FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Ferreira, CR
   Ziegler, SG
   Gupta, A
   Groden, C
   Hsu, KS
   Gahl, WA
AF Ferreira, Carlos R.
   Ziegler, Shira G.
   Gupta, Ashutosh
   Groden, Catherine
   Hsu, Kevin S.
   Gahl, William A.
TI Treatment of Hypophosphatemic Rickets in Generalized Arterial
   Calcification of Infancy (GACI) without Worsening of Vascular
   Calcification
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE generalized arterial calcification of infancy; hypophosphatemic rickets;
   hypophosphatemia; hyperphosphaturia; ENPP1
ID SURVIVAL; MUTATIONS; SIBLINGS; ENPP1
AB Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification. (C) 2016 Wiley Periodicals, Inc.
C1 [Ferreira, Carlos R.; Groden, Catherine; Hsu, Kevin S.; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Ferreira, Carlos R.] Childrens Natl Hlth Syst, Div Genet & Metab, Washington, DC USA.
   [Ziegler, Shira G.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
   [Gupta, Ashutosh] Avera Med Grp, Pediat Specialists, Sioux Falls, SD USA.
RP Ferreira, CR (reprint author), NHGRI, 10 Ctr Dr,Bldg 10,Room 5D38, Bethesda, MD 20892 USA.
EM ferreiracr@mail.nih.gov
FU National Human Genome Research Institute
FX Grant sponsor: National Human Genome Research Institute.
NR 12
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAY
PY 2016
VL 170
IS 5
BP 1308
EP 1311
DI 10.1002/ajmg.a.37574
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA DR5LH
UT WOS:000379944000031
PM 26857895
ER

PT J
AU Zhang, TF
   Tang, XG
   Huang, XX
   Liu, QX
   Jiang, YP
   Zhou, QF
AF Zhang, Tian-Fu
   Tang, Xin-Gui
   Huang, Xian-Xiong
   Liu, Qiu-Xiang
   Jiang, Yan-Ping
   Zhou, Qi-Fa
TI High-Temperature Dielectric Relaxation Behaviors of Relaxer-Like
   PbZrO3-SrTiO3 Ceramics for Energy-Storage Applications
SO ENERGY TECHNOLOGY
LA English
DT Article
DE ceramics; energy storage; lead; oxides; strontium
ID PBZRO3 THIN-FILMS; SOL-GEL PROCESS; PHASE-TRANSITION; FERROELECTRIC
   CERAMICS; PERFORMANCE; DENSITY; MICROSTRUCTURE; EFFICIENCY; ZIRCONATE;
   SRTIO3
AB (1-x)PbZrO3-xSrTiO(3) (x: 10, 20, and 30 mol%) ceramics were prepared by a conventional mixed-oxide solid-state reaction method. The relaxer behaviors of the PbZrO3-SrTiO3 ceramics were examined in the temperature range of 120-523 K. A broad dielectric maximum that shifted to higher temperature with increasing frequency signified the relaxer-type behaviors of these ceramics. The value of the relaxation parameter of gamma=1.73, estimated from the linear fit of the modified Curie-Weiss law, indicated the relaxer nature. High-temperature dielectric relaxation phenomena were found in the temperature region of 600-850 K. The activation energy, calculated from impedance measurements of samples, suggested that the dielectric relaxation was a result of oxygen vacancies generated during the sintering process. The energy-storage density calculated from hysteresis loops reached about 0.46 Jcm(-3) for the PSZT30 ceramic at room temperature.
C1 [Zhang, Tian-Fu; Tang, Xin-Gui; Huang, Xian-Xiong; Liu, Qiu-Xiang; Jiang, Yan-Ping] Guangdong Univ Technol, Sch Phys & Optoelect Engn, Guangzhou, Guangdong, Peoples R China.
   [Zhou, Qi-Fa] Univ Southern Calif, NIH, Transducer Resource Ctr, Los Angeles, CA USA.
   [Zhou, Qi-Fa] Univ Southern Calif, Dept Biomed Engn, Los Angeles, CA USA.
RP Tang, XG (reprint author), Guangdong Univ Technol, Sch Phys & Optoelect Engn, Guangzhou, Guangdong, Peoples R China.
EM xgtang@gdut.edu.cn
FU National Natural Science Foundation of China [11202054, 11574057]
FX This work was supported by the National Natural Science Foundation of
   China (Grant Nos. 11202054 and 11574057).
NR 51
TC 2
Z9 2
U1 9
U2 15
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 2194-4288
EI 2194-4296
J9 ENERGY TECHNOL-GER
JI Energy Technol.
PD MAY
PY 2016
VL 4
IS 5
BP 633
EP 640
DI 10.1002/ente.201500436
PG 8
WC Energy & Fuels
SC Energy & Fuels
GA DR5UZ
UT WOS:000379969200010
ER

PT J
AU Fleisher, TA
   Madkaikar, M
   Rosenzweig, SD
AF Fleisher, Thomas A.
   Madkaikar, Manisha
   Rosenzweig, Sergio D.
TI Application of Flow Cytometry in the Evaluation of Primary
   Immunodeficiencies
SO INDIAN JOURNAL OF PEDIATRICS
LA English
DT Review
DE Primary immunodeficiency; Flow cytometry; Diagnosis
ID CHRONIC GRANULOMATOUS-DISEASE; DIAGNOSTIC-CRITERIA; DIGEORGE-SYNDROME;
   TRANSPLANTATION; CLASSIFICATION; DEFICIENCY; DISORDERS; MUTATIONS;
   SURVIVAL
AB Primary immunodeficiency disorders (PIDDs) are a heterogeneous group of inherited disorders of the immune system. Currently more than 250 different PIDDs with a known genetic defect have been recognized. The diagnosis of many of these disorders is supported strongly by a wide variety of flow cytometry applications. Flow cytometry offers a rapid and sensitive tool for diagnosis and classification of PIDDs. It is applicable in the initial workup and subsequent management of several primary immunodeficiency diseases. As our understanding of the pathogenesis and management of these diseases increases, the majority of these tests can be easily established in the diagnostic laboratory. Thus, the focus of this article is on the application of flow cytometry in the diagnosis and/or evaluation of PIDDs.
C1 [Fleisher, Thomas A.; Rosenzweig, Sergio D.] NIH, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C306,10 Ctr Dr,MSC1508, Bethesda, MD USA.
   [Madkaikar, Manisha] Natl Inst Immunohaematol ICMR, Dept Pediat Immunol & Leukocyte Biol, KEM Campus, Mumbai, Maharashtra, India.
RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C306,10 Ctr Dr,MSC1508, Bethesda, MD USA.
EM tfleishe@mail.nih.gov
FU Intramural Research Program of the NIH Clinical Center, National
   Institutes of Health, Bethesda, MD, USA
FX This work was supported by the Intramural Research Program of the NIH
   Clinical Center, National Institutes of Health, Bethesda, MD, USA.
NR 29
TC 1
Z9 1
U1 3
U2 3
PU ALL INDIA INST MEDICAL SCIENCES
PI NEW DELHI
PA ANSARI NAGAR, NEW DELHI 110 029, INDIA
SN 0019-5456
EI 0973-7693
J9 INDIAN J PEDIATR
JI Indian J. Pediatr.
PD MAY
PY 2016
VL 83
IS 5
BP 444
EP 449
DI 10.1007/s12098-015-2011-0
PG 6
WC Pediatrics
SC Pediatrics
GA DR3QY
UT WOS:000379818900014
PM 26865168
ER

PT J
AU Contrera, KJ
   Betz, J
   Deal, JA
   Choi, JS
   Ayonayon, HN
   Harris, T
   Helzner, E
   Martin, KR
   Mehta, K
   Pratt, S
   Rubin, SM
   Satterfield, S
   Yaffe, K
   Garcia, M
   Simonsick, EM
   Lin, FR
AF Contrera, Kevin J.
   Betz, Josh
   Deal, Jennifer A.
   Choi, Janet S.
   Ayonayon, Hilsa N.
   Harris, Tamara
   Helzner, Elizabeth
   Martin, Kathryn R.
   Mehta, Kala
   Pratt, Sheila
   Rubin, Susan M.
   Satterfield, Suzanne
   Yaffe, Kristine
   Garcia, Melissa
   Simonsick, Eleanor M.
   Lin, Frank R.
CA Hlth ABC Study
TI Association of Hearing Impairment and Emotional Vitality in Older Adults
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
   SCIENCES
LA English
DT Article
DE Anxiety; Depression; Emotional vitality; Hearing; Mental health; Sensory
   impairment
ID HEALTH; DEPRESSION; WOMEN; LIFE
AB Objectives: To better understand the potential impact of hearing impairment (HI) and hearing aid use on emotional vitality and mental health in older adults.
   Method: We investigated the cross-sectional association of HI with emotional vitality in 1,903 adults aged 76-85 years in the Health ABC study adjusted for demographic and cardiovascular risk factors. Hearing was defined by the speech frequency pure tone average (no impairment < 25 dB, mild impairment 25-40 dB, and moderate or greater impairment > 40 dB). Emotional vitality was defined as having a high sense of personal mastery, happiness, low depressive symptomatology, and low anxiety.
   Results: Compared with individuals with no HI, participants with moderate or greater HI had a 23% lower odds of emotional vitality (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.59-0.99). Hearing aid use was not associated with better emotional vitality (OR = 0.98; 95% CI: 0.81-1.20).
   Discussion: HI is associated with lower odds of emotional vitality in older adults. Further studies are needed to examine the longitudinal impact of HI on mental health and well-being.
C1 [Contrera, Kevin J.; Choi, Janet S.; Pratt, Sheila] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Betz, Josh; Lin, Frank R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
   [Deal, Jennifer A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA.
   [Helzner, Elizabeth] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA.
   [Martin, Kathryn R.] Univ Aberdeen, Inst Appl Hlth Sci, Sch Med & Dent, Aberdeen AB9 1FX, Scotland.
   [Mehta, Kala] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
   [Pratt, Sheila] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
   [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
   [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
   [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
   [Garcia, Melissa; Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Lin, Frank R.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, 2024 East Monument St,Suite 2-700, Baltimore, MD 21205 USA.
RP Lin, FR (reprint author), Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, 2024 East Monument St,Suite 2-700, Baltimore, MD 21205 USA.
EM flin1@jhmi.edu
OI Betz, Joshua/0000-0003-4488-9799
FU NIH [K23DC011279]; Eleanor Schwartz Charitable Foundation; Triological
   Society; Johns Hopkins Institute for Clinical and Translational
   Research; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106,
   R01-AG028050]; NINR [R01-NR012459]; NIA Intramural Research Program
FX This study was funded by the NIH grant K23DC011279; the Eleanor Schwartz
   Charitable Foundation; the Triological Society; the Johns Hopkins
   Institute for Clinical and Translational Research; the NIA contracts
   N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; the NIA grant
   R01-AG028050; the NINR grant R01-NR012459; and the NIA Intramural
   Research Program.
NR 22
TC 0
Z9 0
U1 7
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5014
EI 1758-5368
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD MAY
PY 2016
VL 71
IS 3
BP 400
EP 404
DI 10.1093/geronb/gbw005
PG 5
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
   Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA DR3PF
UT WOS:000379814400002
PM 26883806
ER

PT J
AU Kopczynski, J
   Kowalik, A
   Chlopek, M
   Wang, ZF
   Gozdz, S
   Lasota, J
   Miettinen, M
AF Kopczynski, Janusz
   Kowalik, Artur
   Chlopek, Malgorzata
   Wang, Zeng-Feng
   Gozdz, Stanislaw
   Lasota, Jerzy
   Miettinen, Markku
TI Oncogenic Activation of the Wnt/beta-Catenin Signaling Pathway in Signet
   Ring Stromal Cell Tumor of the Ovary
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE signet ring stromal cell tumor of the ovary; beta-catenin;
   immunohistochemistry; next-generation sequencing; Sanger sequencing;
   gain-of-function mutation
ID COACTIVATOR SRC FAMILY; OF-THE-LITERATURE; BETA-CATENIN; DIAGNOSTIC
   PITFALL; HYALINE GLOBULES; KRUKENBERG TUMOR; MUTATION; CARCINOMAS;
   EXPRESSION; CTNNB1
AB Signet ring stromal cell tumor (SRSCT) of the ovary is a very rare benign ovarian neoplasm. To date, no underlying genetic mechanism has been identified. In this study, 50 oncogenes and tumor suppressor genes were evaluated for mutations in a typical SRSCT using the next-generation DNA sequencing approach. An in-frame deletion of 30 nucleotides in the glycogen serine kinase-3 beta phosphorylation region of the beta-catenin gene (CTNNB1) was identified, and the finding was confirmed by Sanger sequencing. This deletion (c.68_97del) at the protein level would lead to a p.Ser23_Ser33delinsThr oncogenic-type mutation. Subsequent immunohistochemistry showed prominent nuclear accumulation of beta-catenin and cyclin D1 in tumor cells. Thus, mutational activation of the Wnt/beta-catenin pathway could be a crucial event in the molecular pathogenesis of SRSCT of the ovary. These findings may also assist in the diagnosis of this rare tumor.
C1 [Kopczynski, Janusz] Jan Kochanowski Univ Humanities & Sci, Dept Surg Pathol, Kielce, Poland.
   [Kowalik, Artur; Chlopek, Malgorzata] Jan Kochanowski Univ Humanities & Sci, Dept Mol Diagnost, Kielce, Poland.
   [Gozdz, Stanislaw] Jan Kochanowski Univ Humanities & Sci, Dept Chemotherapy, Holycross Canc Ctr, Kielce, Poland.
   [Gozdz, Stanislaw] Jan Kochanowski Univ Humanities & Sci, Fac Hlth Sci, Kielce, Poland.
   [Wang, Zeng-Feng; Lasota, Jerzy; Miettinen, Markku] NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room B1B47, Bethesda, MD 20892 USA.
RP Lasota, J (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room B1B47, Bethesda, MD 20892 USA.
EM jerzy.lasota@nih.gov
RI Kielce, SCO/O-6702-2016; Gozdz, Stanislaw/D-3300-2013
NR 31
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 1541-2016
EI 1533-4058
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD MAY-JUN
PY 2016
VL 24
IS 5
BP E28
EP E33
PG 6
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA DR0SN
UT WOS:000379617300001
PM 26509912
ER

PT J
AU Wolfe, F
   Fitzcharles, MA
   Goldenberg, DL
   Hauser, W
   Katz, RL
   Mease, PJ
   Russell, AS
   Russell, IJ
   Walitt, B
AF Wolfe, Frederick
   Fitzcharles, Mary-Ann
   Goldenberg, Don L.
   Haeuser, Winfried
   Katz, Robert L.
   Mease, Philip J.
   Russell, Anthony S.
   Russell, I. Jon
   Walitt, Brian
TI Comparison of Physician-Based and Patient-Based Criteria for the
   Diagnosis of Fibromyalgia
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID CONCORDANCE CORRELATION-COEFFICIENT; OF-RHEUMATOLOGY 1990; WOLFE ET-AL;
   EVALUATE REPRODUCIBILITY; RELIABILITY; CLASSIFICATION; AGREEMENT;
   ARTICLE
AB Objective. The American College of Rheumatology (ACR) 2010 preliminary fibromyalgia diagnostic criteria require symptom ascertainment by physicians. The 2011 survey or research modified ACR criteria use only patient self-report. We compared physician-based (MD) (2010) and patient-based (PT) (2011) criteria and criteria components to determine the degree of agreement between criteria methodology.
   Methods. We studied prospectively collected, previously unreported rheumatology practice data from 514 patients and 30 physicians in the ACR 2010 study. We evaluated the widespread pain index, polysymptomatic distress (PSD) scale, tender point count (TPC), and fibromyalgia diagnosis using 2010 and 2011 rules. Bland-Altman 95% limits of agreement (LOA), kappa statistic, Lin's concordance coefficient, and the area under the receiver operating curve (ROC) were used to measure agreement and discrimination.
   Results. MD and PT diagnostic agreement was substantial (83.4%, kappa=0.67). PSD scores differed slightly (12.3 MD, 12.8 PT; P=0.213). LOA for PSD were -8.5 and 7.7, with bias of -0.42. The TPC was strongly associated with both the MD (r=0.779) and PT PSD scales (r=0.702).
   Conclusion. There was good agreement in MD and PT fibromyalgia diagnosis and other measures among rheumatology patients. Low bias scores indicate consistent results for physician and patient measures, but large values for LOA indicate many widely discordant pairs. There is acceptable agreement in diagnosis and PSD for research, but insufficient agreement for clinical decisions and diagnosis. We suggest adjudication of symptom data by patients and physicians, as recommended by the 2010 ACR criteria.
C1 [Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS USA.
   [Wolfe, Frederick] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
   [Fitzcharles, Mary-Ann] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
   [Goldenberg, Don L.] Newton Wellesley Hosp, Newton, MA USA.
   [Goldenberg, Don L.] Tufts Univ, Sch Med, Newton, MA USA.
   [Haeuser, Winfried] Klinikum Saarbrucken, Munich, Germany.
   [Haeuser, Winfried] Tech Univ Munich, Munich, Germany.
   [Katz, Robert L.] Rush Med Coll, Chicago, IL 60612 USA.
   [Mease, Philip J.] Swedish Med Ctr, Seattle, WA USA.
   [Mease, Philip J.] Univ Washington, Seattle, WA 98195 USA.
   [Russell, Anthony S.] Univ Alberta, Edmonton, AB, Canada.
   [Russell, I. Jon] Fibromyalgia Res & Consulting, San Antonio, TX USA.
   [Walitt, Brian] NINR, NIH, Bethesda, MD 20892 USA.
RP Wolfe, F (reprint author), 1035 N Emporia,Suite 288, Wichita, KS 67214 USA.
EM fwolfe@arthritis-research.org
FU Department of Veterans Affairs; National Institute of Nursing Research,
   a division of the NIH; Pfizer; Eli Lilly; Theravance
FX Dr. I. J. Russell's work was partly supported by the Department of
   Veterans Affairs. Dr. Walitt's work was partly supported by the
   Intramural Research Program of the National Institute of Nursing
   Research, a division of the NIH.; Dr. Goldenberg is on the advisory
   board for Pfizer and has received consulting fees from Pfizer (less than
   $10,000). Dr. Hauser has received honoraria from Abbott Germany,
   Grunenthal, Janssen-Cilag, and Pfizer (less than $10,000 each). Dr.
   Mease has received consulting fees from Eli Lilly and Pfizer (more than
   $10,000 each). Dr. I. J. Russell has received consulting fees, speaking
   fees, and/or honoraria from Eli Lilly, Pfizer, and Theravance (more than
   $10,000 each).
NR 29
TC 2
Z9 2
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD MAY
PY 2016
VL 68
IS 5
BP 652
EP 659
DI 10.1002/acr.22742
PG 8
WC Rheumatology
SC Rheumatology
GA DQ9UC
UT WOS:000379553800011
PM 26414294
ER

PT J
AU Wasko, MC
   Dasgupta, A
   Sears, GI
   Fries, JF
   Ward, MM
AF Wasko, Mary Chester
   Dasgupta, Abhijit
   Sears, Genevieve Ilse
   Fries, James F.
   Ward, Michael M.
TI Prednisone Use and Risk of Mortality in Patients With Rheumatoid
   Arthritis: Moderation by Use of Disease-Modifying Antirheumatic Drugs
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID PROPENSITY SCORE; GLUCOCORTICOIDS; METHOTREXATE; ASSOCIATION; SURVIVAL;
   OUTCOMES; THERAPY
AB Objective. Medications for rheumatoid arthritis (RA) may affect survival. However, studies often include limited followup and do not account for selection bias in treatment allocation. Using a large longitudinal database, we examined the association between prednisone use and mortality in RA, and whether this risk was modified with concomitant disease-modifying antirheumatic drug (DMARD) use, after controlling for propensity for treatment with prednisone and individual DMARDs.
   Methods. In a prospective study of 5,626 patients with RA followed for up to 25 years, we determined the risk of death associated with prednisone use alone and combined treatment of prednisone with methotrexate (MTX) or sulfasalazine. We used the random forests method to generate propensity scores for prednisone use and each DMARD at study entry and during followup. Mortality risks were estimated using multivariate Cox models that included propensity scores.
   Results. During followup (median 4.97 years), 666 patients (11.8%) died. In a multivariate, propensity-adjusted model, prednisone use was associated with an increased risk of death (hazard ratio [HR] 2.83 [95% confidence interval (95% CI) 1.03-7.76]). However, there was a significant interaction between prednisone use and MTX use (P=0.03), so that risk was attenuated when patients were treated with both medications (HR 0.99 [95% CI 0.18-5.36]). However, combination treatment also weakened the protective association of MTX with mortality. Results were similar for sulfasalazine.
   Conclusion. Prednisone use was associated with a significantly increased risk of mortality in patients with RA. This association was mitigated by concomitant DMARD use, but combined treatment also negated the previously reported beneficial association of MTX with survival in RA.
C1 [Wasko, Mary Chester; Sears, Genevieve Ilse] Allegheny Hlth Network, Pittsburgh, PA USA.
   [Dasgupta, Abhijit; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Fries, James F.] Stanford Univ, Stanford, CA 94305 USA.
RP Wasko, MC (reprint author), Western Penn Hosp, Suite 2600,North Tower,4800 Friendship Ave, Pittsburgh, PA 15224 USA.
EM mcwasko@wpahs.org
FU National Institute of Arthritis and Musculoskeletal and Skin
   Diseases/NIH [AR-43584]
FX Supported by the Intramural Research Program, National Institute of
   Arthritis and Musculoskeletal and Skin Diseases/NIH (grant AR-43584).
NR 15
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD MAY
PY 2016
VL 68
IS 5
BP 706
EP 710
DI 10.1002/acr.22722
PG 5
WC Rheumatology
SC Rheumatology
GA DQ9UC
UT WOS:000379553800019
ER

PT J
AU Grenga, I
   Donahue, RN
   Lepone, LM
   Richards, J
   Schlom, J
AF Grenga, Italia
   Donahue, Renee N.
   Lepone, Lauren M.
   Richards, Jacob
   Schlom, Jeffrey
TI A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances
   antigen-specific T-cell responses
SO CLINICAL & TRANSLATIONAL IMMUNOLOGY
LA English
DT Article
ID CANCER-PATIENTS; PD-1/PD-L1 BLOCKADE; CD8-T-CELL MEMORY; CD4-T-CELL
   HELP; ACUTE INFECTION; PD-1 BLOCKADE; TUMOR-CELLS; ANTIBODY; MELANOMA;
   IMMUNOTHERAPY
AB Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being investigated for the treatment of infectious diseases and cancer, with the aim of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) is a fully human IgG1 MAb targeting programmed death-ligand 1 (PD-L1), which differs from other checkpoint-blocking antibodies in its ability to mediate antibody-dependent cell-mediated cytotoxicity. These studies were conducted to define whether avelumab could enhance the detection of antigen-specific immune response in in vitro assays. Peripheral blood mononuclear cells from 17 healthy donors were stimulated in vitro, with and without avelumab, with peptide pools encoding for cytomegalovirus, Epstein-Barr virus, influenza and tetanus toxin or the negative peptide control encoding for human leukocyte antigen. These studies show for the first time that the addition of avelumab to an antigen-specific IVS assay (a) increased the frequency of activated antigen-specific CD8(+) T lymphocytes, and did so to a greater extent than that seen with commercially available PD-L1-blocking antibodies, (b) reduced CD4(+) T-cell proliferation and (c) induced a switch in the production of Th2 to Th1 cytokines. Moreover, there was an inverse correlation between the enhancement of CD8(+) T-cell activation and reduction in CD4(+) T-cell proliferation induced by avelumab. These findings provide the rationale for the use of avelumab anti-PD-L1 in in vitro assays to monitor patient immune responses to immunotherapies.
C1 [Grenga, Italia; Donahue, Renee N.; Lepone, Lauren M.; Richards, Jacob; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
NR 45
TC 2
Z9 2
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2050-0068
J9 CLIN TRANSL IMMUNOL
JI Clin. Transl. Immunol.
PD MAY
PY 2016
VL 5
AR e83
DI 10.1038/cti.2016.27
PG 12
WC Immunology
SC Immunology
GA DQ6UN
UT WOS:000379340900003
PM 27350882
ER

PT J
AU Fletez-Brant, K
   Spidlen, J
   Brinkman, RR
   Roederer, M
   Chattopadhyay, PK
AF Fletez-Brant, Kipper
   Spidlen, Josef
   Brinkman, Ryan R.
   Roederer, Mario
   Chattopadhyay, Pratip K.
TI flowClean: Automated Identification and Removal of Fluorescence
   Anomalies in Flow Cytometry Data
SO CYTOMETRY PART A
LA English
DT Article
DE high throughput; quality control; flow cytometry; automated
ID BIOCONDUCTOR
AB Modern flow cytometry systems can be coupled to plate readers for high-throughput acquisition. These systems allow hundreds of samples to be analyzed in a single day. Quality control of the data remains challenging, however, and is further complicated when a large number of parameters is measured in an experiment. Our examination of 29,228 publicly available FCS files from laboratories worldwide indicates 13.7% have a fluorescence anomaly. In particular, fluorescence measurements for a sample over the collection time may not remain stable due to fluctuations in fluid dynamics; the impact of instabilities may differ between samples and among parameters. Therefore, we hypothesized that tracking cell populations (which represent a summary of all parameters) in centered log ratio space would provide a sensitive and consistent method of quality control. Here, we present flowClean, an algorithm to track subset frequency changes within a sample during acquisition, and flag time periods with fluorescence perturbations leading to the emergence of false populations. Aberrant time periods are reported as a new parameter and added to a revised data file, allowing users to easily review and exclude those events from further analysis. We apply this method to proof-of-concept datasets and also to a subset of data from a recent vaccine trial. The algorithm flags events that are suspicious by visual inspection, as well as those showing more subtle effects that might not be consistently flagged by investigators reviewing the data manually, and out-performs the current state-of-the-art. flowClean is available as an R package on Bioconductor, as a module on the free-to-use GenePattern web server, and as a plugin for FlowJo X. (C) 2016 International Society for Advancement of Cytometry
C1 [Fletez-Brant, Kipper] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
   [Fletez-Brant, Kipper] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
   [Fletez-Brant, Kipper; Roederer, Mario; Chattopadhyay, Pratip K.] NIAID, Vaccine Res Ctr, NIH, Baltimore, MD USA.
   [Spidlen, Josef; Brinkman, Ryan R.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada.
RP Chattopadhyay, PK (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5612, Bethesda, MD 20892 USA.
EM pchattop@mail.nih.gov
RI Brinkman, Ryan/B-1108-2008; 
OI Brinkman, Ryan/0000-0002-9765-2990; Chattopadhyay,
   Pratip/0000-0002-5457-9666
FU Scholars Program, International Society for the Advancement of
   Cytometry; NIH [NIH R01-EB008400]; NSERC
FX Grant sponsor: Scholars Program, International Society for the
   Advancement of Cytometry (to JS, PC); Grant sponsor: NIH; Grant number:
   NIH R01-EB008400; Grant sponsor: NSERC (to JS, RRB).
NR 13
TC 2
Z9 2
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD MAY
PY 2016
VL 89A
IS 5
BP 461
EP 471
DI 10.1002/cyto.a.22837
PG 11
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DR0NK
UT WOS:000379604000007
PM 26990501
ER

PT J
AU Fowler, NH
   Cheah, CY
   Gascoyne, RD
   Gribben, J
   Neelapu, SS
   Ghia, P
   Bollard, C
   Ansell, S
   Curran, M
   Wilson, WH
   O'Brien, S
   Grant, C
   Little, R
   Zenz, T
   Nastoupil, LJ
   Dunleavy, K
AF Fowler, Nathan H.
   Cheah, Chan Yoon
   Gascoyne, Randy D.
   Gribben, John
   Neelapu, Sattva S.
   Ghia, Paolo
   Bollard, Catherine
   Ansell, Stephen
   Curran, Michael
   Wilson, Wyndham H.
   O'Brien, Susan
   Grant, Cliona
   Little, Richard
   Zenz, Thorsten
   Nastoupil, Loretta J.
   Dunleavy, Kieron
TI Role of the tumor microenvironment in mature B-cell lymphoid
   malignancies
SO HAEMATOLOGICA
LA English
DT Review
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CLASSICAL HODGKIN-LYMPHOMA; CHIMERIC
   ANTIGEN RECEPTOR; REGULATORY T-CELLS; PHASE-II TRIAL; EXPRESS
   HIGH-LEVELS; DEATH LIGAND 1; FOLLICULAR LYMPHOMA; IN-VITRO;
   HELICOBACTER-PYLORI
AB The tumor microenvironment is the cellular and molecular environment in which the tumor exists and with which it continuously interacts. In B-cell lymphomas, this microenvironment is intriguing in that it plays critical roles in the regulation of tumor cell survival and proliferation, fostering immune escape as well as the development of treatment resistance. The purpose of this review is to summarize the proceedings of the Second Annual Summit on the Immune Microenvironment in Hematologic Malignancies that took place on September 11-12, 2014 in Dublin, Ireland. We provide a timely overview of the composition and biological relevance of the cellular and molecular microenvironment interface and discuss the role of interactions between the microenvironment and neoplastic cells in a variety of B-cell lymphomas. In addition, we focus on various novel therapeutic strategies that target the tumor microenvironment, including agents that modulate B-cell receptor pathways and immune-checkpoints, chimeric antigen receptor T cells and immunomodulatory agents.
C1 [Fowler, Nathan H.; Cheah, Chan Yoon; Neelapu, Sattva S.; Curran, Michael; Nastoupil, Loretta J.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX USA.
   [Cheah, Chan Yoon] Pathwest Lab Med WA, Dept Haematol, Perth, WA, Australia.
   [Cheah, Chan Yoon] Sir Charles Gairdner Hosp, Perth, WA, Australia.
   [Cheah, Chan Yoon] Univ Western Australia, Perth, WA, Australia.
   [Gascoyne, Randy D.] British Columbia Canc Res Ctr, Vancouver, BC, Canada.
   [Gribben, John] Barts Canc Inst, Dept Haematooncol, London, England.
   [Ghia, Paolo] Univ Vita Salute San Raffaele, Div Expt Oncol, IRCCS Ist Sci San Raffaele, Milan, Italy.
   [Ghia, Paolo] Osped San Raffaele, Dept Oncohematol, Milan, Italy.
   [Bollard, Catherine] Childrens Res Inst, Washington, DC USA.
   [Ansell, Stephen] Mayo Clin, Div Hematol, Rochester, MN USA.
   [Wilson, Wyndham H.; Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
   [O'Brien, Susan] Univ Calif Irvine, Irvine, CA USA.
   [Grant, Cliona] St James Hosp, Dublin, Ireland.
   [Little, Richard] NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
   [Zenz, Thorsten] Heidelberg Univ, Bergheimer Str 58, D-69115 Heidelberg, Germany.
RP Fowler, NH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX USA.
EM nfowler@mdanderson.org
RI Ghia, Paolo/K-7138-2016; 
OI Ghia, Paolo/0000-0003-3750-7342; Cheah, Chan Yoon/0000-0001-7988-1565
FU AbbVie Inc.; Acerta Pharma; Celgene Corporation; F. Hoffman-La Roche
   LTD; Infinity Pharmaceuticals, Inc.; Pharmacyclics, Inc.; TG
   Therapeutics, Inc.
FX This manuscript was developed, in part, based on discussions from the
   Second Annual Summit on the Immune Microenvironment in Hematologic
   Malignancies that took place on September 11-12, 2014, in Dublin,
   Ireland. The Second Annual Summit was sponsored by a grant from AbbVie
   Inc., Acerta Pharma, Celgene Corporation, F. Hoffman-La Roche LTD,
   Infinity Pharmaceuticals, Inc., Pharmacyclics, Inc., and TG
   Therapeutics, Inc. Project management support for this manuscript was
   provided by BioConnections, LLC.
NR 152
TC 2
Z9 2
U1 2
U2 5
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAY
PY 2016
VL 101
IS 5
BP 531
EP 540
DI 10.3324/haematol.2015.139493
PG 10
WC Hematology
SC Hematology
GA DQ7ND
UT WOS:000379393500018
PM 27132279
ER

PT J
AU Henriksen, S
   Cumming, BG
   Read, JCA
AF Henriksen, Sid
   Cumming, Bruce G.
   Read, Jenny C. A.
TI A Single Mechanism Can Account for Human Perception of Depth in Mixed
   Correlation Random Dot Stereograms
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID SIZE-DISPARITY CORRELATION; HORIZONTAL DISPARITY; BINOCULAR DISPARITY;
   CROSS-CORRELATION; MOTION DIRECTION; VISUAL-CORTEX; ENERGY-MODEL; V1
   NEURONS; STEREOPSIS; VISION
AB In order to extract retinal disparity from a visual scene, the brain must match corresponding points in the left and right retinae. This computationally demanding task is known as the stereo correspondence problem. The initial stage of the solution to the correspondence problem is generally thought to consist of a correlation-based computation. However, recent work by Doi et al suggests that human observers can see depth in a class of stimuli where the mean binocular correlation is 0 (half-matched random dot stereograms). Half-matched random dot stereograms are made up of an equal number of correlated and anticorrelated dots, and the binocular energy model-a well-known model of V1 binocular complex cell-sfails to signal disparity here. This has led to the proposition that a second, match-based computation must be extracting disparity in these stimuli. Here we show that a straightforward modification to the binocular energy model-adding a point output nonlinearity-is by itself sufficient to produce cells that are disparity-tuned to half-matched random dot stereograms. We then show that a simple decision model using this single mechanism can reproduce psychometric functions generated by human observers, including reduced performance to large disparities and rapidly updating dot patterns. The model makes predictions about how performance should change with dot size in half-matched stereograms and temporal alternation in correlation, which we test in human observers. We conclude that a single correlation-based computation, based directly on already-known properties of V1 neurons, can account for the literature on mixed correlation random dot stereograms.
C1 [Henriksen, Sid; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
   [Henriksen, Sid; Read, Jenny C. A.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
RP Henriksen, S (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.; Henriksen, S (reprint author), Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
EM sid.henriksen@gmail.com
OI Read, Jenny/0000-0002-9029-5185
FU Wellcome Trust/NIH [100931/Z/13/Z]
FX SH was funded by a joint Wellcome Trust/NIH studentship (ref
   100931/Z/13/Z; http://www.wellcome.ac.uk). The funders had no role in
   the study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 49
TC 1
Z9 1
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004906
DI 10.1371/journal.pcbi.1004906
PG 21
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100017
PM 27196696
ER

PT J
AU Neuwald, AF
   Altschul, SF
AF Neuwald, Andrew F.
   Altschul, Stephen F.
TI Bayesian Top-Down Protein Sequence Alignment with Inferred
   Position-Specific Gap Penalties
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID GIBBS SAMPLING STRATEGIES; DIRICHLET MIXTURES; CLUSTAL OMEGA;
   OPTIMIZATION; DIALIGN; MODELS; MAFFT; PERFORMANCE; NUCLEOTIDE; DATABASE
AB We describe a Bayesian Markov chain Monte Carlo (MCMC) sampler for protein multiple sequence alignment (MSA) that, as implemented in the program GISMO and applied to large numbers of diverse sequences, is more accurate than the popular MSA programs MUSCLE, MAFFT, Clustal-Omega and Kalign. Features of GISMO central to its performance are: (i) It employs a "top-down" strategy with a favorable asymptotic time complexity that first identifies regions generally shared by all the input sequences, and then realigns closely related subgroups in tandem. (ii) It infers position-specific gap penalties that favor insertions or deletions (indels) within each sequence at alignment positions in which indels are invoked in other sequences. This favors the placement of insertions between conserved blocks, which can be understood as making up the proteins' structural core. (iii) It uses a Bayesian statistical measure of alignment quality based on the minimum description length principle and on Dirichlet mixture priors. Consequently, GISMO aligns sequence regions only when statistically justified. This is unlike methods based on the ad hoc, but widely used, sum-of-the-pairs scoring system, which will align random sequences. (iv) It defines a system for exploring alignment space that provides natural avenues for further experimentation through the development of new sampling strategies for more efficiently escaping from suboptimal traps. GISMO's superior performance is illustrated using 408 protein sets containing, on average, 235 sequences. These sets correspond to NCBI Conserved Domain Database alignments, which have been manually curated in the light of available crystal structures, and thus provide a means to assess alignment accuracy. GISMO fills a different niche than other MSA programs, namely identifying and aligning a conserved domain present within a large, diverse set of full length sequences. The GISMO program is available at http://gismo.igs.umaryland.edu/.
C1 [Neuwald, Andrew F.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
   [Neuwald, Andrew F.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
   [Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Neuwald, AF (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.; Neuwald, AF (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
EM aneuwald@som.umaryland.edu
FU NIH Intramural Research Program
FX SFA was funded by the NIH Intramural Research Program. AFN received no
   specific funding for this work. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 36
TC 2
Z9 2
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004936
DI 10.1371/journal.pcbi.1004936
PG 21
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100032
PM 27192614
ER

PT J
AU Sheng, ZZ
   Schramm, CA
   Connors, M
   Morris, L
   Mascola, JR
   Kwong, PD
   Shapiro, L
AF Sheng, Zizhang
   Schramm, Chaim A.
   Connors, Mark
   Morris, Lynn
   Mascola, John R.
   Kwong, Peter D.
   Shapiro, Lawrence
TI Effects of Darwinian Selection and Mutability on Rate of Broadly
   Neutralizing Antibody Evolution during HIV-1 Infection
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MEMORY B-CELLS; GERMINAL CENTER; SOMATIC HYPERMUTATION; AFFINITY
   MATURATION; DETECTING SELECTION; IMMUNE-RESPONSE; MUTATION; CENTERS;
   SEQUENCES; VIRUS
AB Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2-fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages.
C1 [Sheng, Zizhang; Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
   [Sheng, Zizhang; Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Syst Biol, New York, NY USA.
   [Connors, Mark] NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Morris, Lynn] Natl Inst Communicable Dis, Natl Hlth Lab Serv, Ctr HIV & STIs, Johannesburg, South Africa.
   [Morris, Lynn] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.
   [Morris, Lynn] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Congella, South Africa.
   [Mascola, John R.; Kwong, Peter D.; Shapiro, Lawrence] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Shapiro, L (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.; Shapiro, L (reprint author), Columbia Univ, Dept Syst Biol, New York, NY USA.; Shapiro, L (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shapiro@convex.hhmi.columbia.edu
FU HIVRAD NIH grant [P01-AI104722]; Intramural Research Program of the
   Vaccine Research Center, National Institute of Allergy and Infectious
   Diseases; National Human Genome Research Institute, National Institutes
   of Health; National Institute of Allergy and Infectious Diseases
   (NIAID), National Institutes for Health (NIH), U.S. Department of Health
   and Human Services
FX Support for this work was provided by a HIVRAD NIH grant P01-AI104722 to
   LS and the Intramural Research Program of the Vaccine Research Center,
   National Institute of Allergy and Infectious Diseases and the National
   Human Genome Research Institute, National Institutes of Health. Studies
   on the CAPRISA participant CAP256 were supported by the National
   Institute of Allergy and Infectious Diseases (NIAID), National
   Institutes for Health (NIH), U.S. Department of Health and Human
   Services. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 52
TC 4
Z9 4
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004940
DI 10.1371/journal.pcbi.1004940
PG 26
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100034
PM 27191167
ER

PT J
AU Tian, PF
   Best, RB
AF Tian, Pengfei
   Best, Robert B.
TI Structural Determinants of Misfolding in Multidomain Proteins
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID CLAMP SPECTROSCOPY MONITORS; KINETIC PARTITIONING MECHANISM; SINGLE
   PROTEIN; FOLDING KINETICS; MOLECULAR SIMULATION; ENERGY LANDSCAPES;
   TRANSITION-STATES; CRYSTAL-STRUCTURE; CONTACT ORDER; PDZ DOMAINS
AB Recent single molecule experiments, using either atomic force microscopy (AFM) or Forster resonance energy transfer (FRET) have shown that multidomain proteins containing tandem repeats may form stable misfolded structures. Topology-based simulation models have been used successfully to generate models for these structures with domain-swapped features, fully consistent with the available data. However, it is also known that some multidomain protein folds exhibit no evidence for misfolding, even when adjacent domains have identical sequences. Here we pose the question: what factors influence the propensity of a given fold to undergo domain-swapped misfolding? Using a coarse-grained simulation model, we can reproduce the known propensities of multidomain proteins to form domain-swapped misfolds, where data is available. Contrary to what might be naively expected based on the previously described misfolding mechanism, we find that the extent of misfolding is not determined by the relative folding rates or barrier heights for forming the domains present in the initial intermediates leading to folded or misfolded structures. Instead, it appears that the propensity is more closely related to the relative stability of the domains present in folded and misfolded intermediates. We show that these findings can be rationalized if the folded and misfolded domains are part of the same folding funnel, with commitment to one structure or the other occurring only at a relatively late stage of folding. Nonetheless, the results are still fully consistent with the kinetic models previously proposed to explain misfolding, with a specific interpretation of the observed rate coefficients. Finally, we investigate the relation between interdomain linker length and misfolding, and propose a simple alchemical model to predict the propensity for domain-swapped misfolding of multidomain proteins.
C1 [Tian, Pengfei; 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
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases of the National Institutes of Health
FX This project was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases of the
   National Institutes of Health. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 77
TC 0
Z9 0
U1 8
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004933
DI 10.1371/journal.pcbi.1004933
PG 28
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100030
PM 27163669
ER

PT J
AU Vattikuti, S
   Thangaraj, P
   Xie, HW
   Gotts, SJ
   Martin, A
   Chow, CC
AF Vattikuti, Shashaank
   Thangaraj, Phyllis
   Xie, Hua W.
   Gotts, Stephen J.
   Martin, Alex
   Chow, Carson C.
TI Canonical Cortical Circuit Model Explains Rivalry, Intermittent Rivalry,
   and Rivalry Memory
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID NEURONAL COMPETITION MODELS; BINOCULAR-RIVALRY; WORKING-MEMORY;
   PERCEPTUAL BISTABILITY; REVERSIBLE FIGURES; NETWORK MODEL; DYNAMICS;
   MECHANISMS; MOTION; CORTEX
AB It has been shown that the same canonical cortical circuit model with mutual inhibition and a fatigue process can explain perceptual rivalry and other neurophysiological responses to a range of static stimuli. However, it has been proposed that this model cannot explain responses to dynamic inputs such as found in intermittent rivalry and rivalry memory, where maintenance of a percept when the stimulus is absent is required. This challenges the universality of the basic canonical cortical circuit. Here, we show that by including an overlooked realistic small nonspecific background neural activity, the same basic model can reproduce intermittent rivalry and rivalry memory without compromising static rivalry and other cortical phenomena. The background activity induces a mutual-inhibition mechanism for short-term memory, which is robust to noise and where fine-tuning of recurrent excitation or inclusion of sub-threshold currents or synaptic facilitation is unnecessary. We prove existence conditions for the mechanism and show that it can explain experimental results from the quartet apparent motion illusion, which is a prototypical intermittent rivalry stimulus.
C1 [Vattikuti, Shashaank; Thangaraj, Phyllis; Xie, Hua W.; Chow, Carson C.] NIDDK, Math Biol Sect, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
   [Gotts, Stephen J.; Martin, Alex] NIMH, Cognit Neuropsychol Sect, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Vattikuti, S (reprint author), NIDDK, Math Biol Sect, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM vattikutis@mail.nih.gov; carsonc@mail.nih.gov
OI Thangaraj, Phyllis/0000-0003-3968-1563
FU NIH; NIDDK; NIMH
FX This work was supported by the Intramural Research Program of the NIH,
   NIDDK and NIMH. The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 54
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004903
DI 10.1371/journal.pcbi.1004903
PG 22
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100015
PM 27138214
ER

PT J
AU Welch, L
   Brooksbank, C
   Schwartz, R
   Morgan, SL
   Gaeta, B
   Kilpatrick, AM
   Mietchen, D
   Moore, BL
   Mulder, N
   Pauley, M
   Pearson, W
   Radivojac, P
   Rosenberg, N
   Rosenwald, A
   Rustici, G
   Warnow, T
AF Welch, Lonnie
   Brooksbank, Cath
   Schwartz, Russell
   Morgan, Sarah L.
   Gaeta, Bruno
   Kilpatrick, Alastair M.
   Mietchen, Daniel
   Moore, Benjamin L.
   Mulder, Nicola
   Pauley, Mark
   Pearson, William
   Radivojac, Predrag
   Rosenberg, Naomi
   Rosenwald, Anne
   Rustici, Gabriella
   Warnow, Tandy
TI Applying, Evaluating and Refining Bioinformatics Core Competencies (An
   Update from the Curriculum Task Force of ISCB's Education Committee)
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
ID FRAMEWORK; AFRICA
C1 [Welch, Lonnie] Ohio Univ, Sch Elect Engn & Comp Sci, Athens, OH 45701 USA.
   [Brooksbank, Cath; Morgan, Sarah L.] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge, England.
   [Schwartz, Russell] Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA.
   [Schwartz, Russell] Carnegie Mellon Univ, Computat Biol Dept, Pittsburgh, PA 15213 USA.
   [Gaeta, Bruno] UNSW, Sch Comp Sci & Engn, Sydney, NSW, Australia.
   [Kilpatrick, Alastair M.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [Mietchen, Daniel] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Moore, Benjamin L.] Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
   [Mulder, Nicola] Univ Cape Town, Dept Integrat Biomed Sci, IDM, Computat Biol Grp, Cape Town, South Africa.
   [Pauley, Mark] Univ Nebraska, Sch Interdisciplinary Informat, Omaha, NE 68182 USA.
   [Pearson, William] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
   [Radivojac, Predrag] Indiana Univ, Sch Informat & Comp, Bloomington, IN USA.
   [Rosenberg, Naomi] Tufts Univ, Sch Med, Boston, MA 02111 USA.
   [Rosenwald, Anne] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
   [Rustici, Gabriella] Univ Cambridge, Cambridge Syst Biol Ctr, Sch Biol Sci, Cambridge, England.
   [Warnow, Tandy] Univ Illinois, Dept Comp Sci, 1304 W Springfield Ave, Urbana, IL 61801 USA.
   [Warnow, Tandy] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
RP Welch, L (reprint author), Ohio Univ, Sch Elect Engn & Comp Sci, Athens, OH 45701 USA.
EM welch@ohio.edu
RI Schwartz, Russell/A-1998-2016; 
OI Schwartz, Russell/0000-0002-4970-2252; Brooksbank,
   Catherine/0000-0001-9395-7001; Rustici, Gabriella/0000-0003-3085-1271;
   Pearson, William/0000-0002-0727-3680; Kilpatrick,
   Alastair/0000-0002-4795-8799; Mietchen, Daniel/0000-0001-9488-1870
NR 11
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2016
VL 12
IS 5
AR e1004943
DI 10.1371/journal.pcbi.1004943
PG 4
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DQ6XA
UT WOS:000379348100036
PM 27175996
ER

PT J
AU Kleinstreuer, NC
AF Kleinstreuer, N. C.
TI Of Mice, Math, and Modeling
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Kleinstreuer, N. C.] NIEHS, NTP Interagency Ctr Evaluat Alternat Toxicol Meth, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2016
VL 106
IS 5
SI SI
MA L2
BP 349
EP 349
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DQ2HT
UT WOS:000379024100003
ER

PT J
AU Maull, E
AF Maull, E.
TI An Expert-Driven Approach to Identifying Reference Developmental
   Toxicants
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Maull, E.] NIEHS, NICEATM, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2016
VL 106
IS 5
SI SI
MA W3
BP 378
EP 378
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DQ2HT
UT WOS:000379024100060
ER

PT J
AU Kleinstreuer, NC
AF Kleinstreuer, N. C.
TI Testing in Alternative Assays with a Range of Reference Developmental
   Toxicants
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Kleinstreuer, N. C.] NIEHS, NTP, NICEATM, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2016
VL 106
IS 5
SI SI
MA W4
BP 379
EP 379
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DQ2HT
UT WOS:000379024100061
ER

PT J
AU Catlin, NR
   Foster, P
   Mylchreest, E
   Miller, L
   Cunny, HC
   Mcintyre, BS
AF Catlin, N. R.
   Foster, P.
   Mylchreest, E.
   Miller, L.
   Cunny, H. C.
   Mcintyre, B. S.
TI Teratogenicity of the Herbal Supplement Vinpocetine in Harlan-Sprague
   Dawley Rats
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Catlin, N. R.; Foster, P.; Cunny, H. C.; Mcintyre, B. S.] NIEHS, Div Natl Toxicol Program, Durham, NC USA.
   [Mylchreest, E.; Miller, L.] Southern Res Inst, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2016
VL 106
IS 5
SI SI
MA 3
BP 386
EP 386
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DQ2HT
UT WOS:000379024100072
ER

PT J
AU Tucker, DK
   Fenton, SE
   Bouknight, SA
AF Tucker, D. K.
   Fenton, S. E.
   Bouknight, S. A.
TI Increased Susceptibility to Mammary Carcinogenesis following a Prenatal
   Exposure to BPA Analogs
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Tucker, D. K.] Univ N Carolina, Chapel Hill, NC USA.
   [Tucker, D. K.; Fenton, S. E.] NIEHS, NTP Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Bouknight, S. A.] Pathol Associates Inc, Charles River Labs, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2016
VL 106
IS 5
SI SI
MA P25
BP 416
EP 416
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DQ2HT
UT WOS:000379024100129
ER

PT J
AU Powers, SW
   Hershey, AD
   Coffey, CS
   Chamberlin, LA
   Ecklund, DJD
   Sullivan, SM
   Klingner, EA
   Yankey, JW
   Kashikar-Zuck, S
   Korbee, LL
   Costigan, ML
   Riss, HH
   Porter, LL
AF Powers, Scott W.
   Hershey, Andrew D.
   Coffey, Christopher S.
   Chamberlin, Leigh A.
   Ecklund, Dixie J. D.
   Sullivan, Stephanie M.
   Klingner, Elizabeth A.
   Yankey, Jon W.
   Kashikar-Zuck, Susmita
   Korbee, Leslie L.
   Costigan, Michele L.
   Riss, Holly H.
   Porter, Linda L.
TI The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report
   on Baseline Characteristics of Participants
SO HEADACHE
LA English
DT Article
DE randomized clinical trial; pediatrics; headache characterization;
   headache days; preventive medication
ID POPULATION; CHILDREN; HEADACHE; AMITRIPTYLINE; DIAGNOSIS
AB Objective.-To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).
   Methods.-Children and adolescents (age 8-17 years old, inclusive) diagnosed with migraine with or without aura, having headaches at least four times per month were enrolled from 2012 through 2014. The trial involved a baseline period (minimum of 28 days) during which prospective diaries were completed and demographics and headache features obtained.
   Results.-A total of 488 children and adolescents (mean age 14.0 +/- 2.4 years) agreed to participate in the trial, with 361 randomized and 127 not randomized. Randomized subjects had a 5.5 +/- 3.1 year history of headaches, with 15.1 +/- 7.1 headache days per month (based upon retrospective report at screening visit). Prospective diaries reported 11.5 +/- 6.1 headache days per 28 day baseline. Across this 28 day period, reported headache days per week were stable (about 3 headache days per week). Recording of individual headache features by diary (n = 4136 headache days) showed characteristics consistent with migraine (mean duration 10.5 +/- 8.1 hours, mean severity 6.0 +/- 2.1, 60% throbbing, 55% with activity worsening headaches, 55% with photophobia, and 47% with phonophobia).
   Conclusions.-Baseline data from the CHAMP Study suggested that the randomized sample was representative of the real world population of children and adolescents that present for treatment of migraine. Headaches in children and adolescents recorded during a 28 day prospective baseline period in this multi-site comparative effectiveness study did not change over the course of the baseline period, even though a clear diagnosis, recommendation for effective acute treatment, and standardized education about healthy habits occurred prior to the diary collection period.
C1 [Powers, Scott W.; Hershey, Andrew D.; Kashikar-Zuck, Susmita] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA.
   [Powers, Scott W.; Chamberlin, Leigh A.; Sullivan, Stephanie M.; Kashikar-Zuck, Susmita] Cincinnati Childrens Hosp Med Ctr, Div Behav Med & Clin Psychol, Cincinnati, OH 45229 USA.
   [Hershey, Andrew D.] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH 45229 USA.
   [Coffey, Christopher S.; Ecklund, Dixie J. D.; Klingner, Elizabeth A.; Yankey, Jon W.; Costigan, Michele L.; Riss, Holly H.] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
   [Korbee, Leslie L.] Cincinnati Childrens Hosp Med Ctr, Off Clin & Translat Res, Cincinnati, OH 45229 USA.
   [Porter, Linda L.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Powers, SW (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 7039, Cincinnati, OH 45229 USA.
FU National Institute of Neurological Disorders and Stroke; Eunice Kennedy
   Shriver National Institute of Child Health and Human Development of the
   National Institutes of Health [U01NS076788, U01NS077108]; National
   Center for Advancing Translational Sciences of the National Institute of
   Health [UL1RR026314]; Cincinnati Children's Research Foundation
FX Funding for the Childhood and Adolescent Migraine Prevention (CHAMP)
   Study was provided by the National Institute of Neurological Disorders
   and Stroke and the Eunice Kennedy Shriver National Institute of Child
   Health and Human Development of the National Institutes of Health (Grant
   #U01NS076788; PIs: Scott W. Powers, PhD, ABPP, FAHS and Andrew D.
   Hershey, MD, PhD, FAHS and Grant #U01NS077108; PI: Christopher S.
   Coffey, PhD), National Center for Advancing Translational Sciences of
   the National Institute of Health (Grant #UL1RR026314; PIs: James Heubi,
   MD, Joel Tsevat, MD); and Cincinnati Children's Research Foundation.
NR 16
TC 3
Z9 3
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-8748
EI 1526-4610
J9 HEADACHE
JI Headache
PD MAY
PY 2016
VL 56
IS 5
BP 859
EP 870
DI 10.1111/head.12810
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA DQ4EP
UT WOS:000379157000005
ER

PT J
AU Yong, KJ
   Milenic, DE
   Baidoo, KE
   Brechbiel, MW
AF Yong, Kwon Joong
   Milenic, Diane E.
   Baidoo, Kwamena E.
   Brechbiel, Martin W.
TI Mechanisms of Cell Killing Response from Low Linear Energy Transfer
   (LET) Radiation Originating from Lu-177 Radioimmunotherapy Targeting
   Disseminated Intraperitoneal Tumor Xenografts
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE Lu-177-Radioimmunotherapy (RIT); DNA double strand breaks; DNA repair;
   apoptosis; micrometastatic disease
ID DISSEMINATED PERITONEAL DISEASE; ANTIBODY-BASED THERAPY; DNA-DAMAGE
   REPAIR; INDUCED APOPTOSIS; STRAND BREAKS; CYCLE ARREST; CANCER;
   PB-212-TCMC-TRASTUZUMAB; MODEL; IRRADIATION
AB Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy beta(-)-emissions (500 keV(max); 130 keV(ave)) along with gamma-emission for imaging makes Lu-177 (T-1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with alpha-particle radiation. RIT with Lu-177-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with Lu-177-trastuzumab comparatively to animals treated with a non-specific control, Lu-177-HuIgG, and then to prior published results obtained using Pb-212-trastuzumab, an alpha-particle RIT agent. Lu-177-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein Pb-212-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. Lu-177-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of beta(-)- and alpha-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving alpha- and beta(-)-particle RIT for the management of intraperitoneal disease.
C1 [Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr MSC-1002, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr MSC-1002, Bethesda, MD 20892 USA.
EM halroya@gmail.com; milenic.dm71q@nih.gov; kwamena.baidoo@nih.gov;
   martinwb@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research, National
   Institutes of Health, 10 Center Drive MSC-1002 Bethesda, MD, USA
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research, National
   Institutes of Health, 10 Center Drive MSC-1002, Bethesda, MD 20892, USA
NR 45
TC 1
Z9 1
U1 1
U2 2
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD MAY
PY 2016
VL 17
IS 5
AR 736
DI 10.3390/ijms17050736
PG 18
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA DP9BJ
UT WOS:000378791400126
ER

PT J
AU Chan, JD
   McCorvy, JD
   Acharya, S
   Johns, ME
   Day, TA
   Roth, BL
   Marchant, JS
AF Chan, John D.
   McCorvy, John D.
   Acharya, Sreemoyee
   Johns, Malcolm E.
   Day, Timothy A.
   Roth, Bryan L.
   Marchant, Jonathan S.
TI A Miniaturized Screen of a Schistosoma mansoni Serotonergic G
   Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective
   Inhibitors
SO PLOS PATHOGENS
LA English
DT Article
ID RISPERIDONE; INACTIVATION; ANTAGONISTS; PLANARIAN; GENOMICS; POTENT;
   DRUGS; CAMP
AB Schistosomiasis is a tropical parasitic disease afflicting similar to 200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevant targets ('target selection') and pharmacologically profiling them is challenging. Remarkably, even though over a quarter of current human therapeutics target rhodopsin-like G protein coupled receptors (GPCRs), no library screen of a flatworm GPCR has yet been reported. Here, we have pharmacologically profiled a schistosome serotonergic GPCR (Sm. 5HTR) implicated as a downstream modulator of PZQ efficacy, in a miniaturized screening assay compatible with high content screening. This approach employs a split luciferase based biosensor sensitive to cellular cAMP levels that resolves the proximal kinetics of GPCR modulation in intact cells. Data evidence a divergent pharmacological signature between the parasitic serotonergic receptor and the closest human GPCR homolog (Hs. 5HTR7), supporting the feasibility of optimizing parasitic selective pharmacophores. New ligands, and chemical series, with potency and selectivity for Sm. 5HTR over Hs. 5HTR7 are identified in vitro and validated for in vivo efficacy against schistosomules and adult worms. Sm. 5HTR also displayed a property resembling irreversible inactivation, a phenomenon discovered at Hs. 5HTR7, which enhances the appeal of this abundantly expressed parasite GPCR as a target for anthelmintic ligand design. Overall, these data underscore the feasibility of profiling flatworm GPCRs in a high throughput screening format competent to resolve different classes of GPCR modulators. Further, these data underscore the promise of Sm. 5HTR as a chemotherapeutically vulnerable node for development of next generation anthelmintics.
C1 [Chan, John D.; Johns, Malcolm E.; Marchant, Jonathan S.] Univ Minnesota, Dept Pharmacol, 3-249 Millard Hall, Minneapolis, MN 55455 USA.
   [McCorvy, John D.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA.
   [Acharya, Sreemoyee; Day, Timothy A.] Iowa State Univ, Dept Biomed Sci, Ames, IA USA.
   [Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Eshelmann Sch Pharm, Chapel Hill, NC USA.
   [Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH PDSP, Chapel Hill, NC USA.
   [Marchant, Jonathan S.] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA.
RP Marchant, JS (reprint author), Univ Minnesota, Dept Pharmacol, 3-249 Millard Hall, Minneapolis, MN 55455 USA.; Marchant, JS (reprint author), Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA.
EM march029@umn.edu
FU NIH [GM088790]; University of Minnesota Medical School Innovation
   Research Grant; NIH (PDSP) [R01MH61887]; Stem Cell Biology Training
   Grant [T32GM113846]
FX Work in the Marchant lab was supported by the NIH (GM088790) and a
   University of Minnesota Medical School Innovation Research Grant. Work
   in the Roth Lab was supported by NIH (PDSP and R01MH61887 to JDM and
   BLR). JDC was supported by Stem Cell Biology Training Grant
   (T32GM113846). The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 2
Z9 2
U1 4
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2016
VL 12
IS 5
AR e1005651
DI 10.1371/journal.ppat.1005651
PG 26
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DQ6VV
UT WOS:000379344500039
PM 27187180
ER

PT J
AU Delviks-Frankenberry, KA
   Nikolaitchik, OA
   Burdick, RC
   Gorelick, RJ
   Keele, BF
   Hu, WS
   Pathak, VK
AF Delviks-Frankenberry, Krista A.
   Nikolaitchik, Olga A.
   Burdick, Ryan C.
   Gorelick, Robert J.
   Keele, Brandon F.
   Hu, Wei-Shau
   Pathak, Vinay K.
TI Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1
   Recombination and Genetic Variation
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-POLYMERASE-II; RETROVIRAL SHUTTLE
   VECTOR; SINGLE REPLICATION CYCLE; BLOOD MONONUCLEAR-CELLS; IN-VIVO;
   REVERSE-TRANSCRIPTASE; VIF PROTEIN; MUTATION-RATE; RELATIVE CONTRIBUTION
AB Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethalmutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 x 10(-5) mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 x 10(-21) and 1 x 10(-11), respectively) and its contribution to viralmutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic variation is substantially lower than that from mutations during error-prone replication.
C1 [Delviks-Frankenberry, Krista A.; Burdick, Ryan C.; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
   [Nikolaitchik, Olga A.; Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
   [Gorelick, Robert J.; Keele, Brandon F.] Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res Inc, Frederick, MD USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.; Hu, WS (reprint author), NCI, Viral Recombinat Sect, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
EM wei-shau.hu@nih.gov; vinay.pathak@nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
   Center for Cancer Research; Intramural AIDS Targeted Antiviral Program;
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX This work was supported in part by the Intramural Research Program of
   the NIH, National Cancer Institute, Center for Cancer Research, and by
   Intramural AIDS Targeted Antiviral Program grant funding (to VKP and to
   WSH). This project has been funded in whole or in part with Federal
   funds from the National Cancer Institute, National Institutes of Health,
   under Contract No. HHSN261200800001E. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 103
TC 3
Z9 3
U1 3
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2016
VL 12
IS 5
AR e1005646
DI 10.1371/journal.ppat.1005646
PG 26
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DQ6VV
UT WOS:000379344500036
PM 27186986
ER

PT J
AU Sakai, S
   Kauffman, KD
   Sallin, MA
   Sharpe, AH
   Young, HA
   Ganusov, VV
   Barber, DL
AF Sakai, Shunsuke
   Kauffman, Keith D.
   Sallin, Michelle A.
   Sharpe, Arlene H.
   Young, Howard A.
   Ganusov, Vitaly V.
   Barber, Daniel L.
TI CD4 T Cell-Derived IFN-gamma Plays a Minimal Role in Control of
   Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively
   Repressed by PD-1 to Prevent Lethal Disease
SO PLOS PATHOGENS
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; IMMUNE-RESPONSE; CD8(+) T;
   IN-VIVO; PROTECTION; VACCINE; MICE; PATHOGENESIS; ANTIGEN
AB IFN-gamma-producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-gamma contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-gamma production by CD4 T cells is desirable in Mtb infection. Here we show that IFN-gamma accounts for only similar to 30% of CD4 T cell-dependent cumulative bacterial control in the lungs over the first six weeks of infection, but >80% of control in the spleen. Moreover, increasing the IFN-gamma-producing capacity of CD4 T cells by similar to 2 fold exacerbates lung infection and leads to the early death of the host, despite enhancing control in the spleen. In addition, we show that the inhibitory receptor PD-1 facilitates host resistance to Mtb by preventing the detrimental over-production of IFN-gamma by CD4 T cells. Specifically, PD-1 suppressed the parenchymal accumulation of and pathogenic IFN-gamma production by the CXCR3(+)KLRG1(-)CX3CR1(-) subset of lung-homing CD4 T cells that otherwise mediates control of Mtb infection. Therefore, the primary role for T cell-derived IFN-gamma in Mtb infection is at extra-pulmonary sites, and the host-protective subset of CD4 T cells requires negative regulation of IFN-gamma production by PD-1 to prevent lethal immune-mediated pathology.
C1 [Sakai, Shunsuke; Kauffman, Keith D.; Sallin, Michelle A.; Barber, Daniel L.] NIAID, T Lymphocyte Biol Unit, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Sharpe, Arlene H.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Sharpe, Arlene H.] Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA.
   [Sharpe, Arlene H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
   [Young, Howard A.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Ganusov, Vitaly V.] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA.
RP Barber, DL (reprint author), NIAID, T Lymphocyte Biol Unit, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM barberd@niaid.nih.gov
FU Intramural Research Program of NIAID, NIH; American Heart Foundation;
   Kyoto University Foundation; NIH-JSPS intramural fellowship
FX This work was supported by the Intramural Research Program of NIAID, NIH
   awarded to DLB, the American Heart Foundation grant to VVG, the Kyoto
   University Foundation fellowship and the NIH-JSPS intramural fellowship
   to SS. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 73
TC 7
Z9 7
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2016
VL 12
IS 5
AR e1005667
DI 10.1371/journal.ppat.1005667
PG 22
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DQ6VV
UT WOS:000379344500049
PM 27244558
ER

PT J
AU Tanofsky-Kraff, M
   Crosby, RD
   Vannucci, A
   Kozlosky, M
   Shomaker, LB
   Brady, SM
   Sbrocco, T
   Pickworth, CK
   Stephens, M
   Young, JF
   Olsen, CH
   Kelly, NR
   Radin, R
   Cassidy, O
   Wilfley, DE
   Reynolds, JC
   Yanovski, JA
AF Tanofsky-Kraff, Marian
   Crosby, Ross D.
   Vannucci, Anna
   Kozlosky, Merel
   Shomaker, Lauren B.
   Brady, Sheila M.
   Sbrocco, Tracy
   Pickworth, Courtney K.
   Stephens, Mark
   Young, Jami F.
   Olsen, Cara H.
   Kelly, Nichole R.
   Radin, Rachel
   Cassidy, Omni
   Wilfley, Denise E.
   Reynolds, James C.
   Yanovski, Jack A.
TI Effect of Adapted Interpersonal Psychotherapy versus Health Education on
   Mood and Eating in the Laboratory Among Adolescent Girls with Loss of
   Control Eating
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE loss of control eating; interpersonal psychotherapy; highly-palatable
   food intake; negative affective states; adolescence
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; EXCESS
   WEIGHT-GAIN; PSYCHOLOGICAL TREATMENTS; OVERWEIGHT CHILDREN; HIGH-RISK;
   BODY-FAT; DISORDER; OBESITY; MAINTENANCE
AB Objective: Interpersonal psychotherapy (IPT) is aimed at improving negative affect that is purported to contribute to the development and maintenance of loss-of-control (LOC) eating. Although youth who report LOC over eating tend to consume more snack-foods than those without LOC, it is unknown if IPT impacts objective energy intake.
   Methods: To test if IPT improves mood and eating in the laboratory, we examined a sample of 88 girls with LOC eating who were randomized to either IPT (n=46) or a standard-of-care health education (HE) group program. At baseline, and 6-month (follow-up 1) and 1year (follow-up 2) following the initiation of the groups, girls consumed lunch from a multi-item meal with an instruction designed to model a LOC episode. Girls also reported mood state immediately before each meal.
   Results: Girls in IPT experienced no significant changes in pre-meal state depressive affect, while girls in HE experienced a non-significant improvement by follow-up 1 and then returned to baseline by follow-up 2 (p < 0.04). We found no significant group difference for changes in total intake relative to girls' daily energy needs (p's >= 0.25). However, IPT reduced, while HE increased, the percentage of daily energy needs consumed from snack-foods by follow-up 2 (p=0.04). Within-groups, HE increased their snack food intake from follow-up 1 to follow-up 2 (p=0.01).
   Conclusions: In adolescent girls with LOC, IPT did not change total intake at the test meal and was associated with reduced snack-food intake. Data are required to determine if IPT effectively prevents excess weight gain in the longer-term. (C) 2015 Wiley Periodicals, Inc.
C1 [Tanofsky-Kraff, Marian; Vannucci, Anna; Sbrocco, Tracy; Radin, Rachel; Cassidy, Omni] Uniformed Serv Univ Hlth Sci, Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
   [Tanofsky-Kraff, Marian; Vannucci, Anna; Shomaker, Lauren B.; Brady, Sheila M.; Pickworth, Courtney K.; Kelly, Nichole R.; Radin, Rachel; Cassidy, Omni; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, NIH, 10 Ctr Dr,1103, Bethesda, MD USA.
   [Crosby, Ross D.] Neuropsychiat Res Inst, 120 South 8th St,Box 1415, Fargo, ND USA.
   [Crosby, Ross D.] Univ N Dakota, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, 1919 Elm St North, Fargo, ND USA.
   [Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, 10 Ctr Dr,MSC 1078, Bethesda, MD USA.
   [Shomaker, Lauren B.; Kelly, Nichole R.] Colorado State Univ, Dept Human Dev & Family Studies, 410 Pitkin St,Campus Delivery 1570, Ft Collins, CO 80523 USA.
   [Stephens, Mark] Uniformed Serv Univ Hlth Sci, Dept Family Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
   [Young, Jami F.] Rutgers State Univ, Appl & Profess Psychol, 152 Frelinghuysen Rd, Piscataway, NJ USA.
   [Olsen, Cara H.] Uniformed Serv Univ Hlth Sci, Preventat Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
   [Wilfley, Denise E.] Washington Univ, Sch Med, Dept Psychiat, 660 South Euclid,Campus Box 8134, St Louis, MO 63110 USA.
   [Reynolds, James C.] NIH, Div Nucl Med, Radiol & Imaging Sci Dept, Hatfield Clin Res Ctr, 10 Ctr Dr,MSC 1103, Bethesda, MD USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
FU NIDDK [1R01DK080906]; USUHS [R072IC]; NICHD Intramural Research Program
   [Z1A-HD-00641]
FX Supported by 1R01DK080906 from NIDDK (to M.T.K.), R072IC from USUHS (to
   M.T.K.) and Z1A-HD-00641 from NICHD Intramural Research Program (to
   J.A.Y.).
NR 40
TC 0
Z9 0
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
EI 1098-108X
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD MAY
PY 2016
VL 49
IS 5
BP 490
EP 498
DI 10.1002/eat.22496
PG 9
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA DP6ZJ
UT WOS:000378648400006
PM 26790360
ER

PT J
AU Travison, TG
   O'Donnell, CJ
   Bhasin, S
   Massaro, JM
   Hoffmann, U
   Vasan, RS
   D'Agostino, RB
   Basaria, S
AF Travison, Thomas G.
   O'Donnell, Christopher J.
   Bhasin, Shalender
   Massaro, Joseph M.
   Hoffmann, Udo
   Vasan, Ramachandran S.
   D'Agostino, Ralph B., Sr.
   Basaria, Shehzad
TI Circulating Sex Steroids and Vascular Calcification in
   Community-Dwelling Men: The Framingham Heart Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CORONARY-ARTERY CALCIUM; CARDIOVASCULAR RISK-FACTORS; TANDEM
   MASS-SPECTROMETRY; ABDOMINAL AORTIC CALCIFICATION; HORMONE-BINDING
   GLOBULIN; SERUM TESTOSTERONE; DISEASE EVENTS; ELDERLY-MEN;
   ATHEROSCLEROSIS MESA; COMPUTED-TOMOGRAPHY
AB Context: The relationship between sex steroids and atherosclerosis is poorly understood.
   Objective: To describe the association of serum total T (TT), calculated free T (cFT), estrone (El), estradiol (E2), and SHBG to vascular calcification in adult men.
   Design: Observational study (Framingham Heart Study). Analyses are cross-sectional. TT, El, and E2 were measured by liquid chromatography-tandem mass spectrometry, and SHBG by immunofluorometric assay. Estimates of association were obtained by Tobit regression, which acknowledges the influence of floor effects on outcomes.
   Setting: General community.
   Participants: A total of 1654 community-dwelling men from the Offspring and Third Generation cohorts of the Framingham Heart Study.
   Main Outcome Measures: Coronary artery calcification (CAC), abdominal aortic calcification, and thoracic aortic calcification were measured by computed tomography.
   Results: Mean (standard deviation [SD]) age was 49 (10) years. Mean (SD) TT, cFT, and SHBG were: 616 (224) ng/dL, 111 (45) pg/mL, and 46 (23) nmol/L, respectively. Mean (SD) E2 and El were 28 (10) and 39 (14) pg/mL. Vascular calcification at all sites was negatively associated with TT and cFT and positively associated with E2 and El. A 100-ng/dL between-subjects increase in TT was associated with a mean (95% confidence interval) age-adjusted difference in CAC of 23% (-41%, 4%) (P =.02). After model adjustment for other cardiovascular risk factors, the estimated associations between T and vascular calcification scores were statistically nonsignificant.
   Conclusions: Decreased circulating T and E2 levels are associated with an age-adjusted increase in CAC, but these associations appear to express relationships either attributable to or mediated by established cardiovascular risk factors.
C1 [Travison, Thomas G.] Hebrew SeniorLife Inst Aging Res, Roslindale, MA 02131 USA.
   [Travison, Thomas G.; Bhasin, Shalender; Basaria, Shehzad] Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, 75 Francis St, Boston, MA 02115 USA.
   [Travison, Thomas G.; O'Donnell, Christopher J.; Bhasin, Shalender; Hoffmann, Udo; Basaria, Shehzad] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [O'Donnell, Christopher J.; Massaro, Joseph M.; Vasan, Ramachandran S.; D'Agostino, Ralph B., Sr.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
   [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
   [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
   [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
   [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
RP Travison, TG (reprint author), Hebrew SeniorLife Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM tgt@hsl.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Institutes of Health [1RO1AG31206, 5R01DK092938]; Boston Claude
   D. Pepper Older Americans Independence Center from the National
   Institute on Aging [5P30AG031679]; CDC Foundation; National Heart, Lung,
   and Blood Institute [N01-HC-25195]
FX This work was supported primarily by National Institutes of Health
   Grants 1RO1AG31206 and 5R01DK092938 (to S.Bh. and R.S.V.). Additional
   support was provided by the Boston Claude D. Pepper Older Americans
   Independence Center Grant 5P30AG031679 from the National Institute on
   Aging and by a grant from the CDC Foundation. The Framingham Heart Study
   is supported by the National Heart, Lung, and Blood Institute Contract
   N01-HC-25195.
NR 54
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAY
PY 2016
VL 101
IS 5
BP 2160
EP 2167
DI 10.1210/jc.2015-4299
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DP9MG
UT WOS:000378819700033
PM 26930184
ER

PT J
AU Witter, JP
AF Witter, James P.
TI Introduction: PROMIS a first look across diseases
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Witter, James P.] NIAMS, Rheumat Dis Clin Program, Div Skin & Rheumat Dis, NIH,DHHS, One Democracy Plaza,6701 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
RP Witter, JP (reprint author), NIAMS, Rheumat Dis Clin Program, Div Skin & Rheumat Dis, NIH,DHHS, One Democracy Plaza,6701 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
EM witterj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD MAY
PY 2016
VL 73
BP 87
EP 88
DI 10.1016/j.jclinepi.2016.02.014
PG 2
WC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA DP4KM
UT WOS:000378464800019
PM 26931294
ER

PT J
AU Cook, KF
   Jensen, SE
   Schalet, BD
   Beaumont, JL
   Arntmand, D
   Czajkowski, S
   Dewalt, DA
   Fries, JF
   Pilkonis, PA
   Reeve, BB
   Stone, AA
   Weinfurt, KP
   Cella, D
AF Cook, Karon F.
   Jensen, Sally E.
   Schalet, Benjamin D.
   Beaumont, Jennifer L.
   Arntmand, Dagmar
   Czajkowski, Susan
   Dewalt, Darren A.
   Fries, James F.
   Pilkonis, Paul A.
   Reeve, Bryce B.
   Stone, Arthur A.
   Weinfurt, Kevin P.
   Cella, David
TI PROMIS measures of pain, fatigue, negative affect, physical function,
   and social function demonstrated clinical validity across a range of
   chronic conditions
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Responsiveness; Validity; Psychometrics; Outcomes research;
   Patient-reported outcomes
ID QUALITY-OF-LIFE; PATIENT-REPORTED OUTCOMES; MINIMALLY IMPORTANT
   DIFFERENCES; INFORMATION-SYSTEM PROMIS; CANCER-PATIENTS; RESPONSIVENESS;
   EXACERBATION
AB Objective: To present an overview of a series of studies in which the clinical validity of the National Institutes of Health's Patient Reported Outcome Measurement Information System (NIH; PROMIS) measures was evaluated, by domain, across six clinical populations.
   Study Design and Setting: Approximately 1,500 individuals at baseline and 1,300 at follow-up completed PROMIS measures. The analyses reported in this issue were conducted post hoc, pooling data across six previous studies, and accommodating the different designs of the six, within-condition, parent studies. Changes in T-scores, standardized response means, and effect sizes were calculated in each study. When a parent study design allowed, known groups validity was calculated using a linear mixed model.
   Results: The results provide substantial support for the clinical validity of nine PROMIS measures in a range of chronic conditions.
   Conclusion: The cross-condition focus of the analyses provided a unique and multifaceted perspective on how PROMIS measures function in "real-world" clinical settings and provides external anchors that can support comparative effectiveness research. The current body of clinical validity evidence for the nine PROMIS measures indicates the success of NIH PROMIS in developing measures that are effective across a range of chronic conditions. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Cook, Karon F.; Jensen, Sally E.; Schalet, Benjamin D.; Beaumont, Jennifer L.; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 633 N St Clair,19th Floor, Chicago, IL 60611 USA.
   [Jensen, Sally E.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Div Organ Transplant, 251 E Huron,Galter 3-150, Chicago, IL 60611 USA.
   [Arntmand, Dagmar] Univ Washington, Sch Med, Dept Rehabil Med, 4907 25th Ave NE, Seattle, WA 98105 USA.
   [Czajkowski, Susan] NHLBI, Bldg 31,Room 5A52,31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA.
   [Dewalt, Darren A.] Univ N Carolina, Sch Med, Div Gen Internal Med, CB 7590,725 Martin Luther King Jr Blvd, Chapel Hill, NC 27599 USA.
   [Dewalt, Darren A.] Univ N Carolina, Sch Med, Cecil G Sheps Ctr Hlth Serv Res, CB 7590,725 Martin Luther King Jr Blvd, Chapel Hill, NC 27599 USA.
   [Fries, James F.] Stanford Univ, Sch Med, Dept Med, 300 Pasteur Dr H3580, Stanford, CA 94305 USA.
   [Pilkonis, Paul A.] Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA.
   [Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, CB 7590,725 Martin Luther King Jr Blvd, Chapel Hill, NC 27599 USA.
   [Stone, Arthur A.] Univ So Calif, 635 Downey Way, Los Angeles, CA USA.
   [Weinfurt, Kevin P.] Duke Univ, Sch Med, Dept Psychiat, 2400 Pratt St, Durham, NC 27705 USA.
RP Cook, KF (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 633 N St Clair,19th Floor, Chicago, IL 60611 USA.
EM karon.cook@northwestern.edu
FU National Institutes of Health (NIH) [U54AR057951, U01AR052177,
   R01CA60068, U54AR057943, U54AR057926, U01AR057948, U01AR052170,
   U01AR057954, U01AR052171, U01AR052181, U01AR057956, U01AR052158,
   U01AR057929, U01AR057936, U01AR052155, U01AR057971, U01AR057940,
   U01AR057967, U01AR052186]
FX PROMIS was funded with cooperative agreements from the National
   Institutes of Health (NIH) Common Fund Initiative (Northwestern
   University, PI: David Cella, PhD, U54AR057951, U01AR052177, R01CA60068;
   Northwestern University, PI: Richard C. Gershon, PhD, U54AR057943;
   American Institutes for Research, PI: Susan (San) D. Keller, PhD,
   U54AR057926; State University of New York, Stony Brook, PIs: Joan E.
   Broderick, PhD, and Arthur A. Stone, PhD, U01AR057948, U01AR052170;
   University of Washington, Seattle, PIs: Heidi M. Crane, MD, MPH, Paul K.
   Crane, MD, MPH, and Donald L. Patrick, PhD, U01AR057954; University of
   Washington, Seattle, PI: Dagmar Amtmann, PhD, U01AR052171; University of
   North Carolina, Chapel Hill, PI: Harry A. Guess, MD, PhD (deceased),
   Darren A. DeWalt, MD, MPH, U01AR052181; Children's Hospital of
   Philadelphia, PI: Christopher B. Forrest, MD, PhD, U01AR057956; Stanford
   University, PI: James F. Fries, MD, U01AR052158; Boston University, PIs:
   Alan Jette, PT, PhD, Stephen M. Haley, PhD (deceased), and David Scott
   Tulsky, PhD (University of Michigan, Ann Arbor), U01AR057929; University
   of California, Los Angeles, PIs: Dinesh Khanna, MD (University of
   Michigan, Ann Arbor), and Brennan Spiegel, MD, MSHS, U01AR057936;
   University of Pittsburgh, PI: Paul A. Pilkonis, PhD, U01AR052155;
   Georgetown University, PIs: Carol. M. Moinpour, PhD (Fred Hutchinson
   Cancer Research Center, Seattle), and Arnold L. Potosky, PhD,
   U01AR057971; Children's Hospital Medical Center, Cincinnati, PE Esi M.
   Morgan DeWitt, MD, MSCE, U01AR057940; University of Maryland, Baltimore,
   PT: Lisa M. Shulman, MD, U01AR057967; and Duke University, PI: Kevin P.
   Weinfurt, PhD, U01AR052186).
NR 38
TC 4
Z9 4
U1 2
U2 2
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 MAY
PY 2016
VL 73
BP 89
EP 102
DI 10.1016/j.jclinepi.2015.08.038
PG 14
WC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA DP4KM
UT WOS:000378464800020
PM 26952842
ER

PT J
AU Schalet, BD
   Pilkonis, PA
   Yu, L
   Dodds, N
   Johnston, KL
   Yount, S
   Riley, W
   Cella, D
AF Schalet, Benjamin D.
   Pilkonis, Paul A.
   Yu, Lan
   Dodds, Nathan
   Johnston, Kelly L.
   Yount, Susan
   Riley, William
   Cella, David
TI Clinical validity of PROMIS Depression, Anxiety, and Anger across
   diverse clinical samples
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE PROMS; Depression; Anxiety; Anger; Chronic conditions; Item bank
ID MINIMALLY IMPORTANT DIFFERENCES; OBSTRUCTIVE PULMONARY-DISEASE;
   INFORMATION-SYSTEM PROMIS(R); QUALITY-OF-LIFE; EMOTIONAL DISTRESS;
   CANCER-PATIENTS; OLDER-ADULTS; DISORDERS; INSTRUMENTS; SYMPTOMS
AB Objectives: The purpose of this study was to evaluate the responsiveness to change of the PROMIS negative affect measures (depression, anxiety, and anger) using longitudinal data collected in six chronic health conditions.
   Study Design and Setting: Individuals with major depressive disorder (MDD), back pain, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and cancer completed PROMIS negative affect instruments as computerized adaptive test or as fixed-length short form at baseline and a clinically relevant follow-up interval. Participants also completed global ratings of health. Linear mixed effects models and standardized response means (SRM) were estimated at baseline and follow-up.
   Results: A total of 903 individuals participated (back pain, n = 218; cancer, n = 304; CHF, n = 60; COPD, n = 125; MDD, n = 196). All three negative affect instruments improved significantly for treatments of depression and pain. Depression improved for CHF patients (anxiety and anger not administered), whereas anxiety improved significantly in COPD groups (stable and exacerbation). Response to treatment was not assessed in cancer. Subgroups of patients reporting better or worse health showed a corresponding positive or negative average SRM for negative affect across samples.
   Conclusion: This study provides evidence that the PROMIS negative affect scores are sensitive to change in intervention studies in which negative affect is expected to change. These results inform the estimation of meaningful change and enable comparative effectiveness research. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Schalet, Benjamin D.; Yount, Susan; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
   [Pilkonis, Paul A.; Yu, Lan; Dodds, Nathan; Johnston, Kelly L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
   [Yu, Lan] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
   [Riley, William] NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA.
RP Schalet, BD (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
EM b-schalet@northwestem.edu
FU National Institutes of Health Common Fund Initiative [U54AR057951,
   U01AR052177, R01CA60068, U54AR057943, U54AR057926, U01AR057948,
   U01AR052170, U01AR057954, U01AR052171, U01AR052181, U01AR057956,
   U01AR052158, U01AR057929, U01AR057936, U01AR052155, U01AR057971,
   U01AR057940, U01AR057967, U01AR052186]
FX PROMIS was funded with cooperative agreements from the National
   Institutes of Health Common Fund Initiative (Northwestern University,
   PI: D.C., U54AR057951, U01AR052177, R01CA60068; Northwestern University,
   PI: Richard C. Gershon, PhD, U54AR057943; American Institutes for
   Research, PI: Susan (San) D. Keller, PhD, U54AR057926; State University
   of New York, Stony Brook, PIs: Joan E. Broderick, PhD and Arthur A.
   Stone, PhD, U01AR057948, U01AR052170; University of Washington, Seattle,
   PIs: Heidi M. Crane, MD, MPH, Paul K. Crane, MD, MPH, and Donald L.
   Patrick, PhD, U01AR057954; University of Washington, Seattle, PI: Dagmar
   Amtmann, PhD, U01AR052171; University of North Carolina, Chapel Hill,
   PI: Harry A. Guess, MD, PhD (deceased), Darren A. DeWalt, MD, MPH,
   U01AR052181; Children's Hospital of Philadelphia, PI: Christopher B.
   Forrest, MD, PhD, U01AR057956; Stanford University, PI: James F. Fries,
   MD, U01AR052158; Boston University, PIs: Alan Jette, PT, PhD, Stephen M.
   Haley, PhD (deceased), and David Scott Talsky, PhD (University of
   Michigan, Ann Arbor), U01AR057929; University of California, Los
   Angeles, PIs: Dinesh Khanna, MD (University of Michigan, Ann Arbor) and
   Brennan Spiegel, MD, MSHS, U01AR057936; University of Pittsburgh, PI:
   Paul A. Pilkonis, PhD, U01AR052155; Georgetown University, PIs: Carol.
   M. Moinpour, PhD (Fred Hutchinson Cancer Research Center, Seattle) and
   Arnold L. Potosky, PhD, U01AR057971; Children's Hospital Medical Center,
   Cincinnati, PI: Esi M. Morgan DeWitt, MD, MSCE, U01AR057940; University
   of Maryland, Baltimore, PI: Lisa M. Shulman, MD, U01AR057967; and Duke
   University, PI: Kevin P. Weinfurt, PhD, U01AR052186). NIH Science
   Officers on this project have included Deborah Ader, PhD, Vanessa Ameen,
   MD (deceased), Susan Czajkowski, PhD, Basil Eldadah, MD, PhD, Lawrence
   Fine, MD, DrPH, Lawrence Fox, MD, PhD, Lynne Haverkos, MD, MPH, Thomas
   Hilton, PhD, Laura Lee Johnson, PhD, Michael Kozak, PhD, Peter Lyster,
   PhD, Donald Mattison, MD, Claudia Moy, PhD, Louis Quatrano, PhD, Bryce
   Reeve, PhD, William Riley, PhD, Peter Scheidt, MD, Ashley Wilder Smith,
   PhD, MPH, Susana Serrate-Sztein, MD, William Phillip Tonkins, DrPH,
   Ellen Werner, PhD, Tisha Wiley, PhD, and James Witter, MD, PhD. The
   contents of this article use data developed under PROMIS. These contents
   do not necessarily represent an endorsement by the US Federal Government
   or PROMIS. See www.nihpromis.org for additional information on the
   PROMIS initiative.
NR 36
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Z9 2
U1 3
U2 3
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 MAY
PY 2016
VL 73
BP 119
EP 127
DI 10.1016/j.jclinepi.2015.08.036
PG 9
WC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA DP4KM
UT WOS:000378464800023
PM 26931289
ER

