Ruppin and Noam Auslander (University of Maryland
and Tel-Aviv University) for stimulating discussions. The comments of
three anonymous reviewers are also kindly acknowledged.
NR 123
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U1 12
U2 47
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD DEC 3
PY 2015
VL 17
IS 6
BP 651
EP 662
DI 10.1016/j.stem.2015.11.012
PG 12
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CY1AS
UT WOS:000366139100008
PM 26637942
ER
PT J
AU Sastry, N
Zheng, W
Liu, GX
Wang, HL
Chen, X
Cai, M
Contractor, P
Sgobio, C
Sun, LX
Xie, CS
Cai, HB
AF Sastry, Namratha
Zheng, Wang
Liu, Guoxiang
Wang, Helen
Chen, Xi
Cai, Michael
Contractor, Parth
Sgobio, Carmelo
Sun, Lixin
Xie, Chengsong
Cai, Huaibin
TI No apparent transmission of transgenic alpha-synuclein into
nigrostriatal dopaminergic neurons in multiple mouse models
SO TRANSLATIONAL NEURODEGENERATION
LA English
DT Article
DE Parkinson's disease; alpha-synuclein; Propagation; Dopaminergic neurons;
Transgenic mice
ID PARKINSONS-DISEASE; SYNAPTIC DYSFUNCTION; MICE; NEURODEGENERATION;
EXPRESSION; SYSTEMS
AB Background: alpha-synuclein (alpha-syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson's disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of alpha-syn to propagate between or across neighboring neurons and supposedly "infect" them with a prion-like mechanism. However, much of this research has used stereotaxic injections of heterologous alpha-syn fibrils to induce the spreading of inclusions in the rodent brains. Whether alpha-syn is able to transmit from the host cells to their neighboring cells in vivo is unclear.
Methods: Using immunestaining, we examined the potential propagation of alpha-syn into nigrostriatal dopaminergic (DA) neurons in three lines of transgenic mice that overexpress human wild-type alpha-syn (h alpha-syn) in different neuron populations.
Results: After testing for three different routes by which h alpha-syn propagation might occur, we were unable to find any evidence that h alpha-syn behaved like a prion and could be transmitted overtime into the DA neurons initially lack of h alpha-syn expression.
Conclusions: In transgenic mice h alpha-syn does not have the ability to propagate at pathologically significant levels between or across neurons. It must be noted that these observations do not disprove the studies that show its prion-like qualities, but rather that propagation is not detectable in transgenic models that do not use any injections of heterologous proteins or viral vectors to induce a spreading state.
C1 [Sastry, Namratha; Zheng, Wang; Liu, Guoxiang; Wang, Helen; Chen, Xi; Contractor, Parth; Sgobio, Carmelo; Sun, Lixin; Xie, Chengsong; Cai, Huaibin] NIA, Transgenics Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Cai, Michael] NIMH, Unit Synapse Dev Plast, Clin Brain Disorder Branch, NIH, Bethesda, MD 20892 USA.
RP Cai, HB (reprint author), NIA, Transgenics Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A112,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov
OI Sastry, Namratha/0000-0003-4056-6044
NR 24
TC 1
Z9 1
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2047-9158
J9 TRANSL NEURODEGENER
JI Transl. Neurodegener.
PD DEC 3
PY 2015
VL 4
AR UNSP 23
DI 10.1186/s40035-015-0046-9
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CY3OJ
UT WOS:000366318800001
PM 26635953
ER
PT J
AU Effoe, VS
Chen, HY
Moran, A
Bertoni, AG
Bluemke, DA
Seeman, T
Darwin, C
Watson, KE
Rodriguez, CJ
AF Effoe, Valery S.
Chen, Haiying
Moran, Andrew
Bertoni, Alain G.
Bluemke, David A.
Seeman, Teresa
Darwin, Christine
Watson, Karol E.
Rodriguez, Carlos J.
TI Acculturation is associated with left ventricular mass in a multiethnic
sample: the Multi-Ethnic Study of Atherosclerosis
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
DE Acculturation; Left ventricular mass index; Cardiovascular risk; Ethnic
disparities
ID UNITED-STATES; RISK-FACTORS; SOCIOECONOMIC-STATUS; HISPANIC IMMIGRANTS;
NORTHERN MANHATTAN; MEXICAN-AMERICANS; ASIAN-AMERICANS; HYPERTENSION;
HEALTH; SUBGROUPS
AB Background: Acculturation involves stress-related processes and health behavioral changes, which may have an effect on left ventricular (LV) mass, a risk factor for cardiovascular disease (CVD). We examined the relationship between acculturation and LV mass in a multiethnic cohort of White, African-American, Hispanic and Chinese subjects.
Methods: Cardiac magnetic resonance assessment was available for 5004 men and women, free of clinical CVD at baseline. Left ventricular mass index was evaluated as LV mass indexed by body surface area. Acculturation was characterized based on language spoken at home, place of birth and length of stay in the United States (U. S.), and a summary acculturation score ranging from 0 = least acculturated to 5 = most acculturated. Mean LV mass index adjusted for traditional CVD risk factors was compared across acculturation levels.
Results: Unadjusted mean LV mass index was 78.0 +/- 16.3 g/m(2). In adjusted analyses, speaking exclusively English at home compared to non-English language was associated with higher LV mass index (81.3 +/- 0.4 g/m(2) vs 79.9 +/- 0.5 g/m(2), p = 0.02). Among foreign-born participants, having lived in the U. S. for >= 20 years compared to < 10 years was associated with greater LV mass index (81.6 +/- 0.7 g/m(2) vs 79.5 +/- 1.1 g/m(2), p = 0.02). Compared to those with the lowest acculturation score, those with the highest score had greater LV mass index (78.9 +/- 1.1 g/m(2) vs 81.1 +/- 0.4 g/m(2), p = 0.002). There was heterogeneity in which measure of acculturation was associated with LV mass index across ethnic groups.
Conclusions: Greater acculturation is associated with increased LV mass index in this multiethnic cohort. Acculturation may involve stress-related processes as well as behavioral changes with a negative effect on cardiovascular health.
C1 [Effoe, Valery S.; Chen, Haiying; Bertoni, Alain G.; Rodriguez, Carlos J.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27127 USA.
[Moran, Andrew] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Seeman, Teresa] Univ Calif Los Angeles, Div Geriatr, Los Angeles, CA USA.
[Darwin, Christine] Univ Calif Los Angeles, Res Ctr, Los Angeles, CA USA.
[Watson, Karol E.] Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90024 USA.
RP Rodriguez, CJ (reprint author), Wake Forest Sch Med, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27127 USA.
EM crodrigu@wakehealth.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR
[UL1-TR-000040, UL1-TR-001079]; NHLBI [R01 HL104199]
FX The authors thank the other investigators, the staff, and the
participants of the MESA study for their valuable contributions. A full
list of participating MESA investigators and institutions can be found
at http://www.mesa-nhlbi.org. 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-95166, N01-HC-95167, N01-HC-95168 and
N01-HC-95169 from the National Heart, Lung, and Blood Institute and by
grants UL1-TR-000040 and UL1-TR-001079 from NCRR. The research was also
partially supported by NHLBI grant R01 HL104199 (Epidemiologic
Determinants of Cardiac Structure and Function among Hispanics).
NR 33
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U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD DEC 3
PY 2015
VL 15
AR 161
DI 10.1186/s12872-015-0157-3
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CX6WM
UT WOS:000365842400002
PM 26631068
ER
PT J
AU Jin, WF
Tang, QS
Wan, MM
Cui, KR
Zhang, Y
Ren, G
Ni, B
Sklar, J
Przytycka, TM
Childs, R
Levens, D
Zhao, KJ
AF Jin, Wenfei
Tang, Qingsong
Wan, Mimi
Cui, Kairong
Zhang, Yi
Ren, Gang
Ni, Bing
Sklar, Jeffrey
Przytycka, Teresa M.
Childs, Richard
Levens, David
Zhao, Keji
TI Genome-wide detection of DNase I hypersensitive sites in single cells
and FFPE tissue samples
SO NATURE
LA English
DT Article
ID CHROMATIN ACCESSIBILITY; SUPER-ENHANCERS; EXPRESSION; GENE; SEQ;
PATTERNS; IDENTITY; DISTINCT; REVEALS; DIFFERENTIATION
AB DNase I hypersensitive sites (DHSs) provide important information on the presence of transcriptional regulatory elements and the state of chromatin in mammalian cells(1-3). Conventional DNase sequencing (DNase-seq) for genome-wide DHSs profiling is limited by the requirement of millions of cells(4,5). Here we report an ultrasensitive strategy, called single-cell DNase sequencing (scDNase-seq) for detection of genome-wide DHSs in single cells. We show that DHS patterns at the single-cell level are highly reproducible among individual cells. Among different single cells, highly expressed gene promoters and enhancers associated with multiple active histone modifications display constitutive DHS whereas chromatin regions with fewer histone modifications exhibit high variation of DHS. Furthermore, the single-cell DHSs predict enhancers that regulate cell-specific gene expression programs and the cell-to-cell variations of DHS are predictive of gene expression. Finally, we apply scDNase-seq to pools of tumour cells and pools of normal cells, dissected from formalin-fixed paraffin-embedded tissue slides from patients with thyroid cancer, and detect thousands of tumour-specific DHSs. Many of these DHSs are associated with promoters and enhancers critically involved in cancer development. Analysis of the DHS sequences uncovers one mutation (chr18: 52417839G> C) in the tumour cells of a patient with follicular thyroid carcinoma, which affects the binding of the tumour suppressor protein p53 and correlates with decreased expression of its target gene TXNL1. In conclusion, scDNase-seq can reliably detect DHSs in single cells, greatly extending the range of applications of DHS analysis both for basic and for translational research, and may provide critical information for personalized medicine.
C1 [Jin, Wenfei; Tang, Qingsong; Cui, Kairong; Zhang, Yi; Ren, Gang; Zhao, Keji] NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Wan, Mimi; Sklar, Jeffrey] Yale Univ, Dept Pathol, Sch Med, New Haven, CT 06520 USA.
[Zhang, Yi; Ni, Bing] Peoples Liberat Army, Mil Med Univ 3, Inst Immunol, Chongqing 400038, Peoples R China.
[Ren, Gang] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China.
[Przytycka, Teresa M.] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA.
[Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Levens, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
RI Levens, David/C-9216-2009
OI Levens, David/0000-0002-7616-922X
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute; Intramural Research Program of National Library of Medicine;
Center for Cancer Research of the National Cancer Institute of the
National Institutes of Health
FX We thank J. Cooper and B. Z. Stanton for reading the manuscript, the
National Heart, Lung, and Blood Institute DNA Sequencing Core Facility
for sequencing the libraries and the National Heart, Lung, and Blood
Institute Flow Cytometry Core facility for sorting the cells. The work
was supported by Division of Intramural Research, National Heart, Lung,
and Blood Institute (to K.Z.), Intramural Research Program of National
Library of Medicine (to T.M.P.) and the Center for Cancer Research of
the National Cancer Institute (to D.L.) of the National Institutes of
Health.
NR 39
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U1 5
U2 26
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 DEC 3
PY 2015
VL 528
IS 7580
BP 142
EP +
DI 10.1038/nature15740
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CX3NO
UT WOS:000365606000065
PM 26605532
ER
PT J
AU Fauci, AS
Marston, HD
AF Fauci, Anthony S.
Marston, Hilary D.
TI Ending the HIV-AIDS Pandemic - Follow the Science
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID ANTIRETROVIRAL THERAPY; INFECTION
C1 [Fauci, Anthony S.; Marston, Hilary D.] NIAID, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 4
TC 11
Z9 12
U1 1
U2 6
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 DEC 3
PY 2015
VL 373
IS 23
BP 2197
EP 2199
DI 10.1056/NEJMp1502020
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX5LM
UT WOS:000365743100002
PM 26624554
ER
PT J
AU Nichol, G
Leroux, B
Wang, H
Callaway, CW
Sopko, G
Weisfeldt, M
Stiell, I
Morrison, LJ
Aufderheide, TP
Cheskes, S
Christenson, J
Kudenchuk, P
Vaillancourt, C
Rea, TD
Idris, AH
Colella, R
Isaacs, M
Straight, R
Stephens, S
Richardson, J
Condle, J
Schmicker, RH
Egan, D
May, S
Ornato, JP
AF Nichol, Graham
Leroux, Brian
Wang, Henry
Callaway, Clifton W.
Sopko, George
Weisfeldt, Myron
Stiell, Ian
Morrison, Laurie J.
Aufderheide, Tom P.
Cheskes, Sheldon
Christenson, Jim
Kudenchuk, Peter
Vaillancourt, Christian
Rea, Thomas D.
Idris, Ahamed H.
Colella, Riccardo
Isaacs, Marshal
Straight, Ron
Stephens, Shannon
Richardson, Joe
Condle, Joe
Schmicker, Robert H.
Egan, Debra
May, Susanne
Ornato, Joseph P.
CA ROC Investigators
TI Trial of Continuous or Interrupted Chest Compressions during CPR
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HOSPITAL CARDIAC-ARREST; EMERGENCY CARDIOVASCULAR CARE;
HEART-ASSOCIATION GUIDELINES; CARDIOPULMONARY-RESUSCITATION;
VENTRICULAR-FIBRILLATION; LAY RESCUERS; SURVIVAL; OUTCOMES;
CATHETERIZATION; RATIONALE
AB BACKGROUND
During cardiopulmonary resuscitation (CPR) in patients with out-of-hospital cardiac arrest, the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival. We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations.
METHODS
This cluster-randomized trial with crossover included 114 emergency medical service (EMS) agencies. Adults with non-trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions (intervention group) or interrupted chest compressions (control group). The primary outcome was the rate of survival to hospital discharge. Secondary outcomes included the modified Rankin scale score (on a scale from 0 to 6, with a score of <= 3 indicating favorable neurologic function). CPR process was measured to assess compliance.
RESULTS
Of 23,711 patients included in the primary analysis, 12,653 were assigned to the intervention group and 11,058 to the control group. A total of 1129 of 12,613 patients with available data (9.0%) in the intervention group and 1072 of 11,035 with available data (9.7%) in the control group survived until discharge (difference, -0.7 percentage points; 95% confidence interval [CI], -1.5 to 0.1; P = 0.07); 7.0% of the patients in the intervention group and 7.7% of those in the control group survived with favorable neurologic function at discharge (difference, -0.6 percentage points; 95% CI, -1.4 to 0.1, P = 0.09). Hospital-free survival was significantly shorter in the intervention group than in the control group (mean difference, -0.2 days; 95% CI, -0.3 to -0.1; P = 0.004).
CONCLUSIONS
In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions. (Funded by the National Heart, Lung, and Blood Institute and others; ROC CCC ClinicalTrials.gov number, NCT01372748.)
C1 [Nichol, Graham] Univ Washington, Harborview Ctr Prehospital Emergency Care, Seattle, WA 98195 USA.
[Nichol, Graham; Leroux, Brian; Schmicker, Robert H.; May, Susanne] Clin Trial Ctr, Seattle, WA USA.
[Kudenchuk, Peter; Rea, Thomas D.] Univ Washington, Seattle King Cty Ctr Resuscitat Res, Seattle, WA 98195 USA.
[Wang, Henry; Stephens, Shannon] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Richardson, Joe] Birmingham Fire & Rescue Serv, Birmingham, AL USA.
[Callaway, Clifton W.; Condle, Joe] Univ Pittsburgh, Pittsburgh Resuscitat Network, Pittsburgh, PA USA.
[Sopko, George; Egan, Debra] NHLBI, Bethesda, MD 20892 USA.
[Weisfeldt, Myron] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Stiell, Ian; Vaillancourt, Christian] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa Ontario Prehosp Adv Life Support Resuscita, Ottawa, ON, Canada.