PT J
AU Li, J
   Chang, YC
   Wu, CH
   Liu, J
   Kwon-Chung, KJ
   Huang, SH
   Shimada, H
   Fante, R
   Fu, XW
   Jong, A
AF Li, Jingbo
   Chang, Yun C.
   Wu, Chun-Hua
   Liu, Jennifer
   Kwon-Chung, Kyung J.
   Huang, Sheng-He
   Shimada, Hiro
   Fante, Rob
   Fu, Xiaowei
   Jong, Ambrose
TI The 14-3-3 Gene Function of Cryptococcus neoformans Is Required for its
   Growth and Virulence
SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
LA English
DT Article
DE Cryptococcus neoformans; 14-3-3; microvesicles; blood-brain barrier;
   brain invasion
ID MICROVASCULAR ENDOTHELIAL-CELLS; BLOOD-BRAIN-BARRIER; PROTEIN-KINASE-C;
   YEAST SACCHAROMYCES-CEREVISIAE; ADRENAL CHROMAFFIN CELLS;
   CENTRAL-NERVOUS-SYSTEM; FISSION YEAST; 14-3-3-PROTEINS; INVASION;
   INFECTION
AB Cryptococcus neoformans is a life-threatening pathogenic yeast that causes devastating meningoencephalitis. The mechanism of cryptococcal brain invasion is largely unknown, and recent studies suggest that its extracellular microvesicles may be involved in the invasion process. The 14-3-3 protein is abundant in the extracellular microvesicles of C. neoformans, and the 14-3-3-GFP fusion has been used as the microvesicle's marker. However, the physiological role of 14-3-3 has not been explored. In this report, we have found that C. neoformans contains a single 14-3-3 gene that apparently is an essential gene. To explore the functions of 14-3-3, we substituted the promoter region of the 14-3-3 with the copper-controllable promoter CTR4. The CTR4 regulatory strain showed an enlarged cell size, drastic changes in morphology, and a decrease in the thickness of the capsule under copper-enriched conditions. Furthermore, the mutant cells produced a lower amount of total proteins in their extracellular microvesicles and reduced adhesion to human brain microvascular endothelial cells in vitro. Proteomic analyses of the protein components under 14-3-3-overexpressed and -suppressed conditions revealed that the 14-3-3 function(s) might be associated with the microvesicle biogenesis. Our results support that 14-3-3 has diverse pertinent roles in both physiology and pathogenesis in C. neoformans. Its gene functions are closely relevant to the pathogenesis of this fungus.
C1 [Li, Jingbo; Wu, Chun-Hua; Liu, Jennifer; Jong, Ambrose] Childrens Hosp Los Angeles, Saban Res Inst, Div Hematol Oncol, Los Angeles, CA 90027 USA.
   [Huang, Sheng-He] Childrens Hosp Los Angeles, Saban Res Inst, Div Infect Dis, Los Angeles, CA 90027 USA.
   [Shimada, Hiro; Fante, Rob; Fu, Xiaowei] Childrens Hosp Los Angeles, Dept Pathol, Saban Res Inst, Los Angeles, CA 90027 USA.
   [Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Jong, A (reprint author), Childrens Hosp Los Angeles, Saban Res Inst, Div Hematol Oncol, Los Angeles, CA 90027 USA.
EM ajong@chla.usc.edu
FU Public Health Service grants [R01-NS047599, R21-NS083967]
FX This project was financially supported by Public Health Service grants
   R01-NS047599 (A.J.) and R21-NS083967 (S.H.H.). We also thank Dr. A.
   Casadevall for kindly providing us with the anti-GXM monoclonal antibody
   (18b7).
NR 42
TC 0
Z9 0
U1 1
U2 4
PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
PI SEOUL
PA KOREA SCI TECHNOL CENTER #507,  635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL
   135-703, SOUTH KOREA
SN 1017-7825
EI 1738-8872
J9 J MICROBIOL BIOTECHN
JI J. Microbiol. Biotechnol.
PD MAY
PY 2016
VL 26
IS 5
BP 918
EP 927
DI 10.4014/jmb.1508.08051
PG 10
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA DP8QA
UT WOS:000378761500013
PM 26437944
ER

PT J
AU Binukumar, BK
   Pant, HC
AF Binukumar, B. K.
   Pant, Harish C.
TI TFP5/TP5 peptide provides neuroprotection in the MPTP model of
   Parkinson's disease
SO NEURAL REGENERATION RESEARCH
LA English
DT Review
DE cyclin-dependent kinase 5; Parkinson's disease; neurodegeneration;
   therapeutic target; TP5 TFP5/TP5 peptide; MPTP
ID CYCLIN-DEPENDENT KINASE-5; NIGROSTRIATAL DOPAMINERGIC-NEURONS;
   AMYOTROPHIC-LATERAL-SCLEROSIS; CDK5 ACTIVATOR P35; PROTEIN-KINASE; LEWY
   BODIES; TAU HYPERPHOSPHORYLATION; CDC2-LIKE KINASE; OXIDATIVE STRESS;
   ALPHA-SYNUCLEIN
AB Cyclin-dependent kinase 5 (Cdk5) is a member of the serine-threonine kinase family of cyclin-dependent kinases. Cdk5 is critical to normal mammalian nervous system development and plays important regulatory roles in multiple cellular functions. Recent evidence indicates that Cdk5 is inappropriately activated in several neurodegenerative conditions, including Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. During neurotoxicity, p35 is cleaved to form p25. Binding of p25 with Cdk5 leads deregulation of Cdk5 resulting in number of neurodegenerative pathologies. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Here we show that inhibition of p25/Cdk5 hyperactivation through TFP5/TP5, truncated 24-aa peptide derived from the Cdk5 activator p35 rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show inhibition of Cdk5/p25-hyperactivation by TFP5/TP5 peptide, which identifies Cdk5/p25 as a potential therapeutic target to reduce neurodegeneration in PD.
C1 [Binukumar, B. K.; Pant, Harish C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Pant, HC (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM panth@ninds.nih.gov
NR 40
TC 1
Z9 1
U1 2
U2 10
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
   INDIA
SN 1673-5374
EI 1876-7958
J9 NEURAL REGEN RES
JI Neural Regen. Res.
PD MAY
PY 2016
VL 11
IS 5
BP 698
EP 701
DI 10.4103/1673-5374.182681
PG 4
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA DP5LF
UT WOS:000378537700002
PM 27335538
ER

PT J
AU Klein, MM
   Treister, R
   Raij, T
   Pascual-Leone, A
   Park, L
   Nurmikko, T
   Lenz, F
   Lefaucheur, JP
   Lang, M
   Hallett, M
   Fox, M
   Costello, A
   Carr, DB
   Ayache, SS
   Oaklander, AL
AF Klein, Max M.
   Treister, Roi
   Raij, Tommi
   Pascual-Leone, Alvaro
   Park, Lawrence
   Nurmikko, Turo
   Lenz, Fred
   Lefaucheur, Jean-Pascal
   Lang, Magdalena
   Hallett, Mark
   Fox, Michael
   Costello, Ann
   Carr, Daniel B.
   Ayache, Samar S.
   Oaklander, Anne Louise
TI Repetitive transcranial magnetic stimulation for pain: is it too early
   to standardise repetitive transcranial magnetic stimulation protocols?
   Reply
SO PAIN
LA English
DT Letter
C1 [Klein, Max M.; Treister, Roi; Lang, Magdalena; Fox, Michael; Oaklander, Anne Louise] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA.
   [Raij, Tommi; Fox, Michael] Northwestern Univ, Feinberg Sch Med, Phys Med & Rehabil, Chicago, IL 60611 USA.
   [Pascual-Leone, Alvaro; Fox, Michael] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02115 USA.
   [Park, Lawrence] NIMH, US NIH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
   [Nurmikko, Turo] Walton Ctr NHS Fdn Trust, Pain Res Inst, Neurosci Res Ctr, Liverpool, Merseyside, England.
   [Lenz, Fred] Johns Hopkins Med Inst, Dept Neurosurg, Baltimore, MD 21205 USA.
   [Lefaucheur, Jean-Pascal; Ayache, Samar S.] Univ Paris Est Creteil, Hop Henri Mondor, Fac Med Creteil, Serv Physiol Explorat Fonct,EA 4391, Creteil, France.
   [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Costello, Ann] US FDA, Div Neurol & Phys Med Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Bethesda, MD 20014 USA.
   [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Anesthesiol, Boston, MA 02111 USA.
   [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
   [Carr, Daniel B.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
   [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA.
RP Klein, MM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA.
EM mklein@mgh.harvard.edu
NR 1
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 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD MAY
PY 2016
VL 157
IS 5
BP 1175
EP 1176
DI 10.1097/j.pain.0000000000000504
PG 3
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA DQ0GA
UT WOS:000378875600027
PM 27081841
ER

PT J
AU Panch, SR
   Yau, YY
   Fitzhugh, CD
   Hsieh, MM
   Tisdale, JF
   Leitman, SF
AF Panch, Sandhya R.
   Yau, Yu Ying
   Fitzhugh, Courtney D.
   Hsieh, Matthew M.
   Tisdale, John F.
   Leitman, Susan F.
TI Hematopoietic progenitor cell mobilization is more robust in healthy
   African American compared to Caucasian donors and is not affected by the
   presence of sickle cell trait
SO TRANSFUSION
LA English
DT Article
ID COLONY-STIMULATING FACTOR; BLOOD STEM-CELL; FACTOR G-CSF;
   ETHNIC-DIFFERENCES; HEMOGLOBIN LEVELS; UNRELATED DONORS; BONE-MARROW;
   NEUTROPENIA; TRANSPLANTATION; POPULATION
AB BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF)-stimulated hematopoietic progenitor cells (HPCs) collected by apheresis have become the predominant graft source for HPC transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, body mass index [BMI]) and baseline hematologic counts affect HPC mobilization, leading to variability in CD34+ apheresis yields. Racial differences in HPC mobilization are less well characterized.
   STUDY DESIGN AND METHODS: We retrospectively analyzed data from 1096 consecutive G-CSF-stimulated leukapheresis procedures in healthy allogeneic African American (AA) or Caucasian donors.
   RESULTS: In a multivariate analysis, after adjusting for age, sex, BMI, baseline platelet and mononuclear cell counts, and daily G-CSF dose, peak CD34+ cell mobilization was significantly higher among AAs (n=215) than Caucasians (n=881; 123 +/- 87 x 10(6) cells/L vs. 75 +/- 47 x 10(6) cells/L; p < 0.0001). A ceiling effect was observed with increasing G-CSF dose (10 mu g/kg/day vs. 16 mu g/kg/day) in AAs (123 +/- 88 x 10(6) cells/L vs. 123 +/- 87 x 10(6) cells/L) but not in Caucasians (74 +/- 46 x 10(6) cells/L vs. 93 +/- 53 x 10(6) cells/L; p < 0.001). In AA donors, the presence of sickle cell trait (SCT; n=41) did not affect CD341 mobilization (peak CD34+ 123 +/- 91 x 10(6) cells/L vs. 107 +/- 72 x 10(6) cells/L, HbAS vs. HbAA; p=0.34). Adverse events were minimal and similar across race.
   CONCLUSIONS: AAs demonstrated significantly better CD34 mobilization responses to G-CSF than Caucasians. This was independent of other demographic and hematologic variables. Studying race-associated pharmacogenomics in relation to G-CSF may improve dosing strategies. Adverse event profile and CD34 mobilization were similar in AA donors with and without SCT. Our findings suggest that it would be safe to include healthy AA donors with SCT in unrelated donor registries.
C1 [Panch, Sandhya R.; Fitzhugh, Courtney D.; Hsieh, Matthew M.; Tisdale, John F.] NHLBI, Hematol Transfus Med, Bldg 10, Bethesda, MD 20892 USA.
   [Yau, Yu Ying; Leitman, Susan F.] NIDDK, Dept Transfus Med, Clin Ctr, NIH, Bethesda, MD 20892 USA.
   [Fitzhugh, Courtney D.; Hsieh, Matthew M.; Tisdale, John F.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Leitman, SF (reprint author), NIH, Bldg 10,Room 1N-248, Bethesda, MD 20892 USA.
EM sleitman@nih.gov
FU NHLBI; NIDDK; Clinical Center, NIH
FX This work was supported by the intramural research programs of the
   NHLBI, NIDDK and the Clinical Center, NIH.
NR 30
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAY
PY 2016
VL 56
IS 5
BP 1058
EP 1065
DI 10.1111/trf.13551
PG 8
WC Hematology
SC Hematology
GA DP5RS
UT WOS:000378555700011
PM 27167356
ER

PT J
AU Bernier, M
   Wahl, D
   Ali, A
   Allard, J
   Faulkner, S
   Wnorowski, A
   Sanghvi, M
   Moaddel, R
   Alfaras, I
   Mattison, JA
   Tarantini, S
   Tucsek, Z
   Ungvari, Z
   Csiszar, A
   Pearson, KJ
   de Cabo, R
AF Bernier, Michel
   Wahl, Devin
   Ali, Ahmed
   Allard, Joanne
   Faulkner, Shakeela
   Wnorowski, Artur
   Sanghvi, Mitesh
   Moaddel, Ruin
   Alfaras, Irene
   Mattison, Julie A.
   Tarantini, Stefano
   Tucsek, Zsuzsanna
   Ungvari, Zoltan
   Csiszar, Anna
   Pearson, Kevin J.
   de Cabo, Rafael
TI Resveratrol supplementation confers neuroprotection in cortical brain
   tissue of nonhuman primates fed a high-fat/sucrose diet
SO AGING-US
LA English
DT Article
DE Rhesus monkeys; cDNA microarray; inflammation; endothelial nitric oxide
   synthase; brain vasculature
ID HIGH-FAT DIET; BODY-MASS INDEX; NF-KAPPA-B; ALZHEIMER-DISEASE;
   HYDROGEN-SULFIDE; INFLAMMATORY RESPONSE; MICROGLIAL ACTIVATION;
   COGNITIVE IMPAIRMENT; HUNTINGTONS-DISEASE; MEMORY PERFORMANCE
AB Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-kappa B activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress.
C1 [Bernier, Michel; Wahl, Devin; Ali, Ahmed; Allard, Joanne; Faulkner, Shakeela; Alfaras, Irene; Mattison, Julie A.; Pearson, Kevin J.; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
   [Allard, Joanne] Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA.
   [Wnorowski, Artur] Med Univ Lublin, Dept Biopharm, PL-20093 Lublin, Poland.
   [Wnorowski, Artur; Sanghvi, Mitesh; Moaddel, Ruin] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
   [Tarantini, Stefano; Tucsek, Zsuzsanna; Ungvari, Zoltan; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
   [Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA.
RP de Cabo, R (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016
OI de Cabo, Rafael/0000-0002-3354-2442
FU Intramural Research Program of the NIH, National Institute on Aging;
   National Center for Complementary and Integrative Health [AT006526];
   Office of Dietary Supplements, NIH; American Heart Association
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute on Aging, the National Center for Complementary
   and Integrative Health (AT006526 to Z.U.), the Office of Dietary
   Supplements, NIH, and the American Heart Association (S.T., A.C., Z.T.,
   and Z.U.).
NR 78
TC 4
Z9 4
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD MAY
PY 2016
VL 8
IS 5
BP 899
EP 916
PG 18
WC Cell Biology
SC Cell Biology
GA DO5CL
UT WOS:000377801100010
PM 27070252
ER

PT J
AU Wehrlen, L
   Krumlauf, M
   Ness, E
   Maloof, D
   Bevans, M
AF Wehrlen, Leslie
   Krumlauf, Mike
   Ness, Elizabeth
   Maloof, Damiana
   Bevans, Margaret
TI Systematic collection of patient reported outcome research data: A
   checklist for clinical research professionals
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Patient reported outcome; Self-reported data; Patient diary; Clinical
   trials; Guidance; Questionnaire
ID QUALITY-OF-LIFE; CONSORT PRO EXTENSION; ADVANCED LUNG-CANCER; PRACTICES
   TASK-FORCE; RANDOMIZED-TRIALS; ONCOLOGY; CHALLENGES; PROTOCOL;
   RECOMMENDATIONS; SUPPORT
AB Understanding the human experience is no longer an outcome explored strictly by social and behavioral researchers. Increasingly, biomedical researchers are also including patient reported outcomes (PROs) in their clinical research studies not only due to calls for increased patient engagement in research but also healthcare. Collecting PROs in clinical research studies offers a lens into the patient's unique perspective providing important information to industry sponsors and the FDA. Approximately 30% of trials include PROs as primary or secondary endpoints and a quarter of FDA new drug, device and biologic applications include PRO data to support labeling claims. In this paper PRO, represents any information obtained directly from the patient or their proxy, without interpretation by another individual to ascertain their health, evaluate symptoms or conditions and extends the reference of PRO, as defined by the FDA, to include other sources such as patient diaries.
   Consumers and clinicians consistently report that PRO data are valued, and can aide when deciding between treatment options; therefore an integral part of clinical research. However, little guidance exists for clinical research professionals (CRPs) responsible for collecting PRO data on the best practices to ensure quality data collection so that an accurate assessment of the patient's view is collected. Therefore the purpose of this work was to develop and validate a checklist to guide quality collection of PRO data. The checklist synthesizes best practices from published literature and expert opinions addressing practical and methodological challenges CRPs often encounter when collecting PRO data in research settings. Published by Elsevier Inc.
C1 [Wehrlen, Leslie; Krumlauf, Mike; Bevans, Margaret] NIH, Dept Nursing, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
   [Ness, Elizabeth] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Maloof, Damiana] Newton Wellesley Hosp, Newton, MA 02462 USA.
RP Wehrlen, L (reprint author), NIH, Ctr Clin, Dept Nursing, 9000 Rockville Pike,10,2B12,MSC 1151, Bethesda, MD 20892 USA.
EM lwehrlen@nih.gov; krumlaum@cc.nih.gov; nesse@mail.nih.gov;
   dmaloof@partners.org; mbevans@cc.nih.gov
OI Wehrlen, Leslie/0000-0002-7909-0293
FU Intramural Research Program of the NIH, Clinical Center
FX The authors thank Informationist Judith Welsh, NIH Library, for
   developing the database search strategies and performing the literature
   searches in support of this review. We also sincerely thank our expert
   reviewers Nancy Kline-Leidy, PhD, Sally Brown, RN, BSN, MGA, OCN (R),
   CBCN, CCRP, Lisa Hansen, RN, MS, AOCN (R), Melanie Calvert, PhD and
   Madeleine King, PhD for their willingness, time, thoughtful review and
   expert consultation. This work was supported in part by the Intramural
   Research Program of the NIH, Clinical Center.
NR 61
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAY
PY 2016
VL 48
BP 21
EP 29
DI 10.1016/j.cct.2016.03.005
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DP4IF
UT WOS:000378458900003
PM 27002223
ER

PT J
AU Chandler, RK
   Finger, MS
   Farabee, D
   Schwartz, RP
   Condon, T
   Dunlap, LJ
   Zarkin, GA
   McCollister, K
   McDonald, RD
   Laska, E
   Bennett, D
   Kelly, SM
   Hillhouse, M
   Mitchell, SG
   O'Grady, KE
   Lee, JD
AF Chandler, Redonna K.
   Finger, Matthew S.
   Farabee, David
   Schwartz, Robert P.
   Condon, Timothy
   Dunlap, Laura J.
   Zarkin, Gary A.
   McCollister, Kathryn
   McDonald, Ryan D.
   Laska, Eugene
   Bennett, David
   Kelly, Sharon M.
   Hillhouse, Maureen
   Mitchell, Shannon G.
   O'Grady, Kevin E.
   Lee, Joshua D.
TI The SOMATICS collaborative: Introduction to a National Institute on Drug
   Abuse cooperative study of pharmacotherapy for opioid treatment in
   criminal justice settings
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Interim methadone; Extended-release naltrexone; Opioid; relapse
   prevention; Jail; Criminal justice
ID INTERIM METHADONE-MAINTENANCE; FORCED WITHDRAWAL; RANDOMIZED-TRIAL; FORM
   90; RELIABILITY; INTERVIEW; PRISON
AB Background: Among the nearly 750,000 inmates in U.S. jails, 12% report using opioids regularly, 8% report use in the month prior to their offense, and 4% report use at the time of their offense. Although ample evidence exists that medications effectively treat Opiate Use Disorder (OUD) in the community, strong evidence is lacking in jail settings. The general lack of medications for OUD in jail settings may place persons suffering from OUD at high risk for relapse to drug use and overdose following release from jail.
   Methods: The three study sites in this collaborative are pooling data for secondary analyses from three open-label randomized effectiveness trials comparing: (1) the initiation of extended-release naltrexone [XR-NTX] in Sites 1 and 2 and interim methadone in Site 3 with enhanced treatment-as usual (ETAU); (2) the additional benefit of patient navigation plus medications at Sites 2 and 3 vs. medication alone vs. ETAU. Participants are adults with OUD incarcerated in jail and transitioning to the community.
   Results: We describe the rationale, specific aims, and designs of three separate studies harmonized to enhance their scientific yield to investigate how to best prevent jail inmates from relapsing to opioid use and associated problems as they transition back to the community.
   Conclusions: Conducting drug abuse research during incarceration is challenging and study designs with data harmonization across different sites can increase the potential value of research to develop effective treatments for individuals in jail with OUD. Published by Elsevier Inc.
C1 [Chandler, Redonna K.; Finger, Matthew S.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA.
   [Farabee, David; Hillhouse, Maureen] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, UCLA Integrated Subst Abuse Programs, Los Angeles, CA 90024 USA.
   [Schwartz, Robert P.; Kelly, Sharon M.; Mitchell, Shannon G.] Friends Res Inst, Baltimore, MD USA.
   [Condon, Timothy] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA.
   [Dunlap, Laura J.; Zarkin, Gary A.] RTI Int, Res Triangle Pk, NC USA.
   [McCollister, Kathryn] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
   [McDonald, Ryan D.; Lee, Joshua D.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10003 USA.
   [Laska, Eugene] NYU, Sch Med, Dept Psychiat, New York, NY 10003 USA.
   [O'Grady, Kevin E.] Univ Maryland, College Pk, MD 20742 USA.
RP Chandler, RK (reprint author), NIDA, 6001 Execut Blvd,Room 5185,MSC 9565, Bethesda, MD 20892 USA.
EM redonna.chandler@nih.gov
OI Laska, Eugene/0000-0001-6799-1361
FU National Institutes of Health; National Institute on Drug Abuse [U01
   DA033336, U01 DA034743, U01 DA013636]
FX Support for the three studies of the SOMATICS research collaborative are
   provided by the National Institutes of Health and the National Institute
   on Drug Abuse and include U01 DA033336; U01 DA034743; U01 DA013636.
   Study drug is provided in-kind by Alkermes PLC to the NYU and UCLA
   studies.; The authors would like to thank the National Institute on Drug
   Abuse for its support for this collaborative.
NR 34
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAY
PY 2016
VL 48
BP 166
EP 172
DI 10.1016/j.cct.2016.05.003
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DP4IF
UT WOS:000378458900022
PM 27180088
ER

PT J
AU Trivellin, G
   Correa, RR
   Batsis, M
   Faucz, FR
   Chittiboina, P
   Bjelobaba, I
   Larco, DO
   Quezado, M
   Daly, AF
   Stojilkovic, SS
   Wu, TJ
   Beckers, A
   Lodish, MB
   Stratakis, CA
AF Trivellin, Giampaolo
   Correa, Ricardo R.
   Batsis, Maria
   Faucz, Fabio R.
   Chittiboina, Prashant
   Bjelobaba, Ivana
   Larco, Darwin O.
   Quezado, Martha
   Daly, Adrian F.
   Stojilkovic, Stanko S.
   Wu, T. John
   Beckers, Albert
   Lodish, Maya B.
   Stratakis, Constantine A.
TI Screening for GPR101 defects in pediatric pituitary corticotropinomas
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE GPR101; Cushing's disease; ACTH-secreting adenomas
ID PROTEIN-COUPLED RECEPTOR; MESSENGER-RNA EXPRESSION;
   EPIDERMAL-GROWTH-FACTOR; GENETIC-VARIATION; LARGE COHORT; ADENOMAS;
   HYPOTHALAMUS; CELLS; EGFR; AIP
AB Cushing's disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. In this study, we investigated the orphan G-protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormone secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we extracted DNA from peripheral blood and pituitary tumor samples (n = 36). No increased GPR101 expression was observed in tumors compared with normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were observed. GPR101 is not overexpressed in ACTH-secreting tumors compared with NPs. In conclusion, rare germline GPR101 variant was found in one patient with CD, but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.
C1 [Trivellin, Giampaolo; Correa, Ricardo R.; Batsis, Maria; Faucz, Fabio R.; Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
   [Correa, Ricardo R.; Batsis, Maria; Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Training Programs, NIH, Bethesda, MD USA.
   [Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Bjelobaba, Ivana; Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, NIH, Bethesda, MD USA.
   [Larco, Darwin O.; Wu, T. John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
   [Quezado, Martha] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Daly, Adrian F.; Beckers, Albert] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol & Clin Genet, Domaine Univ Sart Tilman, Liege, Belgium.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.; Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Training Programs, NIH, Bethesda, MD USA.
EM stratakc@mail.nih.gov
RI Daly, Adrian /E-2178-2011; 
OI Daly, Adrian /0000-0001-6130-2975; Trivellin,
   Giampaolo/0000-0003-2384-4153
FU Intramural Research Program of Eunice Kennedy Shriver National Institute
   of Child Health and Human Development, National Institutes of Health,
   Bethesda, Maryland, USA; Fonds d'Investissement pour la Recherche
   Scientifique of the Centre Hospitalier Universitaire de Liege,
   University of Liege, Liege, Belgium; NIH [RO3HD078645]; National Science
   Foundation [IOS1052288]
FX This research was supported by the Intramural Research Program of Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health, Bethesda, Maryland, USA; the
   Fonds d'Investissement pour la Recherche Scientifique of the Centre
   Hospitalier Universitaire de Liege, University of Liege, Liege, Belgium;
   and NIH RO3HD078645 and National Science Foundation IOS1052288 grants.
NR 23
TC 0
Z9 0
U1 3
U2 4
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
   ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD MAY
PY 2016
VL 23
IS 5
BP 357
EP 365
DI 10.1530/ERC-16-0091
PG 9
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DP1XO
UT WOS:000378282900006
ER

PT J
AU Zhuang, ZP
   Yang, CZ
   Ryska, A
   Ji, Y
   Hou, YY
   Graybill, SD
   Bullova, P
   Lubensky, IA
   Kloppel, G
   Pacak, K
AF Zhuang, Zhengping
   Yang, Chunzhang
   Ryska, Ales
   Ji, Yuan
   Hou, Yingyong
   Graybill, Sky D.
   Bullova, Petra
   Lubensky, Irina A.
   Kloeppel, Guenter
   Pacak, Karel
TI HIF2A gain-of-function mutations detected in duodenal gangliocytic
   paraganglioma
SO ENDOCRINE-RELATED CANCER
LA English
DT Letter
ID PHEOCHROMOCYTOMAS; POLYCYTHEMIA
C1 [Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Yang, Chunzhang] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
   [Ryska, Ales] Charles Univ Prague, Med Fac Hosp, Fingerland Dept Pathol, Hradec Kralove, Czech Republic.
   [Ji, Yuan; Hou, Yingyong] Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai 200433, Peoples R China.
   [Graybill, Sky D.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA.
   [Bullova, Petra; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
   [Bullova, Petra] Slovak Acad Sci, Inst Virol, Dept Mol Med, Bratislava, Slovakia.
   [Lubensky, Irina A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
   [Kloeppel, Guenter] Tech Univ Munich, Dept Pathol, Consultat Ctr Pancreas & Neuroendocrine Tumors, D-80290 Munich, Germany.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008735-15]
NR 10
TC 2
Z9 2
U1 3
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
   ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD MAY
PY 2016
VL 23
IS 5
BP L13
EP L16
DI 10.1530/ERC-16-0148
PG 4
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DP1XO
UT WOS:000378282900001
PM 27130043
ER

PT J
AU Long, C
   Fureman, B
   Dingledine, R
AF Long, Cara
   Fureman, Brandy
   Dingledine, Ray
TI 2014 Epilepsy Benchmarks: Progress and Opportunities
SO EPILEPSY CURRENTS
LA English
DT Editorial Material
C1 Amer Epilepsy Soc, Res, Chicago, IL USA.
   [Fureman, Brandy] NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Dingledine, Ray] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA.
   [Fureman, Brandy] Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
RP Fureman, B (reprint author), NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Fureman, B (reprint author), Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
EM Bfureman@efa.org
FU NINDS NIH HHS [R01 NS097776, U01 NS058158]
NR 3
TC 0
Z9 0
U1 0
U2 0
PU AMER EPILEPSY SOCIETY
PI WEST HARTFORD
PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA
SN 1535-7597
EI 1535-7511
J9 EPILEPSY CURR
JI Epilepsy Curr.
PD MAY-JUN
PY 2016
VL 16
IS 3
BP 179
EP 181
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP2WR
UT WOS:000378354700019
PM 27330449
ER

PT J
AU Caplan, R
   Mefford, H
   Berl, M
   Chang, B
   Lin, J
   Mazarati, A
   Fureman, B
   Dingledine, R
AF Caplan, Rochelle
   Mefford, Heather
   Berl, Madison
   Chang, Bernard
   Lin, Jack
   Mazarati, Andrey
   Fureman, Brandy
   Dingledine, Ray
CA Amer Epilepsy Soc
   Natl Inst Neurological Disorders S
TI 2014 Epilepsy Benchmarks Area I: Understanding the Causes of the
   Epilepsies and Epilepsy-Related Neurologic, Psychiatric, and Somatic
   Conditions
SO EPILEPSY CURRENTS
LA English
DT Editorial Material
ID DE-NOVO MUTATIONS; FOCAL CORTICAL DYSPLASIA; MIGRATING PARTIAL SEIZURES;
   OF-FUNCTION MUTATIONS; GRIN2A MUTATIONS; LOBE EPILEPSY; ENCEPHALOPATHY;
   ENCEPHALITIS; RECEPTOR; GAIN
C1 [Caplan, Rochelle] Univ Calif Los Angeles, Los Angeles, CA USA.
   [Mefford, Heather] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Berl, Madison] Childrens Natl Med Ctr, Washington, DC 20010 USA.
   [Chang, Bernard] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA.
   [Lin, Jack] Univ Calif Irvine, Med Ctr, Dept Clin Neurol, Orange, CA USA.
   [Mazarati, Andrey] Univ Calif Los Angeles, Dept Pediat, Div Neurol, Los Angeles, CA 90024 USA.
   [Fureman, Brandy] NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Dingledine, Ray] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA.
   [Fureman, Brandy] Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
RP Fureman, B (reprint author), NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Fureman, B (reprint author), Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
EM BFureman@efa.org
FU NINDS NIH HHS [R01 NS097776]
NR 37
TC 0
Z9 0
U1 2
U2 2
PU AMER EPILEPSY SOCIETY
PI WEST HARTFORD
PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA
SN 1535-7597
EI 1535-7511
J9 EPILEPSY CURR
JI Epilepsy Curr.
PD MAY-JUN
PY 2016
VL 16
IS 3
BP 182
EP 186
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP2WR
UT WOS:000378354700020
PM 27330450
ER

PT J
AU Galanopoulou, AS
   Wong, M
   Binder, D
   Hartman, AL
   Powell, EM
   Roopra, A
   Staba, R
   Vezzani, A
   Fureman, B
   Dingledine, R
AF Galanopoulou, Aristea S.
   Wong, Michael
   Binder, Devin
   Hartman, Adam L.
   Powell, Elizabeth M.
   Roopra, Avtar
   Staba, Richard
   Vezzani, Annamaria
   Fureman, Brandy
   Dingledine, Ray
CA Amer Epilepsy Soc
   Natl Inst Neurological Disorders S
TI 2014 Epilepsy Benchmarks Area II: Prevent Epilepsy and Its Progression
SO EPILEPSY CURRENTS
LA English
DT Editorial Material
ID TEMPORAL-LOBE EPILEPSY; BLOOD-BRAIN-BARRIER; DRAVET SYNDROME; STATUS
   EPILEPTICUS; KETOGENIC DIET; MOUSE MODEL; RAT MODEL; EPILEPTOGENESIS;
   SEIZURES; BIOMARKERS
C1 [Galanopoulou, Aristea S.] Montefiore Med Ctr, Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci,Neurol & Neurosc, Saul R Korey Dept Neurol,Lab Dev Epilepsy, Bronx, NY 10467 USA.
   [Wong, Michael] Washington Univ, Sch Med, Dept Neurol, Neurol Pediat & Neurobiol, St Louis, MO 63110 USA.
   [Wong, Michael] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO USA.
   [Binder, Devin] Univ Calif Riverside, Ctr Glial Neuronal Interact, Div Biomed Sci, Sch Med, Riverside, CA 92521 USA.
   [Hartman, Adam L.] Johns Hopkins Univ, Johns Hopkins Sch Med, Bloomberg Sch Publ Hlth,Neurol & Pediat,Dept Neur, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA.
   [Powell, Elizabeth M.] Univ Maryland, Sch Med, Dept Anat & Neurobiol Psychiat & Bioengn, Baltimore, MD 21201 USA.
   [Roopra, Avtar] Univ Wisconsin, Dept Neurosci, Neurosci, Madison, WI USA.
   [Staba, Richard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [Vezzani, Annamaria] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Expt Neurol, Milan, Italy.
   [Fureman, Brandy] NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Dingledine, Ray] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
   [Fureman, Brandy] Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
RP Fureman, B (reprint author), NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Fureman, B (reprint author), Epilepsy Fdn Amer, 8301 Profess Pl, Landover, MD USA.
EM bfureman@efa.org
FU NINDS NIH HHS [R01 NS097776, U01 NS058158]
NR 48
TC 0
Z9 0
U1 2
U2 4
PU AMER EPILEPSY SOCIETY
PI WEST HARTFORD
PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA
SN 1535-7597
EI 1535-7511
J9 EPILEPSY CURR
JI Epilepsy Curr.
PD MAY-JUN
PY 2016
VL 16
IS 3
BP 187
EP 191
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP2WR
UT WOS:000378354700021
PM 27330451
ER

PT J
AU Dlugos, D
   Worrell, G
   Davis, K
   Stacey, W
   Szaflarski, J
   Kanner, A
   Sunderam, S
   Rogawski, M
   Jackson-Ayotunde, P
   Loddenkemper, T
   Diehl, B
   Fureman, B
   Dingledine, R
AF Dlugos, Dennis
   Worrell, Greg
   Davis, Kathryn
   Stacey, William
   Szaflarski, Jerzy
   Kanner, Andres
   Sunderam, Sridhar
   Rogawski, Mike
   Jackson-Ayotunde, Patrice
   Loddenkemper, Tobias
   Diehl, Beate
   Fureman, Brandy
   Dingledine, Ray
CA Epilepsy Benchmark Stewards
TI 2014 Epilepsy Benchmarks Area III: Improve Treatment Options for
   Controlling Seizures and Epilepsy-Related Conditions Without Side
   Effects
SO EPILEPSY CURRENTS
LA English
DT Editorial Material
ID TEMPORAL-LOBE EPILEPSY; FOCAL CORTICAL DYSPLASIA; TARGETED RESPONSIVE
   NEUROSTIMULATION; REFRACTORY PARTIAL SEIZURES; INTRACTABLE EPILEPSY;
   EZOGABINE RETIGABINE; LONG-TERM; SOMATIC MUTATIONS; MAMMALIAN TARGET;
   CONTROLLED-TRIAL
C1 [Dlugos, Dennis] Univ Penn, Childrens Hosp Philadelphia, Neurol & Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Worrell, Greg] Mayo Clin, Neurol, Mayo Syst Electrophysiol Lab, Dept Neurol, Rochester, MN USA.
   [Worrell, Greg] Mayo Clin, Dept Biomed Engn, Rochester, MN USA.
   [Davis, Kathryn] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Stacey, William] Univ Michigan, Dept Neurol, Dept Biomed Engn, Neurol, Ann Arbor, MI 48109 USA.
   [Szaflarski, Jerzy] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA.
   [Szaflarski, Jerzy] UAB Epilepsy Ctr, Birmingham, AL USA.
   [Kanner, Andres] Univ Miami, Miller Sch Med, Dept Neurol, Neurol Clin, Miami, FL 33136 USA.
   [Sunderam, Sridhar] Univ Kentucky, Dept Biomed Engn, Lexington, KY USA.
   [Rogawski, Mike] UC Davis Sch Med, Ctr Neurotherapeut Discovery & Dev, Sacramento, CA USA.
   [Rogawski, Mike] UC Davis Sch Med, Dept Neurol, Sacramento, CA USA.
   [Jackson-Ayotunde, Patrice] Univ Maryland Eastern Shore, Dept Pharmaceut Sci, Princess Anne, MD USA.
   [Loddenkemper, Tobias] Boston Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA USA.
   [Loddenkemper, Tobias] Harvard Univ, Sch Med, Boston, MA USA.
   [Diehl, Beate] UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London, England.
   [Fureman, Brandy] NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Dingledine, Ray] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA.
   [Fureman, Brandy] 8301 Profess Pl, Landover, MD USA.
RP Fureman, B (reprint author), NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Fureman, B (reprint author), 8301 Profess Pl, Landover, MD USA.
EM bfureman@efa.org
RI Stacey, William/D-1123-2009
OI Stacey, William/0000-0002-8359-8057
FU NINDS NIH HHS [R01 NS097776]
NR 54
TC 0
Z9 0
U1 0
U2 0
PU AMER EPILEPSY SOCIETY
PI WEST HARTFORD
PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA
SN 1535-7597
EI 1535-7511
J9 EPILEPSY CURR
JI Epilepsy Curr.
PD MAY-JUN
PY 2016
VL 16
IS 3
BP 192
EP 197
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP2WR
UT WOS:000378354700022
PM 27330452
ER

PT J
AU Goldman, AM
   LaFrance, WC
   Benke, T
   Asato, M
   Drane, D
   Pack, A
   Syed, T
   Doss, R
   Lhatoo, S
   Fureman, B
   Dingledine, R
AF Goldman, Alica M.
   LaFrance, W. Curt, Jr.
   Benke, Tim
   Asato, Miya
   Drane, Dan
   Pack, Alison
   Syed, Tanvir
   Doss, Robert
   Lhatoo, Samden
   Fureman, Brandy
   Dingledine, Ray
CA Amer Epilepsy Soc
   Natl Inst Neurological Disorders S
TI 2014 Epilepsy Benchmarks Area IV: Limit or Prevent Adverse Consequence
   of Seizures and Their Treatment Across The Lifespan
SO EPILEPSY CURRENTS
LA English
DT Editorial Material
ID PSYCHOGENIC NONEPILEPTIC SEIZURES; SUDDEN UNEXPECTED DEATH;
   ANTIEPILEPTIC DRUG EXPOSURE; TEMPORAL-LOBE EPILEPSY; QUALITY-OF-LIFE;
   AGE 6 YEARS; TARGETED RESPONSIVE NEUROSTIMULATION; JUVENILE MYOCLONIC
   EPILEPSY; RISK-FACTORS; CONVULSIVE SEIZURES
C1 [Goldman, Alica M.] Baylor Coll Med, Dept Neurol, One Baylor Plaza,NB222, Houston, TX 77030 USA.
   [LaFrance, W. Curt, Jr.] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02903 USA.
   [LaFrance, W. Curt, Jr.] Brown Univ, Alpert Med Sch, Dept Psychiat, Providence, RI 02903 USA.
   [Benke, Tim] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
   [Benke, Tim] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA.
   [Benke, Tim] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA.
   [Benke, Tim] Univ Colorado, Sch Med, Dept Otolaryngol, Aurora, CO USA.
   [Asato, Miya] Childrens Hosp Pittsburgh, Div Child Neurol, Pediat & Psychiat, Pittsburgh, PA 15213 USA.
   [Drane, Dan] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
   [Drane, Dan] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
   [Drane, Dan] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA.
   [Pack, Alison] Columbia Univ, Dept Neurol, Neurol, Med Ctr, New York, NY USA.
   [Syed, Tanvir] Univ Hosp Case Med Ctr, Neurol, Cleveland, OH USA.
   [Doss, Robert] Minnesota Epilepsy Grp PA, St Paul, MN USA.
   [Doss, Robert] Univ Minnesota Twin Cities, Dept Neurol, St Paul, MN USA.
   [Lhatoo, Samden] Case Western Reserve Univ, Sch Med, Dept Neurol, Cleveland, OH 44106 USA.
   [Fureman, Brandy] NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Dingledine, Ray] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA.
   [Fureman, Brandy] Epilepsy Fdn, 8301 Profess Pl, Landover, MD USA.
RP Fureman, B (reprint author), NINDS, Channels Synapses & Circuits Cluster, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Fureman, B (reprint author), Epilepsy Fdn, 8301 Profess Pl, Landover, MD USA.
EM bfureman@efa.org
FU NINDS NIH HHS [R01 NS097776]
NR 77
TC 0
Z9 0
U1 1
U2 1
PU AMER EPILEPSY SOCIETY
PI WEST HARTFORD
PA 342 NORTH MAIN STREET, WEST HARTFORD, CT 06117-2507 USA
SN 1535-7597
EI 1535-7511
J9 EPILEPSY CURR
JI Epilepsy Curr.
PD MAY-JUN
PY 2016
VL 16
IS 3
BP 198
EP 205
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DP2WR
UT WOS:000378354700023
PM 27330453
ER

PT J
AU Izen, R
   Stuart, YE
   Jiang, YX
   Bolnick, DI
AF Izen, Rebecca
   Stuart, Yoel E.
   Jiang, Yuexin
   Bolnick, Daniel I.
TI Coarse- and fine-grained phenotypic divergence among threespine
   stickleback from alternating lake and stream habitats
SO EVOLUTIONARY ECOLOGY RESEARCH
LA English
DT Article
DE cline; Gasterosteus aculeatus; habitat preference; matching habitat
   choice; microgeographic variation; threespine stickleback
ID GENE FLOW; ADAPTIVE DIVERGENCE; GASTEROSTEUS-ACULEATUS;
   NATURAL-SELECTION; PARAPATRIC LAKE; MICROGEOGRAPHIC ADAPTATION;
   POPULATIONS; EVOLUTION; PLASTICITY; PARALLEL
AB Background: Habitat characteristics can vary over small spatial scales at which gene flow is expected to swamp any effect of divergent natural selection. However, fine-grained ('microgeographic') adaptive divergence may still be feasible if individuals exhibit dispersal behaviours that improve the match between their phenotype and habitat. For example, threespine stickleback (Gasterosteus aculeatus) from lake and stream habitats maintain differences across a narrow ecotone because of non-random gene flow. However, it is unknown whether dispersal bias might also contribute to even finer-scale divergence within habitats, in response to microhabitat variation within lakes and within streams.
   Question: Does stickleback morphology co-vary with flow regime within stream populations, controlling for distance from adjoining lake populations?
   Data: We sampled stickleback along a transect through alternating lake and stream habitats. Within each stream, multiple traps were set at 50 m intervals. We recorded microhabitat data (flow rate and depth) at each trap. We measured morphology (gill rakers, head shape, fin shape, standard length) of more than 900 stickleback captured from these traps.
   Analysis: We used multivariate analyses of covariance and linear models to test for: (1) phenotypic divergence between lake and stream stickleback, (2) divergence among stream sites as a function of their distance from an adjoining lake, and (3) covariation between local flow regime (at each trap) and the morphology of stickleback captured from that trap.
   Conclusions: Fish from different flow regimes within a stream show phenotypic variation that is not due to clinal transitions from lake to stream. We found covariation between local flow regime and either fin morphology or gill raker length in different streams. The total effect size of stream microhabitat on morphology was greater than the effect size of habitat (lake vs. stream), for overall multivariate data and for a subset of univariate traits. These findings imply that local adaptation can occur on a finer spatial scale than is typically expected, perhaps as a result of non-random dispersal.
C1 [Izen, Rebecca] NHLBI, Genet & Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Izen, Rebecca; Stuart, Yoel E.; Jiang, Yuexin; Bolnick, Daniel I.] Univ Texas Austin, Dept Integrat Biol, Austin, TX 78712 USA.
   [Jiang, Yuexin] Airbnb, San Francisco, CA USA.
RP Izen, R (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 6C103, Bethesda, MD 20892 USA.
EM rebecca.izen@gmail.com
FU David and Lucille Packard Foundation; Howard Hughes Medical Institute;
   NSF [DEB-1144773]
FX Special thanks go to Julia Saltz and Scott Egan for discussions and
   comments on the manuscript. W.E. Stutz, K. Ballare, and R. Carlson
   assisted with field collections. This work was supported by the David
   and Lucille Packard Foundation, the Howard Hughes Medical Institute, and
   NSF grant DEB-1144773 to D.I.B.
NR 63
TC 2
Z9 2
U1 12
U2 18
PU EVOLUTIONARY ECOLOGY LTD
PI TUCSON
PA UNIV ARIZONA, 321 BIOSCIENCES WEST, TUCSON, AZ 85721 USA
SN 1522-0613
EI 1937-3791
J9 EVOL ECOL RES
JI Evol. Ecol. Res.
PD MAY
PY 2016
VL 17
IS 3
BP 437
EP 457
PG 21
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
   Heredity
GA DP0GV
UT WOS:000378168300009
ER

PT J
AU Santosh, KC
   Wendling, L
   Antani, S
   Thoma, GR
AF Santosh, K. C.
   Wendling, Laurent
   Antani, Sameer
   Thoma, George R.
TI Overlaid Arrow Detection for Labeling Regions of Interest in Biomedical
   Images
SO IEEE INTELLIGENT SYSTEMS
LA English
DT Article
ID DESCRIPTOR
C1 [Santosh, K. C.] Univ S Dakota, Dept Comp Sci, Vermillion, SD 57069 USA.
   [Wendling, Laurent] Univ Paris 05, Paris, France.
   [Antani, Sameer; Thoma, George R.] Natl Lib Med, Bethesda, MD 20894 USA.
RP Santosh, KC (reprint author), Univ S Dakota, Dept Comp Sci, Vermillion, SD 57069 USA.
EM santosh.kc@usd.edu; laurent.wendling@parisdescartes.fr;
   sameer.antani@nih.gov; george.thoma@nih.gov
FU National Institutes of Health, National Library of Medicine; Lister Hill
   National Center for Biomedical Communications
FX The Intramural Research Program of the National Institutes of Health,
   National Library of Medicine, and Lister Hill National Center for
   Biomedical Communications supported this work. We thank the National
   Institutes of Health Fellows Editorial Board for their editorial
   assistance.
NR 12
TC 0
Z9 0
U1 0
U2 1
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1541-1672
EI 1941-1294
J9 IEEE INTELL SYST
JI IEEE Intell. Syst.
PD MAY-JUN
PY 2016
VL 31
IS 3
BP 66
EP 75
PG 10
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
   Electronic
SC Computer Science; Engineering
GA DP3WW
UT WOS:000378427600011
ER

PT J
AU Song, HM
   Vijayasarathy, C
   Zeng, Y
   Marangoni, D
   Bush, RA
   Wu, ZJ
   Sieving, PA
AF Song, Hongman
   Vijayasarathy, Camasamudram
   Zeng, Yong
   Marangoni, Dario
   Bush, Ronald A.
   Wu, Zhijian
   Sieving, Paul A.
TI NADPH Oxidase Contributes to Photoreceptor Degeneration in
   Constitutively Active RAC1 Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE photoreceptor degeneration; RAC1; NADPH oxidase; reactive oxygen
   species; oxidative stress
ID CONE CELL-DEATH; OXIDATIVE STRESS; RETINAL DEGENERATION;
   RETINITIS-PIGMENTOSA; NAD(P)H OXIDASES; OUTER SEGMENTS; MACULAR
   DEGENERATION; MEDIATED ACTIVATION; ROD PHOTORECEPTORS; MOUSE MODELS
AB PURPOSE. The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1.
   METHODS. Transgenic (Tg)-CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP.
   RESULTS. Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a-and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP-transduced retinas.
   CONCLUSIONS. Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway.
C1 [Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA.
   [Wu, Zhijian] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA.
   [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sieving, PA (reprint author), BG 31,RM6A03,31 Ctr Dr, Bethesda, MD 20892 USA.
EM paulsieving@nei.nih.gov
FU NIH Intramural Research Programs of the National Institute on Deafness
   and Other Communication Disorders; NEI, Bethesda, Maryland, United
   States
FX Supported by the NIH Intramural Research Programs of the National
   Institute on Deafness and Other Communication Disorders and the NEI,
   Bethesda, Maryland, United States.
NR 80
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Z9 2
U1 3
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2016
VL 57
IS 6
BP 2864
EP 2875
DI 10.1167/iovs.15-18974
PG 12
WC Ophthalmology
SC Ophthalmology
GA DO8OA
UT WOS:000378041700057
PM 27233035
ER

PT J
AU Young, MF
AF Young, Marian F.
TI Skeletal biology: Where matrix meets mineral
SO MATRIX BIOLOGY
LA English
DT Editorial Material
ID EXTRACELLULAR-MATRIX; ARTICULAR-CARTILAGE; COLLAGEN; BONE;
   METALLOPROTEINASES; FIBRILLOGENESIS; PROTEOGLYCANS; OSTEONECTIN;
   INTEGRINS
AB The skeleton is unique from all other tissues in the body because of its ability to mineralize. The incorporation of mineral into bones and teeth is essential to give them strength and structure for body support and function. For years, researchers have wondered how mineralized tissues form and repair. A major focus in this context has been on the role of the extracellular matrix, which harbors key regulators of the mineralization process. In this introductory minireview, we will review some key concepts of matrix biology as it related to mineralized tissues. Concurrently, we will highlight the subject of this special issue covering many aspects of mineralized tissues, including bones and teeth and their associated structures cartilage and tendon. Areas of emphasis are on the generation and analysis of new animal models with permutations of matrix components as well as the development of new approaches for tissue engineering for repair of damaged hard tissue. In assembling key topics on mineralized tissues written by leaders in our field, we hope the reader will get a broad view of the topic and all of its fascinating complexities. Published by Elsevier B.V.
C1 [Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM myoung@dir.nidcr.nih.gov
NR 30
TC 2
Z9 2
U1 3
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 1
EP 6
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700001
PM 27131884
ER

PT J
AU Mertz, EL
   Makareeva, E
   Mirigian, LS
   Koon, KY
   Perosky, JE
   Kozloff, KM
   Leikin, S
AF Mertz, E. L.
   Makareeva, E.
   Mirigian, L. S.
   Koon, K. Y.
   Perosky, J. E.
   Kozloff, K. M.
   Leikin, S.
TI Makings of a brittle bone: Unexpected lessons from a low protein diet
   study of a mouse OI model
SO MATRIX BIOLOGY
LA English
DT Article
DE Osteogenesis imperfecta; Bone; Mineralization; Collagen; Raman
   microspectroscopy; Biomechanics
ID DOMINANT OSTEOGENESIS IMPERFECTA; MURINE MODEL; MUTATIONS; STRENGTH;
   COLLAGEN; MATRIX; DEGRADATION; ADAPTATIONS; PHENOTYPE; FRAGILITY
AB Glycine substitutions in type I collagen appear to cause osteogenesis imperfecta (OI) by disrupting folding of the triple helix, the structure of which requires Gly in every third position. It is less clear, however, whether the resulting bone malformations and fragility are caused by effects of intracellular accumulation of misfolded collagen on differentiation and function of osteoblasts, effects of secreted misfolded collagen on the function of bone matrix, or both. Here we describe a study originally conceived for testing how reducing intracellular accumulation of misfolded collagen would affect mice with a Gly610 to Cys substitution in the triple helical region of the alpha 2(I) chain. To stimulate degradation of misfolded collagen by autophagy, we utilized a low protein diet. The diet had beneficial effects on osteoblast differentiation and bone matrix mineralization, but also affected bone modeling and suppressed overall animal growth. Our more important observations, however, were not related to the diet. They revealed how altered osteoblast function and deficient bone formation by each cell caused by the G610C mutation combined with increased osteoblastogenesis might make the bone more brittle, all of which are common OI features. In G610C mice, increased bone formation surface compensated for reduced mineral apposition rate, resulting in normal cortical area and thickness at the cost of altering cortical modeling process, retaining woven bone, and reducing the ability of bone to absorb energy through plastic deformation. Reduced collagen and increased mineral density in extracellular matrix of lamellar bone compounded the problem, further reducing bone toughness. The latter observations might have particularly important implications for understanding OI pathophysiology and designing more effective therapeutic interventions. Published by Elsevier B.V.
C1 [Mertz, E. L.; Makareeva, E.; Mirigian, L. S.; Koon, K. Y.; Leikin, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA.
   [Perosky, J. E.; Kozloff, K. M.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
RP Leikin, S (reprint author), NICHD, NIH, Bldg 9,Rm 1E-127, Bethesda, MD 20892 USA.
EM leikins@mail.nih.gov
RI Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU Intramural Research Program of the National Institute of Child Health
   and Human Development (NICHD), National Institutes of Health
   [1ZIAHD000256, 1ZIAHD008810]
FX This work was funded in part by the Intramural Research Program of the
   National Institute of Child Health and Human Development (NICHD),
   National Institutes of Health (projects # 1ZIAHD000256 and
   1ZIAHD008810). Electron Microscopy was performed at the Microscopy and
   Imaging Core of NICHD with the assistance of Lynne Holtzclaw and Louis
   (Chip) Dye.
NR 38
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 29
EP 42
DI 10.1016/j.matbio.2016.03.005
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700004
PM 27039252
ER

PT J
AU Lu, XY
   Li, WJ
   Fukumoto, S
   Yamada, Y
   Evans, CA
   Diekwisch, T
   Luan, XH
AF Lu, Xuanyu
   Li, Wenjin
   Fukumoto, Satoshi
   Yamada, Yoshihiko
   Evans, Carla A.
   Diekwisch, Tom
   Luan, Xianghong
TI The ameloblastin extracellular matrix molecule enhances bone fracture
   resistance and promotes rapid bone fracture healing
SO MATRIX BIOLOGY
LA English
DT Article
DE Ameloblastin; Bone fracture; Fracture healing; Mesenchymal stem cells;
   Proliferation
ID GROWTH; MICE; MINERALIZATION; CELLS; GENE; PROLIFERATION; EXPRESSION;
   AMELOGENIN; NETWORKS; FIBROSIS
AB The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN(Delta 5-6) truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Lu, Xuanyu; Diekwisch, Tom; Luan, Xianghong] Univ Illinois, Coll Dent, Brodie Lab Craniofacial Genet, Dept Oral Biol, 801 South Pauline, Chicago, IL 60612 USA.
   [Lu, Xuanyu; Evans, Carla A.; Luan, Xianghong] Univ Illinois, Coll Dent, Brodie Lab Craniofacial Genet, Dept Orthodont, Chicago, IL 60612 USA.
   [Li, Wenjin] Shanxi Univ, Dept Prosthodont, Taiyuan 030006, Shanxi, Peoples R China.
   [Fukumoto, Satoshi; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA.
   [Diekwisch, Tom] Texas A&M Baylor, Coll Dent, Dept Periodont, Dallas, TX USA.
RP Diekwisch, T; Luan, XH (reprint author), Univ Illinois, Coll Dent, Brodie Lab Craniofacial Genet, Dept Oral Biol, 801 South Pauline, Chicago, IL 60612 USA.
EM dlekwisch@bcd.tamhsc.edu; luan@uic.edu
FU National Institute of Dental and Craniofacial Research grant [R01
   DE019155]
FX Generous support by National Institute of Dental and Craniofacial
   Research grant R01 DE019155 to XL is gratefully acknowledged.
NR 48
TC 2
Z9 2
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 113
EP 126
DI 10.1016/j.matbio.2016.02.007
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700010
PM 26899203
ER

PT J
AU Myren, M
   Kirby, DJ
   Noonan, ML
   Maeda, A
   Owens, RT
   Ricard-Blum, S
   Kram, V
   Kilts, TM
   Young, MF
AF Myren, Maja
   Kirby, David J.
   Noonan, Megan L.
   Maeda, Azusa
   Owens, Rick T.
   Ricard-Blum, Sylvie
   Kram, Vardit
   Kilts, Tina M.
   Young, Marian F.
TI Biglycan potentially regulates angiogenesis during fracture repair by
   altering expression and function of endostatin
SO MATRIX BIOLOGY
LA English
DT Review
DE Biglycan; Fracture healing; Angiogenesis; Endostatin
ID LEUCINE-RICH PROTEOGLYCANS; MATRIX COMPONENT BIGLYCAN;
   ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; TARGETED DISRUPTION; CANCELLOUS
   BONE; DEFICIENT MICE; DECORIN; OSTEOPOROSIS; DISEASE
AB The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth during bone healing [1]. By infusing barium sulfate (BaSO4) into WTand Bgn-deficient mice we discovered the positive effect of Bgn in modulating angiogenesis during fracture healing. Using micro-computed tomography angiography we found significant differences in the vessel size and volume among other parameters. To further understand the mechanistic basis for this, we explored the relationship between Bgn and the anti-angiogenic protein endostatin. Immunohistochemistry (INC) showed co-localization of Bgn and endostatin in regions of bone formation, with increased endostatin staining in Bgn-KO compared to WT at 14 days post-fracture. To further elucidate the relationship between Bgn and endostatin, an endothelial cell tube formation assay was used. This study showed that endothelial cells treated with endostatin had significantly decreased vessel length and vessel branches compared to untreated cells, while cells treated with endostatin and Bgn at a 1:1 M ratio had vessel length and vessel branches comparable to untreated cells. This indicated that Bgn was able to mitigate the inhibitory effect of endostatin on endothelial cell growth. In summary, these results suggest that Bgn is needed for proper blood vessel formation during fracture healing, and one mechanism by which Bgn impacts angiogenesis is through inhibition of endostatin. Published by Elsevier B.V.
C1 [Myren, Maja; Kirby, David J.; Noonan, Megan L.; Maeda, Azusa; Kram, Vardit; Kilts, Tina M.; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Owens, Rick T.] Life Cell Corp, Branchburg, NJ 08876 USA.
   [Ricard-Blum, Sylvie] Univ Lyon 1, ICBMS, CNRS UMR 5246, F-69622 Villeurbanne, France.
RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, NIH, 9000 Rockville Pike,Bldg 30 Room 211, Bethesda, MD 20892 USA.
EM Myoung@dir.nidcr.nih.gov
FU Intramural program of the NIDCR, NIH, DHHS [Z01 DE000379-21]
FX This research was supported in part by the Intramural program of the
   NIDCR, NIH, DHHS (Z01 DE000379-21). We would like to thank, Dr. Rhonda
   Prisby (University of Delaware) for sharing her expertise in vessel
   casting in vivo and Dr. Neal Fedarko for advice on the use of the HUVEC
   system. We also wish to thank Ms. Aalia Farukhi for her technical
   assistance and Ms. Li Li for her help in sectioning femurs for
   immunohistochemistry.
NR 37
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U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 141
EP 150
DI 10.1016/j.matbio.2016.03.008
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700012
PM 27072616
ER

PT J
AU Duverger, O
   Beniash, E
   Morasso, MI
AF Duverger, Olivier
   Beniash, Elia
   Morasso, Maria I.
TI Keratins as components of the enamel organic matrix
SO MATRIX BIOLOGY
LA English
DT Review
DE Keratins; Enamel; Organic matrix; Caries; Tooth
ID AMINO-ACID-COMPOSITION; TUFT PROTEIN; DENTAL ENAMEL; TOOTH ENAMEL;
   ORAL-HEALTH; CARIES; MINERALIZATION; TEETH; CHILDREN; GROWTH
AB Dental enamel is the hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century, its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150 years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair. Published by Elsevier B.V.
C1 [Duverger, Olivier; Morasso, Maria I.] NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Beniash, Elia] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial Regenerat, Pittsburgh, PA 15260 USA.
   [Beniash, Elia] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA.
   [Beniash, Elia] McGowan Inst Regenerat Med, Pittsburgh, PA 15203 USA.
RP Morasso, MI (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA.; Beniash, E (reprint author), Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial Regenerat, Pittsburgh, PA 15260 USA.; Beniash, E (reprint author), Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA.; Beniash, E (reprint author), McGowan Inst Regenerat Med, Pittsburgh, PA 15203 USA.
EM ebeniash@pitt.edu; morasso@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
   Musculoskeletal and Skin Diseases of the National Institutes of Health
   (ZIA) [AR041124-14]; Intramural Research Program of the National
   Institute of Arthritis and Musculoskeletal and Skin Diseases of the
   National Institutes of Health (NIH/NIDCR) [DE016703]
FX This work was supported by the Intramural Research Program of the
   National Institute of Arthritis and Musculoskeletal and Skin Diseases of
   the National Institutes of Health (ZIA AR041124-14 (MIM) and NIH/NIDCR
   grant DE016703 (EB).
NR 41
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Z9 0
U1 5
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 260
EP 265
DI 10.1016/j.matbio.2015.12.007
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700022
PM 26709044
ER

PT J
AU Xu, H
   Snider, TN
   Wimer, HF
   Yamada, SS
   Yang, T
   Holmbeck, K
   Foster, BL
AF Xu, H.
   Snider, T. N.
   Wimer, H. F.
   Yamada, S. S.
   Yang, T.
   Holmbeck, K.
   Foster, B. L.
TI Multiple essential MT1-MMP functions in tooth root formation,
   dentinogenesis, and tooth eruption
SO MATRIX BIOLOGY
LA English
DT Article
DE Extracellular matrix; Matrix metalloproteinases; Dentin; Bone formation;
   Periodontal
ID RAT DENTAL FOLLICLE; BONE MORPHOGENETIC PROTEIN-2; HORMONE-RELATED
   PROTEIN; CRE TRANSGENIC MICE; OSTERIX-CRE; MATRIX METALLOPROTEINASES;
   PERIODONTAL-LIGAMENT; WINCHESTER-SYNDROME; GENE-EXPRESSION; NULL MICE
AB Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP-/-) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Xu, H.] Peking Univ, Dept Pediat Dent, Sch & Hosp Stomatol, Beijing 100871, Peoples R China.
   [Xu, H.; Foster, B. L.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
   [Snider, T. N.] Univ Michigan, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA.
   [Snider, T. N.] NIH, Med Res Scholars Program, Bldg 10, Bethesda, MD 20892 USA.
   [Wimer, H. F.] Smithsonian Inst, Natl Museum Nat Hist, Dept Vertebrate Zool, Washington, DC 20560 USA.
   [Wimer, H. F.; Yamada, S. S.; Yang, T.; Holmbeck, K.] NIDCR, NIH, Bethesda, MD USA.
   [Foster, B. L.] Ohio State Univ, Coll Dent, Biosci Div, 4163 Poste Hall,305 W 12th Ave, Columbus, OH 43210 USA.
RP Foster, BL (reprint author), Ohio State Univ, Coll Dent, Biosci Div, 4163 Poste Hall,305 W 12th Ave, Columbus, OH 43210 USA.
EM foster.1004@osu.edu
FU Intramural Research Programs of the National Institute of Arthritis and
   Musculoskeletal and Skin Diseases (NIAMS); National Institute for Dental
   and Craniofacial Research (NIDCR) of the National Institutes of Health
   (NIH, Bethesda, MD); NIAMS/NIH [AR066110]; Peking University School and
   Hospital of Stomatology; NIH Medical Research Scholars Program (MRSP);
   NIH; NIH from the Doris Duke Charitable Foundation; American Association
   for Dental Research; Howard Hughes Medical Institute; Colgate-Palmolive
   Company
FX This research was supported by the Intramural Research Programs of the
   National Institute of Arthritis and Musculoskeletal and Skin Diseases
   (NIAMS; to BLF) and the National Institute for Dental and Craniofacial
   Research (NIDCR; to KH) of the National Institutes of Health (NIH,
   Bethesda, MD), grant AR066110 from NIAMS/NIH (to BLF), by a 2014-2015
   Overseas Research and Personal Training Fund from Peking University
   School and Hospital of Stomatology (to HX), and by the NIH Medical
   Research Scholars Program (MRSP)(to TNS). MRSP is a public private
   partnership supported jointly by the NIH and generous contributions to
   the Foundation for the NIH from the Doris Duke Charitable Foundation,
   the American Association for Dental Research, the Howard Hughes Medical
   Institute, and the Colgate-Palmolive Company, as well as alumni of
   student research programs and other individual supporters. The authors
   thank Dr. Pamela G. Robey (NIDCR/NIH) for her support and critical
   review of the manuscript.
NR 92
TC 2
Z9 2
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 266
EP 283
DI 10.1016/j.matbio.2016.01.002
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700023
PM 26780723
ER

PT J
AU Marinovich, R
   Soenjaya, Y
   Wallace, GQ
   Zuskov, A
   Dunkman, A
   Foster, BL
   Ao, M
   Bartman, K
   Lam, V
   Rizkalla, A
   Beier, F
   Somerman, MJ
   Holdsworth, DW
   Soslowsky, LJ
   Lagugne-Labarthet, F
   Goldberg, HA
AF Marinovich, Ryan
   Soenjaya, Yohannes
   Wallace, Gregory Q.
   Zuskov, Andre
   Dunkman, Andrew
   Foster, Brian L.
   Ao, Min
   Bartman, Kevin
   Lam, Vida
   Rizkalla, Amin
   Beier, Frank
   Somerman, Martha J.
   Holdsworth, David W.
   Soslowsky, Louis J.
   Lagugne-Labarthet, Francois
   Goldberg, Harvey A.
TI The role of bone sialoprotein in the tendon-bone insertion
SO MATRIX BIOLOGY
LA English
DT Article
DE Bone sialoprotein; Osteopontin; Enthesis; Quadriceps tendon;
   Supraspinatus tendon; Calcified fibrocartilage
ID BSP-NULL MICE; FIBROCARTILAGE CELLS; ACHILLES-TENDON; KNEE-JOINT;
   IN-VITRO; MINERALIZATION; HYDROXYAPATITE; ENTHESIS; COLLAGEN;
   OSTEOPONTIN
AB Tendons/ligaments insert into bone via a transitional structure, the enthesis, which is susceptible to injury and difficult to repair. Fibrocartilaginous entheses contain fibrocartilage in their transitional zone, part of which is mineralized. Mineral-associated proteins within this zone have not been adequately characterized. Members of the Small Integrin Binding Ligand N-linked Glycoprotein (SIBLING) family are acidic phosphoproteins expressed in mineralized tissues. Here we show that two SIBLING proteins, bone sialoprotein (BSP) and osteopontin (OPN), are present in the mouse enthesis. Histological analyses indicate that the calcified zone of the quadriceps tendon enthesis is longer in Bsp(-/-) mice, however no difference is apparent in the supraspinatus tendon enthesis. In an analysis of mineral content within the calcified zone, micro-CT and Raman spectroscopy reveal that the mineral content in the calcified fibrocartilage of the quadriceps tendon enthesis are similar between wild type and Bsp(-/-) mice. Mechanical testing of the patellar tendon shows that while the tendons fail under similar loads, the Bsp(-/-) patellar tendon is 7.5% larger in cross sectional area than wild type tendons, resulting in a 16.5% reduction in failure stress. However, Picrosirius Red staining shows no difference in collagen organization. Data collected here indicate that BSP is present in the calcified fibrocartilage of murine entheses and suggest that BSP plays a regulatory role in this structure, influencing the growth of the calcified fibrocartilage in addition to the weakening of the tendon mechanical properties. Based on the phenotype of the Bsp(-/-) mouse enthesis, and the known in vitro functional properties of the protein, BSP may be a useful therapeutic molecule in the reattachment of tendons and ligaments to bone. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Marinovich, Ryan; Bartman, Kevin; Goldberg, Harvey A.] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada.
   [Soenjaya, Yohannes; Rizkalla, Amin] Univ Western Ontario, Biomed Engn Program, London, ON N6A 5C1, Canada.
   [Wallace, Gregory Q.; Lagugne-Labarthet, Francois] Univ Western Ontario, Dept Chem, London, ON N6A 5C1, Canada.
   [Zuskov, Andre; Dunkman, Andrew; Soslowsky, Louis J.] Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA.
   [Foster, Brian L.] Ohio State Univ, Coll Dent, Div Biosci, Columbus, OH 43210 USA.
   [Ao, Min; Somerman, Martha J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
   [Lam, Vida; Rizkalla, Amin; Goldberg, Harvey A.] Univ Western Ontario, Sch Dent, London, ON N6A 5C1, Canada.
   [Beier, Frank] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada.
   [Holdsworth, David W.] Univ Western Ontario, Dept Surg, London, ON N6A 5C1, Canada.
   [Holdsworth, David W.] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5C1, Canada.
RP Goldberg, HA (reprint author), Univ Western Ontario, Sch Dent, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada.
EM hagoldbe@uwo.ca
RI Holdsworth, David/F-6315-2012
FU Canadian Institutes for Health Research (CIHR) [FRN130572]; Intramural
   Research Program of the National Institute of Arthritis and
   Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of
   Health (NIH); NIAMS [AR 066110]; Penn Center for Musculoskeletal
   Disorders (NIH/NIAMS) [P30 AR050950]; Joint Motion Program, a CIHR; AO
   Foundation (Davos, Switzerland); Natural Science and Engineering
   Research Council Discovery grant program; Ontario Dental Association
FX This research was supported by the Canadian Institutes for Health
   Research (CIHR) (FRN130572 - HAG), the Intramural Research Program of
   the National Institute of Arthritis and Musculoskeletal and Skin
   Diseases (NIAMS) of the National Institutes of Health (NIH) (MJS), NIAMS
   grant AR 066110 (BLF), and at the Penn Center for Musculoskeletal
   Disorders (NIH/NIAMS, P30 AR050950 - LJS). YS was supported by The Joint
   Motion Program, a CIHR funded Strategic Training Initiative in Health
   Research (STIHR), and the AO Foundation (Davos, Switzerland). FLL's and
   GQW's contribution to this work was supported by the Natural Science and
   Engineering Research Council Discovery grant program. VL was supported
   by an Ontario Dental Association sponsored studentship provided through
   the Schulich Dentistry Summer Student Research Program.
NR 45
TC 1
Z9 1
U1 10
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
EI 1569-1802
J9 MATRIX BIOL
JI Matrix Biol.
PD MAY-JUL
PY 2016
VL 52-54
SI SI
BP 325
EP 338
DI 10.1016/j.matbio.2016.01.016
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DP0PC
UT WOS:000378190700027
PM 26826499
ER

PT J
AU Comi, AM
   Sahin, M
   Hammill, A
   Kaplan, EH
   Juhasz, C
   North, P
   Ball, KL
   Levin, AV
   Cohen, B
   Morris, J
   Lo, W
   Roach, ES
AF Comi, Anne M.
   Sahin, Mustafa
   Hammill, Adrienne
   Kaplan, Emma H.
   Juhasz, Csaba
   North, Paula
   Ball, Karen L.
   Levin, Alex V.
   Cohen, Bernard
   Morris, Jill
   Lo, Warren
   Roach, E. Steve
TI Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE Sturge-Weber syndrome; GNAQ; somatic mutation; port-wine birthmark;
   glaucoma; seizures
ID EXUDATIVE RETINAL-DETACHMENT; PULSED DYE-LASER; VASCULAR MALFORMATIONS;
   RAPAMYCIN; CHILDREN; MODEL; MICE; ABNORMALITIES; TRANSDUCTION;
   HEMANGIOMA
AB Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS.
C1 [Comi, Anne M.; Kaplan, Emma H.] Kennedy Krieger Inst, Dept Neurol, 801 North Broadway, Baltimore, MD 21205 USA.
   [Comi, Anne M.; Kaplan, Emma H.] Johns Hopkins Univ, Sch Med, 801 North Broadway, Baltimore, MD USA.
   [Comi, Anne M.; Cohen, Bernard] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
   [Sahin, Mustafa] Boston Childrens Hosp, Dept Radiol, Boston, MA USA.
   [Sahin, Mustafa] Harvard Univ, Sch Med, Boston, MA USA.
   [Hammill, Adrienne] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
   [Hammill, Adrienne] Univ Cincinnati, Cincinnati, OH USA.
   [Juhasz, Csaba] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
   [Juhasz, Csaba] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
   [North, Paula] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
   [Ball, Karen L.] Sturge Weber Fdn, Randolph, NJ USA.
   [Levin, Alex V.] Thomas Jefferson Univ, Wills Eye Hosp, Sidney Kimmel Med Coll, Dept Ophthalmol, Philadelphia, PA 19107 USA.
   [Levin, Alex V.] Thomas Jefferson Univ, Wills Eye Hosp, Sidney Kimmel Med Coll, Dept Pediat, Philadelphia, PA 19107 USA.
   [Cohen, Bernard] Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA.
   [Morris, Jill] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Lo, Warren; Roach, E. Steve] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
   [Lo, Warren; Roach, E. Steve] Ohio State Univ, Coll Med, Dept Neurol, Columbus, OH 43210 USA.
   [Lo, Warren; Roach, E. Steve] Nationwide Childrens Hosp, Columbus, OH USA.
RP Comi, AM (reprint author), Kennedy Krieger Inst, Dept Neurol, 801 North Broadway, Baltimore, MD 21205 USA.; Comi, AM (reprint author), Johns Hopkins Univ, Sch Med, 801 North Broadway, Baltimore, MD USA.
EM comi@kennedykrieger.org
OI Bischoff, Joyce/0000-0002-6367-1974; Hammill,
   Adrienne/0000-0003-0820-4924
FU National Institute of Neurological Disorders and Stroke of the National
   Institutes of Health [R13NS090861]; Sturge-Weber Foundation
FX This Work was funded by the National Institute of Neurological Disorders
   and Stroke of the National Institutes of Health under Award Number
   R13NS090861 (Comi) and by the Sturge-Weber Foundation.
NR 54
TC 1
Z9 1
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD MAY
PY 2016
VL 58
BP 12
EP 24
DI 10.1016/j.pediatrneurol.2015.11.009
PG 13
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA DP0NZ
UT WOS:000378187800003
PM 27268758
ER

PT J
AU Fessler, MB
   Summer, RS
AF Fessler, Michael B.
   Summer, Ross S.
TI Surfactant Lipids at the Host-Environment Interface Metabolic Sensors,
   Suppressors, and Effectors of Inflammatory Lung Disease
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE lung; surfactant; phospholipid; cholesterol; innate immunity
ID RESPIRATORY-DISTRESS-SYNDROME; LOW-DENSITY-LIPOPROTEIN;
   MASS-SPECTROMETRIC CHARACTERIZATION; PHOSPHOLIPID OXIDATION-PRODUCTS;
   SYNCYTIAL VIRUS-INFECTION; ALVEOLAR LINING MATERIAL; LPS-BINDING
   PROTEIN; OXIDIZED PHOSPHOLIPIDS; EPITHELIAL-CELLS; INNATE IMMUNITY
AB The lipid composition of pulmonary surfactant is unlike that of any other body fluid. This extracellular lipid reservoir is also uniquely susceptible by virtue of its direct and continuous exposure to environmental oxidants, inflammatory agents, and pathogens. Historically, the greatest attention has been focused on those biophysical features of surfactant that serve to reduce surface tension at the air-liquid interface. More recently, surfactant lipids have also been recognized as bioactive molecules that maintain immune quiescence in the lung but can also be remodeled by the inhaled environment into neolipids that mediate key roles in inflammation, immunity, and fibrosis. This review focuses on the roles in inflammatory and infectious lung disease of two classes of native surfactant lipids, glycerophospholipids and sterols, and their corresponding oxidized species, oxidized glycerophospholipids and oxysterols. We highlight evidence that surfactant composition is sensitive to circulating lipoproteins and that the lipid milieu of the alveolus should thus be recognized as susceptible to diet and common systemic metabolic disorders. We also discuss intriguing evidence suggesting that oxidized surfactant lipids may represent an evolutionary link between immunity and tissue homeostasis that arose in the primordial lung. Taken together, the emerging picture is one in which the unique environmental susceptibility of the lung, together with its unique extracellular lipid requirements, may have made this organ both an evolutionary hub and an engine for lipid-immune cross-talk.
C1 [Fessler, Michael B.] NIEHS, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA.
   [Summer, Ross S.] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA.
   [Summer, Ross S.] Thomas Jefferson Univ, Jane & Leonard Korman Lung Ctr, Philadelphia, PA 19107 USA.
RP Fessler, MB (reprint author), NIEHS, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA.
EM fesslerm@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
   Health Sciences [Z01 ES102005]; National Institute of Alcohol Abuse and
   Alcoholism [R21 AA023571]; National Heart, Lung, and Blood Institute
   [R01 HL105490]
FX This work was supported by the National Institutes of Health, the
   National Institute of Environmental Health Sciences (Z01 ES102005), the
   National Institute of Alcohol Abuse and Alcoholism (R21 AA023571), and
   the National Heart, Lung, and Blood Institute (R01 HL105490).
NR 132
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Z9 2
U1 1
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD MAY
PY 2016
VL 54
IS 5
BP 624
EP 635
DI 10.1165/rcmb.2016-0011PS
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA DO2EJ
UT WOS:000377592300004
PM 26859434
ER

PT J
AU Foxman, B
   Seitz, SM
   Rothenberg, R
AF Foxman, Betsy
   Seitz, Sandra Melnick
   Rothenberg, Richard
TI Epidemiology and the microbiome
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID CESAREAN-SECTION; DISEASE; ASSOCIATION; DYSBIOSIS; DELIVERY
C1 [Foxman, Betsy] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Seitz, Sandra Melnick] NIH, Ctr Sci Review, Bldg 10, Bethesda, MD 20892 USA.
   [Rothenberg, Richard] Georgia State Univ, Div Epidemiol & Biostat, Atlanta, GA 30303 USA.
RP Foxman, B (reprint author), Univ Michigan, Ctr Mol & Clin Epidemiol Infect Dis, Sch Publ Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM bfoxman@umich.edu
OI Foxman, Betsy/0000-0001-6682-238X
NR 32
TC 0
Z9 0
U1 6
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD MAY
PY 2016
VL 26
IS 5
BP 386
EP 387
DI 10.1016/j.annepidem.2016.04.007
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DO2WN
UT WOS:000377641800014
PM 27180115
ER

PT J
AU Sobczynska-Malefora, A
   Pangilinan, F
   Plant, GT
   Velkova, A
   Harrington, DJ
   Molloy, AM
   Brody, LC
AF Sobczynska-Malefora, Agata
   Pangilinan, Faith
   Plant, Gordon T.
   Velkova, Aneliya
   Harrington, Dominic J.
   Molloy, Anne M.
   Brody, Lawrence C.
TI Association of a transcobalamin II genetic variant with falsely low
   results for the holotranscobalamin immunoassay
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Holotranscobalamin; monoclonal antibody; single nucleotide polymorphism;
   transcobalamin; vitamin B-12; cobalamin
ID NORMAL HUMAN-SERUM; METHYLMALONIC ACID; VITAMIN-B-12 STATUS; DEFICIENCY;
   TRANSPORT; COBALAMIN
AB Background The clinical use of holotranscobalamin (holoTC) testing to evaluate vitamin B-12 status has increased in recent years. We present two patients (African Caribbean and Indian heritage), in which the holoTC assay indicated severe B-12 deficiency (< 5 pmol/L). Additional clinical tests revealed that these patients had normal levels of total vitamin B-12 in blood and unremarkable levels of two other markers of vitamin B-12 status, homocysteine and methylmalonic acid. We hypothesized that these patients carry a variant in the transcobalamin gene (TCN2) that influences the most widely commercially available holoTC test -Active-B-12 (Axis-Shield Diagnostics Ltd).
   Design Exon sequencing of the TCN2 gene was carried out. Protein characterization included total transcobalamin (TCN2) detection by Western blot, and holoTC by 57 Co-labelled B-12 binding followed by size fractionation.
   Results Exon sequencing of TCN2 revealed both patients were homozygous for the minor allele of rs35838082 (p.R215W). Western blot and chromatographic analyses revealed that the serum of these patients contains intact transcobalamin and that this variant-containing protein binds vitamin B-12. The variant is rare in Caucasians (minor allele frequency (MAF) < 0.01) but more common in South Asians (MAF similar to 0.02) and those of African origin (MAF similar to 0.25).
   Conclusions The impeded ability to detect normal levels of holoTC in these two patients may be due to this variant interfering with the detection of holoTC by one or both of the monoclonal antibodies currently employed in the Active-B-12 test. Laboratories should be aware of this variant and use confirmatory tests when applicable.
C1 [Sobczynska-Malefora, Agata; Harrington, Dominic J.] Viapath, St Thomas Hosp, Nutristasis Unit, North Wing,Westminster Bridge Rd, London SE1 7EH, England.
   [Pangilinan, Faith; Velkova, Aneliya; Brody, Lawrence C.] NHGRI, Med Genom & Metab Genet Branch, 50 South Dr, Bethesda, MD 20892 USA.
   [Plant, Gordon T.] Guys & St Thomas NHS Fdn Trust, Med Eye Unit, Moorfields Eye Hosp, Natl Hosp Neurol & Neurosurg, London, England.
   [Molloy, Anne M.] Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland.
   [Plant, Gordon T.] St Thomas Hosp, Med Eye Unit, North Wing,Westminster Bridge Rd, London SE1 7EH, England.
   [Molloy, Anne M.] Trinity Biomed Sci Inst, Sch Med, Room 6-09,Pearse St, Dublin 2, Ireland.
RP Sobczynska-Malefora, A (reprint author), Viapath, St Thomas Hosp, Nutristasis Unit, North Wing,Westminster Bridge Rd, London SE1 7EH, England.
EM agata.malefora@viapath.co.uk
FU National Human Genome Research Institute
FX The Intramural Research Program of the National Human Genome Research
   Institute funded this work. We also thank Axis-Shield for their support
   with the investigations of these cases and Ms. Deborah Gibson of Medical
   Eye Unit, Ophthalmology, Guy's and St. Thomas' NHS Foundation Trust for
   her support and coordination of patient visits. We thank the Molecular
   Haemostasis Unit at Viapath, St. Thomas' Hospital for extracting DNA.
NR 16
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
EI 1365-2362
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD MAY
PY 2016
VL 46
IS 5
BP 434
EP 439
DI 10.1111/eci.12617
PG 6
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DK1DB
UT WOS:000374651600008
PM 26951924
ER