[Morrison, Laurie J.; Cheskes, Sheldon] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
[Christenson, Jim; Straight, Ron] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Aufderheide, Tom P.; Colella, Riccardo] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA.
[Idris, Ahamed H.; Isaacs, Marshal] Univ Texas SW Med Ctr Dallas, Dallas Ft Worth Ctr Resuscitat Res, Dallas, TX 75390 USA.
[Ornato, Joseph P.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA.
RP Nichol, G (reprint author), Box 359727,325 Ninth Ave, Seattle, WA 98104 USA.
EM nichol@uw.edu
RI morrison, laurie/A-6325-2012;
OI morrison, laurie/0000-0001-8369-9774; Welsford,
Michelle/0000-0003-2682-641X; Ferguson, Niall/0000-0002-6213-5264;
Guffey, Danielle/0000-0003-3721-614X
FU National Heart, Lung, and Blood Institute
FX Funded by the National Heart, Lung, and Blood Institute and others
NR 32
TC 24
Z9 26
U1 1
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 DEC 3
PY 2015
VL 373
IS 23
BP 2203
EP 2214
DI 10.1056/NEJMoa1509139
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX5LM
UT WOS:000365743100004
PM 26550795
ER
PT J
AU Nelson, KB
Blair, E
AF Nelson, Karin B.
Blair, Eve
TI Prenatal Factors in Cerebral Palsy Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA.
[Blair, Eve] Telethon Kids Inst, Subiaco, WA, Australia.
RP Nelson, KB (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM nelsonk@ninds.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 2
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 DEC 3
PY 2015
VL 373
IS 23
BP 2288
EP 2289
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX5LM
UT WOS:000365743100017
PM 26630148
ER
PT J
AU Ito, T
Nishio, A
Wangemann, P
Griffith, AJ
AF Ito, T.
Nishio, A.
Wangemann, P.
Griffith, A. J.
TI PROGRESSIVE IRREVERSIBLE HEARING LOSS IS CAUSED BY STRIA VASCULARIS
DEGENERATION IN AN Slc26a4-INSUFFICIENT MOUSE MODEL OF LARGE VESTIBULAR
AQUEDUCT SYNDROME
SO NEUROSCIENCE
LA English
DT Article
DE deafness; doxycycline; fluctuation; hypomorphic; SLC26A4; stria
vascularis
ID KCNJ10 PROTEIN EXPRESSION; PENDRED-SYNDROME; INNER-EAR; CAUSES DEAFNESS;
MARGINAL CELLS; INHIBITION; CONTRIBUTES; ENLARGEMENT; MECHANISMS;
MUTATIONS
AB Hearing loss of patients with enlargement of the vestibular aqueduct (EVA) can fluctuate or progress, with overall downward progression. The most common detectable cause of EVA is mutations of SLC26A4. We previously described a transgenic Slc26a4-insufficient mouse model of EVA in which Slc26a4 expression is controlled by doxycycline administration. Mice that received doxycycline from conception until embryonic day 17.5 (DE17.5; doxycycline discontinued at embryonic day 17.5) had fluctuating hearing loss between 1 and 6 months of age with an overall downward progression after 6 months of age. In this study, we characterized the cochlear functional and structural changes underlying irreversible hearing loss in DE17.5 mice at 12 months of age. The endocochlear potential was decreased and inversely correlated with auditory brainstem response thresholds. The stria vascularis was thickened and edematous in ears with less severe hearing loss, and thinned and atrophic in ears with more severe hearing loss. There were pathologic changes in marginal cell morphology and gene expression that were not observed at 3 months. We conclude that strial dysfunction and degeneration are the primary causes of irreversible progressive hearing loss in our Slc26a4-insufficient mouse model of EVA. This model of primary strial atrophy may be used to explore the mechanisms of progressive hearing loss due to strial dysfunction. Published by Elsevier Ltd. on behalf of IBRO.
C1 [Ito, T.; Nishio, A.; Griffith, A. J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD 20892 USA.
[Wangemann, P.] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, 35A Convent Dr,Room GF 103, Bethesda, MD 20892 USA.
EM griffita@nidcd.nih.gov
FU NIH [Z01-DC000060, Z01-DC000080, R01-DC012151]; JSPS Research Fellowship
for Japanese Biomedical and Behavioral Researchers at NIH
FX This work was supported by NIH intramural research funds Z01-DC000060
and Z01-DC000080. A.N. was supported in part by a JSPS Research
Fellowship for Japanese Biomedical and Behavioral Researchers at NIH.
P.W. was supported by NIH grant R01-DC012151. We thank Tracy Fitzgerald
and our NIDCD colleagues for helpful suggestions and advice, Ken
Kitamura for support, and Inna Belyantseva, Tom Friedman and Mike Hoa
for critical reading of the manuscript.
NR 33
TC 3
Z9 3
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD DEC 3
PY 2015
VL 310
BP 188
EP 197
DI 10.1016/j.neuroscience.2015.09.016
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CV3HM
UT WOS:000364149800015
PM 26363152
ER
PT J
AU Gaughan, AE
Stevens, FR
Linard, C
Patel, NN
Tatem, AJ
AF Gaughan, A. E.
Stevens, F. R.
Linard, C.
Patel, N. N.
Tatem, A. J.
TI Exploring nationally and regionally defined models for large area
population mapping
SO INTERNATIONAL JOURNAL OF DIGITAL EARTH
LA English
DT Article
DE human population modeling; random forest regression; dasymetric mapping;
gridded population datasets
ID CLIMATE-CHANGE; RANDOM FORESTS; RISK; MAPS; AFRICA; CENSUS; SURFACES;
MALARIA; DISEASE; IMPACT
AB Interactions between humans, diseases, and the environment take place across a range of temporal and spatial scales, making accurate, contemporary data on human population distributions critical for a variety of disciplines. Methods for disaggregating census data to finer-scale, gridded population density estimates continue to be refined as computational power increases and more detailed census, input, and validation datasets become available. However, the availability of spatially detailed census data still varies widely by country. In this study, we develop quantitative guidelines for choosing regionally-parameterized census count disaggregation models over country-specific models. We examine underlying methodological considerations for improving gridded population datasets for countries with coarser scale census data by investigating regional versus country-specific models used to estimate density surfaces for redistributing census counts. Consideration is given to the spatial resolution of input census data using examples from East Africa and Southeast Asia. Results suggest that for many countries more accurate population maps can be produced by using regionally-parameterized models where more spatially refined data exists than that which is available for the focal country. This study highlights the advancement of statistical toolsets and considerations for underlying data used in generating widely used gridded population data.
C1 [Gaughan, A. E.; Stevens, F. R.] Univ Louisville, Dept Geog & Geosci, Louisville, KY 40292 USA.
[Linard, C.] Univ Libre Bruxelles, Biol Control & Spatial Ecol, Brussels, Belgium.
[Patel, N. N.] George Mason Univ, Dept Geog & Geoinformat Sci, Fairfax, VA 22030 USA.
[Tatem, A. J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, A. J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Tatem, A. J.] Flowminder Fdn, Stockholm, Sweden.
RP Gaughan, AE (reprint author), Univ Louisville, Dept Geog & Geosci, Louisville, KY 40292 USA.
EM ae.gaughan@louisville.edu
OI Stevens, Forrest/0000-0002-9328-3753
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; NIH/NIAID [U19AI089674]; Bill and Melinda Gates Foundation
[OPP1106427, 1032350]; Fonds National de la Recherche Scientifique
(F.R.S./FNRS), Brussels, Belgium
FX This work was supported by the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health; NIH/NIAID [grant
number U19AI089674]; and the Bill and Melinda Gates Foundation [grant
number OPP1106427], [grant number 1032350]. CL is supported by the Fonds
National de la Recherche Scientifique (F.R.S./FNRS), Brussels, Belgium.
This work forms part of the outputs of the WorldPop Project
(www.worldpop.org.uk) and Flowminder Foundation (www.flowminder.org).
NR 55
TC 1
Z9 1
U1 3
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1753-8947
EI 1753-8955
J9 INT J DIGIT EARTH
JI Int. J. Digit. Earth
PD DEC 2
PY 2015
VL 8
IS 12
BP 989
EP 1006
DI 10.1080/17538947.2014.965761
PG 18
WC Geography, Physical; Remote Sensing
SC Physical Geography; Remote Sensing
GA DB5JW
UT WOS:000368551400003
ER
PT J
AU Konova, AB
Moeller, SJ
Tomasi, D
Goldstein, RZ
AF Konova, Anna B.
Moeller, Scott J.
Tomasi, Dardo
Goldstein, Rita Z.
TI Effects of chronic and acute stimulants on brain functional connectivity
hubs
SO BRAIN RESEARCH
LA English
DT Article
DE Cocaine; Addiction; Dopamine; Methylphenidate; Brain hubs; Resting-state
connectivity; Functional magnetic resonance; imaging
ID SPONTANEOUS FLUCTUATIONS; COCAINE ADDICTION; DEFAULT NETWORK;
METHYLPHENIDATE; DOPAMINE; CORTEX; DEPENDENCE; DISORDERS; SEVERITY;
CIRCUITS
AB The spatial distribution and strength of information processing 'hubs' are essential features of the brain's network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20 mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention.
This article is part of a Special Issue entitled SI:Addiction circuits. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Konova, Anna B.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Moeller, Scott J.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Moeller, Scott J.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
[Tomasi, Dardo] NIAAA, Bethesda, MD 20892 USA.
RP Goldstein, RZ (reprint author), Icahn Sch Med Mt Sinai, Leon & Norma Hess Ctr Sci & Med, Dept Psychiat, 1470 Madison Ave, New York, NY 10029 USA.
EM rita.goldstein@mssm.edu
RI Moeller, Scott/L-5549-2016
OI Moeller, Scott/0000-0002-4449-0844
FU National Institute on Drug Abuse [1R01DA023579, 1F32DA030017-01];
National Institute of Mental Health [T32MH019524]
FX This research was conducted with grant support from the National
Institute on Drug Abuse (1R01DA023579 to R.Z.G. and 1F32DA030017-01 to
S.J.M) and the National Institute of Mental Health (T32MH019524 training
award in Systems and Integrative Neuroscience to A.B.K.).
NR 50
TC 6
Z9 6
U1 3
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2015
VL 1628
SI SI
BP 147
EP 156
DI 10.1016/j.brainres.2015.02.002
PN A
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CZ9IV
UT WOS:000367412200014
PM 25721787
ER
PT J
AU Cruz, FC
Rubio, FJ
Hope, BT
AF Cruz, Fabio C.
Rubio, F. Javier
Hope, Bruce T.
TI Using c-fos to study neuronal ensembles in corticostriatal circuitry of
addiction
SO BRAIN RESEARCH
LA English
DT Article
DE Conditioned cues; Daun02 inactivation; Drug environment;
Self-administration; Extinction; Prefrontal cortex; Nucleus accumbens
ID NUCLEUS-ACCUMBENS NEURONS; FREELY MOVING RATS; COCAINE-SEEKING BEHAVIOR;
EARLY GENE-EXPRESSION; SIGNAL-REGULATED KINASE; SELF-ADMINISTRATION
SESSIONS; MESSENGER-RNA EXPRESSION; MEDIUM SPINY NEURONS; INDUCIBLE
TRANSCRIPTION FACTORS; INDUCED LOCOMOTOR SENSITIZATION
AB Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. Here we review how Fos and the c-fos promoter have been employed to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. This work has allowed identification of unique molecular and electrophysiological alterations within Fos-expressing neuronal ensembles that may contribute to the development and expression of learned associations in addiction.
This article is part of a Special Issue entitled SI:Addiction circuits. Published by Elsevier B.V.
C1 [Cruz, Fabio C.; Rubio, F. Javier; Hope, Bruce T.] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
FU National Institute on Drug Abuse, Intramural Research Program, NIH
[DA000467-11]
FX This research was supported by the National Institute on Drug Abuse,
Intramural Research Program, NIH (Grant no. DA000467-11).
NR 251
TC 10
Z9 10
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2015
VL 1628
SI SI
BP 157
EP 173
DI 10.1016/j.brainres.2014.11.005
PN A
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA CZ9IV
UT WOS:000367412200015
PM 25446457
ER
PT J
AU Kravitz, AV
Tomasi, D
LeBlanc, KH
Baler, R
Volkow, ND
Bonci, A
Ferre, S
AF Kravitz, Alexxai V.
Tomasi, Dardo
LeBlanc, Kimberly H.
Baler, Ruben
Volkow, Nora D.
Bonci, Antonello
Ferre, Sergi
TI Cortico-striatal circuits: Novel therapeutic targets for substance use
disorders
SO BRAIN RESEARCH
LA English
DT Review
DE Frontal cortex; Cortico-striatal; fMRI; TMS; DBS; Substance use disorder
ID DEEP BRAIN-STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; ADENOSINE
A(2A) RECEPTORS; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL;
REDUCES ETHANOL-CONSUMPTION; DOPAMINE D2 RECEPTORS; DRUG-ADDICTION;
COCAINE-SEEKING; INDUCED REINSTATEMENT
AB It is widely believed that substance use disorder (SUD) results from both pre-alterations (vulnerability) and/or post-alterations (drug effects) on cortico-striatal circuits. These circuits are essential for cognitive control, motivation, reward dependent learning, and emotional processing. As such, dysfunctions in cortico-striatal circuits are thought to relate to the core features of SUD, which include compulsive drug use, loss of the ability to control drug intake, and the emergence of negative emotional states (Koob and Volkow, 2010. Neuropsychopharmacology 35(1), 217-238). While the brain circuits underlying SUD have been studied in human patients largely through imaging studies, experiments in animals have allowed researchers to examine the specific cell-types within these circuits to reveal their role in behavior relevant to SUD. Here, we will review imaging studies on cortico-striatal systems that are altered in SUD, and describe animal experiments that relate SUD to specific neural projections and cell types within this circuitry. We will end with a discussion of novel clinical approaches such as deep brain stimulation (DBS), repeated transcranial magnetic stimulation (rTMS), and pharmacological targeting of G protein-coupled receptor (GPCR) heteromers that may provide promising avenues for modulating these circuits to combat SUD in humans.
This article is part of a Special Issue entitled SI:Addiction circuits. (C) 2015 Published by Elsevier B.V.
C1 [Kravitz, Alexxai V.; LeBlanc, Kimberly H.] NIDDKD, Bethesda, MD USA.
[Kravitz, Alexxai V.; Baler, Ruben; Volkow, Nora D.; Bonci, Antonello; Ferre, Sergi] NIDA, Baltimore, MD 21224 USA.
[Tomasi, Dardo] NIAAA, Bethesda, MD USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
[Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
RP Bonci, A (reprint author), NIDA, Baltimore, MD 21224 USA.
EM antonello.bonci@nih.gov
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
NR 147
TC 14
Z9 14
U1 5
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2015
VL 1628
SI SI
BP 186
EP 198
DI 10.1016/j.brainres.2015.03.048
PN A
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CZ9IV
UT WOS:000367412200017
PM 25863130
ER
PT J
AU Marchant, NJ
Kaganovsky, K
Shaham, Y
Bossert, JM
AF Marchant, Nathan J.
Kaganovsky, Konstantin
Shaham, Yavin
Bossert, Jennifer M.