PT J
AU DeRoo, L
   Skjaerven, R
   Wilcox, A
   Klungsoyr, K
   Wikstrom, AK
   Morken, NH
   Cnattingius, S
AF DeRoo, Lisa
   Skjaerven, Rolv
   Wilcox, Allen
   Klungsoyr, Kari
   Wikstrom, Anna-Karin
   Morken, Nils-Halvdan
   Cnattingius, Sven
TI Placental abruption and long-term maternal cardiovascular disease
   mortality: a population-based registry study in Norway and Sweden
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Placental abruption; Cardiovascular disease; Women; Mortality
ID BIRTH CERTIFICATE DATA; PREGNANCY COMPLICATIONS; UNITED-STATES;
   RISK-FACTORS; TIME-SCALE; FOLLOW-UP; WOMEN; PREECLAMPSIA; METAANALYSIS;
   SMOKING
AB Women with preeclamptic pregnancies have increased long-term cardiovascular disease (CVD) mortality. We explored this mortality risk among women with placental abruption, another placental pathology. We used linked Medical Birth Registry and Death Registry data to study CVD mortality among over two million women with a first singleton birth between 1967 and 2002 in Norway and 1973 and 2003 in Sweden. Women were followed through 2009 and 2010, respectively, to ascertain subsequent pregnancies and mortality. Cox regression analysis was used to estimate associations between placental abruption and cardiovascular mortality adjusting for maternal age, education, year of the pregnancy and country. There were 49,944 deaths after an average follow-up of 23 years, of which 5453 were due to CVD. Women with placental abruption in first pregnancy (n = 10,981) had an increased risk of CVD death (hazard ratio 1.8; 95 % confidence interval 1.3, 2.4). Results were essentially unchanged by excluding women with pregestational hypertension, preeclampsia or diabetes. Women with placental abruption in any pregnancy (n = 23,529) also had a 1.8-fold increased risk of CVD mortality (95 % confidence interval 1.5, 2.2) compared with women who never experienced the condition. Our findings provide evidence that placental abruption, like other placental complications of pregnancy, is associated with women's increased risk of later CVD mortality.
C1 [DeRoo, Lisa; Skjaerven, Rolv; Klungsoyr, Kari; Morken, Nils-Halvdan] Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway.
   [Skjaerven, Rolv; Klungsoyr, Kari] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
   [Wilcox, Allen] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Wikstrom, Anna-Karin] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.
   [Morken, Nils-Halvdan] Univ Bergen, Dept Clin Sci, Bergen, Norway.
   [Wikstrom, Anna-Karin; Cnattingius, Sven] Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
   [Wikstrom, Anna-Karin; Cnattingius, Sven] Karolinska Inst, Stockholm, Sweden.
RP DeRoo, L (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Postboks 7804, N-5018 Bergen, Norway.
EM Lisa.De.Roo@igs.uib.no
OI Wilcox, Allen/0000-0002-3376-1311
FU Norwegian Research Council; European Union [259679]; Intramural Research
   Program of the NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Norwegian Research Council, the
   European Union's Seventh Framework Program (FP2007-2001; under Grant
   Agreement 259679), and the Intramural Research Program of the NIH,
   National Institute of Environmental Health Sciences. We thank Drs. Donna
   Baird and Anne Marie Z. Jukic for providing helpful comments on this
   manuscript.
NR 36
TC 3
Z9 3
U1 1
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
EI 1573-7284
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD MAY
PY 2016
VL 31
IS 5
BP 501
EP 511
DI 10.1007/s10654-015-0067-9
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DO6KZ
UT WOS:000377893600007
PM 26177801
ER

PT J
AU Morris, LS
   Kundu, P
   Irvine, MA
   Harrison, NA
   Robbins, TW
   Daw, N
   Bullmore, ET
   Voon, V
AF Morris, Laurel S.
   Kundu, Prantik
   Irvine, Michael A.
   Harrison, Neil A.
   Robbins, Trevor W.
   Daw, Nathaniel
   Bullmore, Edward T.
   Voon, Valerie
TI LATENT SUBSTRATES OF COMPULSIVITY AND BEHAVIOURAL FLEXIBILITY
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Morris, Laurel S.; Kundu, Prantik; Irvine, Michael A.; Bullmore, Edward T.; Voon, Valerie] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 0QQ, England.
   [Morris, Laurel S.; Robbins, Trevor W.; Bullmore, Edward T.; Voon, Valerie] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
   [Kundu, Prantik] NIMH, Sect Funct Imaging Methods, Bethesda, MD 20814 USA.
   [Harrison, Neil A.] Brighton & Sussex Med Sch, Dept Psychiat, Brighton BN1 9PX, E Sussex, England.
   [Robbins, Trevor W.] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England.
   [Daw, Nathaniel; Voon, Valerie] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Daw, Nathaniel; Voon, Valerie] NYU, Dept Psychiat, New York, NY 10003 USA.
   [Bullmore, Edward T.; Voon, Valerie] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England.
   [Bullmore, Edward T.] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England.
OI Kundu, Prantik/0000-0001-9367-3068
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAY
PY 2016
VL 26
IS 5
SI SI
BP 892
EP 893
DI 10.1016/j.euroneuro.2015.06.025
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DO4GK
UT WOS:000377739600019
ER

PT J
AU Negussie, AH
   Partanen, A
   Mikhail, AS
   Xu, S
   Abi-Jaoudeh, N
   Maruvada, S
   Wood, BJ
AF Negussie, Ayele H.
   Partanen, Ari
   Mikhail, Andrew S.
   Xu, Sheng
   Abi-Jaoudeh, Nadine
   Maruvada, Subha
   Wood, Bradford J.
TI Thermochromic tissue-mimicking phantom for optimisation of thermal
   tumour ablation
SO INTERNATIONAL JOURNAL OF HYPERTHERMIA
LA English
DT Article
DE HIFU; laser; microwave; RF; thermal phantom; thermal therapy; thermal
   ablation; thermochromic; tissue-mimicking
ID INTENSITY FOCUSED ULTRASOUND; HYPERTHERMIA; RADIOFREQUENCY; TEMPERATURE;
   THERAPY; DELIVERY
AB Purpose The purpose of this study was to (1) develop a novel tissue-mimicking thermochromic (TMTC) phantom that permanently changes colour from white to magenta upon heating above ablative temperatures, and (2) assess its utility for specific applications in evaluating thermal therapy devices.Materials and methods Polyacrylamide gel mixed with thermochromic ink was custom made to produce a TMTC phantom that changes its colour upon heating above biological ablative temperatures (> 60 degrees C). The thermal properties of the phantom were characterised, and compared to those of human tissue. In addition, utility of this phantom as a tool for the assessment of laser and microwave thermal ablation was examined.Results The mass density, thermal conductivity, and thermal diffusivity of the TMTC phantom were measured as 10331.0kg/m(3), 0.590 +/- 0.015 W/m.K, and 0.145 +/- 0.002mm(2)/s, respectively, and found to be in agreement with reported values for human soft tissues. Heating the phantom with laser and microwave ablation devices produced clearly demarcated regions of permanent colour change geographically corresponding to regions with temperature elevations above 60 degrees C.Conclusion The TMTC phantom provides direct visualisation of ablation dynamics, including ablation volume and geometry as well as peak absolute temperatures within the treated region post-ablation. This phantom can be specifically tailored for different thermal therapy modalities, such as radiofrequency, laser, microwave, or therapeutic ultrasound ablation. Such modality-specific phantoms may enable better quality assurance, device characterisation, and ablation parameter optimisation, or optimise the study of dynamic heating parameters integral to drug device combination therapies relying upon heat.
C1 [Negussie, Ayele H.; Partanen, Ari; Mikhail, Andrew S.; Xu, Sheng; Abi-Jaoudeh, Nadine; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, MSC 1182,Bldg 10,Room 1C341, Bethesda, MD 20892 USA.
   [Partanen, Ari] Philips, Clin Sci MR Therapy, Andover, MA USA.
   [Maruvada, Subha] US FDA, Silver Spring, MD USA.
RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, MSC 1182,Bldg 10,Room 1C341, Bethesda, MD 20892 USA.
EM bwood@nih.gov
OI Partanen, Ari/0000-0003-1985-149X; Mikhail, Andrew/0000-0001-9206-5765
FU Philips
FX A.H.N., A.S.M., S.X., N.A.-J., S.M. and B.J.W. have no conflict of
   interest to declare. A. P. is a paid employee of Philips. The authors
   alone are responsible for the content and writing of the paper.
NR 32
TC 1
Z9 1
U1 2
U2 9
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0265-6736
EI 1464-5157
J9 INT J HYPERTHER
JI Int. J. Hyperthermia
PD MAY
PY 2016
VL 32
IS 3
BP 239
EP 243
DI 10.3109/02656736.2016.1145745
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DO4QD
UT WOS:000377767000003
PM 27099078
ER

PT J
AU Pena-Munzenmayer, G
   George, AT
   Shull, GE
   Melvin, JE
   Catalan, MA
AF Pena-Munzenmayer, Gaspar
   George, Alvin T.
   Shull, Gary E.
   Melvin, James E.
   Catalan, Marcelo A.
TI Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl-/HCO3-
   exchanger
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID THICK ASCENDING LIMB; ACID-BASE TRANSPORT; GLAND ACINAR-CELLS; SQUID
   GIANT-AXONS; CHLORIDE TRANSPORT; NA+HCO3-COTRANSPORTER; INTERCALATED
   CELLS; ANION-EXCHANGER; MURINE DUODENUM; SECRETION
AB Ae4 (Slc4a9) belongs to the Slc4a family of Cl-/HCO3- exchangers and Na+-HCO3- cotransporters, but its ion transport cycle is poorly understood. In this study, we find that native Ae4 activity in mouse salivary gland acinar cells supports Na+-dependent Cl-/HCO3- exchange that is comparable with that obtained upon heterologous expression of mouse Ae4 and human AE4 in CHO-K1 cells. Additionally, whole cell recordings and ion concentration measurements demonstrate that Na+ is transported by Ae4 in the same direction as HCO3- (and opposite to that of Cl-) and that ion transport is not associated with changes in membrane potential. We also find that Ae4 can mediate Na+-HCO3- cotransport-like activity under Cl--free conditions. However, whole cell recordings show that this apparent Na+-HCO3- cotransport activity is in fact electroneutral HCO3-/Na+-HCO3- exchange. Although the Ae4 anion exchanger is thought to regulate intracellular Cl-concentration in exocrine gland acinar cells, our thermodynamic calculations predict that the intracellular Na+, Cl-, and HCO3- concentrations required for Ae4-mediated Cl-influx differ markedly from those reported for acinar secretory cells at rest or under sustained stimulation. Given that K+ ions share many properties with Na+ ions and reach intracellular concentrations of 140-150 mM (essentially the same as extracellular [Na+]), we hypothesize that Ae4 could mediate K+-dependent Cl-/HCO3- exchange. Indeed, we find that Ae4 mediates Cl-/HCO3- exchange activity in the presence of K+ as well as Cs+, Li+, and Rb+. In summary, our results strongly suggest that Ae4 is an electroneutral Cl-/nonselective cation-HCO3- exchanger. We postulate that the physiological role of Ae4 in secretory cells is to promote Cl- influx in exchange for K+(Na+) and HCO3- ions.
C1 [Pena-Munzenmayer, Gaspar; George, Alvin T.; Melvin, James E.; Catalan, Marcelo A.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA.
   [Shull, Gary E.] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA.
RP Catalan, MA (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA.
EM marcelo.catalan@nih.gov
FU Intramural Research Program of the National Institute of Dental and
   Craniofacial Research, National Institutes of Health (NIH); NIH grant
   [DK050594]
FX This study was supported by the Intramural Research Program of the
   National Institute of Dental and Craniofacial Research, National
   Institutes of Health (NIH; to J.E. Melvin) and NIH grant DK050594 (to
   G.E. Shull).
NR 41
TC 1
Z9 1
U1 2
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1295
EI 1540-7748
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD MAY
PY 2016
VL 147
IS 5
BP 423
EP 436
DI 10.1085/jgp.201611571
PG 14
WC Physiology
SC Physiology
GA DO3WV
UT WOS:000377714100005
PM 27114614
ER

PT J
AU Sushchyk, S
   Xi, ZX
   Wang, JB
AF Sushchyk, Sarah
   Xi, Zheng-Xiong
   Wang, Jia Bei
TI Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A
   Promising Treatment for Prevention of Cocaine Relapse
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ENDOGENOUS OPIOID SYSTEM; RECEPTOR KNOCKOUT MICE; BETA-ENDORPHIN;
   NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR; DOPAMINE-RECEPTORS;
   GENE-EXPRESSION; RATS; REINSTATEMENT; DEPENDENCE
AB Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (L-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects of L-THP and LDN on cocaine self-administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination of L-THP and LDN reduces drug-seeking behavior during reinstatement more potently than L-THP alone. Additionally, the combination of L-THP and LDN attenuates the sedative locomotor effect induced by L-THP. Furthermore, we revealed that treatment with the combination of L-THP and LDN has an upregulatory effect on both plasma beta-endorphin and hypothalamic POMC that was not observed in L-THP-treated groups. These results suggest that the combination of L-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention.
C1 [Sushchyk, Sarah; Wang, Jia Bei] Univ Maryland, Dept Pharmaceut Sci, 20 N Pine St Room N527, Baltimore, MD 21201 USA.
   [Xi, Zheng-Xiong] Natl Inst Drug Abuse, Intramural Res Program, Mol Targets & Medicat Discovery Branch, Baltimore, MD 21224 USA.
RP Wang, JB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmacol, 20 N Pine St Room N527, Baltimore, MD 21201 USA.
EM jwang@rx.umaryland.edu
FU National Institutes of Health National Institute on Drug Abuse
   [DA-031401]; National Institute on Drug Abuse Intramural Research
   Program
FX The National Institutes of Health National Institute on Drug Abuse
   [Grant DA-031401 (J.B.W.)] and the National Institute on Drug Abuse
   Intramural Research Program supported this work. The authors declare no
   finical conflict.
NR 57
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAY
PY 2016
VL 357
IS 2
BP 248
EP 257
DI 10.1124/jpet.115.229542
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DO3ON
UT WOS:000377691000003
PM 26903543
ER

PT J
AU Yasujima, T
   Saito, K
   Moore, R
   Negishi, M
AF Yasujima, Tomoya
   Saito, Kosuke
   Moore, Rick
   Negishi, Masahiko
TI Phenobarbital and Insulin Reciprocate Activation of the Nuclear Receptor
   Constitutive Androstane Receptor through the Insulin Receptor
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MEDIATED GLUCOSE-METABOLISM; CYP2B2 GENE-EXPRESSION; RAT HEPATOCYTES;
   CAR; PHOSPHORYLATION; INDUCTION; BINDING; LIVER; FOXO1; TRANSACTIVATION
AB Phenobarbital (PB) antagonized insulin to inactivate the insulin receptor and attenuated the insulin receptor downstream protein kinase B(AKT)-forkhead box protein O1 and extracellular signal-regulated kinase 1/2 signals in mouse primary hepatocytes and HepG2 cells. Hepatic AKT began dephosphorylation in an early stage of PB treatment, and blood glucose levels transiently increased in both wild-type and constitutive androstane receptor (CAR) knockout (KO) mice. On the other hand, blood glucose levels increased in wild-type mice, but not KO mice, in later stages of PB treatment. As a result, PB, acting as an insulin receptor antagonist, elicited CAR-independent increases and CAR-dependent decreases of blood glucose levels at these different stages of treatment, respectively. Reciprocally, insulin activation of the insulin receptor repressed CAR activation and induction of its target CYP2B6 gene in HepG2 cells. Thus, PB and insulin cross-talk through the insulin receptor to regulate glucose and drug metabolism reciprocally.
C1 [Yasujima, Tomoya; Saito, Kosuke; Moore, Rick; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
   National Institute of Environmental Health Sciences [Z01ES71005-01]
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health and National Institute of Environmental
   Health Sciences [Grant Z01ES71005-01].
NR 24
TC 0
Z9 0
U1 1
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAY
PY 2016
VL 357
IS 2
BP 367
EP 374
DI 10.1124/jpet.116.232140
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DO3ON
UT WOS:000377691000016
PM 26994072
ER

PT J
AU Eiden, R
   Schuetzel, P
   Huestis, M
AF Eiden, Rina
   Schuetzel, Pamela
   Huestis, Marilyn
TI Prenatal Tobacco and Cannabis Exposure: Effects on Infant Regulation via
   Fetal Growth, Maternal Stress, and Anger/Hostility.
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 40th Anniversary Annual Meeting of the
   Developmental-Neurotoxicology-Society Held in Conjunction with the 56th
   Annual Meeting of the Teratology-Society
CY JUN 25-29, 2016
CL San Antonio, TX
SP Dev Neurotoxicol Soc, Teratol Soc
C1 [Eiden, Rina; Schuetzel, Pamela] SUNY Buffalo, Buffalo, NY USA.
   [Huestis, Marilyn] Natl Inst Drug Abuse, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
EI 1872-9738
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2016
VL 55
MA DNTS P12
BP 74
EP 75
PG 2
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA DO6WC
UT WOS:000377923200051
ER

PT J
AU Li, SP
   Zhao, YH
   Zhao, Z
   Wu, XL
   Sun, LF
   Liu, QS
   Wu, YK
AF Li, Shengping
   Zhao, Yanhe
   Zhao, Zheng
   Wu, Xiuling
   Sun, Lifang
   Liu, Qingsong
   Wu, Yunkun
TI Crystal Structure of the GRAS Domain of SCARECROW-LIKE7 in Oryza sativa
SO PLANT CELL
LA English
DT Article
ID SIGNAL-TRANSDUCTION; ARABIDOPSIS ROOT; TRANSCRIPTION FACTOR;
   GENE-EXPRESSION; PROTEIN FAMILY; DNA-BINDING; GIBBERELLIN; RESPONSES;
   REGULATOR; MECHANISM
AB GRAS proteins belong to a plant-specific protein family with many members and play essential roles in plant growth and development, functioning primarily in transcriptional regulation. Proteins in the family are minimally defined as containing the conserved GRAS domain. Here, we determined the structure of the GRAS domain of Os-SCL7 from rice (Oryza sativa) to 1.82 angstrom. The structure includes cap and core subdomains and elucidates the features of the conserved GRAS LRI, VHIID, LRII, PFYRE, and SAW motifs. The structure is a dimer, with a clear groove to accommodate double-stranded DNA. Docking a DNA segment into the groove to generate an Os-SCL7/DNA complex provides insight into the DNA binding mechanism of GRAS proteins. Furthermore, the in vitro DNA binding property of Os-SCL7 and model-defined recognition residues are assessed by electrophoretic mobility shift analysis and mutagenesis assays. These studies reveal the structure and preliminary DNA interaction mechanisms of GRAS proteins and open the door to in-depth investigation and understanding of the individual pathways in which they play important roles.
C1 [Li, Shengping; Zhao, Yanhe; Wu, Xiuling; Sun, Lifang; Wu, Yunkun] Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350002, Peoples R China.
   [Zhao, Zheng] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Liu, Qingsong] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Peoples R China.
RP Wu, YK (reprint author), Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350002, Peoples R China.
EM wuyk@fjirsm.ac.cn
FU National Nature Science Foundation of China [31270790, 31470741,
   31500218]; National Thousand Talents Program of China
FX We thank beamline (BL17U1) staff at Shanghai Synchrotron Radiation
   Facility for assistance in data collection and D. Sauer for manuscript
   preparation. This work was financially supported by the National Nature
   Science Foundation of China (31270790, 31470741, and 31500218) and the
   National Thousand Talents Program of China.
NR 47
TC 6
Z9 6
U1 9
U2 18
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 1040-4651
EI 1532-298X
J9 PLANT CELL
JI Plant Cell
PD MAY
PY 2016
VL 28
IS 5
BP 1025
EP 1034
DI 10.1105/tpc.16.00018
PG 10
WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
GA DO9BT
UT WOS:000378080000008
PM 27081181
ER

PT J
AU Cong, Y
   McArthur, MA
   Cohen, M
   Jahrling, PB
   Janosko, KB
   Josleyn, N
   Kang, K
   Zhang, TF
   Holbrook, MR
AF Cong, Yu
   McArthur, Monica A.
   Cohen, Melanie
   Jahrling, Peter B.
   Janosko, Krisztina B.
   Josleyn, Nicole
   Kang, Kai
   Zhang, Tengfei
   Holbrook, Michael R.
TI Characterization of Yellow Fever Virus Infection of Human and Non-human
   Primate Antigen Presenting Cells and Their Interaction with CD4(+) T
   Cells
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II EXPRESSION; MHC CLASS-II;
   VISCEROTROPIC DISEASE; 17D VACCINE; RESPONSES; DYNAMICS; STRAIN;
   TRANSCRIPTION; ASIBI
AB Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4(+) T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-gamma and IL-2 production in CD4(+) T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4(+) T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.
C1 [Cong, Yu; Cohen, Melanie; Jahrling, Peter B.; Janosko, Krisztina B.; Josleyn, Nicole; Zhang, Tengfei; Holbrook, Michael R.] NIAID, Integrated Res Facil, Frederick, MD 21703 USA.
   [McArthur, Monica A.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA.
   [McArthur, Monica A.] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
   [Kang, Kai] Gears Inc, Lanham, MD USA.
RP Holbrook, MR (reprint author), NIAID, Integrated Res Facil, Frederick, MD 21703 USA.
EM Michael.holbrook@nih.gov
FU Battelle Memorial Institute; NIAID [HHSN2722007000161, R01-AI036525, U19
   AI082655]
FX YC, TZ, NJ, MC, KBJ and MRH were supported by Battelle Memorial
   Institute's prime contract with NIAID (Contract # HHSN2722007000161).
   MAM was supported in part by NIAID grants R01-AI036525 and U19 AI082655
   (CCHI). The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 33
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U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2016
VL 10
IS 5
AR e0004709
DI 10.1371/journal.pntd.0004709
PG 25
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DO4QY
UT WOS:000377769300050
PM 27191161
ER

PT J
AU Franca, CT
   Hostetler, JB
   Sharma, S
   White, MT
   Lin, E
   Kiniboro, B
   Waltmann, A
   Darcy, AW
   Suen, CSNLW
   Siba, P
   King, CL
   Rayner, JC
   Fairhurst, RM
   Mueller, I
AF Franca, Camila T.
   Hostetler, Jessica B.
   Sharma, Sumana
   White, Michael T.
   Lin, Enmoore
   Kiniboro, Benson
   Waltmann, Andreea
   Darcy, Andrew W.
   Suen, Connie S. N. Li Wai
   Siba, Peter
   King, Christopher L.
   Rayner, Julian C.
   Fairhurst, Rick M.
   Mueller, Ivo
TI An Antibody Screen of a Plasmodium vivax Antigen Library Identifies
   Novel Merozoite Proteins Associated with Clinical Protection
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID NEW-GUINEAN CHILDREN; MALARIA TRANSMISSION INTENSITY; P. FALCIPARUM;
   IMMUNE-RESPONSES; SURFACE PROTEIN; INFECTION; ACQUISITION; PREVENTION;
   PARASITES; REVEALS
AB Background
   Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design.
   Methodology/Principal Findings
   In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure, and socioeconomic and clinical indicators. 29 antigenic targets of natural immunity were identified. Of these, 12 highly-immunogenic proteins were strongly associated with age and thus cumulative lifetime exposure in Solomon Islanders (P<0.001-0.027). A subset of 6 proteins, selected on the basis of immunogenicity and expression levels, were used to examine antibody levels in plasma samples from a population of young Papua New Guinean children with well-characterized individual differences in exposure. This analysis identified a strong association between reduced risk of clinical disease and antibody levels to P12, P41, and a novel hypothetical protein that has not previously been studied, PVX_081550 (IRR 0.46-0.74; P<0.001-0.041).
   Conclusion/Significance
   These data emphasize the benefits of an unbiased screening approach in identifying novel vaccine candidate antigens. Functional studies are now required to establish whether PVX_081550 is a key component of the naturally-acquired protective immune response, a biomarker of immune status, or both.
C1 [Franca, Camila T.; White, Michael T.; Waltmann, Andreea; Suen, Connie S. N. Li Wai; Mueller, Ivo] Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Melbourne, Vic 3050, Australia.
   [Franca, Camila T.; Waltmann, Andreea; Suen, Connie S. N. Li Wai; Mueller, Ivo] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia.
   [Hostetler, Jessica B.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Hostetler, Jessica B.; Sharma, Sumana; Rayner, Julian C.] Wellcome Trust Sanger Inst, Malaria Programme, Hinxton, England.
   [White, Michael T.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, Ctr Outbreak Anal & Modelling, London, England.
   [Lin, Enmoore; Kiniboro, Benson; Siba, Peter] PNG Inst Med Res, Vector Borne Dis Unit, Madang, Papua N Guinea.
   [Darcy, Andrew W.] Minist Hlth, Natl Hlth Training & Res Inst, Honiara, Solomon Islands.
   [King, Christopher L.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
   [Mueller, Ivo] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain.
RP Mueller, I (reprint author), Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Melbourne, Vic 3050, Australia.; Mueller, I (reprint author), Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia.; Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Rayner, JC (reprint author), Wellcome Trust Sanger Inst, Malaria Programme, Hinxton, England.; Mueller, I (reprint author), Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain.
EM jr9@sanger.ac.uk; rfairhurst@niaid.nih.gov; ivomueller@fastmail.fm
OI Franca, Camila/0000-0001-5885-4410; Rayner, Julian/0000-0002-9835-1014;
   Li Wai Suen, Connie/0000-0003-0529-0804
FU Southwest Pacific International Centre of Excellence in Malaria Research
   (NIH) [U19AI089686]; National Institutes of Health [AI063135]; National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health; National Health & Medical Research Council [1021544]; Malaria
   Elimination Science Alliance (MESA); Wellcome Trust [098051]; UK Medical
   Research Council [MR/J002283/1]; NHMRC Senior Research Fellowship
   [1043345]; University of Melbourne - Melbourne International
   Postgraduate Scholarship
FX This study was funded in part by the Southwest Pacific International
   Centre of Excellence in Malaria Research (NIH grant U19AI089686
   "Research to control and eliminate malaria in the Southwest Pacific"),
   the National Institutes of Health (AI063135), the Intramural Research
   Program, National Institute of Allergy and Infectious Diseases, National
   Institutes of Health), the National Health & Medical Research Council
   (#1021544), the Malaria Elimination Science Alliance (MESA), the
   Wellcome Trust (#098051), and the UK Medical Research Council
   (MR/J002283/1). This work was also made possible through Victorian State
   Government Operational Infrastructure Support and Australian Government
   NHMRC IRIISS. IM is supported by an NHMRC Senior Research Fellowship
   (#1043345) and CTF is supported by the University of Melbourne -
   Melbourne International Postgraduate Scholarship. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
NR 45
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Z9 5
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2016
VL 10
IS 5
AR e0004639
DI 10.1371/journal.pntd.0004639
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DO4QY
UT WOS:000377769300023
PM 27182597
ER

PT J
AU Inbar, E
   Lawyer, P
   Sacks, D
   Podini, D
AF Inbar, Ehud
   Lawyer, Philip
   Sacks, David
   Podini, Daniele
TI The Potential Use of Forensic DNA Methods Applied to Sand Fly Blood Meal
   Analysis to Identify the Infection Reservoirs of Anthroponotic Visceral
   Leishmaniasis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID KALA-AZAR; IDENTIFICATION; CULICIDAE; INFANTUM; SAMPLES; INDIA; FOCUS
AB Background
   In the Indian sub-continent, visceral leishmaniasis (VL), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite Leishmania donovani and transmitted by the sand fly Phlebotomus argentipes. VL is prevalent in northeast India where it is believed to have an exclusive anthroponotic transmission cycle. There are four distinct cohorts of L. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured VL cases, patients with post kala azar dermal leishmaniasis (PKDL), and asymptomatic individuals. The relative contribution of each group to sustaining the transmission cycle of VL is not known.
   Methodology/Principal Findings
   To answer this critical epidemiological question, we have addressed the feasibility of an approach that would use forensic DNA methods to recover human DNA profiles from the blood meals of infected sand flies that would then be matched to reference DNA sampled from individuals living or working in the vicinity of the sand fly collections. We found that the ability to obtain readable human DNA fingerprints from sand flies depended entirely on the size of the blood meal and the kinetics of its digestion. Useable profiles were obtained from most flies within the first 24 hours post blood meal (PBM), with a sharp decline at 48 hours and no readable profiles at 72 hours. This early time frame necessitated development of a sensitive, nested-PCR method compatible with detecting L. donovani within a fresh, 24 hours blood meal in flies fed on infected hamsters.
   Conclusion/Significance
   Our findings establish the feasibility of the forensic DNA method to directly trace the human source of an infected blood meal, with constraints imposed by the requirement that the flies be recovered for analysis within 24 hours of their infective feed.
C1 [Inbar, Ehud; Lawyer, Philip; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Podini, Daniele] George Washington Univ, Dept Forens Sci, Columbian Coll Arts & Sci, Washington, DC 20052 USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
FU Bill and Melinda Gates Foundation [2013-0783-2]
FX DS and EH received funding from The Bill and Melinda Gates Foundation
   http://www.gatesfoundation.org/ grant # 2013-0783-2 Epidemology of
   Visceral Leishmaniasis in Bihar, India. The funders had no role in the
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 25
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U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2016
VL 10
IS 5
AR e0004706
DI 10.1371/journal.pntd.0004706
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DO4QY
UT WOS:000377769300048
PM 27192489
ER

PT J
AU Reiner, RC
   Achee, N
   Barrera, R
   Burkot, TR
   Chadee, DD
   Devine, GJ
   Endy, T
   Gubler, D
   Hombach, J
   Kleinschmidt, I
   Lenhart, A
   Lindsay, SW
   Longini, I
   Mondy, M
   Morrison, AC
   Perkins, TA
   Vazquez-Prokopec, G
   Reiter, P
   Ritchie, SA
   Smith, DL
   Strickman, D
   Scott, TW
AF Reiner, Robert C., Jr.
   Achee, Nicole
   Barrera, Roberto
   Burkot, Thomas R.
   Chadee, Dave D.
   Devine, Gregor J.
   Endy, Timothy
   Gubler, Duane
   Hombach, Joachim
   Kleinschmidt, Immo
   Lenhart, Audrey
   Lindsay, Steven W.
   Longini, Ira
   Mondy, Mathias
   Morrison, Amy C.
   Perkins, T. Alex
   Vazquez-Prokopec, Gonzalo
   Reiter, Paul
   Ritchie, Scott A.
   Smith, David L.
   Strickman, Daniel
   Scott, Thomas W.
TI Quantifying the Epidemiological Impact of Vector Control on Dengue
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID TREATED HOUSE SCREENS; AEDES-AEGYPTI; VIRUS TRANSMISSION;
   DEVELOPING-COUNTRIES; INSECTICIDE; MEXICO; PREVENTION; CHIKUNGUNYA;
   INFECTION; MOSQUITOS
C1 [Reiner, Robert C., Jr.] Indiana Univ, Bloomington Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.
   [Reiner, Robert C., Jr.; Lindsay, Steven W.; Perkins, T. Alex; Smith, David L.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Achee, Nicole; Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
   [Barrera, Roberto] Ctr Dis Control & Prevent CDC, San Juan, PR USA.
   [Burkot, Thomas R.] James Cook Univ, Australian Inst Trop Hlth & Med, Cairns, Qld, Australia.
   [Chadee, Dave D.] Univ W Indies, Dept Life Sci, Fac Sci & Agr, St Augustine Campus, St Augustine, Trinid & Tobago.
   [Devine, Gregor J.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
   [Endy, Timothy] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA.
   [Gubler, Duane] Duke NUS Med Sch, Signature Res Program Emerging Infect Dis, Singapore, Singapore.
   [Hombach, Joachim] World Hlth Org, Initiat Vaccine Res, Geneva, Switzerland.
   [Kleinschmidt, Immo] Univ London London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, Trop Epidemiol Grp, Keppel St, London WC1E 7HT, England.
   [Kleinschmidt, Immo] Univ Witwatersrand, Sch Hlth Sci, Dept Pathol, Johannesburg, South Africa.
   [Lenhart, Audrey] Ctr Dis Control & Prevent, Ctr Global Hlth, Div Parasit Dis & Malaria, Entomol Branch, Atlanta, GA USA.
   [Lindsay, Steven W.] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
   [Longini, Ira] Univ Florida, Dept Biostat, Gainesville, FL USA.
   [Mondy, Mathias] Univ Calif Davis, Innovat Vector Control Consortium, Davis, CA 95616 USA.
   [Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
   [Vazquez-Prokopec, Gonzalo] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA.
   [Reiter, Paul] Inst Pasteur, Dept Med Entomol, Paris, France.
   [Ritchie, Scott A.] James Cook Univ, Coll Publ Hlth Med & Vet Sci, Australian Inst Trop Hlth & Med, Cairns, Qld, Australia.
   [Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
   [Strickman, Daniel] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Reiner, RC (reprint author), Indiana Univ, Bloomington Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.; Reiner, RC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM rcreiner@indiana.edu
FU Partnership for Dengue Control (PDC); Fondation Merieux; Research and
   Policy for Infectious Disease Dynamics program of the Science and
   Technology Directory; Fogarty International Center, National Institutes
   of Health (NIH); Bill & Melinda Gates Foundation [OPP1053338];
   Department of Homeland Security
FX This review was supported by the Partnership for Dengue Control (PDC)
   and the Fondation Merieux. This work was supported by the Research and
   Policy for Infectious Disease Dynamics program of the Science and
   Technology Directory, Department of Homeland Security, and Fogarty
   International Center, National Institutes of Health (NIH); SWL was
   supported by the Bill & Melinda Gates Foundation (OPP1053338). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 58
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U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2016
VL 10
IS 5
AR e0004588
DI 10.1371/journal.pntd.0004588
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DO4QY
UT WOS:000377769300013
PM 27227829
ER

PT J
AU Song, MJ
   Bharti, K
AF Song, Min Jae
   Bharti, Kapil
TI Looking into the future: Using induced pluripotent stem cells to build
   two and three dimensional ocular tissue for cell therapy and disease
   modeling
SO BRAIN RESEARCH
LA English
DT Review
DE Retinal degeneration; Age related macular degeneration; Transplantation;
   Retinal pigment epithelium; Induced pluripotent stem cells; Tissue
   engineering; Microfluidics; 3D disease models
ID RETINAL-PIGMENT EPITHELIUM; SORSBYS FUNDUS DYSTROPHY; ORGANS-ON-CHIPS;
   HUMAN IPS CELLS; MACULAR DEGENERATION; GENE-EXPRESSION; DIRECTED
   DIFFERENTIATION; SUBRETINAL IMPLANTATION; VITELLIFORM DYSTROPHY;
   MOLECULAR SIGNATURE
AB Retinal degenerative diseases are the leading cause of irreversible vision loss in developed countries. In many cases the diseases originate in the homeostatic unit in the back of the eye that contains the retina, retinal pigment epithelium (RPE) and the choriocapillaris. RPE is a central and a critical component of this homeostatic unit, maintaining photoreceptor function and survival on the apical side and choriocapillaris health on the basal side. In diseases like age-related macular degeneration (AMD), it is thought that RPE dysfunctions cause disease-initiating events and as the RPE degenerates photoreceptors begin to die and patients start loosing vision. Patient-specific induced pluripotent stem (iPS) cell-derived RPE provides direct access to a patient's genetics and allow the possibility of identifying the initiating events of RPE-associated degenerative diseases. Furthermore, iPS cell-derived RPE cells are being tested as a potential cell replacement in disease stages. with RPE atrophy. In this article we summarize the recent progress in the field of iPS cell-derived RPE "disease modeling" and cell therapies and also discuss the possibilities of developing a model of the entire homeostatic unit to aid in studying disease processes in the future. This article is part of a Special Issue entitled SI: PSC and the brain. Published by Elsevier B.V.
C1 [Song, Min Jae; Bharti, Kapil] NEI, Unit Ocular & Stem Cell Translat Res, 10 Ctr Dr,Room 10B10, Bethesda, MD 20892 USA.
RP Bharti, K (reprint author), NEI, Unit Ocular & Stem Cell Translat Res, 10 Ctr Dr,Room 10B10, Bethesda, MD 20892 USA.
EM kapilbharti@nei.nih.gov
FU Intramural NIH HHS [ZIA EY000531-02]
NR 117
TC 2
Z9 3
U1 16
U2 34
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 MAY 1
PY 2016
VL 1638
SI SI
BP 2
EP 14
DI 10.1016/j.brainres.2015.12.011
PN A
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DN8EH
UT WOS:000377311500002
PM 26706569
ER

PT J
AU Pei, Y
   Peng, J
   Behl, M
   Sipes, NS
   Shockley, KR
   Rao, MS
   Tice, RR
   Zeng, XM
AF Pei, Ying
   Peng, Jun
   Behl, Mamta
   Sipes, Nisha S.
   Shockley, Keith R.
   Rao, Mahendra S.
   Tice, Raymond R.
   Zeng, Xianmin
TI Comparative neurotoxicity screening in human iPSC-derived neural stem
   cells, neurons and astrocytes
SO BRAIN RESEARCH
LA English
DT Article
DE Neurotoxicity; Drug screening; iPSC; Neural stem cells; Neurons;
   Astrocytes; Lineage-specific reporter lines
ID CENTRAL-NERVOUS-SYSTEM; DOPAMINERGIC-NEURONS; DEVELOPMENTAL
   NEUROTOXICITY; PARKINSONS-DISEASE; IN-VITRO; DEFINED CONDITIONS;
   BISPHENOL-A; PC12 CELLS; METHYLMERCURIC CHLORIDE; EFFICIENT GENERATION
AB Induced pluripotent stem cells (iPSC) and their differentiated derivatives offer a unique source of human primary cells for toxicity screens. Here, we report on the comparative cytotoxicity of 80 compounds (neurotoxicants, developmental neurotoxicants, and environmental compounds) in iPSC as well as isogenic iPSC-derived neural stem cells (NSC), neurons, and astrocytes. All compounds were tested over a 24-h period at 10 and 100 mu M, in duplicate, with cytotoxicity measured using the MTT assay. Of the 80 compounds tested, 50 induced significant cytotoxicity in at least one cell type; per cell type, 32, 38, 46, and 41 induced significant cytotoxicity in iPSC, NSC, neurons, and astrocytes, respectively. Four compounds (valinomycin, 3,3',5,5'-tetrabromobisphenol, deltamethrin, and triphenyl phosphate) were cytotoxic in all four cell types. Retesting these compounds at 1, 10, and 100 mu M using the same exposure protocol yielded consistent results as compared with the primary screen. Using rotenone, we extended the testing to seven additional iPSC lines of both genders; no substantial difference in the extent of cytotoxicity was detected among the cell lines. Finally, the cytotoxicity assay was simplified by measuring luciferase activity using lineage-specific luciferase reporter iPSC lines which were generated from the parental iPSC line. This article is part of a Special Issue entitled SI: PSC and the brain. (C) 2015 Published by Elsevier B.V.
C1 [Pei, Ying; Zeng, Xianmin] XCell Sci Inc, Novato, CA 94945 USA.
   [Peng, Jun; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA USA.
   [Behl, Mamta; Sipes, Nisha S.; Shockley, Keith R.; Tice, Raymond R.] NIEHS, NIH, Res Triangle Pk, NC 27713 USA.
   [Rao, Mahendra S.] NxCell Sci, Novato, CA USA.
RP Zeng, XM (reprint author), XCell Sci Inc, Novato, CA 94945 USA.
EM xzeng@xcellscience.com
FU SBIR Grant from NIEHS [1R43ES023522-01]
FX This work was supported in part by an SBIR Grant from the NIEHS,
   1R43ES023522-01 (Zeng) to XCell. We thank all members of our laboratory
   for helpful discussions. We would like also to thank Dr. Kristen Ryan
   for her valuable input in reviewing this manuscript. The views expressed
   in this paper are those of the authors and do not necessarily reflect
   the statements, opinions, views, conclusions, or policies of the
   National Institute of Environmental Health Sciences (NIEHS), the
   National Institutes of Health (NIH), or the United States government.
   Mention of trade names or commercial products does not constitute
   endorsement or recommendation for use. The authors declare they have no
   actual or potential competing financial interests.
NR 135
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U1 2
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 MAY 1
PY 2016
VL 1638
SI SI
BP 57
EP 73
DI 10.1016/j.brainres.2015.07.048
PN A
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA DN8EH
UT WOS:000377311500006
PM 26254731
ER

PT J
AU Levy, M
   Boulis, N
   Rao, M
   Svendsen, CN
AF Levy, Michael
   Boulis, Nicholas
   Rao, Mahendra
   Svendsen, Clive N.
TI Regenerative cellular therapies for neurologic diseases
SO BRAIN RESEARCH
LA English
DT Article
DE Stem cell; Regeneration; Neurologic disease
ID AMYOTROPHIC-LATERAL-SCLEROSIS; MESENCHYMAL STEM-CELLS; FETAL NIGRAL
   TRANSPLANTATION; LONG-TERM SAFETY; PARKINSONS-DISEASE;
   HUNTINGTONS-DISEASE; ISCHEMIC-STROKE; BILATERAL TRANSPLANTATION;
   NEUROTROPHIC FACTOR; MULTIPLE-SCLEROSIS
AB The promise of stem cell regeneration has been the hope of many neurologic patients with permanent damage to the central nervous system. There are hundreds of stem cell trials worldwide intending to test the regenerative capacity of stem cells in various neurological conditions from Parkinson's disease to multiple sclerosis. Although no stem cell therapy is clinically approved for use in any human disease indication, patients are seeking out trials and asking clinicians for guidance. This review summarizes the current state of regenerative stem cell transplantation divided into seven conditions for which trials are currently active: demyelinating diseases/spinal cord injury, amyotrophic lateral sclerosis, stroke, Parkinson's disease, Huntington's disease, macular degeneration and peripheral nerve diseases. This article is part of a Special Issue entitled SI: PSC and the brain. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Levy, Michael] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
   [Boulis, Nicholas] Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA.
   [Rao, Mahendra] NIH, Ctr Regenerat Med, Bldg 10, Bethesda, MD 20892 USA.
   [Svendsen, Clive N.] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, Los Angeles, CA 90048 USA.
RP Levy, M (reprint author), Johns Hopkins Neurol, Pathol 509, 1800 E Orleans St, Baltimore, MD 21287 USA.; Svendsen, CN (reprint author), Cedars Sinai Med Ctr, Regenerat Med Inst, AHSP 8th Floor,8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM mlevy@jhmi.edu; Clive.Svendsen@cshs.org
OI Levy, Michael/0000-0002-7969-8346
FU NIH [NS078555]; Guthy Jackson Charitable Foundation; Acorda; Sanofi;
   NeuralStem; Genentech; NIH; Cox Foundation; Virginia Gentleman's
   Foundation; Department of Defense; Taubman Foundation
FX Dr. Levy receives research support from NIH (Grant no. NS078555), Guthy
   Jackson Charitable Foundation, Acorda, Sanofi, NeuralStem and Genentech,
   and serves as a consultant for Chugai Pharmaceuticals,
   Glaxo-Smith-Kline, Medimmune. Dr. Levy's contribution to the manuscript
   was to write the introduction, stem cell types and demyelinating disease
   sections and to critically revise the manuscript.; Dr. Boulis receives
   research support from NIH, NeuralStem, the Cox Foundation, the Virginia
   Gentleman's Foundation, Department of Defense, Taubman Foundation and
   served as a consultant for NeuralStem. Dr. Boulis's contribution to the
   manuscript was to write the section on peripheral nerve disease and
   stroke sections and to critically revise the manuscript.
NR 71
TC 4
Z9 4
U1 6
U2 22
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 MAY 1
PY 2016
VL 1638
SI SI
BP 88
EP 96
DI 10.1016/j.brainres.2015.06.053
PN A
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DN8EH
UT WOS:000377311500008
PM 26239912
ER

PT J
AU Yang, Z
   Zuo, XN
   McMahon, KL
   Craddock, RC
   Kelly, C
   de Zubicaray, GI
   Hickie, I
   Bandettini, PA
   Castellanos, FX
   Milham, MP
   Wright, MJ
AF Yang, Zhi
   Zuo, Xi-Nian
   McMahon, Katie L.
   Craddock, R. Cameron
   Kelly, Clare
   de Zubicaray, Greig I.
   Hickie, Ian
   Bandettini, Peter A.
   Castellanos, F. Xavier
   Milham, Michael P.
   Wright, Margaret J.
TI Genetic and Environmental Contributions to Functional Connectivity
   Architecture of the Human Brain
SO CEREBRAL CORTEX
LA English
DT Article
DE connectome; environmental contribution; heritability; intrinsic
   connectivity network; twins
ID HUMAN CEREBRAL-CORTEX; RESTING-STATE FMRI; INDEPENDENT COMPONENT
   ANALYSIS; SURFACE-BASED ANALYSIS; DEFAULT MODE NETWORK; WORKING-MEMORY;
   LIFE-SPAN; PREFRONTAL CORTEX; GEOMETRICALLY ACCURATE; MRI
AB One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain.
C1 [Yang, Zhi; Zuo, Xi-Nian] Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China.
   [Yang, Zhi; Zuo, Xi-Nian] Chinese Acad Sci, Inst Psychol, MRI Res Ctr, Beijing 100101, Peoples R China.
   [Yang, Zhi; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
   [McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia.
   [Craddock, R. Cameron; Milham, Michael P.] Child Mind Inst, New York, NY USA.
   [Craddock, R. Cameron; Milham, Michael P.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
   [Kelly, Clare; Castellanos, F. Xavier] NYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA.
   [de Zubicaray, Greig I.] Univ Queensland, Sch Psychol, Brisbane, Qld, Australia.
   [Hickie, Ian] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia.
   [Wright, Margaret J.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
RP Zuo, XN (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China.; Zuo, XN (reprint author), Chinese Acad Sci, Inst Psychol, MRI Res Ctr, Beijing 100101, Peoples R China.; Milham, MP (reprint author), Child Mind Inst, New York, NY USA.
EM zuoxn@psych.ac.cn; michael.milham@childmind.org
RI de Zubicaray, Greig/B-1763-2008; Yang, Zhi/E-2493-2012; McMahon,
   Katie/C-6440-2009; 
OI de Zubicaray, Greig/0000-0003-4506-0579; Yang, Zhi/0000-0002-2222-2312;
   McMahon, Katie/0000-0002-6357-615X; Craddock,
   Cameron/0000-0002-4950-1303; Wright, Margaret/0000-0001-7133-4970;
   Castellanos, Francisco/0000-0001-9192-9437
FU National Basic Research (973) Program [2015CB351702]; Natural Science
   Foundation of China [81270023, 81571756, 81278412, 81171409, 81000583,
   81471740, 81220108014]; Beijing Nova Program for Science and Technology
   [XXJH2015B079]; Outstanding Young Investigator Award of Institute of
   Psychology, Chinese Academy of Sciences; Foundation of Beijing Key
   Laboratory of Mental Disorders [2014JSJB03]; Chinese Academy of Sciences
   [KSZD-EW-TZ-002]; NIH [U01MH099059, R01MH083246, R01HD050735]; NIMH
   BRAINS [R01MH094639-01]; Chinese Academy of Sciences K.C. Wong Education
   Foundation; National Basic Research (973) Program of China
FX This work was supported by the National Basic Research (973) Program
   (grant number: 2015CB351702), the Natural Science Foundation of China
   (grant numbers: 81270023, 81571756, 81278412, 81171409, 81000583,
   81471740, 81220108014), the Beijing Nova Program for Science and
   Technology (XXJH2015B079 to Z.Y.), the Outstanding Young Investigator
   Award of Institute of Psychology, Chinese Academy of Sciences (to Z.Y.),
   the Foundation of Beijing Key Laboratory of Mental Disorders (2014JSJB03
   to Z.Y.), the Key Research Program and the Hundred Talents Program of
   the Chinese Academy of Sciences (KSZD-EW-TZ-002 to X.N.Z), NIH
   (U01MH099059, R01MH083246, R01HD050735), NIMH BRAINS (R01MH094639-01 to
   M.P.M), and gifts from Phyllis Green and Randolph Cowen to F.X.C. and
   M.P.M. M.P.M and X.N.Z are members of an international collaboration
   team supported by the Chinese Academy of Sciences K.C. Wong Education
   Foundation. Funding to pay the Open Access publication charges for this
   article was provided by the National Basic Research (973) Program of
   China.
NR 117
TC 4
Z9 5
U1 5
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD MAY
PY 2016
VL 26
IS 5
BP 2341
EP 2352
DI 10.1093/cercor/bhw027
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DO0LD
UT WOS:000377469500040
PM 26891986
ER

PT J
AU Aktar, A
   Rahman, MA
   Afrin, S
   Faruk, MO
   Uddin, T
   Akter, A
   Sami, MIN
   Yasmin, T
   Chowdhury, F
   Khan, AI
   Leung, DT
   LaRocque, RC
   Charles, RC
   Bhuiyan, TR
   Mandlik, A
   Kelly, M
   Kovac, P
   Xu, P
   Calderwood, SB
   Harris, JB
   Qadri, F
   Ryan, ET
AF Aktar, Amena
   Rahman, M. Arifur
   Afrin, Sadia
   Faruk, M. Omar
   Uddin, Taher
   Akter, Aklima
   Sami, M. Israk Nur
   Yasmin, Tahirah
   Chowdhury, Fahima
   Khan, Ashraful I.
   Leung, Daniel T.
   LaRocque, Regina C.
   Charles, Richelle C.
   Bhuiyan, Taufiqur Rahman
   Mandlik, Anjali
   Kelly, Meagan
   Kovac, Pavol
   Xu, Peng
   Calderwood, Stephen B.
   Harris, Jason B.
   Qadri, Firdausi
   Ryan, Edward T.
TI O-Specific Polysaccharide-Specific Memory B Cell Responses in Young
   Children, Older Children, and Adults Infected with Vibrio cholerae O1
   Ogawa in Bangladesh
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID ORAL KILLED CHOLERA; IMMUNE-RESPONSES; VIBRIO-CHOLERAE-O139 BENGAL;
   HOUSEHOLD CONTACTS; CROSS-PROTECTION; SPATIAL-ANALYSIS; VACCINE;
   LIPOPOLYSACCHARIDE; ANTIGEN; DIARRHEA
AB Cholera caused by Vibrio cholerae O1 confers at least 3 to 10 years of protection against subsequent disease regardless of age, despite a relatively rapid fall in antibody levels in peripheral blood, suggesting that memory B cell responses may play an important role in protection. The V. cholerae O1-specific polysaccharide (OSP) component of lipopolysaccharide (LPS) is responsible for serogroup specificity, and it is unclear if young children are capable of developing memory B cell responses against OSP, a T cell-independent antigen, following cholera. To address this, we assessed OSP-specific memory B cell responses in young children (2 to 5 years, n = 11), older children (6 to 17 years, n = 21), and adults (18 to 55 years, n = 28) with cholera caused by V. cholerae O1 in Dhaka, Bangladesh. We also assessed memory B cell responses against LPS and vibriocidal responses, and plasma antibody responses against OSP, LPS, and cholera toxin B subunit (CtxB; a T cell-dependent antigen) on days 2 and 7, as well as days 30, 90, and 180 after convalescence. In all age cohorts, vibriocidal responses and plasma OSP, LPS, and CtxB-specific responses peaked on day 7 and fell toward baseline over the follow-up period. In comparison, we were able to detect OSP memory B cell responses in all age cohorts of patients with detectable responses over baseline for 90 to 180 days. Our results suggest that OSP-specific memory B cell responses can occur following cholera, even in the youngest children, and may explain in part the age-independent induction of long-term immunity following naturally acquired disease.
C1 [Aktar, Amena; Rahman, M. Arifur; Afrin, Sadia; Faruk, M. Omar; Uddin, Taher; Akter, Aklima; Sami, M. Israk Nur; Yasmin, Tahirah; Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, GPO Box 128, Dhaka 1000, Bangladesh.
   [Leung, Daniel T.; LaRocque, Regina C.; Charles, Richelle C.; Mandlik, Anjali; Kelly, Meagan; Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Leung, Daniel T.; LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   [Kovac, Pavol; Xu, Peng] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
   [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
   [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.; Ryan, ET (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA.; Ryan, ET (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM etryan@mgh.harvard.edu
RI Xu, Peng/K-7036-2012; 
OI leung, daniel/0000-0001-8401-0801
FU HHS \ National Institutes of Health (NIH) [R01 AI106878, U01 AI058935,
   R03 AI063079, K08 AI089721, K08AI100923]; HHS \ NIH \ Fogarty
   International Center (FIC) [TW005572]; Swedish Sida grant INT-ICDDR
   [B-HN-01-AV]
FX This work, including the efforts of Daniel T. Leung, Richelle C.
   Charles, Stephen B. Calderwood, Firdausi Qadri, and Edward T. Ryan, was
   funded by HHS vertical bar National Institutes of Health (NIH) (R01
   AI106878, U01 AI058935, R03 AI063079, K08 AI089721, and K08AI100923).
   This work, including the efforts of Amena Aktar, Taher Uddin, and
   Taufiqur Rahman Bhuiyan, was funded by HHS vertical bar NIH vertical bar
   Fogarty International Center (FIC) (TW005572).; We have also received
   funding from Swedish Sida grant INT-ICDDR, B-HN-01-AV for Firdausi
   Qadri.
NR 53
TC 0
Z9 0
U1 8
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAY
PY 2016
VL 23
IS 5
BP 427
EP 435
DI 10.1128/CVI.00647-15
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DO0GE
UT WOS:000377456600006
PM 27009211
ER

PT J
AU Kim, J
   Davis, JW
   Klein, EA
   Magi-Galluzzi, C
   Lotan, Y
   Ward, JF
   Pisters, LL
   Basler, JW
   Pettaway, CA
   Stephenson, A
   Tapia, EMLN
   Efstathiou, E
   Wang, XM
   Dog, KA
   Lee, JJ
   Gorlov, IP
   Vornik, LA
   Hoque, AM
   Prokhorova, IN
   Parnes, HL
   Lippman, SM
   Thompson, IM
   Brown, PH
   Logothetis, CJ
   Troncoso, P
AF Kim, Jeri
   Davis, John W.
   Klein, Eric A.
   Magi-Galluzzi, Cristina
   Lotan, Yair
   Ward, John F.
   Pisters, Louis L.
   Basler, Joseph W.
   Pettaway, Curtis A.
   Stephenson, Andrew
   Tapia, Elsa M. Li Ning
   Efstathiou, Eleni
   Wang, Xuemei
   Dog, Kim-Anh
   Lee, J. Jack
   Gorlov, Ivan P.
   Vornik, Lana A.
   Hoque, Ashraful M.
   Prokhorova, Ina N.
   Parnes, Howard L.
   Lippman, Scott M.
   Thompson, Ian M.
   Brown, Powel H.
   Logothetis, Christopher J.
   Troncoso, Patricia
TI Tissue Effects in a Randomized Controlled Trial of Short-term
   Finasteride in Early Prostate Cancer
SO EBIOMEDICINE
LA English
DT Article
DE Prostate cancer; 5 alpha-reductase inhibitors; Finasteride; Cancer
   prevention; Biomarkers
ID 5-ALPHA-REDUCTASE INHIBITOR DUTASTERIDE; ANDROGEN RECEPTOR; PREVENTION
   TRIAL; STEM-CELL; ER-BETA; PROGRESSION; EXPRESSION; CASTRATION; MARKERS;
   TYPE-1
AB Background: In the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.
   Methods: From 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5 mg finasteride or placebo daily in a double-blind study during the 4-6 weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ER beta, UBE2C, SRD5A2, and VEGF) differentiating high-and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.
   Findings: We found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.
   Interpretation: We showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Kim, Jeri; Tapia, Elsa M. Li Ning; Efstathiou, Eleni; Logothetis, Christopher J.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
   [Davis, John W.; Ward, John F.; Pisters, Louis L.; Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
   [Klein, Eric A.; Stephenson, Andrew] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA.
   [Magi-Galluzzi, Cristina] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44195 USA.
   [Lotan, Yair] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
   [Basler, Joseph W.; Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
   [Wang, Xuemei; Dog, Kim-Anh; Lee, J. Jack; Gorlov, Ivan P.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
   [Vornik, Lana A.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
   [Hoque, Ashraful M.; Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
   [Prokhorova, Ina N.; Troncoso, Patricia] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92093 USA.
RP Kim, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM jekim@mdanderson.org
FU NCI NIH HHS [N01CN35159]
NR 29
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD MAY
PY 2016
VL 7
BP 85
EP 93
DI 10.1016/j.ebiom.2016.03.047
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO0HJ
UT WOS:000377459700021
PM 27322462
ER

PT J
AU Meng, QY
   Ying, Z
   Noble, E
   Zhao, YQ
   Agrawal, R
   Mikhail, A
   Zhuang, YM
   Tyagi, E
   Zhang, Q
   Lee, JH
   Morselli, M
   Orozco, L
   Guo, WL
   Kilts, TM
   Zhu, J
   Zhang, B
   Pellegrini, M
   Xiao, XS
   Young, MF
   Gomez-Pinilla, F
   Yang, X
AF Meng, Qingying
   Ying, Zhe
   Noble, Emily
   Zhao, Yuqi
   Agrawal, Rahul
   Mikhail, Andrew
   Zhuang, Yumei
   Tyagi, Ethika
   Zhang, Qing
   Lee, Jae-Hyung
   Morselli, Marco
   Orozco, Luz
   Guo, Weilong
   Kilts, Tina M.
   Zhu, Jun
   Zhang, Bin
   Pellegrini, Matteo
   Xiao, Xinshu
   Young, Marian F.
   Gomez-Pinilla, Fernando
   Yang, Xia
TI Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and
   Brain Disorders
SO EBIOMEDICINE
LA English
DT Article
DE Systems nutrigenomics; Fructose; Omega-3 fatty acid; DHA; Epigenome;
   Transcriptome; Brain networks; Metabolic diseases; Brain disorders;
   Extracellular matrix
ID ABNORMAL COLLAGEN FIBRILS; N-3 FATTY-ACIDS; EXTRACELLULAR-MATRIX;
   ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; NEUROLOGICAL DISORDERS;
   SYNAPTIC PLASTICITY; INSULIN-RESISTANCE; GUT MICROBIOTA; DEFICIENT MICE
AB Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. (C) 2016 The Authors. Published by Elsevier B.V.
C1 [Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Xiao, Xinshu; Gomez-Pinilla, Fernando; Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.
   [Morselli, Marco; Orozco, Luz; Guo, Weilong; Pellegrini, Matteo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Kilts, Tina M.; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Zhu, Jun; Zhang, Bin] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Gomez-Pinilla, Fernando] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA.
   [Lee, Jae-Hyung] Kyung Hee Univ, Sch Dent, Dept Maxillofacial Biomed Engn, Seoul 130701, South Korea.
   [Guo, Weilong] Tsinghua Univ, Ctr Synthet & Syst Biol, TNLIST, Beijing 100084, Peoples R China.
RP Gomez-Pinilla, F; Yang, X (reprint author), Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.; Gomez-Pinilla, F (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA.
EM fgomezpi@mednet.ucla.edu; xyang123@ucla.edu
RI zhang, qing/I-4902-2016; 
OI Guo, Weilong/0000-0001-5199-1359; Agrawal, Rahul/0000-0001-8128-3724
FU NHGRI NIH HHS [U01 HG008451]; NIDDK NIH HHS [R01 DK104363]; NINDS NIH
   HHS [R01 NS050465]
NR 56
TC 3
Z9 3
U1 4
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD MAY
PY 2016
VL 7
BP 157
EP 166
DI 10.1016/j.ebiom.2016.04.008
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO0HJ
UT WOS:000377459700028
PM 27322469
ER

PT J
AU Parker, KS
   Crowley, JR
   Stephens-Shields, AJ
   van Bokhoven, A
   Lucia, MS
   Lai, HH
   Andriole, GL
   Hooton, TM
   Mullins, C
   Henderson, JP
AF Parker, Kaveri S.
   Crowley, Jan R.
   Stephens-Shields, Alisa J.
   van Bokhoven, Adrie
   Lucia, M. Scott
   Lai, H. Henry
   Andriole, Gerald L.
   Hooton, Thomas M.
   Mullins, Chris
   Henderson, Jeffrey P.
TI Urinary Metabolomics Identifies a Molecular Correlate of Interstitial
   Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the
   Study of Chronic Pelvic Pain (MAPP) Research Network Cohort
SO EBIOMEDICINE
LA English
DT Article
ID SYNDROME/INTERSTITIAL CYSTITIS; SEX DIFFERENCE; SULFATION; RECEPTOR;
   CLASSIFICATION; METABOLISM; SYMPTOMS; MARKERS; STRESS; SITES
AB Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratorymarkers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3 alpha-ol-17-one sulfate (Etio-S), a sulfoconjugated 5-beta reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites) and could resolve high-from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3-6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
C1 [Parker, Kaveri S.; Henderson, Jeffrey P.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, Box 8051,660 S Euclid Ave, St Louis, MO 63110 USA.
   [Parker, Kaveri S.; Henderson, Jeffrey P.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA.
   [Parker, Kaveri S.; Crowley, Jan R.; Henderson, Jeffrey P.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
   [Lai, H. Henry; Andriole, Gerald L.] Washington Univ, Sch Med, Dept Surg, Div Urol Surg, St Louis, MO 63110 USA.
   [Lai, H. Henry] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA.
   [Stephens-Shields, Alisa J.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Hooton, Thomas M.] Univ Miami, Sch Med, Dept Med, Div Infect Dis, Miami, FL USA.
   [van Bokhoven, Adrie; Lucia, M. Scott] Univ Colorado, Dept Pathol, Aurora, CO USA.
   [Mullins, Chris] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
RP Henderson, JP (reprint author), Washington Univ, Sch Med, Ctr Womens Infect Dis Res, Box 8051,660 S Euclid Ave, St Louis, MO 63110 USA.
EM jhenderson@DOM.wustl.edu
FU NCATS NIH HHS [UL1 TR001082]; NIDDK NIH HHS [U01 DK082316]
NR 33
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD MAY
PY 2016
VL 7
BP 167
EP 174
DI 10.1016/j.ebiom.2016.03.040
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO0HJ
UT WOS:000377459700029
PM 27322470
ER

PT J
AU Heacock, M
   Kelly, CB
   Asante, KA
   Birnbaum, LS
   Bergman, AL
   Brune, MN
   Buka, I
   Carpenter, DO
   Chen, AM
   Huo, X
   Kamel, M
   Landrigan, PJ
   Magalini, F
   Diaz-Barriga, F
   Neira, M
   Omar, M
   Pascale, A
   Ruchirawat, M
   Sly, L
   Sly, PD
   Van den Berg, M
   Suk, WA
AF Heacock, Michelle
   Kelly, Carol Bain
   Asante, Kwadwo Ansong
   Birnbaum, Linda S.
   Bergman, Ake Lennart
   Brune, Marie-Noel
   Buka, Irena
   Carpenter, David O.
   Chen, Aimin
   Huo, Xia
   Kamel, Mostafa
   Landrigan, Philip J.
   Magalini, Federico
   Diaz-Barriga, Fernando
   Neira, Maria
   Omar, Magdy
   Pascale, Antonio
   Ruchirawat, Mathuros
   Sly, Leith
   Sly, Peter D.
   Van den Berg, Martin
   Suk, William A.
TI E-Waste and Harm to Vulnerable Populations: A Growing Global Problem
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID CHILDRENS HEALTH; ENVIRONMENT; EXPOSURE; PACIFIC; CHINA; GHANA; RISK
AB BACKGROUND: Electronic waste (e-waste) is produced in staggering quantities, estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling is a source of much-needed income in many low-to middle-income countries. However, its handling and disposal in underdeveloped countries is often unsafe and leads to contaminated environments. Rudimentary and uncontrolled processing methods often result in substantial harmful chemical exposures among vulnerable populations, including women and children. E-waste hazards have not yet received the attention they deserve in research and public health agendas.
   OBJECTIVES: We provide an overview of the scale and health risks. We review international efforts concerned with environmental hazards, especially affecting children, as a preface to presenting next steps in addressing health issues stemming from the global e-waste problem.
   DISCUSSION: The e-waste problem has been building for decades. Increased observation of adverse health effects from e-waste sites calls for protecting human health and the environment from e-waste contamination. Even if e-waste exposure intervention and prevention efforts are implemented, legacy contamination will remain, necessitating increased awareness of e-waste as a major environmental health threat.
   CONCLUSION: Global, national, and local levels efforts must aim to create safe recycling operations that consider broad security issues for people who rely on e-waste processing for survival. Paramount to these efforts is reducing pregnant women and children's e-waste exposures to mitigate harmful health effects. With human environmental health in mind, novel dismantling methods and remediation technologies and intervention practices are needed to protect communities.
C1 [Heacock, Michelle; Birnbaum, Linda S.; Suk, William A.] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Kelly, Carol Bain] MDB Inc, Durham, NC USA.
   [Asante, Kwadwo Ansong] CSIR, Water Res Inst, Accra, Ghana.
   [Bergman, Ake Lennart] Sodertalje Univ, Swedish Toxicol Sci Res Ctr, Sodertalje, Sweden.
   [Brune, Marie-Noel; Neira, Maria] WHO, CH-1211 Geneva, Switzerland.
   [Buka, Irena] Univ Alberta, Edmonton, AB, Canada.
   [Carpenter, David O.] SUNY Albany, Rensselaer, NY USA.
   [Chen, Aimin] Univ Cincinnati, Cincinnati, OH USA.
   [Huo, Xia] Shantou Univ, Coll Med, Shantou, Peoples R China.
   [Kamel, Mostafa] Basel Convent Reg Ctr Training & Technol Transfer, Giza, Egypt.
   [Landrigan, Philip J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
   [Magalini, Federico] United Nations Univ, Inst Sustainabil & Peace, Bonn, Germany.
   [Diaz-Barriga, Fernando] Univ Autonoma San Luis Potosi, San Luis Potosi, Mexico.
   [Omar, Magdy] Cairo Univ, Giza, Egypt.
   [Pascale, Antonio] Univ Republica, Sch Med, Dept Toxicol, Montevideo, Uruguay.
   [Ruchirawat, Mathuros] Chulabhorn Res Inst, Bangkok, Thailand.
   [Sly, Leith; Sly, Peter D.] Queensland Childrens Med Res Inst, Brisbane, Qld, Australia.
   [Van den Berg, Martin] Univ Utrecht, Utrecht, Netherlands.
RP Heacock, M (reprint author), NIEHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM HeacockM@niehs.nih.gov
FU NIEHS NIH HHS [P30 ES006096]; World Health Organization [001]
NR 46
TC 8
Z9 8
U1 27
U2 44
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 550
EP 555
DI 10.1289/ehp.1509699
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000009
PM 26418733
ER

PT J
AU Kleinstreuer, NC
   Ceger, PC
   Allen, DG
   Strickland, J
   Chang, XQ
   Hamm, J
   Casey, WM
AF Kleinstreuer, Nicole C.
   Ceger, Patricia C.
   Allen, David G.
   Strickland, Judy
   Chang, Xiaoqing
   Hamm, Jonathan T.
   Casey, Warren M.
TI A Curated Database of Rodent Uterotrophic Bioactivity
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
ID ESTROGEN-RECEPTOR; OECD PROGRAM; TOXCAST PROGRAM; BISPHENOL-A; RAT
   UTERUS; CHEMICALS; ASSAY; TOXICITY; VALIDATE; BIOASSAY
AB BACKGROUND: Novel in vitro methods are being developed to identify chemicals that may interfere with estrogen receptor (ER) signaling, but the results are difficult to put into biological context because of reliance on reference chemicals established using results from other in vitro assays and because of the lack of high-quality in vivo reference data. The Organisation for Economic Co-operation and Development (OECD)-validated rodent uterotrophic bioassay is considered the "gold standard" for identifying potential ER agonists.
   OBJECTIVES: We performed a comprehensive literature review to identify and evaluate data from uterotrophic studies and to analyze study variability.
   METHODS: We reviewed 670 articles with results from 2,615 uterotrophic bioassays using 235 unique chemicals. Study descriptors, such as species/strain, route of administration, dosing regimen, lowest effect level, and test outcome, were captured in a database of uterotrophic results. Studies were assessed for adherence to six criteria that were based on uterotrophic regulatory test guidelines. Studies meeting all six criteria (458 bioassays on 118 unique chemicals) were considered guideline-like (GL) and were subsequently analyzed.
   RESULTS: The immature rat model was used for 76% of the GL studies. Active outcomes were more prevalent across rat models (74% active) than across mouse models (36% active). Of the 70 chemicals with at least two GL studies, 18 (26%) had discordant outcomes and were classified as both active and inactive. Many discordant results were attributable to differences in study design (e.g., injection vs. oral dosing).
   CONCLUSIONS: This uterotrophic database provides a valuable resource for understanding in vivo outcome variability and for evaluating the performance of invitro assays that measure estrogenic activity.
C1 [Kleinstreuer, Nicole C.; Ceger, Patricia C.; Allen, David G.; Strickland, Judy; Chang, Xiaoqing; Hamm, Jonathan T.] Integrated Lab Syst, Res Triangle Pk, NC USA.
   [Casey, Warren M.] NIEHS, NICEATM, Div Natl Toxicol Program, NIH,Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kleinstreuer, NC (reprint author), NIEHS, NTP, 530 Davis Dr,Keystone Bldg, Durham, NC 27713 USA.
EM nicole.kleinstreuer@nih.gov
OI Kleinstreuer, Nicole/0000-0002-7914-3682
FU  [HHSN27320140003C]
FX Integrated Laboratory Systems staff provided technical support for
   NICEATM under NIEHS contract HHSN27320140003C, but do not represent the
   NIEHS, the NTP, or the official positions of any federal agency.
NR 35
TC 3
Z9 3
U1 1
U2 4
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 556
EP 562
DI 10.1289/ehp.1510183
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000010
PM 26431337
ER

PT J
AU Boyd, WA
   Smith, MV
   Co, CA
   Pirone, JR
   Rice, JR
   Shockley, KR
   Freedman, JH
AF Boyd, Windy A.
   Smith, Marjolein V.
   Co, Caroll A.
   Pirone, Jason R.
   Rice, Julie R.
   Shockley, Keith R.
   Freedman, Jonathan H.
TI Developmental Effects of the ToxCast (TM) Phase I and Phase II Chemicals
   in Caenorhabditis elegans and Corresponding Responses in Zebrafish,
   Rats, and Rabbits
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID C. ELEGANS; MODEL; TOXICITY; NEUROTOXICITY; EXPOSURE; GROWTH; ASSAY
AB BACKGROUND: Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity.
   METHODS: The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency's (EPA's) ToxCast Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC(50)), and lowest effective concentration (LEC).
   RESULTS: Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active <= 200 mu M in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%).
   CONCLUSIONS: Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast T libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical's potential toxicity to humans.
C1 [Boyd, Windy A.; Rice, Julie R.; Freedman, Jonathan H.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.] Social & Sci Syst Inc, Durham, NC USA.
   [Shockley, Keith R.] NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Room 1300,HSC A,500 S Preston St, Louisville, KY 40202 USA.
EM jonathan.freedman@louisville.edu
OI Boyd, Windy/0000-0003-3803-3716
FU NIH Office of Research Infrastructure Programs [P40 OD010440]; National
   Toxicology Program Division; Intramural Research Program of the National
   Institute of Environmental Health Sciences (NIEHS)/National Institutes
   of Health (NIH) [Z01ES102045, Z01ES102046]
FX We acknowledge the support of K. Houck and S. Little [U.S. Environmental
   Protection Agency (EPA)] for providing the chemical library and chemical
   properties data. Some strains were provided by the Caenorhabditis
   Genetic Center, which is funded by NIH Office of Research Infrastructure
   Programs (P40 OD010440); This work was supported in part by the National
   Toxicology Program Division and by the Intramural Research Program of
   the National Institute of Environmental Health Sciences (NIEHS)/National
   Institutes of Health (NIH) (Z01ES102045 and Z01ES102046). M.V.S.,
   C.A.C., and J.R.P. are employed by Social & Scientific Systems Inc.,
   Durham, North Carolina.
NR 32
TC 3
Z9 3
U1 5
U2 8
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 586
EP 593
DI 10.1289/ehp.1409645
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000014
PM 26496690
ER

PT J
AU Tual, S
   Silverman, DT
   Koutros, S
   Blair, A
   Sandler, DP
   Lebailly, P
   Andreotti, G
   Hoppin, JA
   Freeman, LEB
AF Tual, Severine
   Silverman, Debra T.
   Koutros, Stella
   Blair, Aaron
   Sandler, Dale P.
   Lebailly, Pierre
   Andreotti, Gabriella
   Hoppin, Jane A.
   Freeman, Laura E. Beane
TI Use of Dieselized Farm Equipment and Incident Lung Cancer: Findings from
   the Agricultural Health Study Cohort
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID OCCUPATIONAL-EXPOSURE; ENDOTOXIN-EXPOSURE; ENGINE EXHAUST;
   AIR-POLLUTION; RISK; EMISSIONS; WORKERS; METAANALYSIS; CANADA
AB BACKGROUND: Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer.
   OBJECTIVES: We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993-1997) to 2010-2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA.
   METHODS: Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure.
   RESULTS: Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05).
   CONCLUSIONS: This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted.
C1 [Tual, Severine; Lebailly, Pierre] INSERM, UMR Canc & Prevent 1086, Caen, France.
   [Tual, Severine; Lebailly, Pierre] Univ Caen, F-14032 Caen, France.
   [Tual, Severine; Lebailly, Pierre] Ctr Lutte Canc Francois Baclesse, Caen, France.
   [Silverman, Debra T.; Koutros, Stella; Blair, Aaron; Andreotti, Gabriella; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, Rockville, MD USA.
   [Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA.
   [Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
RP Freeman, LEB (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20852 USA.
EM freemala@mail.nih.gov
OI Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the National Cancer Institute
   [Z01CP010119]; National Institute of Environmental Health Sciences
   [Z01ES049030]; Fondation de France; Comprehensive Cancer Care Francois
   Baclesse; French National Institute for Agricultural Medicine
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute, Z01CP010119, and the National Institute of
   Environmental Health Sciences, Z01ES049030. S.T. received grants from
   the Fondation de France, the Comprehensive Cancer Care Francois
   Baclesse, and the French National Institute for Agricultural Medicine
   for her PhD thesis.
NR 28
TC 0
Z9 0
U1 4
U2 10
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 611
EP 618
DI 10.1289/ehp.1409238
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000017
PM 26452295
ER

PT J
AU Kim, MT
   Huang, RL
   Sedykh, A
   Wang, WY
   Xia, MH
   Zhu, H
AF Kim, Marlene Thai
   Huang, Ruili
   Sedykh, Alexander
   Wang, Wenyi
   Xia, Menghang
   Zhu, Hao
TI Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using
   Antioxidant Response Element Reporter Gene Assay Models and Big Data
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID ENVIRONMENTAL CHEMICALS; RISK-ASSESSMENT; LIVER-DISEASES; CELL-SURVIVAL;
   TOXICITY; NRF2; PATHWAY; QSAR; EXPRESSION; TOXICOLOGY
AB BACKGROUND: Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program.
   OBJECTIVE: The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data.
   METHODS: Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified.
   RESULTS: The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs.
   CONCLUSION: Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources.
C1 [Kim, Marlene Thai; Zhu, Hao] Rutgers State Univ, Dept Chem, Camden, NJ 08102 USA.
   [Kim, Marlene Thai; Sedykh, Alexander; Wang, Wenyi; Zhu, Hao] Rutgers State Univ, Ctr Computat & Integrat Biol, Camden, NJ 08102 USA.
   [Huang, Ruili; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA.
   [Sedykh, Alexander] Multicase Inc, Beachwood, OH USA.
RP Zhu, H (reprint author), Rutgers State Univ, 315 Penn St, Camden, NJ 08102 USA.
EM hao.zhu99@rutgers.edu
FU National Institute of Environmental Health Sciences/National Institutes
   of Health (NIH) [R15ES023148]; Colgate-Palmolive Grant for Alternative
   Research
FX This research was supported in part by the National Institute of
   Environmental Health Sciences/National Institutes of Health (NIH) under
   award R15ES023148 (H.Z., W.W., and M.T.K.) and by the Colgate-Palmolive
   Grant for Alternative Research (H.Z., W.W., and M.T.K.). A.S. is
   employed by Multicase Inc., Beachwood, Ohio.
NR 65
TC 4
Z9 4
U1 1
U2 7
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 634
EP 641
DI 10.1289/ehp.1509763
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000020
PM 26383846
ER

PT J
AU Mitro, SD
   Birnbaum, LS
   Needham, BL
   Zota, AR
AF Mitro, Susanna D.
   Birnbaum, Linda S.
   Needham, Belinda L.
   Zota, Ami R.
TI Cross-sectional Associations between Exposure to Persistent Organic
   Pollutants and Leukocyte Telomere Length among US Adults in NHANES,
   2001-2002
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; PERIPHERAL-BLOOD LEUKOCYTES;
   NATIONAL-HEALTH; QUANTITATIVE PCR; LUNG-CANCER; RISK; CELLS
AB BACKGROUND: Exposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL.
   OBJECTIVES: We examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001-2002.
   METHODS: We created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the AhR: a) non-dioxin-like PCBs (composed of 10 non-dioxin-like PCBs; no AhR affinity and no TEF); b) non-ortho PCBs (composed of 2 non-ortho-substituted PCBs with high TEFs); and c) toxic equivalency (TEQ) (composed of 7 dioxins, 9 furans, 2 non-ortho-substituted PCBs, and 6 mono-ortho-substituted PCBs; weighted by TEF). We tested the association between each metric and LTL using linear regression, adjusting for demographics, blood cell count and distribution, and another metric with a different TEF (i.e., non-ortho PCBs and TEQ adjusted for non-dioxin-like PCBs; non-dioxin-like PCBs adjusted for non-ortho PCBs).
   RESULTS: In adjusted models, each doubling of serum concentrations of non-ortho PCBs and TEQ was associated with 3.74% (95% CI: 2.10, 5.40) and 5.29% (95% CI: 1.66, 9.05) longer LTLs, respectively. Compared with the lowest quartile, the highest quartile of exposure was associated with 9.16% (95% CI: 2.96, 15.73) and 7.84% (95% CI: -0.53, 16.92) longer LTLs, respectively. Non-dioxin-like PCBs were not associated with LTL.
   CONCLUSIONS: POPs with high TEFs and AhR affinity were associated with longer LTL. Because many dioxin-associated cancers are also associated with longer LTL, these results may provide insight into the mechanisms underlying PCB- and dioxin-related carcinogenesis.
C1 [Mitro, Susanna D.; Zota, Ami R.] George Washington Univ, Sch Publ Hlth, Milken Inst, Dept Environm & Occupat Hlth, Washington, DC USA.
   [Birnbaum, Linda S.] NCI, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
   [Needham, Belinda L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
RP Zota, AR (reprint author), Milken Inst, Sch Publ Hlth, Dept Environm & Occupat Hlth, 950 New Hampshire Ave NW,Suite 414, Washington, DC 20052 USA.
EM azota@gwu.edu
FU National Institute of Environmental Health Sciences [R00ES019881];
   intramural research program of the National Cancer Institute, National
   Institutes of Health
FX This study was funded by the National Institute of Environmental Health
   Sciences (R00ES019881) and the intramural research program of the
   National Cancer Institute, National Institutes of Health.
NR 40
TC 3
Z9 3
U1 1
U2 4
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP 651
EP 658
DI 10.1289/ehp.1510187
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000022
PM 26452299
ER

PT J
AU Lind, L
   Lind, PM
   Lejonklou, MH
   Dunder, L
   Bergman, A
   Guerrero-Bosagna, C
   Lampa, E
   Lee, HK
   Legler, J
   Nadal, A
   Pak, YK
   Phipps, RP
   Vandenberg, LN
   Zalko, D
   Agerstrand, M
   Oberg, M
   Blumberg, B
   Heindel, JJ
   Birnbaum, LS
AF Lind, Lars
   Lind, P. Monica
   Lejonklou, Margareta H.
   Dunder, Linda
   Bergman, Ake
   Guerrero-Bosagna, Carlos
   Lampa, Erik
   Lee, Hong Kyu
   Legler, Juliette
   Nadal, Angel
   Pak, Youngmi Kim
   Phipps, Richard P.
   Vandenberg, Laura N.
   Zalko, Daniel
   Agerstrand, Marlene
   Oberg, Mattias
   Blumberg, Bruce
   Heindel, Jerrold J.
   Birnbaum, Linda S.
TI Uppsala Consensus Statement on Environmental Contaminants and the Global
   Obesity Epidemic
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID ENDOCRINE-DISRUPTING CHEMICALS; PERSISTENT ORGANIC POLLUTANTS; PRENATAL
   EXPOSURE; BISPHENOL-A; FOOD-INTAKE; MICE; WEIGHT; OVERWEIGHT; PREGNANCY;
   INSULIN
AB From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8-9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.
C1 [Lind, Lars] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden.
   [Lind, P. Monica; Lejonklou, Margareta H.; Dunder, Linda] Uppsala Univ, Dept Occupat & Environm Med, Uppsala, Sweden.
   [Bergman, Ake; Oberg, Mattias] Swedish Toxicol Sci Res Ctr Swetox, Sodertalje, Sweden.
   [Guerrero-Bosagna, Carlos] Linkoping Univ, Dept Phys Chem & Biol, Linkoping, Sweden.
   [Lampa, Erik] Uppsala Clin Res UCR Ctr, Uppsala, Sweden.
   [Lee, Hong Kyu] Eulji Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
   [Legler, Juliette] Vrije Univ Amsterdam, Inst Environm Studies, Amsterdam, Netherlands.
   [Nadal, Angel] Univ Miguel Hernandez Elche, CIBERDEM Inst Bioingn, CIBER Diabet Enfermedades Metab Asociadas, Alicante, Spain.
   [Pak, Youngmi Kim] Kyung Hee Univ, Coll Med, Dept Physiol, Seoul, South Korea.
   [Phipps, Richard P.] Univ Rochester, Dept Environm Med, Rochester, NY USA.
   [Vandenberg, Laura N.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Environm Hlth Sci, Amherst, MA 01003 USA.
   [Zalko, Daniel] INRA, UMR1331, Toxalim Res Ctr Food Toxicol, F-31931 Toulouse, France.
   [Zalko, Daniel] Univ Toulouse 3, INPT, Univ Toulouse, F-31062 Toulouse, France.
   [Agerstrand, Marlene] Stockholm Univ, Dept Environm Sci & Analyt Chem, S-10691 Stockholm, Sweden.
   [Blumberg, Bruce] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
   [Heindel, Jerrold J.; Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Lind, L (reprint author), Uppsala Univ, Dept Med Sci, Akad Sjukhuset, Entrance 40,Plan 5, S-75185 Uppsala, Sweden.
EM lars.lind@medsci.uu.se
RI Nadal, Angel/G-6721-2014; 
OI Nadal, Angel/0000-0003-4178-2152; H Lejonklou,
   Margareta/0000-0002-0620-7104; Lee, Hong Kyu/0000-0002-4926-0984
NR 24
TC 2
Z9 2
U1 4
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2016
VL 124
IS 5
BP A81
EP A83
DI 10.1289/ehp.1511115
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DN4ZZ
UT WOS:000377077000003
PM 27135406
ER

PT J
AU Matyas, C
   Wen-Shin, L
   Erdelyi, K
   Varga, ZV
   Mukhopadhyay, P
   Radovits, T
   Merkely, B
   Pacher, P
AF Matyas, C.
   Wen-Shin, L.
   Erdelyi, K.
   Varga, Z. V.
   Mukhopadhyay, P.
   Radovits, T.
   Merkely, B.
   Pacher, P.
TI Cannabidiol is a novel treatment for autoimmune myocarditis
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Meeting Abstract
C1 [Matyas, C.; Wen-Shin, L.; Erdelyi, K.; Varga, Z. V.; Mukhopadhyay, P.; Pacher, P.] NIAAA, NIH, Bethesda, MD USA.
   [Radovits, T.; Merkely, B.] Semmelweis Univ, Heart & Vasc Ctr, H-1085 Budapest, Hungary.
NR 0
TC 0
Z9 0
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1388-9842
EI 1879-0844
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD MAY
PY 2016
VL 18
SU 1
SI SI
MA P543
BP 138
EP 138
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DN5KZ
UT WOS:000377107501102
ER

PT J
AU Joshi, AS
   Fei, N
   Greenberg, ML
AF Joshi, Amit S.
   Fei, Naomi
   Greenberg, Miriam L.
TI Get1p and Get2p are required for maintenance of mitochondrial morphology
   and normal cardiolipin levels
SO FEMS YEAST RESEARCH
LA English
DT Article
DE cardiolipin; mitochondria morphology; Barth syndrome
ID ANCHORED PROTEIN INSERTION; SACCHAROMYCES-CEREVISIAE; BARTH-SYNDROME;
   LYMPHOBLAST MITOCHONDRIA; SUPERCOMPLEX FORMATION; YEAST MITOCHONDRIA;
   RESPIRATORY-CHAIN; ER MEMBRANE; PHOSPHOLIPIDS; COMPLEX
AB Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes. CL deficiency leads to defects in mitochondrial function. Using a targeted synthetic lethality screen to identify defects that exacerbate CL deficiency, we determined that deletion of mitochondrial morphology genes in cells lacking CL leads to severe growth defects. We show that ER membrane proteins Get1p and Get2p are required for maintaining normal levels of CL. We propose that these proteins regulate the level of CL by maintaining wild type-like tubular mitochondrial morphology. The genetic interactions observed in this study identify novel physiological modifiers that are required for maintenance of CL levels and mitochondrial morphology.
C1 [Joshi, Amit S.; Fei, Naomi; Greenberg, Miriam L.] Wayne State Univ, Dept Biol Sci, 5047 Gullen Mall, Detroit, MI 48202 USA.
   [Joshi, Amit S.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Greenberg, ML (reprint author), Wayne State Univ, Dept Biol Sci, 5047 Gullen Mall, Detroit, MI 48202 USA.
EM mgreenberg@wayne.edu
FU National Institutes of Health [RO1 HL 117880]; Barth Syndrome
   Foundation; WSU
FX This work was supported by grants from National Institutes of Health
   (RO1 HL 117880) and The Barth Syndrome Foundation to MLG, WSU Graduate
   Enhancement Research Fellowship and Graduate Enhancement Research Funds
   to ASJ, and a WSU Undergraduate Research Grant to NF.
NR 49
TC 1
Z9 1
U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1567-1356
EI 1567-1364
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD MAY
PY 2016
VL 16
IS 3
AR fow019
DI 10.1093/femsyr/fow019
PG 6
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA DO0PO
UT WOS:000377481000008
ER

PT J
AU Tilly, K
   Bestor, A
   Rosa, PA
AF Tilly, Kit
   Bestor, Aaron
   Rosa, Patricia A.
TI Functional Equivalence of OspA and OspB, but Not OspC, in Tick
   Colonization by Borrelia burgdorferi
SO INFECTION AND IMMUNITY
LA English
DT Article
ID OUTER-SURFACE-PROTEIN; LYME-DISEASE SPIROCHETE; CRYSTAL-STRUCTURE;
   MAMMALIAN INFECTION; MONOCLONAL-ANTIBODY; ANTIGENIC VARIATION; VLSE;
   HOST; EXPRESSION; CYCLE
AB Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse-tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization.
C1 [Tilly, Kit; Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Tilly, K; Rosa, PA (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM ktilly@niaid.nih.gov; prosa@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases (DIR, NIAID)
FX This work, including the efforts of Kit Tilly, Aaron Bestor, and
   Patricia A Rosa, was funded by Division of Intramural Research, National
   Institute of Allergy and Infectious Diseases (DIR, NIAID).
NR 50
TC 1
Z9 1
U1 4
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2016
VL 84
IS 5
BP 1565
EP 1573
DI 10.1128/IAI.00063-16
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DN5KT
UT WOS:000377106600030
PM 26953324
ER

PT J
AU Tchounwou, PB
AF Tchounwou, Paul B.
TI Twelfth International Symposium on Recent Advances in Environmental
   Health Research
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Editorial Material
DE international symposium; environmental science; biomedical science;
   public health
AB During the past century, environmental hazards have become a major concern, not only to public health professionals, but also to the society at large because of their tremendous health, socio-cultural and economic impacts. Various anthropogenic or natural factors have been implicated in the alteration of ecosystem integrity, as well as in the development of a wide variety of acute and/or chronic diseases in humans. It has also been demonstrated that many environmental agents, acting either independently or in combination with other toxins, may induce a wide range of adverse health outcomes. Understanding the role played by the environment in the etiology of human diseases is critical to designing cost-effective control/prevention measures. This special issue of International Journal of Environmental Research and Public Health includes the proceedings of the Twelfth International Symposium on Recent Advances in Environmental Health Research. The Symposium provided an excellent opportunity to discuss the scientific advances in biomedical, environmental, and public health research that addresses global environmental health issues.
C1 [Tchounwou, Paul B.] Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
NR 5
TC 0
Z9 0
U1 1
U2 1
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD MAY
PY 2016
VL 13
IS 5
AR 470
DI 10.3390/ijerph13050470
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA DN7LI
UT WOS:000377256900027
ER

PT J
AU Reinhardt, M
   Schlogl, M
   Bonfiglio, S
   Votruba, SB
   Krakoff, J
   Thearle, MS
AF Reinhardt, M.
   Schlogl, M.
   Bonfiglio, S.
   Votruba, S. B.
   Krakoff, J.
   Thearle, M. S.
TI Lower core body temperature and greater body fat are components of a
   human thrifty phenotype
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
ID ENERGY-EXPENDITURE; LEAN MEN; OBESITY; WEIGHT; THERMOGENESIS; MICE;
   DETERMINANTS; METABOLISM; RESPONSES; BALANCE
AB BACKGROUND/OBJECTIVES: In small studies, a thrifty human phenotype, defined by a greater 24-hour energy expenditure (EE) decrease with fasting, is associated with less weight loss during caloric restriction. In rodents, models of diet-induced obesity often have a phenotype including a reduced EE and decreased core body temperature. We assessed whether a thrifty human phenotype associates with differences in core body temperature or body composition.
   SUBJECTS/METHODS: Data for this cross-sectional analysis were obtained from 77 individuals participating in one of two normal physiology studies while housed on our clinical research unit. Twenty-four-hour EE using a whole-room indirect calorimeter and 24-h core body temperature were measured during 24 h each of fasting and 200% overfeeding with a diet consisting of 50% carbohydrates, 20% protein and 30% fat. Body composition was measured by dual X-ray absorptiometry. To account for the effects of body size on EE, changes in EE were expressed as a percentage change from 24-hour EE (% EE) during energy balance.
   RESULTS: A greater % EE decrease with fasting correlated with a smaller % EE increase with overfeeding (r = 0.27, P = 0.02). The % EE decrease with fasting was associated with both fat mass and abdominal fat mass, even after accounting for covariates (beta = -0.16 (95% CI: -0.26, -0.06) % EE per kg fat mass, P = 0.003; beta = -0.0004 (-0.0007, -0.00004) % EE kg(-1) abdominal fat mass, P = 0.03). In men, a greater % EE decrease in response to fasting was associated with a lower 24-h core body temperature, even after adjusting for covariates (beta = 1.43 (0.72, 2.15) % EE per 0.1 degrees C, P = 0.0003).
   CONCLUSIONS: Thrifty individuals, as defined by a larger EE decrease with fasting, were more likely to have greater overall and abdominal adiposity as well as lower core body temperature consistent with a more efficient metabolism.
C1 [Reinhardt, M.; Schlogl, M.; Bonfiglio, S.; Votruba, S. B.; Krakoff, J.; Thearle, M. S.] Natl Inst Diabet & Digest & Kidney Dis, Dept Hlth & Human Serv, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch,NIH, Phoenix, AZ 85016 USA.
   [Reinhardt, M.] Univ Leipzig, Dept Diagnost & Intervent Radiol, D-04109 Leipzig, Germany.
   [Schlogl, M.] Univ Zurich Hosp, Dept Geriatr & Aging Res, CH-8091 Zurich, Switzerland.
RP Reinhardt, M (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch Na, NIH, 4212N 16th St, Phoenix, AZ 85016 USA.
EM martin.reinhardt@nih.gov
FU Intramural Research Program of the National Institutes of Health,
   National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank the dietary, nursing and technical staff of the National
   Institutes of Health Clinical Unit in Phoenix, AZ, USA, for their
   assistance. Most of all, the authors thank the volunteers for their
   participation in the study. This research was supported by the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Diabetes and Digestive and Kidney Diseases.
NR 41
TC 2
Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
EI 1476-5497
J9 INT J OBESITY
JI Int. J. Obes.
PD MAY
PY 2016
VL 40
IS 5
BP 754
EP 760
DI 10.1038/ijo.2015.229
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DO2NK
UT WOS:000377616500004
PM 26499440
ER

PT J
AU Ovejero, D
   Gafni, RI
   Collins, MT
AF Ovejero, Diana
   Gafni, Rachel I.
   Collins, Michael T.
TI 1,25-Dihydroxyvitamin D as Monotherapy for XLH: Back to the Future?
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Editorial Material
ID X-LINKED HYPOPHOSPHATEMIA; FIBROBLAST GROWTH FACTOR-23; TUMOR-INDUCED
   OSTEOMALACIA; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLITES; D-RESISTANT
   RICKETS; PHOSPHATE HOMEOSTASIS; SERUM PHOSPHATE; BONE RESPONSE; FGF
   RECEPTOR
C1 [Ovejero, Diana; Gafni, Rachel I.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders & Mineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders & Mineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
EM mc247k@nih.gov
NR 52
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2016
VL 31
IS 5
BP 925
EP 928
DI 10.1002/jbmr.2858
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DN7PX
UT WOS:000377270400002
PM 27093323
ER

PT J
AU Bi, RY
   Fan, Y
   Lauter, K
   Hu, J
   Watanabe, T
   Cradock, J
   Yuan, Q
   Gardella, T
   Mannstadt, M
AF Bi, Ruiye
   Fan, Yi
   Lauter, Kelly
   Hu, Jing
   Watanabe, Tomoyuki
   Cradock, Jim
   Yuan, Quan
   Gardella, Thomas
   Mannstadt, Michael
TI Diphtheria Toxin- and GFP-Based Mouse Models of Acquired
   Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone
   Analog
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE ANIMAL MODELS; THERAPEUTICS; DISORDERS OF CALCIUM/PHOSPHATE METABOLISM;
   CELL/TISSUE SIGNALING-ENDOCRINE PATHWAYS
ID CALCIUM; ABLATION; RECEPTOR; PTH; CALCIFICATION; RESPONSES; THERAPY;
   REVEALS; INTACT; BONE
AB Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 x 5 mu g/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP-guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. (C) 2015 American Society for Bone and Mineral Research.
C1 [Bi, Ruiye; Lauter, Kelly; Watanabe, Tomoyuki; Gardella, Thomas; Mannstadt, Michael] Massachusetts Gen Hosp, Endocrine Unit, Thier 1123,50 Blossom St, Boston, MA 02474 USA.
   [Bi, Ruiye; Lauter, Kelly; Watanabe, Tomoyuki; Gardella, Thomas; Mannstadt, Michael] Harvard Univ, Sch Med, Boston, MA USA.
   [Bi, Ruiye; Fan, Yi] Sichuan Univ, West China Sch Stomatol, Chengdu 610064, Sichuan, Peoples R China.
   [Fan, Yi] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA.
   [Hu, Jing; Yuan, Quan] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610064, Sichuan, Peoples R China.
   [Cradock, Jim] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
RP Mannstadt, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1123,50 Blossom St, Boston, MA 02474 USA.
EM mannstadt@mgh.harvard.edu
FU NIH [R01-DK100584, X01 NS073537-01, P01-DK11794, T32DK007028]; China
   State Key Laboratory of Oral Diseases Open Funding [SKLOD2015OF01];
   BrIDGs Program; NIH Common Fund; National Center for Advancing
   Translational Sciences
FX This work was supported by the NIH grants R01-DK100584 and X01
   NS073537-01 (to MM), P01-DK11794, project I (to TJG), T32DK007028 (to
   KL); and China State Key Laboratory of Oral Diseases Open Funding
   SKLOD2015OF01 (to RB). This research was supported in part by the BrIDGs
   Program, the NIH Common Fund and the National Center for Advancing
   Translational Sciences. We thank Wenping Zhao for technical help; Henry
   Kronenberg, John Potts, and Deborah Mitchell for comments on this
   manuscript; and Elizabeth Monis for proofreading.
NR 26
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2016
VL 31
IS 5
BP 975
EP 984
DI 10.1002/jbmr.2769
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DN7PX
UT WOS:000377270400007
PM 26678919
ER

PT J
AU Sanda, P
   Kee, T
   Gupta, N
   Stopfer, M
   Bazhenov, M
AF Sanda, Pavel
   Kee, Tiffany
   Gupta, Nitin
   Stopfer, Mark
   Bazhenov, Maxim
TI Classification of odorants across layers in locust olfactory pathway
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE locust olfaction; odor discrimination; network model; odor concentration
ID OSCILLATING NEURAL ASSEMBLIES; ANTENNAL LOBE; POPULATION ACTIVITY;
   SAMPLING TIME; HONEY-BEE; REPRESENTATIONS; ODORS; DISCRIMINATION;
   INFORMATION; NEURONS
AB Olfactory processing takes place across multiple layers of neurons from the transduction of odorants in the periphery, to odor quality processing, learning, and decision making in higher olfactory structures. In insects, projection neurons (PNs) in the antennal lobe send odor information to the Kenyon cells (KCs) of the mushroom bodies and lateral horn neurons (LHNs). To examine the odor information content in different structures of the insect brain, antennal lobe, mushroom bodies and lateral horn, we designed a model of the olfactory network based on electrophysiological recordings made in vivo in the locust. We found that populations of all types (PNs, LHNs, and KCs) had lower odor classification error rates than individual cells of any given type. This improvement was quantitatively different from that observed using uniform populations of identical neurons compared with spatially structured population of neurons tuned to different odor features. This result, therefore, reflects an emergent network property. Odor classification improved with increasing stimulus duration: for similar odorants, KC and LHN ensembles reached optimal discrimination within the first 300-500 ms of the odor response. Performance improvement with time was much greater for a population of cells than for individual neurons. We conclude that, for PNs, LHNs, and KCs, ensemble responses are always much more informative than single-cell responses, despite the accumulation of noise along with odor information.
C1 [Sanda, Pavel; Kee, Tiffany; Bazhenov, Maxim] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Kee, Tiffany] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
   [Gupta, Nitin; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA.
   [Gupta, Nitin] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India.
RP Bazhenov, M (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
EM bazhenov@salk.edu
OI Gupta, Nitin/0000-0002-8408-3848
FU National Institutes of Health-National Institute on Deafness and Other
   Communications Disorders [R01 DC012943, R01 DC011422]
FX This research was supported by the National Institutes of
   Health-National Institute on Deafness and Other Communications Disorders
   (R01 DC012943 and R01 DC011422).
NR 61
TC 0
Z9 0
U1 2
U2 10
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD MAY
PY 2016
VL 115
IS 5
BP 2303
EP 2316
DI 10.1152/jn.00921.2015
PG 14
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA DN6VF
UT WOS:000377213900007
PM 26864765
ER

PT J
AU Fabbri, E
   An, Y
   Zoli, M
   Tanaka, T
   Simonsick, EM
   Kitner-Triolo, MH
   Studenski, SA
   Resnick, SM
   Ferrucci, L
AF Fabbri, Elisa
   An, Yang
   Zoli, Marco
   Tanaka, Toshiko
   Simonsick, Eleanor M.
   Kitner-Triolo, Melissa H.
   Studenski, Stephanie A.
   Resnick, Susan M.
   Ferrucci, Luigi
TI Association Between Accelerated Multimorbidity and Age-Related Cognitive
   Decline in Older Baltimore Longitudinal Study of Aging Participants
   without Dementia
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE multimorbidity; cognition; cognitive decline; aging; older adults
ID PROCESSING-SPEED; VERBAL FLUENCY; ALZHEIMERS-DISEASE; HEALTH;
   PREVALENCE; TRAJECTORIES; COMORBIDITY; PROGRESSION; POPULATION;
   IMPAIRMENT
AB ObjectivesTo explore the association between rate of physical health deterioration, operationalized as rising multimorbidity overtime, and longitudinal decline in cognitive function in older adults without dementia.
   DesignLongitudinal (Baltimore Longitudinal Study of Aging (BLSA)).
   SettingCommunity.
   ParticipantsBLSA participants aged 65 and older followed for an average of 3 years and free of dementia or mild cognitive impairment (MCI) at baseline and follow-up (N = 756).
   MeasurementsStandardized neurocognitive tests evaluating mental status, memory, executive function, processing speed, and verbal fluency were administered. Multimorbidity was assessed at each visit as number of diagnosed chronic diseases from a predefined list. Faster accumulation of chronic diseases was defined as upper quartile of rate of change in number of diseases over time (0.25 diseases/year).
   ResultsFaster accumulation of chronic diseases was significantly associated with greater rate of decline on the Category (P = .01) and Letter (P = .01) Fluency Tests. Similar trends were also found for the Trail-Making Test Parts A (P = .08) and B (P = .07); no association was found with rate of change in visual and verbal memory.
   ConclusionAlthough further investigations are required to validate the results and fully understand the underlying mechanisms, these findings suggest that accelerated deterioration of physical health is associated with accelerated decline with aging in specific cognitive domains in older adults without dementia.
C1 [Fabbri, Elisa; Tanaka, Toshiko; Simonsick, Eleanor M.; Studenski, Stephanie A.; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Longitudinal Study Sect, Clin Res Branch,NIH, Baltimore, MD 21224 USA.
   [Fabbri, Elisa; Zoli, Marco] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy.
   [An, Yang; Kitner-Triolo, Melissa H.; Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
RP Fabbri, E (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM elisa.fabbri@nih.gov
FU Intramural Research Program of the National Institutes of Health,
   National Institute on Aging (NIA); NIA [03-AG-0325]
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute on Aging (NIA). Data
   for these analyses were obtained BLSA, a study performed by NIA (Grant
   03-AG-0325).
NR 41
TC 2
Z9 2
U1 5
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
IS 5
BP 965
EP 972
DI 10.1111/jgs.14092
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DO1FD
UT WOS:000377523000004
PM 27131225
ER

PT J
AU Rajan, A
   Berns, A
   Ringborg, U
   Celis, J
   Ponder, B
   Caldas, C
   Livingston, D
   Bristow, RG
   Hecht, TT
   Tursz, T
   van Luenen, H
   Bono, P
   Helander, T
   Searnon, K
   Smyth, JF
   Louvard, D
   Eggermont, A
   van Harten, WH
AF Rajan, A.
   Berns, A.
   Ringborg, U.
   Celis, J.
   Ponder, B.
   Caldas, C.
   Livingston, D.
   Bristow, R. G.
   Hecht, T. T.
   Tursz, T.
   van Luenen, H.
   Bono, P.
   Helander, T.
   Searnon, K.
   Smyth, J. F.
   Louvard, D.
   Eggermont, A.
   van Harten, W. H.
TI Excellent translational research in oncology: A journey towards novel
   and more effective anti-cancer therapies
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE Performance assessment; Excellence; Translational research; Quality
   improvement
ID CANCER CORE EUROPE
AB Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will aspire to this status. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.
C1 [Rajan, A.; Berns, A.; van Luenen, H.; van Harten, W. H.] Netherlands Canc Inst, Amsterdam, Netherlands.
   [Ringborg, U.] Karolinska Inst, S-10401 Stockholm, Sweden.
   [Celis, J.] Danish Canc Soc, Copenhagen, Denmark.
   [Ponder, B.; Caldas, C.; Searnon, K.] Cambridge Canc Ctr, Cambridge, England.
   [Livingston, D.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
   [Bristow, R. G.] Princess Margaret Canc Ctr, Toronto, ON, Canada.
   [Hecht, T. T.] NCI, Translat Res Program, Bethesda, MD 20892 USA.
   [Tursz, T.; Eggermont, A.] Inst Gustave Roussy, Villejuif, France.
   [Bono, P.; Helander, T.] Univ Helsinki, Cent Hosp, Ctr Canc, FIN-00014 Helsinki, Finland.
   [Smyth, J. F.] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
   [Louvard, D.] Inst Curie, F-75231 Paris, France.
RP van Harten, WH (reprint author), Netherlands Canc Inst, Grp Leader Psychosocial Res & Epidemiol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM w.v.harten@nki.nl
OI Caldas, Carlos/0000-0003-3547-1489
FU Cancer Research UK [9675]
NR 12
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
EI 1878-0261
J9 MOL ONCOL
JI Mol. Oncol.
PD MAY
PY 2016
VL 10
IS 5
BP 645
EP 651
DI 10.1016/j.molonc.2015.12.007
PG 7
WC Oncology
SC Oncology
GA DN8EA
UT WOS:000377310800001
PM 26797050
ER

PT J
AU Jacobson, KA
   Muller, CE
AF Jacobson, Kenneth A.
   Mueller, Christa E.
TI Medicinal chemistry of adenosine, P2Y and P2X receptors
SO NEUROPHARMACOLOGY
LA English
DT Review
DE ATP; Nucleosides; Nucleotides; GPCR; Ion channel; Agonists; Antagonists
ID ECTO-NUCLEOTIDASE INHIBITORS; PROTEIN-COUPLED RECEPTORS; CHRONIC
   NEUROPATHIC PAIN; CENTRAL-NERVOUS-SYSTEM; HUMAN P2Y(12) RECEPTOR;
   STRUCTURE-BASED DESIGN; GATED ION CHANNELS; ALLOSTERIC MODULATION;
   PURINERGIC RECEPTORS; IN-VIVO
AB Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A(1) and A(3) AR agonists, P2Y(1)R and P2Y(12)R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A(2A)AR and P2Y(2)R are already used clinically, P2Y(12)R antagonists are widely used antithrombotics and an antagonist of the A(2A)AR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A(1)AR or A(3)AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain, diabetes, ischemic protection and many other conditions.
   This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Published by Elsevier Ltd.
C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Mueller, Christa E.] Univ Bonn, Inst Pharmaceut, PharmaCtr Bonn, Pharmaceut Chem 1, Bonn, Germany.
RP Jacobson, KA (reprint author), Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kennethj@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009; Muller, Christa/C-7748-2014
OI Jacobson, Kenneth/0000-0001-8104-1493; Muller,
   Christa/0000-0002-0013-6624
FU NIDDK Intramural Research Program, NIH [ZIA DK031117]; BMBF [00160112]
FX KAJ acknowledges support from the NIDDK Intramural Research Program (ZIA
   DK031117), NIH. CEM was supported by the BMBF Grant 00160112 (German
   Federal Ministry for Education and Research) within the BioPharma
   initiative "Neuroallianz".
NR 192
TC 14
Z9 14
U1 10
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD MAY
PY 2016
VL 104
SI SI
BP 31
EP 49
DI 10.1016/j.neuropharm.2015.12.001
PG 19
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DN8HR
UT WOS:000377320300004
PM 26686393
ER

PT J
AU Ferre, S
   Bonaventura, J
   Tomasi, D
   Navarro, G
   Moreno, E
   Cortes, A
   Lluis, C
   Casado, V
   Volkow, ND
AF Ferre, Sergi
   Bonaventura, Jordi
   Tomasi, Dardo
   Navarro, Gemma
   Moreno, Estefania
   Cortes, Antonio
   Lluis, Carme
   Casado, Vicent
   Volkow, Nora D.
TI Allosteric mechanisms within the adenosine A(2A) -dopamine D-2 receptor
   heterotetramer
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Adenosine A2A receptor; Dopamine D2 receptor; Heteromer; Striatum;
   Caffeine; Parkinson's disease
ID G-PROTEIN; PARKINSONS-DISEASE; STRIATOPALLIDAL NEURONS; FUNCTIONAL
   SELECTIVITY; QUATERNARY STRUCTURE; D2 RECEPTORS; RAT STRIATUM; C-FOS;
   HETEROMERS; ANTAGONISTS
AB The structure constituted by a G protein coupled receptor (GPCR) homodimer and a G protein provides a main functional unit and oligomeric entities can be viewed as multiples of dimers. For GPCR heteromers, experimental evidence supports a tetrameric structure, comprised of two different homodimers, each able to signal with its preferred G protein. GPCR homomers and heteromers can act as the conduit of allosteric interactions between orthosteric ligands. The well-known agonist/agonist allosteric interaction in the adenosine A(2A) receptor (A(2A)R)-dopamine D-2 receptor (D2R) heteromer, by which A(2A)R agonists decrease the affinity of D2R agonists, gave the first rationale for the use of A(2A)R antagonists in Parkinson's disease. We review new pharmacological findings that can be explained in the frame of a tetrameric structure of the A(2A)R-D2R heteromer: first, ligand-independent allosteric modulations by the D2R that result in changes of the binding properties of A(2A)R ligands; second, differential modulation of the intrinsic efficacy of D2R ligands for G protein-dependent and independent signaling; third, the canonical antagonistic Gs-Gi interaction within the frame of the heteromer; and fourth, the ability of A(2A)R antagonists, including caffeine, to also exert the same allosteric modulations of D2R ligands than A(2A)R agonists, while A(2A)R agonists and antagonists counteract each other's effects. These findings can have important clinical implications when evaluating the use of A(2A)R antagonists. They also call for the need of monitoring caffeine intake when evaluating the effect of D2R ligands, when used as therapeutic agents in neuropsychiatric disorders or as probes in imaging studies.
   This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. Published by Elsevier Ltd.
C1 [Ferre, Sergi; Bonaventura, Jordi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Tomasi, Dardo; Volkow, Nora D.] NIAAA, NIH, Bethesda, MD USA.
   [Navarro, Gemma; Moreno, Estefania; Cortes, Antonio; Lluis, Carme; Casado, Vicent] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Fac Biol, E-08028 Barcelona, Spain.
   [Navarro, Gemma; Moreno, Estefania; Cortes, Antonio; Lluis, Carme; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, IRP, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
FU intramural funds of National Institute on Drug Abuse; Spanish
   "Ministerio de Ciencia y Tecnologia" [SAF2011-23813]; Government of
   Catalonia [2009-SGR-12]; "Centro de Investigacion Biomedica en Red sobre
   Enfermedades Neurodegenerativas" (CIBERNED) [CB06/05/0064]
FX Work supported by the intramural funds of the National Institute on Drug
   Abuse and from Spanish "Ministerio de Ciencia y Tecnologia"
   (SAF2011-23813), from the Government of Catalonia (2009-SGR-12) and a
   grant (CB06/05/0064) from "Centro de Investigacion Biomedica en Red
   sobre Enfermedades Neurodegenerativas" (CIBERNED).
NR 54
TC 9
Z9 10
U1 13
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD MAY
PY 2016
VL 104
SI SI
BP 154
EP 160
DI 10.1016/j.neuropharm.2015.05.028
PG 7
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DN8HR
UT WOS:000377320300013
PM 26051403
ER

PT J
AU Coughlin, JW
   Brantley, PJ
   Champagne, CM
   Vollmer, WM
   Stevens, VJ
   Funk, K
   Dalcin, AT
   Jerome, GJ
   Myers, VH
   Tyson, C
   Batch, BC
   Charleston, J
   Loria, CM
   Bauck, A
   Hollis, JF
   Svetkey, LP
   Appel, LJ
AF Coughlin, Janelle W.
   Brantley, Phillip J.
   Champagne, Catherine M.
   Vollmer, William M.
   Stevens, Victor J.
   Funk, Kristine
   Dalcin, Arlene T.
   Jerome, Gerald J.
   Myers, Valerie H.
   Tyson, Crystal
   Batch, Bryan C.
   Charleston, Jeanne
   Loria, Catherine M.
   Bauck, Alan
   Hollis, Jack F.
   Svetkey, Laura P.
   Appel, Lawrence J.
CA Weight Loss Maintenance Collaborat
TI The Impact of Continued Intervention on Weight: Five-Year Results from
   the Weight Loss Maintenance Trial
SO OBESITY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE MODIFICATION; LONG-TERM
   MAINTENANCE; EXTENDED-CARE; MISSING DATA; OBESITY; STRATEGIES;
   REDUCTION; ADULTS
AB Objective: In the Weight Loss Maintenance (WLM) Trial, a personal contact (PC) intervention sustained greater weight loss relative to a self-directed (SD) group over 30 months. This study investigated the effects of continued intervention over an additional 30 months and overall weight change across the entire WLM Trial.
   Methods: WLM had 3 phases. Phase 1 was a 6-month weight loss program. In Phase 2, those who lost >= 4 kg were randomized to a 30-month maintenance trial. In Phase 3, PC participants (n=196, three sites) were re-randomized to no further intervention (PC-Control) or continued intervention (PC-Active) for 30 more months; 218 SD participants were also followed.
   Results: During Phase 3, weight increased 1.0 kg in PC-Active and 0.5 kg in PC-Control (mean difference 0.6 kg; 95% CI: 21.4 to 2.7; P=0.54). Mean weight change over the entire study was 23.2 kg in those originally assigned to PC (PC-Combined) and -1.6 kg in SD (mean difference -1.6 kg; 95% CI: -3.0 to -0.1; P=0.04).
   Conclusions: After 30 months of the PC maintenance intervention, continuation for another 30 months provided no additional benefit. However, across the entire study, weight loss was slightly greater in those originally assigned to PC.
C1 [Coughlin, Janelle W.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Coughlin, Janelle W.; Dalcin, Arlene T.; Charleston, Jeanne; Appel, Lawrence J.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
   [Brantley, Phillip J.; Champagne, Catherine M.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
   [Vollmer, William M.; Stevens, Victor J.; Funk, Kristine; Bauck, Alan; Hollis, Jack F.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
   [Jerome, Gerald J.; Appel, Lawrence J.] Johns Hopkins Univ, Div Gen Internal Med, Baltimore, MD USA.
   [Jerome, Gerald J.] Towson Univ, Dept Kinesiol, Towson, MD USA.
   [Myers, Valerie H.] Klein Buendel Inc, Golden, CO USA.
   [Tyson, Crystal; Svetkey, Laura P.] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA.
   [Tyson, Crystal; Batch, Bryan C.; Svetkey, Laura P.] Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC USA.
   [Tyson, Crystal; Batch, Bryan C.; Svetkey, Laura P.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC USA.
   [Loria, Catherine M.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Coughlin, JW (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.; Coughlin, JW (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
EM jwilder3@jhmi.edu
FU National Heart, Lung, and Blood Institute [5-U01 HL68734, 5-U01 HL68676,
   5-U01 HL68790, 5-U01 HL68920, 5-UO1 HL68955, 5RC1HL099437]
FX Sponsored by National Heart, Lung, and Blood Institute grants 5-U01
   HL68734, 5-U01 HL68676, 5-U01 HL68790, 5-U01 HL68920, 5-UO1 HL68955, and
   5RC1HL099437.
NR 26
TC 0
Z9 0
U1 3
U2 6
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 MAY
PY 2016
VL 24
IS 5
BP 1046
EP 1053
DI 10.1002/oby.21454
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DO1DU
UT WOS:000377519500009
PM 26991814
ER

PT J
AU Anderson, MJ
   Schimmang, T
   Lewandoski, M
AF Anderson, Matthew J.
   Schimmang, Thomas
   Lewandoski, Mark
TI An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural
   Crest Specification and Anterior-Posterior Axis Extension
SO PLOS GENETICS
LA English
DT Article
ID INNER-EAR; GENE-EXPRESSION; MOUSE EMBRYO; SEGMENTATION CLOCK;
   FOLIC-ACID; CELL-DEATH; DEVELOPMENTAL DEFECTS; TARGETED DISRUPTION;
   PROTOONCOGENE INT-2; PRIMITIVE STREAK
AB During vertebrate axis extension, adjacent tissue layers undergo profound morphological changes: within the neuroepithelium, neural tube closure and neural crest formation are occurring, while within the paraxial mesoderm somites are segmenting from the presomitic mesoderm (PSM). Little is known about the signals between these tissues that regulate their coordinated morphogenesis. Here, we analyze the posterior axis truncation of mouse Fgf3 null homozygotes and demonstrate that the earliest role of PSM-derived FGF3 is to regulate BMP signals in the adjacent neuroepithelium. FGF3 loss causes elevated BMP signals leading to increased neuroepithelium proliferation, delay in neural tube closure and premature neural crest specification. We demonstrate that elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant, suggesting that excessive BMP signals cause the Fgf3 axis defect. To test this in vivo we increased BMP signaling in Fgf3 mutants by removing one copy of Noggin, which encodes a BMP antagonist. In such mutants, all parameters of the Fgf3 phenotype were exacerbated: neural tube closure delay, premature neural crest specification, and premature axis termination. Conversely, genetically decreasing BMP signaling in Fgf3 mutants, via loss of BMP receptor activity, alleviates morphological defects. Aberrant apoptosis is observed in the Fgf3 mutant tailbud. However, we demonstrate that cell death does not cause the Fgf3 phenotype: blocking apoptosis via deletion of pro-apoptotic genes surprisingly increases all Fgf3 defects including causing spina bifida. We demonstrate that this counterintuitive consequence of blocking apoptosis is caused by the increased survival of BMP-producing cells in the neuroepithelium. Thus, we show that FGF3 in the caudal vertebrate embryo regulates BMP signaling in the neuroepithelium, which in turn regulates neural tube closure, neural crest specification and axis termination. Uncovering this FGF3-BMP signaling axis is a major advance toward understanding how these tissue layers interact during axis extension with important implications in human disease.
C1 [Anderson, Matthew J.; Lewandoski, Mark] NCI, Genet Vertebrate Dev Sect, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA.
   [Schimmang, Thomas] Univ Valladolid, Inst Mol Biol & Genet, Valladolid, Spain.
   [Schimmang, Thomas] CSIC, Valladolid, Spain.
RP Lewandoski, M (reprint author), NCI, Genet Vertebrate Dev Sect, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA.
EM Lewandom@mail.nih.gov
FU Center for Cancer Research of the Intramural Research Program of the
   National Institutes of Health through the National Cancer Institute
FX This work was supported by the Center for Cancer Research of the
   Intramural Research Program of the National Institutes of Health through
   the National Cancer Institute. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 124
TC 0
Z9 0
U1 6
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2016
VL 12
IS 5
AR e1006018
DI 10.1371/journal.pgen.1006018
PG 30
WC Genetics & Heredity
SC Genetics & Heredity
GA DN6PH
UT WOS:000377197100020
PM 27144312
ER

PT J
AU Cai, WL
   Wei, YH
   Jarnik, M
   Reich, J
   Lilly, MA
AF Cai, Weili
   Wei, Youheng
   Jarnik, Michal
   Reich, John
   Lilly, Mary A.
TI The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome
   Function
SO PLOS GENETICS
LA English
DT Article
ID PHOSPHOTYROSINE-INDEPENDENT LIGAND; TUMOR-SUPPRESSOR PROTEINS; RAG
   GTPASES; DIRECT TARGET; GAP ACTIVITY; SEA COMPLEX; SH2 DOMAIN;
   CELL-DEATH; IN-VITRO; DROSOPHILA
AB TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans. Here we define the in vivo role of the GATOR2 component Wdr24 in Drosophila. Using a combination of genetic, biochemical, and cell biological techniques we demonstrate that Wdr24 has both TORC1 dependent and independent functions in the regulation of cellular metabolism. Through the characterization of a null allele, we show that Wdr24 is a critical effector of the GATOR2 complex that promotes the robust activation of TORC1 and cellular growth in a broad array of Drosophila tissues. Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. Notably, we find that two additional members of the GATOR2 complex, Mio and Seh1, also have a TORC1 independent role in the regulation of lysosome function. These findings represent a surprising and previously unrecognized function of GATOR2 complex components in the regulation of lysosomes. Consistent with our findings in Drosophila, through the characterization of a wdr24(-/-) knockout HeLa cell line we determined that Wdr24 promotes lysosome acidification and autophagic flux in mammalian cells. Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes.
C1 [Cai, Weili; Wei, Youheng; Jarnik, Michal; Reich, John; Lilly, Mary A.] NICHHD, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
RP Lilly, MA (reprint author), NICHHD, Cell Biol & Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
EM lillym@helix.nih.gov
FU Intramural Program of the Eunice Kennedy Shriver National Institute of
   Child Health and Human Development, NIH [ZIA HD001613 16]
FX This work was supported by the Intramural Program of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development, NIH
   with a grant (ZIA HD001613 16) to MAL. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 67
TC 2
Z9 2
U1 2
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2016
VL 12
IS 5
AR e1006036
DI 10.1371/journal.pgen.1006036
PG 28
WC Genetics & Heredity
SC Genetics & Heredity
GA DN6PH
UT WOS:000377197100037
PM 27166823
ER

PT J
AU Isles, AR
   Ingason, A
   Lowther, C
   Walters, J
   Gawlick, M
   Stober, G
   Rees, E
   Martin, J
   Little, RB
   Potter, H
   Georgieva, L
   Pizzo, L
   Ozaki, N
   Aleksic, B
   Kushima, I
   Ikeda, M
   Iwata, N
   Levinson, DF
   Gejman, PV
   Shi, JX
   Sanders, AR
   Duan, JB
   Willis, J
   Sisodiya, S
   Costain, G
   Werge, TM
   Degenhardt, F
   Giegling, I
   Rujescu, D
   Hreidarsson, SJ
   Saemundsen, E
   Ahn, JW
   Ogilvie, C
   Girirajan, SD
   Stefansson, H
   Stefansson, K
   O'Donovan, MC
   Owen, MJ
   Bassett, A
   Kirov, G
AF Isles, Anthony R.
   Ingason, Andres
   Lowther, Chelsea
   Walters, James
   Gawlick, Micha
   Stoeber, Gerald
   Rees, Elliott
   Martin, Joanna
   Little, Rosie B.
   Potter, Harry
   Georgieva, Lyudmila
   Pizzo, Lucilla
   Ozaki, Norio
   Aleksic, Branko
   Kushima, Itaru
   Ikeda, Masashi
   Iwata, Nakao
   Levinson, Douglas F.
   Gejman, Pablo V.
   Shi, Jianxin
   Sanders, Alan R.
   Duan, Jubao
   Willis, Joseph
   Sisodiya, Sanjay
   Costain, Gregory
   Werge, Thomas M.
   Degenhardt, Franziska
   Giegling, Ina
   Rujescu, Dan
   Hreidarsson, Stefan J.
   Saemundsen, Evald
   Ahn, Joo Wook
   Ogilvie, Caroline
   Girirajan, Santhosh D.
   Stefansson, Hreinn
   Stefansson, Kari
   O'Donovan, Michael C.
   Owen, Michael J.
   Bassett, Anne
   Kirov, George
TI Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in
   Schizophrenia and Neurodevelopmental Disorders
SO PLOS GENETICS
LA English
DT Article
ID COPY-NUMBER VARIANTS; PRADER-WILLI-SYNDROME; GENOMIC DISORDERS; AUTISM;
   POPULATION; SPECTRUM; REGION; BRAIN; ILLNESS; GENES
AB Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally expressed imprinted genes in the contribution of Copy Number Variants (CNVs) at this interval to the incidence of psychotic illness. This work will have tangible benefits for patients with 15q11.2-q13.3 duplications by aiding genetic counseling.
C1 [Isles, Anthony R.; Walters, James; Rees, Elliott; Martin, Joanna; Little, Rosie B.; Potter, Harry; O'Donovan, Michael C.; Owen, Michael J.; Kirov, George] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
   [Ingason, Andres; Stefansson, Hreinn; Stefansson, Kari] DeCode Genet, Reykjavik, Iceland.
   [Lowther, Chelsea; Costain, Gregory; Bassett, Anne] Univ Toronto, Clin Genet Res Program, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
   [Gawlick, Micha; Stoeber, Gerald] Univ Wurzburg, D-97070 Wurzburg, Germany.
   [Georgieva, Lyudmila] Oxford Gene Technol, Begbroke, Oxon, England.
   [Pizzo, Lucilla; Girirajan, Santhosh D.] Dept Biochem & Mol Biol, University Pk, PA USA.
   [Pizzo, Lucilla; Girirajan, Santhosh D.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA.
   [Ozaki, Norio; Aleksic, Branko; Kushima, Itaru] Nagoya Univ, Dept Psychiat, Grad Sch Med, Showa Ku, Nagoya, Aichi 4648601, Japan.
   [Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan.
   [Levinson, Douglas F.] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA.
   [Gejman, Pablo V.; Duan, Jubao] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Med Ctr Dr, Bethesda, MD 20892 USA.
   [Sanders, Alan R.; Duan, Jubao] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA.
   [Sanders, Alan R.; Duan, Jubao] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
   [Willis, Joseph; Sisodiya, Sanjay] UCL Inst Neurol, Queen Sq, London, England.
   [Werge, Thomas M.] Univ Copenhagen, Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Mental Hlth Serv Copenhagen, Copenhagen, Denmark.
   [Degenhardt, Franziska] Univ Bonn, Inst Human Genet, Bonn, Germany.
   [Giegling, Ina; Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany.
   [Hreidarsson, Stefan J.; Saemundsen, Evald] State Diagnost & Counselling Ctr, Kopavogur, Iceland.
   [Saemundsen, Evald] Univ Iceland, Fac Med, Reykjavik, Iceland.
   [Ahn, Joo Wook; Ogilvie, Caroline] Guys & St Thomas NHS Fdn Trust, London, England.
RP Owen, MJ (reprint author), Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
EM owenmj@cardiff.ac.uk; kirov@cardiff.ac.uk
RI Aleksic, Branko/G-1540-2011; 
OI Aleksic, Branko/0000-0001-8982-4580; Martin, Joanna/0000-0002-8911-3479;
   Owen, Michael/0000-0003-4798-0862; Walters, James/0000-0002-6980-4053;
   Potter, Harry/0000-0002-8398-0264
FU European Union [115008]; EU [GA 286213]; National Institute of Mental
   Health [R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587,
   R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01
   MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469, U01
   MH79470]; Ministry of Education, Culture, Sports, Science and Technology
   of Japan; European Community [279062, HEALTH-F2-2010-241909]; Department
   of Health's NIHR Biomedical Research Centres; Canadian Institutes of
   Health Research (CIHR) [MOP-89066, MOP-111238]; German Federal Ministry
   of Education and Research (BMBF) through the Integrated Network
   IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental
   Disorders), under the auspices of the e:Med Programme; BONFOR grant
   program of the Medical Faculty Bonn; Medical Research Council (MRC)
   Centre [G0800509]; Genetics Society Summer Studentship [G0801418]
FX The research leading to these results has received support from:
   Iceland: The Innovative Medicines Initiative Joint Undertaking under
   grant agreement no. 115008 of which resources are composed of EFPIA
   in-kind contribution and financial contribution from the European
   Union's Seventh Framework Programme (FP7/2007-2013) and EU funded
   FP7-People-2011-IAPP grant PsychDPC (GA 286213). Molecular Genetics of
   Schizophrenia (MGS) study: Funding support for the Genome-Wide
   Association of Schizophrenia Study was provided by the National
   Institute of Mental Health (R01 MH67257, R01 MH59588, R01 MH59571, R01
   MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01
   MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289 U01 MH46318,
   U01 MH79469, and U01 MH79470). Work in Japan was funded by a
   Grant-in-Aid for "Integrated research on neuropsychiatric disorders"
   carried out under the Strategic Research Program for Brain Sciences and
   the Brain Mapping by Integrated Neurotechnologies for Disease Studies
   (Brain/MINDS) by the Ministry of Education, Culture, Sports, Science and
   Technology of Japan. Work at UCL, London, was partly supported by
   European Community's Seventh Framework Programme (EpiPGX, grant number
   279062) and the Department of Health's NIHR Biomedical Research Centres
   funding scheme. Work in Canada was partly funded by the Canadian
   Institutes of Health Research (CIHR): MOP-89066 and MOP-111238 and a
   Doctoral Award to CL. Work at the University of Bonn, Germany was
   supported by the German Federal Ministry of Education and Research
   (BMBF) through the Integrated Network IntegraMent (Integrated
   Understanding of Causes and Mechanisms in Mental Disorders), under the
   auspices of the e:Med Programme and the BONFOR grant program of the
   Medical Faculty Bonn. Work at Cardiff University was supported by
   Medical Research Council (MRC) Centre (G0800509) and Program Grants
   (G0801418), a Genetics Society Summer Studentship, and the European
   Community's Seventh Framework Programme (HEALTH-F2-2010-241909 (Project
   EU-GEI). The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 39
TC 2
Z9 2
U1 5
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2016
VL 12
IS 5
AR e1005993
DI 10.1371/journal.pgen.1005993
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA DN6PH
UT WOS:000377197100007
PM 27153221
ER

PT J
AU Smith, JG
   Felix, JF
   Morrison, AC
   Kalogeropoulos, A
   Trompet, S
   Wilk, JB
   Gidlof, O
   Wang, XC
   Morley, M
   Mendelson, M
   Joehanes, R
   Ligthart, S
   Shan, XY
   Bis, JC
   Wang, YA
   Sjogren, M
   Ngwa, J
   Brandimarto, J
   Stott, DJ
   Aguilar, D
   Rice, KM
   Sesso, HD
   Demissie, S
   Buckley, BM
   Taylor, KD
   Ford, I
   Yao, C
   Liu, CY
   Sotoodehnia, N
   van der Harst, P
   Stricker, BHC
   Kritchevsky, SB
   Liu, YM
   Gaziano, JM
   Hofman, A
   Moravec, CS
   Uitterlinden, AG
   Kellis, M
   van Meurs, JB
   Margulies, KB
   Dehghan, A
   Levy, D
   Olde, B
   Psaty, BM
   Cupples, LA
   Jukema, JW
   Djousse, L
   Franco, OH
   Boerwinkle, E
   Boyer, LA
   Newton-Cheh, C
   Butler, J
   Vasan, RS
   Cappola, TP
   Smith, NL
AF Smith, J. Gustav
   Felix, Janine F.
   Morrison, Alanna C.
   Kalogeropoulos, Andreas
   Trompet, Stella
   Wilk, Jemma B.
   Gidloef, Olof
   Wang, Xinchen
   Morley, Michael
   Mendelson, Michael
   Joehanes, Roby
   Ligthart, Symen
   Shan, Xiaoyin
   Bis, Joshua C.
   Wang, Ying A.
   Sjoegren, Marketa
   Ngwa, Julius
   Brandimarto, Jeffrey
   Stott, David J.
   Aguilar, David
   Rice, Kenneth M.
   Sesso, Howard D.
   Demissie, Serkalem
   Buckley, Brendan M.
   Taylor, Kent D.
   Ford, Ian
   Yao, Chen
   Liu, Chunyu
   Sotoodehnia, Nona
   van der Harst, Pim
   Stricker, Bruno H. Ch.
   Kritchevsky, Stephen B.
   Liu, Yongmei
   Gaziano, J. Michael
   Hofman, Albert
   Moravec, Christine S.
   Uitterlinden, Andre G.
   Kellis, Manolis
   van Meurs, Joyce B.
   Margulies, Kenneth B.
   Dehghan, Abbas
   Levy, Daniel
   Olde, Bjoern
   Psaty, Bruce M.
   Cupples, L. Adrienne
   Jukema, J. Wouter
   Djousse, Luc
   Franco, Oscar H.
   Boerwinkle, Eric
   Boyer, Laurie A.
   Newton-Cheh, Christopher
   Butler, Javed
   Vasan, Ramachandran S.
   Cappola, Thomas P.
   Smith, Nicholas L.
CA CHARGE-SCD Consortium
   EchoGen Consortium
   QT-IGC Consortium
   CHARGE-QRS Consortium
TI Discovery of Genetic Variation on Chromosome 5q22 Associated with
   Mortality in Heart Failure
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PRESERVED EJECTION FRACTION; EPIDEMIOLOGY
   CHARGE CONSORTIUM; AGING RESEARCH; HUMAN-POPULATIONS; AFRICAN ANCESTRY;
   VARIANTS; RISK; METAANALYSIS; SURVIVAL
AB Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10(-9)). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10(-40)) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10(-4)). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
C1 [Smith, J. Gustav; Gidloef, Olof; Olde, Bjoern] Lund Univ, Dept Cardiol, Dept Clin Sci, Lund, Sweden.
   [Smith, J. Gustav] Skane Univ Hosp, Dept Heart Failure & Valvular Dis, Lund, Sweden.
   [Smith, J. Gustav; Wang, Xinchen; Kellis, Manolis; Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
   [Smith, J. Gustav; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA USA.
   [Smith, J. Gustav; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
   [Smith, J. Gustav; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Smith, J. Gustav; Sjoegren, Marketa] Lund Univ, Dept Clin Sci, Malmo, Sweden.
   [Felix, Janine F.; Ligthart, Symen; Stricker, Bruno H. Ch.; Hofman, Albert; Uitterlinden, Andre G.; Dehghan, Abbas; Franco, Oscar H.] Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
   [Felix, Janine F.] Netherlands Genom Initiat, Netherlands Consortium Healthy Aging NGI NCHA, Leiden, Netherlands.
   [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
   [Kalogeropoulos, Andreas] Emory Univ, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
   [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
   [Trompet, Stella] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
   [Wilk, Jemma B.; Sesso, Howard D.; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Wilk, Jemma B.; Sesso, Howard D.; Gaziano, J. Michael; Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA.
   [Wang, Xinchen; Kellis, Manolis; Boyer, Laurie A.] MIT, Dept Biol, Cambridge, MA USA.
   [Morley, Michael; Shan, Xiaoyin; Brandimarto, Jeffrey; Margulies, Kenneth B.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Mendelson, Michael; Joehanes, Roby; Yao, Chen; Liu, Chunyu; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
   [Mendelson, Michael; Joehanes, Roby; Yao, Chen; Liu, Chunyu; Levy, Daniel] NHLBI, Populat Sci, Bethesda, MD 20892 USA.
   [Mendelson, Michael] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
   [Bis, Joshua C.; Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Wang, Ying A.] Novartis Inst BioMed Res, Cambridge, MA USA.
   [Ngwa, Julius; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Stott, David J.] Univ Glasgow, Acad Sect Geriatr Med, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland.
   [Aguilar, David] Baylor Coll Med, Houston, TX 77030 USA.
   [Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
   [Taylor, Kent D.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA.
   [Taylor, Kent D.] Harbor UCLA, Med Ctr, Dept Pediat, Torrance, CA USA.
   [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
   [Sotoodehnia, Nona; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
   [van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
   [Stricker, Bruno H. Ch.; Uitterlinden, Andre G.; van Meurs, Joyce B.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
   [Stricker, Bruno H. Ch.] Inspectorate Hlth Care, The Hague, Netherlands.
   [Stricker, Bruno H. Ch.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
   [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Geronotol & Geriatr Med, Dept Internal Med, Winston Salem, NC USA.
   [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
   [Moravec, Christine S.] Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA.
   [Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
   [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
   [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
   [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
   [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
   [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA.
   [Smith, Nicholas L.] Dept Veteran Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
RP Smith, JG (reprint author), Lund Univ, Dept Cardiol, Dept Clin Sci, Lund, Sweden.
EM gustav.smith@med.lu.se
RI Mendelson, Michael/I-2874-2014; Djousse, Luc/F-5033-2017; 
OI Mendelson, Michael/0000-0001-7590-3958; Djousse,
   Luc/0000-0002-9902-3047; Kalogeropoulos, Andreas/0000-0002-1284-429X;
   Ramachandran, Vasan/0000-0001-7357-5970; Dehghan,
   Abbas/0000-0001-6403-016X
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
   HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
   HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
   HHSN268201100012C, N01-HC-55015, N01-HC-55016, N01-HC-55018,
   N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
   R01HL59367, R01HL086694]; National Human Genome Research Institute
   [U01HG004402]; National Institutes of Health [HHSN268200625226C,
   HHSN268200782096C]; National Institutes of Health and NIH Roadmap for
   Medical Research [UL1RR025005]; NIH, National Institutes of
   Environmental Health Sciences; NHLBI [HHSN268 201200036C,
   HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
   N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652,
   R01HL105756, R01HL103612, R01HL120393, N01-HC-25195, NIH R01HL105993];
   National Institute of Neurological Disorders and Stroke (NINDS);
   National Institute on Aging (NIA) [R01AG023629]; National Center for
   Advancing Translational Sciences; CTSI [UL1TR000124]; National Institute
   of Diabetes and Digestive and Kidney Disease Diabetes Research Center
   (DRC) [DK063491]; Affymetrix, Inc [N02-HL-6-4278]; National Heart Lung
   Blood Institute [2K24HL04334, R01HL077477, R01HL093328]; NIA
   [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; Intramural
   Research Program of the NIH, National Institute on Aging; Bristol-Myers
   Squibb; Netherlands Heart Foundation [2001 D 032]; European commission
   [223004]; Netherlands Genomics Initiative (Netherlands Consortium for
   Healthy Aging) [050-060-810]; Netherlands Organisation of Scientific
   Research NWO Investments [175.010.2005.011, 911-03-012]; Research
   Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands
   Genomics Initiative (NGI)/Netherlands Organisation for Scientific
   Research (NWO) [050-060-810]; Erasmus Medical Center and Erasmus
   University, Rotterdam; Netherlands Organization for the Health Research
   and Development (ZonMw); Research Institute for Diseases in the Elderly
   (RIDE); Ministry of Education, Culture and Science; Ministry for Health,
   Welfare and Sports; European Commission; Municipality of Rotterdam;
   Nestl; Nutrition (Nestec Ltd.); Metagenics Inc.; AXA; Swedish Cancer
   Society; Swedish Medical Research Council; Swedish Dairy Association;
   Albert Pahlsson and Gunnar Nilsson Foundations; Malm city council;
   Swedish National Health Service; Marta Winkler Foundation; Swedish Heart
   Association; Swedish Heart-Lung Foundation; Swedish Research Council;
   European Research Council; Skane University Hospital in Lund; Crafoord
   Foundation; National Cancer Institute [CA-34944, CA-40360, CA-097193];
   National Heart, Lung, and Blood Institute, Bethesda, MD [HL-26490,
   HL-34595]
FX Support for research reported in this article is listed below by study.
   ARIC and ARIC2: The Atherosclerosis Risk in Communities 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,
   N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
   N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694),
   National Human Genome Research Institute contract U01HG004402, and
   National Institutes of Health contract HHSN268200625226C. The authors
   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. This research was supported in part by the
   intramural research program of the NIH, National Institutes of
   Environmental Health Sciences. CHS: This Cardiovascular Health Study
   research was supported by NHLBI contracts HHSN268 201200036C,
   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 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. The content is solely the
   responsibility of the authors and does not necessarily represent the
   official views of the National Institutes of Health. FHS: The Framingham
   Heart Study was supported by NHLBI (Contract No. N01HC-25195) and its
   contract with Affymetrix, Inc for genotyping services (Contract No.
   N02-HL-6-4278). This work was also supported in part by grants from the
   National Heart Lung Blood Institute 2K24HL04334, R01HL077477, and
   R01HL093328 (all to RSV). This study is based on analyses by Framingham
   Heart Study investigators participating in the SNP Health Association
   Resource (SHARe) project. MAGNet: The gene expression study was
   supported by NHLBI (NIH R01HL105993). Health ABC: This research was
   supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The
   genome-wide association study was funded by NIA grant 1R01AG032098-01A1
   to Wake Forest University Health Sciences and genotyping services were
   provided by the Center for Inherited Disease Research (CIDR). CIDR is
   fully funded through a federal contract from the National Institutes of
   Health to The Johns Hopkins University, contract number
   HHSN268200782096C. This research was supported
NR 66
TC 2
Z9 2
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2016
VL 12
IS 5
AR e1006034
DI 10.1371/journal.pgen.1006034
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA DN6PH
UT WOS:000377197100035
PM 27149122
ER

PT J
AU Carpentier, A
   Nimgaonkar, I
   Chu, V
   Xia, YC
   Hu, ZY
   Liang, TJ
AF Carpentier, Arnaud
   Nimgaonkar, Ila
   Chu, Virginia
   Xia, Yuchen
   Hu, Zongyi
   Liang, T. Jake
TI Hepatic differentiation of human pluripotent stem cells in miniaturized
   format suitable for high-throughput screen
SO STEM CELL RESEARCH
LA English
DT Article
DE Pluripotent stem cells; Hepatic differentiation; High-throughput assay;
   384-Well plates
ID HEPATOCYTE-LIKE CELLS; EFFICIENT DIFFERENTIATION; C VIRUS; ENDODERM;
   CULTURE; GENERATION
AB The establishment of protocols to differentiate human pluripotent stem cells (hPSCs) including embryonic (ESC) and induced pluripotent (iPSC) stem cells into functional hepatocyte-like cells (HLCs) creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses) in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3 weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli. Published by Elsevier B.V.
C1 [Carpentier, Arnaud; Nimgaonkar, Ila; Chu, Virginia; Xia, Yuchen; Hu, Zongyi; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Carpentier, Arnaud] Twincore, Inst Expt Virol, Hannover, Germany.
RP Carpentier, A; Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.; Carpentier, A (reprint author), Twincore, Inst Expt Virol, Hannover, Germany.
EM arnaud.carpentier@twincore.de; jakel@bdg10.niddk.nih.gov
OI Xia, Yuchen/0000-0001-8460-3893
FU International Liver Cancer Association (ILCA) fellowship; Intramural
   Research Program of NIDDK [Z01 DK54504, DK54505]
FX We wish to thank Kevin Chen (NIH Stem Cell Unit) for the monolayer
   adapted H9-ESC cell line and for his advice concerning adaptation of
   colony-type culture into monolayer SC culture. We thank also Zhensheng
   Zhang, Ronda Sapp, Fang Zhang, and Frank Q Li (NIDDK, LDB) for their
   technical assistance and helpful discussions. Yuchen Xia is sponsored by
   The International Liver Cancer Association (ILCA) fellowship. This work
   was supported by the Intramural Research Program of the NIDDK (Z01
   DK54504 and DK54505).
NR 21
TC 3
Z9 4
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD MAY
PY 2016
VL 16
IS 3
BP 640
EP 650
DI 10.1016/j.scr.2016.03.009
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
   Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA DN9RD
UT WOS:000377416900014
PM 27062358
ER

PT J
AU Simon, N
   FitzGerald, D
AF Simon, Nathan
   FitzGerald, David
TI Immunotoxin Therapies for the Treatment of Epidermal Growth Factor
   Receptor-Dependent Cancers
SO TOXINS
LA English
DT Review
DE immunotoxin; EGFR; cancer therapeutic; clinical development
ID CELL LUNG-CANCER; HUMAN PANCREATIC-CANCER; FACTOR FUSION PROTEIN;
   PHASE-III TRIAL; CONFERS ENHANCED TUMORIGENICITY; HUMAN GLIOBLASTOMA
   CELLS; MALIGNANT BRAIN-TUMORS; MONOCLONAL-ANTIBODY; FACTOR-ALPHA;
   PSEUDOMONAS EXOTOXIN
AB Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have progressed to human trials. This review summarizes much of the past and current work in the development of immunotoxins for targeting EGFR-driven cancers.
C1 [Simon, Nathan; FitzGerald, David] NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,37-5124, Bethesda, MD 20892 USA.
RP FitzGerald, D (reprint author), NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,37-5124, Bethesda, MD 20892 USA.
EM nathan.simon@nih.gov; fitzgerd@helix.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX This work and open access publication costs were supported by the
   Intramural Research Program of the National Institutes of Health,
   National Cancer Institute, Center for Cancer Research.
NR 149
TC 2
Z9 2
U1 3
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD MAY
PY 2016
VL 8
IS 5
AR 137
DI 10.3390/toxins8050137
PG 23
WC Toxicology
SC Toxicology
GA DN9VH
UT WOS:000377428300018
ER

PT J
AU Yahiro, K
   Hirayama, T
   Moss, J
   Noda, M
AF Yahiro, Kinnosuke
   Hirayama, Toshiya
   Moss, Joel
   Noda, Masatoshi
TI New Insights into VacA Intoxication Mediated through Its Cell Surface
   Receptors
SO TOXINS
LA English
DT Review
DE vacuolating cytotoxin (VacA); receptors; receptor-like protein tyrosine
   phosphatase (RPTP); RPTP; low-density lipoprotein receptor-related
   protein-1 (LRP1)
ID PYLORI VACUOLATING CYTOTOXIN; TYROSINE-PHOSPHATASE-BETA; GASTRIC
   EPITHELIAL-CELLS; IDIOPATHIC THROMBOCYTOPENIC PURPURA; ANION-SELECTIVE
   CHANNELS; CYTOCHROME-C RELEASE; HELICOBACTER-PYLORI; LIPID RAFTS; TOXIN
   VACA; IN-VITRO
AB Helicobacter pylori (H. pylori), a major cause of gastroduodenal diseases, produces VacA, a vacuolating cytotoxin associated with gastric inflammation and ulceration. The C-terminal domain of VacA plays a crucial role in receptor recognition on target cells. We have previously identified three proteins (i.e., RPTP, RPTP, and LRP1) that serve as VacA receptors. These receptors contribute to the internalization of VacA into epithelial cells, activate signal transduction pathways, and contribute to cell death and gastric ulceration. In addition, other factors (e.g., CD18, sphingomyelin) have also been identified as cell-surface, VacA-binding proteins. Since we believe that, following interactions with its host cell receptors, VacA participates in events leading to disease, a better understanding of the cellular function of VacA receptors may provide valuable information regarding the mechanisms underlying the pleiotropic actions of VacA and the pathogenesis of H. pylori-mediated disease. In this review, we focus on VacA receptors and their role in events leading to cell damage.
C1 [Yahiro, Kinnosuke; Noda, Masatoshi] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan.
   [Hirayama, Toshiya] Nagasaki Univ, Inst Trop Med, Dept Bacteriol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
   [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan.
EM yahirok@faculty.chiba-u.jp; hirayama@nagasaki-u.ac.jp;
   mossj@nhlbi.nih.gov; noda@faculty.chiba-u.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
   Japan Science and Technology Agency; Institute of Tropical Medicine,
   Nagasaki University; National Institutes of Health, National Heart,
   Lung, and Blood Institute
FX This work was supported by Grants-in-Aid for Scientific Research from
   the Ministry of Education, Culture, Sports, Science and Technology of
   Japan, Improvement of Research Environment for Young Researchers from
   the Japan Science and Technology Agency and the Cooperative Research
   Grant of the Institute of Tropical Medicine, Nagasaki University, 2012
   and 2014. Dr. Joel Moss was supported by the Intramural Research
   Program, National Institutes of Health, National Heart, Lung, and Blood
   Institute.
NR 100
TC 1
Z9 1
U1 1
U2 1
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD MAY
PY 2016
VL 8
IS 5
AR 152
DI 10.3390/toxins8050152
PG 12
WC Toxicology
SC Toxicology
GA DN9VH
UT WOS:000377428300033
ER

PT J
AU Gross, TG
   Biondi, A
AF Gross, Thomas G.
   Biondi, Andrea
TI Paediatric non-Hodgkin lymphoma in low and middle income countries
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article; Proceedings Paper
CT 5th International Symposium on Childhood, Adolescent and Young Adult
   Non-Hodgkin Lymphoma (NHL)
CY OCT 21-24, 2015
CL Varese, ITALY
DE paediatric; non-Hodgkin lymphoma; developing countries
ID ENDEMIC BURKITT-LYMPHOMA; CHILDREN; ADOLESCENTS; CHILDHOOD; CANCER;
   ONCOLOGY; SURVIVAL; MALAWI
AB Great advances have been made in the treatment of paediatric non-Hodgkin lymphoma (NHL). In high-income countries (HIC), cure rates now exceed 85%. However, in low- and middle-income countries (LMIC), cure rates remain less than 50%. It is estimated that over 90% of paediatric NHL worldwide occur in LMIC; therefore, even modest improvements in outcome would have significant impact in reducing the burden of paediatric NHL globally. This article will discuss some of the issues required to improve the outcome of paediatric NHL in LMIC using data presented at the Fifth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma held in Varese, Italy, 2015 to illustrate these issues. Additionally, potential bi-directional benefits for patients in both LMIC and HIC from future collaborations will be discussed.
C1 [Gross, Thomas G.] NCI, Ctr Global Hlth, Rockville, MD USA.
   [Biondi, Andrea] Univ Milano Bicocca, San Gerardo Hosp, Fondaz MBBM, Paediat Clin, Monza, Italy.
RP Gross, TG (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM thomas.gross@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 21
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAY
PY 2016
VL 173
IS 4
SI SI
BP 651
EP 654
DI 10.1111/bjh.14030
PG 4
WC Hematology
SC Hematology
GA DN7JY
UT WOS:000377252800014
PM 27098084
ER

PT J
AU Lewis, GD
   Semigran, MJ
   Givertz, MM
   Malhotra, R
   Anstrom, KJ
   Hernandez, AF
   Shah, MR
   Braunwald, E
AF Lewis, Gregory D.
   Semigran, Marc J.
   Givertz, Michael M.
   Malhotra, Rajeev
   Anstrom, Kevin J.
   Hernandez, Adrian F.
   Shah, Monica R.
   Braunwald, Eugene
TI Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction
   Design and Rationale for Oral Iron Repletion Effects on Oxygen Uptake in
   Heart Failure
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE clinical trial; exercise; heart failure; iron; oxygen consumption
ID QUALITY-OF-LIFE; INTRAVENOUS IRON; SKELETAL-MUSCLE; FERRIC
   CARBOXYMALTOSE; WORK CAPACITY; SCIENTIFIC STATEMENT; REPLACEMENT
   THERAPY; EXERCISE TOLERANCE; DEFICIENCY ANEMIA; PROGNOSTIC VALUE
AB Iron deficiency is present in approximate to 50% of patients with heart failure and is an independent predictor of mortality. Despite growing recognition of the functional and prognostic significance of iron deficiency, randomized multicenter trials exploring the use of oral iron supplementation in heart failure, a therapy that is inexpensive, readily available, and safe, have not been performed. Moreover, patient characteristics that influence responsiveness to oral iron in patients with heart failure have not been defined. Although results of intravenous iron repletion trials have been promising, regularly treating patients with intravenous iron products is both expensive and poses logistical challenges for outpatients. Herein, we describe the rationale for the Oral Iron Repletion effects on Oxygen Uptake in Heart Failure (IRONOUT HF) trial. This National Institute of Health-sponsored trial will investigate oral iron polysaccharide compared with matching placebo with the primary end point of change in exercise capacity as measured by peak oxygen consumption at baseline and at 16 weeks.
C1 [Lewis, Gregory D.; Semigran, Marc J.; Malhotra, Rajeev] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA.
   [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div, Boston, MA 02115 USA.
   [Anstrom, Kevin J.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA.
   [Shah, Monica R.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
   [Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA.
RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Div Cardiol, Bigelow 800,Fruit St, Boston, MA 02114 USA.
EM glewis@partners.org
OI Malhotra, Rajeev/0000-0003-0120-4630
FU National Heart, Lung, and Blood Institute (NHLBI) [U10 HL084904, U10
   HL110312, U10 HL110337, U10 HL110342, U10 HL110262, U10 HL110297, U10
   HL110302, U10 HL110309, U10 HL110336, U10 HL110338]
FX This study was supported by grants from the National Heart, Lung, and
   Blood Institute (NHLBI; coordinating center: U10 HL084904; regional
   clinical centers: U10 HL110312, U10 HL110337, U10 HL110342, U10
   HL110262, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, and
   U10 HL110338).
NR 59
TC 4
Z9 4
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAY
PY 2016
VL 9
IS 5
AR e000345
DI 10.1161/CIRCHEARTFAILURE.115.000345
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DN0IS
UT WOS:000376748200001
ER

PT J
AU Nie, YJ
   Yang, D
   Oppenheim, JJ
AF Nie, Yingjie
   Yang, De
   Oppenheim, Joost J.
TI Alarmins and Antitumor Immunity
SO CLINICAL THERAPEUTICS
LA English
DT Review
DE alarmin; biomarker; damage-associated molecular patterns; immune
   response; pattern recognition receptor; tumor immunity
ID HUMAN DENDRITIC CELLS; EOSINOPHIL-DERIVED NEUROTOXIN;
   CHROMOSOMAL-PROTEIN HMGN1; NUCLEOSOME-BINDING PROTEIN-1; INHIBITS
   TUMOR-GROWTH; RECEPTOR 2 FPR2; INNATE IMMUNITY; ADAPTIVE IMMUNITY;
   EPITHELIAL-CELLS; HUMAN-MONOCYTES
AB Purpose: Alarmins are constitutively present endogenous molecules that essentially act as early warning signals for the immune system. We provide a brief overview of major alarmins and highlight their roles in tumor immunity.
   Methods: We searched PubMed up to January 10, 2016, using alarmins and/or damage-associated molecular patterns (DAMPs), as key words. We selected and reviewed articles that focused on the discovery and functions of alarmin and their roles in tumor immunity.
   Findings: Alarmins are essentially endogenous immunostimulatory DAMP molecules that are exposed in response to danger (eg, infection or tissue injury) as a result of degranulation, cell death, or induction. They are sensed by chemotactic receptors and pattern recognition receptors to induce immune responses by promoting the recruitment and activation of leukocytes, particularly antigen-presenting cells. (C) 2016 Published by Elsevier HS Journals, Inc.
C1 [Nie, Yingjie; Yang, De; Oppenheim, Joost J.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
   [Nie, Yingjie] Guizhou Prov Peoples Hosp, Guiyang, Guizhou, Peoples R China.
   [Yang, De] Leidos Biomed Res Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Oppenheim, JJ (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
EM oppen-heij@mail.nih.gov
FU National Cancer Institute of the National Institutes of Health
   [HHSN261200800001E]
FX This project was funded in whole or in part with federal funds from the
   National Cancer Institute of the 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. All
   authors contributed equally to this work.
NR 154
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
EI 1879-114X
J9 CLIN THER
JI Clin. Ther.
PD MAY
PY 2016
VL 38
IS 5
BP 1042
EP 1053
DI 10.1016/j.clinthera.2016.03.021
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DN6AJ
UT WOS:000377152700007
PM 27101817
ER

PT J
AU Fong, KSK
   Hufnagel, RB
   Khadka, VS
   Corley, MJ
   Maunakea, AK
   Fogelgren, B
   Ahmed, ZM
   Lozanoff, S
AF Fong, Keith S. K.
   Hufnagel, Robert B.
   Khadka, Vedbar S.
   Corley, Michael J.
   Maunakea, Alika K.
   Fogelgren, Ben
   Ahmed, Zubair M.
   Lozanoff, Scott
TI A mutation in the tuft mouse disrupts TET1 activity and alters the
   expression of genes that are crucial for neural tube closure
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Anterior cranial cephalocele; Midfacial cleft; Neural tube defect;
   Encephalocele; Exencephaly; Anencephaly; Epigenetic
ID PLANAR CELL POLARITY; HEMATOPOIETIC STEM-CELLS; DNA DEMETHYLATION;
   RNA-SEQ; POSTNATAL-DEVELOPMENT; READ ALIGNMENT; ES CELLS; DEFECTS;
   5-HYDROXYMETHYLCYTOSINE; TRANSCRIPTION
AB Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse.
C1 [Fong, Keith S. K.; Fogelgren, Ben; Lozanoff, Scott] Univ Hawaii, John A Burns Sch Med, Dept Anat Biochem & Physiol, Honolulu, HI 96813 USA.
   [Hufnagel, Robert B.; Ahmed, Zubair M.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Dept Pediat,Div Human Genet, 3333 Burnet Ave,ML 7003, Cincinnati, OH 45229 USA.
   [Hufnagel, Robert B.] NEI, Unit Pediat Dev & Genet Ophthalmol, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
   [Khadka, Vedbar S.] Univ Hawaii, John A Burns Sch Med, Off Biostat & Quantitat Hlth Sci, Honolulu, HI 96813 USA.
   [Corley, Michael J.; Maunakea, Alika K.] Univ Hawaii, John A Burns Sch Med, Epigen Res Program, Dept Native Hawaiian Hlth, Honolulu, HI 96813 USA.
   [Ahmed, Zubair M.] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, BioPk Bldg1,800 West Baltimore St,Room 404, Baltimore, MD 21201 USA.
RP Fong, KSK (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Anat Biochem & Physiol, Honolulu, HI 96813 USA.
EM ksfong@hawaii.edu
OI Fong, Keith/0000-0001-6845-1754
FU Hawai'i Community Foundation [13ADVC-60316]; National Institutes of
   Health [U54MD007584, P20GM103466, 1K01DK087852, R03DK100738,
   R01DC012564, R01DK064752]; Cincinnati Children's Hospital Medical
   Center; March of Dimes Foundation [5-FY14-56]; Queen's Health Systems
   Native Hawaiian Health Initiative
FX This work was supported by grants from the Hawai'i Community Foundation
   13ADVC-60316 (K.S.K.F.) and in part by the National Institutes of Health
   U54MD007584 and P20GM103466 (V.S.K.), 1K01DK087852, R03DK100738 (B.F.),
   R01DC012564 (Z.M.A.), R01DK064752 (S.L.), the Cincinnati Children's
   Hospital Medical Center (R.B.H.), the March of Dimes Foundation
   #5-FY14-56 (B.F.), and the Queen's Health Systems Native Hawaiian Health
   Initiative (A.K.M.). Sequencing services and use of the Histopathology
   Core at the University of Hawai'i was enabled in part by the National
   Institutes of Health (P20GM103457, G12MD007601 and P30GM103341).
NR 68
TC 0
Z9 0
U1 5
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD MAY 1
PY 2016
VL 9
IS 5
BP 585
EP 596
DI 10.1242/dmm.024109
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA DN5DP
UT WOS:000377086800010
PM 26989192
ER

PT J
AU Marusak, HA
   Kuruvadi, N
   Vila, AM
   Shattuck, DW
   Joshi, SH
   Joshi, AA
   Jella, PK
   Thomason, ME
AF Marusak, Hilary A.
   Kuruvadi, Nisha
   Vila, Angela M.
   Shattuck, David W.
   Joshi, Shantanu H.
   Joshi, Anand A.
   Jella, Pavan K.
   Thomason, Moriah E.
TI Interactive effects of BDNF Val66Met genotype and trauma on limbic brain
   anatomy in childhood
SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
LA English
DT Article
DE Brain-derived neurotrophic factor; Early adversity; Mood disorders; Gray
   matter volume; Medial prefrontal cortex; Adolescence
ID POSTTRAUMATIC-STRESS-DISORDER; EARLY-LIFE STRESS; NEUROTROPHIC FACTOR;
   HIPPOCAMPAL VOLUME; MOOD DISORDERS; POLYMORPHISM; DEPRESSION; ADVERSITY;
   AMYGDALA; PLASTICITY
AB Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain.
C1 [Marusak, Hilary A.; Vila, Angela M.; Thomason, Moriah E.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, 71 E Ferry St, Detroit, MI 48202 USA.
   [Marusak, Hilary A.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA.
   [Kuruvadi, Nisha] Liberty Univ, Coll Osteopath Med, Lynchburg, VA USA.
   [Shattuck, David W.; Joshi, Shantanu H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [Joshi, Anand A.] Univ So Calif, Brain & Creat Inst, Los Angeles, CA USA.
   [Joshi, Anand A.] Univ So Calif, Signal & Image Proc Inst, Los Angeles, CA USA.
   [Jella, Pavan K.] Wayne State Univ, Dept Radiol, Detroit, MI USA.
   [Thomason, Moriah E.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
   [Thomason, Moriah E.] NICHD, Perinatol Res Branch, NIH, DHSS, Detroit, MI USA.
RP Thomason, ME (reprint author), Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, 71 E Ferry St, Detroit, MI 48202 USA.; Thomason, ME (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.; Thomason, ME (reprint author), NICHD, Perinatol Res Branch, NIH, DHSS, Detroit, MI USA.
EM moriah@wayne.edu
FU Merrill Palmer Skillman Institute; Department of Pediatrics, Wayne State
   University (WSU) School of Medicine, a National Alliance for Research on
   Schizophrenia and Depression Young Investigator Award; NIH National
   Institute of Environmental Health Sciences [P30 ES020957, R21 ES026022];
   NIH National Institute of Neurological Disorders And Stroke [R01
   NS074980]; NIH National Cancer Institute [P30 CA022453]
FX Research reported in this publication was supported, in part, by the
   Merrill Palmer Skillman Institute and the Department of Pediatrics,
   Wayne State University (WSU) School of Medicine, a National Alliance for
   Research on Schizophrenia and Depression Young Investigator Award (MET),
   NIH National Institute of Environmental Health Sciences awards P30
   ES020957 and R21 ES026022 (MET), and the NIH National Institute of
   Neurological Disorders And Stroke award R01 NS074980 (DWS and AAJ). The
   content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Institutes of
   Health. The WSU Genomics Core is supported, in part, by NIH National
   Cancer Institute award P30 CA022453. The authors thank Zahid Latif and
   Yashwanth Katkuri of WSU for their assistance in neuroimaging data
   acquisition, Kayla Martin, Gregory H. Baldwin, Rita Elias, Melissa
   Youmans, Mallory Gardner, Amy Katherine Swartz, Timothy Lozon, Berta
   Rihan, and Ali Daher of WSU for assistance in participant recruitment
   and data collection, Julianne Facca, Matthew Hess, and Susan Land of the
   WSU Applied Genomics Technology Center for assistance with genetic
   analyses, and the children and families who generously shared their
   time.
NR 67
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1018-8827
EI 1435-165X
J9 EUR CHILD ADOLES PSY
JI Eur. Child Adolesc. Psych.
PD MAY
PY 2016
VL 25
IS 5
BP 509
EP 518
DI 10.1007/s00787-015-0759-4
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DN6NK
UT WOS:000377191700006
PM 26286685
ER

PT J
AU Gosmann, NP
   Vaz, LV
   DeSousa, DA
   Koller, SH
   Pine, DS
   Manfro, GG
   Salum, GA
AF Gosmann, N. P.
   Vaz, L. V.
   DeSousa, D. A.
   Koller, S. H.
   Pine, D. S.
   Manfro, G. G.
   Salum, G. A.
TI Anxiety in childhood across the globe: findings from meta-regression
   analyses of the past 15 years (1998-2013)
SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
LA English
DT Article
ID MENTAL-HEALTH; CHILDREN; TRENDS; COHORTS; SCALE
C1 [Gosmann, N. P.; DeSousa, D. A.; Manfro, G. G.; Salum, G. A.] HCPA, Anxiety Disorders Outpatient Program Child & Adol, Ramiro Barcelos 2350,Room 2201A, BR-90035003 Porto Alegre, RS, Brazil.
   [Gosmann, N. P.; Manfro, G. G.; Salum, G. A.] Natl Inst Dev Psychiat Children & Adolescents INC, Sao Paulo, Brazil.
   [Vaz, L. V.; DeSousa, D. A.; Koller, S. H.] Univ Fed Rio Grande do Sul, Inst Psychol, Ctr Psychol Studies At Risk Populat, Porto Alegre, RS, Brazil.
   [Pine, D. S.] NIMH, Emot & Dev Branch, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
RP Gosmann, NP (reprint author), HCPA, Anxiety Disorders Outpatient Program Child & Adol, Ramiro Barcelos 2350,Room 2201A, BR-90035003 Porto Alegre, RS, Brazil.; Gosmann, NP (reprint author), Natl Inst Dev Psychiat Children & Adolescents INC, Sao Paulo, Brazil.
EM natanpgosmann@gmail.com
RI Koller, Silvia/B-2629-2008; 
OI Koller, Silvia/0000-0001-9109-6674; Salum, Giovanni/0000-0002-7537-7289;
   Gosmann, Natan Pereira/0000-0001-9618-5596
NR 10
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1018-8827
EI 1435-165X
J9 EUR CHILD ADOLES PSY
JI Eur. Child Adolesc. Psych.
PD MAY
PY 2016
VL 25
IS 5
BP 556
EP 560
DI 10.1007/s00787-015-0785-2
PG 5
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DN6NK
UT WOS:000377191700011
ER

PT J
AU Meena, NP
   Zhu, G
   Mittelstadt, PR
   Torchia, MLG
   Pourcelot, M
   Arnoult, D
   Ashwell, JD
   Munitic, I
AF Meena, Netra Pal
   Zhu, Guozhi
   Mittelstadt, Paul R.
   Torchia, Maria Letizia Giardino
   Pourcelot, Marie
   Arnoult, Damien
   Ashwell, Jonathan D.
   Munitic, Ivana
TI The TBK1-binding domain of optineurin promotes type I interferon
   responses
SO FEBS LETTERS
LA English
DT Article
DE optineurin; TBK1; type I interferon
ID AMYOTROPHIC-LATERAL-SCLEROSIS; BINDING KINASE 1; AUTOPHAGY RECEPTOR
   OPTINEURIN; OPEN-ANGLE GLAUCOMA; KAPPA-B ACTIVATION; MYOSIN-VI; TBK1;
   MUTATIONS; PROTEIN; NEMO
AB Pathogen-associated molecular pattern (PAMP) recognition leads to TANK-binding kinase (TBK1) polyubiquitination and activation by transautophosphorylation, resulting in IFN- production. Here, we describe a mouse model of optineurin insufficiency (Optn(157)) in which the TBK1-interacting N-terminus of optineurin was deleted. PAMP-stimulated cells from Optn(157) mice had reduced TBK1 activity, no phosphorylation of optineurin Ser(187), and mounted low IFN- responses. In contrast to pull-down assays where the presence of N-terminus was sufficient for TBK1 binding, both the N-terminal and the ubiquitin-binding regions of optineurin were needed for PAMP-induced binding. This report establishes optineurin as a positive regulator TBK1 via a bipartite interaction between these molecules.
C1 [Meena, Netra Pal; Zhu, Guozhi; Mittelstadt, Paul R.; Torchia, Maria Letizia Giardino; Ashwell, Jonathan D.; Munitic, Ivana] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
   [Pourcelot, Marie; Arnoult, Damien] Hop Paul Brousse, INSERM, UMR S 1197, Villejuif, France.
   [Pourcelot, Marie; Arnoult, Damien] Univ Paris Saclay, Villejuif, France.
   [Munitic, Ivana] Univ Rijeka, Dept Biotechnol, Lab Mol Immunol, Rijeka 51000, Croatia.
   [Meena, Netra Pal] NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA.
RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.; Munitic, I (reprint author), Univ Rijeka, Dept Biotechnol, Lab Mol Immunol, Rijeka 51000, Croatia.
EM jda@pop.nci.nih.gov; ivana.munitic@biotech.uniri.hr
FU Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute, National Institutes of Health; Croatian Science
   Foundation [7459]; University of Rijeka; Fondation ARC (Association pour
   La Recherche contre le Cancer); ANRS (Agence Nationale pour la Recherche
   sur le SIDA); Universite Paris-Sud
FX We are grateful to Lino Tessarollo and Eileen Southon (Mouse Cancer
   Genetics Program, NCI-Frederick, Frederick, MD) for assistance during
   generation of Optn Delta<SUP>157</SUP> mice, Dr. Ivan Dikic for
   anti-phospho-S177 optineurin antibody, and Ehydel Castro and Bei Dong
   for expert technical assistance. This work was supported by the
   Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute, National Institutes of Health, the Croatian Science
   Foundation grant #7459 and the support of the University of Rijeka to
   IM, grants from Fondation ARC (Association pour La Recherche contre le
   Cancer) and the ANRS (Agence Nationale pour la Recherche sur le SIDA) to
   DA, and fellowship to MP from Universite Paris-Sud.
NR 38
TC 1
Z9 1
U1 10
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD MAY
PY 2016
VL 590
IS 10
BP 1498
EP 1508
DI 10.1002/1873-3468.12176
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DN5MD
UT WOS:000377111500011
PM 27086836
ER