TI Role of corticostriatal circuits in context-induced reinstatement of
drug seeking
SO BRAIN RESEARCH
LA English
DT Review
DE Abstinence; Alcohol; Cocaine; Context; Craving; Cue; Extinction; Drug
self-administration; Heroin; Punishment; Reinstatement; Relapse; Review
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS SHELL; CUE-INDUCED
REINSTATEMENT; MEDIAL PREFRONTAL CORTEX;
PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; METABOTROPIC GLUTAMATE RECEPTORS;
SELF-ADMINISTERED COCAINE; DOPAMINE D-1-FAMILY RECEPTORS; EXTINGUISHED
ALCOHOL-SEEKING; HEROIN-SEEKING
AB Drug addiction is characterized by persistent relapse vulnerability during abstinence. In abstinent drug users, relapse is often precipitated by re-exposure to environmental contexts that were previously associated with drug use. This clinical scenario is modeled in preclinical studies using the context-induced reinstatement procedure, which is based on the ABA renewal procedure. In these studies, context-induced reinstatement of drug seeking is reliably observed in laboratory animals that were trained to self-administer drugs abused by humans. In this review, we summarize neurobiological findings from preclinical studies that have focused on the role of corticostriatal circuits in context-induced reinstatement of heroin, cocaine, and alcohol seeking. We also discuss neurobiological similarities and differences in the corticostriatal mechanisms of context-induced reinstatement across these drug classes. We conclude by briefly discussing future directions in the study of context-induced relapse to drug seeking in rat models. Our main conclusion from the studies reviewed is that there are both similarities (accumbens shell, ventral hippocampus, and basolateral amygdala) and differences (medial prefrontal cortex and its projections to accumbens) in the neural mechanisms of context-induced reinstatement of cocaine, heroin, and alcohol seeking.
This article is part of a Special Issue entitled SI:Addiction circuits. Published by Elsevier B.V.
C1 [Marchant, Nathan J.; Kaganovsky, Konstantin; Shaham, Yavin; Bossert, Jennifer M.] NIDA, Behav Neurosci Branch, IRP, Baltimore, MD 21224 USA.
[Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
RP Marchant, NJ (reprint author), NIDA, Behav Neurosci Branch, IRP, Baltimore, MD 21224 USA.
EM nathan.marchant@nih.gov; jennifer.bossert@nih.gov
OI Kaganovsky, Konstantin/0000-0002-1577-109X
FU National Institute on Drug Abuse, Intramural Research Program; National
Health and Medical Research Council [1053308]
FX Research was supported by the National Institute on Drug Abuse,
Intramural Research Program. N.J.M. received support from Early Career
Fellowship 1053308 by the National Health and Medical Research Council.
The authors declare that they do not have any conflicts of interest
(financial or otherwise) related to the data presented in this
manuscript.
NR 139
TC 13
Z9 13
U1 3
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2015
VL 1628
SI SI
BP 219
EP 232
DI 10.1016/j.brainres.2014.09.004
PN A
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CZ9IV
UT WOS:000367412200020
PM 25199590
ER
PT J
AU Qosa, H
Miller, DS
Pasinelli, P
Trotti, D
AF Qosa, Hisham
Miller, David S.
Pasinelli, Piera
Trotti, Davide
TI Regulation of ABC efflux transporters at blood-brain barrier in health
and neurological disorders
SO BRAIN RESEARCH
LA English
DT Review
DE ABC efflux transporters; Blood-brain barrier; Neuroprotection;
Pharmacoresistance
ID P-GLYCOPROTEIN EXPRESSION; CANCER RESISTANCE PROTEIN; BINDING CASSETTE
TRANSPORTERS; MEDIATED UP-REGULATION; TUMOR-NECROSIS-FACTOR; MEDICALLY
INTRACTABLE EPILEPSY; MICROVESSEL ENDOTHELIAL-CELLS; DIESEL EXHAUST
PARTICLES; FOCAL CORTICAL DYSPLASIA; CULTURED RAT ASTROCYTES
AB The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govem expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases. This article is part of a Special Issue entitled SI: Neuroprotection. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Qosa, Hisham; Pasinelli, Piera; Trotti, Davide] Thomas Jefferson Univ, Dept Neurosci, Farber Inst Neurosci, Weinberg Unit ALS Res, Philadelphia, PA 19107 USA.
[Miller, David S.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Qosa, H (reprint author), Thomas Jefferson Univ, Dept Neurosci, Farber Inst Neurosci, Weinberg Unit ALS Res, 900 Walnut St, Philadelphia, PA 19107 USA.
EM hisham.qosa@jefferson.edu; davide.trotti@jefferson.edu
FU National Institute of Health [RO1-NS074886]; Target ALS; NIH/NIEHS;
Farber Family Foundation
FX This work was supported by the National Institute of Health grant
RO1-NS074886 (to DT), and by a program grant from Target ALS (to DT, PP
and DSM) and the Intramural Research program NIH/NIEHS. The Weinberg
Unit for ALS research is also supported by the Farber Family Foundation.
NR 212
TC 16
Z9 16
U1 10
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD DEC 2
PY 2015
VL 1628
SI SI
BP 298
EP 316
DI 10.1016/j.brainres.2015.07.005
PG 19
WC Neurosciences
SC Neurosciences & Neurology
GA CZ9IW
UT WOS:000367412300007
PM 26187753
ER
PT J
AU Yakunina, M
Artamonova, T
Borukhov, S
Makarova, KS
Severinov, K
Minakhin, L
AF Yakunina, Maria
Artamonova, Tatyana
Borukhov, Sergei
Makarova, Kira S.
Severinov, Konstantin
Minakhin, Leonid
TI A non-canonical multisubunit RNA polymerase encoded by a giant
bacteriophage
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ESCHERICHIA-COLI; MASS-SPECTROMETRY; SIGMA SUBUNITS; ACTIVE-CENTER;
PHI-KZ; PURIFICATION; PSEUDOMONAS; GENOME; CONSERVATION; INHIBITION
AB The infection of Pseudomonas aeruginosa by the giant bacteriophage phiKZ is resistant to host RNA polymerase (RNAP) inhibitor rifampicin. phiKZ encodes two sets of polypeptides that are distantly related to fragments of the two largest subunits of cellular multisubunit RNAPs. Polypeptides of one set are encoded by middle phage genes and are found in the phiKZ virions. Polypeptides of the second set are encoded by early phage genes and are absent from virions. Here, we report isolation of a five-subunit RNAP from phiKZ-infected cells. Four subunits of this enzyme are cellular RNAP subunits homologs of the non-virion set; the fifth subunit is a protein of unknown function. In vitro, this complex initiates transcription from late phiKZ promoters in rifampicin-resistant manner. Thus, this enzyme is a non-virion phiKZ RNAP responsible for transcription of late phage genes. The phiKZ RNAP lacks identifiable assembly and promoter specificity subunits/factors characteristic for eukaryal, archaeal and bacterial RNAPs and thus provides a unique model for comparative analysis of the mechanism, regulation and evolution of this important class of enzymes.
C1 [Yakunina, Maria; Artamonova, Tatyana; Borukhov, Sergei; Severinov, Konstantin; Minakhin, Leonid] Peter Great St Petersburg Polytech Univ, St Petersburg 195251, Russia.
[Yakunina, Maria; Severinov, Konstantin; Minakhin, Leonid] Rutgers State Univ, Waksman Inst, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
[Borukhov, Sergei] Rowan Univ, Sch Osteopath Med, Stratford, NJ 08084 USA.
[Makarova, Kira S.] NIH, Natl Biotechnol Ctr, NLM, Bethesda, MD 20894 USA.
[Severinov, Konstantin] Skolkovo Inst Sci & Technol, Skolkovo 143026, Russia.
RP Severinov, K (reprint author), Peter Great St Petersburg Polytech Univ, St Petersburg 195251, Russia.
EM severik@waksman.rutgers.edu; minakhin@waksman.rutgers.edu
RI Severinov, Konstantin/C-8545-2016; Yakunina, Maria
Vyacheslavovna/A-5842-2014
FU Ministry of Education and Science of the Russian Federation
[14.B25.31.0004]; National Institutes of Health (NIH) [GM59295]
FX Ministry of Education and Science of the Russian Federation
[14.B25.31.0004 to K.S.]; National Institutes of Health (NIH) [GM59295
to K.S.]. Funding for open access charge: Ministry of Education and
Science of the Russian Federation [14.B25.31.0004 to K.S.].
NR 38
TC 3
Z9 3
U1 2
U2 6
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 DEC 2
PY 2015
VL 43
IS 21
BP 10411
EP 10420
DI 10.1093/nar/gkv1095
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CY4WZ
UT WOS:000366410900037
PM 26490960
ER
PT J
AU Wang, HL
Qi, J
Zhang, SL
Wang, HK
Morales, M
AF Wang, Hui-Ling
Qi, Jia
Zhang, Shiliang
Wang, Huikun
Morales, Marisela
TI Rewarding Effects of Optical Stimulation of Ventral Tegmental Area
Glutamatergic Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE addiction; aversion; dopamine; reward; VGluT2; VTA
ID DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; LATERAL HABENULA; GABA NEURONS;
PROJECTIONS; MIDBRAIN; AVERSION; AXONS
AB Ventral tegmental area (VTA) neurons play roles in reward and aversion. The VTA has three major neuronal phenotypes: dopaminergic, GABAergic, and glutamatergic. VTA glutamatergic neurons-expressing vesicular glutamate transporter-2 (VGluT2)-project to limbic and cortical regions, but also excite neighboring dopaminergic neurons. Here, we test whether local photoactivation of VTA VGluT2 neurons expressing Channelrhodopsin-2 (ChR2) under the VGluT2 promoter causes place preference and supports operant responding for the stimulation. By using a Cre-dependent viral vector, ChR2 (tethered to mCherry) was expressed in VTA glutamatergic neurons of VGluT2::Cre mice. The mCherry distribution was evaluated by immunolabeling. By confocal microscopy, we detected expression of mCherry in VTA cell bodies and local processes. In contrast, VGluT2 expression was restricted to varicosities, some of them coexpressing mCherry. By electron microscopy, we determined that mCherry-VGluT2 varicosities correspond to axon terminals, forming asymmetric synapses on neighboring dopaminergic neurons. These findings indicate that ChR2 was present in terminals containing glutamatergic synaptic vesicles and involved in local synaptic connections. Photoactivation of VTA slices from ChR2-expressing mice induced AMPA/NMDA receptor-dependent firing of dopaminergic neurons projecting to the nucleus accumbens. VTA photoactivation of ChR2-expressing mice reinforced instrumental behavior and established place preferences. VTA injections of AMPA or NMDA receptor antagonists blocked optical self-stimulation and place preference. These findings suggest a role in reward function for VTA glutamatergic neurons through local excitatory synapses on mesoaccumbens dopaminergic neurons.
C1 [Wang, Hui-Ling; Qi, Jia; Zhang, Shiliang; Wang, Huikun; Morales, Marisela] NIDA, Neuronal Networks Sect, NIH, Baltimore, MD 21224 USA.
RP Morales, M (reprint author), NIDA, Intramural Res Program, Neuronal Networks Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mmorales@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
FX The Intramural Research Program of the National Institute on Drug Abuse
supported this research.
NR 26
TC 7
Z9 7
U1 1
U2 10
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 DEC 2
PY 2015
VL 35
IS 48
BP 15948
EP 15954
DI 10.1523/JNEUROSCI.3428-15.2015
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA CX9WD
UT WOS:000366055500016
PM 26631475
ER
PT J
AU Nguyen, C
Lu, MJ
Fan, ZY
Bi, XM
Kellman, P
Zhao, SH
Li, DB
AF Nguyen, Christopher
Lu, Minjie
Fan, Zhaoyang
Bi, Xiaoming
Kellman, Peter
Zhao, Shihua
Li, Debiao
TI Contrast-free detection of myocardial fibrosis in hypertrophic
cardiomyopathy patients with diffusion-weighted cardiovascular magnetic
resonance
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Hypertrophic cardiomyopathy; HCM; Diffusion-weighting; Cardiovascular
magnetic resonance; Extracellular volume mapping; ECV
ID LATE GADOLINIUM-ENHANCEMENT; PROGNOSTIC-SIGNIFICANCE; QUANTIFICATION;
INFARCTION; DISEASE; HEART
AB Backgrounds: Previous studies have shown that diffusion-weighted cardiovascular magnetic resonance (DW-CMR) is highly sensitive to replacement fibrosis of chronic myocardial infarction. Despite this sensitivity to myocardial infarction, DW-CMR has not been established as a method to detect diffuse myocardial fibrosis. We propose the application of a recently developed DW-CMR technique to detect diffuse myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients and compare its performance with established CMR techniques.
Methods: HCM patients (N = 23) were recruited and scanned with the following protocol: standard morphological localizers, DW-CMR, extracellular volume (ECV) CMR, and late gadolinium enhanced (LGE) imaging for reference. Apparent diffusion coefficient (ADC) and ECV maps were segmented into 6 American Heart Association (AHA) segments. Positive regions for myocardial fibrosis were defined as: ADC > 2.0 mu m(2)/ms and ECV > 30 %. Fibrotic and non-fibrotic mean ADC and ECV values were compared as well as ADC-derived and ECV-derived fibrosis burden. In addition, fibrosis regional detection was compared between ADC and ECV calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) using ECV as the gold-standard reference.
Results: ADC (2.4 +/- 0.2 mu m(2)/ms) of fibrotic regions (ADC > 2.0 mu m(2)/ms) was significantly (p < 0.01) higher than ADC (1.5 +/- 0.2 mu m(2)/ms) of non-fibrotic regions. Similarly, ECV (35 +/- 4 %) of fibrotic regions (ECV > 30 %) was significantly (p < 0.01) higher than ECV (26 +/- 2 %) of non-fibrotic regions. In fibrotic regions defined by ECV, ADC (2.2 +/- 0.3 mu m(2)/ms) was again significantly (p < 0.05) higher than ADC (1.6 +/- 0.3 mu m(2)/ms) of non-fibrotic regions. In fibrotic regions defined by ADC criterion, ECV (34 +/- 5 %) was significantly (p < 0.01) higher than ECV (28 +/- 3 %) in non-fibrotic regions. ADC-derived and ECV-derived fibrosis burdens were in substantial agreement (intra-class correlation = 0.83). Regional detection between ADC and ECV of diffuse fibrosis yielded substantial agreement (kappa = 0.66) with high sensitivity, specificity, PPV, NPV, and accuracy (0.80, 0.85, 0.81, 0.85, and 0.83, respectively).
Conclusion: DW-CMR is sensitive to diffuse myocardial fibrosis and is capable of characterizing the extent of fibrosis in HCM patients.
C1 [Nguyen, Christopher; Fan, Zhaoyang; Li, Debiao] Cedars Sinai Med Ctr, Biomed Imaging Res Inst, Los Angeles, CA 90048 USA.
[Nguyen, Christopher; Li, Debiao] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA.
[Lu, Minjie; Zhao, Shihua] Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China.
[Lu, Minjie; Zhao, Shihua] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China.
[Lu, Minjie; Zhao, Shihua] Fuwai Hosp, Peking Union Med Coll, Beijing, Peoples R China.
[Bi, Xiaoming] Siemens Healthcare, MR R&D, Los Angeles, CA USA.
[Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Zhao, SH (reprint author), Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China.
EM cjr.zhaoshihua@vip.163.com; Debiao.Li@cshs.org
FU National Institute of Health National Institute of Biomedical Imaging
and Bioengineering [1F31EB018152-01A1]; National Natural Science
Foundation of China [81370036, 81130029]; Fundamental Research Funds for
the Central Universities of China [3332013105]; Capital Clinically
Characteristic Applied Research Fund of China [Z151100004015141];
Beijing Natural Science Foundation [7152124]
FX This study was supported in part by the research grants of National
Institute of Health National Institute of Biomedical Imaging and
Bioengineering (1F31EB018152-01A1), National Natural Science Foundation
of China (81370036 and 81130029), the Fundamental Research Funds for the
Central Universities of China (3332013105), Capital Clinically
Characteristic Applied Research Fund of China (Z151100004015141), and
Beijing Natural Science Foundation (7152124).
NR 27
TC 4
Z9 4
U1 0
U2 5
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 DEC 2
PY 2015
VL 17
AR 107
DI 10.1186/s12968-015-0214-1
PG 7
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CX6EJ
UT WOS:000365793700001
PM 26631061
ER
PT J
AU Blake, KD
Kaufman, AR
Lorenzo, J
Augustson, EM
AF Blake, Kelly D.
Kaufman, Annette R.
Lorenzo, Joshua
Augustson, Erik M.
TI A Descriptive Study of Television News Coverage of Tobacco in the United
States: Frequency of Topics, Frames, Exemplars, and Efficacy
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID NEWSPAPER COVERAGE; MEDIA ADVOCACY; SMOKING; ATTITUDES; ISSUES; HEALTH;
AUSTRALIA; BEHAVIOR; EXPOSURE; POLICIES
AB There is a positive correlation between recall of tobacco-related television news and perceived risks of smoking and thoughts about quitting. The authors used Cision US, Inc., to create a sampling frame (N=61,027) of local and national television news coverage of tobacco from October 1, 2008, to September 30, 2009, and to draw a nationally representative sample (N=730) for content analysis. The authors conducted a descriptive study to determine the frequency and proportion of stories containing specified tobacco topics, frames, sources, and action messages, and the valence of the coverage. Valence was generally neutral; 68% of stories took a balanced stance, with 26% having a tenor supportive of tobacco control and 6% opposing tobacco control. The most frequently covered topics included smoking bans (n=195) and cessation (n=156). The least covered topics included hookah (n=1) and menthol (n=0). The majority of coverage lacked quoting any source (n=345); government officials (n=144) were the most quoted sources. Coverage lacked action messages or resources; 29 stories (<4%) included a message about cessation or advocacy, and 8 stories (1%) contained a resource such as a quitline. Television news can be leveraged by health communication professionals to increase awareness of underrepresented topics in tobacco control.
C1 [Blake, Kelly D.] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
[Kaufman, Annette R.; Augustson, Erik M.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
[Lorenzo, Joshua] Univ S Florida, Coll Publ Hlth, Tampa, FL USA.
RP Blake, KD (reprint author), NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,Room 3E222,MSC 9671, Bethesda, MD 20892 USA.
EM kelly.blakez@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 0
Z9 0
U1 2
U2 18
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD DEC 2
PY 2015
VL 20
IS 12
BP 1415
EP 1421
DI 10.1080/10810730.2015.1018651
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CW8XO
UT WOS:000365282900007
PM 26176379
ER
PT J
AU Brown, JR
Tesar, B
Yu, LJ
Werner, L
Takebe, N
Mikler, E
Reynolds, HM
Thompson, C
Fisher, DC
Neuberg, D
Freedman, AS
AF Brown, Jennifer R.
Tesar, Bethany
Yu, Lijian
Werner, Lillian
Takebe, Naoko
Mikler, Evgeny
Reynolds, Hazel M.
Thompson, Christina
Fisher, David C.
Neuberg, Donna
Freedman, A. S.
TI Obatoclax in combination with fludarabine and rituximab is
well-tolerated and shows promising clinical activity in relapsed chronic
lymphocytic leukemia
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Chronic lymphocytic leukemia; phase I-III trials; obatoclax; BCL-2;
fludarabine; rituximab
ID PAN-BCL-2 FAMILY ANTAGONIST; MIMETIC GX15-070 OBATOCLAX;
PROGRESSION-FREE SURVIVAL; MESYLATE GX15-070; OPEN-LABEL; PHASE-I;
CELLS; CYCLOPHOSPHAMIDE; INHIBITOR; APOPTOSIS
AB Obatoclax is a small molecule mimetic of the BH3 domain of BCL-2 family proteins. This phase 1 study combining obatoclax with FR was undertaken in chronic lymphocytic leukemia (CLL) patients relapsed after at least one prior therapy. Obatoclax was given as a 3-h infusion on days 1 and 3 and escalated through three dose levels, with standard dose FR days 1-5. Thirteen patients were enrolled, with a median of two prior therapies. One dose-limiting toxicity (DLT) of a 2-week treatment delay for persistent grade 2-3 neutropenia was observed at the highest obatoclax dose (20 mg/m(2)), but no maximum tolerated dose (MTD) was reached. The overall response rate (ORR) was 85%, with 15% complete responses (CRs) by NCI-96 criteria and 54% by IWCLL 2008 criteria. Median time to progression was 20 months. It is concluded that obatoclax can be safely administered to relapsed CLL patients in combination with FR and shows promising clinical activity.
C1 [Brown, Jennifer R.; Tesar, Bethany; Yu, Lijian; Mikler, Evgeny; Reynolds, Hazel M.; Thompson, Christina; Fisher, David C.; Freedman, A. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Brown, Jennifer R.; Tesar, Bethany; Yu, Lijian; Fisher, David C.; Freedman, A. S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Takebe, Naoko] NCI, Invest Drug Branch, NIH, Bethesda, MD 20892 USA.
RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM jbrown2@partners.org
FU NIH [K23 CA115682-01]; Scholar in Clinical Research of the Leukemia and
Lymphoma Society
FX We are indebted to the nurses and clinical research staff of the
Dana-Farber Cancer Institute for their excellent care of these patients
and to the patients for their participation in this study. JRB was
supported by NIH grant K23 CA115682-01 and is a Scholar of the American
Society of Hematology as well as a Scholar in Clinical Research of the
Leukemia and Lymphoma Society.
NR 39
TC 3
Z9 3
U1 0
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD DEC 2
PY 2015
VL 56
IS 12
BP 3336
EP 3342
DI 10.3109/10428194.2015.1048441
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA CX2IX
UT WOS:000365521500017
PM 25971907
ER
PT J
AU Martinez, NJ
Titus, SA
Wagner, AK
Simeonov, A
AF Martinez, Natalia J.
Titus, Steven A.
Wagner, Amanda K.
Simeonov, Anton
TI High-throughput fluorescence imaging approaches for drug discovery using
in vitro and in vivo three-dimensional models
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE drug discovery; fluorescent imaging; high content; high-throughput
screen; three-dimensional cellular models; whole-animal imaging
ID CELL-CULTURE MODELS; TUMOR SPHEROID MODEL; SUPERRESOLUTION MICROSCOPY;
ZEBRAFISH EMBRYOS; 3D CULTURE; QUANTITATIVE-ANALYSIS; COCULTURE SYSTEMS;
BREAST-CANCER; ASSAY; PLATFORM
AB Introduction: High-resolution microscopy using fluorescent probes is a powerful tool to investigate individual cell structure and function, cell subpopulations and mechanisms underlying cellular responses to drugs. Additionally, responses to drugs more closely resemble those seen in vivo when cells are physically connected in three-dimensional (3D) systems (either 3D cell cultures or whole organisms), as opposed to traditional monolayer cultures. Combined, the use of imaging-based 3D models in the early stages of drug development has the potential to generate biologically relevant data that will increase the likelihood of success for drug candidates in human studies.Areas covered: The authors discuss current methods for the culturing of cells in 3D as well as approaches for the imaging of whole-animal models and 3D cultures that are amenable to high-throughput settings and could be implemented to support drug discovery campaigns. Furthermore, they provide critical considerations when discussing imaging these 3D systems for high-throughput chemical screenings.Expert opinion: Despite widespread understanding of the limitations imposed by the two-dimensional versus the 3D cellular paradigm, imaging-based drug screening of 3D cellular models is still limited, with only a few screens found in the literature. Image acquisition in high throughput, accurate interpretation of fluorescent signal, and uptake of staining reagents can be challenging, as the samples are in essence large aggregates of cells. The authors recognize these shortcomings that need to be overcome before the field can accelerate the utilization of these technologies in large-scale chemical screens.
C1 [Martinez, Natalia J.; Titus, Steven A.; Wagner, Amanda K.; Simeonov, Anton] Natl Inst Hlth, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Simeonov, A (reprint author), Natl Inst Hlth, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
EM asimeono@mail.nih.gov
FU National Institutes of Health
FX The authors are employees of and are supported by the National
Institutes of Health. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 100
TC 5
Z9 5
U1 6
U2 45
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD DEC 2
PY 2015
VL 10
IS 12
BP 1347
EP 1361
DI 10.1517/17460441.2015.1091814
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CW9UR
UT WOS:000365344200001
PM 26394277
ER
PT J
AU Imashimizu, M
Takahashi, H
Oshima, T
McIntosh, C
Bubunenko, M
Court, DL
Kashlev, M
AF Imashimizu, Masahiko
Takahashi, Hiroki
Oshima, Taku
McIntosh, Carl
Bubunenko, Mikhail
Court, Donald L.
Kashlev, Mikhail
TI Visualizing translocation dynamics and nascent transcript errors in
paused RNA polymerases in vivo (vol 16, 98, 2015)
SO GENOME BIOLOGY
LA English
DT Correction
C1 [Imashimizu, Masahiko; McIntosh, Carl; Bubunenko, Mikhail; Court, Donald L.; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Takahashi, Hiroki] Chiba Univ, Med Mycol Res Ctr, Chuo Ku, Chiba 2608673, Japan.
[Oshima, Taku] Nara Inst Sci & Technol, Grad Sch Biol Sci, Ikoma, Nara 6300192, Japan.
RP Kashlev, M (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA.
EM kashlevm@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD DEC 2
PY 2015
VL 16
AR 270
DI 10.1186/s13059-015-0845-4
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CX3CE
UT WOS:000365572300001
PM 26631078
ER
PT J
AU Powers, RA
Leili, J
Hagman, B
Cohn, A
AF Powers, Rachael A.
Leili, Jennifer
Hagman, Brett
Cohn, Amy
TI The Impact of College Education on Rape Myth Acceptance, Alcohol
Expectancies, and Bystander Attitudes
SO DEVIANT BEHAVIOR
LA English
DT Article
ID SEXUAL AGGRESSION; COMMUNITY SAMPLE; EXPERIENCES; WOMEN; VICTIMIZATION;
METAANALYSIS; STUDENTS; BEHAVIOR; GENDER; PERCEPTIONS
AB The purpose of this study was to examine the impact of education on rape myth acceptance, alcohol expectancies, and bystander attitudes. A sample of 126 community members and college students who had consumed alcohol within the past 90 days were administered surveys. College experience was unrelated to rape myth acceptance, alcohol expectancies, and bystander intentions. In line with previous research, two rape myth subscales were inversely related to bystander attitudes. In regard to alcohol expectancies and bystander attitudes, only one subscale was marginally significant. Ancillary analysis indicated that rape myth acceptance varied as a function of age, with older individuals less likely to support rape myths.
C1 [Powers, Rachael A.; Leili, Jennifer] Univ S Florida, Tampa, FL 33620 USA.
[Hagman, Brett] NIAAA, Washington, DC USA.
[Cohn, Amy] Schroeder Inst Tobacco Res & Policy Studies, LEGACY, Washington, DC USA.
RP Powers, RA (reprint author), Univ S Florida, Dept Criminol, 4202 E Fowler Ave,SOC 107, Tampa, FL 33620 USA.
EM powersr@usf.edu
FU Rape Prevention Education grant by Centers for Disease Control and
Prevention (CDC) through the Florida Department of Health (DOH)
FX This project was supported by funding from the Rape Prevention Education
grant provided by the Centers for Disease Control and Prevention (CDC)
through the Florida Department of Health (DOH). The contents are solely
the responsibility of the authors and do not necessarily represent the
official view of the U.S. Department of Health and Human Services, the
CDC, or DOH.
NR 41
TC 0
Z9 0
U1 9
U2 29
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0163-9625
EI 1521-0456
J9 DEVIANT BEHAV
JI Deviant Behav.
PD DEC 2
PY 2015
VL 36
IS 12
BP 956
EP 973
DI 10.1080/01639625.2014.982747
PG 18
WC Criminology & Penology; Psychology, Social; Sociology
SC Criminology & Penology; Psychology; Sociology
GA CU7EF
UT WOS:000363698500002
ER
PT J
AU Hall, KD
AF Hall, Kevin D.
TI Computational modeling of body composition dynamics in response to diet
and physical activity interventions
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Meeting Abstract
C1 [Hall, Kevin D.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD DEC
PY 2015
VL 69
SU 1
MA LS018
BP S6
EP S6
PG 1
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DS7ZG
UT WOS:000381001500019
ER
PT J
AU Shankavaram, U
Maachani, UB
Zhao, S
Camphausen, K
Tandle, A
AF Shankavaram, Uma
Maachani, Uday Bhanu
Zhao, Shuping
Camphausen, Kevin
Tandle, Anita
TI Molecular profiling of MPS1 gene silencing in U251 glioma cell line
SO GENOMICS DATA
LA English
DT Article
DE Gene silencing; U251; Glioma; Microarray; Cancer
ID HUMAN GLIOBLASTOMA; BIOCONDUCTOR; EXPRESSION; CANCER
AB Aneuploidy has been recognized as a common characteristic of cancers. Aneuploidy frequently results from errors of the mitotic checkpoint, the major cell cycle control mechanism that acts to prevent chromosome missegregation. Mutation of the genes that control chromosome segregation during mitosis may explain the high rate of chromosomal instability and aneuploidy, a characteristic of most solid tumors, including glioblastoma (GBM) (Gordon et al., 2012 [1]; Singh et al., 2012 [2]). Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint kinase that is overexpressed in several human cancers (Kilpinen et al., 2010 [3]; Mills et al., 1992 [4]; Yuan et al., 2006 [5]). In our previous publication, we have shown the role of MPS1 kinase in DNA repair and enhanced radiosensitivity in GBM (Maachani et al., 2015 [6]). Here, we provide methodological and analytical details of that study, to compare mRNA expression profile of siMPS1-silenced U251 cells with untransfected control, and siRNA control (siNeg) at 6, 24, and 48 h after transfection. The raw data of this study is deposited in Gene Expression Omnibus under the accession number GSE57091. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Shankavaram, Uma; Maachani, Uday Bhanu; Zhao, Shuping; Camphausen, Kevin; Tandle, Anita] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Shankavaram, U (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM uma@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 8
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD DEC
PY 2015
VL 6
BP 36
EP 39
DI 10.1016/j.gdata.2015.08.003
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4NG
UT WOS:000377759200013
PM 26392922
ER
PT J
AU Gomez-Verjan, JC
Estrella-Parra, EA
Gonzalez-Sanchez, I
Rivero-Segura, NA
Vazquez-Martinez, R
Magos-Guerrero, G
Mendoza-Villanueva, D
Cerbon-Cervantes, MA
Reyes-Chilpa, R
AF Gomez-Verjan, J. C.
Estrella-Parra, E. A.
Gonzalez-Sanchez, I.
Rivero-Segura, N. A.
Vazquez-Martinez, R.
Magos-Guerrero, G.
Mendoza-Villanueva, D.
Cerbon-Cervantes, M. A.
Reyes-Chilpa, R.
TI Toxicogenomic analysis of pharmacological active coumarins isolated from
Calophyllum brasiliense
SO GENOMICS DATA
LA English
DT Article
AB Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree, mainly distributed in South and Central America. It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA + A/BB (3: 1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3: 1) was administered orally to malemice (CD-1) at dose of 100 mg/kg/daily, for 1 week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drugmetabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Gomez-Verjan, J. C.; Estrella-Parra, E. A.; Gonzalez-Sanchez, I.; Reyes-Chilpa, R.] Univ Nacl Autonoma Mexico, Inst Quim, Mexico City, DF, Mexico.
[Rivero-Segura, N. A.; Vazquez-Martinez, R.; Cerbon-Cervantes, M. A.] Univ Nacl Autonoma Mexico, Inst Nacl Perinatol, Fac Quim, Unidad Invest Reproducc Humana, Mexico City, DF, Mexico.
[Magos-Guerrero, G.] Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Lab Fitofarmacol, Mexico City, DF, Mexico.
[Mendoza-Villanueva, D.] NIH, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD USA.