PT J
AU Sharova, LV
   Sharov, AA
   Piao, YL
   Stagg, CA
   Amano, T
   Qian, Y
   Dudekula, D
   Schlessinger, D
   Ko, MSH
AF Sharova, Lioudmila V.
   Sharov, Alexei A.
   Piao, Yulan
   Stagg, Carole A.
   Amano, Tomokazu
   Qian, Yong
   Dudekula, Dawood
   Schlessinger, David
   Ko, Minoru S. H.
TI Emergence of undifferentiated colonies from mouse embryonic stem cells
   undergoing differentiation by retinoic acid treatment
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Article
DE Retinoic acid; Zscan4; Mouse embryonic stem cells; Pluripotency
ID GENE-EXPRESSION; TRANSCRIPTION FACTORS; SELF-RENEWAL; IN-VITRO; ES
   CELLS; ZSCAN4; MICROARRAY; REPRESSION; INDUCTION; MAINTAINS
AB Retinoic acid (RA) is one of the most potent inducers of differentiation of mouse embryonic stem cells (ESCs). However, previous studies show that RA treatment of cells cultured in the presence of a leukemia inhibitory factor (LIF) also result in the upregulation of a gene called Zscan4, whose transient expression is a marker for undifferentiated ESCs. We explored the balance between these two seemingly antagonistic effects of RA. ESCs indeed differentiated in the presence of LIF after RA treatment, but colonies of undifferentiated ESCs eventually emerged from these differentiated cells - even in the presence of RA. These colonies, named secondary colonies, consist of three cell types: typical undifferentiated ESCs expressing pluripotency genes such as Pou5f1, Sox2, and Nanog; cells expressing Zscan4; and endodermal-like cells located at the periphery of the colony. The capacity to form secondary colonies was confirmed for all eight tested ESC lines. Cells from the secondary colonies - after transfer to the standard ESC medium - retained pluripotency, judged by their strong alkaline phosphatase (ALP) staining, typical colony morphology, gene expression profile, stable karyotype, capacity to differentiate into all three germ layers in embryoid body formation assays, and successful contribution to chimeras after injection into blastocysts. Based on flow cytometry analysis (FACS), the proportion of Zscan4-positive cells in secondary colonies was higher than in standard ESC colonies, which may explain the capacity of ESCs to resist the differentiating effects of RA and instead form secondary colonies of undifferentiated ESCs. This hypothesis is supported by cell-lineage tracing analysis, which showed that most cells in the secondary colonies were descendents of cells transiently expressing Zscan4.
C1 [Sharova, Lioudmila V.; Sharov, Alexei A.; Piao, Yulan; Stagg, Carole A.; Amano, Tomokazu; Qian, Yong; Dudekula, Dawood; Schlessinger, David; Ko, Minoru S. H.] NIA, NIH, Baltimore, MD 21224 USA.
   [Ko, Minoru S. H.] Keio Univ, Dept Syst Med, Sch Med, Tokyo 1608582, Japan.
RP Ko, MSH (reprint author), NIA, NIH, Baltimore, MD 21224 USA.; Ko, MSH (reprint author), Keio Univ, Dept Syst Med, Sch Med, Tokyo 1608582, Japan.
EM ko.minoru@keio.jp
FU 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 29
TC 0
Z9 0
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
EI 1543-706X
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD MAY
PY 2016
VL 52
IS 5
BP 616
EP 624
DI 10.1007/s11626-016-0013-5
PG 9
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA DN2XO
UT WOS:000376926500014
PM 27130680
ER

PT J
AU Blume, ED
   Rosenthal, DN
   Rossano, JW
   Baldwin, JT
   Eghtesady, P
   Morales, DLS
   Cantor, RS
   Conway, J
   Lorts, A
   Almond, CS
   Naftel, DC
   Kirklin, JK
AF Blume, Elizabeth D.
   Rosenthal, David N.
   Rossano, Joseph W.
   Baldwin, J. Timothy
   Eghtesady, Pirooz
   Morales, David L. S.
   Cantor, Ryan S.
   Conway, Jennifer
   Lorts, Angela
   Almond, Christopher S.
   Naftel, David C.
   Kirklin, James K.
CA Pedimacs Investigators
TI Outcomes of children implanted with ventricular assist devices in the
   United States: First analysis of the Pediatric Interagency Registry for
   Mechanical Circulatory Support (PediMACS)
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE pediatric; ventricular assist devices; mechanical circulatory support;
   children; heart failure; transplant
ID HEART-TRANSPLANTATION; MORBIDITY; EVOLUTION
AB BACKGROUND: Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care.
   METHODS: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients <19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events.
   RESULTS: Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) <1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52).
   CONCLUSIONS: PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.
C1 [Blume, Elizabeth D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA USA.
   [Rosenthal, David N.; Almond, Christopher S.] Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Cardiol, Palo Alto, CA 94304 USA.
   [Rossano, Joseph W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Baldwin, J. Timothy] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
   [Eghtesady, Pirooz] St Louis Childrens Hosp, Div Cardiothorac Surg, St Louis, MO 63178 USA.
   [Morales, David L. S.; Lorts, Angela] Cincinnati Childrens Hosp Med Ctr, Inst Heart, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
   [Cantor, Ryan S.; Naftel, David C.; Kirklin, James K.] Univ Alabama Birmingham, Div Cardiothorac Surg, Birmingham, AL USA.
   [Cantor, Ryan S.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
   [Conway, Jennifer] Univ Alberta, Stollery Childrens Hosp, Edmonton, AB, Canada.
RP Lorts, A (reprint author), Cincinnati Childrens Hosp Med Ctr, Inst Heart, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM angela.lorts@cchmc.org
OI Eghtesady, Pirooz/0000-0001-7161-8391; Cantor, Ryan/0000-0002-3102-2638
NR 7
TC 9
Z9 9
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD MAY
PY 2016
VL 35
IS 5
BP 578
EP 584
DI 10.1016/j.healun.2016.01.1227
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
   Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
   Transplantation
GA DN3HB
UT WOS:000376951900007
PM 27009673
ER

PT J
AU Goey, AKL
   Chau, CH
   Sissung, TM
   Cook, KM
   Venzon, DJ
   Castro, A
   Ransom, TR
   Henrich, CJ
   McKee, TC
   McMahon, JB
   Grkovic, T
   Cadelis, MM
   Copp, BR
   Gustafson, KR
   Figg, WD
AF Goey, Andrew K. L.
   Chau, Cindy H.
   Sissung, Tristan M.
   Cook, Kristina M.
   Venzon, David J.
   Castro, Amaya
   Ransom, Tanya R.
   Henrich, Curtis J.
   McKee, Tawnya C.
   McMahon, James B.
   Grkovic, Tanja
   Cadelis, Melissa M.
   Copp, Brent R.
   Gustafson, Kirk R.
   Figg, William D.
TI Screening and Biological Effects of Marine Pyrroloiminoquinone
   Alkaloids: Potential Inhibitors of the HIF-1 alpha/p300 Interaction
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID SMALL-MOLECULE; LATRUNCULIA-BREVIS; ANTITUMOR-ACTIVITY; DISCORHABDIN-C;
   HYPOXIA; SPONGES; CANCER; THERAPY; ANGIOGENESIS; TRANSCRIPTION
AB Inhibition of the hypoxia-inducible factor 1 alpha (HIF-1 alpha) pathway by disrupting its association with the transcriptional coactivator p300 inhibits angiogenesis and tumor development. Development of HIF-1 alpha/p300 inhibitors has been hampered by preclinical toxicity; therefore, we aimed to identify novel HIF-la/p300 inhibitors. Using a cell-free assay designed to test compounds that block HIF-1 alpha/p300 binding, 170 298 crude natural product extracts and prefractionated samples were screened, identifying 25 active extracts. One of these extracts, originating from the marine sponge Latrunculia sp., afforded six pyrroloiminoquinone alkaloids that were identified as positive hits (IC50 values: 1-35 mu M). Luciferase assays confirmed inhibition of HIF-1 alpha transcriptional activity by discorhabdin B (1) and its dimer (2), 3-dihydrodiscorhabdin C (3), makaluvamine F (5), discorhabdin H (8), discorhabdin L (9), and discorhabdin W (11) in HCT 116 colon cancer cells (0.1-10 mu M, p < 0.05). Except for 11, all of these compounds also reduced HIF-1 alpha transcriptional activity in LNCaP prostate cancer cells (0.1-10 mu M, p < 0.05). These effects occurred at noncytotoxic concentrations (<50% cell death) under hypoxic conditions. At the downstream HIF-1 alpha target level, compound 8 (0.5 mu M) significantly decreased VEGF secretion in LNCaP cells (p < 0.05). In COLO 205 colon cancer cells no activity was shown in the luciferase or cytotoxicity assays. Pyrroloiminoquinone alkaloids are a novel class of HIF-1 alpha inhibitors, which interrupt the protein protein interaction between HIF-1 alpha and p300 and consequently reduce HIF-related transcription.
C1 [Goey, Andrew K. L.; Chau, Cindy H.; Sissung, Tristan M.; Cook, Kristina M.; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.
   [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   [Castro, Amaya; Ransom, Tanya R.; Henrich, Curtis J.; McKee, Tawnya C.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
   [Henrich, Curtis J.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Grkovic, Tanja; Cadelis, Melissa M.; Copp, Brent R.] Univ Auckland, Sch Chem Sci, Auckland 1142, New Zealand.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016; Copp, Brent/D-3706-2009
OI Copp, Brent/0000-0001-5492-5269
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research; Frederick National Laboratory for Cancer Research,
   National Institutes of Health [HHSN261200800001E]
FX Thanks to the Natural Products Support Group at NCI-Frederick for
   extract preparation, and S. Tarasov and M. Dyba (Biophysics Resource
   Core, Structural Biophysics Laboratory, CCR) and H. Bokesch (MTL) for
   assistance with high resolution mass spectrometry. We thank Dr. M.
   Stoffels for advice. This research was supported by the Intramural
   Research Program of the National Institutes of Health, National Cancer
   Institute, Center for Cancer Research. This project was also 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 U.S. Government.
NR 36
TC 2
Z9 2
U1 10
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD MAY
PY 2016
VL 79
IS 5
BP 1267
EP 1275
DI 10.1021/acs.jnatprod.5b00846
PG 9
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA DN5ZR
UT WOS:000377150900006
PM 27140429
ER

PT J
AU Vasquez, YM
   Wu, SP
   Anderson, ML
   Hawkins, SM
   Creighton, CJ
   Ray, M
   Tsai, SY
   Tsai, MJ
   Lydon, JP
   DeMayo, FJ
AF Vasquez, Yasmin M.
   Wu, San-Pin
   Anderson, Matthew L.
   Hawkins, Shannon M.
   Creighton, Chad J.
   Ray, Madhumita
   Tsai, Sophia Y.
   Tsai, Ming-Jer
   Lydon, John P.
   DeMayo, Francesco J.
TI Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic
   Glandular Morphogenesis
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID FACTOR-I; PROGESTERONE-RECEPTOR; CELL-PROLIFERATION; INVERSE AGONISTS;
   MOUSE UTERUS; UTERINE; ESTROGEN; IMPLANTATION; DISEASE; SF-1
AB Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production.
C1 [Vasquez, Yasmin M.; Tsai, Sophia Y.; Tsai, Ming-Jer; Lydon, John P.; DeMayo, Francesco J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Anderson, Matthew L.; Hawkins, Shannon M.] Baylor Univ, Dept Obstet & Gynecol, Houston, TX 77030 USA.
   [Anderson, Matthew L.; Creighton, Chad J.] Baylor Coll Med, Div Biostat, Dept Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Wu, San-Pin; Ray, Madhumita] NIEHS, Pregnancy & Female Reprod Grp, POB 12233, Res Triangle Pk, NC 27709 USA.
RP DeMayo, FJ (reprint author), NIEHS, Reprod & Dev Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD B3-02, Res Triangle Pk, NC 27709 USA.
EM francesco.demayo@nih.gov
FU National Institutes of Health (NIH) [R01 HD042311, U54 HD007495]; NCI
   [P30 CA125123]; Eunice Kennedy Shriver National Institute of Child
   Health and Human Development/National Institutes of Health (National
   Centers for Translational Research in Reproduction and Infertility)
   [P50-HD28934]
FX This work was supported by National Institutes of Health (NIH) Grants
   R01 HD042311 (to F.J.D.), U54 HD007495, (to F.J.D. and S.M.H.), and NCI
   P30 CA125123 (C.J.C.). Serum assays for progesterone and estradiol were
   performed by The University of Virginia Center for Research in
   Reproduction Ligand Assay and Analysis Core which is supported by the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development/National Institutes of Health (National Centers for
   Translational Research in Reproduction and Infertility) Grant
   P50-HD28934.
NR 61
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2016
VL 30
IS 5
BP 518
EP 532
DI 10.1210/me.2015-1215
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DN6TT
UT WOS:000377209900004
PM 27018534
ER

PT J
AU Lamas-Gonzalez, O
   Bravo, S
   Sanz, AB
   de la Iglesia, AB
   Eijo, AC
   Ortiz, A
   Watnick, T
   Germino, GG
   Diaz, C
   Garcia-Gonzalez, MA
AF Lamas-Gonzalez, Olaya
   Bravo, Susana
   Belen Sanz, Ana
   Barcia de la Iglesia, Ana
   Cordido Eijo, Adrian
   Ortiz, Alberto
   Watnick, Terry
   Germino, Gregory G.
   Diaz, Candido
   Garcia-Gonzalez, Miguel A.
TI IDENTIFICATION OF NEW SIGNALLING PATHWAYS RELATED TO POLYCYSTIC KIDNEY
   DISEASE (PKD): FROM ANIMAL MODELS TO TREATMENT
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Meeting Abstract
CT 53rd ERA-EDTA Congress
CY MAY 21-24, 2016
CL Vienna, AUSTRIA
SP European Renal Assoc, European Dialysis & Transplant Assoc
C1 [Lamas-Gonzalez, Olaya; Barcia de la Iglesia, Ana; Cordido Eijo, Adrian; Diaz, Candido; Garcia-Gonzalez, Miguel A.] Hlth Res Inst Santiago IDIS, Grp Genet & Dev Biol Renal Dis, Santiago De Compostela, Spain.
   [Bravo, Susana] Hlth Res Inst Santiago IDIS, Prote Unit, Santiago De Compostela, Spain.
   [Belen Sanz, Ana; Ortiz, Alberto] IIS Fdn Jimenez Diaz, Lab Nephrol, Madrid, Spain.
   [Watnick, Terry] Univ Maryland, Sch Med, Nephrol, Baltimore, MD 21201 USA.
   [Germino, Gregory G.] NIDDK, Polycyst Kidney Dis Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2016
VL 31
SU 1
MA SP024
BP 95
EP 95
PG 1
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA DM8ZU
UT WOS:000376653800207
ER

PT J
AU Peng, XY
   Jiang, LP
   Tu, HB
   Chen, C
   Nie, M
   Li, XM
   Xing, XP
   Li, XW
   Chen, LM
AF Peng, Xiaoyan
   Jiang, Lanping
   Tu, Hongbin
   Chen, Chen
   Nie, Min
   Li, Xuemei
   Xing, Xiaoping
   Li, Xuewang
   Chen, Limeng
TI FREQUENT MUTATIONS OF CHINESE GITELMAN SYNDROME PATIENTS: FROM GENOTYPE
   TO CLINICAL AND PATHOLOGICAL FEATURES
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Meeting Abstract
CT 53rd ERA-EDTA Congress
CY MAY 21-24, 2016
CL Vienna, AUSTRIA
SP European Renal Assoc, European Dialysis & Transplant Assoc
C1 [Peng, Xiaoyan; Jiang, Lanping; Chen, Chen; Nie, Min; Li, Xuemei; Xing, Xiaoping; Li, Xuewang; Chen, Limeng] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
   [Peng, Xiaoyan; Jiang, Lanping; Chen, Chen; Li, Xuemei; Li, Xuewang; Chen, Limeng] Beijing Union Med Coll Hosp, Nephrol, Beijing, Peoples R China.
   [Tu, Hongbin] NIDDK, NIH, Bethesda, MD 20892 USA.
   [Nie, Min; Xing, Xiaoping] Beijing Union Med Coll Hosp, Endocrinol, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2016
VL 31
SU 1
MA MP035
BP 354
EP 354
PG 1
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA DM8ZU
UT WOS:000376653801288
ER

PT J
AU Peters, TL
   Beard, JD
   Umbach, DM
   Allen, K
   Keller, J
   Mariosa, D
   Sandler, DP
   Schmidt, S
   Fang, F
   Ye, WM
   Kamel, F
AF Peters, Tracy L.
   Beard, John D.
   Umbach, David M.
   Allen, Kelli
   Keller, Jean
   Mariosa, Daniela
   Sandler, Dale P.
   Schmidt, Silke
   Fang, Fang
   Ye, Weimin
   Kamel, Freya
TI Blood levels of trace metals and amyotrophic lateral sclerosis
SO NEUROTOXICOLOGY
LA English
DT Article
DE Amyotrophic lateral sclerosis; Motor neuron disease; Risk factors; Trace
   metals; Case-Control study
ID MOTOR-NEURON DISEASE; NEURODEGENERATIVE DISEASES; NATIONAL REGISTRY;
   SPINAL-CORDS; MANGANESE; SELENIUM; RISK; VETERANS; EXPOSURE; ELEMENTS
AB Some trace metals may increase risk of amyotrophic lateral sclerosis (ALS), whereas others may be beneficial. Our goal was to examine associations of ALS with blood levels of selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn). We conducted a case-control study of 163 neurologist confirmed patients from the National Registry of Veterans with ALS and 229 frequency-matched veteran controls. We measured metal levels in blood using inductively coupled plasma mass spectrometry and estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between ALS and a doubling of metal levels using unconditional logistic regression, adjusting for age, gender, and race/ethnicity. ALS was inversely associated with both Se (OR = 0.4, 95% CI: 0.2-0.8) and Zn (OR = 0.4, 95% CI: 0.2-0.8). Inverse associations with Se were stronger in patients with bulbar compared to spinal onset, worse function, longer diagnostic delay, and longer collection delay; inverse associations with Zn were stronger for those with worse function and longer collection delay. In contrast, ALS was positively associated with Cu (OR = 3.4, 95% CI: 1.5-7.9). For Mn, no linear trend was evident (OR = 0.9, 95% CI: 0.6-1.3, P-trend = 0.51). Associations of Se, Zn, Cu, and Mn with ALS were independent of one another. Adjustment for lead levels attenuated the positive association of ALS with Cu but did not change associations with Se, Zn, or Mn. In conclusion, Se and Zn were inversely associated with ALS, particularly among those with worse function, suggesting that supplementation with these metals may benefit such patients, while Cu was positively associated with ALS. Deficiencies of Se and Zn and excess Cu may have a role in ALS etiology. Published by Elsevier Inc.
C1 [Peters, Tracy L.; Beard, John D.; Sandler, Dale P.; Kamel, Freya] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
   [Peters, Tracy L.; Mariosa, Daniela; Fang, Fang; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Beard, John D.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
   [Umbach, David M.] NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Allen, Kelli] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
   [Allen, Kelli] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
   [Allen, Kelli] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
   [Keller, Jean] Westat Corp, Durham, NC USA.
   [Schmidt, Silke] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM kamel@niehs.nih.gov
OI Kamel, Freya/0000-0001-5052-6615
FU Intramural Research Program of the National Institutes of
   Health,National Institute of Environmental Health Sciences
   [Z01-ES-049005]; National Institutes of Health, National Institute of
   Environmental Health Sciences [R01-ES-013244]; ALS Association
   [ALSA-1230]; Swedish Research Council; Karolinska Institutet; Swedish
   Society of Medical Research; National Institute for Occupational Safety
   and Health/Centers for Disease Control and Prevention [T42OH00867302];
   Office of Research and Development, Cooperative Studies Program,
   Department of Veterans Affairs (CSP) [500A]
FX We thank K Levine (Research Triangle Institute) and BJ Collins (National
   Toxicology Program) for measuring blood metal levels. This work was
   supported by the Intramural Research Program of the National Institutes
   of Health,National Institute of Environmental Health Sciences
   (Z01-ES-049005), by grants from the National Institutes of Health,
   National Institute of Environmental Health Sciences (R01-ES-013244), the
   ALS Association (ALSA-1230), the Swedish Research Council, the
   Karolinska Institutet, and the Swedish Society of Medical Research, and
   by a training grant from the National Institute for Occupational Safety
   and Health/Centers for Disease Control and Prevention (T42OH00867302).
   The National Registry of Veterans with ALS and its DNA bank were
   supported by the Office of Research and Development, Cooperative Studies
   Program, Department of Veterans Affairs (CSP #500A).
NR 43
TC 2
Z9 2
U1 5
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD MAY
PY 2016
VL 54
BP 119
EP 126
DI 10.1016/j.neuro.2016.03.022
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA DN4RE
UT WOS:000377054100013
PM 27085208
ER

PT J
AU Harper, LM
   Mele, L
   Landon, MB
   Carpenter, MW
   Ramin, SM
   Reddy, UM
   Casey, B
   Wapner, RJ
   Varner, MW
   Thorp, JM
   Sciscione, A
   Catalano, P
   Harper, M
   Saade, G
   Caritis, SN
   Sorokin, Y
   Peaceman, AM
   Tolosa, JE
AF Harper, Lorie M.
   Mele, Lisa
   Landon, Mark B.
   Carpenter, Marshall W.
   Ramin, Susan M.
   Reddy, Uma M.
   Casey, Brian
   Wapner, Ronald J.
   Varner, Michael W.
   Thorp, John M., Jr.
   Sciscione, Anthony
   Catalano, Patrick
   Harper, Margaret
   Saade, George
   Caritis, Steve N.
   Sorokin, Yoram
   Peaceman, Alan M.
   Tolosa, Jorge E.
CA Eunice Kennedy Shriver Natl Inst C
TI Carpenter-Coustan Compared With National Diabetes Data Group Criteria
   for Diagnosing Gestational Diabetes
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID MELLITUS; PREGNANCY; OUTCOMES
AB OBJECTIVE: Use of Carpenter-Coustan compared with National Diabetes Data Group criteria increases the number of women diagnosed with gestational diabetes mellitus (GDM) by 30-50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment.
   METHODS: This was a secondary analysis of a randomized trial for treatment of mild GDM diagnosed using Carpenter-Coustan criteria. We evaluated the effect of treatment within two mutually exclusive diagnostic groups: 1) women who met the stricter National Diabetes Data Group as well as Carpenter-Coustan criteria (National Diabetes Data Group), and 2) those diagnosed by Carpenter-Coustan but not meeting National Diabetes Data Group criteria (Carpenter-Coustan only). Maternal outcomes examined were pregnancy-induced hypertension, shoulder dystocia, maternal weight gain, and cesarean delivery. Neonatal outcomes were large for gestational age, macrosomia (greater than 4,000 g), fat mass, small for gestational age, and a composite outcome of perinatal death, birth injury, hypoglycemia, hyperbilirubinemia, and hyperinsulinemia. Analysis of variance or the Breslow-Day test, as appropriate, was used to test for the interaction between diagnostic criteria and GDM treatment on the outcomes of interest.
   RESULTS: Of 958 patients, 560 (58.5%) met National Diabetes Data Group criteria and 398 (41.5%) met Carpenter-Coustan only. Compared with untreated women, the direction of treatment effect did not differ by diagnostic criteria used and was consistent with the original trial. The P value for interaction between diagnostic criteria and treatment status was not significant for any outcome.
   CONCLUSION: The overall beneficial treatment effect on pregnancy-induced hypertension, shoulder dystocia, cesarean delivery, and macrosomia was seen in patients diagnosed by the higher National Diabetes Data Group and by the lower thresholds of the Carpenter-Coustan criteria.
C1 Univ Alabama Birmingham, Dept Obstet, Birmingham, AL 35233 USA.
   Univ Alabama Birmingham, Dept Gynecol, Birmingham, AL 35233 USA.
   Ohio State Univ, Columbus, OH 43210 USA.
   Brown Univ, Providence, RI 02912 USA.
   Univ Texas Houston, Hlth Sci Ctr, Childrens Mem Hermann Hosp, Houston, TX USA.
   Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   Columbia Univ, New York, NY USA.
   Univ Utah, Salt Lake City, UT USA.
   Univ N Carolina, Chapel Hill, NC USA.
   Drexel Univ, Philadelphia, PA 19104 USA.
   Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
   Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
   Univ Texas Med Branch, Galveston, TX 77555 USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
   Wayne State Univ, Detroit, MI USA.
   Northwestern Univ, Chicago, IL 60611 USA.
   Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
   George Washington Univ, Ctr Biostat, Washington, DC USA.
   Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Harper, LM (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, 1700 6th Ave South,Suite 10270, Birmingham, AL 35233 USA.
EM lmharper@uabmc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869,
   HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410,
   HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers
   Grant [M01-RR00034]; National Center for Research Resources
   [UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (NICHD) (HD27915, HD34116,
   HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860,
   HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801), General
   Clinical Research Centers Grant (M01-RR00034), and the National Center
   for Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764,
   C06-RR11234).
NR 13
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 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2016
VL 127
IS 5
BP 893
EP 898
DI 10.1097/AOG.0000000000001383
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DN3CW
UT WOS:000376941000014
PM 27054932
ER

PT J
AU Soto-Pantoja, DR
   Sipes, JM
   Martin-Manso, G
   Westwood, B
   Morris, NL
   Ghosh, A
   Emenaker, NJ
   Roberts, DD
AF Soto-Pantoja, D. R.
   Sipes, J. M.
   Martin-Manso, G.
   Westwood, B.
   Morris, N. L.
   Ghosh, A.
   Emenaker, N. J.
   Roberts, D. D.
TI Dietary fat overcomes the protective activity of thrombospondin-1
   signaling in the ApcMin/+ model of colon cancer
SO ONCOGENESIS
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; APC(MIN/+) MOUSE MODEL; COLORECTAL-CANCER;
   INDUCED OBESITY; ADIPOSE INFLAMMATION; INSULIN-RESISTANCE;
   GENE-EXPRESSION; TUMOR-GROWTH; MICE; ANGIOGENESIS
AB Thrombospondin 1 is a glycoprotein that regulates cellular phenotype through interactions with its cellular receptors and extracellular matrix-binding partners. Thrombospondin 1 locally regulates angiogenesis and inflammatory responses that contribute to colorectal carcinogenesis in Apc(Min/+) mice. The ability of thrombospondin 1 to regulate responses of cells and tissues to a variety of stresses suggested that loss of thrombospondin 1 may also have broader systemic effects on metabolism to modulate carcinogenesis. Apc(Min/+):Thbs1(-/-) mice exhibited decreased survival and higher tumor multiplicities in the small and large intestine relative to Apc(Min/+) mice when fed a low (5%) fat western diet. However, the protective effect of endogenous thrombospondin 1 was lost when the mice were fed a western diet containing 21% fat. Biochemical profiles of liver tissue identified systemic metabolic changes accompanying the effects of thrombospondin 1 and dietary lipid intake on tumorigenesis. A high-fat western diet differentially regulated elements of amino acid, energy and lipid metabolism in Apc(Min/+):Thbs1(-/-) mice relative to Apc(Min/+):Thbs1(+/+) mice. Metabolic changes in ketone body and tricarboxylic acid cycle intermediates indicate functional interactions between Apc and thrombospondin 1 signaling that control mitochondrial function. The cumulative diet-dependent differential changes observed in Apc(Min/+):Thbs1(-/-) versus Apc(Min/+) mice include altered amino acid and lipid metabolism, mitochondrial dysfunction, eicosanoids and ketone body formation. This metabolic profile suggests that the protective role of thrombospondin 1 to decrease adenoma formation in Apc(Min/+) mice results in part from improved mitochondrial function.
C1 [Soto-Pantoja, D. R.] Wake Forest Sch Med, Ctr Comprehens Canc, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA.
   [Soto-Pantoja, D. R.; Westwood, B.] Wake Forest Sch Med, Ctr Comprehens Canc, Dept Surg, Winston Salem, NC 27157 USA.
   [Sipes, J. M.; Martin-Manso, G.; Ghosh, A.; Roberts, D. D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
   [Morris, N. L.] Leidos Biomed Res, Natl Lab Canc Res, Chem Biol Lab, Frederick, MD USA.
   [Emenaker, N. J.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Soto-Pantoja, DR (reprint author), Wake Forest Sch Med, Ctr Comprehens Canc, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA.; Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM dsotopan@wakehealth.edu; droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU Intramural Research Program of the NIH/NCI; Nutritional Science Research
   Group, Division of Cancer Prevention, NIH/NCI; NCI Transition Career
   Development Award [K22 1K22CA181274-01A1]
FX This work was supported by the Intramural Research Program of the
   NIH/NCI (DDR), the Nutritional Science Research Group, Division of
   Cancer Prevention, NIH/NCI (NE) and the NCI Transition Career
   Development Award K22 1K22CA181274-01A1 (DSP).
NR 68
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD MAY
PY 2016
VL 5
AR e230
DI 10.1038/oncsis.2016.37
PG 10
WC Oncology
SC Oncology
GA DN0TX
UT WOS:000376779000005
PM 27239962
ER

PT J
AU Tzani, I
   Ivanov, IP
   Andreev, DE
   Dmitriev, RI
   Dean, KA
   Baranov, PV
   Atkins, JF
   Loughran, G
AF Tzani, Ioanna
   Ivanov, Ivaylo P.
   Andreev, Dmitri E.
   Dmitriev, Ruslan I.
   Dean, Kellie A.
   Baranov, Pavel V.
   Atkins, John F.
   Loughran, Gary
TI Systematic analysis of the PTEN 5 ' leader identifies a major AUU
   initiated proteoform
SO OPEN BIOLOGY
LA English
DT Article
DE PTEN-L; non-AUG; AUU; uORF
ID EUKARYOTIC TRANSLATION INITIATION; START CODON RECOGNITION; AUTISM
   SPECTRUM DISORDERS; TRANSFER-RNA; TUMOR-SUPPRESSOR; MAMMALIAN-CELLS;
   MESSENGER-RNAS; MODULATES AUTOREGULATION; NUCLEOTIDE RESOLUTION; GAUSSIA
   LUCIFERASE
AB Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms.
C1 [Tzani, Ioanna; Andreev, Dmitri E.; Dmitriev, Ruslan I.; Dean, Kellie A.; Baranov, Pavel V.; Atkins, John F.; Loughran, Gary] Natl Univ Ireland Univ Coll Cork, Sch Biochem & Cell Biol, Cork, Ireland.
   [Ivanov, Ivaylo P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
   [Andreev, Dmitri E.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119992, Russia.
   [Atkins, John F.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
RP Loughran, G (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Biochem & Cell Biol, Cork, Ireland.
EM g.loughran@ucc.ie
RI Andreev, Dmitry/I-6346-2012; Baranov, Pavel/A-2782-2011; 
OI Baranov, Pavel/0000-0001-9017-0270; Loughran, Gary/0000-0002-2683-5597;
   Dean, Kellie/0000-0002-3213-8181; Andreev, Dmitry/0000-0001-5320-3045;
   Atkins, John/0000-0001-7933-0165; Dmitriev, Ruslan/0000-0002-0347-8718
FU Science Foundation Ireland [08/IN.I/B1889, 12/IP/1492, 13/SIRG/2144,
   12/IA/1335]; Health Research Board [PhD/2007/04]; Russian Science
   Foundation [14-14-00127]
FX This work was supported by Science Foundation Ireland [08/IN.I/B1889;
   12/IP/1492] to G.L., I.P.I. and J.F.A., [13/SIRG/2144] to R.I.D. and
   [12/IA/1335] to P.V.B.; Health Research Board [PhD/2007/04] to I.T. and
   K.A.D. Russian Science Foundation [14-14-00127] to D.E.A. Funding for
   open access charge: Health Research Board [PhD/2007/04].
NR 73
TC 0
Z9 0
U1 2
U2 4
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2046-2441
J9 OPEN BIOL
JI Open Biol
PD MAY
PY 2016
VL 6
IS 5
AR 150203
DI 10.1098/rsob.150203
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DN3LV
UT WOS:000376964600001
ER

PT J
AU Witter, JP
AF Witter, James P.
TI The Promise of Patient -Reported Outcomes Measurement Information
   System-Turning Theory into Reality: A Uniform Approach to
   Patient-Reported Outcomes Across Rheumatic Diseases
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE PROMIS; Patient assessment; Validation; Universal
ID QUALITY-OF-LIFE; PHYSICAL FUNCTION; TASK-FORCE; ARTHRITIS; HEALTH;
   INSTRUMENTS; VALIDITY; FLARES
AB PROMIS, the Patient -Reported Outcomes Measurement Information System, is opening new possibilities to explore and learn how patient (or proxy) self -report of core symptoms and health -related quality of life can meaningfully advance clinical research and patient care. PROMIS leverages Item Response Theory to agnostically assess, across diseases and conditions or clinical settings, numerous universally applicable core "domains" of health (symptoms and functioning) from the patient perspective. Importantly, PROMIS is enabling the testing and adoption of computerized adaptive testing, which holds great potential to minimize patient burden while maximizing accuracy.
C1 [Witter, James P.] NIAMSD, Rheumat Dis Clin Program, One Democracy Plaza,6701 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
RP Witter, JP (reprint author), NIAMSD, Rheumat Dis Clin Program, One Democracy Plaza,6701 Democracy Blvd,Suite 800, Bethesda, MD 20892 USA.
EM james.witter@nih.gov
NR 19
TC 2
Z9 2
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 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD MAY
PY 2016
VL 42
IS 2
BP 377
EP +
DI 10.1016/j.rdc.2016.01.007
PG 19
WC Rheumatology
SC Rheumatology
GA DN0YO
UT WOS:000376793200014
PM 27133496
ER

PT J
AU Visternichan, O
   Taizhanova, D
   Zholdybayeva, E
   Tarlykov, P
AF Visternichan, O.
   Taizhanova, D.
   Zholdybayeva, E.
   Tarlykov, P.
TI CLINICO-LABORATORY PREDICTORS OF CORONARY RESTENOSIS IN MAN OF KAZAKH
   NATIONALITY
SO THROMBOSIS RESEARCH
LA English
DT Meeting Abstract
CT 24th Biennial International Congress on Thrombosis / EMLTD Congress
CY MAY 04-07, 2016
CL Istanbul, TURKEY
SP EMLTD
C1 [Visternichan, O.] Karaganda State Med Univ, Internal Dis Dept 1, Karaganda, Kazakhstan.
   [Taizhanova, D.] Karaganda State Med Univ, Karaganda, Kazakhstan.
   [Zholdybayeva, E.; Tarlykov, P.] Natl Biotechnol Ctr, Astana, Kazakhstan.
RI Akhmadyarova, Bota/R-4730-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD MAY
PY 2016
VL 141
SU 1
MA C0122
BP S39
EP S39
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DN0PR
UT WOS:000376766300106
ER

PT J
AU Williams, RC
   Opelz, G
   McGarvey, CJ
   Weil, EJ
   Chakkera, HA
AF Williams, Robert C.
   Opelz, Gerhard
   McGarvey, Chelsea J.
   Weil, E. Jennifer
   Chakkera, Harini A.
TI The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney
   Allografts From Deceased Donors
SO TRANSPLANTATION
LA English
DT Article
ID RENAL-TRANSPLANTATION; GRAFT-SURVIVAL; OUTCOMES; IMMUNOSUPPRESSION;
   PATIENT; FOCUS; MODEL; ERA; AGE
AB Background. Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Methods. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Results. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. Conclusions. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.
C1 [Williams, Robert C.; Weil, E. Jennifer] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
   [Opelz, Gerhard] Heidelberg Univ, Inst Immunol, Dept Transplantat Immunol, Heidelberg, Germany.
   [McGarvey, Chelsea J.] Mayo Clin, Mayo Clin Hosp, Phoenix, AZ USA.
   [Chakkera, Harini A.] Mayo Clin, Div Nephrol, Phoenix, AZ USA.
RP Williams, RC (reprint author), NIDDK, NIH, PECRB, 1550 East Indian Sch Rd, Phoenix, AZ 85014 USA.
EM williamsr@mail.nih.gov
FU Health Resources and Services Administration [234-2005-370011C]
FX This work was supported in part by Health Resources and Services
   Administration contract 234-2005-370011C. The content is the
   responsibility of the authors alone and 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 25
TC 7
Z9 7
U1 6
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD MAY
PY 2016
VL 100
IS 5
BP 1094
EP 1102
DI 10.1097/TP.0000000000001115
PG 9
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA DN5QU
UT WOS:000377126000025
PM 26901078
ER

PT J
AU Turkbey, B
   Rosenkrantz, AB
AF Turkbey, Baris
   Rosenkrantz, Andrew B.
TI Engaging and educating patients in prostate imaging via social media
SO ABDOMINAL RADIOLOGY
LA English
DT Editorial Material
ID CANCER; BIOPSY
C1 [Turkbey, Baris] NCI, Mol Imaging Program, NIH, Ctr Dr,Room B3B85, Bethesda, MD 20892 USA.
   [Rosenkrantz, Andrew B.] NYU, Dept Radiol, Langone Med Ctr, 560 1St Ave, New York, NY 10016 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Ctr Dr,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 2366-004X
EI 2366-0058
J9 ABDOM RADIOL
JI Abdom. Radiol.
PD MAY
PY 2016
VL 41
IS 5
BP 798
EP 798
DI 10.1007/s00261-016-0748-1
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DM5QD
UT WOS:000376404200002
PM 27138436
ER

PT J
AU George, AK
   Turkbey, B
   Valayil, SG
   Muthigi, A
   Mertan, F
   Kongnyuy, M
   Pinto, PA
AF George, Arvin K.
   Turkbey, Baris
   Valayil, Subin G.
   Muthigi, Akhil
   Mertan, Francesca
   Kongnyuy, Michael
   Pinto, Peter A.
TI A urologist's perspective on prostate cancer imaging: past, present, and
   future
SO ABDOMINAL RADIOLOGY
LA English
DT Article
DE Prostate cancer; Imaging; Image-guided biopsy; Cancer diagnosis; Staging
ID FUSION-GUIDED BIOPSY; PELVIC LYMPH-NODES; ACTIVE SURVEILLANCE; BONE
   METASTASES; TRANSRECTAL ULTRASOUND; RADICAL PROSTATECTOMY;
   MULTIPARAMETRIC MRI; KALLIKREIN MARKERS; ANTIGEN LEVELS; PET/CT
AB Prostate cancer is unique in that unlike other solid organ malignancies, only recently has imaging been employed to routinely detect and localize disease. The introduction of transrectal ultrasound was a significant development, transitioning digitally guided prostate biopsies to ultrasound guidance. The arrival of multiparametric MRI has become the next major step, transforming the way Urologist's diagnose, stage, and treat prostate cancer. Recent recommendations against PSA screening have changed the landscape of urologic oncology with the changing needs being reflected in the initiation of additional robust imaging techniques at different time points in prostate cancer care. The current review aims to provide a clinical perspective in the history, current standard of care, and novel imaging modalities in the evaluation of prostate cancer.
C1 [George, Arvin K.; Turkbey, Baris; Valayil, Subin G.; Muthigi, Akhil; Mertan, Francesca; Kongnyuy, Michael; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
   [Turkbey, Baris; Mertan, Francesca] NCI, Mol Imaging Program, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
RP George, AK (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
EM arvinkgeorge@gmail.com
FU Intramural Research Program of the National Institutes of Health (NIH),
   National Cancer Institute, Center for Cancer Research; National Cancer
   Institute; Center for Cancer Research; Center for Interventional
   Oncology; Intramural Research Program of the National Institutes of
   Health (NIH), National Cancer Institute, Center for Interventional
   Oncology
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health (NIH), National Cancer Institute, Center
   for Cancer Research, and the Center for Interventional Oncology. NIH and
   Philips Healthcare have a cooperative research and development
   agreement. NIH and Philips share intellectual property in the field.
   This research was also made possible through the National Institutes of
   Health Medical Research Scholars Program, a public-private partnership
   supported jointly by the NIH and generous contributions to the
   Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable
   Foundation, The Alexandria Real Estate Equities, Inc. and Mr. and Mrs.
   Joel S. Marcus, and the Howard Hughes Medical Institute, as well as
   other private donors. For a complete list, please visit the Foundation
   website at:
   http://fnih.org/work/education-training-0/medical-research-scholars-prog
   ram.
NR 112
TC 5
Z9 5
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 2366-004X
EI 2366-0058
J9 ABDOM RADIOL
JI Abdom. Radiol.
PD MAY
PY 2016
VL 41
IS 5
BP 805
EP 816
DI 10.1007/s00261-016-0751-6
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DM5QD
UT WOS:000376404200006
PM 27138438
ER

PT J
AU Berman, RM
   Brown, AM
   Chang, SD
   Sankineni, S
   Kadakia, M
   Wood, BJ
   Pinto, PA
   Choyke, PL
   Turkbey, B
AF Berman, Rose M.
   Brown, Anna M.
   Chang, Silvia D.
   Sankineni, Sandeep
   Kadakia, Meet
   Wood, Bradford J.
   Pinto, Peter A.
   Choyke, Peter L.
   Turkbey, Baris
TI DCE MRI of prostate cancer
SO ABDOMINAL RADIOLOGY
LA English
DT Article
DE DCE MRI; Prostate cancer; Multi-parametric MRI
ID CONTRAST-ENHANCED MRI; ENDOTHELIAL GROWTH-FACTOR; RADICAL PROSTATECTOMY;
   LOCAL RECURRENCE; PERIPHERAL ZONE; 3 T; DIAGNOSIS; TISSUE;
   DIFFERENTIATION; RADIOTHERAPY
AB DCE MRI is an established component of multi-parametric MRI of the prostate. The sequence highlights the vascularization of cancerous lesions, allowing readers to corroborate suspicious findings on T2W and DW MRI and to note subtle lesions not visible on the other sequences. In this article, we review the technical aspects, methods of evaluation, limitations, and future perspectives of DCE MRI.
C1 [Berman, Rose M.; Brown, Anna M.; Sankineni, Sandeep; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
   [Brown, Anna M.] Duke Univ, Sch Med, Durham, NC USA.
   [Chang, Silvia D.] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada.
   [Kadakia, Meet; Pinto, Peter A.] Univ Nicaragua, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
   [Wood, Bradford J.] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
NR 59
TC 1
Z9 1
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 2366-004X
EI 2366-0058
J9 ABDOM RADIOL
JI Abdom. Radiol.
PD MAY
PY 2016
VL 41
IS 5
BP 844
EP 853
DI 10.1007/s00261-015-0589-3
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DM5QD
UT WOS:000376404200009
PM 27193787
ER

PT J
AU Balansky, R
   Ganchev, G
   Iltcheva, M
   Micale, RT
   La Maestra, S
   D'Oria, C
   Steele, VE
   De Flora, S
AF Balansky, Roumen
   Ganchev, Gancho
   Iltcheva, Marietta
   Micale, Rosanna T.
   La Maestra, Sebastiano
   D'Oria, Chiara
   Steele, Vernon E.
   De Flora, Silvio
TI Selective inhibition by aspirin and naproxen of mainstream cigarette
   smoke-induced genotoxicity and lung tumors in female mice
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Lung tumors; Cigarette smoke; Chemoprevention; Aspirin; Naproxen
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CANCER-RISK; N-ACETYLCYSTEINE;
   TOBACCO-SMOKE; HISTOPATHOLOGICAL ALTERATIONS; CHEMOPREVENTIVE AGENTS;
   BREAST-CANCER; RODENT MODELS; EXPOSED MICE; DNA-DAMAGE
AB The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used.
C1 [Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta] Natl Oncol Ctr, Sofia 1756, Bulgaria.
   [Micale, Rosanna T.; La Maestra, Sebastiano; D'Oria, Chiara; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
   [Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
EM rubalansky@sbaloncology.bg; drganchoganchev@abv.bg;
   mariettailtcheva@yahoo.com; rosannamicale@yahoo.it;
   lamaestra78@yahoo.it; doria.chiara@libero.it; steelev@mail.nih.gov;
   sdf@unige.it
FU US National Cancer Institute [HHSN-2612012000151]
FX This study was supported by the US National Cancer Institute (Contract
   #HHSN-2612012000151).
NR 48
TC 1
Z9 1
U1 2
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
EI 1432-0738
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD MAY
PY 2016
VL 90
IS 5
BP 1251
EP 1260
DI 10.1007/s00204-015-1550-5
PG 10
WC Toxicology
SC Toxicology
GA DJ6EQ
UT WOS:000374303400018
PM 26104855
ER

PT J
AU Chung, JY
   Cho, H
   Hewitt, SM
AF Chung, Joon-Yong
   Cho, Hanbyoul
   Hewitt, Stephen M.
TI The paraffin-embedded RNA metric (PERM) for RNA isolated from
   formalin-fixed, paraffin-embedded tissue
SO BIOTECHNIQUES
LA English
DT Article
DE formalin-fixed; paraffin-embedded; RNA integrity; molecular pathology
ID TIME RT-PCR; QUALITY ASSESSMENT; DNA ASSAY; QUANTIFICATION; INTEGRITY;
   RECOVERY; IMPACT
AB RNA isolated from formalin-fixed, paraffin-embedded (FFPE) tissue is commonly evaluated in both investigative and diagnostic pathology. However, the quality of the data is directly impacted by RNA quality. The RNA integrity number (RIN), an algorithm based on a combination of electrophoretic features, is widely applied to RNA isolated from paraffin-embedded tissue, but it is a poor indicator of the quality of that RNA. Here we describe the novel paraffin-embedded RNA metric (PERM) for quantifying the quality of RNA from FFPE tissue. The PERM is based on a formula that approximates a weighted area-under-the-curve analysis of an electropherogram of the extracted RNA. Using biochemically degraded RNAs prepared from experimentally fixed mouse kidney specimens, we demonstrate that PERM values correlate with mRNA transcript measurements determined using the QuantiGene system. Furthermore, PERM values correlate with real-time PCR data. Our results demonstrate that the PERM can be used to qualify RNA for different end-point studies and may be a valuable tool for molecular studies using RNA extracted from FFPE tissue.
C1 [Chung, Joon-Yong; Cho, Hanbyoul; Hewitt, Stephen M.] NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, MSC 1500, Bethesda, MD 20892 USA.
   [Cho, Hanbyoul] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea.
RP Hewitt, SM (reprint author), NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, MSC 1500, Bethesda, MD 20892 USA.
EM geneiock@helix.nih.gov
OI Chung, Joon-Yong/0000-0001-5041-5982
FU Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research
FX This study was supported by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research. The authors would
   like to thank Kris Ylaya and Candice Perry for excellent technical
   assistance. This paper is subject to the NIH Public Access Policy.
NR 16
TC 2
Z9 2
U1 2
U2 2
PU BIOTECHNIQUES OFFICE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0736-6205
EI 1940-9818
J9 BIOTECHNIQUES
JI Biotechniques
PD MAY
PY 2016
VL 60
IS 5
BP 239
EP +
DI 10.2144/000114415
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DM5WA
UT WOS:000376419900003
PM 27177816
ER

PT J
AU Magnani, JW
   Wang, N
   Benjamin, EJ
   Garcia, ME
   Bauer, DC
   Butler, J
   Ellinor, PT
   Kritchevsky, S
   Marcus, GM
   Newman, A
   Phillips, CL
   Sasai, H
   Satterfield, S
   Sullivan, LM
   Harris, TB
AF Magnani, Jared W.
   Wang, Na
   Benjamin, Emelia J.
   Garcia, Melissa E.
   Bauer, Douglas C.
   Butler, Javed
   Ellinor, Patrick T.
   Kritchevsky, Stephen
   Marcus, Gregory M.
   Newman, Anne
   Phillips, Caroline L.
   Sasai, Hiroyuki
   Satterfield, Suzanne
   Sullivan, Lisa M.
   Harris, Tamara B.
CA Hlth Aging Body Composition Study
TI . Atrial Fibrillation and Declining Physical Performance in Older Adults
   The Health, Aging, and Body Composition Study
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE aging; atrial fibrillation; epidemiology; medicare; physical exercise
ID QUALITY-OF-LIFE; MEDICARE BENEFICIARIES; CARDIOVASCULAR-DISEASE;
   INFLAMMATORY MARKERS; INCIDENT DISABILITY; EXERCISE CAPACITY; WEIGHT
   CHANGE; SINUS RHYTHM; GAIT SPEED; RISK
AB Background-Age is the foremost risk factor for atrial fibrillation (AF), and AF has a rising prevalence in older adults. How AF may contribute to decline in physical performance in older adults has had limited investigation. We examined the associations of incident AF and 4-year interval declines in physical performance at ages 70, 74, 78, and 82 years in the Health, Aging, and Body Composition (Health ABC) Study.
   Methods and Results-Health ABC is a prospective cohort of community-dwelling older adults (n=3075). The study conducted serial assessments of physical performance with the Health ABC physical performance battery (scored 0-4), grip strength, 2-minute walk distance, and 400-m walking time. Incident AF was identified from the Center for Medicare and Medicaid Services and related to 4-year interval decline in physical performance. After exclusions, the analysis included 2753 Health ABC participants (52% women, 41% black race). Participants with AF had a significantly greater 4-year physical performance battery decline than those without AF at age 70, 74, 78, and 82, with mean estimated decline ranging from -0.08 to -0.10 U (95% confidence interval, -0.18 to -0.01; P<0.05 for all estimates) after multivariable adjustment. Grip strength, walk distance, and walk time similarly showed significantly greater declines at each 4-year age interval in participants with AF.
   Conclusions-In community-based cohort older adults, incident AF was associated with increased risk of decline in physical performance. Further research is essential to identify mechanisms and preventive strategies for how AF may contribute toward declining physical performance in older adults.
C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
   [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Boston, MA USA.
   [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02118 USA.
   [Wang, Na; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Garcia, Melissa E.; Phillips, Caroline L.] NIA, Intramural Res Program, NIH, Bethesda, MD USA.
   [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
   [Butler, Javed] SUNY Stony Brook, Stony Brook, NY USA.
   [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
   [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
   [Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Populat & Med Genet, Cambridge, MA USA.
   [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
   [Marcus, Gregory M.] Univ Calif San Francisco, Dept Med, Div Cardiol, Sect Cardiac Electrophysiol, San Francisco, CA 94143 USA.
   [Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
   [Sasai, Hiroyuki] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
   [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
   [Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu
OI Sasai, Hiroyuki/0000-0001-8120-6163
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
   N01-AG-6-2106]; NIA [R01AG028050, R03AG045075]; NINR [R01-NR012459,
   1RC1HL101056, 1R01HL102214, 1R01AG028321]; NIH [1RO1HL092577,
   1K24HL105780]; American Heart Association [13EIA14220013]; Fondation
   Leducq [14CVD01]; Doris Duke Charitable Foundation [2015084]
FX This research was funded by National Institute on Aging (NIA) Contracts
   N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grants R01AG028050 and
   R03AG045075, NINR grant R01-NR012459 and 1RC1HL101056; 1R01HL102214;
   1R01AG028321; NIH grants 1RO1HL092577(Dr Benjamin and Dr Ellinor) and
   1K24HL105780 (Dr Ellinor); and awards from the American Heart
   Association (13EIA14220013) and the Fondation Leducq 14CVD01 (Dr
   Ellinor). This work was supported Grant 2015084 from the Doris Duke
   Charitable Foundation.
NR 52
TC 0
Z9 0
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3149
EI 1941-3084
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD MAY
PY 2016
VL 9
IS 5
AR e003525
DI 10.1161/CIRCEP.115.003525
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DN0KA
UT WOS:000376751600004
PM 27052031
ER

PT J
AU Tang, DM
   Urrunaga, NH
   Von Rosenvinge, EC
AF Tang, Derek M.
   Urrunaga, Nathalie H.
   Von Rosenvinge, Erik C.
TI Pseudomembranous colitis: Not always Clostridium difficile
SO CLEVELAND CLINIC JOURNAL OF MEDICINE
LA English
DT Review
ID OF-THE-LITERATURE; COLLAGENOUS COLITIS; CYTOMEGALOVIRUS COLITIS;
   ULCERATIVE-COLITIS; ISCHEMIC COLITIS; DIAGNOSIS; ENTEROCOLITIS;
   GUIDELINES; INFECTION; DISEASE
AB Although Clostridium difficile infection is the cause of most cases of pseudomembranous colitis, clinicians should consider less common causes, especially if pseudomembranes are seen on endoscopy but testing remains negative for C difficile or if presumed C difficile infection does not respond to treatment. Histologic review of colonic mucosal biopsy specimens can provide clues to the underlying cause.
C1 [Tang, Derek M.] NIDDK, Digest Dis Branch, NIH, 10 Ctr Dr,Bldg 10,5NW-2740, Bethesda, MD 20892 USA.
   [Urrunaga, Nathalie H.; Von Rosenvinge, Erik C.] Univ Maryland, Sch Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA.
   [Von Rosenvinge, Erik C.] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA.
RP Tang, DM (reprint author), NIDDK, Digest Dis Branch, NIH, 10 Ctr Dr,Bldg 10,5NW-2740, Bethesda, MD 20892 USA.
FU National Institutes of Health (NIH) National Institute of Diabetes and
   Digestive and Kidney Disease (NIDDK) [5 T32 DK067872-07]; Intramural
   Research Program of the NIDDK, NIH
FX Nathalie H. Urrunaga, MD, MS, was supported by Grant Number 5 T32
   DK067872-07 from the National Institutes of Health (NIH) National
   Institute of Diabetes and Digestive and Kidney Disease (NIDDK). This
   document was also supported by the Intramural Research Program of the
   NIDDK, NIH.
NR 48
TC 1
Z9 1
U1 1
U2 2
PU CLEVELAND CLINIC
PI CLEVELAND
PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA
SN 0891-1150
EI 1939-2869
J9 CLEV CLIN J MED
JI Clevel. Clin. J. Med.
PD MAY
PY 2016
VL 83
IS 5
BP 361
EP 366
DI 10.3949/ccjm.83a.14183
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DM6WH
UT WOS:000376493000011
PM 27168512
ER

PT J
AU Hsieh, YH
   Rothman, RE
   Laeyendecker, OB
   Kelen, GD
   Avornu, A
   Patel, EU
   Kim, J
   Irvin, R
   Thomas, DL
   Quinn, TC
AF Hsieh, Yu-Hsiang
   Rothman, Richard E.
   Laeyendecker, Oliver B.
   Kelen, Gabor D.
   Avornu, Ama
   Patel, Eshan U.
   Kim, Jim
   Irvin, Risha
   Thomas, David L.
   Quinn, Thomas C.
TI Evaluation of the Centers for Disease Control and Prevention
   Recommendations for Hepatitis C Virus Testing in an Urban Emergency
   Department
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HCV; emergency department; undiagnosed infection; HCV testing; CDC
   recommendations
ID INJECTION-DRUG USERS; UNITED-STATES; INFECTION; CARE; HEALTH; BARRIERS
AB Background. The Centers for Disease Control and Prevention (CDC) recommends 1-time hepatitis C virus (HCV) testing in the 1945-1965 birth cohort, in addition to targeted risk-based testing. Emergency departments (EDs) are key venues for HCV testing because of the population served and success in HIV screening. We determined the burden of undocumented HCV infection in our ED, providing guidance for implementation of ED-based HCV testing.
   Methods. An 8-week seroprevalence study was conducted in an urban ED in 2013. All patients with excess blood collected for clinical purposes were included. Demographic and clinical information including documented HCV infection was obtained from electronic medical records. HCV antibody testing was performed on excess samples.
   Results. Of 4713 patients, 652 (13.8%) were HCV antibody positive. Of these, 204 (31.3%) had undocumented HCV infection. Among patients with undocumented infections, 99 (48.5%) would have been diagnosed based on birth cohort testing, and an additional 54 (26.5%) would be identified by risk-based testing. If our ED adhered to the CDC guidelines, 51 (25.0%) patients with undocumented HCV would not have been tested. Given an estimated 7727 unique ED patients with HCV infection in a 1-year period, birth cohort plus risk-based testing would identify 1815 undocumented infections, and universal testing would identify additional 526 HCV-infected persons.
   Conclusions. Birth cohort-based testing would augment identification of undocumented HCV infections in this ED 2-fold, relative to risk-based testing only. However, our data demonstrate that one-quarter of infections would remain undiagnosed if current CDC birth cohort recommendations were employed, suggesting that in high-risk urban ED settings a practice of universal 1-time testing might be more effective.
C1 [Hsieh, Yu-Hsiang; Rothman, Richard E.; Kelen, Gabor D.; Avornu, Ama; Kim, Jim] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21209 USA.
   [Rothman, Richard E.; Irvin, Risha; Thomas, David L.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21209 USA.
   [Laeyendecker, Oliver B.; Patel, Eshan U.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Hsieh, YH (reprint author), Johns Hopkins Univ, Dept Emergency Med, 5801 Smith Ave,Davis Bldg,Ste 3220, Baltimore, MD 21209 USA.
EM yhsieh1@jhmi.edu
OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286;
   Patel, Eshan/0000-0003-2174-5004
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases [K01AI100681]; National Institute on Drug Abuse at
   the National Institutes of Health [R37DA013806]
FX This work was supported by the Division of Intramural Research, National
   Institute of Allergy and Infectious Diseases (K01AI100681 to Y.-H.H.)
   and the National Institute on Drug Abuse (R37DA013806 to D.L.T.) at the
   National Institutes of Health.
NR 28
TC 4
Z9 4
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY 1
PY 2016
VL 62
IS 9
BP 1059
EP 1065
DI 10.1093/cid/ciw074
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM5IO
UT WOS:000376381800001
PM 26908800
ER

PT J
AU Green, KY
AF Green, Kim Y.
TI Noroviruses and B Cells
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE norovirus; B cells; immunocompromised; virus tropism
ID VACCINE DEVELOPMENT; INFECTION; GASTROENTERITIS; PATHOGENESIS; VIRUS;
   MODEL; STRAIN; CALVES
C1 [Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Green, KY (reprint author), NIH, 50 S Dr,Bldg 50,Rm 6318, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
NR 25
TC 1
Z9 1
U1 1
U2 1
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 MAY 1
PY 2016
VL 62
IS 9
BP 1139
EP 1140
DI 10.1093/cid/ciw063
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM5IO
UT WOS:000376381800013
PM 26908783
ER

PT J
AU Glidden, DV
   Amico, KR
   Liu, AY
   Hosek, SG
   Anderson, PL
   Buchbinder, SP
   McMahan, V
   Mayer, KH
   David, B
   Schechter, M
   Grinsztejn, B
   Guanira, J
   Grant, RM
AF Glidden, David V.
   Amico, K. Rivet
   Liu, Albert Y.
   Hosek, Sybil G.
   Anderson, Peter L.
   Buchbinder, Susan P.
   McMahan, Vanessa
   Mayer, Kenneth H.
   David, Burns
   Schechter, Mauro
   Grinsztejn, Beatriz
   Guanira, Juan
   Grant, Robert M.
TI Symptoms, Side Effects and Adherence in the iPrEx Open-Label Extension
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV prevention; pre-exposure prophylaxis; tenofovir/emtricitabine; PrEP
ID PREEXPOSURE PROPHYLAXIS; HIV-INFECTION; ANTIRETROVIRAL PROPHYLAXIS;
   BANGKOK TENOFOVIR; RENAL-FUNCTION; AFRICAN WOMEN; DOUBLE-BLIND; TRIAL;
   MEN; EMTRICITABINE
AB Background. Blinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study.
   Methods. In the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months.
   Results. Symptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months. Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort.
   Conclusions. PrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports.
C1 [Glidden, David V.] Univ Calif San Francisco, San Francisco, CA 94158 USA.
   [Amico, K. Rivet] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Liu, Albert Y.; Buchbinder, Susan P.] San Francisco Dept Publ Hlth, Bridge HIV, San Francisco, CA USA.
   [Hosek, Sybil G.] John H Stroger Jr Hosp Cook Cty, Chicago, IL USA.
   [Anderson, Peter L.] Univ Colorado, Denver, CO 80202 USA.
   [McMahan, Vanessa] Univ Washington, Seattle, WA 98195 USA.
   [Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA.
   [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [David, Burns] NIAID, Rockville, MD USA.
   [Schechter, Mauro] Hosp Escola Sao Francisco Assis, Projeto Pra Onze, Rio De Janeiro, Brazil.
   [Schechter, Mauro] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
   [Grinsztejn, Beatriz] Fiocruz MS, Evandro Chagas Natl Inst Infect Dis, BR-21045900 Rio De Janeiro, Brazil.
   [Guanira, Juan] Invest Med Salud, Lima, Peru.
   [Grant, Robert M.] Gladstone Inst Virol & San Francisco AIDS Fdn, San Francisco, CA USA.
RP Glidden, DV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 550 16th St, San Francisco, CA 94158 USA.
EM david.glidden@ucsf.edu
OI Guanira, Juan/0000-0002-2746-3086
FU National Institute of Allergy and Infectious Diseases [U01 AI106499, UM1
   AI068619, U01 AI064002, R03 AI120819, R03 AI122908]; US National
   Institutes of Health; Bill and Melinda Gates Foundation
FX This work was supported by the National Institute of Allergy and
   Infectious Diseases. (U01 AI106499, UM1 AI068619, U01 AI064002, R03
   AI120819, R03 AI122908). Study medication was donated by Gilead
   Sciences. The iPrEx studies were sponsored by the US National Institutes
   of Health with cofunding from the Bill and Melinda Gates Foundation.
NR 22
TC 3
Z9 3
U1 3
U2 6
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 MAY 1
PY 2016
VL 62
IS 9
BP 1172
EP 1177
DI 10.1093/cid/ciw022
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM5IO
UT WOS:000376381800019
PM 26797207
ER

PT J
AU Thiebaut, R
   Jarne, A
   Routy, JP
   Sereti, I
   Fischl, M
   Ive, P
   Speck, RF
   D'Offizi, G
   Casari, S
   Commenges, D
   Foulkes, S
   Natarajan, V
   Croughs, T
   Delfraissy, JF
   Tambussi, G
   Levy, Y
   Lederman, MM
AF Thiebaut, Rodolphe
   Jarne, Ana
   Routy, Jean-Pierre
   Sereti, Irini
   Fischl, Margaret
   Ive, Prudence
   Speck, Roberto F.
   D'Offizi, Gianpiero
   Casari, Salvatore
   Commenges, Daniel
   Foulkes, Sharne
   Natarajan, Ven
   Croughs, Therese
   Delfraissy, Jean-Francois
   Tambussi, Guiseppe
   Levy, Yves
   Lederman, Michael M.
TI Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected
   Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy:
   Results of 2 Phase II Multicenter Studies
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE interleukin-7; HIV; immune restoration; T-cell recovery; CD4
ID MORTALITY; RECOVERY
AB Background. Phase I/II studies in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections of recombinant human interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect of repeated cycles of r-hIL-7 (20 mu g/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/mu L.
   Methods. INSPIRE 2 was a single-arm trial conducted in the United States and Canada. INSPIRE 3 was a 2 arm trial with 3: 1 randomization to r-hIL-7 versus control conducted in Europe and South Africa. Participants with plasma HIV RNA levels <50 copies/mL during antiretroviral therapy and with CD4 T-cell counts between 101 and 400 cells/mu L were eligible. A repeat cycle was administered when CD4 T-cell counts fell to < 550 cells/mu L.
   Results. A total of 107 patients were treated and received 1 (n = 107), 2 (n = 74), 3 (n = 14), or 4 (n = 1) r-hIL-7 cycles during a median follow-up of 23 months. r-hIL-7 was well tolerated. Four grade 4 events were observed, including 1 case of asymptomatic alanine aminotransferase elevation. After the second cycle, anti-r-hIL-7 binding antibodies developed in 82% and 77% of patients in INSPIRE 2 and 3, respectively (neutralizing antibodies in 38% and 37%), without impact on the CD4 T-cell response. Half of the patients spent >63% of their follow-up time with a CD4 T-cell count > 500 cells/mu L.
   Conclusions. Repeated cycles of r-hIL-7 were well tolerated and achieved sustained CD4 T-cell restoration to > 500 cells/mu L in the majority of study participants.
C1 [Thiebaut, Rodolphe; Jarne, Ana; Commenges, Daniel] Bordeaux Univ, IINSERM U1219, INRIA SISTM, F-33076 Bordeaux, France.
   [Croughs, Therese; Delfraissy, Jean-Francois] INSERM ANRS, Paris, France.
   [Levy, Yves] Univ Paris Est, Vaccine Res Inst Creteil, Serv Immunol Clin & Malad Infect,INSERM U955, Fac Med,Hopital H Mondor A Chenevier,AP HP, Creteil, France.
   [Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
   [Sereti, Irini] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Natarajan, Ven] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA.
   [Fischl, Margaret] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA.
   [Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Ive, Prudence] Clin HIV Res Unit, Johannesburg, South Africa.
   [Foulkes, Sharne] JOSHA Res, Bloemfontein, South Africa.
   [Speck, Roberto F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis, CH-8006 Zurich, Switzerland.
   [D'Offizi, Gianpiero] Inst Infect Dis Lazzaro Spallanzani, Rome, Italy.
   [Casari, Salvatore] Infect & Trop Dis Unit, Brescia, Italy.
   [Tambussi, Guiseppe] Ist Sci San Raffaele, I-20132 Milan, Italy.
RP Thiebaut, R (reprint author), Univ Bordeaux, INSERM U897, INRIA SISTM, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM rodolphe.thiebaut@u-bordeaux.fr
RI Speck, Roberto/O-2433-2016; Infektiologie, USZ/A-6921-2011
FU Vaccine Research Institute; National Institute of Allergy and Infectious
   Diseases, NIH
FX This work was supported by the Vaccine Research Institute (grant to A.
   J.) and the Intramural Research Program of the National Institute of
   Allergy and Infectious Diseases, NIH (I. S.).
NR 20
TC 7
Z9 7
U1 1
U2 1
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 MAY 1
PY 2016
VL 62
IS 9
BP 1178
EP 1185
DI 10.1093/cid/ciw065
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM5IO
UT WOS:000376381800020
PM 26908786
ER

PT J
AU Cieciera, M
   Kratochwil, C
   Moltz, J
   Kauczor, HU
   Holland-Letz, T
   Choyke, P
   Mier, W
   Haberkorn, U
   Giesel, FL
AF Cieciera, Matthaeus
   Kratochwil, Clemens
   Moltz, Jan
   Kauczor, Hans-Ulrich
   Holland-Letz, Tim
   Choyke, Peter
   Mier, Walter
   Haberkorn, Uwe
   Giesel, Frederik L.
TI Semi-automatic 3D-volumetry of liver metastases from neuroendocrine
   tumors to improve combination therapy with Lu-177-DOTATOC and
   Y-90-DOTATOC
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID RECEPTOR RADIONUCLIDE THERAPY; SOMATOSTATIN ANALOGS; RADIOPEPTIDE
   THERAPY; SELECTIVE ARTERIAL; LUNG; CT; ACCURACY; CANCER; PRRT
AB PURPOSE
   Patients with neuroendocrine tumors (NET) often present with disseminated liver metastases and can be treated with a number of different nuclides or nuclide combinations in peptide receptor radionuclide therapy (PRRT) depending on tumor load and lesion diameter. For quantification of disseminated liver lesions, semi-automatic lesion detection is helpful to determine tumor burden and tumor diameter in a time efficient manner. Here, we aimed to evaluate semi-automated measurement of total metastatic burden for therapy stratification.
   METHODS
   Nineteen patients with liver metastasized NET underwent contrast-enhanced 1.5 T MRI using gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid. Liver metastases (n=1537) were segmented using Fraunhofer MEVIS Software for three-dimensional (3D) segmentation. All lesions were stratified according to longest 3D diameter >20 mm or <= 20 mm and relative contribution to tumor load was used for therapy stratification.
   RESULTS
   Mean count of lesions <= 20 mm was 67.5 and mean count of lesions > 20 mm was 13.4. However, mean contribution to total tumor volume of lesions <= 20 mm was 24%, while contribution of lesions > 20 mm was 76%.
   CONCLUSION
   Semi-automatic lesion analysis provides useful information about lesion distribution in predominantly liver metastasized NET patients prior to PRRT. As conventional manual lesion measurements are laborious, our study shows this new approach is more efficient and less operator-dependent and may prove to be useful in the decision making process selecting the best combination PRRT in each patient.
C1 [Cieciera, Matthaeus; Kratochwil, Clemens; Mier, Walter; Haberkorn, Uwe; Giesel, Frederik L.] Univ Heidelberg Hosp, Dept Nucl Med, Heidelberg, Germany.
   [Kauczor, Hans-Ulrich] Univ Heidelberg Hosp, Dept Radiol, Heidelberg, Germany.
   [Moltz, Jan] Fraunhofer MEVIS, Inst Med Imaging Comp, Bremen, Germany.
   [Holland-Letz, Tim] German Canc Res Ctr, Dept Biostat, Heidelberg, Germany.
   [Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
   [Haberkorn, Uwe; Giesel, Frederik L.] DKFZ Heidelberg, Clin Cooperat Unit Nucl Med, Heidelberg, Germany.
RP Giesel, FL (reprint author), Univ Heidelberg Hosp, Dept Nucl Med, Heidelberg, Germany.
EM f.giesel@dkfz-heidelberg.de
NR 17
TC 0
Z9 0
U1 1
U2 2
PU TURKISH SOC RADIOLOGY
PI ANKARA
PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY
SN 1305-3825
EI 1305-3612
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD MAY-JUN
PY 2016
VL 22
IS 3
BP 201
EP 206
DI 10.5152/dir.2015.15304
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DM8DH
UT WOS:000376590400001
PM 27015320
ER

PT J
AU Ten Hagen, KG
AF Ten Hagen, Kelly G.
TI Novel or reproducible: That is the question
SO GLYCOBIOLOGY
LA English
DT Editorial Material
C1 [Ten Hagen, Kelly G.] NIDCR, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Ten Hagen, KG (reprint author), NIDCR, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD MAY
PY 2016
VL 26
IS 5
BP 429
EP 429
DI 10.1093/glycob/cww036
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DM5OI
UT WOS:000376398800001
PM 27030408
ER

PT J
AU Gildersleeve, JC
   Wright, WS
AF Gildersleeve, Jeffrey C.
   Wright, Whitney Shea
TI Diverse molecular recognition properties of blood group A binding
   monoclonal antibodies
SO GLYCOBIOLOGY
LA English
DT Article
DE Anti-glycan antibodies; blood group antigen; glycan microarray
ID ANTI-A; SERUM ANTIBODIES; ABO ANTIBODIES; VI ANTIGENS; PROSTVAC-VF;
   MICROARRAY; SPECIFICITY; SURVIVAL; OLIGOSACCHARIDES; DETERMINANTS
AB Information about specificity and affinity is critical for use of carbohydrate-binding antibodies. Herein, we evaluated eight monoclonal antibodies to the blood group A (BG-A) antigen. Antibodies 87-G, 9A, HE-10, HE-24, HE-193, HE-195, T36 and Z2A were profiled on a glycan microarray to assess specificity, relative affinity and the influence of glycan density on recognition. Our studies highlight several noteworthy recognition properties. First, most antibodies bound GalNAc alpha 1-3Gal and the BG-A trisaccharide nearly as well as larger BG-A oligosaccharides. Second, several antibodies only bound the BG-A trisaccharide when displayed on certain glycan chains. These first two points indicate that the carrier glycan chains primarily influence selectivity, rather than binding strength. Third, binding of some antibodies was highly dependent on glycan density, illustrating the importance of glycan presentation for recognition. Fourth, some antibodies recognized the tumor-associated Tn antigen, and one antibody only bound the variant composed of a GalNAc-alpha-linked to a serine residue. Collectively, these results provide new insights into the recognition properties of anti-BG-A antibodies.
C1 [Gildersleeve, Jeffrey C.; Wright, Whitney Shea] NCI, Biol Chem Lab, NIH, 376 Boyles St, Frederick, MD 21702 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, NIH, 376 Boyles St, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
FU National Cancer Institute, NIH
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute, NIH.
NR 36
TC 2
Z9 2
U1 4
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD MAY
PY 2016
VL 26
IS 5
BP 443
EP 448
DI 10.1093/glycob/cwv171
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DM5OI
UT WOS:000376398800003
PM 26755806
ER

PT J
AU Goldstein, BA
   Polley, EC
   Briggs, FBS
   van der Laan, MJ
   Hubbard, A
AF Goldstein, Benjamin A.
   Polley, Eric C.
   Briggs, Farren B. S.
   van der Laan, Mark J.
   Hubbard, Alan
TI Testing the Relative Performance of Data Adaptive Prediction Algorithms:
   A Generalized Test of Conditional Risk Differences
SO INTERNATIONAL JOURNAL OF BIOSTATISTICS
LA English
DT Article
DE risk prediction; cross-validation; semi-parametric models; machine
   learning
ID CROSS-VALIDATION; VARIANCE
AB Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical medicine has tended to rely on comparisons of fit metrics like C-statistics. However, for many data adaptive modelling procedures such approaches are not suitable. In these cases, statisticians have used cross-validation, which can make inference challenging. In this paper we propose a general approach that focuses on the "conditional" risk difference (conditional on the model fits being fixed) for the improvement in prediction risk. Specifically, we derive a Wald-type test statistic and associated confidence intervals for cross-validated test sets utilizing the independent validation within cross-validation in conjunction with a test for multiple comparisons. We show that this test maintains proper Type I Error under the null fit, and can be used as a general test of relative fit for any semi-parametric model alternative. We apply the test to a candidate gene study to test for the association of a set of genes in a genetic pathway.
C1 [Goldstein, Benjamin A.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
   [Polley, Eric C.] NCI, NIH, Biometr Res Branch, 6130 Execut Blvd EPN RM 8146, Bethesda, MD 20892 USA.
   [Briggs, Farren B. S.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [van der Laan, Mark J.; Hubbard, Alan] Univ Calif Berkeley, Div Biostat, Sch Publ Hlth, Berkeley, CA 94720 USA.
RP Goldstein, BA (reprint author), Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
EM ben.goldstein@duke.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [K25
   DK097279]; National Institutes of Health NRSA Trainee [T32 HG 00047];
   Russell M. Grossman Endowment
FX BAG was funded in part by National Institute of Diabetes and Digestive
   and Kidney Diseases K25 DK097279, a National Institutes of Health NRSA
   Trainee appointment on grant T32 HG 00047 and the Russell M. Grossman
   Endowment. FBSB is a National Multiple Sclerosis Society Post-Doctoral
   Fellow (FG 1847A1/1).
NR 19
TC 0
Z9 0
U1 2
U2 3
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 2194-573X
EI 1557-4679
J9 INT J BIOSTAT
JI Int. J. Biostat.
PD MAY
PY 2016
VL 12
IS 1
SI SI
BP 117
EP 129
DI 10.1515/ijb-2015-0014
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA DM8JV
UT WOS:000376609500009
PM 26529567
ER

PT J
AU Pourmorteza, A
   Chen, MY
   van der Pals, J
   Arai, AE
   McVeigh, ER
AF Pourmorteza, Amir
   Chen, Marcus Y.
   van der Pals, Jesper
   Arai, Andrew E.
   McVeigh, Elliot R.
TI Correlation of CT-based regional cardiac function (SQUEEZ) with
   myocardial strain calculated from tagged MRI: an experimental study
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Myocardial function; Tagged MRI; Contractility; CT SQUEEZ
ID CORONARY-ARTERY-DISEASE; LEFT-VENTRICULAR FUNCTION; COMPUTED-TOMOGRAPHY;
   CHEST-PAIN; ANGIOGRAPHY; IMAGES
AB The objective of this study was to investigate the correlation between local myocardial function estimates from CT and myocardial strain from tagged MRI in the same heart. Accurate detection of regional myocardial dysfunction can be an important finding in the diagnosis of functionally significant coronary artery disease. Tagged MRI is currently a reference standard for noninvasive regional myocardial function analysis; however, it has practical drawbacks. We have developed a CT imaging protocol and automated image analysis algorithm for estimating regional cardiac function from a few heartbeats. This method tracks the motion of the left ventricular (LV) endocardial surface to produce local function maps: we call the method Stretch Quantification of Endocardial Engraved Zones (SQUEEZ). Myocardial infarction was created by ligation of the left anterior descending coronary artery for 2 h followed by reperfusion in canine models. Tagged and cine MRI scans were performed during the reperfusion phase and first-pass contrast enhanced CT scans were acquired. The average delay between the CT and MRI scans was <1 h. Circumferential myocardial strain (E-cc) was calculated from the tagged MRI data. The agreement between peak systolic E-cc and SQUEEZ was investigated in 162 segments in the 9 hearts. Linear regression and Bland-Altman analysis was used to assess the correlation between the two metrics of local LV function. The results show good agreement between SQUEEZ and E-cc: (r = 0.71, slope = 0.78, p < 0.001). Furthermore, Bland-Altman showed a small bias of -0.02 with 95 % confidence interval of 0.1, and standard deviation of 0.05 representing similar to 6.5 % of the dynamic range of LV function. The good agreement between the estimates of local myocardial function obtained from CT SQUEEZ and tagged MRI provides encouragement to investigate the use of SQUEEZ for measuring regional cardiac function at a low clinical dose in humans.
C1 [Pourmorteza, Amir] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Chen, Marcus Y.; van der Pals, Jesper; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging Lab, Cardiopulmonary Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [McVeigh, Elliot R.] Univ Calif San Diego, Dept Bioengn, San Diego, CA 92103 USA.
   [McVeigh, Elliot R.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
   [McVeigh, Elliot R.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
RP Pourmorteza, A (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM amir.pourmorteza@nih.gov
FU Maryland Innovation Initiative grant [115127]
FX This research was supported in part by the Maryland Innovation
   Initiative grant (115127) titled "Diagnostic Method for Rapid Detection
   of Significant Coronary Heart Disease".
NR 18
TC 1
Z9 1
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
EI 1573-0743
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD MAY
PY 2016
VL 32
IS 5
BP 817
EP 823
DI 10.1007/s10554-015-0831-7
PG 7
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA DN0QG
UT WOS:000376767900014
PM 26706935
ER

PT J
AU Dorfman, J
   Rosen, D
   Pine, D
   Ernst, M
AF Dorfman, Julia
   Rosen, Dana
   Pine, Daniel
   Ernst, Monique
TI Anxiety and Gender Influence Reward-Related Processes in Children and
   Adolescents
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID ATTENTIONAL CONTROL-THEORY; INCENTIVE DELAY TASK; RISK-TAKING BEHAVIOR;
   DECISION-MAKING; COGNITIVE CONTROL; SEX-DIFFERENCES; DEPRESSED
   ADOLESCENTS; PEDIATRIC ANXIETY; ANTISACCADE TASK; GAMBLING TASK
AB Objective: This study examined the effects of pediatric anxiety and its interaction with gender on reward processes. Based on the purported greater sensitivity to risk in females than males and the propensity for risk aversion in anxiety, clinical anxiety and female gender were hypothesized to act synergistically in reducing reward sensitivity and increasing risk aversion in a pediatric population. Methods: This hypothesis was tested in two separate experiments using two independent samples. Both experiments compared clinically anxious with typically developing (TD) youth, 8-18 years. Experiment 1 used a decision-making task, the Wheel of Fortune task (WOF), to examine risk taking as a function of varying levels of risk and reward in 36 anxious and 61 TD youths. Experiment 2 used an incentive delay task, the Pinata task, to examine sensitivity to reward and motivation to work for a reward in 38 anxious and 30 TD youth. Percent bet, reaction time, and accuracy were analyzed as a function of gender and diagnostic group. Results: As hypothesized, anxiety was associated with reduced risk taking and sensitivity to reward. However, contrary to prediction, this effect was seen in males and not in females. These findings are consistent across both experiments. In experiment 1 (WOF), betting rate (i.e., risk taking) was significantly lower in anxious than in TD males (F[1;53]=7.07, p=0.01), whereas anxious females did not differ from TD females (F[1,42]=1.2, p=0.28). In experiment 2 (Pinata), anxiety impaired performance accuracy in males (F[1;36]=8.39; p<0.01) but not females (F[1;28]=0.6; p=0.445). Conclusions: Anxiety affected reward function differently in males and females. Contrary to hypothesis, anxious females behaved similarly to TD females on both tasks. However, anxious males were significantly more risk averse and less accurate than TD males. These findings suggest that therapeutic interventions for anxiety, which use manipulations of reward processes, should consider gender for optimal outcome.
C1 [Dorfman, Julia; Rosen, Dana; Pine, Daniel; Ernst, Monique] NIMH, Dept Dev & Affect Neurosci, Bethesda, MD 20892 USA.
RP Ernst, M (reprint author), 9000 Rockville Pike,Bldg 15k,Room 118, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
NR 63
TC 0
Z9 0
U1 4
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD MAY
PY 2016
VL 26
IS 4
BP 380
EP 390
DI 10.1089/cap.2015.0008
PG 11
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA DM9KK
UT WOS:000376684600009
PM 26779590
ER

PT J
AU Machiela, MJ
   Zhou, WY
   Caporaso, N
   Dean, M
   Gapstur, SM
   Goldin, L
   Stevens, VL
   Yeager, M
   Chanock, SJ
AF Machiela, Mitchell J.
   Zhou, Weiyin
   Caporaso, Neil
   Dean, Michael
   Gapstur, Susan M.
   Goldin, Lynn
   Stevens, Victoria L.
   Yeager, Meredith
   Chanock, Stephen J.
TI Mosaic 13q14 deletions in peripheral leukocytes of non-hematologic
   cancer cases and healthy controls
SO JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DETECTABLE CLONAL MOSAICISM;
   TUMOR-SUPPRESSOR GENE; B-CELL LYMPHOCYTOSIS; ARLTS1 CYS148ARG VARIANT;
   FAMILIAL BREAST-CANCER; PROSTATE-CANCER; HUMAN GENOME; ASSOCIATION; RISK
AB Loss of 13q14.3 is a chromosomal event found in similar to 50% of B-cell chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) cases. Surveys of somatic alterations in solid tumors have shown sporadic 13q14.3 loss in many different tumor types, but not at high frequency in any specific tumor type. In our recent survey of the single-nucleotide polymorphism (SNP) microarray data from 127 000 cancer-free or solid tumor cases, we observed mosaic 13q14.3 loss as common autosomal somatic large structural events (>2 Mb in size) in blood and buccal-derived DNA. Herein, we examined this region more closely investigating structural mosaic events <2 Mb using SNP microarray data in 46 254 non-hematologic cancer cases and 36 229 controls. We detected 60 individuals with 13q14.3 mosaic loss, 1 mosaic copy neutral uniparental disomy and 13 individuals with homozygosity. Although 13q14.3 loss size was variable, the minimally deleted region (MDR) (chr13: 49 590 000-49 983 100; GRCh36) was comparable to what is classically reported in MBL and CLL. Breakpoint analysis of the estimated boundaries reveals enrichment for genes and open chromatin. The frequency of 13q14.3 loss significantly increases with increasing age (P-value = 0.028), but was not significantly different between non-hematological cancer cases and controls (0.084% versus 0.058%; P-value = 0.19). These findings suggest that mosaic 13q14.3 losses accumulate with age. Individuals with detected mosaic 13q14.3 deletions may be early, undetected cases of MBL or CLL, but not necessarily all will develop MBL and CLL.
C1 [Machiela, Mitchell J.; Zhou, Weiyin; Caporaso, Neil; Dean, Michael; Goldin, Lynn; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Zhou, Weiyin; Yeager, Meredith] Leidos Biomed Res, Canc Genom Res Lab, Frederick, MD USA.
   [Dean, Michael] Frederick Natl Lab, Lab Expt Immunol, Ctr Canc Res, Frederick, MD USA.
   [Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Gaithersburg, MD 20852 USA.
EM chanocks@mail.nih.gov
OI Dean, Michael/0000-0003-2234-0631; Machiela,
   Mitchell/0000-0001-6538-9705
FU Intramural Research Program of the National Cancer Institute's Division
   of Cancer Epidemiology; American Cancer Society
FX This study was funded by the Intramural Research Program of the National
   Cancer Institute's Division of Cancer Epidemiology and the American
   Cancer Society.
NR 43
TC 3
Z9 3
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1434-5161
EI 1435-232X
J9 J HUM GENET
JI J. Hum. Genet.
PD MAY
PY 2016
VL 61
IS 5
BP 411
EP 418
DI 10.1038/jhg.2015.166
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DM7AK
UT WOS:000376504100007
PM 26763882
ER

PT J
AU Danforth, ME
   Reisen, WK
   Barker, CM
AF Danforth, Mary E.
   Reisen, William K.
   Barker, Christopher M.
TI The Impact of Cycling Temperature on the Transmission of West Nile Virus
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE West Nile virus; mosquito-borne disease; vector competence; extrinsic
   incubation period; Culex tarsalis
ID CULEX-TARSALIS DIPTERA; KERN-COUNTY; EXTRINSIC INCUBATION; ENCEPHALITIS
   VIRUSES; MOSQUITOS DIPTERA; VECTOR COMPETENCE; AEDES-AEGYPTI;
   CALIFORNIA; CULICIDAE; FLUCTUATIONS
AB West Nile virus (WNV) is an important cause of disease in humans and animals. Risk of WNV infection varies seasonally, with the greatest risk during the warmest parts of the year due in part to the accelerated extrinsic incubation rate of the virus in mosquitoes. Rates of extrinsic incubation have been shown in constant-temperature studies to increase as an approximately linear function of temperature, but for other vector-borne pathogens, such as malaria or dengue virus, nonlinear relationships have been demonstrated under cycling temperatures near the thermal limits of pathogen replication. Using typical daily air temperature profiles from three key periods of WNV amplification in a hyperendemic area of WNV activity in California's Central Valley, as well as a fourth temperature profile based on exposures that would result from daily mosquito host-seeking and resting behavior, we explored the impacts of cycling temperatures on WNV transmission by Culex tarsalis Coquillett, one of the principal vectors in the western United States. The daily cycling temperature ranges studied were representative of those that occur across much of California, but they did not significantly alter the extrinsic incubation period of WNV compared with estimates from mean temperatures alone. This suggests that within the relatively broad range we studied, WNV incubation rates are a simple function of mean temperature. Realistic daily temperature patterns that reflected mosquitoes' avoidance of daytime high temperatures during summer reduced transmission over time compared with air temperatures, indicating that adjustment for mosquito exposure temperatures would be prudent for calculating risk.
C1 [Danforth, Mary E.; Reisen, William K.; Barker, Christopher M.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, One Shields Ave, Davis, CA 95616 USA.
   [Barker, Christopher M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Barker, CM (reprint author), Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, One Shields Ave, Davis, CA 95616 USA.; Barker, CM (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM medanforth@ucdavis.edu; wkreisen@gmail.com; cmbarker@ucdavis.edu
FU Mosquito Research Foundation [2013-17]; Research and Policy for
   Infectious Disease Dynamics (RAPIDD) program of the Science and
   Technology Directorate, Department of Homeland Security and Fogarty
   International Center, National Institutes of Health
FX We thank Ying Fang, Sandra Garcia, Sarah Wheeler, and Veronica Armijos
   (Center for Vectorborne Diseases, Department of Pathology, Microbiology,
   and Immunology, School of Veterinary Medicine, University of California,
   Davis) for technical support and Dr. Philip Kass (Department of
   Population Health and Reproduction, School of Veterinary Medicine,
   University of California, Davis) for statistical advice and editing.
   This research was funded by Grant 2013-17 from the Mosquito Research
   Foundation. CMB acknowledges additional support from the Research and
   Policy for Infectious Disease Dynamics (RAPIDD) program of the Science
   and Technology Directorate, Department of Homeland Security and Fogarty
   International Center, National Institutes of Health.
NR 34
TC 3
Z9 3
U1 11
U2 24
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-2585
EI 1938-2928
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD MAY
PY 2016
VL 53
IS 3
BP 681
EP 686
DI 10.1093/jme/tjw013
PG 6
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA DM6II
UT WOS:000376454800028
PM 27026160
ER

PT J
AU Handziuk, V
   Pud, S
   Coppola, M
   Kisner, A
   Vitusevich, S
AF Handziuk, V.
   Pud, S.
   Coppola, M.
   Kisner, A.
   Vitusevich, S.
TI Features of noise in ultrathin gold nanowire structures
SO JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT
LA English
DT Article
DE adsorbates and surfactants (experiments); structures and conformations
   (experiments); surface spectroscopy; STM etc (experiment); current
   fluctuations
ID AU NANOWIRES; TRANSPORT
AB Bundles of ultrathin gold nanowires (Au NWs, 2 nm in diameter) were fabricated and subsequently assembled onto electrodes. Electrical measurements and noise spectroscopy techniques were applied for sample characterization. The peculiarities of noise behavior in the system of bundles of ultrathin gold nanowires were studied. The measured power spectral density of flicker noise was proportional to current squared, which reflects ohmic behavior in NW structures. Lorentzian-shaped components were revealed in the noise spectra. They are suggested to be the result of the participation of molecules adsorbed on the NW surface in transport phenomena. The presence of molecular interfaces was confirmed by high-resolution transmission electron micrographs. The adsorbed molecules play an important role in charge transport and therefore determine electrical and noise properties of the NW structures. The results should be taken into account for the development of NW devices for sensing and molecular electronics applications.
C1 [Handziuk, V.; Pud, S.; Coppola, M.; Vitusevich, S.] Forschungszentrum Julich, Peter Grunberg Inst PGI 8, Leo Brandtstr 1, D-52425 Julich, Germany.
   [Kisner, A.] NIDA, Intramural Res Program, Neuronal Circuits & Behav Unit, Baltimore, MD 21224 USA.
RP Handziuk, V; Pud, S; Coppola, M; Vitusevich, S (reprint author), Forschungszentrum Julich, Peter Grunberg Inst PGI 8, Leo Brandtstr 1, D-52425 Julich, Germany.; Kisner, A (reprint author), NIDA, Intramural Res Program, Neuronal Circuits & Behav Unit, Baltimore, MD 21224 USA.
EM v.handziuk@fz-juelich.de; s.pud@tudelft.nl; m.coppola@fz-juelich.de;
   kisner.alexandre169@gmail.com; s.vitusevich@fz-juelich.de
OI Handziuk, Volodymyr/0000-0002-4344-0052
NR 16
TC 1
Z9 1
U1 3
U2 10
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1742-5468
J9 J STAT MECH-THEORY E
JI J. Stat. Mech.-Theory Exp.
PD MAY
PY 2016
AR 054023
DI 10.1088/1742-5468/2016/05/054023
PG 8
WC Mechanics; Physics, Mathematical
SC Mechanics; Physics
GA DM7HP
UT WOS:000376529600051
ER

PT J
AU Iwasa, KH
   Florescu, AM
AF Iwasa, Kuni H.
   Florescu, Ana Maria
TI A molecule that detects the length of DNA by using chain fluctuations
SO JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT
LA English
DT Article
DE fluctuations (theory); molecular motors
ID CHROMATIN; NUCLEOSOMES; BIOLOGY; ACF
AB A class of nucleosome remodelling motors translocates the nucleosomes, to which they are attached, towards the middle of the DNA chain in the presence of ATP during in vitro experiments. This biological activity is likely based on a physical mechanism for detecting and comparing the lengths of the flanking polymer chains. Here we propose that a pivoting mode of DNA fluctuations near the surface of the nucleosome coupled with a binding reaction with a DNA binding site of the motor provides a physical basis for length detection. Since the mean frequency of the fluctuations is higher for a shorter chain than a longer one due to its lower drag coefficient, a shorter chain has a higher rate of receptor binding, which triggers the ATP-dependent activity of the remodelling motor. The dimerisation of these units allows the motor to compare the length of the flanking DNA chains, enabling the translocation of the nucleosome towards the centre of the DNA.
C1 [Iwasa, Kuni H.; Florescu, Ana Maria] Max Planck Inst Phys Komplexer Syst, Nothnitzer Str 38, D-01187 Dresden, Germany.
   [Iwasa, Kuni H.] NIH, Porter Neurosci Res Ctr, 35A Convent Dr, Bethesda, MD 20892 USA.
   [Florescu, Ana Maria] SISSA, Via Bonomea 265, I-34136 Trieste, Italy.
RP Iwasa, KH; Florescu, AM (reprint author), Max Planck Inst Phys Komplexer Syst, Nothnitzer Str 38, D-01187 Dresden, Germany.; Iwasa, KH (reprint author), NIH, Porter Neurosci Res Ctr, 35A Convent Dr, Bethesda, MD 20892 USA.; Florescu, AM (reprint author), SISSA, Via Bonomea 265, I-34136 Trieste, Italy.
EM iwasa@mailaps.org; aflorescu@sissa.it
NR 20
TC 1
Z9 1
U1 3
U2 3
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1742-5468
J9 J STAT MECH-THEORY E
JI J. Stat. Mech.-Theory Exp.
PD MAY
PY 2016
AR 054030
DI 10.1088/1742-5468/2016/05/054030
PG 12
WC Mechanics; Physics, Mathematical
SC Mechanics; Physics
GA DM7HP
UT WOS:000376529600058
ER

PT J
AU Huizer-Pajkos, A
   Kane, AE
   Howlett, SE
   Mach, J
   Mitchell, SJ
   de Cabo, R
   Le Couteur, DG
   Hilmer, SN
AF Huizer-Pajkos, Aniko
   Kane, Alice E.
   Howlett, Susan E.
   Mach, John
   Mitchell, Sarah J.
   de Cabo, Rafael
   Le Couteur, David G.
   Hilmer, Sarah N.
TI Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model:
   The Influence of Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
ID EXTENDS LIFE-SPAN; OLDER-ADULTS; CLINICAL-PHARMACOLOGY; UNITED-STATES;
   MICE; ACETAMINOPHEN; AGE; MEDICATIONS; FRAILTY; RATS
AB We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n = 10) and old (n = 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2 +/- 13 counts, polypharmacy 32 +/- 7 counts, p < .05) and front paw wire holding impulse (control -2.45 +/- 1.02 N s, polypharmacy +1.99 +/- 1.19 N s, p < .05), loss of improvement in rotarod latency (control -59 +/- 11 s, polypharmacy -1.7 +/- 17 s, p < .05), and lowered blood pressure (control -0.2 +/- 3 mmHg, polypharmacy 11 +/- 4 mmHg, p < .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice.
C1 [Huizer-Pajkos, Aniko; Kane, Alice E.; Mach, John; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Clin Pharmacol, St Leonards, NSW 2065, Australia.
   [Huizer-Pajkos, Aniko; Kane, Alice E.; Mach, John; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Aged Care, St Leonards, NSW 2065, Australia.
   [Huizer-Pajkos, Aniko; Kane, Alice E.; Mach, John; Hilmer, Sarah N.] Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia.
   [Kane, Alice E.; Mach, John; Le Couteur, David G.; Hilmer, Sarah N.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
   [Howlett, Susan E.] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada.
   [Howlett, Susan E.] Dalhousie Univ, Dept Med Geriatr Med, Halifax, NS, Canada.
   [Mitchell, Sarah J.; de Cabo, Rafael] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
   [Le Couteur, David G.] Concord Hosp, Ageing & Alzheimers Inst, Concord, NSW, Australia.
RP Hilmer, SN (reprint author), Royal N Shore Hosp, Lab Ageing & Pharmacol, Kolling Bldg,Pacific Highway, St Leonards, NSW 2065, Australia.
EM sarah.hilmer@sydney.edu.au
RI de Cabo, Rafael/J-5230-2016; 
OI de Cabo, Rafael/0000-0002-3354-2442; Kane, Alice/0000-0002-4303-0491;
   Howlett, Susan/0000-0001-5351-6308; , rafael/0000-0003-2830-5693
FU Penney Ageing Research Unit, Royal North Shore Hospital, Australia;
   National Institute on Aging, National Institutes of Health
FX This study was funded by the Penney Ageing Research Unit, Royal North
   Shore Hospital, Australia. Rafael de Cabo and Sarah Mitchell are
   supported by the National Institute on Aging, National Institutes of
   Health.
NR 55
TC 6
Z9 6
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2016
VL 71
IS 5
BP 571
EP 577
DI 10.1093/gerona/glv046
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DM5OE
UT WOS:000376398400002
PM 25940962
ER

PT J
AU de Pablo-Bernal, RS
   Canizares, J
   Rosado, I
   Galva, MI
   Alvarez-Rios, AI
   Carrillo-Vico, A
   Ferrando-Martinez, S
   Munoz-Fernandez, MA
   Benhnia, MRE
   Pacheco, YM
   Ramos, R
   Leal, M
   Ruiz-Mateos, E
AF Sara de Pablo-Bernal, Rebeca
   Canizares, Julio
   Rosado, Isaac
   Isabel Galva, Maria
   Isabel Alvarez-Rios, Ana
   Carrillo-Vico, Antonio
   Ferrando-Martinez, Sara
   Angeles Munoz-Fernandez, Maria
   Benhnia, Mohammed Rafii-El-Idrissi
   Maria Pacheco, Yolanda
   Ramos, Raquel
   Leal, Manuel
   Ruiz-Mateos, Ezequiel
TI Monocyte Phenotype and Polyfunctionality Are Associated With Elevated
   Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional
   and Cognitive Decline in Elderly Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Inflammation; Aging; Monocyte function; CMV; Cognitive; Mini-mental
ID DISEASE; PROGRESSION; ACTIVATION; ALZHEIMERS; EXPANSION; RESPONSES;
   LINEAGE; CD163
AB Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (alpha), IL1-beta (beta), IL-6, IL-8, TNF-alpha, and IL-10 of elderly adults (median 83 [67-90] years old; n = 20) compared with young controls (median 35 [27-40] years old; n = 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-alpha (p = .001), IL1-beta (p = .001), IL-6 (p = .002), and IL-8 (p = .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline.
C1 [Sara de Pablo-Bernal, Rebeca; Rosado, Isaac; Benhnia, Mohammed Rafii-El-Idrissi; Maria Pacheco, Yolanda; Leal, Manuel; Ruiz-Mateos, Ezequiel] Univ Seville, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomedicine Seville, Lab Immunovirol,IBiS,Virgen del Rocio Univ Hosp,C, Seville, Spain.
   [Canizares, Julio; Isabel Galva, Maria; Ramos, Raquel] Heliopolis Nursing Home, Seville, Spain.
   [Isabel Alvarez-Rios, Ana] Univ Seville, Virgen del Rocio Univ Hosp IBiS, Dept Clin Biochem, CSIC,SAS, Seville, Spain.
   [Carrillo-Vico, Antonio] Univ Seville, Virgen del Rocio Univ Hosp, Dept Med Biochem & Mol Biol & Immunol, Sch Med,Inst Biomed Seville,IBiS,CSIC, Seville, Spain.
   [Carrillo-Vico, Antonio] Inst Salud Carlos III, Red Temat Invest Cooperat Envejecimiento & Fragil, Seville, Spain.
   [Ferrando-Martinez, Sara] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Angeles Munoz-Fernandez, Maria] Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Lab Mol Immunobiol, Madrid, Spain.
   [Angeles Munoz-Fernandez, Maria] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain.
   [Benhnia, Mohammed Rafii-El-Idrissi] Univ Seville, Sch Med, Dept Biochem & Mol Biol & Immunol, Seville, Spain.
RP Ruiz-Mateos, E (reprint author), Virgen del Rocio Univ Hosp, Lab Immunovirol Lab 211, Inst Biomed Seville, Avda Manuel Siurot S-N, Seville 41013, Spain.
EM ezequiel.ruizmateos@gmail.com
RI IBIS, NEUROINMUNO/O-9306-2015; Carrillo Vico, Antonio/K-5265-2014; rafii
   el idrissi benhnia, mohammed/F-3019-2015; Pacheco, Yolanda/C-8457-2015; 
OI Carrillo Vico, Antonio/0000-0002-8516-0999; rafii el idrissi benhnia,
   mohammed/0000-0001-7405-9476; Ruiz-Mateos, Ezequiel/0000-0001-6747-7813
FU Redes Tematicas de Investigacion en SIDA [ISCIII RETIC RD12/0017/0029,
   RD06/0006/0035]; Proyecto de Excelencia, Consejeria de Innovacion,
   Ciencia y Empresa [P11-CTS-06313]; Consejeria Andaluza de Salud
   [PI-0278-2010]; Instituto de Salud Carlos III [CPII014/00025]; Ministry
   of Economy and Competitiveness [RYC-2010-07419]
FX This study was supported by Redes Tematicas de Investigacion en SIDA
   (ISCIII RETIC RD12/0017/0029 and RD06/0006/0035), Proyecto de
   Excelencia, Consejeria de Innovacion, Ciencia y Empresa (P11-CTS-06313),
   and Consejeria Andaluza de Salud (PI-0278-2010). E.R.-M received grants
   from (Instituto de Salud Carlos III CPII014/00025). This work was
   supported in part by Ramon y Cajal grant from Ministry of Economy and
   Competitiveness RYC-2010-07419 to M.R.B.
NR 28
TC 2
Z9 2
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2016
VL 71
IS 5
BP 610
EP 618
DI 10.1093/gerona/glv121
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DM5OE
UT WOS:000376398400007
PM 26286603
ER

PT J
AU Shardell, M
   Semba, RD
   Rosano, C
   Kalyani, RR
   Bandinelli, S
   Chia, CW
   Ferrucci, L
AF Shardell, Michelle
   Semba, Richard D.
   Rosano, Caterina
   Kalyani, Rita R.
   Bandinelli, Stefania
   Chia, Chee W.
   Ferrucci, Luigi
TI Plasma Klotho and Cognitive Decline in Older Adults: Findings From the
   InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Biomarkers; Cognition; Epidemiology
ID COMMUNITY-DWELLING ADULTS; MINI-MENTAL-STATE; CEREBROSPINAL-FLUID;
   UNITED-STATES; EXPRESSION; HORMONE; DISEASE; IMPAIRMENT; PREVALENCE;
   MORTALITY
AB Background: The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults.
   Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline.
   Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82).
   Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes.
C1 [Shardell, Michelle; Chia, Chee W.; Ferrucci, Luigi] NIA, Translat Gerontol Branch, 3001 S Hanover St, Baltimore, MD 21224 USA.
   [Semba, Richard D.] Wilmer Eye Inst, Johns Hopkins Med Inst, Baltimore, MD 21287 USA.
   [Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Kalyani, Rita R.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
   [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
RP Shardell, M (reprint author), NIA, Translat Gerontol Branch, 3001 S Hanover St, Baltimore, MD 21224 USA.
EM michelle.shardell@nih.gov
OI Rosano, Caterina/0000-0002-0909-1506; Rosano,
   Caterina/0000-0002-4271-6010
FU National Institutes of Health [R01AG027012, R01HL111271, R21HL112662,
   K23DK093583]; National Institute on Aging [263MD9164, 263 MD 821336,
   N01-AG-1-1, N01-AG-10211, N01-AG-5-0002]; Intramural Research Program of
   the National Institute on Aging, NIH
FX This study was funded by grants from the National Institutes of Health
   R01AG027012, R01HL111271, R21HL112662 (Dr. Semba), K23DK093583 (Dr.
   Kalyani); National Institute on Aging contracts 263MD9164 (Dr. Ferrucci)
   and 263 MD 821336, N01-AG-1-1, N01-AG-10211, and N01-AG-5-0002 (Dr.
   Bandinelli); and the Intramural Research Program of the National
   Institute on Aging, NIH (Drs. Ferrucci and Shardell).
NR 40
TC 2
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U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAY
PY 2016
VL 71
IS 5
BP 677
EP 682
DI 10.1093/gerona/glv140
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DM5OE
UT WOS:000376398400018
PM 26297657
ER

PT J
AU Byrne, KM
   Levy, KY
   Reese, EM
AF Byrne, Karen M.
   Levy, Kimberly Y.
   Reese, Erika M.
TI Following the Rules Set by Accreditation Agencies and Governing Bodies
   to Maintain In-Compliance Status: Applying Critical Thinking Skills When
   Evaluating the Need for Change in the Clinical Laboratory
SO LABORATORY MEDICINE
LA English
DT Article
ID BLOOD; QUALITY
AB Maintaining an in-compliance clinical laboratory takes continuous awareness and review of standards, regulations, and best practices. A strong quality assurance program and well informed leaders who maintain professional networks can aid in this necessary task. This article will discuss a process that laboratories can follow to interpret, understand, and comply with the rules and standards set by laboratory accreditation bodies.
C1 [Byrne, Karen M.; Levy, Kimberly Y.; Reese, Erika M.] NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Byrne, KM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM kbyrne@cc.nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-5027
EI 1943-7730
J9 LAB MED
JI Lab. Med.
PD MAY
PY 2016
VL 47
IS 2
BP E21
EP E26
DI 10.1093/labmed/lmw007
PG 6
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA DM8YU
UT WOS:000376651200003
PM 26945880
ER

PT J
AU Ohkuni, K
   Takahashi, Y
   Fulp, A
   Lawrimore, J
   Au, WC
   Pasupala, N
   Levy-Myers, R
   Warren, J
   Strunnikov, A
   Baker, RE
   Kerscher, O
   Bloom, K
   Basrai, MA
AF Ohkuni, Kentaro
   Takahashi, Yoshimitsu
   Fulp, Alyona
   Lawrimore, Josh
   Au, Wei-Chun
   Pasupala, Nagesh
   Levy-Myers, Reuben
   Warren, Jack
   Strunnikov, Alexander
   Baker, Richard E.
   Kerscher, Oliver
   Bloom, Kerry
   Basrai, Munira A.
TI SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of
   centromeric histone H3 variant Cse4 and prevents its mislocalization to
   euchromatin
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID BUDDING YEAST KINETOCHORE; SACCHAROMYCES-CEREVISIAE; CENP-A; PROTEIN-A;
   ECTOPIC LOCALIZATION; HIR PROTEINS; HUMAN-CELLS; SUMOYLATION;
   DEGRADATION; CONJUGATION
AB Centromeric histone H3, CENP-A(Cse4), is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-A(Cse)4 restricts its localization to centromeres. Mislocalization of CENP-A(Cse4) is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro. Ubiquitination of Cse4 by the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal physiological conditions. Accumulation of sumoylated Cse4 species and increased stability of Cse4 in slx5 Delta strains suggest that sumoylation precedes ubiquitin-mediated proteolysis of Cse4. Slx5-mediated Cse4 proteolysis is independent of Psh1, since slx5 Delta psh1 Delta strains exhibit higher levels of Cse4 stability and mislocalization than either slx5 Delta or psh1 Delta strains. Our results demonstrate a role for Slx5 in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain genome stability.
C1 [Ohkuni, Kentaro; Takahashi, Yoshimitsu; Au, Wei-Chun; Levy-Myers, Reuben; Warren, Jack; Basrai, Munira A.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Fulp, Alyona; Lawrimore, Josh; Bloom, Kerry] Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA.
   [Pasupala, Nagesh; Levy-Myers, Reuben; Kerscher, Oliver] Coll William & Mary, Dept Biol, Williamsburg, VA 23187 USA.
   [Strunnikov, Alexander] Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.
   [Baker, Richard E.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA.
RP Basrai, MA (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM basraim@nih.gov
OI Strunnikov, Alexander/0000-0002-9058-2256
FU National Institutes of Health Intramural Research Program; National
   Science Foundation Grant [MBC 1051970]; National Institutes of Health
   R37 Grant [GM32238]
FX We thank members of the Basrai laboratory for helpful discussions and
   comments on the manuscript. We gratefully acknowledge Charlie Boone,
   Frank Holstege, and Sue Biggins for reagents and advice, Tatiana Karpova
   (Fluorescent Imaging Facility, National Cancer Institute) for assistance
   with cell biology experiments, Kathy McKinnon (Vaccine Branch FACS Core,
   National Cancer Institute) for assistance with FACS, and Anita Corbett,
   Ian Cheeseman, Michael Lichten, Tom Misteli, and Peter Kaiser for
   comments on the manuscript. This work was supported by the National
   Institutes of Health Intramural Research Program to M.B., National
   Science Foundation Grant MBC 1051970 to O.K., and National Institutes of
   Health R37 Grant GM32238 to K.B.
NR 60
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U1 0
U2 2
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 MAY 1
PY 2016
VL 27
IS 9
BP 1500
EP 1510
DI 10.1091/mbc.E15-12-0827
PG 11
WC Cell Biology
SC Cell Biology
GA DM6IZ
UT WOS:000376456500009
ER

PT J
AU Pourshafie, N
   Lee, PR
   Chen, KL
   Harmison, GG
   Bott, LC
   Katsuno, M
   Sobue, G
   Burnett, BG
   Fischbeck, KH
   Rinaldi, C
AF Pourshafie, Naemeh
   Lee, Philip R.
   Chen, Ke-lian
   Harmison, George G.
   Bott, Laura C.
   Katsuno, Masahisa
   Sobue, Gen
   Burnett, Barrington G.
   Fischbeck, Kenneth H.
   Rinaldi, Carlo
TI MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and
   Bulbar Muscular Atrophy
SO MOLECULAR THERAPY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; FAST AXONAL-TRANSPORT; BLOOD-BRAIN-BARRIER;
   HUNTINGTONS-DISEASE; MOUSE MODEL; NEURODEGENERATION; EXPRESSION;
   MICRORNAS; DELIVERY; NEURONS
AB Spinal and bulbar muscular atrophy (SBMA) is a currently untreatable adult-onset neuromuscular disease caused by expansion of a polyglutamine repeat in the androgen receptor (AR). In SBMA, as in other polyglutamine diseases, a toxic gain of function in the mutant protein is an important factor in the disease mechanism; therefore, reducing the mutant protein holds promise as an effective treatment strategy. In this work, we evaluated a microRNA (miRNA) to reduce AR expression. From a list of predicted miRNAs that target human AR, we selected microRNA-298 (miR-298) for its ability to downregulate AR mRNA and protein levels when transfected in cells overexpressing wild-type and mutant AR and in SBMA patient-derived fibroblasts. We showed that miR-298 directly binds to the 3'-untranslated region of the human AR transcript, and counteracts AR toxicity in vitro. Intravenous delivery of miR-298 with adeno-associated virus serotype 9 vector resulted in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in SBMA mice. Our findings support the development of miRNAs as a therapeutic strategy for SBMA and other neurodegenerative disorders caused by toxic proteins.
C1 [Pourshafie, Naemeh; Chen, Ke-lian; Harmison, George G.; Bott, Laura C.; Fischbeck, Kenneth H.; Rinaldi, Carlo] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Lee, Philip R.] Eunice Kennedy Shriver Natl Inst Child & Human De, Sect Nervous Syst Dev & Plast, NIH, Bethesda, MD USA.
   [Bott, Laura C.] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
   [Katsuno, Masahisa; Sobue, Gen] Nagoya Univ, Grad Sch Med, Dept Neurol, Nagoya, Aichi 4648601, Japan.
   [Sobue, Gen] Nagoya Univ, Grad Sch Med, Brain & Mind Res Ctr, Nagoya, Aichi 4648601, Japan.
   [Burnett, Barrington G.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
   [Rinaldi, Carlo] Univ Oxford, Dept Physiol Anat & Genet, Le Gros Clark Bldg,Room 114,South Parks Rd, Oxford OX1 3QX, England.
RP Rinaldi, C (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Rinaldi, C (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Le Gros Clark Bldg,Room 114,South Parks Rd, Oxford OX1 3QX, England.
EM carlo.rinaldi@dpag.ox.ac.uk
FU Intramural Research Program of the National Institute of Neurological
   Disorders and Stroke, NIH; Division of Intramural Research of NICHD;
   Association Francaise contre les Myopathies
FX The authors thank SignaGen Laboratories (Rockvile, MD, USA) for the AAV9
   virus production. This research was supported by the Intramural Research
   Program of the National Institute of Neurological Disorders and Stroke,
   NIH. Philip R. Lee was supported by funds from the Division of
   Intramural Research of NICHD. Carlo Rinaldi was supported by a
   fellowship from the Association Francaise contre les Myopathies. The
   authors declare no conflict of interest.
NR 47
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Z9 1
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
IS 5
BP 937
EP 945
DI 10.1038/mt.2016.13
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DM5ZC
UT WOS:000376428100011
PM 26755334
ER

PT J
AU Kajimura, J
   Kyoizumi, S
   Kubo, Y
   Misumi, M
   Yoshida, K
   Hayashi, T
   Imai, K
   Ohishi, W
   Nakachi, K
   Weng, NP
   Young, LF
   Shieh, JH
   Moore, MA
   van den Brink, MRM
   Kusunoki, Y
AF Kajimura, Junko
   Kyoizumi, Seishi
   Kubo, Yoshiko
   Misumi, Munechika
   Yoshida, Kengo
   Hayashi, Tomonori
   Imai, Kazue
   Ohishi, Waka
   Nakachi, Kei
   Weng, Nan-ping
   Young, Lauren F.
   Shieh, Jae-Hung
   Moore, Malcolm A.
   van den Brink, Marcel R. M.
   Kusunoki, Yoichiro
TI Relationship between spontaneous gamma H2AX foci formation and
   progenitor functions in circulating hematopoietic stem and progenitor
   cells among atomic-bomb survivors
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Hematopoietic stem and progenitor cells; gamma H2AX; Telomere length;
   DNA damage; Atomic-bomb; Self-renewability
ID GLYCOPHORIN-A LOCUS; T-LYMPHOCYTES; DNA-DAMAGE; CHROMOSOME-ABERRATIONS;
   BONE-MARROW; MUTATIONS; REPAIR; AGE; ERYTHROCYTES; POPULATIONS
AB Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (gamma H2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of gamma H2AX foci formation in HSPCs and the radiation dose was observed, but the gamma H2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of gamma H2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of gamma H2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self -renewability of HSPCs may be modified by A-bomb radiation exposure. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Nakachi, Kei; Kusunoki, Yoichiro] Radiat Effects Res Fdn, Dept Mol Biosci, Hiroshima, Japan.
   [Misumi, Munechika] Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan.
   [Ohishi, Waka] Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan.
   [Weng, Nan-ping] Natl Inst Aging, Lab Mol Biol & Immunol, NIH, Baltimore, MD USA.
   [Young, Lauren F.; van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Dept Med & Immunol, 1275 York Ave, New York, NY 10021 USA.
   [Shieh, Jae-Hung; Moore, Malcolm A.] Mem Sloan Kettering Canc Ctr, Dept Cell Biol Program, 1275 York Ave, New York, NY 10021 USA.
RP Kajimura, J; Kusunoki, Y (reprint author), Radiat Effects Res Fdn, Dept Mol Biosci, Hiroshima, Japan.
EM kajimura@rerf.or.jp; ykusunok@rerf.or.jp
FU Japanese Ministry of Health, Labour and Welfare (MHLW); US Department of
   Energy (DOE); DOE [DE-HS0000031]; U.S. National Institute of Allergy and
   Infectious Diseases (NIAID) [HHSN272200900059C]; intramural research
   programs of the National Institutes of Health (NIH), National Institute
   on Aging
FX We thank Mika Yamaoka and Aya Nishikiori for their excellent assistance
   with FACS and fluorescence microscope analyses, respectively. The
   Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki,
   Japan, is a public interest foundation funded by the Japanese Ministry
   of Health, Labour and Welfare (MHLW) and the US Department of Energy
   (DOE). The research was also funded in part through DOE award
   DE-HS0000031 to the National Academy of Sciences. This study was based
   on RERF Research Protocol RP#5-09 and was supported by the U.S. National
   Institute of Allergy and Infectious Diseases (NIAID
   ContractHHSN272200900059C) and in part by the intramural research
   programs of the National Institutes of Health (NIH), National Institute
   on Aging. The views of the authors do not necessarily reflect those of
   the two governments.
NR 42
TC 0
Z9 0
U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD MAY
PY 2016
VL 802
BP 59
EP 65
DI 10.1016/j.mrgentox.2016.04.006
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA DN1CG
UT WOS:000376803300005
PM 27169377
ER

PT J
AU Costa, FHD
   Averbeck, B
   O'Sullivan, SS
   Vincent, MB
   Rosso, AL
   Lees, AJ
   Djamshidian, A
AF de Rezende Costa, Flavio Henrique
   Averbeck, Bruno
   O'Sullivan, Sean S.
   Vincent, Maurice Borges
   Rosso, Ana Lucia
   Lees, Andrew J.
   Djamshidian, Atbin
TI Jumping to conclusions in untreated patients with Parkinson's disease
SO NEUROPSYCHOLOGIA
LA English
DT Article
ID IMPULSE CONTROL DISORDERS; DEEP BRAIN-STIMULATION; REFLECTION
   IMPULSIVITY; COMPULSIVE BEHAVIORS; DOPAMINE AGONISTS; DECISION-MAKING;
   DORSAL STRIATUM; RISK; ADDICTION
AB Background: Jumping to conclusions due to impulsivity has been shown to be a sensitive marker for dopamine dysregulation and addictive behaviour patterns in treated patients with Parkinson's disease (PD). It is unknown whether drug naive PD patients, who have never received dopaminergic therapy also have deficits in information sampling.
   Methods: Twenty five de novo PD patients and twenty matched healthy controls were recruited and tested on the beads task, which is a validated information sampling task to assess reflection impulsivity and a temporal discounting questionnaire.
   Results: Patients gathered significantly less information and made more irrational choices than matched controls. There was, however, no group difference on the temporal discounting questionnaire.
   Conclusions: Poor information sampling and irrational decision making may be an inherent component of the neuropsychological deficit in Parkinson's disease. These findings suggest that underlying impulsivity detected by a metric task is common in de novo PD. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [de Rezende Costa, Flavio Henrique; Vincent, Maurice Borges; Rosso, Ana Lucia] Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Dept Neurol, Movement Disorders Sect, Rio De Janeiro, Brazil.
   [Averbeck, Bruno] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
   [O'Sullivan, Sean S.] Cork Univ Hosp, Dept Neurol, Cork, Ireland.
   [Lees, Andrew J.; Djamshidian, Atbin] Univ London, Dept Mol Neurosci, London, England.
   [Lees, Andrew J.; Djamshidian, Atbin] Univ London, Reta Lila Weston Inst Neurol Studies, London, England.
   [Djamshidian, Atbin] Med Univ Innsbruck, Dept Neurol, Anichstr 35, A-6020 Innsbruck, Austria.
RP Djamshidian, A (reprint author), Med Univ Innsbruck, Dept Neurol, Anichstr 35, A-6020 Innsbruck, Austria.
EM atbin.djamshidian-tehrani@i-med.ac.at
NR 43
TC 0
Z9 0
U1 3
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD MAY
PY 2016
VL 85
BP 19
EP 23
DI 10.1016/j.neuropsychologia.2016.03.002
PG 5
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DM7ND
UT WOS:000376546400003
ER

PT J
AU Dorfman, J
   Benson, B
   Farber, M
   Pine, D
   Ernst, M
AF Dorfman, Julia
   Benson, Brenda
   Farber, Madeline
   Pine, Daniel
   Ernst, Monique
TI Altered striatal intrinsic functional connectivity in pediatric anxiety
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Anxiety; Adolescence; Neuroimaging; Resting state fMRI; Reward; Striatum
ID RESTING-STATE FMRI; SOCIAL-ANXIETY; RISK-AVOIDANCE; BASAL GANGLIA;
   PHYSIOLOGICAL CONDITION; BEHAVIORAL-INHIBITION; DEPRESSED ADOLESCENTS;
   AFFECTIVE-DISORDERS; MOTIVATED BEHAVIOR; NUCLEUS-ACCUMBENS
AB Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders.
   The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons.
   Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area.
   The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Dorfman, Julia; Benson, Brenda; Farber, Madeline; Pine, Daniel; Ernst, Monique] NIMH, 9000 Rockville Pike,Bldg 15k, Bethesda, MD 20892 USA.
RP Dorfman, J (reprint author), 9000 Rockville Pike,Bldg 15k,Room 115, Bethesda, MD 20892 USA.
EM dorfman.julia@gmail.com; bbenson@mail.nih.gov; madeline.farber@nih.gov;
   pined@mail.nih.gov; ernstm@mail.nih.gov
FU NIMH Intramural Research Program
FX This work was supported by NIMH Intramural Research Program. We would
   like to thank Dana Rosen for help with data processing, Joel Stoddard
   M.D. and AFNI group (especially Richard C. Reynolds pH.D. and Gang Chen,
   pH.D.) for assistance with image analysis. In addition, we thank Jillian
   L Wiggins, pH.D. for help with scientific software.
NR 75
TC 0
Z9 0
U1 4
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD MAY
PY 2016
VL 85
BP 159
EP 168
DI 10.1016/j.neuropsychologia.2016.03.019
PG 10
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DM7ND
UT WOS:000376546400017
PM 27004799
ER

PT J
AU Leischow, SJ
   Muramoto, ML
   Matthews, E
   Floden, LL
   Grana, RA
AF Leischow, Scott J.
   Muramoto, Myra L.
   Matthews, Eva
   Floden, Lysbeth L.
   Grana, Rachel A.
TI Adolescent Smoking Cessation With Bupropion: The Role of Adherence
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID DEPENDENCE; PREDICTORS
AB Introduction: While many medications can be effective aids to quitting tobacco, real world adherence to smoking cessation medications may render a potentially effective medication ineffective. The present study investigated the role of adherence on treatment outcomes in a bupropion dose-response study among adolescent smokers trying to quit smoking.
   Methods: Three hundred twelve adolescent boys (n = 143) and girls (n = 169) between the ages of 14-17 were enrolled in the study, and were randomly assigned to use either 300 mg, 150 mg or placebo bupropion to quit smoking. Among the eligibility criterion, participants had to smoke at least six cigarettes per day, be motivated to quit smoking (self report), have an exhaled carbon monoxide level greater than or equal to 10 ppm, and report at least two previous quit attempts. Adherence to medication was determined by both self-report and actual counts of unused medication and empty medication packaging. Smoking status was determined by a combination of self-report and biochemical verification (breath carbon monoxide and urine cotinine).
   Results: Cotinine-confirmed quit rates were significantly higher as a function of high adherence (20.69%) relative to low adherence (0.00%) in the 300-mg Bupropion Sustained Release group. Overall adherence in all study conditions in this highly controlled study was high (74%), but was significantly lower in non-white participants.
   Conclusions: Effectiveness of bupropion for adolescent smoking cessation is contingent on achieving high rates of medication adherence, but considerable variations in adherence impacted outcomes.
   Implications: Few studies have assessed the safety and efficacy of medications to help adolescent smokers quit, and we conducted one such study assessing bupropion. In this analysis of that original study, we assess the role of adherence in use of medication and quit rates. We found that adherence was related to outcomes, particularly in the 300-mg dose of bupropion.
C1 [Leischow, Scott J.] Mayo Clin Arizona, Dept Res, MCCRB 2-205, Scottsdale, AZ 85259 USA.
   [Muramoto, Myra L.; Matthews, Eva; Floden, Lysbeth L.] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA.
   [Grana, Rachel A.] Natl Canc Inst, Tobacco Control Res Branch, Bethesda, MD USA.
RP Leischow, SJ (reprint author), Mayo Clin Arizona, Dept Res, MCCRB 2-205, Scottsdale, AZ 85259 USA.
EM leischow.scott@mayo.edu
FU National Cancer Institute at the National Institutes of Health [RO1
   CA77081]; Robert Wood Johnson Foundation (RWJF) [043549];
   GlaxoSmithKline
FX This work was supported by the National Cancer Institute at the National
   Institutes of Health (RO1 CA77081) and The Robert Wood Johnson
   Foundation (RWJF grant number 043549). GlaxoSmithKline provided study
   medication and placebo, financial support for cotinine analyses, subject
   screening, data cleaning, and review of the draft manuscript.
NR 7
TC 3
Z9 3
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD MAY
PY 2016
VL 18
IS 5
BP 1202
EP 1205
DI 10.1093/ntr/ntv179
PG 4
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA DM4XN
UT WOS:000376350700098
PM 26567274
ER

PT J
AU Williams, JK
   Cashion, AK
   Shekar, S
   Ginsburg, GS
AF Williams, Janet K.
   Cashion, Ann K.
   Shekar, Sam
   Ginsburg, Geoffrey S.
TI Genomics, clinical research, and learning health care systems:
   Strategies to improve patient care
SO NURSING OUTLOOK
LA English
DT Article
ID RESEARCH AGENDA; SCIENCE; RECORD
C1 [Williams, Janet K.] Univ Iowa, Amer Acad Nursing, 50 Newton Rd, Iowa City, IA 52242 USA.
   [Cashion, Ann K.] NINR, NIH, Bethesda, MD 20892 USA.
   [Shekar, Sam] Northrop Grumman Informat Syst Hlth Div, Mclean, VA USA.
   [Ginsburg, Geoffrey S.] Duke Univ, Durham, NC USA.
RP Williams, JK (reprint author), Univ Iowa, Amer Acad Nursing, 50 Newton Rd, Iowa City, IA 52242 USA.
EM janet-williams@uiowa.edu
NR 18
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD MAY-JUN
PY 2016
VL 64
IS 3
BP 225
EP 228
DI 10.1016/j.outlook.2015.12.006
PG 4
WC Nursing
SC Nursing
GA DM4QT
UT WOS:000376332500006
PM 26821732
ER

PT J
AU Lei, LF
   Yang, GP
   Wang, JL
   Chuang, DM
   Song, WH
   Tang, BS
   Jiang, H
AF Lei, Li-Fang
   Yang, Guo-Ping
   Wang, Jun-Ling
   Chuang, De-Maw
   Song, Wei-Hong
   Tang, Bei-Sha
   Jiang, Hong
TI Safety and efficacy of valproic acid treatment in SCA3/MJD patients
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Efficacy; PolyQ disease; Spinocerebellar ataxia type 3/Machado-Joseph
   disease; Tolerability; Valproic acid
ID HISTONE DEACETYLASE INHIBITORS; PLACEBO-CONTROLLED TRIAL; CREB-BINDING
   PROTEIN; SPINOCEREBELLAR ATAXIA; POLYGLUTAMINE DISORDERS;
   HUNTINGTONS-DISEASE; CLINICAL-FEATURES; CEREBELLAR-ATAXIA; MOOD
   STABILIZERS; BIPOLAR DISORDER
AB Background: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is one of 10 known polyglutamine (polyQ) diseases. In Drosophila and rat models of polyQ diseases, histone deacetylation (HDAC) inhibitors improved locomotor function and survival time by increasing histone acetylation levels and modulating gene expression. Valproic acid (VPA) is a pan-HDAC inhibitor used clinically to treat bipolar and seizure disorders. We evaluated the clinical safety and efficacy of VPA treatment for SCA3/MJD patients.
   Methods: First, a randomized, open-label, dose-escalation method was used to evaluate tolerance to single-dose VPA administration in 12 SCA3/MJD patients. Patients were randomly assigned to three groups of four subjects, each with an oral dosage of 400 mg, 600 mg, or 800 mg (twice daily (bid) for one day). VPA was well-tolerated for one-dose by all patient groups. Second, a randomized, double-blind, placebo-controlled, dose-controlled study evaluated the safety and efficacy of multi-dose VPA (oral administration, twice daily (bid) for 12 weeks) in 36 SCA3/MJD patients. Patients received either low dose VPA (800 mg/day), high-dose VPA (1200 mg/day), or placebo (n = 12 subjects per group). Symptoms were evaluated using the Scale for Assessment and Rating of Ataxia (SARA).
   Results: Multi-dose VPA treatment improved SARA measures of locomotor function. Major adverse effects included dizziness and loss of appetite.
   Conclusions: VPA is a potentially beneficial agent for the treatment of SCA3/MJD. These results also provide insight into possible future therapeutics for polyQ diseases. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Lei, Li-Fang; Wang, Jun-Ling; Tang, Bei-Sha; Jiang, Hong] Cent S Univ, Dept Neurol, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.
   [Lei, Li-Fang] Cent S Univ, Dept Neurol, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China.
   [Yang, Guo-Ping] Cent S Univ, Clin Pharmacol Ctr, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China.
   [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
   [Song, Wei-Hong] Univ British Columbia, Dept Psychiat, Brain Res Ctr, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
   [Tang, Bei-Sha; Jiang, Hong] Cent S Univ, Key Lab Hunan Prov Neurodegenerat Disorders, Changsha 410008, Hunan, Peoples R China.
   [Tang, Bei-Sha; Jiang, Hong] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
RP Jiang, H (reprint author), Cent S Univ, Dept Neurol, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.
EM jianghong73868@126.com
FU National Basic Research Program (973 Program) [2011CB510002,
   2012CB944601, 2012CB517902]; National Natural Science Foundation of
   China [81471156, 81271260]; Hunan Funds for Distinguished Young
   Scientists [14JJ1008]; Clinical Research Funds of Xiangya Hospital
   [2014L03]; High-Level Medical Personnel of Hunan Province 225 Project;
   Intramural Research Program of the National Institute of Mental Health,
   National Institutes of Health (IRP-NIMH-NIH)
FX This study was supported in part by the National Basic Research Program
   (973 Program; Nos. 2011CB510002, 2012CB944601, and 2012CB517902 to HJ),
   the National Natural Science Foundation of China (nos. 81471156and
   81271260 to HJ), the Hunan Funds for Distinguished Young Scientists
   (nos. 14JJ1008 to HJ), Clinical Research Funds of Xiangya Hospital
   (2014L03 to Hong Jiang), the High-Level Medical Personnel of Hunan
   Province 225 Project, and the Intramural Research Program of the
   National Institute of Mental Health, National Institutes of Health
   (IRP-NIMH-NIH). The authors thank all of the participants for their
   involvement in this study, and are grateful to the physicians who cared
   for them. Ioline Henter and Peter Leeds (NIMH, NIH, USA) provided
   excellent editorial assistance.
NR 32
TC 0
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U1 4
U2 7
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 MAY
PY 2016
VL 26
BP 55
EP 61
DI 10.1016/j.parkreldis.2016.03.005
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DM9ST
UT WOS:000376706700009
PM 26997655
ER

PT J
AU Bastian, H
AF Bastian, Hilda
TI Nondisclosure of Financial Interest in Clinical Practice Guideline
   Development: An Intractable Problem?
SO PLOS MEDICINE
LA English
DT Editorial Material
ID CONFLICTS
C1 [Bastian, Hilda] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Bastian, H (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM hilda.bastian@nih.gov
OI Bastian, Hilda/0000-0001-8544-7386
NR 12
TC 5
Z9 5
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD MAY
PY 2016
VL 13
IS 5
AR e1002030
DI 10.1371/journal.pmed.1002030
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DN2NK
UT WOS:000376900100018
PM 27243232
ER

PT J
AU Veiga, LHS
   Holmberg, E
   Anderson, H
   Pottern, L
   Sadetzki, S
   Adams, MJ
   Sakata, R
   Schneider, AB
   Inskip, P
   Bhatti, P
   Johansson, R
   Neta, G
   Shore, R
   de Vathaire, F
   Damber, L
   Kleinerman, R
   Hawkins, MM
   Tucker, M
   Lundell, M
   Lubin, JH
AF Veiga, Lene H. S.
   Holmberg, Erik
   Anderson, Harald
   Pottern, Linda
   Sadetzki, Siegal
   Adams, M. Jacob
   Sakata, Ritsu
   Schneider, Arthur B.
   Inskip, Peter
   Bhatti, Parveen
   Johansson, Robert
   Neta, Gila
   Shore, Roy
   de Vathaire, Florent
   Damber, Lena
   Kleinerman, Ruth
   Hawkins, Michael M.
   Tucker, Margaret
   Lundell, Marie
   Lubin, Jay H.
TI Thyroid Cancer after Childhood Exposure to External Radiation: An
   Updated Pooled Analysis of 12 Studies
SO RADIATION RESEARCH
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; SKIN HEMANGIOMA; TINEA-CAPITIS;
   IONIZING-RADIATION; CHERNOBYL ACCIDENT; DETECTION LIMITS;
   CLINICAL-TRIALS; RISK; RADIOTHERAPY; IRRADIATION
AB Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation. (C) 2016 by Radiation Research Society
C1 [Veiga, Lene H. S.; Inskip, Peter; Kleinerman, Ruth; Tucker, Margaret; Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
   [Neta, Gila] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA.
   [Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Inst Radiat Protect & Dosimetry, Rio De Janeiro, Brazil.
   [Holmberg, Erik] Sahlgrens Univ Hosp, Dept Oncol & Radiat Phys, Gothenburg, Sweden.
   [Holmberg, Erik] Sahlgrens Univ Hosp, Ctr Oncol, Gothenburg, Sweden.
   [Anderson, Harald] Lund Univ, Dept Canc Epidemiol, Lund, Sweden.
   [Anderson, Harald] US PHS, Nord Countries Childhood Canc Survival Grp, Bethesda, MD USA.
   [Pottern, Linda] US PHS, Bethesda, MD USA.
   [Sadetzki, Siegal] Tel Aviv Univ, Canc & Radiat Epidemiol Unit, Gertner Inst, Chaim Sheba Med Ctr, IL-69978 Tel Aviv, Israel.
   [Sadetzki, Siegal] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Adams, M. Jacob] Univ Rochester, Sch Med & Dent, Dept Publ Hlth Sci, Rochester, NY USA.
   [Sakata, Ritsu; Shore, Roy] Radiat Effects Res Fdn, Hiroshima, Japan.
   [Schneider, Arthur B.] Univ Illinois, Coll Med, Sect Endocrinol Diabet & Metab, Chicago, IL USA.
   [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
   [Johansson, Robert; Damber, Lena] Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden.
   [de Vathaire, Florent] Inst Gustave Roussy, Canc Epidemiol Res Unit, Natl Inst Hlth & Med Res, Villejuif, France.
   [Hawkins, Michael M.] Univ Birmingham, Ctr Childhood Canc Survivor Studies, Dept Publ Hlth & Epidemiol, Birmingham, W Midlands, England.
   [Lundell, Marie] Karolinska Univ Hosp, Radiumhemmet, Dept Med Phys, Stockholm, Sweden.
   [Lundell, Marie] Karolinska Inst, Stockholm, Sweden.
RP Lubin, JH (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM lubinj@mail.nih.gov
RI de Vathaire, Florent/L-2983-2016; 
OI Holmberg, Erik/0000-0001-5107-4550; Adams, Michael
   Jacob/0000-0002-3245-5793
FU Intramural Research Program of the U.S. National Institutes of Health
   (NIH), National Cancer Institute, Division of Cancer Epidemiology and
   Genetics; National Cancer Institute [U24 CA55727]; Children's Cancer
   Research Fund; Lance Armstrong Foundation [147149]; Intramural Research
   Program of the NIH, National Cancer Institute, Division of Cancer
   Epidemiology and Genetics
FX This study was supported by the Intramural Research Program of the U.S.
   National Institutes of Health (NIH), National Cancer Institute, Division
   of Cancer Epidemiology and Genetics. The Childhood Cancer Survivor Study
   was funded by the National Cancer Institute (grant no. U24 CA55727), the
   Children's Cancer Research Fund, the Lance Armstrong Foundation (grant
   no. 147149) and the Intramural Research Program of the NIH, National
   Cancer Institute, Division of Cancer Epidemiology and Genetics. We would
   also like to acknowledge members of the Nordic Countries Childhood
   Cancer Survivor Study Group, who have contributed to the Nordic
   Countries Childhood Cancer Survivor Study, including: H. Hertz, J. Olsen
   (Denmark); G. Jonmundsson, H. Tulinius (Iceland); M. Lanning, R. Sankila
   (Finland); H. Dollner, F. Langmark (Norlway) and H. Anderson, S.
   Garwicz, T. Moller and G. Svahn-Tapper (Sweden). We particularly wish to
   recognize the late Dr. Elaine Ron, who initiated and guided this pooling
   project.
NR 45
TC 3
Z9 3
U1 4
U2 7
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD MAY
PY 2016
VL 185
IS 5
BP 473
EP 484
DI 10.1667/RR14213.1
PG 12
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
   Nuclear Medicine & Medical Imaging
GA DN0LI
UT WOS:000376755000004
PM 27128740
ER

PT J
AU Wolcott, HN
   Fouch, MJ
   Hsu, ER
   DiJoseph, LG
   Bernaciak, CA
   Corrigan, JG
   Williams, DE
AF Wolcott, Holly N.
   Fouch, Matthew J.
   Hsu, Elizabeth R.
   DiJoseph, Leo G.
   Bernaciak, Catherine A.
   Corrigan, James G.
   Williams, Duane E.
TI Modeling time-dependent and -independent indicators to facilitate
   identification of breakthrough research papers
SO SCIENTOMETRICS
LA English
DT Article; Proceedings Paper
CT 15th International Conference of the
   International-Society-for-Scientometrics-and-Informetrics (ISSI)
CY JUN 29-JUL 04, 2015
CL Bogazici Univ, Istanbul, TURKEY
SP Int Soc Scientometr & Informetr, Hacettepe Univ, Sci & Technol Res Council Turkey, Turkish Acad Network & Informat Ctr
HO Bogazici Univ
DE Transformative research; Breakthrough prediction; Indicators; Co-author
   network metrics; Citation velocity
ID SCIENTIFIC LITERATURE; CITATION COUNTS; SCIENCE
AB Research funding organizations invest substantial resources to monitor mission-relevant research findings to identify and support promising new lines of inquiry. To that end, we have been pursuing the development of tools to identify research publications that have a strong likelihood of driving new avenues of research. This paper describes our work towards incorporating multiple time-dependent and -independent features of publications into a model to identify candidate breakthrough papers as early as possible following publication. We used multiple random forest models to assess the ability of indicators to reliably distinguish a gold standard set of breakthrough publications as identified by subject matter experts from among a comparison group of similar Thomson Reuters Web of Science (TM) publications. These indicators were then tested for their predictive value in random forest models. Model parameter optimization and variable selection were used to construct a final model based on indicators that can be measured within 6 months post-publication; the final model had an estimated true positive rate of 0.77 and false positive rate of 0.01.
C1 [Wolcott, Holly N.; Fouch, Matthew J.; DiJoseph, Leo G.; Bernaciak, Catherine A.] Thomson Reuters, Intellectual Property & Sci, Rockville, MD 20850 USA.
   [Hsu, Elizabeth R.; Corrigan, James G.] NCI, Off Sci Planning & Assessment, Bethesda, MD 20892 USA.
   [Williams, Duane E.] UberResearch, Bethesda, MD 20814 USA.
RP Williams, DE (reprint author), UberResearch, Bethesda, MD 20814 USA.
EM corrigan@mail.nih.gov; duane@uberresearch.com
FU NIH [HHS263201000058B]
FX This study was improved by contributions from Danielle Daee (NCI); Di
   Cross, and Joshua Schnell (Thomson Reuters); and extends work by Ilya
   Ponomarev (formerly Thomson Reuters) and Charles Hackett (National
   Institutes of Allergy and Infectious Diseases). This work was supported
   in part by NIH contract #HHS263201000058B.
NR 22
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U1 8
U2 15
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0138-9130
EI 1588-2861
J9 SCIENTOMETRICS
JI Scientometrics
PD MAY
PY 2016
VL 107
IS 2
BP 807
EP 817
DI 10.1007/s11192-016-1861-1
PG 11
WC Computer Science, Interdisciplinary Applications; Information Science &
   Library Science
SC Computer Science; Information Science & Library Science
GA DM3VA
UT WOS:000376273600027
ER

PT J
AU Gokhale, NA
AF Gokhale, Nikhil A.
TI Supporting Research-Inspired Entrepreneurial Activities in India
SO TECHNOLOGY INNOVATION MANAGEMENT REVIEW
LA English
DT Article
DE entrepreneurship; research-inspired entrepreneurship; financial risk;
   business; economy
AB Nations built on innovation, entrepreneurship, and production are able to dominate the world economy. However, risk taking has traditionally been discouraged in developing nations. The uncertainty and financial insecurity associated with entrepreneurial activities are the greatest barriers that budding entrepreneurs need to overcome in order to transition into successful entrepreneurs. This challenge needs substantial effort and steady support from society. Easy access to information, mentorship, and a network of venture capitalists and angel investors also play critical roles in promoting entrepreneurial activities. To this end, the Government of India recently launched a nationwide campaign to promote entrepreneurial activities across the country. Some of the recently emerging trends indicate that scientific and technological innovators from India are now willing to be a part of the global entrepreneurial revolution. Research-inspired entrepreneurial initiatives are expected to play a key role in facilitating India's economic growth in the coming years. This article focuses on the initiatives undertaken by the Indian Government and by various academic institutes to facilitate entrepreneurial activities across the country.
C1 [Gokhale, Nikhil A.] RK Univ, Fac Doctoral Studies & Res, Rajkot, Gujarat, India.
   [Gokhale, Nikhil A.] NIH, Biomed Res, Bethesda, MD USA.
   [Gokhale, Nikhil A.] Univ Massachusetts, Sch Med, Biomed Res, Amherst, MA 01003 USA.
RP Gokhale, NA (reprint author), Univ Illinois, Chicago, IL USA.
NR 10
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U1 3
U2 6
PU CARLETON UNIV GRAPHIC SERVICES
PI OTTAWA
PA DUNTON TOWER RM 2122, 1125 COLONEL BY DR, OTTAWA, ON K1A 5B6, CANADA
SN 1927-0321
J9 TECHNOL INNOV MANAG
JI Technol. Innov. Manag. Rev.
PD MAY
PY 2016
BP 10
EP 14
PG 5
WC Management
SC Business & Economics
GA DM8OB
UT WOS:000376622700003
ER

PT J
AU Ryan, N
   Chorley, B
   Tice, RR
   Judson, R
   Corton, JC
AF Ryan, Natalia
   Chorley, Brian
   Tice, Raymond R.
   Judson, Richard
   Corton, J. Christopher
TI Moving Toward Integrating Gene Expression Profiling Into High-Throughput
   Testing: A Gene Expression Biomarker Accurately Predicts Estrogen
   Receptor alpha Modulation in a Microarray Compendium
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE estrogen receptor; gene expression profiling; MCF-7 cell line; biomarker
ID BREAST-CANCER-CELLS; ENDOCRINE-DISRUPTING CHEMICALS; CHIP-SEQ DATA;
   IN-VITRO; CONNECTIVITY MAP; PROTEIN; TRANSCRIPTION; ACTIVATION;
   ESTRADIOL; PATHWAYS
AB Microarray profiling of chemical-induced effects is being increasingly used in medium- and high-throughput formats. Computational methods are described here to identify molecular targets from whole-genome microarray data using as an example the estrogen receptor alpha (ER alpha), often modulated by potential endocrine disrupting chemicals. ER alpha biomarker genes were identified by their consistent expression after exposure to 7 structurally diverse ER alpha agonists and 3 ER alpha antagonists in ER alpha-positive MCF-7 cells. Most of the biomarker genes were shown to be directly regulated by ER alpha as determined by ESR1 gene knockdown using siRNA as well as through chromatin immunoprecipitation coupled with DNA sequencing analysis of ER alpha-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm by comparison to annotated gene expression datasets from experiments using MCF-7 cells, including those evaluating the transcriptional effects of hormones and chemicals. Using 141 comparisons from chemical- and hormone-treated cells, the biomarker gave a balanced accuracy for prediction of ER alpha activation or suppression of 94% and 93%, respectively. The biomarker was able to correctly classify 18 out of 21 (86%) ER reference chemicals including "very weak" agonists. Importantly, the biomarker predictions accurately replicated predictions based on 18 in vitro high-throughput screening assays that queried different steps in ER alpha signaling. For 114 chemicals, the balanced accuracies were 95% and 98% for activation or suppression, respectively. These results demonstrate that the ER alpha gene expression biomarker can accurately identify ER alpha modulators in large collections of microarray data derived from MCF-7 cells.
C1 [Ryan, Natalia] US EPA, ORISE, Res Triangle Pk, NC 27711 USA.
   [Ryan, Natalia; Chorley, Brian; Corton, J. Christopher] US EPA, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA.
   [Tice, Raymond R.] US EPA, NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27711 USA.
   [Judson, Richard] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA.
RP Corton, JC (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Integrated Syst Toxicol Div, 109 TW Alexander Dr MD-B143-06, Res Triangle Pk, NC 27711 USA.
EM corton.chris@epa.gov
FU U.S. EPA; National Institute of Environmental Health Sciences
FX The information in this document has been funded in part by the U.S. EPA
   and by the National Institute of Environmental Health Sciences.
NR 59
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U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAY
PY 2016
VL 151
IS 1
BP 88
EP 103
DI 10.1093/toxsci/kfw026
PG 16
WC Toxicology
SC Toxicology
GA DM9CU
UT WOS:000376662800008
PM 26865669
ER

PT J
AU Xu, L
   Zheng, J
   Margittai, M
   Nussinov, R
   Ma, BY
AF Xu, Liang
   Zheng, Jie
   Margittai, Martin
   Nussinov, Ruth
   Ma, Buyong
TI How Does Hyperphopsphorylation Promote Tau Aggregation and Modulate
   Filament Structure and Stability?
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Tau; Alzheimer's disease; amyloid; hyperphosphorylation; paired helical
   filaments
ID PAIRED HELICAL FILAMENTS; MOLECULAR-DYNAMICS SIMULATIONS; ASSEMBLY
   IN-VITRO; PACE FORCE-FIELD; SOLID-STATE NMR; ALZHEIMERS-DISEASE; PROTEIN
   AGGREGATION; 4-REPEAT TAU; NEURODEGENERATIVE DISEASE; ABNORMAL
   PHOSPHORYLATION
AB Tau proteins are hyperphosphorylated at common sites in their N- and C-terminal domains in at least three neurodegenerative diseases, Parkinson, dementia with Lewy bodies, and Alzheimer's, suggesting specific pathology but general mechanism. Full-length human tau filament comprises a rigid core and a two-layered fuzzy coat. Tau is categorized into two groups of isoforms, with either four repeats (R1-R4) or three repeats (R1, R3, and R4); their truncated constructs are respectively called K18 and K19. Using multiscale molecular dynamics simulations, we explored the conformational consequences of hyperhposphorylation on tau's repeats. Our lower conformational energy filament models suggest a rigid filament core with a radius of similar to 30 to 40 angstrom and an outer layer with a thickness of similar to 140 angstrom consisting of a double-layered polyelectrolyte. The presence of the phosphorylated terminal domains alters the relative stabilities in the K18 ensemble, thus shifting the populations of the full-length filaments. However, the structure with the straight repeats in the core region is still the most stable, similar to the truncated K18 peptide species without the N- and C-terminus. Our simulations across different scales of resolution consistently reveal that hyperphosphorylation of the two terminal domains decreases the attractive interactions among the Nand C-terminus and repeat domain. To date, the relationship on the conformational level between phosphorylation and aggregation has not been understood. Our results suggest that the exposure of the repeat domain upon hyperphosphorylation could enhance tau filament aggregation. Thus, we discovered that even though these neurodegenerative diseases vary and their associated tau filaments are phosphorylated to different extents, remarkably, the three pathologies appear to share a common tau aggregation mechanism.
C1 [Xu, Liang] Dalian Univ Technol, Sch Chem, Dalian 116024, Peoples R China.
   [Zheng, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
   [Margittai, Martin] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
   [Nussinov, Ruth; Ma, Buyong] NCI, Basic Res Program, Leidos Biomed Res Inc, Canc & Inflammat Program,Asesor Docente, Frederick, MD 21702 USA.
RP Ma, BY (reprint author), NCI, Basic Res Program, Leidos Biomed Res Inc, Canc & Inflammat Program,Asesor Docente, Frederick, MD 21702 USA.
EM mabuyong@mail.nih.gov
RI Zheng, Jie/B-5057-2013; Ma, Buyong/F-9491-2011
OI Zheng, Jie/0000-0003-1547-3612; Ma, Buyong/0000-0002-7383-719X
FU Federal funds from the National Cancer Institute, National Institutes of
   Health [HHSN261200800001E]; Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research; China Scholarship
   Council [CSC201306065001]; NSF [CBET-0952624, CBET-1510099]; Alzheimer
   Association [2015-NIRG-341372]; National Institute of Neurological
   Disorders and Stroke [R01NS076619]
FX This project was funded in whole or in part with Federal funds from the
   National Cancer Institute, National Institutes of Health, under contract
   number HHSN261200800001E. This research was supported (in part) by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. L.X. thanks the China Scholarship Council
   (CSC201306065001) for financial support. J.Z. thanks the NSF (CAREER
   Awards CBET-0952624 and CBET-1510099) and Alzheimer Association, New
   Investigator Research Grant (2015-NIRG-341372), for financial support.
   This project was supported by National Institute of Neurological
   Disorders and Stroke Grant R01NS076619 (to M.M.).
NR 91
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U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD MAY
PY 2016
VL 7
IS 5
BP 565
EP 575
DI 10.1021/acschemneuro.5b00294
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
   & Neurology
GA DM4RI
UT WOS:000376334000007
PM 26854860
ER

PT J
AU Gallant, KMH
   Weaver, CM
   Towler, DA
   Thuppal, SV
   Bailey, RL
AF Gallant, Kathleen M. Hill
   Weaver, Connie M.
   Towler, Dwight A.
   Thuppal, Sowmyanarayanan V.
   Bailey, Regan L.
TI Nutrition in Cardioskeletal Health
SO ADVANCES IN NUTRITION
LA English
DT Article
DE calcium; phosphorus; bone health; cardiovascular diseases; vitamin D
ID CHRONIC KIDNEY-DISEASE; D-BINDING PROTEIN; SMOOTH-MUSCLE-CELLS; DIETARY
   PHOSPHORUS INTAKE; MINERAL-BONE DISORDER; STAGE RENAL-DISEASE; TIBIAL
   ARTERY CALCIFICATION; VITAMIN-D SUPPLEMENTATION; SERUM 25-HYDROXYVITAMIN
   D; PARATHYROID-HORMONE
AB Bone and heart health are linked through a variety of cellular, endocrine, and metabolic mechanisms, including the bidirectional effects of mineral-regulating hormones parathyroid hormone and fibroblast growth factor 23. Nutrition plays an important role in the development of both cardiovascular and bone disease. This review describes current knowledge on the relations between the cardiovascular system and bone and the influence of key nutrients involved in mineral metabolism-calcium, vitamin D, and phosphorus-on heart and bone health, as well as the racial/ethnic differences in cardiovascular disease and osteoporosis and the influence that nutrition has on these disparities.
C1 [Gallant, Kathleen M. Hill; Weaver, Connie M.; Thuppal, Sowmyanarayanan V.; Bailey, Regan L.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA.
   [Towler, Dwight A.] Univ Texas SW Med Ctr Dallas, Div Endocrine, Internal Med, Dallas, TX 75390 USA.
   [Bailey, Regan L.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
RP Gallant, KMH (reprint author), Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA.
EM hillgallant@purdue.edu
OI Towler, Dwight/0000-0003-2107-7923
FU American Society for Nutrition (ASN); National Dairy Council; Dairy
   Australia; Pharmavite; Kraft Foods; Dairy Research Institute; Nestle;
   NIH [HL-069229, HL-114806]
FX This article is a review from the symposium "Improving Cardio-Skeletal
   Health by Exploring the Heart-Bone Connection" held 31 March 2015 at the
   ASN Scientific Sessions and Annual Meeting at Experimental Biology 2015
   in Boston, MA. The symposium was sponsored by the American Society for
   Nutrition (ASN) and supported by the National Dairy Council.; Supported
   by research funding from Dairy Australia, Pharmavite, Kraft Foods, the
   Dairy Research Institute, and Nestle for the pig study described in this
   manuscript (CMW) and by NIH grants HL-069229 and HL-114806 (DAT).
NR 134
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U2 5
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD MAY
PY 2016
VL 7
IS 3
BP 544
EP 555
DI 10.3945/an.115.011189
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DM2GB
UT WOS:000376163900013
ER

PT J
AU Zhang, C
   Kuo, CC
   Moghadam, SH
   Monte, L
   Campbell, SN
   Rice, KC
   Sawchenko, PE
   Masliah, E
   Rissman, RA
AF Zhang, Cheng
   Kuo, Ching-Chang
   Moghadam, Setareh H.
   Monte, Louise
   Campbell, Shannon N.
   Rice, Kenner C.
   Sawchenko, Paul E.
   Masliah, Eliezer
   Rissman, Robert A.
TI Corticotropin-releasing factor receptor-1 antagonism mitigates beta
   amyloid pathology and cognitive and synaptic deficits in a mouse model
   of Alzheimer's disease
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Alzheimer's disease; R121919; Corticotropin-releasing factor receptor;
   Corticotropin-releasing hormone; Hippo-campus; Cognitive deficits;
   Synaptic deficits; Stress; Beta amyloid
ID TAU PHOSPHORYLATION; PSYCHOLOGICAL DISTRESS; PRECURSOR PROTEIN;
   CEREBRAL-CORTEX; CRF RECEPTORS; TG2576 MICE; STRESS; BRAIN;
   NEURODEGENERATION; DEPRESSION
AB Introduction: Stress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models.
   Methods: To test whether antagonism of the type-1 corticotropin-releasing factor receptor (CRFR1) could be used as a disease-modifying treatment for AD, we used a preclinical prevention paradigm and treated 30-day-old AD transgenic mice with the small-molecule, CRFR1-selective antagonist, R121919, for 5 months, and examined AD pathologic and behavioral end points.
   Results: R121919 significantly prevented the onset of cognitive impairment in female mice and reduced cellular and synaptic deficits and beta amyloid and C-terminal fragment-beta levels in both genders. We observed no tolerability or toxicity issues in mice treated with R121919.
   Discussion: CRFR1 antagonism presents a viable disease-modifying therapy for AD, recommending its advancement to early-phase human safety trials. (C) 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
C1 [Zhang, Cheng; Moghadam, Setareh H.; Monte, Louise; Campbell, Shannon N.; Masliah, Eliezer; Rissman, Robert A.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Kuo, Ching-Chang] Univ Oregon, NeuroInformat Ctr, Eugene, OR 97403 USA.
   [Rice, Kenner C.] Natl Inst Drug Abuse & Alcohol Abuse & Alcoholism, Chem Biol Res Branch, NIH, Bethesda, MD USA.
   [Sawchenko, Paul E.] Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
RP Rissman, RA (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
EM rrissman@ucsd.edu
FU NIH [AG032755, AG047484, DK026741, AG010483]; Alzheimer's Art Quilt
   Initiative; Alzheimer's Association; Leona M. and Harry B. Helmsley
   Charitable Trust grant [2012-PG-MED002]; Clayton Medical Research
   Foundation
FX Supported by NIH AG032755, AG047484, DK026741, and AG010483; the
   Alzheimer's Art Quilt Initiative; the Alzheimer's Association; the Leona
   M. and Harry B. Helmsley Charitable Trust grant #2012-PG-MED002; and the
   Clayton Medical Research Foundation. P.E.S. is a senior investigator of
   the Clayton Medical Research Foundation. The authors thank Drs L.
   Squire, S. Nuber, Ling, C. Arias, C. Overk, S. Anderson, A. Adame, and
   K. Lao.
NR 52
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U1 7
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAY
PY 2016
VL 12
IS 5
BP 527
EP 537
DI 10.1016/j.jalz.2015.09.007
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA DM0RT
UT WOS:000376054200002
PM 26555315
ER

PT J
AU Molinuevo, JL
   Cami, J
   Carne, X
   Carrillo, MC
   Georges, J
   Isaac, MB
   Khachaturian, Z
   Kim, SYH
   Morris, JC
   Pasquier, F
   Ritchie, C
   Sperling, R
   Karlawish, J
AF Molinuevo, Jose L.
   Cami, Jordi
   Carne, Xavier
   Carrillo, Maria C.
   Georges, Jean
   Isaac, Maria B.
   Khachaturian, Zaven
   Kim, Scott Y. H.
   Morris, John C.
   Pasquier, Florence
   Ritchie, Craig
   Sperling, Reisa
   Karlawish, Jason
TI Ethical challenges in preclinical Alzheimer's disease observational
   studies and trials: Results of the Barcelona summit
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Alzheimer's disease; Preclinical AD; Ethics; Asymptomatic
ID SERVICES-TASK-FORCE; COGNITIVE IMPAIRMENT; GENETIC RISK; ASSOCIATION
   WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; CLINICAL-TRIALS;
   RESEARCH PARTICIPANTS; DRUG-DEVELOPMENT; APOLIPOPROTEIN-E
AB Alzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Molinuevo, Jose L.] Pasqual Maragall Fdn, Barcelonasseta Brain Res Ctr, Barcelona, Spain.
   [Cami, Jordi] Pompeu Fabra Univ, Barcelona, Spain.
   [Cami, Jordi] Pasqual Maragall Fdn, Barcelona, Spain.
   [Carne, Xavier] Hosp Clin Barcelona, Dept Clin Pharmacol, Barcelona, Spain.
   [Carne, Xavier] IDIBAPS, Barcelona, Spain.
   [Carrillo, Maria C.] Alzheimers Assoc, Med & Sci Relat, Chicago, IL USA.
   [Georges, Jean] Alzheimer Europe, Luxembourg, Luxembourg.
   [Isaac, Maria B.] EMA, London, England.
   [Khachaturian, Zaven] Campaign Prevent Alzheimer 2020 PAD2020, Potomac, MD USA.
   [Kim, Scott Y. H.] NIH, Dept Bioeth, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Morris, John C.] Washington Univ, Sch Med, St Louis, MO USA.
   [Pasquier, Florence] Univ Lille 2, Inserm 1171, CHU, Memory Ctr Lille, Lille, France.
   [Ritchie, Craig] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
   [Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med, Boston, MA 02115 USA.
   [Karlawish, Jason] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Molinuevo, JL (reprint author), Pasqual Maragall Fdn, Barcelonasseta Brain Res Ctr, Barcelona, Spain.
EM jlmolinuevo@fpmaragall.org
FU European Union's Seventh Framework Programme [115736]; EFPIA company
FX The research leading to these results has received support from the
   Innovative Medicines Initiative Joint Undertaking under grant agreement
   no 115736, resources of which are composed of financial contribution
   from the European Union's Seventh Framework Programme (FP7/2007-2013)
   and EFPIA companies' in kind contribution. The authors thank Karine
   Fauria and Carolina Minguillon for their assistance with this article
   preparation and for the logistical planning of the summit. They thank as
   well the institutions that have supported the realization of the summit"
   "Obra social la Caixa" for the summit venue at "Caixa Forum"; Roche,
   Novartis, Lilly, Lumbeck, and Janssen for logistic support; and the
   Pasqual Maragall Foundation for the summit organization. The authors of
   this article presented and discussed their views throughout the meeting.
NR 66
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U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAY
PY 2016
VL 12
IS 5
BP 614
EP 622
DI 10.1016/j.jalz.2016.01.009
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DM0RT
UT WOS:000376054200011
PM 26988427
ER

PT J
AU Allen, NB
   Lloyd-Jones, D
   Hwang, SJ
   Rasmussen-Torvik, L
   Fornage, M
   Morrison, AC
   Baldridge, AS
   Boerwinkle, E
   Levy, D
   Cupples, LA
   Fox, CS
   Thanassoulis, G
   Dufresne, L
   Daviglus, M
   Johnson, AD
   Reis, J
   Rotter, J
   Palmas, W
   Allison, M
   Pankow, JS
   O'Donnell, CJ
AF Allen, Norrina B.
   Lloyd-Jones, Donald
   Hwang, Shih-Jen
   Rasmussen-Torvik, Laura
   Fornage, Myriam
   Morrison, Alanna C.
   Baldridge, Abigail S.
   Boerwinkle, Eric
   Levy, Daniel
   Cupples, L. Adrienne
   Fox, Caroline S.
   Thanassoulis, George
   Dufresne, Line
   Daviglus, Martha
   Johnson, Andrew D.
   Reis, Jared
   Rotter, Jerome
   Palmas, Walter
   Allison, Mathew
   Pankow, James S.
   O'Donnell, Christopher J.
TI Genetic loci associated with ideal cardiovascular health: A
   meta-analysis of genome-wide association studies
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID RISK-FACTOR PROFILE; METABOLIC SYNDROME; MIDDLE-AGE; MEDICARE COSTS;
   LIFETIME RISK; FACTOR BURDEN; DISEASE RISK; LIPID-LEVELS; HEART; DESIGN
AB Background Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait.
   Methods and Results We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical + behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50 +/- 5 years. We performed a meta-analysis of 4 genomewide association studies (total n = 11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P < 2.0 x 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol.
   Conclusion A common single-nucleotide polymorphismin the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.
C1 [Allen, Norrina B.; Lloyd-Jones, Donald; Rasmussen-Torvik, Laura; Baldridge, Abigail S.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
   [Hwang, Shih-Jen; Fox, Caroline S.; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA.
   [Hwang, Shih-Jen; Levy, Daniel; Cupples, L. Adrienne; Fox, Caroline S.; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA.
   [Fornage, Myriam; Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
   [Thanassoulis, George; Dufresne, Line] McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ, Canada.
   [Thanassoulis, George; Dufresne, Line] McGill Univ, Ctr Hlth, Res Inst, Prevent & Genom Cardiol, Montreal, PQ, Canada.
   [Thanassoulis, George] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
   [Daviglus, Martha] Univ Illinois, Chicago, IL USA.
   [Reis, Jared] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Rotter, Jerome] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
   [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA.
   [Allison, Mathew] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA.
   [Pankow, James S.] Univ Minnesota, Minneapolis, MN USA.
   [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Allen, NB (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM Norrina-allen@northwestern.edu
RI Johnson, Andrew/G-6520-2013; 
OI Allison, Matthew/0000-0003-0777-8272
FU Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE)
   consortium; CHARGE Subclinical Atherosclerosis/Coronary Heart Disease
   Working Group
FX We acknowledge the important role of the Cohorts for Heart and Aging
   Research in Genome Epidemiology (CHARGE) consortium and the
   collaboration of the CHARGE Subclinical Atherosclerosis/Coronary Heart
   Disease Working Group in the development and support of this manuscript.
NR 43
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD MAY
PY 2016
VL 175
BP 112
EP 120
DI 10.1016/j.ahj.2015.12.022
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DL5CP
UT WOS:000375655200014
PM 27179730
ER

PT J
AU Yang, HP
   Murphy, KR
   Pfeiffer, RM
   George, N
   Garcia-Closas, M
   Lissowska, J
   Brinton, LA
   Wentzensen, N
AF Yang, Hannah P.
   Murphy, Kelsey R.
   Pfeiffer, Ruth M.
   George, Neena
   Garcia-Closas, Montserrat
   Lissowska, Jolanta
   Brinton, Louise A.
   Wentzensen, Nicolas
TI Lifetime Number of Ovulatory Cycles and Risks of Ovarian and Endometrial
   Cancer Among Postmenopausal Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE age at menarche; age at menopause; endometrial cancer; incessant
   ovulation; lifetime ovulatory cycles; ovarian cancer; ovulation
ID INCESSANT OVULATION; REPRODUCTIVE FACTORS; MENSTRUAL-CYCLE;
   UNITED-STATES; MUTANT P53; MENOPAUSE; OVEREXPRESSION; PATHOGENESIS;
   HYPOTHESIS
AB Previous studies have shown that a greater number of ovulatory cycles, cumulatively summed as lifetime number of ovulatory cycles (LOC), increases ovarian cancer risk, but there is no uniform algorithm with which to compute LOC. The association between LOC and endometrial cancer is less certain. Accordingly, we identified 14 different LOC algorithms in a literature review and calculated LOCs in the Polish Cancer Study (2001-2003). We evaluated the associations of LOC with ovarian and endometrial cancer risks using unconditional logistic regression, with and without adjustment for individual risk factors used in the LOC computations. Our analysis included 302 ovarian cancer cases with 1,356 controls and 532 endometrial cancer cases with 1,286 controls. We found a high correlation between LOC values among the combined controls (r a parts per thousand yen 0.88) and identified 5 groups of similar LOC algorithms. A LOC value in the highest quartile was associated with ovarian cancer risk as computed by 2 algorithms (odds ratio (OR) = 2.22 (95% confidence interval (CI): 1.07, 4.62) and OR = 2.44 (95% CI: 1.22, 4.87)) and with endometrial cancer risk as computed by 1 algorithm (OR = 1.95, 95% CI: 1.11, 3.44). LOC algorithms using a core set of variables widely available in epidemiologic studies may be independently associated with risk of gynecological cancers beyond the contribution of the individual risk factors, such as ages at menopause and menarche.
C1 [Yang, Hannah P.; Murphy, Kelsey R.; Pfeiffer, Ruth M.; Garcia-Closas, Montserrat; Brinton, Louise A.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-238, Rockville, MD 20892 USA.
   [George, Neena] Drexel Univ, Dornsife Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
RP Yang, HP (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-238, Rockville, MD 20892 USA.
EM yanghan@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics Intramural Research Program
   of the National Institutes of Health, National Cancer Institute
FX This research was supported by the Division of Cancer Epidemiology and
   Genetics Intramural Research Program of the National Institutes of
   Health, National Cancer Institute.
NR 34
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U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAY 1
PY 2016
VL 183
IS 9
BP 800
EP 814
DI 10.1093/aje/kwv308
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM1HZ
UT WOS:000376097600005
PM 27190045
ER

PT J
AU Kummet, CM
   Moreno, LM
   Wilcox, AJ
   Romitti, PA
   Deroo, LA
   Munger, RG
   Lie, RT
   Wehby, GL
AF Kummet, Colleen M.
   Moreno, Lina M.
   Wilcox, Allen J.
   Romitti, Paul A.
   Deroo, Lisa A.
   Munger, Ronald G.
   Lie, Rolv T.
   Wehby, George L.
TI Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large
   International Population-Based Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth defects; cleft lip; cleft palate; oral clefts; passive smoking;
   secondhand smoke; smoking
ID QUALITY-OF-LIFE; OROFACIAL CLEFTS; MATERNAL SMOKING;
   ACADEMIC-ACHIEVEMENT; BIRTH-DEFECTS; CHILDREN; HEALTH; VARIANTS; PALATE
AB Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.
C1 [Kummet, Colleen M.; Romitti, Paul A.; Wehby, George L.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
   [Moreno, Lina M.] Univ Iowa, Dept Orthodont, Coll Dent, Iowa City, IA USA.
   [Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC USA.
   [Deroo, Lisa A.; Lie, Rolv T.] Univ Bergen, Fac Med & Dent, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
   [Munger, Ronald G.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA.
   [Munger, Ronald G.] Utah State Univ, Dept Nutr Dietet & Food Sci, Coll Agr & Appl Sci, Logan, UT 84322 USA.
   [Wehby, George L.] Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, 145 N Riverside Dr,100 Coll Publ Hlth Bldg, Iowa City, IA 52242 USA.
   [Wehby, George L.] Univ Iowa, Dept Econ, Coll Liberal Arts & Sci, Iowa City, IA 52242 USA.
   [Wehby, George L.] Univ Iowa, Dept Prevent & Community Dent, Coll Dent, Iowa City, IA USA.
   [Wehby, George L.] Univ Iowa, Publ Policy Ctr, Iowa City, IA USA.
RP Wehby, GL (reprint author), Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, 145 N Riverside Dr,100 Coll Publ Hlth Bldg, Iowa City, IA 52242 USA.
EM george-wehby@uiowa.edu
OI Wilcox, Allen/0000-0002-3376-1311
FU National Institute of Dental and Craniofacial Research, US National
   Institutes of Health (NIH) [1 R01 DE020895]; Intramural Research Program
   of the National Institute of Environmental Health Sciences (NIEHS), NIH
   [ZIA-ES-49027]; Eunice Kennedy Shriver National Institute of Child
   Health and Human Development, NIH [R01 HD39061]; US Centers for Disease
   Control and Prevention [U01-DD000492, U01-D000698, U01-DD001035];
   NIEHS/NIH Intramural Research Program; Norwegian Research Council; NIH
FX This work was supported by the National Institute of Dental and
   Craniofacial Research, US National Institutes of Health (NIH) (grant 1
   R01 DE020895); the Intramural Research Program of the National Institute
   of Environmental Health Sciences (NIEHS), NIH (grant ZIA-ES-49027); the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, NIH (grant R01 HD39061); and the US Centers for Disease
   Control and Prevention (grants U01-DD000492, U01-D000698, and
   U01-DD001035). The Norway Facial Clefts Study was supported by the
   NIEHS/NIH Intramural Research Program and the Norwegian Research
   Council. The Norwegian Mother and Child Cohort Study was supported by
   the NIH, the NIEHS/NIH Intramural Research Program, and the Norwegian
   Research Council.
NR 28
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U1 8
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAY 1
PY 2016
VL 183
IS 9
BP 834
EP 841
DI 10.1093/aje/kwv279
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM1HZ
UT WOS:000376097600008
PM 27045073
ER

PT J
AU Grigorova, YN
   Juhasz, O
   Zernetkina, V
   Fishbein, KW
   Lakatta, EG
   Fedorova, OV
   Bagrov, AY
AF Grigorova, Yulia N.
   Juhasz, Ondrej
   Zernetkina, Valentina
   Fishbein, Kenneth W.
   Lakatta, Edward G.
   Fedorova, Olga V.
   Bagrov, Alexei Y.
TI Aortic Fibrosis, Induced by High Salt Intake in the Absence of
   Hypertensive Response, Is Reduced by a Monoclonal Antibody to
   Marinobufagenin
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; high salt intake; hypertention; marinobufagenin;
   monoclonal antibody; Na/K-ATPase; vascular fibrosis
ID ENDOGENOUS CARDIOTONIC STEROIDS; NACL-SENSITIVE HYPERTENSION; LOWERS
   BLOOD-PRESSURE; NA/K-ATPASE; UREMIC CARDIOMYOPATHY; RATS; HYPERTROPHY;
   FAILURE; SHIFTS
AB BACKGROUND
   Marinobufagenin (MBG) is an endogenous Na/K-ATPase inhibitor, a natriuretic and a vasoconstrictor. MBG is implicated in salt-sensitive hypertension, cardiac hypertrophy, and initiate the pro-fibrotic signaling. Previously it was demonstrated that immunoneutralization of an endogenous MBG by 3E9 anti-MBG-antibody (mAb) in vivo lowered blood pressure (BP) and reversed cardiac fibrosis in salt-sensitive, and in partially nephrectomized rats. In the present study, we investigated whether mAb alleviates vascular remodeling induced in normotensive rats on high salt intake.
   METHODS
   Wistar rats (5 months old) received normal (CTRL; n = 8) or high salt intake (2% NaCl in drinking water) for 4 weeks (n = 16). Rats from the group on a high salt intake were administered vehicle (SALT; n = 8) or mAb (50 A mu g/kg) (SALT-AB; n = 8) during the last week of high salt diet. BP, erythrocyte Na/K-ATPase activity, levels of MBG in plasma and 24-hour urine, and sensitivity of aortic explants to the vasorelaxant effect of sodium nitroprusside (SNP) were measured. Aortic collagen abundance was determined immunohistochemically.
   RESULTS
   In SALT vs. CTRL, heightened levels of MBG were associated with inhibition of erythrocyte Na/K-ATPase in the absence of BP changes. High salt intake was accompanied by a 2.5-fold increase in aortic collagen abundance and by a reduction of sensitivity of aortic explants to the vasorelaxant effect of SNP following endothelin-1-induced constriction. In the SALT-AB group, all NaCl-mediated effects were reversed by immunoneutralization of MBG.
   CONCLUSIONS
   High salt intake in young normotensive rats can induce vascular fibrosis via pressure-independent/MBG-dependent mechanisms, and this remodeling is reduced by immunoneutralization of MBG.
C1 [Grigorova, Yulia N.; Juhasz, Ondrej; Zernetkina, Valentina; Fishbein, Kenneth W.; Lakatta, Edward G.; Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, NIH, Baltimore, MD 21224 USA.
   [Grigorova, Yulia N.] Fed Almazov Med Res Ctr, St Petersburg, Russia.
   [Grigorova, Yulia N.] IM Sechenov Evolutionary Physiol & Biochem Inst, Thorez Pr 44, St Petersburg 194223, Russia.
RP Bagrov, AY (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM bagrova@mail.nih.gov
OI Fishbein, Kenneth/0000-0002-6353-4603
FU Intramural Research Program, National Institute on Aging, National
   Institutes of Health
FX This work was supported by Intramural Research Program, National
   Institute on Aging, National Institutes of Health. We are grateful to
   Ruth Sadler for editorial assistance.
NR 26
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U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD MAY
PY 2016
VL 29
IS 5
BP 641
EP 646
DI 10.1093/ajh/hpv155
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DM1ID
UT WOS:000376098000014
PM 26350300
ER