RP Reyes-Chilpa, R (reprint author), Univ Nacl Autonoma Mexico, Inst Quim, Mexico City, DF, Mexico.
EM carlosverjan@comunidad.unam.mx; chilpa@unam.mx
OI Gonzalez-Sanchez, Ignacio/0000-0003-4282-5062
NR 2
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD DEC
PY 2015
VL 6
BP 258
EP 259
DI 10.1016/j.gdata.2015.10.006
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4NG
UT WOS:000377759200079
PM 26697389
ER
PT J
AU Jia, L
Sun, ZH
Wu, XL
Misteli, T
Sharma, V
AF Jia, Li
Sun, Zhonghe
Wu, Xiaolin
Misteli, Tom
Sharma, Vivek
TI Gene expression analysis upon lncRNA DDSR1 knockdown in human
fibroblasts
SO GENOMICS DATA
LA English
DT Article
DE DDSR1; lncRNA
AB Long non-coding RNAs (lncRNAs) play important roles in regulating diverse biological processes including DNA damage and repair. We have recently reported that the DNA damage inducible lncRNA DNA damage-sensitive RNA1 (DDSR1) regulates DNA repair by homologous recombination (HR). Since lncRNAs also modulate gene expression, we identified gene expression changes upon DDSR1 knockdown in human fibroblast cells. Gene expression analysis after RNAi treatment targeted against DDSR1 revealed 119 genes that show differential expression. Here we provide a detailed description of the microarray data (NCBI GEO accession number GSE67048) and the data analysis procedure associated with the publication by Sharma et al., 2015 in EMBO Reports [1]. Published by Elsevier Inc.
C1 [Misteli, Tom; Sharma, Vivek] NCI, Cell Biol Genomes Grp, NIH, Bethesda, MD 20892 USA.
[Jia, Li] NCI, CCR Collaborat Bioinformat Resource CCBR, NIH, Bethesda, MD 20892 USA.
[Sun, Zhonghe; Wu, Xiaolin] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD 21702 USA.
RP Misteli, T (reprint author), NCI, Cell Biol Genomes Grp, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov; vivek.sharma@nih.gov
NR 2
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-5960
J9 GENOM DATA
JI Genom. Data
PD DEC
PY 2015
VL 6
BP 277
EP 279
DI 10.1016/j.gdata.2015.10.017
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA DO4NG
UT WOS:000377759200087
PM 26697398
ER
PT J
AU Fukushima, M
Doyle, AM
Mullarkey, MP
Mishkin, M
Averbeck, BB
AF Fukushima, Makoto
Doyle, Alex M.
Mullarkey, Matthew P.
Mishkin, Mortimer
Averbeck, Bruno B.
TI Distributed acoustic cues for caller identity in macaque vocalization
SO ROYAL SOCIETY OPEN SCIENCE
LA English
DT Article
DE animal vocalization; macaque; voice recognition; caller identity
ID AUDITORY-CORTEX; RHESUS-MONKEYS; CONSPECIFIC VOCALIZATIONS; JAPANESE
MONKEYS; VOCAL RECOGNITION; NONHUMAN-PRIMATES; PREFRONTAL CORTEX;
MACACA-FUSCATA; TEMPORAL-LOBE; VOICE
AB Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo'call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized.
C1 [Fukushima, Makoto; Doyle, Alex M.; Mullarkey, Matthew P.; Mishkin, Mortimer; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA.
RP Fukushima, M (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA.
EM makoto_fukushima@me.com
OI Fukushima, Makoto/0000-0002-8809-7892
FU Intramural Research Program of the National Institute of Mental Health
(NIMH), NIH, DHHS
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health (NIMH), NIH, DHHS.
NR 54
TC 0
Z9 0
U1 5
U2 5
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2054-5703
J9 ROY SOC OPEN SCI
JI R. Soc. Open Sci.
PD DEC
PY 2015
VL 2
IS 12
AR 150432
DI 10.1098/rsos.150432
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO7NA
UT WOS:000377968100011
PM 27019727
ER
PT J
AU Horkay, F
Shibayama, M
AF Horkay, Ferenc
Shibayama, Mitsuhiro
TI Networks and Biopolymer Assemblies
SO MACROMOLECULAR SYMPOSIA
LA English
DT Proceedings Paper
CT Joint Meeting of the 22nd Polymer-Networks-Group Meeting on Polymer
Networks and Gels (PN and G) / 10th Gel Symposium
CY NOV 10-14, 2014
CL Tokyo, JAPAN
SP Inst Solid State Phys, Univ Tokyo, Polymer Networks Grp
C1 [Horkay, Ferenc] NICHD, Polymer Networks Grp, NIH, Bethesda, MD USA.
[Shibayama, Mitsuhiro] Univ Tokyo, Inst Solid State Phys, Tokyo, Japan.
RP Horkay, F (reprint author), NICHD, Polymer Networks Grp, NIH, Bethesda, MD USA.
RI Shibayama, Mitsuhiro/E-1646-2015
OI Shibayama, Mitsuhiro/0000-0002-8683-5070
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1022-1360
EI 1521-3900
J9 MACROMOL SYMP
JI Macromol. Symp.
PD DEC
PY 2015
VL 358
IS 1
SI SI
BP 9
EP 9
DI 10.1002/masy.201570044
PG 1
WC Polymer Science
SC Polymer Science
GA DN7VE
UT WOS:000377287400001
ER
PT J
AU Horkay, F
AF Horkay, Ferenc
TI Interaction of Cartilage Biopolymers
SO MACROMOLECULAR SYMPOSIA
LA English
DT Proceedings Paper
CT Joint Meeting of the 22nd Polymer-Networks-Group Meeting on Polymer
Networks and Gels (PN and G) / 10th Gel Symposium
CY NOV 10-14, 2014
CL Tokyo, JAPAN
SP Inst Solid State Phys, Univ Tokyo, Polymer Networks Grp
DE aggrecan; collagen; hyaluronic acid; osmotic pressure; small angle
neutron scattering
ID LINK PROTEIN; AGGRECAN MACROMOLECULES; PROTEOGLYCANS; SPECTROSCOPY
AB Aggrecan is a charged biopolymer whose complexes with hyaluronic acid provide the compressive resistance of cartilage. In cartilage extracellular matrix aggrecan-hyaluronic acid complexes are enmeshed within a network of collagen fibrils. Osmotic pressure measurements and small angle neutron scattering (SANS) measurements are reported on solutions of aggrecan and aggrecan-hyaluronic acid complexes. These techniques probe the length scales relevant to the biological functions of cartilage. Osmotic pressure measurements indicate that dissolved aggrecan monomers form microgel-like assemblies. The osmotic pressure of aggrecan-hyaluronic acid complexes decreases with decreasing the ratio of aggrecan to hyaluronic acid. SANS reveals that there is no significant interpenetration between the neighboring aggrecan molecules. Both osmotic pressure measurements and SANS indicate weak interactions between the aggrecan bottlebrushes and collagen fibers.
C1 [Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 South Dr, Bethesda, MD 20892 USA.
RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 South Dr, Bethesda, MD 20892 USA.
EM horkayf@helix.nih.gov
NR 19
TC 0
Z9 0
U1 2
U2 4
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1022-1360
EI 1521-3900
J9 MACROMOL SYMP
JI Macromol. Symp.
PD DEC
PY 2015
VL 358
IS 1
SI SI
BP 78
EP 84
DI 10.1002/masy.201500054
PG 7
WC Polymer Science
SC Polymer Science
GA DN7VE
UT WOS:000377287400010
ER
PT J
AU Arduc, A
Isik, S
Allusoglu, S
Iriz, A
Dogan, BA
Tuna, MM
Gocer, C
Berker, D
Guler, S
AF Arduc, Ayse
Isik, Serhat
Allusoglu, Serpil
Iriz, Ayse
Dogan, Bercem Aycicek
Tuna, Mazhar Muslim
Gocer, Celil
Berker, Dilek
Guler, Serdar
TI Does Acquired Hypothyroidism Affect the Hearing Functions?
SO TURKISH JOURNAL OF ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE Hypothyroidism; hearing function; audiometry
ID BRAIN-STEM RESPONSES; THYROID-HORMONE; EXPRESSION; ONSET; CELL
AB Purpose: It is well known that congenital hypothyroidism can cause hearing loss. However, conflicting results were found in studies investigating hearing functions in acquired hypothyroidism. Therefore, we evaluated the audiometric findings in patients with acquired hypothyroidism.
Material and Method: The study included 58 patients with hypothyroidism and age-and gender-matched 34 healthy controls. Twenty eight (48.27%) patients had subclinical hypothyroidism, and 30 (51.73%) had obvious hypothyroidism. All subjects had a normal otoscopic examination and tympanometry. Pure tone audiometry at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz) was performed in both groups. Blood pressure measurements and the levels of plasma electrolytes, lipids and vitamin B12 were available in all subjects.
Results: Hypothyroidism group and control group were similar with respect to systolic and diastolic blood pressures and plasma glucose, lipid, vitamin B12, calcium, sodium, potassium, and chloride levels. Significantly higher audiometric thresholds (dB) at 250 (10 (0-45) vs. 5 (0-15), p<0.001) and 500 Hz (10 (0-40) vs. 10 (-5-15), p=0.003) were recorded in hypothyroid patients compared to that in healthy controls. Hearing thresholds at 250 and 500 Hz correlated positively with thyroid-stimulating hormone (TSH), and negatively with free triiodothyronine and free thyroxine. Subclinical hypothyroid patients had a higher hearing threshold at 250 Hz than healthy controls (p=0.001).
Discussion: Our study demonstrated that hearing ability decreases in hypothyroidism, even in subclinical hypothyroidism. The changes in TSH and thyroid hormone levels seem to be directly related to the hearing loss in this population of patients.
C1 NIDDK, NIH, Endocrine & Obes Branch, Bethesda, MD 20892 USA.
[Arduc, Ayse; Dogan, Bercem Aycicek; Tuna, Mazhar Muslim; Berker, Dilek] Ankara Numune Training & Res Hosp, Clin Endocrinol & Metab, Ankara, Turkey.
[Allusoglu, Serpil; Iriz, Ayse; Gocer, Celil] Ankara Numune Training & Res Hosp, Otorhinolaryngol Clin, Ankara, Turkey.
[Guler, Serdar] Hitit Univ, Fac Med, Dept Endocrinol & Metab, Corum, Turkey.
RP Arduc, A (reprint author), NIDDK, NIH, Endocrine & Obes Branch, Bethesda, MD 20892 USA.
EM ayse_arduc@yahoo.com
NR 18
TC 0
Z9 0
U1 4
U2 4
PU GALENOS YAYINCILIK
PI FINDIKZADE
PA ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY
SN 1301-2193
J9 TURK J ENDOCRINOL ME
JI Turk. J. Endocrinol. Metab.
PD DEC
PY 2015
VL 19
IS 4
BP 124
EP 129
DI 10.4274/tjem.3051
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK5KK
UT WOS:000374958600003
ER
PT J
AU Winuthayanon, W
Bernhardt, ML
Padilla-Banks, E
Myers, PH
Edin, ML
Lih, FB
Hewitt, SC
Korach, KS
Williams, CJ
AF Winuthayanon, Wipawee
Bernhardt, Miranda L.
Padilla-Banks, Elizabeth
Myers, Page H.
Edin, Matthew L.
Lih, Fred B.
Hewitt, Sylvia C.
Korach, Kenneth S.
Williams, Carmen J.
TI Oviductal estrogen receptor a signaling prevents protease-mediated
embryo death
SO ELIFE
LA English
DT Article
ID FEMALE REPRODUCTIVE-TRACT; ZONA-PELLUCIDA PROTEIN; INNATE IMMUNITY;
CORTICAL GRANULES; OOCYTE MATURATION; MOUSE EGGS; IN-VITRO; MICE; GENE;
FERTILIZATION
AB Development of uterine endometrial receptivity for implantation is orchestrated by cyclic steroid hormone-mediated signals. It is unknown if these signals are necessary for oviduct function in supporting fertilization and preimplantation development. Here we show that conditional knockout (cKO) mice lacking estrogen receptor alpha (ER alpha) in oviduct and uterine epithelial cells have impaired fertilization due to a dramatic reduction in sperm migration. In addition, all successfully fertilized eggs die before the 2-cell stage due to persistence of secreted innate immune mediators including proteases. Elevated protease activity in cKO oviducts causes premature degradation of the zona pellucida and embryo lysis, and wild-type embryos transferred into cKO oviducts fail to develop normally unless rescued by concomitant transfer of protease inhibitors. Thus, suppression of oviductal protease activity mediated by estrogen-epithelial ERa signaling is required for fertilization and preimplantation embryo development. These findings have implications for human infertility and post-coital contraception.
C1 [Winuthayanon, Wipawee; Bernhardt, Miranda L.; Padilla-Banks, Elizabeth; Hewitt, Sylvia C.; Korach, Kenneth S.; Williams, Carmen J.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Winuthayanon, Wipawee] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Pullman, WA 99164 USA.
[Myers, Page H.] NIEHS, Comparat Med Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Edin, Matthew L.] NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Lih, Fred B.] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Winuthayanon, W (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM winuthayanonw@vetmed.wsu.edu; williamsc5@niehs.nih.gov
OI Hewitt, Sylvia/0000-0001-7713-0805
FU National Institute of Environmental Health Sciences [1ZIAES70065,
1ZIAES025034, 1ZIAES050167, 1ZIAES102405]
FX National Institute of Environmental Health Sciences 1ZIAES70065 Wipawee
Winuthayanon Sylvia C Hewitt Kenneth S Korach; National Institute of
Environmental Health Sciences 1ZIAES025034 Matthew L Edin; National
Institute of Environmental Health Sciences 1ZIAES050167 Fred B Lih;
National Institute of Environmental Health Sciences 1ZIAES102405 Miranda
L Bernhardt Elizabeth Padilla-Banks Carmen J Williams; The funder had no
role in study design, data collection and interpretation, or the
decision to submit the work for publication.
NR 57
TC 0
Z9 0
U1 0
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 DEC 1
PY 2015
VL 4
AR e10453
DI 10.7554/eLife.10453
PG 28
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ0MZ
UT WOS:000373899600001
ER
PT J
AU Shi, T
Balsells, E
Wastnedge, E
Singleton, R
Rasmussen, ZA
Zar, HJ
Rath, BA
Madhi, SA
Campbell, S
Vaccari, LC
Bulkow, LR
Thomas, ED
Barnett, W
Hoppe, C
Campbell, H
Nair, H
AF Shi, Ting
Balsells, Evelyn
Wastnedge, Elizabeth
Singleton, Rosalyn
Rasmussen, Zeba A.
Zar, Heather J.
Rath, Barbara A.
Madhi, Shabir A.
Campbell, Stuart
Vaccari, Linda Cheyenne
Bulkow, Lisa R.
Thomas, Elizabeth D.
Barnett, Whitney
Hoppe, Christian
Campbell, Harry
Nair, Harish
TI Risk factors for respiratory syncytial virus associated with acute lower
respiratory infection in children under five years: Systematic review
and meta-analysis
SO JOURNAL OF GLOBAL HEALTH
LA English
DT Review
ID CLINICAL-PREDICTION RULE; CHILDHOOD PNEUMONIA; HOSPITAL ADMISSION; TRACT
INFECTIONS; AFRICAN CHILDREN; RURAL ALASKA; BRONCHIOLITIS; EPIDEMIOLOGY;
DIARRHEA; INFANTS
AB Background Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children.
Methods We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors.
Results We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI.
Conclusions This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.
C1 [Shi, Ting; Balsells, Evelyn; Wastnedge, Elizabeth; Vaccari, Linda Cheyenne; Campbell, Harry; Nair, Harish] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
[Singleton, Rosalyn; Bulkow, Lisa R.] Ctr Dis Control & Prevent CDC, Arctic Invest Program, Div Preparedness & Emerging Infect, NCEZID, Anchorage, AK USA.