PT J
AU Steeves, JA
   Fitzhugh, EC
   Bradwin, G
   McGlynn, KA
   Platz, EA
   Joshu, CE
AF Steeves, J. A.
   Fitzhugh, E. C.
   Bradwin, G.
   McGlynn, K. A.
   Platz, E. A.
   Joshu, C. E.
TI Cross-sectional association between physical activity and serum
   testosterone levels in US men: results from NHANES 1999-2004
SO ANDROLOGY
LA English
DT Article
DE hormones; physical activity; testosterone
ID LIFE-STYLE FACTORS; MIDDLE-AGED MEN; ENDOGENOUS SEX-HORMONES; 3RD
   NATIONAL-HEALTH; METABOLIC SYNDROME; OLDER MEN; CARDIOVASCULAR-DISEASE;
   PLASMA TESTOSTERONE; TESTICULAR FUNCTION; STEROID-HORMONES
AB Testosterone levels and physical activity each play important roles in men's health, but the relationship between the two remains unclear. We evaluated the cross-sectional association between self-reported total physical activity and serum testosterone levels in 738 men (mean age 42.4years, range 20-85years) who participated in National Health and Nutrition Examination Survey 1999-2004. We compared geometric mean testosterone concentrations measured by radioimmunoassay (RIA) and calculated the odds ratio (OR) of having low or low normal testosterone (3.46ng/mL) across tertiles of total physical activity in all men, and men stratified by age (20-49, 50years), and obesity status (BMI<30, 30kg/m(2)). The geometric mean testosterone concentration was 5.31ng/mL; 18.6% of the men had low or low normal serum testosterone levels. Physical activity tertiles were not associated with testosterone levels overall, or when stratified by age or obesity status. Similarly, there was no association between physical activity tertiles and the odds of low or low normal testosterone, overall or by age. However, among non-obese men, those in the highest physical activity tertile were significantly less likely to have low or low normal testosterone than those in the lowest tertile (OR 0.50; 95% CI=0.26-0.95); there was no association among obese men. Greater physical activity was not associated with testosterone levels, but may be associated with a reduced odds of low or low normal testosterone in non-obese men, but not in obese men.
C1 [Steeves, J. A.] Maryville Coll, Div Educ, Maryville, TN USA.
   [Fitzhugh, E. C.] Univ Tennessee, Dept Kinesiol Recreat & Sport Studies, Knoxville, TN USA.
   [Bradwin, G.] Boston Childrens Hosp, Boston, MA USA.
   [McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Platz, E. A.; Joshu, C. E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP McGlynn, KA (reprint author), NCI Shady Grove, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9776, Bethesda, MD 20892 USA.
EM mcglynnk@mail.nih.gov
FU National Cancer Institute; Seraph Foundation; Prostate Cancer Foundation
FX Steeves, J. A. was supported as a Cancer Prevention Fellow by the
   National Cancer Institute. Joshu, C. E. was supported by grants from the
   Seraph Foundation and the Prostate Cancer Foundation. Support for the
   hormone assays was provided by the National Institutes of Health
   Intramural Research Program to McGlynn, K. A.
NR 54
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
EI 2047-2927
J9 ANDROLOGY-US
JI Andrology
PD MAY
PY 2016
VL 4
IS 3
BP 465
EP 472
DI 10.1111/andr.12169
PG 8
WC Andrology
SC Endocrinology & Metabolism
GA DL8HG
UT WOS:000375881200014
PM 26991734
ER

PT J
AU Sapra, KJ
   Eisenberg, ML
   Kim, S
   Chen, Z
   Louis, GMB
AF Sapra, K. J.
   Eisenberg, M. L.
   Kim, S.
   Chen, Z.
   Louis, G. M. Buck
TI Choice of underwear and male fecundity in a preconception cohort of
   couples
SO ANDROLOGY
LA English
DT Article
DE infertility; lifestyle; semen quality; time-to-pregnancy; underwear
ID MODIFIABLE RISK-FACTORS; SEMEN QUALITY; SCROTAL TEMPERATURE; SPERM
   CONCENTRATION; NORMAL MEN; LIFE; FERTILITY; INTEGRITY; INFERTILITY;
   MORPHOLOGY
AB Our objective was to investigate the relationship between male underwear-type worn during daytime/bedtime and male fecundity as measured by semen quality and time-to-pregnancy. We used data from a prospective preconception cohort conducted in 16 counties in Michigan and Texas, USA. 501 couples were enrolled and followed for 12months of trying, which facilitated capture of time-to-pregnancy (in cycles), 6-cycle conception delay, and 12-month infertility. Male partners provided semen samples via in-home collection for next-day semen analysis comprised of 35 semen quality endpoints. At enrollment, men provided information on type of underwear worn during daytime and bedtime and were classified into 6 categories by underwear choice (n=491): (i) briefs day/night, (ii) boxer-briefs day/night, (iii) boxers day/night, (iv) briefs day and boxers/none at night, (v) boxer-briefs day and boxers/none at night, (vi) boxers day and none at night. 473 (96%) men had semen analysis performed. Men switching from their usual daytime underwear to boxers/none for bed (groups 4, 5, 6) had the most evidence of change in semen quality endpoints (10 of 11 differences) relative to men wearing briefs day/night (group 1). Group 4 men had lower percent of sperm with coiled tail (=-0.18, 95% CI: -0.35, -0.01), higher percent round (=0.22, 95% CI: 0.01, 0.42), number of immature sperm (=0.44, 95% CI: 0.11, 0.77), and amplitude head displacement (=0.57, 95% CI: 0.10, 1.03). Group 5 men had higher sperm head perimeter (=0.17, 95% CI: 0.002, 0.34), amplitude head displacement (=0.47, 95% CI: 0.03, 0.91), percent cytoplasmic droplet (=0.44, 95% CI: 0.11, 0.77) and high DNA stainability (=0.39, 95% CI: 0.01, 0.78). After false discovery rate control, no differences remained significant. No significant differences in time-to-pregnancy, conception delay, or infertility were observed. In summary, male underwear choice is associated with few differences in semen parameters; no association with time-to-pregnancy is observed providing reassurance to couples attempting pregnancy.
C1 [Sapra, K. J.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
   [Eisenberg, M. L.] Stanford Univ, Dept Urol & Obstet & Gynecol, Stanford, CA 94305 USA.
   [Kim, S.; Chen, Z.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Rockville, MD USA.
RP Sapra, KJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
EM katherine.sapra@nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358,
   HHSN27500001]
FX This work was supported by the Intramural Research Program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (NICHD) (contracts N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358,
   HHSN27500001). The authors acknowledge the Reproductive Health
   Assessment Team, Biomonitoring and Health Assessment Branch, National
   Institute of Occupational Safety and Health, for conducting the semen
   analyses through a Memo of Understanding with the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development.
NR 41
TC 0
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U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
EI 2047-2927
J9 ANDROLOGY-US
JI Andrology
PD MAY
PY 2016
VL 4
IS 3
BP 500
EP 508
DI 10.1111/andr.12163
PG 9
WC Andrology
SC Endocrinology & Metabolism
GA DL8HG
UT WOS:000375881200019
PM 26939021
ER

PT J
AU Friesen, MC
   Wheeler, DC
   Vermeulen, R
   Locke, SJ
   Zaebst, DD
   Koutros, S
   Pronk, A
   Colt, JS
   Baris, D
   Karagas, MR
   Malats, N
   Schwenn, M
   Johnson, A
   Armenti, KR
   Rothman, N
   Stewart, PA
   Kogevinas, M
   Silverman, DT
AF Friesen, Melissa C.
   Wheeler, David C.
   Vermeulen, Roel
   Locke, Sarah J.
   Zaebst, Dennis D.
   Koutros, Stella
   Pronk, Anjoeka
   Colt, Joanne S.
   Baris, Dalsu
   Karagas, Margaret R.
   Malats, Nuria
   Schwenn, Molly
   Johnson, Alison
   Armenti, Karla R.
   Rothman, Nathanial
   Stewart, Patricia A.
   Kogevinas, Manolis
   Silverman, Debra T.
TI Combining Decision Rules from Classification Tree Models and Expert
   Assessment to Estimate Occupational Exposure to Diesel Exhaust for a
   Case-Control Study
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE case-control; diesel exhaust; exposure assessment methodology;
   occupational exposure; statistical learning
ID CARCINOGENS
AB To efficiently and reproducibly assess occupational diesel exhaust exposure in a Spanish case-control study, we examined the utility of applying decision rules that had been extracted from expert estimates and questionnaire response patterns using classification tree (CT) models from a similar US study.
   First, previously extracted CT decision rules were used to obtain initial ordinal (0-3) estimates of the probability, intensity, and frequency of occupational exposure to diesel exhaust for the 10 182 jobs reported in a Spanish case-control study of bladder cancer. Second, two experts reviewed the CT estimates for 350 jobs randomly selected from strata based on each CT rule's agreement with the expert ratings in the original study [agreement rate, from 0 (no agreement) to 1 (perfect agreement)]. Their agreement with each other and with the CT estimates was calculated using weighted kappa (kappa (w)) and guided our choice of jobs for subsequent expert review. Third, an expert review comprised all jobs with lower confidence (low-to-moderate agreement rates or discordant assignments, n = 931) and a subset of jobs with a moderate to high CT probability rating and with moderately high agreement rates (n = 511). Logistic regression was used to examine the likelihood that an expert provided a different estimate than the CT estimate based on the CT rule agreement rates, the CT ordinal rating, and the availability of a module with diesel-related questions.
   Agreement between estimates made by two experts and between estimates made by each of the experts and the CT estimates was very high for jobs with estimates that were determined by rules with high CT agreement rates (kappa (w): 0.81-0.90). For jobs with estimates based on rules with lower agreement rates, moderate agreement was observed between the two experts (kappa (w): 0.42-0.67) and poor-to-moderate agreement was observed between the experts and the CT estimates (kappa (w): 0.09-0.57). In total, the expert review of 1442 jobs changed 156 probability estimates, 128 intensity estimates, and 614 frequency estimates. The expert was more likely to provide a different estimate when the CT rule agreement rate was < 0.8, when the CT ordinal ratings were low to moderate, or when a module with diesel questions was available.
   Our reliability assessment provided important insight into where to prioritize additional expert review; as a result, only 14% of the jobs underwent expert review, substantially reducing the exposure assessment burden. Overall, we found that we could efficiently, reproducibly, and reliably apply CT decision rules from one study to assess exposure in another study.
C1 [Friesen, Melissa C.; Locke, Sarah J.; Koutros, Stella; Colt, Joanne S.; Baris, Dalsu; Rothman, Nathanial; Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA.
   [Wheeler, David C.] Virginia Commonwealth Univ, Dept Biostat, Med Coll Virginia Campus, Richmond, VA 23298 USA.
   [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
   [Zaebst, Dennis D.] WESTAT Corp, Rockville, MD 20850 USA.
   [Pronk, Anjoeka] TNO, NL-3700 Zeist, Netherlands.
   [Karagas, Margaret R.] Geisel Sch Med Dartmouth, Hanover, NH 03756 USA.
   [Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain.
   [Schwenn, Molly] Maine Canc Registry, Augusta, ME 04333 USA.
   [Johnson, Alison] Vermont Canc Registry, Burlington, VT 05402 USA.
   [Armenti, Karla R.] New Hampshire Dept Hlth & Human Serv, Div Publ Hlth Serv, Bur Publ Hlth Stat & Informat, Concord, NH 03301 USA.
   [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA.
   [Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain.
   [Kogevinas, Manolis] CIBER Epidemiol & Salud Publ, Barcelona 28029, Spain.
   [Kogevinas, Manolis] IMIM Hosp del Mar Med Res Inst, Barcelona 08003, Spain.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA.
EM friesenmc@mail.nih.gov
RI Friesen, Melissa/A-5362-2009; Kogevinas, Manolis/C-3918-2017; Vermeulen,
   Roel/F-8037-2011; 
OI Vermeulen, Roel/0000-0003-4082-8163; Malats, Nuria/0000-0003-2538-3784
FU Intramural Research Program of the Division of Cancer Epidemiology and
   Genetics, National Cancer Institute, National Institutes of Health
FX This study was funded by the Intramural Research Program of the Division
   of Cancer Epidemiology and Genetics, National Cancer Institute, National
   Institutes of Health. We also thank Dr M. Garcia-Closas for her
   involvement in the Spanish Bladder Cancer Study. The authors report no
   conflicts of interest.
NR 15
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD MAY
PY 2016
VL 60
IS 4
BP 467
EP 478
DI 10.1093/annhyg/mev095
PG 12
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA DM1JD
UT WOS:000376100600006
PM 26732820
ER

PT J
AU Ercan, E
   Magro-Checa, C
   Valabregue, R
   Branzoli, F
   Wood, ET
   Steup-Beekman, GM
   Webb, AG
   Huizinga, TWJ
   van Buchem, MA
   Ronen, I
AF Ercan, Ece
   Magro-Checa, Cesar
   Valabregue, Romain
   Branzoli, Francesca
   Wood, Emily T.
   Steup-Beekman, Gerda M.
   Webb, Andrew G.
   Huizinga, Tom W. J.
   van Buchem, Mark A.
   Ronen, Itamar
TI Glial and axonal changes in systemic lupus erythematosus measured with
   diffusion of intracellular metabolites
SO BRAIN
LA English
DT Article
DE neuropsychiatry; gliosis; biomarkers; inflammation; astrocytes
ID MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY;
   MULTIPLE-SCLEROSIS; WHITE-MATTER; SPATIAL STATISTICS; CEREBRAL-ISCHEMIA;
   REVISED CRITERIA; NMR-SPECTROSCOPY; CORPUS-CALLOSUM; BRAIN IMAGES
AB CNS involvement is common in systemic lupus erythematosus (SLE). Using diffusion-weighted imaging, Ercan et al. explore the link between cell-specific microstructural changes and neuropsychiatric symptoms. Increased diffusivity of predominantly glial metabolites is observed in SLE patients with previous CNS symptoms, and may be a marker for inflammation-related glial reactivity.CNS involvement is common in systemic lupus erythematosus (SLE). Using diffusion-weighted imaging, Ercan et al. explore the link between cell-specific microstructural changes and neuropsychiatric symptoms. Increased diffusivity of predominantly glial metabolites is observed in SLE patients with previous CNS symptoms, and may be a marker for inflammation-related glial reactivity.Systemic lupus erythematosus is an inflammatory autoimmune disease with multi-organ involvement. Central nervous system involvement in systemic lupus erythematosus is common and results in several neurological and psychiatric symptoms that are poorly linked to standard magnetic resonance imaging outcome. Magnetic resonance imaging methods sensitive to tissue microstructural changes, such as diffusion tensor imaging and magnetization transfer imaging, show some correlation with neuropsychiatric systemic lupus erythematosus (NPSLE) symptoms. Histological examination of NPSLE brains reveals presence of cerebral oedema, loss of neurons and myelinated axons, microglial proliferation and reactive astrocytosis, microinfacrts and diffuse ischaemic changes, all of which can affect both diffusion tensor imaging and magnetization transfer imaging in a non-specific manner. Here we investigated the underlying cell-type specific microstructural alterations in the brain of patients with systemic lupus erythematosus with and without a history of central nervous system involvement. We did so combining diffusion tensor imaging with diffusion-weighted magnetic resonance spectroscopy, a powerful tool capable of characterizing cell-specific cytomorphological changes based on diffusion of intracellular metabolites. We used a 7 T magnetic resonance imaging scanner to acquire T-1-weighted images, diffusion tensor imaging datasets, and single volume diffusion-weighted magnetic resonance spectroscopy data from the anterior body of the corpus callosum of 13 patients with systemic lupus erythematosus with past NPSLE, 16 patients with systemic lupus erythematosus without past NPSLE, and 19 healthy control subjects. Group comparisons were made between patients with systemic lupus erythematosus with/without past NPSLE and healthy controls on diffusion tensor imaging metrics and on diffusion coefficients of three brain metabolites: the exclusively neuronal/axonal N-acetylaspartate, and the predominantly glial creatine + phosphocreatine and choline compounds. In patients with systemic lupus erythematosus with past NPSLE, significantly higher diffusion tensor imaging mean and radial diffusivities were accompanied by a significantly higher intracellular diffusion of total creatine (0.202 +/- 0.032 mu m(2)/ms, P = 0.018) and total choline (0.142 +/- 0.031 mu m(2)/ms, P = 0.044) compared to healthy controls (0.171 +/- 0.024 mu m(2)/ms, 0.124 +/- 0.018 mu m(2)/ms, respectively). Total N-acetylaspartate, total creatine and total choline diffusion values from all patients with systemic lupus erythematosus correlated positively with systemic lupus erythematosus disease activity index score (P = 0.033, P = 0.040, P = 0.008, respectively).
   Our results indicate that intracellular alterations, and in particular changes in glia, as evidenced by increase in the average diffusivities of total choline and total creatine, correlate with systemic lupus erythematosus activity. The higher diffusivity of total creatine and total choline in patients with NPSLE, as well as the positive correlation of these diffusivities with the systemic lupus erythematosus disease activity index are in line with cytomorphological changes in reactive glia, suggesting that the diffusivities of choline compounds and of total creatine are potentially unique markers for glial reactivity in response to inflammation.
C1 [Ercan, Ece; Webb, Andrew G.; Ronen, Itamar] Leiden Univ, Dept Radiol, CJ Gorter Ctr High Field MRI, Med Ctr, Leiden, Netherlands.
   [Magro-Checa, Cesar; Steup-Beekman, Gerda M.; Huizinga, Tom W. J.] Leiden Univ, Dept Rheumatol, Med Ctr, Leiden, Netherlands.
   [Valabregue, Romain; Branzoli, Francesca] Ctr NeuroImaging Res CENIR, Inst Cerveau & Moelle Epiniere ICM, Paris, France.
   [Valabregue, Romain; Branzoli, Francesca] Univ Paris 06, Sorbonne Univ, Inserm UMR S 1127, CNRS UMR 7225, F-75013 Paris, France.
   [Wood, Emily T.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA.
   [Wood, Emily T.] NINDS, Translat Neuroradiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Wood, Emily T.] NINDS, Neuroimmunol Clin 4, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [van Buchem, Mark A.] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands.
RP Ronen, I (reprint author), Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
EM i.ronen@lumc.nl
OI Wood, Emily/0000-0003-0395-4849; Magro Checa, Cesar/0000-0002-5685-3091;
   Ercan, Ece/0000-0002-8187-2075
FU Dutch Arthritis Association (Reumafonds) [2010_0000135]; National
   Institute of Neurological Disorders and Stroke; NINDS Competitive
   Intramural Graduate Fellowship award; Nederlandse Organisatie voor
   Wetenschappelijk Onderzoek: Grootschalige Onderzoeksfaciliteiten (Dutch
   Organization for Scientific Research: Large-Scale Research Facilities)
   [176.010.2005]
FX A.E.E. was supported by a Dutch Arthritis Association (Reumafonds) grant
   (# 2010_0000135). E.T.W. was supported by Intramural Research Program of
   the National Institute of Neurological Disorders and Stroke and is the
   recipient of an NINDS Competitive Intramural Graduate Fellowship award.
   The C.J. Gorter Center for High Field MRI is supported by grant number
   176.010.2005 from the Nederlandse Organisatie voor Wetenschappelijk
   Onderzoek: Grootschalige Onderzoeksfaciliteiten (Dutch Organization for
   Scientific Research: Large-Scale Research Facilities).
NR 52
TC 2
Z9 2
U1 5
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD MAY 1
PY 2016
VL 139
BP 1447
EP 1457
DI 10.1093/brain/aww031
PN 5
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DM1LQ
UT WOS:000376107200015
PM 26969685
ER

PT J
AU Murphy, J
   Sherman, ME
   Browne, EP
   Caballero, AI
   Punska, EC
   Pfeiffer, RM
   Yang, HP
   Lee, M
   Yang, H
   Gierach, GL
   Arcaro, KF
AF Murphy, Jeanne
   Sherman, Mark E.
   Browne, Eva P.
   Caballero, Ana I.
   Punska, Elizabeth C.
   Pfeiffer, Ruth M.
   Yang, Hannah P.
   Lee, Maxwell
   Yang, Howard
   Gierach, Gretchen L.
   Arcaro, Kathleen F.
TI Potential of breastmilk analysis to inform early events in breast
   carcinogenesis: rationale and considerations
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Review
DE Human breastmilk; Breast cancer; Prevention; Biomarkers; Methods
ID POSTPARTUM MAMMARY-GLAND; FINE-NEEDLE-ASPIRATION; CANCER-RISK; PROMOTER
   METHYLATION; DUCTAL LAVAGE; EPITHELIAL-CELLS; WOMEN; LACTATION; TISSUE;
   PROGRESSION
AB This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g., hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article, we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer.
C1 [Murphy, Jeanne] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Browne, Eva P.; Caballero, Ana I.; Punska, Elizabeth C.; Arcaro, Kathleen F.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA.
   [Pfeiffer, Ruth M.; Yang, Hannah P.; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Lee, Maxwell; Yang, Howard] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Murphy, Jeanne] NCI, Breast & Gynecol Canc Res Grp, 9609 Med Ctr Dr,Off 5E-332, Rockville, MD 20892 USA.
RP Murphy, J (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.; Murphy, J (reprint author), NCI, Breast & Gynecol Canc Res Grp, 9609 Med Ctr Dr,Off 5E-332, Rockville, MD 20892 USA.
EM jeanne.murphy@nih.gov
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU Intramural NIH HHS [Z99 CA999999]
NR 61
TC 0
Z9 0
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD MAY
PY 2016
VL 157
IS 1
BP 13
EP 22
DI 10.1007/s10549-016-3796-x
PG 10
WC Oncology
SC Oncology
GA DM4FW
UT WOS:000376303100002
PM 27107568
ER

PT J
AU Usset, JL
   Raghavan, R
   Tyrer, JP
   McGuire, V
   Sieh, W
   Webb, P
   Chang-Claude, J
   Rudolph, A
   Anton-Culver, H
   Berchuck, A
   Brinton, L
   Cunningham, JM
   DeFazio, A
   Doherty, JA
   Edwards, RP
   Gayther, SA
   Gentry-Maharaj, A
   Goodman, MT
   Hogdall, E
   Jensen, A
   Johnatty, SE
   Kiemeney, LA
   Kjaer, SK
   Larson, MC
   Lurie, G
   Massuger, L
   Menon, U
   Modugno, F
   Moysich, KB
   Ness, RB
   Pike, MC
   Ramus, SJ
   Rossing, MA
   Rothstein, J
   Song, H
   Thompson, PJ
   van den Berg, DJ
   Vierkant, RA
   Wang-Gohrke, S
   Wentzensen, N
   Whittemore, AS
   Wilkens, LR
   Wu, AH
   Yang, HN
   Pearce, CL
   Schildkraut, JM
   Pharoah, P
   Goode, EL
   Fridley, BL
AF Usset, Joseph L.
   Raghavan, Rama
   Tyrer, Jonathan P.
   McGuire, Valerie
   Sieh, Weiva
   Webb, Penelope
   Chang-Claude, Jenny
   Rudolph, Anja
   Anton-Culver, Hoda
   Berchuck, Andrew
   Brinton, Louise
   Cunningham, Julie M.
   DeFazio, Anna
   Doherty, Jennifer A.
   Edwards, Robert P.
   Gayther, Simon A.
   Gentry-Maharaj, Aleksandra
   Goodman, Marc T.
   Hogdall, Estrid
   Jensen, Allan
   Johnatty, Sharon E.
   Kiemeney, Lambertus A.
   Kjaer, Susanne K.
   Larson, Melissa C.
   Lurie, Galina
   Massuger, Leon
   Menon, Usha
   Modugno, Francesmary
   Moysich, Kirsten B.
   Ness, Roberta B.
   Pike, Malcolm C.
   Ramus, Susan J.
   Rossing, Mary Anne
   Rothstein, Joseph
   Song, Honglin
   Thompson, Pamela J.
   van den Berg, David J.
   Vierkant, Robert A.
   Wang-Gohrke, Shan
   Wentzensen, Nicolas
   Whittemore, Alice S.
   Wilkens, Lynne R.
   Wu, Anna H.
   Yang, Hannah
   Pearce, Celeste Leigh
   Schildkraut, Joellen M.
   Pharoah, Paul
   Goode, Ellen L.
   Fridley, Brooke L.
CA Ovarian Canc Assoc Consortium
   Australian Canc Study
TI Assessment of Multifactor Gene-Environment Interactions and Ovarian
   Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BODY-MASS INDEX; SINGLE NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE
   ASSOCIATION; BREAST-CANCER; SUSCEPTIBILITY LOCI; BINDING GLOBULIN;
   ORAL-CONTRACEPTIVES; ENDOMETRIAL CANCER; STEROID-HORMONE; SEX-HORMONES
AB Background: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and nonobese women.
   Methods: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed.
   Results: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology - all, P - 4.9 x 10 (-6)) and ESR1 (rs12661437, endometriosis, histology - all, P - 1.5 x 10 (-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology - endometrioid, P - 8.8 x 10 (-6)).
   Conclusions: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions.
   Impact: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. (C) 2016 AACR.
C1 [Usset, Joseph L.; Raghavan, Rama; Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA.
   [Tyrer, Jonathan P.; Song, Honglin; Pharoah, Paul] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
   [McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
   [Webb, Penelope] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia.
   [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
   [Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
   [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
   [Brinton, Louise; Wentzensen, Nicolas; Yang, Hannah] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
   [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
   [DeFazio, Anna] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Discipline Obstet Gynecol & Neonatol, Westmead, NSW 2145, Australia.
   [Doherty, Jennifer A.] Geisel Sch Med, Dept Epidemiol, Hanover, NH USA.
   [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
   [Gayther, Simon A.; Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
   [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Womens Canc, London, England.
   [Hogdall, Estrid; Jensen, Allan] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
   [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Copenhagen, Denmark.
   [Johnatty, Sharon E.] QIMR Berghofer Med Res Inst, Div Genet & Publ Hlth, Brisbane, Qld, Australia.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
   [Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark.
   [Larson, Melissa C.; Vierkant, Robert A.; Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
   [Lurie, Galina; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
   [Massuger, Leon] Radboud Univ Nijmegen, Med Ctr, Dept Obstet & Gynecol, NL-6525 ED Nijmegen, Netherlands.
   [Modugno, Francesmary] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
   [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
   [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
   [Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
   [Ramus, Susan J.; van den Berg, David J.; Wu, Anna H.; Pearce, Celeste Leigh] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
   [Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
   [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany.
   [Pearce, Celeste Leigh] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Schildkraut, Joellen M.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
   [Pharoah, Paul] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Fridley, BL (reprint author), Univ Kansas, Med Ctr, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM bfridley@kumc.edu
RI Johnatty, Sharon/R-8890-2016; 
OI Johnatty, Sharon/0000-0002-7888-1966; Ramus, Susan/0000-0003-0005-7798
FU Ovarian Cancer Research Fund [PPD/RPCI.07]; European Commission's
   Seventh Framework Programme [223175 - HEALTH-F2-2009-223175]; NIH [P30
   CA168524, R01 CA112523, R01 CA87538, R01 CA58598, R01 CA61107, N01
   CN55424, N01 PC 67001]; Danish Cancer Society [94 22252]; U.S. Army
   Medical Research and Materiel Command [17-01-1-0729]; National Health &
   Medical Research Council of Australia [199600, 400281]; Cancer Councils
   of New South Wales, Victoria, Queensland, South Australi; Tasmania;
   Cancer Foundation of Western Australia; German Federal Ministry of
   Education and Research, Program of Clinical Biomedical Research
   [01GB9401]; German Cancer Research Center; US Army Medical Research and
   Material Command [17-02-1-0669, 17-02-1-0666]; Radboud University
   Nijmegen Medical Centre; Intramural Research Program of the National
   Cancer Institute; Cancer Research UK [C490/A10119, C490/A10124]; Lon V
   Smith Foundation [39420]; California Cancer Research Program
   [00-01389V-20170,2II0200];  [R01 CA122443];  [P30 CA15083];  [P50
   CA136393];  [R01 CA76016];  [U01 CA71966];  [R01 CA16056];  [K07
   CA143047];  [U01 CA69417];  [R01 CA058860];  [P30 CA14089];  [R01
   CA61132];  [N01 PC6701];  [R03 CA113148];  [R03 CA115195];  [R13
   CA110770]
FX The Ovarian Cancer Association Consortium is supported by a grant from
   the Ovarian Cancer Research Fund (PPD/RPCI.07). The COGS project was
   funded through a European Commission's Seventh Framework Programme grant
   (agreement number 223175 - HEALTH-F2-2009-223175). This work was
   supported in part by the NIH [P30 CA168524 (to B.L. Fridley), R01
   CA112523 ( to M.A. Rossing), R01 CA87538 ( to M.A. Rossing), R01 CA58598
   ( to M.T. Goodman), R01 CA61107 ( to A. Jensen, S.K. Kjaer), N01 CN55424
   (to M.T. Goodman), N01 PC 67001(to M.T. Goodman), R01 CA122443 (to
   E.L.Goode), P30 CA15083 (to E.L. Goode), P50 CA136393 (to E.L. Goode),
   R01 CA76016 (to J.M. Schildkraut), U01 CA71966 (to A.S. Whittemore), R01
   CA16056 (to K.B. Moysich), K07 CA143047 (to W. Sieh), U01 CA69417 (to W.
   Sieh), R01 CA058860 (to H. Anton-Culver), P30 CA14089 (to C.L. Pearce
   and S.J. Ramus), R01 CA61132 (to M.C. Pike), N01 PC67010 (to C.L.
   Pearce), R03 CA113148 (to C.L. Pearce), R03 CA115195 (to C.L. Pearce),
   R13 CA110770 (to F. Modugno)]; Danish Cancer Society (94 22252); Mermaid
   1; U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729),
   National Health & Medical Research Council of Australia (199600 and
   400281); Cancer Councils of New South Wales, Victoria, Queensland, South
   Australia and Tasmania; Cancer Foundation of Western Australia; German
   Federal Ministry of Education and Research, Program of Clinical
   Biomedical Research (01GB9401); German Cancer Research Center; US Army
   Medical Research and Material Command (DAMD17-02-1-0669,
   DAMD17-02-1-0666); Mayo Foundation; Minnesota Ovarian Cancer Alliance;
   Fred C. and Katherine B. Andersen Foundation; Radboud University
   Nijmegen Medical Centre; Intramural Research Program of the National
   Cancer Institute (to N. Wentzensen); Cancer Research UK [C490/A10119 and
   C490/A10124 (to P. Pharoah and H. Song)]; Lon V Smith Foundation
   (LVS-39420); Eve Appeal; OAK Foundation; and California Cancer Research
   Program (00-01389V-20170,2II0200).
NR 70
TC 0
Z9 0
U1 2
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAY
PY 2016
VL 25
IS 5
BP 780
EP 790
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DL7VG
UT WOS:000375847600008
PM 26976855
ER

PT J
AU Sinha, R
   Vogtmann, E
   Chen, J
   Amir, A
   Shi, JX
   Sampson, J
   Flores, R
   Knight, R
   Chia, N
AF Sinha, Rashmi
   Vogtmann, Emily
   Chen, Jun
   Amir, Amnon
   Shi, Jianxin
   Sampson, Joshua
   Flores, Roberto
   Knight, Rob
   Chia, Nicholas
TI Fecal Microbiome in Epidemiologic Studies-Response
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
C1 [Sinha, Rashmi; Vogtmann, Emily] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Vogtmann, Emily] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
   [Chen, Jun; Chia, Nicholas] Mayo Clin, Ctr Individualized Med, Microbiome Program, Rochester, MN USA.
   [Chen, Jun; Chia, Nicholas] Mayo Clin, Hlth Sci Res, Rochester, MN USA.
   [Amir, Amnon; Knight, Rob] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [Shi, Jianxin; Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Flores, Roberto] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
   [Knight, Rob] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA.
   [Chia, Nicholas] Mayo Clin, Dept Surg, Rochester, MN USA.
   [Chia, Nicholas] Mayo Coll, Biomed Engn & Physiol, Rochester, MN USA.
RP Chia, N (reprint author), Mayo Clin, Ctr Individualized Med, Microbiome Program, Rochester, MN USA.; Chia, N (reprint author), Mayo Clin, Hlth Sci Res, Rochester, MN USA.; Chia, N (reprint author), Mayo Clin, Dept Surg, Rochester, MN USA.; Chia, N (reprint author), Mayo Coll, Biomed Engn & Physiol, Rochester, MN USA.; Sinha, R (reprint author), NCI, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM sinhar@nih.gov; Chia.Nicholas@mayo.edu
FU Intramural NIH HHS [Z01 CP010127-12]; NCI NIH HHS [R01 CA179243]; NIDDK
   NIH HHS [P30 DK084567]
NR 5
TC 2
Z9 2
U1 4
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAY
PY 2016
VL 25
IS 5
BP 870
EP 871
DI 10.1158/1055-9965.EPI-16-0161
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DL7VG
UT WOS:000375847600027
PM 26961994
ER

PT J
AU Sun, JH
   Aponte, AM
   Menazza, S
   Gucek, M
   Steenbergen, C
   Murphy, E
AF Sun, Junhui
   Aponte, Angel M.
   Menazza, Sara
   Gucek, Marjan
   Steenbergen, Charles
   Murphy, Elizabeth
TI Additive cardioprotection by pharmacological postconditioning with
   hydrogen sulfide and nitric oxide donors in mouse heart: S-sulfhydration
   vs. S-nitrosylation
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Postconditioning; Hydrogen sulfide; Nitric oxide; S-sulfhydration;
   S-nitrosylation
ID ISCHEMIA-REPERFUSION INJURY; CONTRACTILE FUNCTION; MYOCARDIAL-ISCHEMIA;
   CROSS-TALK; H2S; NO; SYNTHASE; NITROXYL; NITROSOTHIOL; ACTIVATION
AB Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-translational modification on protein cysteine residue(s), i.e. S-sulfhydration (SSH). In this study, we examined whether there are changes in protein SSH associated with cardioprotection induced by treatment with H2S on reperfusion. In addition, we also examined whether there is cross talk between H2S and NO. Compared with control, treatment on reperfusion with NaHS (H2S donor, 100 A mu mol/L) significantly reduced post-ischaemic contractile dysfunction and infarct size. A comparable cardioprotective effect could be also achieved by reperfusion treatment with SNAP (NO donor, 10 A mu mol/L). Interestingly, simultaneous reperfusion with both donors had an additive protective effect. In addition, C-PTIO (NO scavenger, 20 A mu mol/L) eliminated the protection induced by NaHS and also the additive protection by SNAP + NaHS together. Using a modified biotin switch method, we observed a small increase in SSH following NaHS treatment on reperfusion. We also found that NaHS treatment on reperfusion increases SNO to a level comparable to that with SNAP treatment. In addition, there was an additive increase in SNO but not SSH when SNAP and NaHS were added together at reperfusion. Thus, part of the benefit of NaHS is an increase in SNO, and the magnitude of the protective effect is related to the magnitude of the increase in SNO.
C1 [Sun, Junhui; Menazza, Sara; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, 10 Ctr Dr,Bldg 10-Room 8N206, Bethesda, MD 20892 USA.
   [Aponte, Angel M.; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, 10 Ctr Dr,Bldg 10-Room 8N206, Bethesda, MD 20892 USA.
   [Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Sun, JH (reprint author), NHLBI, Syst Biol Ctr, NIH, 10 Ctr Dr,Bldg 10-Room 8N206, Bethesda, MD 20892 USA.
EM sun1@mail.nih.gov
FU NIH/NHLBI Intramural Program; NIH [5R01HL039752]
FX This work was supported by the NIH/NHLBI Intramural Program (J.S., A.A.,
   S.M., M.G., and E.M.) and NIH 5R01HL039752 (C.S.).
NR 49
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Z9 6
U1 5
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAY 1
PY 2016
VL 110
IS 1
BP 96
EP 106
DI 10.1093/cvr/cvw037
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DM1MP
UT WOS:000376109700012
PM 26907390
ER

PT J
AU Salive, ME
AF Salive, Marcel E.
TI Future Research Directions for Multimorbidity Involving Cardiovascular
   Diseases
SO CLINICS IN GERIATRIC MEDICINE
LA English
DT Article
DE Multimorbidity; Aging; Chronic disease; Multiple morbidities
ID MULTIPLE CHRONIC CONDITIONS; OLDER-ADULTS; HEALTH-CARE; MORBIDITY;
   FRAMEWORK
AB Multimorbidity, defined as the co-occurrence of two or more chronic conditions, increases with age and may be found in approximately two-thirds of older adults in population studies, commonly including a variety of cardiovascular risk factors and chronic diseases. This article offers a research agenda for cardiovascular disease from a patient-centered multi morbidity perspective. Definitional issues remain for multimorbidity, along with high interest in understanding the inter-relationships between aging, diseases, treatments, and organ dysfunction in the development and progression of multimorbidity. Clinical trials, practice-based and population based observational studies, and linkages of big data can play a role in improving health outcomes among persons with multimorbidity.
C1 [Salive, Marcel E.] NIA, Div Geriatr & Clin Gerontol, NIH, 7201 Wisconsin Ave,Suite 3c307,MSC 9205, Bethesda, MD 20892 USA.
RP Salive, ME (reprint author), NIA, Div Geriatr & Clin Gerontol, NIH, 7201 Wisconsin Ave,Suite 3c307,MSC 9205, Bethesda, MD 20892 USA.
EM msalive@msn.com
FU Intramural NIH HHS [Z99 AG999999]
NR 15
TC 1
Z9 1
U1 3
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0749-0690
EI 1879-8853
J9 CLIN GERIATR MED
JI Clin. Geriatr. Med.
PD MAY
PY 2016
VL 32
IS 2
BP 399
EP +
DI 10.1016/j.cger.2016.01.008
PG 11
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA DM2XZ
UT WOS:000376212700015
PM 27113155
ER

PT J
AU Bornstein, MH
   Hahn, CS
   Putnick, DL
AF Bornstein, Marc H.
   Hahn, Chun-Shin
   Putnick, Diane L.
TI Long-Term Stability of Core Language Skill in Children With Contrasting
   Language Skills
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE language; stability; development; skill
ID COVARIANCE STRUCTURE-ANALYSIS; EARLY HEAD-START; MEASUREMENT INVARIANCE;
   MISSING DATA; PRESCHOOL-CHILDREN; BEHAVIOR PROBLEMS; EARLY-CHILDHOOD;
   FIT INDEXES; VOCABULARY; SPEECH
AB This 4-wave longitudinal study evaluated stability of core language skill in 421 European American and African American children, half of whom were identified as low (n = 201) and half of whom were average-to-high (n = 220) in later language skill. Structural equation modeling supported loadings of multivariate age-appropriate multisource measures of child language on single latent variables of core language skill at 15 and 25 months and 5 and 11 years. Significant stability coefficients were obtained between language latent variables for children of low and average-to-high language skill, even accounting for child positive social interaction and nonverbal intelligence, maternal education and language, and family home environment. Prospects for children with different language skills and intervention implications are discussed.
C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, Publ Hlth Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, Publ Hlth Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural Research Program of the NIH, NICHD
FX This research was supported by the Intramural Research Program of the
   NIH, NICHD.
NR 75
TC 2
Z9 2
U1 4
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
EI 1939-0599
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 2016
VL 52
IS 5
BP 704
EP 716
DI 10.1037/dev0000111
PG 13
WC Psychology, Developmental
SC Psychology
GA DM2UP
UT WOS:000376203800002
PM 26998572
ER

PT J
AU Lawson, KM
   Davis, KD
   McHale, SM
   Almeida, DM
   Kelly, EL
   King, RB
AF Lawson, Katie M.
   Davis, Kelly D.
   McHale, Susan M.
   Almeida, David M.
   Kelly, Erin L.
   King, Rosalind B.
TI Effects of Workplace Intervention on Affective Well-Being in Employees'
   Children
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE adolescence; affective reactivity; negative and positive affect;
   work-family; workplace intervention
ID PUBERTAL MATURATION; DAILY STRESSORS; NEGATIVE AFFECT; ADOLESCENCE;
   HEALTH; WORK; ASSOCIATION; REACTIVITY; GENDER; FAMILY
AB Using a group-randomized field experimental design, this study tested whether a workplace intervention-designed to reduce work-family conflict-buffered against potential age-related decreases in the affective well-being of employees' children. Daily diary data were collected from 9- to 17-year-old children of parents working in an information technology division of a U.S. Fortune 500 company prior to and 12 months after the implementation of the Support-Transform-Achieve-Results (STAR) workplace intervention. Youth (62 with parents in the STAR group, 41 in the usual-practice group) participated in 8 consecutive nightly phone calls, during which they reported on their daily stressors and affect. Well-being was indexed by positive and negative affect and affective reactivity to daily stressful events. The randomized workplace intervention increased youth positive affect and buffered youth from age-related increases in negative affect and affective reactivity to daily stressors. Future research should test specific conditions of parents' work that may penetrate family life and affect youth well-being.
C1 [Lawson, Katie M.] Ball State Univ, Dept Psychol Sci, 113 North Quad Bldg, Muncie, IN 47306 USA.
   [Davis, Kelly D.] Oregon State Univ, Human Dev & Family Sci, Corvallis, OR 97331 USA.
   [McHale, Susan M.; Almeida, David M.] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA.
   [Kelly, Erin L.] MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA.
   [King, Rosalind B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Lawson, KM (reprint author), Ball State Univ, Dept Psychol Sci, 113 North Quad Bldg, Muncie, IN 47306 USA.
EM kmlawson4@bsu.edu
FU NICHD NIH HHS [U01 HD051276, U01 HD051256, U01 HD051217, U01 HD051218]
NR 26
TC 0
Z9 0
U1 4
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
EI 1939-0599
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 2016
VL 52
IS 5
BP 772
EP 777
DI 10.1037/dev0000098
PG 6
WC Psychology, Developmental
SC Psychology
GA DM2UP
UT WOS:000376203800007
PM 26950240
ER

PT J
AU Smith, HE
   Fabritius, AS
   Jaramillo-Lambert, A
   Golden, A
AF Smith, Harold E.
   Fabritius, Amy S.
   Jaramillo-Lambert, Aimee
   Golden, Andy
TI Mapping Challenging Mutations by Whole-Genome Sequencing Aimee
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE forward genetics; variant detection; complex alleles; SNP mapping
ID NEMATODE CAENORHABDITIS-ELEGANS; C-ELEGANS; IDENTIFICATION; GENETICS;
   DROSOPHILA; MUTANTS; SPERMATOGENESIS; ORIGIN; DOMAIN
AB Whole-genome sequencing provides a rapid and powerful method for identifying mutations on a global scale, and has spurred a renewed enthusiasm for classical genetic screens in model organisms. The most commonly characterized category of mutation consists of monogenic, recessive traits, due to their genetic tractability. Therefore, most of the mapping methods for mutation identification by whole-genome sequencing are directed toward alleles that fulfill those criteria (i.e., single-gene, homozygous variants). However, such approaches are not entirely suitable for the characterization of a variety of more challenging mutations, such as dominant and semidominant alleles or multigenic traits. Therefore, we have developed strategies for the identification of those classes of mutations, using polymorphism mapping in Caenorhabditis elegans as our model for validation. We also report an alternative approach for mutation identification from traditional recombinant crosses, and a solution to the technical challenge of sequencing sterile or terminally arrested strains where population size is limiting. The methods described herein extend the applicability of whole-genome sequencing to a broader spectrum of mutations, including classes that are difficult to map by traditional means.
C1 [Smith, Harold E.; Fabritius, Amy S.; Jaramillo-Lambert, Aimee; Golden, Andy] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Smith, HE (reprint author), 8 Ctr Dr, Bethesda, MD 20892 USA.
EM smithhe2@niddk.nih.gov
FU National Institutes of Health (NIH) Office of Research Infrastructure
   Programs [P40 OD10440]; National Institutes of Health, National
   Institute of Diabetes and Digestive and Kidney Diseases
FX We thank members of Michael Krause's lab and the Baltimore Worm Club for
   fruitful discussions, and Sevinc Ercan for sharing the small sample gDNA
   isolation protocol. Some strains were provided by the Caenorhabditis
   Genetics Center, which is funded by the National Institutes of Health
   (NIH) Office of Research Infrastructure Programs (P40 OD10440). This
   study was supported by the Intramural Research Program of the National
   Institutes of Health, National Institute of Diabetes and Digestive and
   Kidney Diseases, and is subject to the NIH Public Access Policy.
NR 47
TC 1
Z9 1
U1 1
U2 4
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAY
PY 2016
VL 6
IS 5
BP 1297
EP 1304
DI 10.1534/g3.116.028316
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DM4CY
UT WOS:000376294400014
PM 26945029
ER

PT J
AU Dever, TE
   Kinzy, TG
   Pavitt, GD
AF Dever, Thomas E.
   Kinzy, Terri Goss
   Pavitt, Graham D.
TI Mechanism and Regulation of Protein Synthesis in Saccharomyces
   cerevisiae
SO GENETICS
LA English
DT Review
DE GCN4; translation elongation; translation initiation
ID EUKARYOTIC TRANSLATION INITIATION; GUANINE-NUCLEOTIDE-EXCHANGE; GCN4
   MESSENGER-RNA; ELONGATION-FACTOR 1A; START CODON RECOGNITION; OPEN
   READING FRAME; C-TERMINAL DOMAIN; ARGININE ATTENUATOR PEPTIDE;
   ACTIN-BINDING PROTEIN; GENOME-WIDE ANALYSIS
AB In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae. The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs.
C1 [Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
   [Kinzy, Terri Goss] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
   [Pavitt, Graham D.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.; Kinzy, TG (reprint author), Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.; Pavitt, GD (reprint author), Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
EM tdever@nih.gov; kinzytg@rwjms.rutgers.edu;
   graham.pavitt@manchester.ac.uk
OI Pavitt, Graham/0000-0002-8593-2418
FU United Kingdom Biotechnology and Biological Sciences Research Council
   [BB/L000652/1, BB/L020157/1, BB/M006565/1]; National Institutes of
   Health (NIH) [GM57483]; Intramural Research Program of the NIH
FX We thank Alan Hinnebusch and the anonymous referee for their insights to
   improve the manuscript. Work in the Pavitt laboratory is funded by
   United Kingdom Biotechnology and Biological Sciences Research Council
   grants BB/L000652/1, BB/L020157/1, and BB/M006565/1. Work in the Kinzy
   laboratory is supported by National Institutes of Health (NIH) grant
   GM57483. Work in the Dever laboratory is supported by the Intramural
   Research Program of the NIH.
NR 474
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Z9 6
U1 10
U2 24
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD MAY
PY 2016
VL 203
IS 1
BP 65
EP 107
DI 10.1534/genetics.115.186221
PG 43
WC Genetics & Heredity
SC Genetics & Heredity
GA DM0DD
UT WOS:000376012100007
PM 27183566
ER

PT J
AU Kukke, SN
   Curatalo, LA
   de Campos, AC
   Hallett, M
   Alter, KE
   Damiano, DL
AF Kukke, Sahana N.
   Curatalo, Lindsey A.
   de Campos, Ana Carolina
   Hallett, Mark
   Alter, Katharine E.
   Damiano, Diane L.
TI Coordination of Reach-to-Grasp Kinematics in Individuals With
   Childhood-Onset Dystonia Due to Hemiplegic Cerebral Palsy
SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
LA English
DT Article
DE Cerebral palsy; coordination; dystonia; kinematics; reach-to-grasp
ID PREHENSION MOVEMENTS; CHILDREN; ARM; HAND; MOTION; PARAMETERS;
   COMPONENTS; APERTURE; STROKE; INDEX
AB Functional reaching is impaired in dystonia. Here, we analyze upper extremity kinematics to quantify timing and coordination abnormalities during unimanual reach-to-grasp movements in individuals with childhood-onset unilateral wrist dystonia. Kinematics were measured during movements of both upper limbs in a patient group (n = 11, age = 17.5 +/- 5 years), and a typically developing control group (n = 9, age = 16.6 +/- 5 years). Hand aperture was computed to study the coordination of reach and grasp. Time-varying joint synergies within one upper limb were calculated using a novel technique based on principal component analysis to study intra-limb coordination. In the non-dominant arm, results indicate reduced coordination between reach and grasp in patients who could not lift the grasped object compared to those who could lift it. Lifters exhibit incoordination in distal upper extremity joints later in the movement and non-lifters lacked coordination throughout the movement and in the whole upper limb. The amount of atypical coordination correlates with dystonia severity in patients. Reduced coordination during movement may reflect deficits in the execution of simultaneous movements, motor planning, or muscle activation. Rehabilitation efforts can focus on particular time points when kinematic patterns deviate abnormally to improve functional reaching in individuals with childhood-onset dystonia.
C1 [Kukke, Sahana N.; de Campos, Ana Carolina] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Kukke, Sahana N.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
   [Curatalo, Lindsey A.; Alter, Katharine E.; Damiano, Diane L.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Curatalo, Lindsey A.] Ortho Clin Diagnost, Rochester, NY USA.
   [de Campos, Ana Carolina] Univ Fed Sao Carlos, Dept Phys Therapy, BR-13560 Sao Carlos, SP, Brazil.
   [Hallett, Mark] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA.
RP Kukke, SN; de Campos, AC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.; Kukke, SN (reprint author), Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.; Curatalo, LA; Alter, KE; Damiano, DL (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.; Curatalo, LA (reprint author), Ortho Clin Diagnost, Rochester, NY USA.; de Campos, AC (reprint author), Univ Fed Sao Carlos, Dept Phys Therapy, BR-13560 Sao Carlos, SP, Brazil.; Hallett, M (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Alter, KE (reprint author), Mt Washington Pediat Hosp, Baltimore, MD USA.
EM kukke@cua.edu; lindsey.curatalo@gmail.com; accampos@ufscar.br;
   hallettm@ninds.nih.gov; kalter@cc.nih.gov; damianod@cc.nih.gov
FU Intramural Research Programs of the National Institutes of Health
   Clinical Center; National Institute of Neurological Disorders and Stroke
   at the National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
   National Institutes of Health Clinical Center and National Institute of
   Neurological Disorders and Stroke at the National Institutes of Health.
NR 31
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U1 0
U2 2
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1534-4320
EI 1558-0210
J9 IEEE T NEUR SYS REH
JI IEEE Trans. Neural Syst. Rehabil. Eng.
PD MAY
PY 2016
VL 24
IS 5
BP 582
EP 590
DI 10.1109/TNSRE.2015.2458293
PG 9
WC Engineering, Biomedical; Rehabilitation
SC Engineering; Rehabilitation
GA DM3XV
UT WOS:000376280900007
PM 26208359
ER

PT J
AU Terse, PS
   Joshi, PS
   Bordelon, NR
   Brys, AM
   Patton, KM
   Arndt, TP
   Sutula, TP
AF Terse, P. S.
   Joshi, P. S.
   Bordelon, N. R.
   Brys, A. M.
   Patton, K. M.
   Arndt, T. P.
   Sutula, T. P.
TI 2-Deoxy-D-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and
   BNP as Potential Early Cardiac Safety Biomarkers
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Article
DE 2-deoxy-D-glucose; NT-proBNP; BNP; vacuolar degeneration
ID ATRIAL-NATRIURETIC-PEPTIDE; MYOCARDIAL-INFARCTION; KETOGENIC DIET;
   TROPONIN-I; CARDIOTOXICITY; ANTICONVULSANT; EPILEPSY; DAMAGE
AB 2-Deoxy-D-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials.
C1 [Terse, P. S.; Joshi, P. S.] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
   [Bordelon, N. R.; Brys, A. M.; Patton, K. M.; Arndt, T. P.] Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA.
   [Bordelon, N. R.] Covance, Greenfield, IN USA.
   [Arndt, T. P.] Covance, Madison, WI USA.
   [Sutula, T. P.] Univ Wisconsin, Madison, WI USA.
RP Terse, PS (reprint author), Natl Ctr Adv Translat Sci, Bethesda, MD USA.
EM tersep@mail.nih.gov
FU NCI-Leidos [HHSN261200800001E]; NINDS under BrIDGS/NCATS Program
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This work
   was supported by NCI-Leidos (Contract No. HHSN261200800001E) and NINDS
   under BrIDGS/NCATS Program.
NR 27
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U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD MAY-JUN
PY 2016
VL 35
IS 3
BP 284
EP 293
DI 10.1177/1091581815624397
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DM2WB
UT WOS:000376207700003
PM 26838190
ER

PT J
AU Brittain, MK
   McGarry, KG
   Moyer, RA
   Babin, MC
   Jett, DA
   Platoff, GE
   Yeung, DT
AF Brittain, Matthew K.
   McGarry, Kevin G.
   Moyer, Robert A.
   Babin, Michael C.
   Jett, David A.
   Platoff, Gennady E., Jr.
   Yeung, David T.
TI Efficacy of Recommended Prehospital Human Equivalent Doses of Atropine
   and Pralidoxime Against the Toxic Effects of Carbamate Poisoning in the
   Hartley Guinea Pig
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Article
DE atropine; 2-PAM Cl; carbamates; pesticide
ID MUSCLE ACETYLCHOLINESTERASE; KINETIC INTERACTIONS; OXIMES;
   ORGANOPHOSPHATE; REACTIVATION; BUTYRYLCHOLINESTERASE; PYRIDOSTIGMINE;
   PHYSOSTIGMINE; INTOXICATION; PRETREATMENT
AB Purpose: Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning (muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride [2-PAM Cl]) could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. Methods: A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. The ChE activity was determined in both the blood and the cerebral cortex. Results: Coadministration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes postchallenge but gradually returned to normal within 24 hours. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 hours after challenge. Conclusion: The results suggest that coadministration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the prehospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning.
C1 [Brittain, Matthew K.; McGarry, Kevin G.; Moyer, Robert A.; Babin, Michael C.] Battelle Mem Inst, 505 King Ave,JM-7, Columbus, OH 43201 USA.
   [Jett, David A.; Yeung, David T.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Platoff, Gennady E., Jr.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Brittain, MK (reprint author), Battelle Mem Inst, 505 King Ave,JM-7, Columbus, OH 43201 USA.
EM brittainm@battelle.org
OI /0000-0001-5692-0170
FU DoD Defense Technical Information Center (DTIC) under the Chemical,
   Biological, Radiological & Nuclear Defense Information Analysis Center
   (CBRNIAC) program [SP0700-00-D-3180, 0687, 832/CB-IO-OOI2]; NIH Office
   of the Director; NIH
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This work
   was supported by the NIH Office of the Director through an interagency
   agreement between the NIAID and Department of Defense (DoD) and prepared
   under the auspices of both the NIH and the DoD Defense Technical
   Information Center (DTIC) under the Chemical, Biological, Radiological &
   Nuclear Defense Information Analysis Center (CBRNIAC) program, Contract
   No. SP0700-00-D-3180, Delivery Order Number 0687, CBRNIAC Task
   832/CB-IO-OOI2.
NR 38
TC 0
Z9 0
U1 3
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
EI 1092-874X
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD MAY-JUN
PY 2016
VL 35
IS 3
BP 344
EP 357
DI 10.1177/1091581816638086
PG 14
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DM2WB
UT WOS:000376207700009
PM 27102179
ER

PT J
AU Boots, CE
   Hill, MJ
   Feinberg, EC
   Lathi, RB
   Fowler, SA
   Jungheim, ES
AF Boots, Christina E.
   Hill, Micah J.
   Feinberg, Eve C.
   Lathi, Ruth B.
   Fowler, Susan A.
   Jungheim, Emily S.
TI Methotrexate does not affect ovarian reserve or subsequent assisted
   reproductive technology outcomes
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Article
DE Methotrexate; Ectopic pregnancy; Ovarian; reserve; In vitro
   fertilization; Pregnancy rate
ID SINGLE-DOSE METHOTREXATE; ECTOPIC PREGNANCY; WOMEN; PERFORMANCE;
   FERTILITY; RESPONSIVENESS; SALPINGECTOMY; CYCLE
AB The purpose of this research was to study whether methotrexate (MTX) as treatment for ectopic pregnancy (EP) impacts the future fertility of women undergoing assisted reproductive technology (ART)
   In a systematic review and multi-center retrospective cohort from four academic and private fertility centers, 214 women underwent an ART cycle before and after receiving MTX as treatment for an EP. Measures of ovarian reserve and responsiveness and rates of clinical pregnancy (CP) and live birth (LB) were compared in the ART cycles prior and subsequent to MTX.
   Seven studies were identified in the systematic review, and primary data from four institutions was included in the final analysis. Women were significantly older in post-MTX cycles (35.3 vs 34.7 years). There were no differences in follicle stimulating hormone, antral follicle count, duration of stimulation, oocytes retrieved, or fertilization rate between pre- and post-MTX cycles. However, post-MTX cycles received a significantly higher total dose of gonadotropins (4206 vs 3961 IU). Overall, 42 % of women achieved a CP and 35 % achieved a LB in the post-MTX ART cycle, which is similar to national statistics. Although no factors were identified that were predictive of LB in young women, the number of oocytes retrieved in the previous ART cycle and current AFC were predictive of LB (AUC 0.76, 0.75) for the older women.
   MTX does not influence ovarian reserve, response to gonadotropin stimulation, and CP or LB rate after ART. MTX remains a safe and effective treatment option for women with asymptomatic EPs.
C1 [Boots, Christina E.; Jungheim, Emily S.] Washington Univ, Obstet & Gynecol, 4444 Forest Pk,Suite 3100, St Louis, MO 63108 USA.
   [Hill, Micah J.] NIH, Program Reprod & Adult Endocrinol, 10 Ctr Dr Room 1-3140,MSC 1109, Bethesda, MD 20892 USA.
   [Feinberg, Eve C.] Fertil Ctr Illinois, Reprod Endocrinol & Infertil, 767 Pk Ave,Suite 190, Highland Pk, IL 60035 USA.
   [Lathi, Ruth B.] Stanford Univ, Obstet & Gynecol, 900 Welch Rd 350, Palo Alto, CA 94304 USA.
   [Fowler, Susan A.] Washington Univ, Bernard Becker Med Lib, 660 Euclid Ave, St Louis, MO 63110 USA.
RP Boots, CE (reprint author), Washington Univ, Obstet & Gynecol, 4444 Forest Pk,Suite 3100, St Louis, MO 63108 USA.
EM bootsc@wudosis.wustl.edu; hillmicah@mail.nih.gov;
   eve.feinberg@integramed.com; rlathi@stanford.edu;
   fowlers@wusm.wustl.edu; jungheime@wudosis.wustl.edu
FU National Research Training Program in Reproductive Medicine - National
   Institute of Health [T32 HD040135-13]; Scientific Advisory Board of
   Vivere Health; Women's Reproductive Health Research Program - National
   Institute of Health [K12 HD063086]; Institute of Clinical and
   Translational Sciences at Washington University [UL1 TR000448]; Barnes
   Jewish Hospital Foundation; March of Dimes; Program in Reproductive and
   Adult Endocrinology, NICHD, NIH, Bethesda, MD
FX C.E.B. received support from the National Research Training Program in
   Reproductive Medicine sponsored by the National Institute of Health (T32
   HD040135-13) and the Scientific Advisory Board of Vivere Health. E.S.J.
   received support from the Women's Reproductive Health Research Program
   sponsored by the National Institute of Health (K12 HD063086), the
   Institute of Clinical and Translational Sciences at Washington
   University (UL1 TR000448), the Barnes Jewish Hospital Foundation, and
   the March of Dimes. This work was supported, in part, by the Program in
   Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD.
NR 27
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U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
EI 1573-7330
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD MAY
PY 2016
VL 33
IS 5
BP 647
EP 656
DI 10.1007/s10815-016-0683-7
PG 10
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA DM4CV
UT WOS:000376294100013
PM 26943917
ER

PT J
AU Przytycka, T
AF Przytycka, Teresa
TI Preface
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
C1 [Przytycka, Teresa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Przytycka, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM przytyck@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
EI 1557-8666
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD MAY
PY 2016
VL 23
IS 5
BP 299
EP 299
DI 10.1089/cmb.2016.29001.tp
PG 1
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Computer Science, Interdisciplinary Applications; Mathematical &
   Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Computer Science; Mathematical & Computational Biology; Mathematics
GA DM1BQ
UT WOS:000376080500001
PM 27159631
ER

PT J
AU Thurm, A
   Himelstein, D
   D'Souza, P
   Rennert, O
   Jiang, SQ
   Olatunji, D
   Longo, N
   Pasquali, M
   Swedo, S
   Salomons, GS
   Carrillo, N
AF Thurm, Audrey
   Himelstein, Daniel
   D'Souza, Precilla
   Rennert, Owen
   Jiang, Susanqi
   Olatunji, Damilola
   Longo, Nicola
   Pasquali, Marzia
   Swedo, Susan
   Salomons, Gajja S.
   Carrillo, Nuria
TI Creatine Transporter Deficiency: Screening of Males with
   Neurodevelopmental Disorders and Neurocognitive Characterization of a
   Case
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE autism; creatine transporter deficiency; developmental disability;
   genetic disease; X-linked
ID LINKED MENTAL-RETARDATION; SLC6A8 DEFICIENCY; AUTISM; PREVALENCE;
   SPECTRUM; DEFECT
AB Objective: Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by. mutations in SLC6A8, the Cr transporter 1 protein gene. cm is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well characterized cohort of children diagnosed with neurodevelopmental disorders. Method: Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. Results: We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Conclusion: Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.
C1 [Thurm, Audrey; Himelstein, Daniel; D'Souza, Precilla; Olatunji, Damilola; Swedo, Susan] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
   [Rennert, Owen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, NIH, Bethesda, MD USA.
   [Jiang, Susanqi; Carrillo, Nuria] NIH, Therapeut Rare & Neglected Dis, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
   [Longo, Nicola] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT USA.
   [Longo, Nicola; Pasquali, Marzia] Associated Reg & Univ Pathologists AAUP Labs, Salt Lake City, UT USA.
   [Pasquali, Marzia] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
   [Salomons, Gajja S.] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Metab Unit, Neurosci Campus Amsterdam, Amsterdam, Netherlands.
RP Thurm, A (reprint author), 10 Ctr Dr,Rrn 1C250,MSC 1255, Bethesda, MD 20892 USA.
EM athurm@mail.nih.gov
RI Carrillo-Carrasco, Nuria/B-9034-2009
OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808
FU Intramural Programs of the National Institute of Mental Health (NIMH)
   [06-M-0102, NCT 00298246, 1ZIAMH1002868]; National Center for Advancing
   Translational Sciences (NCATS), all of the National Institutes of Health
   (NIH)
FX This research was supported by the Intramural Programs of the National
   Institute of Mental Health (NIMH) (Protocol 06-M-0102, NCT 00298246,
   1ZIAMH1002868), and the National Center for Advancing Translational
   Sciences (NCATS), all of the National Institutes of Health (NIH).
NR 26
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U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0196-206X
EI 1536-7312
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD MAY
PY 2016
VL 37
IS 4
BP 322
EP 326
PG 5
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA DM2YD
UT WOS:000376213100008
PM 27096572
ER

PT J
AU Hanson, JA
   Lin, YH
   Dretsch, MN
   Strandjord, SE
   Haub, MD
   Hibbeln, JR
AF Hanson, Jennifer A.
   Lin, Yu-Hong
   Dretsch, Michael N.
   Strandjord, Sarah E.
   Haub, Mark D.
   Hibbeln, Joseph R.
TI Whole food, functional food, and supplement sources of omega-3 fatty
   acids and omega-3 HUFA scores among US soldiers
SO JOURNAL OF FUNCTIONAL FOODS
LA English
DT Article
DE Omega-3 fatty acids; Functional food; Food frequency questionnaire;
   Docosahexaenoic acid; Eicosapentaenoic acid; Military personnel
ID POLYUNSATURATED FATTY-ACIDS; CORONARY-HEART-DISEASE; BODY-MASS INDEX;
   FREQUENCY QUESTIONNAIRE; FISH CONSUMPTION; DEPRESSIVE SYMPTOMS;
   COGNITIVE DECLINE; N-3; VALIDATION; ADULTS
AB A questionnaire to measure consumption of contemporary sources of omega-3 fatty acids including (i) seafood, (ii) poultry and eggs, (iii) omega-3 functional foods, and (iv) dietary supplements was completed by U.S. soldiers (N = 191). Omega-3 highly unsaturated fatty acid (HUFA) scores were higher (p < 0.01) among those who (i) took an omega-3 supplement, (ii) consumed sushi, (iii) consumed omega-3 functional foods, (iv) consumed beef less than twice per week, and (v) ate seafood at least twice a week. Omega-3 HUFA was positively correlated with EPA + DHA intake (beta = 0.39; p < 0.01) and age (beta = 0.14; p = 0.03) and negatively correlated with beef intake (beta = -0.13; p = 0.05) and smoking (beta = -0.12; p = 0.08). Intake of contemporary foods rich in omega-3s were associated with higher biomarker values while smoking and beef intake were associated with lower values. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Hanson, Jennifer A.; Haub, Mark D.] Kansas State Univ, Dept Food Nutr Dietet & Hlth, 212 Justin Hall, Manhattan, KS 66506 USA.
   [Lin, Yu-Hong; Strandjord, Sarah E.; Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Rm 3N-07,MSC 9410, Bethesda, MD 20892 USA.
   [Dretsch, Michael N.] US Army Aeromed Res Lab, Ft Rucker, AL USA.
   [Dretsch, Michael N.] HQ TRADOC, Cognit Dominance Team, Human Dimens Div, Capabil Dev Directorate, Ft Eustis, VA 23604 USA.
   [Strandjord, Sarah E.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, 9500 Euclid Ave NA21, Cleveland, OH USA.
RP Hanson, JA (reprint author), Kansas State Univ, Dept Food Nutr Dietet & Hlth, 212 Justin Hall, Manhattan, KS 66506 USA.
EM jhanson2@ksu.edu
OI Hanson, Jennifer /0000-0003-0437-6489
FU Academy of Nutrition and Dietetics Foundation; Intramural Research
   Program of the National Institute on Alcohol Abuse and Alcoholism, NIH;
   Kansas State University Research Foundation Fellowship Award
FX This project was partially funded by the Herbert D. and Nylda Gemple
   Research Award from the Academy of Nutrition and Dietetics Foundation,
   the Intramural Research Program of the National Institute on Alcohol
   Abuse and Alcoholism, NIH and the Kansas State University Research
   Foundation Fellowship Award.
NR 46
TC 0
Z9 0
U1 9
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1756-4646
J9 J FUNCT FOODS
JI J. Funct. Food.
PD MAY
PY 2016
VL 23
BP 167
EP 176
DI 10.1016/j.jff.2016.02.017
PG 10
WC Food Science & Technology
SC Food Science & Technology
GA DM1ZK
UT WOS:000376145200016
ER

PT J
AU Escaffre, O
   Borisevich, V
   Vergara, LA
   Wen, JW
   Long, D
   Rockx, B
AF Escaffre, Olivier
   Borisevich, Viktoriya
   Vergara, Leoncio A.
   Wen, Julie W.
   Long, Dan
   Rockx, Barry
TI Characterization of Nipah virus infection in a model of human airway
   epithelial cells cultured at an air-liquid interface
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID NOSOCOMIAL TRANSMISSIBILITY; CLINICAL-FEATURES; ENDOTHELIAL-CELLS;
   MALAYSIA; OUTBREAK; ENCEPHALITIS; PATHOGENESIS; BANGLADESH; ADHESION;
   INTERLEUKIN-6
AB Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air-liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.
C1 [Escaffre, Olivier; Borisevich, Viktoriya; Wen, Julie W.; Rockx, Barry] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
   [Vergara, Leoncio A.] Univ Texas Med Branch, Ctr Biomed Engn, Galveston, TX 77555 USA.
   [Long, Dan] NIAID, Rocky Mt Vet Branch, Microscopy Unit, Div Intramural Res,NIH, Hamilton, MT USA.
   [Rockx, Barry] Natl Inst Publ Hlth & Environm RIVM, Dept Rare & Emerging Viral Infect & Response EID, Ctr Infect Dis Control CIb, Bilthoven, Netherlands.
   [Vergara, Leoncio A.] Texas A&M Hlth Sci Ctr, IBT, CTCR, Houston, TX USA.
RP Rockx, B (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.; Rockx, B (reprint author), Natl Inst Publ Hlth & Environm RIVM, Dept Rare & Emerging Viral Infect & Response EID, Ctr Infect Dis Control CIb, Bilthoven, Netherlands.
EM barry.rockx@rivm.nl
FU University of Texas Medical Branch (UTMB) startup funds; National
   Institutes of Health [1R21AI111042-01]; UTMB Center for Tropical
   Diseases Postdoctoral Fellowship
FX This work was supported by the University of Texas Medical Branch (UTMB)
   startup funds and National Institutes of Health [1R21AI111042-01] to B.
   R., and an UTMB Center for Tropical Diseases Postdoctoral Fellowship to
   O. E. The authors would like to thank Dr Alexander N. Freiberg for
   helpful discussions and Dr Vsevolod Popov for technical assistance in
   specimen preparation and electron microscopy.
NR 39
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U1 0
U2 1
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
   BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAY
PY 2016
VL 97
BP 1077
EP 1086
PN 5
PG 10
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA DL7RM
UT WOS:000375837800006
PM 26932515
ER

PT J
AU Macatangay, BJC
   Riddler, SA
   Wheeler, ND
   Spindler, J
   Lawani, M
   Hong, F
   Buffo, MJ
   Whiteside, TL
   Kearney, MF
   Mellors, JW
   Rinaldo, CR
AF Macatangay, Bernard J. C.
   Riddler, Sharon A.
   Wheeler, Nicole D.
   Spindler, Jonathan
   Lawani, Mariam
   Hong, Feiyu
   Buffo, Mary J.
   Whiteside, Theresa L.
   Kearney, Mary F.
   Mellors, John W.
   Rinaldo, Charles R.
TI Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV
   Type 1-Infected Apoptotic Cells
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV-1; therapeutic vaccine; dendritic cell; apoptotic cell; residual
   viremia
ID SUPPRESSIVE ANTIRETROVIRAL THERAPY; T-LYMPHOCYTES; VIRUS; CD8(+);
   VIREMIA; INFECTION; QUANTIFICATION; REACTIVITY; INDUCTION; PLASMA
AB Methods. Antiretroviral therapy (ART)-naive individuals were enrolled, and viremia was suppressed by ART prior to delivery of 4 doses of DC-based vaccine. Participants underwent treatment interruption 6 weeks after the third vaccine dose. The plasma HIV-1 RNA level 12 weeks after treatment interruption was compared to the pre-ART (ie, baseline) level.
   Results. The vaccine was safe and well tolerated but did not prevent viral rebound during treatment interruption. Vaccination resulted in a modest but significant decrease in plasma viremia from the baseline level (from 4.53 log(10) copies/mL to 4.27 log(10) copies/mL;P = .05). Four of 10 participants had a > 0.70 log(10) increase in the HIV-1 RNA load in plasma following vaccination, despite continuous ART. Single-molecule sequencing of HIV-1 RNA in plasma before and after vaccination revealed increases in G > A hypermutants ingag andpol after vaccination, which suggests cytolysis of infected cells.
   Conclusions. A therapeutic HIV-1 vaccine based on DCs loaded with apoptotic bodies was safe and induced T-cell activation and cytolysis, including HIV-1-infected cells, in a subset of study participants.
   Clinical Trials Registration. NCT00510497.
C1 [Macatangay, Bernard J. C.; Riddler, Sharon A.; Wheeler, Nicole D.; Lawani, Mariam; Hong, Feiyu; Mellors, John W.] Univ Pittsburgh, Sch Med, Div Infect Dis, S827 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
   [Buffo, Mary J.; Whiteside, Theresa L.] Univ Pittsburgh, Med Ctr, Hillman Canc Ctr, S827 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
   [Rinaldo, Charles R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, S827 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
   [Spindler, Jonathan; Kearney, Mary F.] NCI, NIH, Bethesda, MD 20892 USA.
RP Macatangay, BJC (reprint author), Univ Pittsburgh, Sch Med, S827 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
EM macatangaybj@upmc.edu
FU National Institutes of Health [P01-AI-43664, P01-CA109688, P01-CA73743,
   N01-HB37165, R37-AI-41870, U19-AI-055794, UL1RR024153, UL1TR000005,
   P30CA047904]; Leidos Biomedical Research; National Cancer Institute
   [12XS547]
FX This work was supported by the National Institutes of Health (grants
   P01-AI-43664, P01-CA109688, P01-CA73743, N01-HB37165, R37-AI-41870,
   U19-AI-055794, UL1RR024153, and UL1TR000005; and award P30CA047904 to
   the University of Pittsburgh Cancer Institute Hillman Cancer Center
   laboratories), Leidos Biomedical Research, and the National Cancer
   Institute (contract 12XS547).
NR 29
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U1 1
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 MAY 1
PY 2016
VL 213
IS 9
BP 1400
EP 1409
DI 10.1093/infdis/jiv582
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM4DM
UT WOS:000376295800007
PM 26647281
ER

PT J
AU Panigrahi, S
   Freeman, ML
   Funderburg, NT
   Mudd, JC
   Younes, SA
   Sieg, SF
   Zidar, DA
   Paiardini, M
   Villinger, F
   Calabrese, LH
   Ransohoff, RM
   Jain, MK
   Lederman, MM
AF Panigrahi, Soumya
   Freeman, Michael L.
   Funderburg, Nicholas T.
   Mudd, Joseph C.
   Younes, Souheil A.
   Sieg, Scott F.
   Zidar, David A.
   Paiardini, Mirko
   Villinger, Francois
   Calabrese, Leonard H.
   Ransohoff, Richard M.
   Jain, Mukesh K.
   Lederman, Michael M.
TI SIV/SHIV Infection Triggers Vascular Inflammation, Diminished Expression
   of Kruppel-like Factor 2 and Endothelial Dysfunction
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE SIV; SHIV; endothelial dysfunction; eNOS; KLF2; immunohistochemistry;
   simvastatin; oxLDL; LPS
ID HUMAN-IMMUNODEFICIENCY-VIRUS; POTENT ANTIRETROVIRAL THERAPY; CHRONIC
   HIV-INFECTION; IMMUNE ACTIVATION; PROINFLAMMATORY ACTIVATION;
   TRANSCRIPTIONAL REGULATOR; MONOCYTE ACTIVATION; CARDIOVASCULAR RISK;
   HEART-DISEASE; COAGULATION
AB Background. Human immunodeficiency virus (HIV) infection is associated with increased risk of thromboembolic and cardiovascular comorbid conditions. Although systemic inflammation is linked to cardiovascular risk, direct evidence of vascular inflammation and endothelial dysfunction is lacking.
   Methods. We examined by immunofluorescence microscopy thoracic aortas from 16 simian immunodeficiency virus (SIV)- or simian-human immunodeficiency virus (SHIV)-infected and 16 uninfected rhesus macaques.
   Results. Focal endothelial proliferation and subendothelial inflammatory cells were found in sections of all infected animals, compared with minimal changes in sections from the 16 uninfected controls. In the infected animals, we detected increased endothelial levels of bacterial 16s ribosomal DNA as well as increased subendothelial accumulation of CD68(+) monocytes/macrophages (P < .001) and CD8(+) T lymphocytes (P < .001). Endothelial dysfunction was manifested by decreased levels of endothelial nitric oxide synthase (P < .005) and Kruppel-like factor 2 (KLF2) (P < .005). KLF2 expression was decreased in primary human aortic endothelial cells exposed to bacterial lipopolysaccharide or to oxidized low-density lipoprotein in vitro, and this could be prevented by simvastatin.
   Conclusions. SIV and SHIV infection lead to endothelial inflammation, dysfunction, and decreased KLF2 expression reflecting early atherosclerotic changes. Translocated bacterial components and lipid oxidation products may induce endothelial dysfunction in HIV infection that could be prevented by statin treatment.
C1 [Panigrahi, Soumya; Freeman, Michael L.; Younes, Souheil A.; Sieg, Scott F.; Zidar, David A.; Jain, Mukesh K.; Lederman, Michael M.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, 2061 Cornell Rd, Cleveland, OH 44106 USA.
   [Calabrese, Leonard H.] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, 2061 Cornell Rd, Cleveland, OH 44106 USA.
   [Ransohoff, Richard M.] Cleveland Clin, Neuroinflammat Res Ctr, Columbus, OH 44195 USA.
   [Funderburg, Nicholas T.] Ohio State Univ, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA.
   [Mudd, Joseph C.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Paiardini, Mirko; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
RP Lederman, MM (reprint author), Case Western Reserve Univ, Sch Med, 2061 Cornell Rd, Cleveland, OH 44106 USA.
EM mxl6@case.edu
FU Fasenmyer Foundation; Case Western Reserve University Center for AIDS
   Research [AI-36219]; Cleveland Immunopathogenesis Consortium (CLIC)
   [AI-76174, R00HL108743, HL126563]; National Institutes of Health [P51
   OD11132]
FX This work was supported by the Fasenmyer Foundation, the Case Western
   Reserve University Center for AIDS Research (grant AI-36219), and the
   Cleveland Immunopathogenesis Consortium (CLIC) (grants AI-76174,
   R00HL108743, and HL126563). The Yerkes National Primate Research Center
   is supported by the National Institutes of Health (base grant P51
   OD11132).
NR 50
TC 3
Z9 3
U1 0
U2 1
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 MAY 1
PY 2016
VL 213
IS 9
BP 1419
EP 1427
DI 10.1093/infdis/jiv749
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM4DM
UT WOS:000376295800009
PM 26671887
ER

PT J
AU Beachler, DC
   Jenkins, G
   Safaeian, M
   Kreimer, AR
   Wentzensen, N
AF Beachler, Daniel C.
   Jenkins, Gwendolyne
   Safaeian, Mahboobeh
   Kreimer, Aimee R.
   Wentzensen, Nicolas
TI Natural Acquired Immunity Against Subsequent Genital Human
   Papillomavirus Infection: A Systematic Review and Meta-analysis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Review
DE human papillomavirus; antibodies; serology; natural immunity; cervix
ID VIRUS-LIKE PARTICLES; UNITED-STATES; HPV INFECTION; CARCINOMAS
   WORLDWIDE; CANCER INCIDENCE; CERVICAL-CANCER; COSTA-RICA; RISK; WOMEN;
   ANTIBODIES
AB Background. Studies have been mixed on whether naturally acquired human papillomavirus (HPV) antibodies may protect against subsequent HPV infection. We performed a systematic review and meta-analysis to assess whether naturally acquired HPV antibodies protect against subsequent genital HPV infection (ie, natural immunity).
   Methods. We searched the MEDLINE and EMBASE databases for studies examining natural HPV immunity against subsequent genital type-specific HPV infection in female and male subjects. We used random-effects models to derive pooled relative risk (RR) estimates for each HPV type.
   Results. We identified 14 eligible studies that included > 24 000 individuals from 18 countries that examined HPV natural immunity. We observed significant protection against subsequent infection in female subjects with HPV-16 (pooled RR, 0.65; 95% confidence interval, .50-.80) and HPV-18 (0.70; .43-.98) but not in male subjects (HPV-16: 1.22; .67-1.77 [P = .05 (test for heterogeneity)]; HPV-18: 1.50; .46-2.55; [P = .15]). We also observed type-specific protection against subsequent infection for a combined measure of HPV-6/11/31/33/35/45/52/58 in female subjects (pooled RR, 0.75; 95% confidence interval, .57-.92). Natural immunity was also evident in female subjects when analyses were restricted to studies that used neutralizing assays, used HPV persistence as an outcome, or reported adjusted analyses (each P < .05).
   Conclusions. HPV antibodies acquired through natural infection provide modest protection against subsequent cervical HPV infection in female subjects.
C1 [Beachler, Daniel C.; Jenkins, Gwendolyne; Safaeian, Mahboobeh; Kreimer, Aimee R.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,RM 6-E220, Bethesda, MD 20892 USA.
RP Beachler, DC (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 9609 Med Ctr Dr,RM 6-E220, Bethesda, MD 20892 USA.
EM daniel.beachler@nih.gov
FU National Cancer Institute at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute at the National Institutes of Health.
NR 49
TC 3
Z9 3
U1 1
U2 7
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 MAY 1
PY 2016
VL 213
IS 9
BP 1444
EP 1454
DI 10.1093/infdis/jiv753
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DM4DM
UT WOS:000376295800012
PM 26690341
ER

PT J
AU Rabassa, M
   Zamora-Ros, R
   Andres-Lacueva, C
   Urpi-Sarda, M
   Bandinelli, S
   Ferrucci, L
   Cherubini, A
AF Rabassa, M.
   Zamora-Ros, R.
   Andres-Lacueva, C.
   Urpi-Sarda, M.
   Bandinelli, S.
   Ferrucci, L.
   Cherubini, A.
TI Association between both total baseline urinary and dietary polyphenols
   and substantial physical performance decline risk in older adults: A
   9-year follow-up of the InCHIANTI study
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Polyphenols; biomarker; physical performance; epidemiology; InCHIANTI
ID LOWER-EXTREMITY FUNCTION; MEDITERRANEAN DIET; MEANINGFUL CHANGE;
   MORTALITY; CONSUMPTION; BIOMARKER; HEALTH; EPIDEMIOLOGY; INVECCHIARE;
   DISABILITY
AB The decline in physical performance that occurs in many older subjects is a strong predictor of falls, hospitalization, institutionalization and mortality. Polyphenols are bioactive compounds that may play a preventive role against physical performance decline due to their antioxidant and anti-inflammatory properties.
   To investigate the association between total urinary polyphenols (TUP) and total dietary polyphenols (TDP) and substantial physical performance decline over a nine-year period among older subjects.
   This longitudinal study included 368 participants aged 65 years or older from the InCHIANTI (Invecchiare in Chianti) study, an Italian population-based cohort. TUP and TDP concentrations were assessed at baseline using the Folin-Ciocalteau (F-C) assay and a validated food frequency questionnaire, respectively. Physical performance was objectively measured at baseline and at nine-year follow-up using the Short Physical Performance Battery (SPPB). A substantial decline in physical performance was considered as a decrease of three or more points in the SPPB score.
   At the nine-year follow-up assessment, 71 participants had suffered a substantial decline in physical performance. In the fully adjusted logistic regression model, participants in the highest TUP tertile had a lower risk of substantial decline in physical performance than those in the lowest tertile (OR, 0.40; 95% CI, 0.17-0.93; P trend=0.033). However, no significant association between TDP intake and physical performance decline was observed.
   This study shows that high TUP concentrations, a biomarker of polyphenol-rich exposure, were associated with lower risk of substantial decline in physical performance in community-dwelling older subjects over a nine-year period. These results suggest that a polyphenol-rich diet may play a role in protecting against physical performance decline in older people.
C1 [Rabassa, M.; Andres-Lacueva, C.; Urpi-Sarda, M.] Univ Barcelona, Pharm & Food Sci Fac, Dept Nutr & Food Sci, Biomarkers & Nutrimetabol Lab,XaRTA,INSA, Campus Torribera, E-08028 Barcelona, Spain.
   [Zamora-Ros, R.] IARC, Nutr & Metab Sect NME, Biomarkers Grp BMA, Lyon, France.
   [Bandinelli, S.] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
   [Ferrucci, L.] Natl Inst Aging, Clin Res Branch, Baltimore, MD USA.
   [Cherubini, A.] Italian Natl Res Ctr Aging IRCCS INRCA, Geriatr & Geriatr Emergency Care, Ancona, Italy.
RP Andres-Lacueva, C (reprint author), Univ Barcelona, Pharm & Food Sci Fac, Dept Nutr & Food Sci, Biomarkers & Nutrimetabol Lab, Campus Torribera,Av Joan 23 S-N, E-08028 Barcelona, Spain.
EM candres@ub.edu
RI Andres-Lacueva, Cristina/J-3377-2012; 
OI Andres-Lacueva, Cristina/0000-0002-8494-4978; Cherubini,
   Antonio/0000-0003-0261-9897
FU Spanish government grants from the Ministry of Economy and
   Competitiveness (MINECO); FEDER (Fondo Europeo de Desarrollo Regional)
   [AGL2009-13906-C02-01]; CONSOLIDER-INGENIO [CSD2007-063]; JPI HDHL
   FOODBALL [PCIN-2014-133]; Generalitat de Catalunya's Agency AGAUR;
   International Nut and Dried Fruit Council Foundation (INC); Bosch i
   Gimpera Foundation [FBG307906]; Italian Ministry of Health; U.S.
   National Institute on Aging (NIA); MINECO [RYC-2011-09677]; Fondo Social
   Europeo
FX The authors are grateful for support granted by Spanish government
   grants from the Ministry of Economy and Competitiveness (MINECO) and
   cofounded by the FEDER (Fondo Europeo de Desarrollo Regional): the
   AGL2009-13906-C02-01, the CONSOLIDER-INGENIO 2010 program, FUN-C-FOOD
   (CSD2007-063), and the JPI HDHL FOODBALL (PCIN-2014-133). We also thank
   the award of 2014SGR1566 from the Generalitat de Catalunya's Agency
   AGAUR. In the framework of the COST Action POSITIVE FA1403. Partially
   funded by the International Nut and Dried Fruit Council Foundation (INC)
   in collaboration with the Bosch i Gimpera Foundation (FBG307906). The
   InCHIANTI study was supported in part by the Italian Ministry of Health
   and by the U.S. National Institute on Aging (NIA). M.U.-S. would like to
   thank the "Ramon y Cajal" program (RYC-2011-09677) from MINECO and the
   Fondo Social Europeo.
NR 48
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD MAY
PY 2016
VL 20
IS 5
BP 478
EP 484
DI 10.1007/s12603-015-0600-2
PG 7
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA DM4BA
UT WOS:000376289300002
PM 27102783
ER