[Singleton, Rosalyn] Alaska Native Tribal Hlth Consortium, Anchorage, AK USA.
[Rasmussen, Zeba A.; Thomas, Elizabeth D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Zar, Heather J.; Barnett, Whitney] Univ Cape Town, Dept Paediat & Child Hlth, Red Cross War Mem Childrens Hosp, ZA-7700 Rondebosch, South Africa.
[Zar, Heather J.; Barnett, Whitney] Univ Cape Town, MRC Unit Child & Adolescent Hlth, ZA-7700 Rondebosch, South Africa.
[Rath, Barbara A.; Hoppe, Christian] Charite, Med Ctr, Dept Pediat, D-13353 Berlin, Germany.
[Madhi, Shabir A.] Univ Witwatersrand, MRC, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa.
[Madhi, Shabir A.] Univ Witwatersrand, Dept Sci & Technol, Natl Res Fdn Vaccine Preventable Dis, Johannesburg, South Africa.
[Madhi, Shabir A.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis, Johannesburg, South Africa.
[Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Campbell, Stuart; Nair, Harish] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Med Informat Ctr, Edinburgh, Midlothian, Scotland.
[Nair, Harish] Publ Hlth Fdn India, New Delhi, India.
RP Nair, H (reprint author), Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Old Med Sch, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
EM harish.nair@ed.ac.uk
RI Nair, Harish/E-7431-2010
OI Nair, Harish/0000-0002-9432-9100
FU China Scholarship Council; Bill and Melinda Gates Foundation
[OPP1088499, OPP1096225]
FX TS is supported by a scholarship from the China Scholarship Council. HC
and HN have received grant funding from the Bill and Melinda Gates
Foundation (OPP1088499 and OPP1096225) for this work.
NR 37
TC 11
Z9 12
U1 2
U2 6
PU UNIV EDINBURGH, GLOBAL HEALTH SOC
PI EDINBURGH
PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG,
ENGLAND
SN 2047-2978
EI 2047-2986
J9 J GLOB HEALTH
JI J. Glob. Health
PD DEC
PY 2015
VL 5
IS 2
BP 203
EP 215
AR UNSP 020416
DI 10.7189/jogh.05.020416
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DI9WJ
UT WOS:000373853100021
PM 26682048
ER
PT J
AU Klamsaengsai, S
Choibamroong, T
AF Klamsaengsai, Sukhuman
Choibamroong, Therdchai
TI Operational Efficiencies of Thai Airports from the Perspective of
Low-Cost Carriers
SO PERTANIKA JOURNAL OF SOCIAL SCIENCE AND HUMANITIES
LA English
DT Article
DE Airport operations; low-cost carriers; operational efficiencies; Thai
airports
ID FULL-SERVICE CARRIERS; AIRLINES
AB The expansion of low-cost carriers (LCC) in the past two decades has increased the number of air passengers and visitors to countries around the globe. The resulting growth of the tourism industry worldwide has challenged airports in shaping their operations. Thus, the purposes of the study were to: 1) investigate efficient areas in airport operations; and 2) investigate inefficient areas in airport operations of Thai airports. Semi-structured interviews were adopted to collect qualitative data from 30 LCC staff. The research results showed that Thailand airports had efficiencies in providing a number of security check points, cooperation of security agencies, standard safety equipment, wide ranges of ancillary services, friendly staff and regular arrangement of airport meetings with airline representatives, whereas capabilities of security staff, airlines and passenger facilities, language ability of airport staff, attitudes of airport staff, service allocation, unequal treatments, price of food and goods and terminal function designs are areas of inefficiencies.
C1 [Klamsaengsai, Sukhuman] Walailak Univ, WMS, Nakhon Si Thammarat, Thailand.
[Choibamroong, Therdchai] NIDA, Grad Sch Tourism Management, Bangkok, Thailand.
RP Klamsaengsai, S (reprint author), Walailak Univ, WMS, Nakhon Si Thammarat, Thailand.
EM ksukhuma@gmail.com; tedchoibamroong@hotmail.com
NR 30
TC 0
Z9 0
U1 1
U2 1
PU UNIVERSITI PUTRA MALAYSIA PRESS
PI SELANGOR
PA SERDANG, SELANGOR, 00000, MALAYSIA
SN 0128-7702
EI 2231-8534
J9 PERTANIKA J SOC SCI
JI Pertanika J. Soc. Sci. Humanit.
PD DEC
PY 2015
VL 23
IS 4
BP 1053
EP 1068
PG 16
WC Social Sciences, Interdisciplinary
SC Social Sciences - Other Topics
GA DI8SX
UT WOS:000373773000019
ER
PT J
AU Hodnett, BL
Schmitt, NC
Thirumala, PD
Duvvuri, U
AF Hodnett, Benjamin L.
Schmitt, Nicole C.
Thirumala, Parthasarathy D.
Duvvuri, Umamaheswar
TI Intraoperative identification of the human communicating nerve during
thyroidectomy
SO JOURNAL OF SURGICAL CASE REPORTS
LA English
DT Article
ID SUPERIOR LARYNGEAL NERVE
AB The human communicating nerve (HCN) is a connection between the superior and recurrent laryngeal nerves that has been described in cadaveric studies. We report a case of an extralaryngeal variant of the HCN that was identified and stimulated intraoperatively during thyroidectomy. This appears to be the first case of intraoperative identification of this anatomic variant, of which the functional significance remains unclear.
C1 [Hodnett, Benjamin L.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Schmitt, Nicole C.] Johns Hopkins Univ, Dept Otorhinolaryngol Head & Neck Surg, NIDCD, NIH, Bethesda, MD USA.
[Thirumala, Parthasarathy D.] UPMC Presbyterian Hosp, Dept Neurol Surg & Neurol, Ctr Clin Neurophysiol, Pittsburgh, PA USA.
[Duvvuri, Umamaheswar] Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Hlth Syst,Eye & Ear Inst, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA.
RP Duvvuri, U (reprint author), Univ Pittsburgh, Sch Med, Dept Otolaryngol, VA Pittsburgh Hlth Syst,Eye & Ear Inst, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA.
EM duvvuriu@upmc.edu
NR 6
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2042-8812
J9 J SURG CASE REP
JI J. Surg. Case Rep.
PD DEC
PY 2015
IS 12
AR UNSP rjv154
DI 10.1093/jscr/rjv154
PG 4
WC Surgery
SC Surgery
GA DH2EO
UT WOS:000372597200006
ER
PT J
AU Nagineni, CN
Kommineni, VK
Ganjbaksh, N
Nagineni, KK
Hooks, JJ
Detrick, B
AF Nagineni, Chandrasekharam N.
Kommineni, Vijay K.
Ganjbaksh, Nader
Nagineni, Krishnasai K.
Hooks, John J.
Detrick, Barbara
TI Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal
Cells: Role in Chemokine Receptor Mediated Age-related Macular
Degeneration
SO AGING AND DISEASE
LA English
DT Article
DE Age-related macular degeneration; Retinal pigment epithelium; Retina;
Inflammation; Choroidal neovascularization; Chemokines; CCR3
ID PIGMENT EPITHELIAL-CELLS; INDUCED CHOROIDAL NEOVASCULARIZATION;
INTERNATIONAL UNION; EOTAXIN RECEPTOR; CCR3; ANGIOGENESIS; EOSINOPHILS;
MECHANISMS; INHIBITION; THERAPY
AB Chemokine reeptor-3 (CCR-3) was shown to be associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). AMD is a vision threatening retinal disease that affects the aging population world-wide. Retinal pigment epithelium and choroid in the posterior part of the retina are the key tissues targeted in the pathogenesis of CNV in AMD. We used human retinal pigment epithelial (HRPE) and choroidal fibroblast (HCHF) cells, prepared from aged adult human donor eyes, to evaluate the expression of major CCR-3 ligands, CCL-5, CCL -7, CCL-11, CCL-24 and CCL-26. Microarray analysis of gene expression in HRPE cells treated with inflammatory cytokine mix (ICM= IFN-gamma+TNF-alpha+IL-1 beta) revealed 75 and 23-fold increase in CCL-5 and CCL-7 respectively, but not CCL-11, CCL-24 and CCL-26. Chemokine secretion studies of the production of CCL5 and CCL7 by HRPE corroborated with the gene expression analysis data. When the HRPE cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent manner. Similar to the gene expression data, the ICM did not enhance HRPE production of CCL-11, CCL-24 and CCL-26. CCL-11 and CCL-26 were increased with IL-4 treatment and this HRPE production was augmented in the presence of TNF-alpha and IL1 beta When HCHF cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent fashion. IL-4 induced low levels of CCL-11 and CCL-26 in HCHF and this production was significantly enhanced by TNF-alpha. Under these conditions, neither HRPE nor HCHF were demonstrated to produce CCL-24. These data demonstrate that chronic inflammation triggers CCL-5 and CCL-7 release by HRPE and HCHF and the subsequent interactions with CCR3 may participate in pathologic processes in AMD.
C1 [Nagineni, Chandrasekharam N.; Kommineni, Vijay K.; Ganjbaksh, Nader; Hooks, John J.] NEI, Lab Immunol, NIH, Bethesda, MD 20892 USA.
[Nagineni, Krishnasai K.] Univ Maryland, Sch Publ Policy, College Pk, MD 20742 USA.
[Detrick, Barbara] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21205 USA.
RP Detrick, B (reprint author), Johns Hopkins Med Inst, Baltimore, MD USA.
EM naginenic@mail.nih.gov; bdetrick@jhmi.edu
FU intramural research program of the National Eye Institute, National
Institutes of Health
FX This research was supported by intramural research program of the
National Eye Institute, National Institutes of Health.
NR 62
TC 1
Z9 1
U1 1
U2 1
PU INT SOC AGING & DISEASE
PI FORT WORTH
PA EDITORIAL OFF, 3400 CAMP BOWIE BLVD, FORT WORTH, TX 76106 USA
SN 2152-5250
J9 AGING DIS
JI Aging Dis.
PD DEC
PY 2015
VL 6
IS 6
BP 444
EP 455
PG 12
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA DE2DE
UT WOS:000370435900005
PM 26618046
ER
PT J
AU Hu, ZY
Hu, X
He, SS
Yim, HJ
Xiao, JB
Swaroop, M
Tanega, C
Zhang, YQ
Yi, GH
Kao, CC
Marugan, J
Ferrer, M
Zheng, W
Southall, N
Liang, TJ
AF Hu, Zongyi
Hu, Xin
He, Shanshan
Yim, Hyung Joon
Xiao, Jingbo
Swaroop, Manju
Tanega, Cordelle
Zhang, Ya-qin
Yi, Guanghui
Kao, C. Cheng
Marugan, Juan
Ferrer, Marc
Zheng, Wei
Southall, Noel
Liang, T. Jake
TI Identification of novel anti-hepatitis C virus agents by a quantitative
high throughput screen in a cell-based infection assay
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Antiviral; HCV inhibitors; High throughput screening; Cell-based assay;
Viral life cycle
ID HOST FACTORS; SERINE-PROTEASE; RNA-POLYMERASE; LIFE-CYCLE; INHIBITORS;
ENTRY; REPLICATION; THERAPY; DRUGS; BINDING
AB Hepatitis C virus (HCV) poses a major health threat to the world. The recent development of direct-acting antivirals (DAAs) against HCV has markedly improved the response rate of HCV and reduced the side effects in comparison to the interferon-based therapy. Despite this therapeutic advance, there is still a need to develop new inhibitors that target different stages of the HCV life cycle because of various limitations of the current regimens. In this study, we performed a quantitative high throughput screening of the Molecular Libraries Small Molecule Repository (MLSMR) of similar to 350,000 chemicals for novel HCV inhibitors using our previously developed cell-based HCV infection assay. Following confirmation and structural clustering analysis, we narrowed down to 158 compounds from the initial similar to 3000 molecules that showed inhibitory activity for further structural and functional analyses. We were able to assign the majority of these compounds to specific stage(s) in the HCV life cycle. Three of them are direct inhibitors of NS3/4A protease. Most of the compounds appear to act on novel targets in HCV life cycle. Four compounds with novel structure and excellent drug-like properties, three targeting HCV entry and one targeting HCV assembly/secretion, were advanced for further development as lead hits. These compounds represent diverse chemotypes that are potential lead compounds for further optimization and may offer promising candidates for the development of novel therapeutics against HCV infection. In addition, they represent novel molecular probes to explore the complex interactions between HCV and the cells. Published by Elsevier B.V.
C1 [Hu, Zongyi; He, Shanshan; Yim, Hyung Joon; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hu, Xin; Xiao, Jingbo; Swaroop, Manju; Tanega, Cordelle; Zhang, Ya-qin; Marugan, Juan; Ferrer, Marc; Zheng, Wei; Southall, Noel] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Yi, Guanghui; Kao, C. Cheng] Indiana Univ, Dept Mol & Cellular Biochem, Bloomington, IN 47405 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM jliang@nih.gov
RI Zheng, Wei/J-8889-2014;
OI Zheng, Wei/0000-0003-1034-0757; Southall, Noel/0000-0003-4500-880X
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Center for Advancing
Translational Sciences, National Institutes of Health
FX We thank Baihua Zhang for her excellent technical work, Paul Shinn for
his preparation of compounds, Sam Michael and Mike Balcom for operating
robot-controlled compound administration and plate reading. This work
was supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases and the National
Center for Advancing Translational Sciences, National Institutes of
Health.
NR 45
TC 0
Z9 0
U1 0
U2 1
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 DEC
PY 2015
VL 124
BP 20
EP 29
DI 10.1016/j.antiviral.2015.10.018
PG 10
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA DE2NE
UT WOS:000370463200003
PM 26515788
ER
PT J
AU Arduc, A
Isik, S
Allusoglu, S
Iriz, A
Dogan, BA
Gocer, C
Tuna, MM
Berker, D
Guler, S
AF Arduc, Ayse
Isik, Serhat
Allusoglu, Serpil
Iriz, Ayse
Dogan, Bercem Aycicek
Gocer, Celil
Tuna, Mazhar Muslim
Berker, Dilek
Guler, Serdar
TI Evaluation of hearing functions in patients with euthyroid Hashimoto's
thyroiditis
SO ENDOCRINE
LA English
DT Article
DE Hashimoto's thyroiditis; Hearing function; Audiometry
ID EVOKED OTOACOUSTIC EMISSIONS; BRAIN-STEM RESPONSES; INNER-EAR; DISEASE;
TESTS
AB Sensorineural hearing loss has been reported in various autoimmune diseases. The relationship between Hashimoto's thyroiditis (HT) and the auditory system has not been previously evaluated. In this study, we investigated the effect of euthyroid HT on the hearing ability of adult patients. The study included 30 patients with newly diagnosed euthyroid HT and 30 age- and gender-matched healthy controls. All subjects had a normal otoscopic examination and tympanometry, and they were negative for rheumatoid factor, antinuclear, anti-smooth muscle, antimitochondrial, antineutrophilcytoplasmic, and antigliadin antibodies. Pure tone audiometry exams at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz) were performed in both groups. Thyroid peroxidase antibody and thyroglobulin antibody (anti-Tg) levels were higher in HT group while TSH, free T4, free T3, plasma electrolytes, glucose, lipid profile, vitamin B12, and blood pressure measurements were similar between the two groups. Higher audiometric thresholds and a higher prevalence of hearing loss at 250, 500, and 6000 Hz were detected in the HT patients than in the healthy controls (P < 0.05). Hearing levels at 250 and 500 Hz correlated positively with anti-Tg levels (rho = 0.650, P = 0.002; rho = 0.719, P < 0.001, respectively), and this association remained significant in linear regression analysis. Anti-Tg-positive HT patients had higher hearing thresholds at 250 and 500 Hz than anti-Tg-negative HT patients. Hearing thresholds were similar between anti-Tg-negative HT patients and the control subjects. This study demonstrated that hearing functions are impaired in HT patients. Thyroid autoimmunity seems to have an important impact on a decreased hearing ability, particularly at lower frequencies, in this population of patients.
C1 [Arduc, Ayse] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD USA.
[Isik, Serhat; Dogan, Bercem Aycicek; Tuna, Mazhar Muslim; Berker, Dilek] Minist Hlth, Ankara Numune Res & Training Hosp, Dept Endocrinol & Metab, Ankara, Turkey.
[Allusoglu, Serpil; Iriz, Ayse; Gocer, Celil] Minist Hlth, Ankara Numune Res & Training Hosp, Dept Otorhinolaryngol, Ankara, Turkey.
[Guler, Serdar] Hitit Univ, Fac Med, Dept Endocrinol & Metab, Corum, Turkey.
RP Arduc, A (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD USA.
EM ayse_arduc@yahoo.com
NR 28
TC 2
Z9 2
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD DEC
PY 2015
VL 50
IS 3
BP 708
EP 714
DI 10.1007/s12020-015-0624-8
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DD7CX
UT WOS:000370082400023
PM 25963023
ER
PT J
AU Davies, MA
Ford, N
Rabie, H
Fatti, G
Stinson, K
Giddy, J
Tanser, F
Technau, KG
Sawry, S
Eley, B
Wood, R
Mofenson, LM
Keiser, O
Boulle, A
AF Davies, Mary-Ann
Ford, Nathan
Rabie, Helena
Fatti, Geoffrey
Stinson, Kathryn
Giddy, Janet
Tanser, Frank
Technau, Karl-Guenter
Sawry, Shobna
Eley, Brian
Wood, Robin
Mofenson, Lynne M.
Keiser, Olivia
Boulle, Andrew
TI Reducing CD4 Monitoring in Children on Antiretroviral Therapy With
Virologic Suppression
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE HIV-1; children; CD4; monitoring; viral load; sub-Saharan Africa;
antiretroviral
ID HIV-INFECTED PATIENTS; CELL COUNT; LYMPHOCYTE; AFRICA; COHORT
AB Background: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART.
Methods: We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after >= 1 year on ART (time 0)] and (2) >= 1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure.
Results: Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children.
Conclusions: This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone.
C1 [Davies, Mary-Ann; Stinson, Kathryn; Boulle, Andrew] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa.
[Ford, Nathan] WHO, HIV AIDS Dept, CH-1211 Geneva, Switzerland.
[Rabie, Helena] Univ Stellenbosch, Tygerberg Acad Hosp, ZA-7600 Stellenbosch, South Africa.
[Fatti, Geoffrey] Kheth Impilo, Cape Town, South Africa.
[Stinson, Kathryn] Med Sans Frontieres, Khayelitsha, South Africa.
[Giddy, Janet] McCord Hosp, Durban, South Africa.
[Tanser, Frank] Hlabisa HIV Program, Cape Town, South Africa.
[Technau, Karl-Guenter] Univ Witwatersrand, Empilweni Serv & Res Unit, Rahima Moosa Mother & Child Hosp, Johannesburg, South Africa.
[Sawry, Shobna] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
[Eley, Brian] Univ Cape Town, Red Cross War Mem Childrens Hosp, ZA-7925 Cape Town, South Africa.
[Eley, Brian] Univ Cape Town, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa.
[Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Gugulethu HIV Program, ZA-7925 Cape Town, South Africa.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Keiser, Olivia] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland.
RP Davies, MA (reprint author), Univ Cape Town, Fac Hlth Sci, Sch Publ Hlth & Family Med, Anzio Rd, ZA-7925 Observatory, South Africa.
EM mary-ann.davies@uct.ac.za
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases
[2U01AI069924-06]; PROSPER fellowship grant from the Swiss National
Science Foundation [3233B_150934]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development and the National Institute of Allergy and
Infectious Diseases (grant number 2U01AI069924-06; Egger, M. A. D.). The
funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript. H. R. has been
paid by AbbVie for teaching activities unrelated to this manuscript. O.
K. was supported by a PROSPER fellowship grant (nr 3233B_150934) from
the Swiss National Science Foundation. The other authors have no
conflicts of interest to disclose.
NR 22
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 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD DEC
PY 2015
VL 34
IS 12
BP 1361
EP 1364
DI 10.1097/INF.0000000000000912
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA DD4BF
UT WOS:000369866700018
PM 26379169
ER
PT J
AU Polman, DJ
Price, DK
Figg, WD
AF Polman, David J.
Price, Douglas K.
Figg, William D.
TI New bigenic mouse model increases the understanding of genetic synergism
in the progression of prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE bigenic mouse model; disease progression; genetic synergism; NF-kappa B
pathway; PTEN; PSGR; prostate cancer; PIK3/Akt pathway
ID KAPPA-B; PTEN; PSGR
C1 [Polman, David J.; Price, Douglas K.; Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 8
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD DEC
PY 2015
VL 16
IS 12
BP 1702
EP 1703
DI 10.1080/15384047.2015.1108498
PG 2
WC Oncology
SC Oncology
GA DD4TS
UT WOS:000369916100002
PM 26552331
ER
PT J
AU Warren, JJ
Matney, SA
Foster, ED
Auld, VA
Roy, SL
AF Warren, Judith J.
Matney, Susan A.
Foster, Erin D.
Auld, Vivian A.
Roy, Susan L.
TI Toward Interoperability: A New Resource to Support Nursing Terminology
Standards
SO CIN-COMPUTERS INFORMATICS NURSING
LA English
DT Editorial Material
C1 [Warren, Judith J.] Warren Associates LLC, Plattsmouth, NE USA.
[Matney, Susan A.] 3M Hlth Informat Syst, Murray, UT USA.
[Foster, Erin D.; Auld, Vivian A.; Roy, Susan L.] Natl Lib Med, Bethesda, MD USA.
RP Warren, JJ (reprint author), Warren Associates LLC, Plattsmouth, NE USA.
FU National Library of Medicine (NLM), National Institutes of Health; NLM
FX This research was supported by the Intramural Research Program of the
National Library of Medicine (NLM), National Institutes of Health. This
research was supported in part by an appointment to the NLM Associate
Fellowship Program sponsored by the NLM and administered by the Oak
Ridge Institute for Science and Education.
NR 20
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1538-2931
EI 1538-9774
J9 CIN-COMPUT INFORM NU
JI CIN-Comput. Inform. Nurs.
PD DEC
PY 2015
VL 33
IS 12
BP 515
EP 519
PG 5
WC Computer Science, Interdisciplinary Applications; Medical Informatics;
Nursing
SC Computer Science; Medical Informatics; Nursing
GA DD4JN
UT WOS:000369888400001
PM 26678815
ER
PT J
AU Nino, PKB
Durik, M
Danser, AHJ
de Vries, R
Musterd-Bhaggoe, UM
Meima, ME
Kavousi, M
Ghanbari, M
Hoeijmakers, JH
O'Donnell, CJ
Franceschini, N
Janssen, GMJ
De Mey, JGR
Liu, YW
Shanahan, CM
Franco, OH
Dehghan, A
Roks, AJM
AF Nino, Paula K. Bautista
Durik, Matej
Danser, A. H. Jan
de Vries, Rene
Musterd-Bhaggoe, Usha M.
Meima, Marcel E.
Kavousi, Maryam
Ghanbari, Mohsen
Hoeijmakers, Jan H.
O'Donnell, Christopher J.
Franceschini, Nora
Janssen, Ger M. J.
De Mey, Jo G. R.
Liu, Yiwen
Shanahan, Catherine M.
Franco, Oscar H.
Dehghan, Abbas
Roks, Anton J. M.
TI Phosphodiesterase 1 regulation is a key mechanism in vascular aging
SO CLINICAL SCIENCE
LA English
DT Review
DE aging; blood pressure; genetic association; phosphodiesterases; vascular
disease
ID CONGESTIVE-HEART-FAILURE; CARDIOVASCULAR-DISEASE RISK;
MUSCLE-CELL-PROLIFERATION; NITRIC-OXIDE; BLOOD-PRESSURE; ENDOTHELIAL
DYSFUNCTION; OXIDATIVE-STRESS; ASSOCIATION; HUMANS; ATHEROSCLEROSIS
AB Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role in human age-related vascular disease. To test our hypothesis, we combined experiments in mice with genomic instability resulting from the defective nucleotide excision repair gene ERCC1 (Ercc1(d/-) mice), human VSMC cultures and population genome-wide association studies (GWAS). Aortic rings of Ercc1(d/-) mice showed 43% reduced responses to the soluble guanylate cyclase (sGC) stimulator sodium nitroprusside (SNP). Inhibition of phosphodiesterase (PDE) 1 and 5 normalized SNP-relaxing effects in Ercc1(d/-) to wild-type (WT) levels. PDE1C levels were increased in lung and aorta. cGMP hydrolysis by PDE in lungs was higher in Ercc1(d/-) mice. No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1(d/-) mice compared with WT. Senescent human VSMC showed elevated PDE1A and PDE1C and PDE5 mRNA levels (11.6-, 9- and 2.3-fold respectively), which associated with markers of cellular senescence. Conversely, PDE1 inhibition lowered expression of these markers. Human genetic studies revealed significant associations of PDE1A single nucleotide polymorphisms with diastolic blood pressure (DBP; beta = 0.28, P = 2.47x10(-5)) and carotid intima-media thickness (cIMT; beta = -0.0061, P = 2.89 x 10(-5)). In summary, these results show that genomic instability and cellular senescence in VSMCs increase PDE1 expression. This might play a role in aging-related loss of vasodilator function, VSMC senescence, increased blood pressure and vascular hypertrophy.
C1 [Nino, Paula K. Bautista; Durik, Matej; Danser, A. H. Jan; de Vries, Rene; Musterd-Bhaggoe, Usha M.; Roks, Anton J. M.] Erasmus MC, Dept Internal Med, Div Vasc Dis & Pharmacol, NL-3015 CN Rotterdam, Netherlands.
[Nino, Paula K. Bautista; Kavousi, Maryam; Ghanbari, Mohsen; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
[Durik, Matej] Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague, Czech Republic.
[Meima, Marcel E.] Erasmus MC, Div Endocrinol, Dept Internal Med, NL-3015 CN Rotterdam, Netherlands.
[Hoeijmakers, Jan H.] Erasmus MC, Dept Genet, NL-3015 CN Rotterdam, Netherlands.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Janssen, Ger M. J.; De Mey, Jo G. R.] Maastricht Univ, Dept Pharmacol, NL-6211 LK Maastricht, Netherlands.
[De Mey, Jo G. R.] Univ Southern Denmark, Inst Mol Med, Dept Cardiovasc & Renal Res, DK-5230 Odense, Denmark.
[Liu, Yiwen; Shanahan, Catherine M.] Kings Coll London, James Black Ctr, Div Cardiovasc, London SE5 9NU, England.
RP Roks, AJM (reprint author), Erasmus MC, Dept Internal Med, Div Vasc Dis & Pharmacol, NL-3015 CN Rotterdam, Netherlands.
EM a.roks@erasmusmc.nl
OI Dehghan, Abbas/0000-0001-6403-016X
FU Academy of Sciences of the Czech Republic [RVO 68378050]; BIOCEV -
Biotechnology and Biomedicine Centre of the Academy of Sciences and
Charles University [CZ.1.05/1.1.00/02.0109]
FX This work was supported by the Academy of Sciences of the Czech Republic
[grant number RVO 68378050 (to M.D.)]; the BIOCEV - Biotechnology and
Biomedicine Centre of the Academy of Sciences and Charles University
[grant number CZ.1.05/1.1.00/02.0109].
NR 47
TC 5
Z9 5
U1 3
U2 11
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0143-5221
EI 1470-8736
J9 CLIN SCI
JI Clin. Sci.
PD DEC 1
PY 2015
VL 129
IS 12
BP 1061
EP 1075
DI 10.1042/CS20140753
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DD1WS
UT WOS:000369714400007
ER
PT J
AU Klion, AD
AF Klion, Amy D.
TI Eosinophilia: a pragmatic approach to diagnosis and treatment
SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
LA English
DT Article
ID HYPEREOSINOPHILIC SYNDROME; IMATINIB; VARIANT; CELLS; FIP1L1-PDGFRA;
INTERLEUKIN-5; INFLAMMATION; MEPOLIZUMAB; EXPRESSION; SECRETION
AB Eosinophilia is associated with a wide variety of allergic, rheumatologic, infectious, neoplastic, and rare idiopathic disorders. Clinical manifestations range from benign asymptomatic presentations to life-threatening complications, including endomyocardial fibrosis and thromboembolism. The prognosis and choice of treatment depend not only on the degree of eosinophilia and severity of organ involvement, but also on the etiology of the eosinophilia. Unfortunately, despite recent advances in molecular and immunologic techniques, the etiology remains unproven in the overwhelming majority of cases. This review presents a practical approach to the diagnosis and treatment of patients presenting with unexplained marked eosinophilia. A brief overview of the mechanisms of eosinophilia and eosinophil pathogenesis is also provided.
C1 [Klion, Amy D.] NIAID, Human Eosinophil Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-29,4 Ctr Dr, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIAID, Human Eosinophil Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-29,4 Ctr Dr, Bethesda, MD 20892 USA.
EM aklion@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was funded by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 40
TC 1
Z9 1
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 1520-4391
EI 1520-4383
J9 HEMATOL-AM SOC HEMAT
JI Hematol.-Am. Soc. Hematol. Educ. Program
PD DEC
PY 2015
BP 92
EP 97
PG 6
WC Education, Scientific Disciplines; Hematology
SC Education & Educational Research; Hematology
GA DD0JU
UT WOS:000369607000014
ER
PT J
AU Bonci, A
AF Bonci, Antonello
TI From single synapses to clinical studies: Therapeutic developments from
optogenetics
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Meeting Abstract
C1 [Bonci, Antonello] NIDA, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
EI 1741-203X
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD DEC
PY 2015
VL 27
SU 1
MA P01
BP S3
EP S3
PG 1
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA DD1UD
UT WOS:000369706400004
ER
PT J
AU Sharov, AA
Schlessinger, D
Ko, MSH
AF Sharov, Alexei A.
Schlessinger, David
Ko, Minoru S. H.
TI ExAtlas: An interactive online tool for meta-analysis of gene expression
data
SO JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY
LA English
DT Article
DE Meta-analysis; correlation matrix; gene set enrichment; ANOVA; PCA;
expected proportion of false positives.
ID WEB-BASED TOOL; MICROARRAY DATA; SET ENRICHMENT; INFORMATION; RESOURCES;
GENMAPP; SYSTEM
AB We have developed ExAtlas, an on-line software tool for meta-analysis and visualization of gene expression data. In contrast to existing software tools, ExAtlas compares multi-component data sets and generates results for all combinations (e.g. all gene expression profiles versus all Gene Ontology annotations). ExAtlas handles both users' own data and data extracted semi-automatically from the public repository (GEO/NCBI database). ExAtlas provides a variety of tools for meta-analyses: (1) standard meta-analysis (fixed erects, random effects, z-score, and Fisher's methods); (2) analyses of global correlations between gene expression data sets; (3) gene set enrichment; (4) gene set overlap; (5) gene association by expression profile; (6) gene specificity; and (7) statistical analysis (ANOVA, pairwise comparison, and PCA). ExAtlas produces graphical outputs, including heatmaps, scatter-plots, bar-charts, and three-dimensional images. Some of the most widely used public data sets (e.g. GNF/BioGPS, Gene Ontology, KEGG, GAD phenotypes, BrainScan, ENCODE ChIP-seq, and protein-protein interaction) are pre-loaded and can be used for functional annotations.
C1 [Sharov, Alexei A.; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Ko, Minoru S. H.] Keio Univ, Sch Med, Sakaguchi Lab, Dept Syst Med, Tokyo 1608582, Japan.
RP Ko, MSH (reprint author), Keio Univ, Sch Med, Sakaguchi Lab, Dept Syst Med, Tokyo 1608582, Japan.
EM sharoval@mail.nih.gov; schlessingerd@mail.nih.gov; ko.minoru@keio.jp
OI Ko, Minoru/0000-0002-3530-3015
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 38
TC 8
Z9 8
U1 2
U2 3
PU IMPERIAL COLLEGE PRESS
PI LONDON
PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND
SN 0219-7200
EI 1757-6334
J9 J BIOINF COMPUT BIOL
JI J. Bioinform. Comput. Biol.
PD DEC
PY 2015
VL 13
IS 6
SI SI
AR 1550019
DI 10.1142/S0219720015500195
PG 13
WC Biochemical Research Methods; Computer Science, Interdisciplinary
Applications; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Computer Science; Mathematical &
Computational Biology
GA DD2OH
UT WOS:000369761500008
PM 26223199
ER
PT J
AU Yucesoy, B
Kissling, GE
Johnson, VJ
Lummus, ZL
Gautrin, D
Cartier, A
Boulet, LP
Sastre, J
Quirce, S
Tarlo, SM
Cruz, MJ
Munoz, X
Luster, MI
Bernstein, DI
AF Yucesoy, Berran
Kissling, Grace E.
Johnson, Victor J.
Lummus, Zana L.
Gautrin, Denyse
Cartier, Andre
Boulet, Louis-Philippe
Sastre, Joaquin
Quirce, Santiago
Tarlo, Susan M.
Cruz, Maria-Jesus
Munoz, Xavier
Luster, Michael I.
Bernstein, David I.
TI N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced
Asthma
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID OCCUPATIONAL ASTHMA; TOLUENE DIISOCYANATE; MOLECULAR-GENETICS;
EPITHELIAL-CELLS; BRONCHIAL-ASTHMA; EXPOSURE; ACETYLATION; RISK; NAT2;
POLYMORPHISMS
AB Objective: To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). Methods: The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 50-nuclease polymerase chain reaction assay. Results: The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA_ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P - 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). Conclusions: These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.
C1 [Yucesoy, Berran; Lummus, Zana L.; Bernstein, David I.] Univ Cincinnati, Div Immunol Allergy & Rheumatol, Cincinnati, OH 45267 USA.
[Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Johnson, Victor J.] BRT Burleson Res Technol, Morrisville, NY USA.
[Gautrin, Denyse; Cartier, Andre] Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, Canada.
[Boulet, Louis-Philippe] Univ Laval, Hop Laval, Ste Foy, PQ G1K 7P4, Canada.
[Sastre, Joaquin] Fdn Jimenez Diaz, Dept Allergy, E-28040 Madrid, Spain.
[Sastre, Joaquin; Quirce, Santiago; Cruz, Maria-Jesus; Munoz, Xavier] CIBER Enfermedades Resp CIBERES, Madrid, Spain.
[Quirce, Santiago] Hosp La Paz IdiPAZ, Dept Allergy, Madrid, Spain.
[Tarlo, Susan M.] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada.
[Tarlo, Susan M.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada.
[Cruz, Maria-Jesus; Munoz, Xavier] Hosp Valle De Hebron, Barcelona, Spain.
[Luster, Michael I.] W Virginia Univ, Sch Publ Hlth, Morgantown, WV 26506 USA.
RP Yucesoy, B (reprint author), Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH 45267 USA.
EM berranyucesoy@gmail.com
FU NIOSH/CDC [R01 OH 008795]; NIH, National Institute of Environmental
Health Sciences
FX This study was supported in part by NIOSH/CDC R01 OH 008795 and the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences.
NR 45
TC 1
Z9 1
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1076-2752
EI 1536-5948
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD DEC
PY 2015
VL 57
IS 12
BP 1331
EP 1336
DI 10.1097/JOM.0000000000000561
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DD4JV
UT WOS:000369889400019
PM 26641831
ER
PT J
AU Schelbert, EB
Piehler, KM
Zareba, KM
Moon, JC
Ugander, M
Messroghli, DR
Valeti, US
Chang, CCH
Shroff, SG
Diez, J
Miller, CA
Schmitt, M
Kellman, P
Butler, J
Gheorghiade, M
Wong, TC
AF Schelbert, Erik B.
Piehler, Kayla M.
Zareba, Karolina M.
Moon, James C.
Ugander, Martin
Messroghli, Daniel R.
Valeti, Uma S.
Chang, Chung-Chou H.
Shroff, Sanjeev G.
Diez, Javier
Miller, Christopher A.
Schmitt, Matthias
Kellman, Peter
Butler, Javed
Gheorghiade, Mihai
Wong, Timothy C.
TI Myocardial Fibrosis Quantified by Extracellular Volume Is Associated
With Subsequent Hospitalization for Heart Failure, Death, or Both Across
the Spectrum of Ejection Fraction and Heart Failure Stage
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular magnetic resonance; extracellular matrix; extracellular
volume fraction; heart failure; myocardial fibrosis; T1 mapping
ID CARDIOVASCULAR MAGNETIC-RESONANCE; LATE GADOLINIUM-ENHANCEMENT; DILATED
CARDIOMYOPATHY; RISK PREDICTION; DISEASE; VALIDATION; HUMANS; T1; CMR;
REPRODUCIBILITY
AB Background-Myocardial fibrosis (MF) in noninfarcted myocardium may be an interstitial disease pathway that confers vulnerability to hospitalization for heart failure, death, or both across the spectrum of heart failure and ejection fraction. Hospitalization for heart failure is an epidemic that is difficult to predict and prevent and requires potential therapeutic targets associated with outcomes.
Method and Results-We quantified MF with cardiovascular magnetic resonance extracellular volume fraction (ECV) measures in 1172 consecutive patients without amyloidosis or hypertrophic or stress cardiomyopathy and assessed associations with outcomes using Cox regression. ECV ranged from 16.6% to 47.8%. Over a median of 1.7 years, 111 patients experienced events after cardiovascular magnetic resonance, 55 had hospitalization for heart failure events, and there were 74 deaths. ECV was more strongly associated with outcomes than "nonischemic" MF observed with late gadolinium enhancement, thus ECV quantified MF in multivariable models. Adjusting for age, sex, renal function, myocardial infarction size, ejection fraction, hospitalization status, and heart failure stage, higher ECV was associated with hospitalization for heart failure (hazard ratio 1.77; 95% CI 1.32 to 2.36 for every 5% increase in ECV), death (hazard ratio 1.87 95% CI 1.45 to 2.40) or both (hazard ratio 1.85, 95% CI 1.50 to 2.27). ECV improved classification of persons at risk and improved model discrimination for outcomes (eg, hospitalization for heart failure: continuous net reclassification improvement 0.33, 95% CI 0.05 to 0.66; P=0.02; 0.16, 95% CI 0.01 to 0.33; P=0.02; integrated discrimination improvement 0.037, 95% CI 0.008 to 0.073; P<0.01).
Conclusion-MF measured by ECV is associated with hospitalization for heart failure, death, or both. MF may represent a principal phenotype of cardiac vulnerability that improves risk stratification. Because MF can be reversible, cells and enzymes regulating collagen could be potential therapeutic targets.
C1 [Schelbert, Erik B.; Zareba, Karolina M.; Chang, Chung-Chou H.; Wong, Timothy C.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15101 USA.
[Schelbert, Erik B.; Piehler, Kayla M.; Zareba, Karolina M.; Wong, Timothy C.] UPMC Cardiovasc Magnet Resonance Ctr, Inst Heart & Vasc, Pittsburgh, PA USA.
[Schelbert, Erik B.; Wong, Timothy C.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15101 USA.
[Shroff, Sanjeev G.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15101 USA.
[Zareba, Karolina M.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Moon, James C.] Barts Heart Ctr, London, England.
[Moon, James C.] UCL, London, England.
[Ugander, Martin] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden.
[Ugander, Martin] Karolinska Univ Hosp, Stockholm, Sweden.
[Messroghli, Daniel R.] Deutsch Herzzentrum Berlin, Dept Congenital Heart Dis & Pediat Cardiol, Berlin, Germany.
[Valeti, Uma S.] Univ Minnesota, Div Cardiol, Minneapolis, MN USA.
[Chang, Chung-Chou H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15101 USA.
[Diez, Javier] Ctr Appl Med Res, Program Cardiovasc Dis, Pamplona, Spain.
[Diez, Javier] Univ Navarra Clin, Pamplona, Spain.
[Miller, Christopher A.; Schmitt, Matthias] Univ Manchester, Ctr Imaging Sci, Manchester M13 9PL, Lancs, England.
[Miller, Christopher A.; Schmitt, Matthias] Univ Manchester, Biomed Imaging Inst, Manchester M13 9PL, Lancs, England.
[Kellman, Peter] NHLBI, Bethesda, MD 20892 USA.
[Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA.
[Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
RP Schelbert, EB (reprint author), Univ Pittsburgh, Cardiovasc Magnet Resonance Ctr, Med & Clin & Translat Sci, Heart & Vasc Inst,UPMC,Sch Med, 200 Lothrop St,PUH A349, Pittsburgh, PA 15101 USA.
EM schelberteb@upmc.edu
RI Diez, Javier/D-7014-2017;
OI Diez, Javier/0000-0002-3414-6919; Schelbert, Erik/0000-0003-0356-4437;
Ugander, Martin/0000-0003-3665-2038; moon, james/0000-0001-8071-1491
FU Pittsburgh Foundation (PA) [M2009-0068]; American Heart Association
Scientist Development grant [09SDG2180083]; T. Franklin Williams
Scholarship Award; Atlantic Philanthropies, Inc; John A. Hartford
Foundation; Association of Specialty Professors; American Heart
Association (Dallas, TX); National Center for Research Resources (NCRR)
[UL1 RR024153]; component of the National Institutes of Health (NIH);
NIH Roadmap for Medical Research
FX This work was supported by a grant from The Pittsburgh Foundation (PA),
Grant M2009-0068; and an American Heart Association Scientist
Development grant (09SDG2180083) including a T. Franklin Williams
Scholarship Award; funding provided by: Atlantic Philanthropies, Inc,
the John A. Hartford Foundation, the Association of Specialty
Professors, and the American Heart Association (Dallas, TX). This work
was also supported by Grant Number UL1 RR024153 from the National Center
for Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research.
NR 43
TC 11
Z9 11
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD DEC
PY 2015
VL 4
IS 12
AR e002613
DI 10.1161/JAHA.115.002613
PG 23
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DD5FI
UT WOS:000369947700035
ER
PT J
AU Jain, M
Smith, M
AF Jain, Minal
Smith, Michaele
TI Commentary on "Effect of an Ankle Foot Orthosis Intervention for
Children With Non-Central Nervous System Cancers: A Pilot Study"
SO PEDIATRIC PHYSICAL THERAPY
LA English
DT Editorial Material
C1 [Jain, Minal; Smith, Michaele] NIH, Mark O Hatfield Clin Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Jain, M (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Bldg 10, Bethesda, MD 20892 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 0898-5669
EI 1538-005X
J9 PEDIATR PHYS THER
JI Pediatr. Phys. Ther.
PD WIN
PY 2015
VL 27
IS 4
BP 432
EP 432
DI 10.1097/PEP.0000000000000188
PG 1
WC Pediatrics; Rehabilitation
SC Pediatrics; Rehabilitation
GA DD1YP
UT WOS:000369719600024
PM 26397092
ER
PT J
AU Feng, LR
Chen, MK
Lukkahatai, N
Hsiao, CP
Kaushal, A
Sechrest, L
Saligan, LN
AF Feng, Li Rebekah
Chen, Mei-kuang
Lukkahatai, Nada
Hsiao, Chao-Pin
Kaushal, Aradhana
Sechrest, Lee
Saligan, Leorey N.
TI Clinical Predictors of Fatigue in Men With Non-Metastatic Prostate
Cancer Receiving External Beam Radiation Therapy
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Article
DE cancer-related fatigue; anemia; radiation therapy; prostate cancer
ID ANDROGEN DEPRIVATION THERAPY; ANEMIA-RELATED SYMPTOMS; RATING-SCALE;
RADIOTHERAPY; DEPRESSION; SURVIVORS; DISEASE; SYSTEM; AXIS
AB Background: Fatigue is one of the most distressing symptoms experienced by people with cancer receiving radiation therapy.
Objectives: The goal of this study is to evaluate clinical predictors of worsening fatigue during external beam radiation therapy (EBRT) in men with non-metastatic prostate cancer.
Methods: Thirty-five men with non-metastatic prostate cancer scheduled for EBRT were followed at baseline, midpoint, and completion of EBRT. The Functional Assessment of Cancer Therapy-Fatigue scale was administered. Demographic and clinical data were obtained by chart review. Paired t-tests, correlations, general linear models, and logistic regressions were used to determine associations between fatigue scores and clinical data.
Findings: Red blood cells, hemoglobin, and hematocrit levels were highly intercorrelated and, therefore, were grouped as one composite variable termed heme. Heme levels at baseline and androgen-deprivation therapy (ADT) were significantly correlated with worsening of fatigue symptoms from baseline to midpoint and endpoint. ADT alone did not have a significant correlation with fatigue, but it indirectly affected fatigue levels by influencing heme markers as treatment progressed. These findings provide evidence that hematologic markers and the use of ADT assist in predicting radiation therapy-related fatigue and guide symptom management.
C1 [Feng, Li Rebekah; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA.
[Chen, Mei-kuang; Sechrest, Lee] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
[Lukkahatai, Nada] Univ Nevada, Sch Nursing, Las Vegas, NV 89154 USA.
[Hsiao, Chao-Pin] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
[Kaushal, Aradhana] NCI, NIH, Bethesda, MD 20892 USA.
RP Saligan, LN (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
FU Intramural Research Program of the National Institute of Nursing
Research of the National Institutes of Health
FX Li Rebekah Feng, PhD, is a group leader and clinical research fellow at
the National Institute of Nursing Research in the National Institutes of
Health in Bethesda, MD; Mei-kuang Chen, PhD, is a research associate in
the Department of Psychology at the University of Arizona in Tucson;
Nada Lukkahatai, PhD, RN, is an assistant professor in the School of
Nursing at the University of Nevada in Las Vegas; Chao-Pin Hsiao, PhD,
RN, is an assistant professor in the Frances Payne Bolton School of
Nursing at Case Western Reserve University in Cleveland, OH; Aradhana
Kaushal, MD, is a radiation oncologist in the National Cancer Institute
at the National Institutes of Health; Lee Sechrest, PhD, is a consultant
in the Department of Psychology at the University of Arizona; and Leorey
N. Saligan, PhD, RN, CRNP, FAAN, is a tenure track investigator at the
National Institute of Nursing Research in the National Institutes of
Health. The authors take full responsibility for the content of the
article. The study was supported, in full, by the Intramural Research
Program of the National Institute of Nursing Research of the National
Institutes of Health. The content of the article has been reviewed by
independent peer reviewers to ensure that it is balanced, objective, and
free from bias. No financial relationships relevant to the content of
this article have been disclosed by the independent peer reviewers or
editorial staff. Saligan can be reached at saliganl@mail.nih.gov, with
copy to editor at CJONEditor@ons.org. (Submitted January 2015. Revision
submitted February 2015. Accepted for publication April 6, 2015.)
NR 32
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
EI 1538-067X
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD DEC
PY 2015
VL 19
IS 6
BP 744
EP 750
DI 10.1188/15.CJON.744-750
PG 7
WC Oncology; Nursing
SC Oncology; Nursing
GA DC5EJ
UT WOS:000369243900017
PM 26583638
ER
EF