PT J
AU Nugent, AC
   Iadarola, ND
   Miller, FG
   Luckenbaugh, DA
   Zarate, CA
AF Nugent, Allison C.
   Iadarola, Nicolas D.
   Miller, Frank G.
   Luckenbaugh, David A.
   Zarate, Carlos A., Jr.
TI Safety of research into severe and treatment-resistant mood disorders:
   analysis of outcome data from 12 years of clinical trials at the US
   National Institute of Mental Health
SO LANCET PSYCHIATRY
LA English
DT Article
ID PLACEBO-CONTROLLED TRIALS; PSYCHIATRIC RESEARCH; RATING-SCALE; DEPRESSED
   INPATIENTS; SUICIDE RISK; ANTIDEPRESSANTS; SENSITIVITY; PREVENTION;
   UNIPOLAR; BENEFITS
AB Background Placebo-controlled trials in drug-free patients have long been considered a key research component in the study of mood disorders and relevant treatment mechanisms. However, concerns have been raised about the ethics of such research, leading to an ongoing debate as to whether placebo controls are ethically acceptable. We aimed to assess the cumulative effects of research in individuals with mood disorders and to provide data to address ethical concerns regarding research in this population.
   Methods We obtained empirical data for patients screened between between Dec 13, 2001, and Jan 31, 2014, with either major depressive disorder or bipolar disorder who were enrolled in one or more of 18 clinical trials at a US National Institute of Mental Health (NIMH) inpatient or outpatient behavioural health research clinic. We assessed the cumulative effects of research in our patient population, including the effects of drug taper, drug washout, and placebo administration on mood state. Two subgroups were examined: patients enrolled in trials explicitly requiring treatment resistance and patients with a current or past history of suicidal ideation or behaviour. We used the percentage change from screening as the primary outcome measure for statistical analysis of change in mood over study periods. This study is registered with ClinicalTrials.gov, number NCT00024635.
   Findings We obtained data for 540 patients; 360 (71%) patients were enrolled in trials requiring treatment resistance, 58 (12%) of 465 patients had suicidal ideation at screening, and 191 (60%) of 321 patients had a history of suicidal ideation. Mean mood severity at screening was in the moderate to severe range. Full participation in research, including drug tapers, drug-free periods, and placebo-controlled trials, had a low risk of symptom exacerbation. Patients undergoing drug taper had a mean increase in symptom severity of 4.2% (SD 19.56, t(degrees of freedom 96) = 1.85; p=0.036). We recorded modest increases in the subgroup who tapered to no medications (mean percentage change 5.1% [SD 18.10], t(56) = 2.12; p=0.039), but increases were not significant in participants enrolled in trials requiring treatment resistance (4.3% [18.60], t(72) = 1.96; p=0.054) and those with a current or past history of suicidal ideation or behaviour (1.8% [18.78], t(51) = 0.68; p=0.50). Six serious adverse events were reported, including one suicide attempt that occurred during the standard treatment phase and not during the clinical trial.
   Interpretation In general, research participation at the NIMH was not detrimental to health and safety, and conferred benefit in many cases. This finding was true not only in our entire research population, but also in treatment-resistant subgroups and subgroups with a history of suicidality. Our study provides evidence to guide ethical analysis of issues in psychiatric research, and to support continued scientific investigation.
C1 [Nugent, Allison C.; Miller, Frank G.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
   [Iadarola, Nicolas D.] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Nugent, AC (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
EM nugenta@mail.nih.gov
OI Nugent, Allison/0000-0003-2569-2480
FU Intramural Research Program, NIMH, National Institutes of Health
FX Intramural Research Program, NIMH, National Institutes of Health.
NR 26
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD MAY
PY 2016
VL 3
IS 5
BP 436
EP 442
DI 10.1016/S2215-0366(16)00006-7
PG 7
WC Psychiatry
SC Psychiatry
GA DM3QW
UT WOS:000376262300025
PM 26971192
ER

PT J
AU Liu, X
   Muller, F
   Wayne, AS
   Pastan, I
AF Liu, Xiufen
   Muller, Fabian
   Wayne, Alan S.
   Pastan, Ira
TI Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas
   Exotoxin A-Based Immunotoxins
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; RECOMBINANT
   IMMUNOTOXIN; IN-VITRO; B-LINEAGE; MCL-1; SURVIVAL; CANCER; APOPTOSIS;
   MALIGNANCIES
AB HA22 (Moxetumomab pasudotox) is a recombinant immunotoxin (RIT), composed of an anti-CD22 Fv fused to a truncated portion of Pseudomonas exotoxin A. HA22 is in clinical trials to treat patients with hairy cell leukemia and acute lymphoblastic leukemia (ALL). LMB-11 is an improved variant of HA22 with reduced immunogenicity, has a longer half-life in the blood and high activity in vitro and in a Burkitt lymphoma model in vivo. Searching for RIT enhancing combination therapies, we found the protein kinase A inhibitor H89 to enhance LMB-11 and HA22 activity 5- to 10-fold on ALL cell lines and on patient-derived ALL samples. In addition, H89 increased the activity of mesothelin-targeting RITs SS1P (38-fold) and RG7787 (7-fold) against the cervical cancer cell line KB31. Unexpectedly we found that the enhancement by H89 was not because of inhibition of protein kinase A; it was partially recapitulated by inhibition of S6K1, which led to inactivation of its downstream targets rpS6 and GSK3 beta, resulting in a fall in MCL1 levels. H89 increased the rate of ADP-ribosylation of eukaryotic elongation factor 2, enhancing the arrest of protein synthesis and the reduction of MCL1 in synergy with the RIT. In summary, H89 increased RIT activity by enhancing the two key events: ADP-ribosylation of eEF2 and reduction of MCL1 levels. Significant enhancement was seen with both CD22- and mesothelin-targeting RITs, indicating that H89 might be a potent addition to RIT treatment of CD22-positive ALL and mesothelin-expressing solid tumors. (C) 2016 AACR.
C1 [Liu, Xiufen; Muller, Fabian; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
   [Wayne, Alan S.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr,Div Hematol Oncol & Bl, Childrens Hosp Los Angeles,Childrens Ctr Canc & B, Los Angeles, CA 90033 USA.
RP Pastan, I (reprint author), NCI, NIH, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU National Cancer Institute [P30CA014089]; Intramural Research Program of
   the NIH, National Cancer Institute; Center for Cancer Research;
   Cooperative Research and Development Agreement [1975]; MedImmune, LLC.;
   German Research Foundation [MU 3619/1-1]
FX The work was supported in part by award number P30CA014089 from the
   National Cancer Institute, the Intramural Research Program of the NIH,
   National Cancer Institute, and the Center for Cancer Research, and by a
   Cooperative Research and Development Agreement (#1975) with MedImmune,
   LLC. F. Muller was supported in part by the German Research Foundation,
   award number MU 3619/1-1.
NR 48
TC 2
Z9 2
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAY
PY 2016
VL 15
IS 5
BP 1053
EP 1062
DI 10.1158/1535-7163.MCT-15-0828
PG 10
WC Oncology
SC Oncology
GA DL7YX
UT WOS:000375857400026
PM 26939705
ER

PT J
AU Pushpanathan, M
   Pooja, S
   Gunasekaran, P
   Rajendhran, J
AF Pushpanathan, Muthuirulan
   Pooja, Sharma
   Gunasekaran, Paramasamy
   Rajendhran, Jeyaprakash
TI Critical Evaluation and Compilation of Physicochemical Determinants and
   Membrane Interactions of MMGP1 Antifungal Peptide
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE antifungal peptide; peptide aggregation; amphipathicity;
   membrane-peptide interaction; DNA-binding property
ID FREE-ENERGY DETERMINANTS; ANTIMICROBIAL PEPTIDE; CANDIDA-ALBICANS;
   LIPID-BILAYERS; MONTE-CARLO; WEB SERVER; AGGREGATION; PREDICTION;
   PROTEINS; BINDING
AB A growing issue of pathogen resistance to antibiotics has fostered the development of innovative approaches for novel drug development. Here, we report the physicochemical and biological properties of an antifungal peptide, MMGP1, based on computational analysis. Computation of physicochemical properties has revealed that the natural biological activities of MMGP1 are coordinated by its intrinsic properties such as net positive charge (+5.04), amphipathicity, high hydrophobicity, low hydrophobic moment, and higher isoelectric point (11.915). Prediction of aggregation hot spots in MMGP1 had revealed the presence of potentially aggregation-prone segments that can nucleate in vivo aggregation (on the membrane), whereas no aggregating regions were predicted for in vitro aggregation (in solutions) of MMGP1. This ability of MMGP1 to form oligomeric aggregates on membrane further substantiates its direct-cell penetrating potency. Monte Carlo simulation of the interactions of MMGP1 in the aqueous phase and different membrane environments revealed that increasing the proportion of acidic lipids on membrane had led to increase in the peptide helicity. Furthermore, the peptide adopts energetically favorable transmembrane configuration, by inserting peptide loop and helix termini into the membrane containing >60% of anionic lipids. The charged lipid-based insertion of MMGP1 into membrane might be responsible for the selectivity of peptide toward fungal cells. Additionally, MMGP1 possessed DNA-binding property. Computational docking has identified DNA-binding residues (TRP3, SER4, MET7, ARG8, PHE10, ALA11, GLY20, THR21, ARG22, MET23, TRP34, and LYS36) in MMGP1 crucial for its DNA-binding property. Furthermore, computational mutation analysis revealed that aromatic amino acids are crucial for in vivo aggregation, membrane insertion, and DNA-binding property of MMGP1. These data provide new insight into the molecular determinants of MMGP1 antifungal activity and also serves as the template for the design of novel peptide antibiotics.
C1 [Pushpanathan, Muthuirulan] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
   [Pooja, Sharma] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20740 USA.
   [Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash] Madurai Kamaraj Univ, Sch Biol Sci, Dept Genet, Madurai 625021, Tamil Nadu, India.
RP Rajendhran, J (reprint author), Madurai Kamaraj Univ, Sch Biol Sci, Dept Genet, Madurai 625021, Tamil Nadu, India.
EM jrajendhran@gmail.com
OI Pushpanathan, Muthuirulan/0000-0001-6240-3073
NR 34
TC 2
Z9 2
U1 3
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD MAY
PY 2016
VL 13
IS 5
BP 1656
EP 1667
DI 10.1021/acs.molpharmaceut.5b00086
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DL3FM
UT WOS:000375519600022
PM 26987762
ER

PT J
AU Nowinski, CJ
   Siderowf, A
   Simuni, T
   Wortman, C
   Moy, C
   Cella, D
AF Nowinski, Cindy J.
   Siderowf, Andrew
   Simuni, Tanya
   Wortman, Catherine
   Moy, Claudia
   Cella, David
TI Neuro-QoL health-related quality of life measurement system: Validation
   in Parkinson's disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE health-related quality of life; patient-reported outcomes; assessment;
   Parkinson's disease
ID SUBJECTIVE MEMORY COMPLAINTS; MILD COGNITIVE IMPAIRMENT;
   PATIENT-REPORTED OUTCOMES; OLDER-PEOPLE; ITEM BANKS; SCALE; CANCER;
   QUESTIONNAIRE; SYMPTOMS; FUTURE
AB IntroductionNeuro-QoL is a multidimensional patient-reported outcome measurement system assessing aspects of physical, mental, and social health identified by neurology patients and caregivers as important. One of the first neurology-specific patient-reported outcome measure systems created using modern test development methods, Neuro-Qol enables brief, yet precise, assessment and the ability to conduct both PD-specific and cross-disease comparisons. We present results of Neuro-QoL clinical validation using a sample of PD patients.
   MethodsA total of 120 PD patients recruited from academic medical centers were assessed at baseline, 1 week, and 6 months. Assessments included Neuro-QoL and general and PD-specific validity measures.
   ResultsParticipants were 62% male and 95% white (average age=66); H & Y stages were 1 (16%), 2 (61%), 3 (18%), and 4 (5%). Internal consistency and test-retest reliability of Neuro-QoL ranged from Cronbach's alphas=0.81 to 0.94 with intraclass correlation coefficients=0.66 to 0.80. Pearson's correlations between Neuro-QoL and legacy measures were generally moderate and in expected directions. UPDRS Part 2 was moderately correlated with Neuro-QoL Upper Extremity and Mobility, respectively (r's=-0.44; -0.59). Parkinson's Disease Questionnaire-39 and Neuro-QoL measures of similar constructs showed strong-to-moderate correlations (r's=0.70-0.44). Neuro-QoL measures of fatigue, mobility, positive emotion, and emotional/behavioral control showed responsiveness to self-reported change.
   ConclusionsNeuro-QoL is valid for use in PD clinical research. Reliability for all but two measures is sufficient for group comparisons, with some evidence supporting responsiveness to change. Neuro-QoL possesses characteristics, such as brevity, flexibility in administration, and suitability, for cross-disease comparisons that may be advantageous to users in a variety of settings. (c) 2016 Movement Disorder Society
C1 [Nowinski, Cindy J.; Wortman, Catherine; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60201 USA.
   [Nowinski, Cindy J.; Simuni, Tanya] Northwestern Univ, Feinberg Sch Med, Dept Neurol, 625 North Michigan,Suite 2700, Chicago, IL 60201 USA.
   [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA.
   [Moy, Claudia] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Nowinski, CJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, 625 North Michigan,Suite 2700, Chicago, IL 60201 USA.
EM c-nowinski@northwestern.edu
NR 37
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U1 7
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAY
PY 2016
VL 31
IS 5
BP 725
EP 733
DI 10.1002/mds.26546
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DL9CR
UT WOS:000375939500019
PM 26919664
ER

PT J
AU Fei, SS
   Mitchell, AD
   Heskett, MB
   Vocke, CD
   Ricketts, CJ
   Peto, M
   Wang, NJ
   Sonmez, K
   Linehan, WM
   Spellman, PT
AF Fei, Suzanne S.
   Mitchell, Asia D.
   Heskett, Michael B.
   Vocke, Cathy D.
   Ricketts, Christopher J.
   Peto, Myron
   Wang, Nicholas J.
   Sonmez, Kemal
   Linehan, W. Marston
   Spellman, Paul T.
TI Patient-specific factors influence somatic variation patterns in von
   Hippel-Lindau disease renal tumours
SO NATURE COMMUNICATIONS
LA English
DT Article
ID COPY-NUMBER ALTERATIONS; DNA-SEQUENCING DATA; MUTATIONAL SIGNATURES;
   NEXT-GENERATION; HUMAN CANCER; CELL CARCINOMA; EVOLUTION; REVEALS;
   GENOMES; GENE
AB Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel-Lindau disease are at risk of developing multiple independent clear cell renal carcinomas. Here we perform whole-genome sequencing on 40 tumours from six von Hippel-Lindau patients. We confirm that the tumours are clonally independent, having distinct somatic single-nucleotide variants. Although tumours from the same patient show many differences, within-patient patterns are discernible. Single-nucleotide substitution type rates are significantly different between patients and show biases in trinucleotide mutation context. We also observe biases in chromosome copy number aberrations. These results show that genetic background and/or environment can influence the types of mutations that occur.
C1 [Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Peto, Myron; Spellman, Paul T.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Mail Code CL6S,2730 SW Moody St, Portland, OR 97201 USA.
   [Vocke, Cathy D.; Ricketts, Christopher J.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
   [Wang, Nicholas J.; Sonmez, Kemal] Oregon Hlth & Sci Univ, Dept Biomed Engn, Mail Code CH13B, Portland, OR 97201 USA.
RP Spellman, PT (reprint author), Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Mail Code CL6S,2730 SW Moody St, Portland, OR 97201 USA.
EM spellmap@ohsu.edu
FU Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research; Oregon Health & Science University's Knight
   Cancer Institute
FX We thank our patients and their families for enabling this
   research-without them, our research could not have happened. This
   research was supported by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research and Oregon Health
   & Science University's Knight Cancer Institute.
NR 37
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U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAY
PY 2016
VL 7
AR 11588
DI 10.1038/ncomms11588
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL9DE
UT WOS:000375940900001
PM 27174753
ER

PT J
AU Krausgruber, T
   Schiering, C
   Adelmann, K
   Harrison, OJ
   Chomka, A
   Pearson, C
   Ahern, PP
   Shale, M
   Oukka, M
   Powrie, F
AF Krausgruber, Thomas
   Schiering, Chris
   Adelmann, Krista
   Harrison, Oliver J.
   Chomka, Agnieszka
   Pearson, Claire
   Ahern, Philip P.
   Shale, Matthew
   Oukka, Mohamed
   Powrie, Fiona
TI T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell
   responses in the intestine
SO NATURE COMMUNICATIONS
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; ROR-GAMMA-T; TRANSCRIPTION FACTOR; TH17
   CELLS; SCID MICE; AUTOIMMUNE INFLAMMATION; DEPENDENT COLITIS; T(H)17
   CELLS; DIFFERENTIATION; IL-23
AB IL-23 is a key driver of pathogenic Th17 cell responses. It has been suggested that the transcription factor T-bet is required to facilitate IL-23-driven pathogenic effector functions; however, the precise role of T-bet in intestinal T cell responses remains elusive. Here, we show that T-bet expression by T cells is not required for the induction of colitis or the differentiation of pathogenic Th17 cells but modifies qualitative features of the IL-23-driven colitogenic response by negatively regulating IL-23R expression. Consequently, absence of T-bet leads to unrestrained Th17 cell differentiation and activation characterized by high amounts of IL-17A and IL-22. The combined increase in IL-17A/IL-22 results in enhanced epithelial cell activation and inhibition of either IL-17A or IL-22 leads to disease amelioration. Our study identifies T-bet as a key modulator of IL-23-driven colitogenic responses in the intestine and has important implications for understanding of heterogeneity among inflammatory bowel disease patients.
C1 [Krausgruber, Thomas; Schiering, Chris; Adelmann, Krista; Chomka, Agnieszka; Pearson, Claire; Shale, Matthew; Powrie, Fiona] Univ Oxford, Translat Gastroenterol Unit, Div Expt Med, Nuffield Dept Clin Med,John Radcliffe Hosp, Oxford OX3 9DU, England.
   [Krausgruber, Thomas; Chomka, Agnieszka; Pearson, Claire; Powrie, Fiona] Univ Oxford, Kennedy Inst Rheumatol, Roosevelt Dr, Oxford OX3 7FY, England.
   [Harrison, Oliver J.; Ahern, Philip P.] Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
   [Oukka, Mohamed] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA 98101 USA.
   [Krausgruber, Thomas] Austrian Acad Sci, CeMM Res Ctr Mol Med, Lazarettgasse 14,AKH BT 25-3, A-1090 Vienna, Austria.
   [Schiering, Chris] Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England.
   [Harrison, Oliver J.] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Parasit Dis Lab,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Ahern, Philip P.] Washington Univ, Ctr Genome Sci & Syst Biol, Sch Med, St Louis, MO 63108 USA.
   [Shale, Matthew] Stanford Univ, Inst Immun Transplantat & Infect, Sch Med, Stanford, CA 94305 USA.
RP Krausgruber, T; Schiering, C; Powrie, F (reprint author), Univ Oxford, Translat Gastroenterol Unit, Div Expt Med, Nuffield Dept Clin Med,John Radcliffe Hosp, Oxford OX3 9DU, England.; Krausgruber, T; Powrie, F (reprint author), Univ Oxford, Kennedy Inst Rheumatol, Roosevelt Dr, Oxford OX3 7FY, England.
EM tkrausgruber@cemm.oeaw.ac.at; chris.schiering@crick.ac.uk;
   fiona.powrie@kennedy.ox.ac.uk
OI Krausgruber, Thomas/0000-0002-1374-0329; Stockenhuber,
   Krista/0000-0003-3608-064X; Schiering, Chris/0000-0001-7902-6024
FU Wellcome Trust; Fondation Louis Jeantet
FX T.K., C.S., K.A., A.C., O.J.H., M.S. and F.P. are supported by the
   Wellcome Trust. F.P. is also supported by Fondation Louis Jeantet. We
   thank Dan Littman for providing the Rorc<SUP>-/-</SUP> strain and Yoram
   Groner for providing Runx3 antibody. We thank all members of the Oxford
   Translational Gastroenterology Unit, the Dunn School of Pathology and
   the Kennedy Institute of Rheumatology for assistance and support. We are
   grateful to Helen Ferry and Kate Alford for essential flow cytometry
   support and the staff of the University of Oxford for excellent animal
   care.
NR 60
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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 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAY
PY 2016
VL 7
AR 11627
DI 10.1038/ncomms11627
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM1NX
UT WOS:000376113600001
PM 27193261
ER

PT J
AU Sharpe, MJ
   Schoenbaum, G
AF Sharpe, Melissa J.
   Schoenbaum, Geoffrey
TI Back to basics: Making predictions in the orbitofrontal-amygdala circuit
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Review
DE Orbitofrontal cortex; Basolateral amygdala; Associative learning;
   State-specific learning
ID ORBITAL PREFRONTAL CORTEX; BASOLATERAL AMYGDALA; REINFORCER DEVALUATION;
   NEURONAL-ACTIVITY; REWARD PREFERENCE; MACACA-MULATTA; LESIONS; TASK;
   EXTINCTION; REVERSAL
AB Underlying many complex behaviors are simple learned associations that allow humans and animals to anticipate the consequences of their actions. The orbitofrontal cortex and basolateral amygdala are two regions which are crucial to this process. In this review, we go back to basics and discuss the literature implicating both these regions in simple paradigms requiring the development of associations between stimuli and the motivationally-significant outcomes they predict. Much of the functional research surrounding this ability has suggested that the orbitofrontal cortex and basolateral amygdala play very similar roles in making these predictions. However, electrophysiological data demonstrates critical differences in the way neurons in these regions respond to predictive cues, revealing a difference in their functional role. On the basis of these data and theories that have come before, we propose that the basolateral amygdala is integral to updating information about cue-outcome contingencies whereas the orbitofrontal cortex is critical to forming a wider network of past and present associations that are called upon by the basolateral amygdala to benefit future learning episodes. The tendency for orbitofrontal neurons to encode past and present contingencies in distinct neuronal populations may facilitate its role in the formation of complex, high-dimensional state-specific associations. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Sharpe, Melissa J.; Schoenbaum, Geoffrey] NIDA, Baltimore, MD 21224 USA.
   [Sharpe, Melissa J.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
   [Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
   [Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
RP Sharpe, MJ; Schoenbaum, G (reprint author), 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM melissa.sharpe@nih.gov; geoffrey.schoenbaum@nih.gov
OI Schoenbaum, Geoffrey/0000-0001-8180-0701
NR 58
TC 2
Z9 2
U1 3
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
EI 1095-9564
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD MAY
PY 2016
VL 131
BP 201
EP 206
DI 10.1016/j.nlm.2016.04.009
PG 6
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
   Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DM3CR
UT WOS:000376224900025
PM 27112314
ER

PT J
AU Holland, PC
   Schiffino, FL
AF Holland, Peter C.
   Schiffino, Felipe L.
TI Mini-review: Prediction errors, attention and associative learning
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Review
DE Attention; Prediction error; Pearce-Hall model; Associability;
   Associative learning
ID AMYGDALA CENTRAL NUCLEUS; POSTERIOR PARIETAL CORTEX; SURPRISE-INDUCED
   ENHANCEMENT; HIPPOCAMPAL CHOLINERGIC INPUT; LESIONS DISRUPT INCREMENTS;
   BASOLATERAL AMYGDALA; ASSOCIABILITY CHANGES; STIMULUS SALIENCE; CUE
   ASSOCIABILITY; SELECTIVE REMOVAL
AB Most modern theories of associative learning emphasize a critical role for prediction error (PE, the difference between received and expected events). One class of theories, exemplified by the Rescorla-Wagner (1972) model, asserts that PE determines the effectiveness of the reinforcer or unconditioned stimulus (US): surprising reinforcers are more effective than expected ones. A second class, represented by the Pearce-Hall (1980) model, argues that PE determines the associability of conditioned stimuli (CSs), the rate at which they may enter into new learning: the surprising delivery or omission of a reinforcer enhances subsequent processing of the CSs that were present when PE was induced. In this mini review we describe evidence, mostly from our laboratory, for PE-induced changes in the associability of both CSs and USs, and the brain systems involved in the coding, storage and retrieval of these altered associability values. This evidence favors a number of modifications to behavioral models of how PE influences event processing, and suggests the involvement of widespread brain systems in animals' responses to PE. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Holland, Peter C.; Schiffino, Felipe L.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
   [Schiffino, Felipe L.] NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Holland, PC (reprint author), Dept Psychol & Brain Sci, 3400 North Charles St, Baltimore, MD 21218 USA.
EM pch@jhu.edu
FU National Institutes of Health [MH-53667]
FX Most of the research described in this article was funded by Grant
   MH-53667 from the National Institutes of Health.
NR 66
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Z9 6
U1 6
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
EI 1095-9564
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD MAY
PY 2016
VL 131
BP 207
EP 215
DI 10.1016/j.nlm.2016.02.014
PG 9
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
   Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DM3CR
UT WOS:000376224900026
PM 26948122
ER

PT J
AU Lovinger, DM
   Morgan, D
AF Lovinger, David M.
   Morgan, David
TI Aryeh Routtenberg (December 1, 1939-February 27, 2016) In Memoriam
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Biographical-Item
ID SELF-STIMULATION; ENTORHINAL CORTEX; DENTATE GYRUS; BRAIN; STARVATION;
   LESIONS; CELLS; RATS
C1 [Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20832 USA.
   [Morgan, David] Univ S Florida, Alzheimer Inst, Tampa, FL 33612 USA.
   [Morgan, David] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL 33612 USA.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Rockville, MD 20832 USA.
NR 16
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
EI 1095-9564
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD MAY
PY 2016
VL 131
BP 216
EP 217
DI 10.1016/j.nlm.2016.04.004
PG 2
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
   Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DM3CR
UT WOS:000376224900027
ER

PT J
AU Kagan, J
   Giang, DD
   Iademarco, MF
   Phung, VTT
   Lau, CY
   Quang, NN
AF Kagan, Jonathan
   Giang, Dao Duc
   Iademarco, Michael F.
   Phung, Van T. T.
   Lau, Chuen-Yen
   Nguyen Ngo Quang
TI Assessing Clinical Research Capacity in Vietnam: A Framework for
   Strengthening Capability for Clinical Trials in Developing Countries
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID HEALTH RESEARCH
AB Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts.
C1 [Kagan, Jonathan] NIAID, NIH, Div Clin Res, 5601 Fishers Ln,Room 4B40, Bethesda, MD 20892 USA.
   [Giang, Dao Duc] Clin Res & Lab Sci, FH1 360, Hanoi, Vietnam.
   [Iademarco, Michael F.] Ctr Dis Control & Prevent, Off Publ Hlth Sci Serv, Ctr Surveillance Epidemiol & Lab Serv, Atlanta, GA USA.
   [Iademarco, Michael F.; Phung, Van T. T.] US Mission, Hlth Affairs Attache Off, Hanoi, Vietnam.
   [Lau, Chuen-Yen] NIAID, NIH, Div Clin Res, Collaborat Clin Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Nguyen Ngo Quang] Vietnam Minist Hlth Adm Sci Technol & Training, Hanoi, Vietnam.
RP Kagan, J (reprint author), NIAID, NIH, Div Clin Res, 5601 Fishers Ln,Room 4B40, Bethesda, MD 20892 USA.
EM jkagan@niaid.nih.gov
FU HHS Office of Global Health Affairs; National Institute of Allergy and
   Infectious Diseases, NIH, HHS; Embassy Science Fellows Program, Office
   of Science and Technology Cooperation, Bureau of Oceans, Environment and
   Science, U.S. Department of State
FX This work was supported by the HHS Office of Global Health Affairs; the
   National Institute of Allergy and Infectious Diseases, NIH, HHS; and the
   Embassy Science Fellows Program, Office of Science and Technology
   Cooperation, Bureau of Oceans, Environment and Science, U.S. Department
   of State.
NR 30
TC 0
Z9 0
U1 1
U2 2
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD MAY-JUN
PY 2016
VL 131
IS 3
BP 396
EP 403
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DM3AK
UT WOS:000376219000005
PM 27252559
ER

PT J
AU Vazquez-Prokopec, GM
   Perkins, TA
   Waller, LA
   Lloyd, AL
   Reiner, RC
   Scott, TW
   Kitron, U
AF Vazquez-Prokopec, Gonzalo M.
   Perkins, T. Alex
   Waller, Lance A.
   Lloyd, Alun L.
   Reiner, Robert C., Jr.
   Scott, Thomas W.
   Kitron, Uriel
TI Coupled Heterogeneities and Their Impact on Parasite Transmission and
   Control
SO TRENDS IN PARASITOLOGY
LA English
DT Review
ID WEST-NILE-VIRUS; AEDES-AEGYPTI; POPULATION-DYNAMICS;
   INFECTIOUS-DISEASES; EPIDEMIC MODELS; DENGUE VECTOR; BORNE DISEASE;
   HOST; BEHAVIOR; AGGREGATION
AB Most host-parasite systems exhibit remarkable heterogeneity in the contribution to transmission of certain individuals, locations, host infectious states, or parasite strains. While significant advancements have been made in the understanding of the impact of transmission heterogeneity in epidemic dynamics and parasite persistence and evolution, the knowledge base of the factors contributing to transmission heterogeneity is limited. We argue that research efforts should move beyond considering the impact of single sources of heterogeneity and account for complex couplings between conditions with potential synergistic impacts on parasite transmission. Using theoretical approaches and empirical evidence from various host-parasite systems, we investigate the ecological and epidemiological significance of couplings between heterogeneities and discuss their potential role in transmission dynamics and the impact of control.
C1 [Vazquez-Prokopec, Gonzalo M.; Kitron, Uriel] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.
   [Vazquez-Prokopec, Gonzalo M.; Perkins, T. Alex; Lloyd, Alun L.; Reiner, Robert C., Jr.; Scott, Thomas W.; Kitron, Uriel] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
   [Perkins, T. Alex] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
   [Waller, Lance A.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
   [Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA.
   [Lloyd, Alun L.] N Carolina State Univ, Dept Math, Box 8205, Raleigh, NC 27695 USA.
   [Reiner, Robert C., Jr.] Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA.
   [Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
RP Vazquez-Prokopec, GM (reprint author), Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.; Vazquez-Prokopec, GM (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM gmvazqu@emory.edu
FU US National Institutes of Heath - National Institute of Allergy and
   Infectious Diseases (NIH/NIAID) [P01AI098670]; Research and Policy for
   Infectious Disease Dynamics (RAPIDD) program of the Science and
   Technology Directory; Fogarty International Center, National Institutes
   of Health; Department of Homeland Security
FX We would like to thank Valerie Paz-Soldan, John Elder, Alan Rothman,
   Louis Lambrechts, and Amy Morrison for helpful comments during the
   development of our ideas. We also appreciate the feedback provided by
   two anonymous reviewers. This research was funded by a grant from the US
   National Institutes of Heath - National Institute of Allergy and
   Infectious Diseases (NIH/NIAID) award number P01AI098670 (T.W.S.
   principal investigator, G.M.V-P. co-principal investigator) and by the
   Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
   the Science and Technology Directory, Department of Homeland Security,
   and Fogarty International Center, National Institutes of Health.
NR 79
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U1 5
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4922
EI 1471-5007
J9 TRENDS PARASITOL
JI Trends Parasitol.
PD MAY
PY 2016
VL 32
IS 5
BP 356
EP 367
DI 10.1016/j.pt.2016.01.001
PG 12
WC Parasitology
SC Parasitology
GA DM0SO
UT WOS:000376056300005
PM 26850821
ER

PT J
AU Dauter, Z
AF Dauter, Zbigniew
TI Objective evaluation of radiation damage in a nucleoprotein complex
SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
LA English
DT Editorial Material
DE radiation damage; nucleoproteins
ID X-RAY-ENERGIES; CRYSTALS
C1 [Dauter, Zbigniew] NCI, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA.
RP Dauter, Z (reprint author), NCI, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA.
EM zdauter@anl.gov
NR 10
TC 0
Z9 0
U1 1
U2 1
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2059-7983
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Struct. Biol.
PD MAY
PY 2016
VL 72
BP 601
EP 602
DI 10.1107/S2059798316006550
PN 5
PG 2
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA DL7WS
UT WOS:000375851700001
PM 27139623
ER

PT J
AU Gonzalez, B
   Rivero-Echeto, C
   Muniz, JA
   Cadet, JL
   Garcia-Rill, E
   Urbano, FJ
   Bisagno, V
AF Gonzalez, Betina
   Rivero-Echeto, Celeste
   Muniz, Javier A.
   Cadet, Jean Lud
   Garcia-Rill, Edgar
   Urbano, Francisco J.
   Bisagno, Veronica
TI Methamphetamine blunts Ca2+ currents and excitatory synaptic
   transmission through D1/5 receptor-mediated mechanisms in the mouse
   medial prefrontal cortex
SO ADDICTION BIOLOGY
LA English
DT Article
DE Dopamine receptors; glutamate; methamphetamine; prefrontal cortex;
   voltage-gated calcium channels
ID CALCIUM-CHANNELS; I-H; DOPAMINE-RECEPTORS; PYRAMIDAL NEURONS;
   UP-REGULATION; RAT; MODULATION; PLASTICITY; D-1; ACTIVATION
AB Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1mg/kg) depressed voltage-dependent calcium currents (I-Ca) and increased hyperpolarization-activated cation current (I-H) amplitude and the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons. Most of these effects were blocked by systemic co-administration of the D1/D5 receptor antagonist SCH23390 (0.5 and 0.05mg/kg). In vitroMETH (i.e. bath-applied to slices from naive-treated animals) was able to emulate its systemic effects on I-Ca and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Ca(v)2.1), N-type Cacna1b (Ca(v)2.2), T-type Ca(v)3.1 Cacna1g, Ca(v)3.2 Cacna1h, Ca(v)3.3 Cacna1i and the auxiliary subunit Cacna2d1 (21); (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D1/5 receptor blockade. Altogether, these altered mechanisms affecting synaptic physiology and transcriptional regulation may underlie PFC functional alterations that could lead to PFC impairments observed in METH-addicted individuals.
C1 [Gonzalez, Betina; Muniz, Javier A.; Bisagno, Veronica] Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn, Inst Invest Farmacol, RA-1053 Buenos Aires, DF, Argentina.
   [Rivero-Echeto, Celeste; Urbano, Francisco J.] Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn, Lab Fisiol & Biol Mol, Inst Fisiol Biol Mol & Neurociencias,Dept Fisiol, RA-1053 Buenos Aires, DF, Argentina.
   [Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD USA.
   [Garcia-Rill, Edgar] Univ Arkansas Med Sci, Ctr Translat Neurosci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA.
RP Bisagno, V (reprint author), ININFA UBA CONICET, Inst Invest Farmacol, Junin 956,Piso 5,Buenos Aires C1113, Buenos Aires, DF, Argentina.
EM vbisagno@ffyb.uba.ar
FU FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica; BID,
   Argentina [1728 OC.AR.T 2012-0924, 1728 OC.AR. PICT-2012-1769]; UBACYT
   [20120130101305BA]; NIH [P20 GM103425];  [PIP 11420100100072]
FX Dr. Bisagno has been authorized to study drug abuse substances in animal
   models by A.N.M.A.T. (National Board of Medicine Food and Medical
   Technology, Ministerio de Salud, Argentina). The authors would like to
   thank Dr. Jose Luis Rozas for his suggestions to improve this manuscript
   and Dr. M. Gustavo Murer for kindly providing the SCH23390 used in this
   study. This work is supported by grants PIP 11420100100072,
   FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica; BID 1728
   OC.AR.T 2012-0924, Argentina (to Dr. Bisagno) and FONCYT-Agencia
   Nacional de Promocion Cientifica y Tecnologica; BID 1728 OC.AR.
   PICT-2012-1769, Argentina and UBACYT 2014-2017 #20120130101305BA (to Dr.
   Urbano). In addition, this work was supported by NIH award P20 GM103425
   to the Center for Translational Neuroscience, UAMS, USA.
NR 56
TC 2
Z9 2
U1 5
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
EI 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD MAY
PY 2016
VL 21
IS 3
BP 589
EP 602
DI 10.1111/adb.12249
PG 14
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA DJ8TN
UT WOS:000374486200006
PM 25871318
ER

PT J
AU Wang, LB
   Zou, F
   Zhai, TY
   Lei, Y
   Tan, SW
   Jin, X
   Ye, EM
   Shao, YC
   Yang, YH
   Yang, Z
AF Wang, Lubin
   Zou, Feng
   Zhai, Tianye
   Lei, Yu
   Tan, Shuwen
   Jin, Xiao
   Ye, Enmao
   Shao, Yongcong
   Yang, Yihong
   Yang, Zheng
TI Abnormal gray matter volume and resting-state functional connectivity in
   former heroin-dependent individuals abstinent for multiple years
SO ADDICTION BIOLOGY
LA English
DT Article
DE Functional connectivity; gray matter volume; heroin addiction;
   impulsivity; multi-year abstinence
ID HUMAN BRAIN; MOTOR CORTEX; NETWORKS; COCAINE; ADDICTION; USERS; FMRI;
   MRI; IMPULSIVITY; DECREASES
AB Previous studies have suggested that heroin addiction is associated with structural and functional brain abnormalities. However, it is largely unknown whether these characteristics of brain abnormalities would be persistent or restored after long periods of abstinence. Considering the very high rates of relapse, we hypothesized that there may exist some latent neural vulnerabilities in abstinent heroin users. In this study, structural and resting-state functional magnetic resonance imaging data were collected from 30 former heroin-dependent (FHD) subjects who were drug free for more than 3 years and 30 non-addicted control (CN) volunteers. Voxel-based morphometry was used to identify possible gray matter volume differences between the FHD and CN groups. Alterations in resting-state functional connectivity in FHD were examined using brain areas with gray matter deficits as seed regions. Significantly reduced gray matter volume was observed in FHD in an area surrounding the parieto-occipital sulcus, which included the precuneus and cuneus. Functional connectivity analyses revealed that the FHD subjects showed reduced positive correlation within the default mode network and visual network and decreased negative correlation between the default mode network, visual network and task positive network. Moreover, the altered functional connectivity was correlated with self-reported impulsivity scores in the FHD subjects. Our findings suggest that disruption of large-scale brain systems is present in former heroin users even after multi-year abstinence, which could serve as system-level neural underpinnings for behavioral dysfunctions associated with addiction.
C1 [Wang, Lubin; Zou, Feng; Zhai, Tianye; Lei, Yu; Tan, Shuwen; Jin, Xiao; Ye, Enmao; Shao, Yongcong; Yang, Zheng] Beijing Inst Basic Med Sci, Cognit & Mental Hlth Res Ctr, 27 Taiping Rd, Beijing 100850, Peoples R China.
   [Yang, Yihong] NIDA, Neuroimaging Res Branch, Baltimore, MD USA.
RP Yang, Z (reprint author), Beijing Inst Basic Med Sci, Cognit & Mental Hlth Res Ctr, 27 Taiping Rd, Beijing 100850, Peoples R China.
EM yangzhengchina@aliyun.com
FU National Science Foundation of China [81271470, 31300840]; Beijing
   Natural Science Foundation [4144092]; Intramural Research Program of the
   National Institute on Drug Abuse, National Institutes of Health
FX This work was supported by the National Science Foundation of China
   (81271470, 31300840) and the Beijing Natural Science Foundation
   (4144092). Y.Y. was supported by the Intramural Research Program of the
   National Institute on Drug Abuse, National Institutes of Health.
NR 57
TC 5
Z9 5
U1 6
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
EI 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD MAY
PY 2016
VL 21
IS 3
BP 646
EP 656
DI 10.1111/adb.12228
PG 11
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA DJ8TN
UT WOS:000374486200010
PM 25727574
ER

PT J
AU El Haj, M
   Antoine, P
   Amouyel, P
   Lambert, JC
   Pasquier, F
   Kapogiannis, D
AF El Haj, Mohamad
   Antoine, Pascal
   Amouyel, Philippe
   Lambert, Jean-Charles
   Pasquier, Florence
   Kapogiannis, Dimitrios
TI Apolipoprotein E (APOE) epsilon 4 and episodic memory decline in
   Alzheimer's disease: A review
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Alzheimer's disease; APOE; Apolipoprotein E; Episodic memory
ID MILD COGNITIVE IMPAIRMENT; CATECHOL-O-METHYLTRANSFERASE; HEALTHY
   OLDER-ADULTS; E GENOTYPE; NEURODEGENERATIVE DISEASES; AUTONOETIC
   CONSCIOUSNESS; AUTOBIOGRAPHICAL MEMORY; VAL(66)MET POLYMORPHISM;
   ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES
AB A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E epsilon 4 (APOE epsilon 4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE epsilon 4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE epsilon 4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE epsilon 4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE epsilon 4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE epsilon 4 (i.e., zero, one, or two epsilon 4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE epsilon 4 and episodic memory decline in AD. (C) 2016 Elsevier B.V. All rights reserved.
C1 [El Haj, Mohamad; Antoine, Pascal] Univ Lille, Lab SCALab, UMR CNRS 9193, F-59653 Villeneuve Dascq, France.
   [Amouyel, Philippe; Lambert, Jean-Charles] Univ Lille 2, Inst Pasteur Lille, INSERM, U744, Lille, France.
   [Pasquier, Florence] Univ Lille Nord France, UDSL & Memory Clin, CHU, Lille, France.
   [Kapogiannis, Dimitrios] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
RP El Haj, M (reprint author), Univ Lille, Lab SCALab, UMR CNRS 9193, F-59653 Villeneuve Dascq, France.
EM mohamad.elhaj@univ-lille3.fr
RI Lambert, jean-charles/A-9553-2014
OI Lambert, jean-charles/0000-0003-0829-7817
FU LABEX (excellence laboratory, program investment for the future)
   DIS-TALZ (Development of Innovative Strategies for a Transdisciplinary
   approach to Alzheimer disease); Intramural Research Program of the
   National Institute on Aging, National Institutes of Health (NIA/NIH)
FX Dr. El Haj, Pr. Antoine, Pr. Philippe Amouyel, Dr. Jean-Charles Lambert,
   and Pr. Florence Pasquier were supported by the LABEX (excellence
   laboratory, program investment for the future) DIS-TALZ (Development of
   Innovative Strategies for a Transdisciplinary approach to Alzheimer
   disease). Dr. Kapogiannis was supported by the Intramural Research
   Program of the National Institute on Aging, National Institutes of
   Health (NIA/NIH).
NR 88
TC 5
Z9 5
U1 6
U2 15
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD MAY
PY 2016
VL 27
BP 15
EP 22
DI 10.1016/j.arr.2016.02.002
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DL3FH
UT WOS:000375519100002
PM 26876367
ER

PT J
AU Wilson, Y
   Danis, M
   White, A
AF Wilson, Yolonda
   Danis, Marion
   White, Amina
TI Response to Open Peer Commentaries on "Bioethicists Can and Should
   Contribute to Addressing Racism"
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Letter
ID RACE
C1 [Wilson, Yolonda] Howard Univ, Washington, DC USA.
   [Danis, Marion; White, Amina] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Danis, M (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,RM 1C118, Bethesda, MD 20892 USA.
EM mdanis@nih.gov
FU Department of Bioethics in the NIH Clinical Center, National Institutes
   of Health intramural program
FX This work was funded in part by the Department of Bioethics in the NIH
   Clinical Center, which is part of National Institutes of Health
   intramural program. We acknowledge the very helpful input of Akilah
   Jefferson, who serves as a fellow in the Department of Bioethics.
NR 13
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD MAY
PY 2016
VL 16
IS 5
BP W1
EP W4
DI 10.1080/15265161.2016.1160163
PG 4
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
   Biomedical Social Sciences
GA DK4TA
UT WOS:000374911100001
PM 27111377
ER

PT J
AU Paulin-Prado, P
   Nishimura, K
   Freimanis-Hance, L
   Hunsberger, S
   Beigel, J
   Fraga, AG
   Hernandez, AAO
   Llamosas-Gallardo, B
   Moreno-Espinosa, S
   Magana-Aquino, M
   Palacios, GMR
   Ramirez-Venegas, A
AF Paulin-Prado, Paulina
   Nishimura, Katherine
   Freimanis-Hance, Laura
   Hunsberger, Sally
   Beigel, John
   Galindo Fraga, Arturo
   Ortiz Hernandez, Ana A.
   Llamosas-Gallardo, Beatriz
   Moreno-Espinosa, Sarbelio
   Magana-Aquino, Martin
   Ruiz Palacios, Guillermo M.
   Ramirez-Venegas, Alejandra
CA Mexico Emerging Infect Dis
TI Clinical characteristics of asthmatic patients with influenza-like
   illness and risk of severe exacerbations in Mexico
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; HUMAN RHINOVIRUS C; BODY-MASS INDEX;
   RESPIRATORY-TRACT; EMERGENCY-DEPARTMENT; HOSPITAL ADMISSIONS;
   VIRAL-INFECTIONS; CHILDREN; ADULTS; OBESITY
AB Background: Patients with chronic inflammatory lung diseases, such as asthma, are at higher risk for influenza-like illness (ILI) complications. Viral infections are known to trigger asthma exacerbations, but a thorough description of the clinical characteristics of ILI-associated asthma exacerbations and the role of viruses as a risk factor for severe exacerbation (SE) in ILI has not been published yet.
   Objective: To investigate risk factors for SE in patients with ILI and asthma.
   Methods: Patients with ILI symptoms were recruited from 6 hospitals of Mexico (LaRed sites) during 2010 to 2014. Those with a previous asthma diagnosis and ILI symptoms and who were 5 years or older were included. Patients were assigned as cases or controls based on symptoms reported. SE was defined when participants presented with wheezing or dyspnea and required hospitalization.
   Results: A total of 486 patients with ILI and a diagnosis of asthma were included. There were no differences in the proportion, number, or type of viral illness among those with and without SE. Those with SE were less likely to report ILI symptoms. Muscle pain and nasal drip were predictors for patients not progressing to SE. A delay in seeking medical care was associated with SE (odds ratio, 2.93; 95% CI, 1.46-5.88).
   Conclusion: The presence of a particular virus did not predict SE. ILI symptoms in asthma patients are not associated with severe exacerbation. Patients with asthma should be encouraged to seek early medical care when ILI symptoms are first noticed to prevent serious complications. (C) 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
C1 [Paulin-Prado, Paulina; Ramirez-Venegas, Alejandra] Inst Nacl Enfermedades Resp, Calzada de Tlalpan 4502,Col Secc 16, Mexico City 14080, DF, Mexico.
   [Nishimura, Katherine; Hunsberger, Sally] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Freimanis-Hance, Laura] Westat Corp, Rockville, MD USA.
   [Beigel, John] Leidos Biomed, Bethesda, MD USA.
   [Galindo Fraga, Arturo] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico.
   [Ortiz Hernandez, Ana A.; Llamosas-Gallardo, Beatriz] Inst Nacl Pediat, Mexico City, DF, Mexico.
   [Moreno-Espinosa, Sarbelio] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico.
   [Magana-Aquino, Martin] Hosp Cent Dr Ignacio Morones Prieto, San Luis Potosi, Mexico.
RP Ramirez-Venegas, A (reprint author), Inst Nacl Enfermedades Resp, Calzada de Tlalpan 4502,Col Secc 16, Mexico City 14080, DF, Mexico.
EM aleravas@hotmail.com
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 AI999999]; NCI
   NIH HHS [HHSN261200800001E]; NIAID NIH HHS [HHSN272200900001C,
   HHSN272200900031C]
NR 40
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 1081-1206
EI 1534-4436
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD MAY
PY 2016
VL 116
IS 5
BP 402
EP 407
DI 10.1016/j.anai.2016.03.007
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA DL8AB
UT WOS:000375860600006
PM 27052815
ER

PT J
AU Powis, SJ
   Colbert, RA
AF Powis, Simon J.
   Colbert, Robert A.
TI HLA-B27: The Story Continues to Unfold
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Editorial Material
ID ANKYLOSING-SPONDYLITIS; ENDOPLASMIC-RETICULUM; HEAVY-CHAINS;
   SPONDYLOARTHRITIS
C1 [Powis, Simon J.] Univ St Andrews, St Andrews, Fife, Scotland.
   [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Colbert, RA (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, Bldg 10,CRC,Room 1-5142,10 Ctr Dr,MSC 1102, Bethesda, MD 20892 USA.
EM colbertr@mail.nih.gov
NR 17
TC 1
Z9 1
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2016
VL 68
IS 5
BP 1057
EP 1059
DI 10.1002/art.39566
PG 3
WC Rheumatology
SC Rheumatology
GA DL3RT
UT WOS:000375551600003
PM 26749536
ER

PT J
AU Newman, KA
   Ahlman, MA
   Hughes, M
   Malayeri, AA
   Pratt, D
   Grayson, PC
AF Newman, Kam A.
   Ahlman, Mark A.
   Hughes, Marybeth
   Malayeri, Ashkan A.
   Pratt, Drew
   Grayson, Peter C.
TI Clinical Images: Diagnosis of giant cell arteritis in an asymptomatic
   patient
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Editorial Material
ID LARGE-VESSEL VASCULITIS
C1 [Newman, Kam A.; Ahlman, Mark A.; Hughes, Marybeth; Malayeri, Ashkan A.; Pratt, Drew; Grayson, Peter C.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Newman, KA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2016
VL 68
IS 5
BP 1135
EP 1135
DI 10.1002/art.39517
PG 1
WC Rheumatology
SC Rheumatology
GA DL3RT
UT WOS:000375551600012
PM 26606396
ER

PT J
AU Fleischer, SJ
   Daridon, C
   Fleischer, V
   Lipsky, PE
   Dorner, T
AF Fleischer, Sarah J.
   Daridon, Capucine
   Fleischer, Vanessa
   Lipsky, Peter E.
   Doerner, Thomas
TI Enhanced Tyrosine Phosphatase Activity Underlies Dysregulated B Cell
   Receptor Signaling and Promotes Survival of Human Lupus B Cells
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID LYN-DEFICIENT MICE; AUTOIMMUNE-DISEASE; NEGATIVE SELECTION;
   ERYTHEMATOSUS; ACTIVATION; KINASE; CD22; SLE; TRANSDUCTION; ASSOCIATION
AB Objective. Systemic lupus erythematosus (SLE) is associated with hyperactivity of B cells and abnormalities of B cell receptor (BCR) signaling. To address the linkage between dysregulated BCR signaling and increased B cell function, we assessed immediate phosphorylation events in lupus B cells.
   Methods. B cells from SLE patients and healthy donors were analyzed by flow cytometry to assess phosphorylated CD22, Syk, and Akt as well as the basal expression of the BCR coreceptors CD22 and CD19. Confocal microscopy studies determined the recruitment of CD22 and the tyrosine phosphatase SH2 domain-containing phosphatase 1 to the activated BCR complex. Additionally, phosphatase activity in SLE versus healthy donor B cells was measured.
   Results. B cells from SLE patients showed diminished Syk phosphorylation and reduced intracellular calcium release after BCR activation as compared to B cells from healthy donors. This was related to an enhanced activity of tyrosine, but not serine/threonine, phosphatases and was corrected by inhibition of tyrosine phosphatase activity. In contrast to reduced Syk phosphorylation after BCR activation, phosphorylation of Akt was significantly increased in SLE B cells. The disturbed balance between Syk and Akt phosphorylation was significantly correlated with B cell survival following BCR engagement. Furthermore, CD27-, but not CD27+, B cells from SLE patients displayed increased expression and phosphorylation of the inhibitory BCR coreceptor CD22.
   Conclusion. These results indicate that an imbalance between serine and tyrosine phosphatases in SLE contributes to an intrinsically disturbed balance of BCR-initiated signaling pathways, resulting in enhanced survival of lupus B cells and differentiation into plasma cells.
C1 [Fleischer, Sarah J.; Daridon, Capucine; Fleischer, Vanessa; Doerner, Thomas] Charite, D-13353 Berlin, Germany.
   [Fleischer, Sarah J.; Daridon, Capucine; Fleischer, Vanessa; Doerner, Thomas] German Rheumatism Res Ctr Berlin, Berlin, Germany.
   [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Dorner, T (reprint author), Charite, Dept Med Rheumatol & Clin Immunol, Charitepl 1, D-10117 Berlin, Germany.
EM thomas.doerner@charite.de
FU DFG [SFB 650, SFB 633 A14, SPP ImmunoBone [Do491/8-2]]
FX Supported by the DFG (SFB 650 project TP12, SFB 650 project TP16, SFB
   633 A14, SPP ImmunoBone [Do491/8-2], and project Do491/7-3).
NR 50
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2016
VL 68
IS 5
BP 1210
EP 1221
DI 10.1002/art.39559
PG 12
WC Rheumatology
SC Rheumatology
GA DL3RT
UT WOS:000375551600021
PM 26713408
ER

PT J
AU Liu, K
   Kurien, BT
   Zimmerman, SL
   Kaufman, KM
   Taft, DH
   Kottyan, LC
   Lazaro, S
   Weaver, CA
   Ice, JA
   Adler, AJ
   Chodosh, J
   Radfar, L
   Rasmussen, A
   Stone, DU
   Lewis, DM
   Li, SB
   Koelsch, KA
   Igoe, A
   Talsania, M
   Kumar, J
   Maier-Moore, JS
   Harris, VM
   Gopalakrishnan, R
   Jonsson, R
   Lessard, JA
   Lu, XL
   Gottenberg, JE
   Anaya, JM
   Cunninghame-Graham, DS
   Huang, AJW
   Brennan, MT
   Hughes, P
   Mei, GG
   Miceli-Richard, C
   Keystone, EC
   Bykerk, VP
   Hirschfield, G
   Xie, G
   Ng, WF
   Nordmark, G
   Eriksson, P
   Omda, R
   Rhodus, NL
   Rischmueller, M
   Rohrer, M
   Sega, BM
   Vvse, TJ
   Wahren-Herlenius, M
   Witte, T
   Pons-Este, B
   Alarcon-Riquelme, ME
   Guthridge, JM
   James, JA
   Lessard, CJ
   Kelly, JA
   Thompson, SD
   Gaffney, PM
   Montgomery, CG
   Edberg, JC
   Kimberly, RP
   Alarcon, GS
   Langefeld, CL
   Gilkeson, GS
   Kamen, DL
   Tsao, BP
   McCune, WJ
   Salmon, JE
   Merrill, JT
   Weisman, MH
   Wallace, DJ
   Utset, T
   Bottinger, EP
   Amos, CI
   Siminovitch, KA
   Mariette, X
   Sivils, KL
   Harley, JB
   Scofield, RH
AF Liu, Ke
   Kurien, Biji T.
   Zimmerman, Sarah L.
   Kaufman, Kenneth M.
   Taft, Diana H.
   Kottyan, Leah C.
   Lazaro, Sara
   Weaver, Carrie A.
   Ice, John A.
   Adler, Adam J.
   Chodosh, James
   Radfar, Lida
   Rasmussen, Astrid
   Stone, Donald U.
   Lewis, David M.
   Li, Shibo
   Koelsch, Kristi A.
   Igoe, Ann
   Talsania, Mitali
   Kumar, Jay
   Maier-Moore, Jacen S.
   Harris, Valerie M.
   Gopalakrishnan, Rajaram
   Jonsson, Roland
   Lessard, James A.
   Lu, Xianglan
   Gottenberg, Jacques -Eric
   Anaya, Juan -Manuel
   Cunninghame-Graham, Deborah S.
   Huang, Andrew J. W.
   Brennan, Michael T.
   Hughes, Pamela
   Mei, Gabor G.
   Miceli-Richard, Corinne
   Keystone, Edward C.
   Bykerk, Vivian P.
   Hirschfield, Gideon
   Xie, Gang
   Ng, Wan-Fai
   Nordmark, Gunnel
   Eriksson, Per
   Omda, Roald
   Rhodus, Nelson L.
   Rischmueller, Maureen
   Rohrer, Michael
   Sega, Barbara M.
   Vvse, Timothy J.
   Wahren-Herlenius, Marie
   Witte, Torsten
   Pons-Este, Bernardo
   Alarcon-Riquelme, Marta E.
   Guthridge, Joel M.
   James, Judith A.
   Lessard, Christopher J.
   Kelly, Jennifer A.
   Thompson, Susan D.
   Gaffney, Patrick M.
   Montgomery, Courtney G.
   Edberg, Jeffrey C.
   Kimberly, Robert P.
   Alarcon, Gracicla S.
   Langefeld, Carl L.
   Gilkeson, Gary S.
   Kamen, Diane L.
   Tsao, Betty P.
   McCune, W. Joseph
   Salmon, Jane E.
   Merrill, Joan T.
   Weisman, Michael H.
   Wallace, Daniel J.
   Utset, Tammy
   Bottinger, Erwin P.
   Amos, Christopher I.
   Siminovitch, Katherine A.
   Mariette, Xavier
   Sivils, Kathy L.
   Harley, John B.
   Scofield, R. Hal
TI X Chromosome Dose and Sex Bias in Autoimmune Diseases
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; JUVENILE
   IDIOPATHIC ARTHRITIS; PREMATURE OVARIAN FAILURE; RHEUMATOID-ARTHRITIS;
   SJOGRENS-SYNDROME; REVISED CRITERIA; WOMEN; CLASSIFICATION;
   ABNORMALITIES
AB Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls.
   Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction.
   Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients.
   Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.
C1 [Liu, Ke; Thompson, Susan D.; Harley, John B.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
   [Liu, Ke; Zimmerman, Sarah L.; Kaufman, Kenneth M.; Taft, Diana H.; Kottyan, Leah C.; Lazaro, Sara; Weaver, Carrie A.; Thompson, Susan D.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
   [Kurien, Biji T.; Maier-Moore, Jacen S.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma Med Res Fdn, Oklahoma City, OK 73190 USA.
   [Kurien, Biji T.; Adler, Adam J.; Maier-Moore, Jacen S.; Scofield, R. Hal] Oklahoma City VA Med Ctr, Oklahoma City, OK USA.
   [Kaufman, Kenneth M.; Harley, John B.] Cincinnati VA Med Ctr, Cincinnati, OH USA.
   [Ice, John A.; Adler, Adam J.; Rasmussen, Astrid; Koelsch, Kristi A.; Igoe, Ann; Kumar, Jay; Harris, Valerie M.; Alarcon-Riquelme, Marta E.; Guthridge, Joel M.; James, Judith A.; Lessard, Christopher J.; Kelly, Jennifer A.; Gaffney, Patrick M.; Montgomery, Courtney G.; Sivils, Kathy L.] Oklahoma Med Res Fdn, 825 NE 13th St,MS24, Oklahoma City, OK 73104 USA.
   [Chodosh, James] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
   [Chodosh, James] Harvard Univ, Sch Med, Boston, MA USA.
   [Radfar, Lida; Lewis, David M.] Univ Oklahoma, Coll Dent, Oklahoma City, OK USA.
   [Radfar, Lida; Stone, Donald U.; Lewis, David M.; Li, Shibo; Talsania, Mitali; Lu, Xianglan; Merrill, Joan T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
   [Stone, Donald U.; Li, Shibo; Talsania, Mitali; Lu, Xianglan; Merrill, Joan T.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA.
   [Maier-Moore, Jacen S.] Univ Texas El Paso, El Paso, TX 79968 USA.
   [Gopalakrishnan, Rajaram; Huang, Andrew J. W.; Hughes, Pamela; Rohrer, Michael] Univ Minnesota, Minneapolis, MN USA.
   [Jonsson, Roland] Univ Bergen, Bergen, Norway.
   [Jonsson, Roland] Haukeland Hosp, N-5021 Bergen, Norway.
   [Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA.
   [Gottenberg, Jacques -Eric] Strasbourg Univ, Strasbourg, France.
   [Anaya, Juan -Manuel] Univ Rosario, Sch Med & Hlth Sci, Bogota, Colombia.
   [Cunninghame-Graham, Deborah S.; Vvse, Timothy J.] Kings Coll London, London WC2R 2LS, England.
   [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
   [Mei, Gabor G.] MedImmune, Gaithersburg, MD USA.
   [Mei, Gabor G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
   [Miceli-Richard, Corinne] Univ Paris 11, Hop Bicetre, AP HP, Le Kremlin Bicetre, France.
   [Miceli-Richard, Corinne] INSERM, U1012, F-94275 Le Kremlin Bicetre, France.
   [Keystone, Edward C.; Bykerk, Vivian P.; Xie, Gang; Siminovitch, Katherine A.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
   [Keystone, Edward C.; Bykerk, Vivian P.; Xie, Gang; Siminovitch, Katherine A.] Univ Toronto, Toronto, ON, Canada.
   [Bykerk, Vivian P.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
   [Bykerk, Vivian P.] Weill Cornell Med, New York, NY USA.
   [Hirschfield, Gideon] Univ Birmingham, Birmingham, W Midlands, England.
   [Xie, Gang; Siminovitch, Katherine A.] Toronto Gen Hosp, Toronto, ON, Canada.
   [Ng, Wan-Fai] NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
   [Eriksson, Per] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Nordmark, Gunnel] Uppsala Univ, Uppsala, Sweden.
   [Eriksson, Per] Linkoping Univ, Linkoping, Sweden.
   [Omda, Roald] Stavanger Univ Hosp, Stavanger, Norway.
   [Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA.
   [Rischmueller, Maureen] Queen Elizabeth Hosp, Woodville South, SA, Australia.
   [Rischmueller, Maureen] Univ Adelaide, Adelaide, SA, Australia.
   [Sega, Barbara M.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
   [Sega, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
   [Wahren-Herlenius, Marie] Karolinska Inst, Stockholm, Sweden.
   [Witte, Torsten] Hannover Med Sch, Hannover, Germany.
   [Pons-Este, Bernardo] Sanatorio Parque, Rosario, Argentina.
   [Alarcon-Riquelme, Marta E.] Ctr Pfizer Univ Granada Junta de Andalucia Genom, Granada, Spain.
   [Edberg, Jeffrey C.; Kimberly, Robert P.; Alarcon, Gracicla S.] Univ Alabama Birmingham, Birmingham, AL USA.
   [Langefeld, Carl L.] Wake Forest Univ, Winston Salem, NC 27109 USA.
   [Gilkeson, Gary S.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC USA.
   [Kamen, Diane L.] Med Univ S Carolina, Charleston, SC USA.
   [Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [McCune, W. Joseph] Univ Michigan, Coll Med, Ann Arbor, MI 48109 USA.
   [Salmon, Jane E.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
   [Salmon, Jane E.] Weill Cornell Med, New York, NY USA.
   [Weisman, Michael H.; Wallace, Daniel J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Wallace, Daniel J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Utset, Tammy] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
   [Bottinger, Erwin P.] Mt Sinai Hosp, New York, NY 10029 USA.
   [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
   [Mariette, Xavier] Univ Paris 11, Hop Univ Paris Sud, AP HP, Le Kremlin Bicetre, France.
   [Mariette, Xavier] INSERM, U1184, F-94275 Le Kremlin Bicetre, France.
RP Harley, JB (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA.; Scofield, RH (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St,MS24, Oklahoma City, OK 73104 USA.
EM John.Harley@cch.mc.org; hal-scofield@omrf.ouhsc.edu
RI Anaya, Juan-Manuel/J-1960-2016
OI Anaya, Juan-Manuel/0000-0002-6444-1249
FU NIH [AR-062755, AI-024717, AI-031584, AI-062629, AI-063274, AI-082714,
   AI-083194, AI-101934]; NIH (National Institute of Dental and
   Craniofacial Research Intramural Research Program); University of
   Oklahoma Health Sciences Center (Clinical and Translational Science
   OCTSI Summer Scholar Program); US Department of Veterans Affairs
   [IMMA9]; US Department of Defense [PR094002]; Alliance for Lupus
   Research; Kirkland Scholar Program; Strategic Research Program at Helse
   Bergen; Western Norway Regional Health Authority; Broegelmann
   Foundation; French Ministry of Health (EvASSESS Programme Hospitalier de
   Recherche Clinique); Swedish Rheumatism Foundation; Arthritis Australia;
   Research to Prevent Blindness; Medical Research Council, UK [G0800629];
   DFG [KFO 250 WI 1031/6-1]; Canadian Institutes of Health Research
   [MOP89955, MOP74621]; Ontario Research Fund [RE05-075]; Canada Research
   Chair Program; Instituto de Salud Carlos III (ISCIII through FEDER)
   [02558]; Allergan; Lilly; UCB; The NIH [AR-042460, AR-048204, AR-048940,
   AR-049084, AR-052125, AR-053483, AR-053734, AR-056360, AR-058959,
   AR-062277, AR-043814, AR-065626, DE-015223, DE-018209, RR-020143,
   GM-103510, GM-104938, HG-008667, TR-001475, HG-006828]
FX Supported by the NIH (grants AR-062755, AI-024717, AI-031584, AI-062629,
   AI-063274, AI-082714, AI-083194, AI-101934, AR-042460, AR-048204,
   AR-048940, AR-049084, AR-052125, AR-053483, AR-053734, AR-056360,
   AR-058959, AR-062277, AR-043814, AR-065626, DE-015223, DE-018209,
   RR-020143, GM-103510, GM-104938, HG-008667, TR-001475, and HG-006828 and
   the National Institute of Dental and Craniofacial Research Intramural
   Research Program), University of Oklahoma Health Sciences Center
   (Clinical and Translational Science OCTSI Summer Scholar Program), US
   Department of Veterans Affairs (award IMMA9 to Drs. Harley and
   Scofield), US Department of Defense (award PR094002), Alliance for Lupus
   Research (award to Dr. Harley), Kirkland Scholar Program (awards to Drs.
   James and Harley), Strategic Research Program at Helse Bergen, Western
   Norway Regional Health Authority, Broegelmann Foundation, French
   Ministry of Health (EvASSESS Programme Hospitalier de Recherche Clinique
   2006), Swedish Rheumatism Foundation, Arthritis Australia, Research to
   Prevent Blindness (unrestricted grant to the Dean McGee Eye Institute
   and the Department of Ophthalmology, University of Oklahoma College of
   Medicine, and Senior Scientific Investigator Award to Dr. Chodosh),
   Medical Research Council, UK (award G0800629), DFG (award KFO 250 WI
   1031/6-1 to Dr. Witte), Canadian Institutes of Health Research (awards
   MOP89955 and MOP74621), Ontario Research Fund (award RE05-075), Canada
   Research Chair Program (award to Dr. Siminovitch), and Instituto de
   Salud Carlos III (ISCIII award 02558 through FEDER funds, to Dr.
   Alarcon-Riquelme).; Dr. Huang has received consulting fees, speaking
   fees, and/or honoraria from Allergan (less than $10,000). Dr. Illei owns
   stock in AstraZeneca. Dr. Scofield has received consulting fees,
   speaking fees, and/ or honoraria from Lilly and UCB (less than $10,000
   each).
NR 45
TC 6
Z9 6
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2016
VL 68
IS 5
BP 1290
EP 1300
DI 10.1002/art.39560
PG 11
WC Rheumatology
SC Rheumatology
GA DL3RT
UT WOS:000375551600030
PM 26713507
ER

PT J
AU Foley, P
   Griffiths, C
   Reich, K
   Leonardi, CL
   Blauvelt, A
   Mehta, NN
   Tsai, TF
   Gong, Y
   Papavassilis, C
   Huang, J
   Fox, T
   van de Kerkhof, P
AF Foley, P.
   Griffiths, C.
   Reich, K.
   Leonardi, C. L.
   Blauvelt, A.
   Mehta, N. N.
   Tsai, T. F.
   Gong, Y.
   Papavassilis, C.
   Huang, J.
   Fox, T.
   van de Kerkhof, P.
TI Secukinumab demonstrates an acceptable safety profile in moderate to
   severe plaque psoriasis: Pooled analysis of 10 phase 2/3 studies
SO AUSTRALASIAN JOURNAL OF DERMATOLOGY
LA English
DT Meeting Abstract
C1 [Foley, P.] St Vincents Hosp, Dept Dermatol, Melbourne, Vic, Australia.
   [Griffiths, C.] Univ Manchester, Manchester, Lancs, England.
   [Reich, K.] SCIderm GmbH, Hamburg, Germany.
   [Leonardi, C. L.] St Louis Univ, Sch Med, St Louis, MO USA.
   [Blauvelt, A.] Oregon Med Res Ctr, Portland, OR USA.
   [Mehta, N. N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD 20892 USA.
   [Tsai, T. F.] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Taipei 10764, Taiwan.
   [Gong, Y.; Huang, J.] Beijing Novartis Pharma Co Ltd, Beijing, Peoples R China.
   [Papavassilis, C.; Fox, T.] Novartis Pharma AG, Basel, Switzerland.
   [van de Kerkhof, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-8380
EI 1440-0960
J9 AUSTRALAS J DERMATOL
JI Australas. J. Dermatol.
PD MAY
PY 2016
VL 57
SU 1
SI SI
BP 50
EP 50
PG 1
WC Dermatology
SC Dermatology
GA DK1PU
UT WOS:000374686200130
ER

PT J
AU Gogtay, N
AF Gogtay, N.
TI CHILDHOOD-ONSET PSYCHOSIS: INSIGHTS FROM NEUROIMAGING STUDIES
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Gogtay, N.] NIMH, Off Clin Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0004-8674
EI 1440-1614
J9 AUST NZ J PSYCHIAT
JI Aust. N. Z. J. Psych.
PD MAY
PY 2016
VL 50
SU 1
BP 3
EP 4
PG 2
WC Psychiatry
SC Psychiatry
GA DL4GI
UT WOS:000375591600003
ER

PT J
AU Coderre, EL
   Smith, JF
   Van Heuven, WJB
   Horwitz, B
AF Coderre, Emily L.
   Smith, Jason F.
   Van Heuven, Walter J. B.
   Horwitz, Barry
TI The functional overlap of executive control and language processing in
   bilinguals
SO BILINGUALISM-LANGUAGE AND COGNITION
LA English
DT Article
DE bilingualism; executive control; language processing; fMRI
ID ANTERIOR CINGULATE CORTEX; VENTROLATERAL PREFRONTAL CORTEX;
   UNDERSTANDING BRAIN NETWORKS; SPANISH-ENGLISH BILINGUALS; INFERIOR
   FRONTAL GYRUS; COGNITIVE CONTROL; FMRI EVIDENCE; VERBAL FLUENCY;
   SENTENCE COMPREHENSION; INHERITED SPEECH
AB The need to control multiple languages is thought to require domain-general executive control in bilinguals such that the executive control and language systems become interdependent. However, there has been no systematic investigation into how and where executive control and language processes overlap in the bilingual brain. If the concurrent recruitment of executive control during bilingual language processing is domain-general and extends to non-linguistic control, we hypothesize that regions commonly involved in language processing, linguistic control, and non-linguistic control may be selectively altered in bilinguals compared to monolinguals. A conjunction of functional magnetic resonance imaging (fMRI) data from a flanker task with linguistic and non-linguistic distractors and a semantic categorization task showed functional overlap in the left inferior frontal gyrus (LIFG) in bilinguals, whereas no overlap occurred in monolinguals. This research therefore identifies a neural locus of functional overlap of language and executive control in the bilingual brain.
C1 [Coderre, Emily L.; Van Heuven, Walter J. B.] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England.
   [Coderre, Emily L.; Smith, Jason F.; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
   [Coderre, Emily L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21231 USA.
   [Smith, Jason F.] Univ Maryland, Dept Psychol, College Pk, MD USA.
   [Smith, Jason F.] Univ Maryland, Maryland Neuroimaging Ctr, College Pk, MD USA.
RP Coderre, EL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Cognit Neurol Neuropsychol, 1629 Thames St,Suite 350, Baltimore, MD 21231 USA.
EM ecoderr1@jhmi.edu
OI van Heuven, Walter/0000-0003-3183-4449; Coderre,
   Emily/0000-0002-2762-4994
FU Intramural Research Program of the NIDCD, NIH
FX The authorswould like to thank Donald Bolger for help with paradigm
   design, and Allen Braun for providing research participants. This
   research was funded in part by the Intramural Research Program of the
   NIDCD, NIH.
NR 103
TC 0
Z9 0
U1 9
U2 16
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1366-7289
EI 1469-1841
J9 BILING-LANG COGN
JI Biling.-Lang. Cogn.
PD MAY
PY 2016
VL 19
IS 3
BP 471
EP 488
DI 10.1017/S1366728915000188
PG 18
WC Linguistics; Psychology, Experimental
SC Linguistics; Psychology
GA DJ4JL
UT WOS:000374171100003
PM 27695385
ER

PT J
AU Theodorou, A
   Phylactides, M
   Forti, L
   Cramarossa, MR
   Spyrou, P
   Gambari, R
   Thein, SL
   Kleanthous, M
AF Theodorou, Andria
   Phylactides, Marios
   Forti, Luca
   Cramarossa, Maria Rita
   Spyrou, Pantelis
   Gambari, Roberto
   Thein, Swee Lay
   Kleanthous, Marina
TI The investigation of resveratrol and analogs as potential inducers of
   fetal hemoglobin
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Fetal hemoglobin; Resveratrol; Beta-thalassemia; Globin; Antioxidant
ID RED WINE ANTIOXIDANT; SICKLE-CELL-ANEMIA; BETA-THALASSEMIA; OXIDATIVE
   STRESS; LIFE-SPAN; ERYTHROID-DIFFERENTIATION; IRON OVERLOAD; RAT HEARTS;
   MICE; PHYTOALEXIN
AB Beta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone. (C) 2015 Published by Elsevier Inc.
C1 [Theodorou, Andria; Phylactides, Marios; Spyrou, Pantelis; Kleanthous, Marina] Cyprus Inst Neurol & Genet, Mol Genet Thalassaemia Dept, 6 Int Airport Ave, CY-2370 Nicosia, Cyprus.
   [Theodorou, Andria; Thein, Swee Lay] Kings Coll London, Fac Life Sci & Med, London WC2R 2LS, England.
   [Forti, Luca; Cramarossa, Maria Rita] Univ Modena & Reggio Emilia, Dept Life Sci, Regio Emilia, Italy.
   [Gambari, Roberto] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy.
   [Thein, Swee Lay] Natl Lung & Blood Inst, NIH, Sickle Cell Branch, Bethesda, MD USA.
RP Phylactides, M (reprint author), Cyprus Inst Neurol & Genet, Mol Genet Thalassaemia Dept, 6 Int Airport Ave, CY-2370 Nicosia, Cyprus.
EM mphylact@cing.ac.cy
OI Kleanthous, Marina/0000-0003-0064-7034; Forti, Luca/0000-0002-5662-7756
FU Republic of Cyprus through the Research Promotion Foundation
   [YGammaEIA/BIOSigma/0609(BE)/01]; European Union's Seventh Framework
   Program [3-6201]; Cyprus Institute of Neurology and Genetics
FX The present study was co-funded by the Republic of Cyprus through the
   Research Promotion Foundation under grant agreement Upsilon Gamma
   EIA/BIO Sigma/0609(BE)/01 (M.K) and by the European Union's Seventh
   Framework Program for Research, Technological Development and
   Demonstration under grant agreement no. 3-6201 (THALAMOSS) (M.K., R.G.
   and S.LT) and through core funding of the Cyprus Institute of Neurology
   and Genetics.
NR 44
TC 0
Z9 0
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 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD MAY
PY 2016
VL 58
BP 6
EP 12
DI 10.1016/j.bcmd.2015.11.007
PG 7
WC Hematology
SC Hematology
GA DJ9CW
UT WOS:000374512600002
PM 27067481
ER

PT J
AU Im, A
   Mitchell, SA
   Steinberg, SM
   Curtis, L
   Berger, A
   Baird, K
   Kuzmina, Z
   Joe, G
   Comis, LE
   Juckett, M
   Avila, D
   Baruffaldi, J
   Masuch, L
   Pirsl, F
   Pavletic, SZ
AF Im, A.
   Mitchell, S. A.
   Steinberg, S. M.
   Curtis, L.
   Berger, A.
   Baird, K.
   Kuzmina, Z.
   Joe, G.
   Comis, L. E.
   Juckett, M.
   Avila, D.
   Baruffaldi, J.
   Masuch, L.
   Pirsl, F.
   Pavletic, S. Z.
TI Prevalence and determinants of fatigue in patients with moderate to
   severe chronic GvHD
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
ID QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE;
   CANCER-RELATED FATIGUE; BONE-MARROW-TRANSPLANTATION; LONG-TERM
   SURVIVORS; SF-36 VITALITY SCALE; HEALTH SURVEY SF-36; SYMPTOM INVENTORY;
   THE-LITERATURE
AB Although fatigue is common after allogeneic hematopoietic cell transplantation, little is known about fatigue in patients with chronic GvHD (cGvHD). The aim of this study was to explore factors associated with fatigue in cGvHD. Data were drawn from a sequentially recruited, cross-sectional study of adults with moderate or severe cGvHD (n = 263). Respondents were classified as fatigued or not fatigued based on their response to a single item regarding loss of energy from the Lee cGvHD Symptom Scale. In univariate analysis, factors significantly associated with fatigue included performance status, number of prior cGvHD therapies, cGvHD symptom bother, self-assessed physical and mental health, nutritional status, walk velocity and self-reported physical activity. There were no significant associations between fatigue and disease-related cGvHD variables. Multivariable logistic regression demonstrated that being less active and having pulmonary and/or muscle/joint symptoms were independently associated with fatigue. In conclusion, clinically significant fatigue was prevalent in more than one-third of subjects with cGvHD, and was disabling. Absence of association with measures of cGvHD severity underscores the need to elucidate the pathogenesis of fatigue and its relationship with inflammatory activity. Pulmonary and muscle/joint symptoms and physical inactivity represent potential targets for intervention in clinical studies.
C1 [Im, A.] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA.
   [Mitchell, S. A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD 20850 USA.
   [Steinberg, S. M.] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Curtis, L.; Avila, D.; Masuch, L.; Pirsl, F.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Berger, A.] NIH, Pain & Palliat Care, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Baird, K.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD USA.
   [Kuzmina, Z.] Hosp Hietzing, Oncol Hematol, Vienna, Austria.
   [Joe, G.; Comis, L. E.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
   [Juckett, M.] Univ Wisconsin, Sch Med & Publ Hlth, Div Hematol & Med Oncol, Madison, WI USA.
   [Baruffaldi, J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate CMRP, Frederick, MD USA.
RP Mitchell, SA (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,East Tower,Room 3-448, Rockville, MD 20850 USA.
EM mitchlls@mail.nih.gov
NR 61
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAY
PY 2016
VL 51
IS 5
BP 705
EP 712
DI 10.1038/bmt.2015.320
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA DL5XO
UT WOS:000375710600016
PM 26828906
ER

PT J
AU Leonardo, FC
   Brugnerotto, AF
   Domingos, IF
   Fertrin, KY
   de Albuquerque, DM
   Bezerra, MAC
   Araujo, AS
   Saad, STO
   Costa, FF
   Menzel, S
   Conran, N
   Thein, SL
AF Leonardo, Flavia C.
   Brugnerotto, Ana F.
   Domingos, Igor F.
   Fertrin, Kleber Y.
   de Albuquerque, Dulcineia M.
   Bezerra, Marcos A. C.
   Araujo, Aderson S.
   Saad, Sara T. O.
   Costa, Fernando F.
   Menzel, Stephan
   Conran, Nicola
   Thein, Swee Lay
TI Reduced rate of sickle-related complications in Brazilian patients
   carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE HbF quantitative trait loci; BCL11A; HMIP-2
ID FETAL-HEMOGLOBIN LEVELS; INTERGENIC VARIANTS; DNA POLYMORPHISMS;
   GENETIC-VARIATION; CELL PATIENTS; HBS1L-MYB; ENHANCER; DISEASE; ANEMIA
AB The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.
C1 [Leonardo, Flavia C.; Brugnerotto, Ana F.; Fertrin, Kleber Y.; de Albuquerque, Dulcineia M.; Saad, Sara T. O.; Costa, Fernando F.; Conran, Nicola] Univ Campinas UNICAMP Campinas, Sch Med, Haematol Ctr, Campinas, SP, Brazil.
   [Domingos, Igor F.; Bezerra, Marcos A. C.] Univ Fed Pernambuco, Dept Genet, Recife, PE, Brazil.
   [Araujo, Aderson S.] Haematol & Haemotherapy Fdn Pernambuco HEMOPE, Recife, PE, Brazil.
   [Menzel, Stephan; Thein, Swee Lay] Kings Coll London, Div Canc Studies, Dept Mol Haematol, Fac Life Sci & Med, London WC2R 2LS, England.
   [Thein, Swee Lay] NHLBI, Sickle Cell Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Leonardo, FC (reprint author), Univ Estadual Campinas, Haematol & Haemotherapy Ctr, Hemoctr, Rua Carlos Chagas,480,Cidade Univ, BR-13083970 Campinas, SP, Brazil.
EM flaviacostaleonardo@gmail.com
NR 15
TC 1
Z9 1
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAY
PY 2016
VL 173
IS 3
BP 456
EP 460
DI 10.1111/bjh.13961
PG 5
WC Hematology
SC Hematology
GA DL2QR
UT WOS:000375480600013
PM 26888013
ER

PT J
AU Ryerson, AB
   Eheman, CR
   Altekruse, SF
   Ward, JW
   Jemal, A
   Sherman, RL
   Henley, SJ
   Holtzman, D
   Lake, A
   Noone, AM
   Anderson, RN
   Ma, JM
   Ly, KN
   Cronin, KA
   Penberthy, L
   Kohler, BA
AF Ryerson, A. Blythe
   Eheman, Christie R.
   Altekruse, Sean F.
   Ward, John W.
   Jemal, Ahmedin
   Sherman, Recinda L.
   Henley, S. Jane
   Holtzman, Deborah
   Lake, Andrew
   Noone, Anne-Michelle
   Anderson, Robert N.
   Ma, Jiemin
   Ly, Kathleen N.
   Cronin, Kathleen A.
   Penberthy, Lynne
   Kohler, Betsy A.
TI Annual Report to the Nation on the Status of Cancer, 1975-2012,
   featuring the increasing incidence of liver cancer
SO CANCER
LA English
DT Editorial Material
DE cancer; incidence; liver cancer; mortality; National Program of Cancer
   Registries (NPCR); North American Association of Central Cancer
   Registries (NAACCR); Surveillance; Epidemiology; and End Results (SEER);
   survival; trends; viral hepatitis
ID SERVICES TASK-FORCE; HEPATITIS-C VIRUS; UNITED-STATES;
   HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; PROSTATE-CANCER;
   RECOMMENDATION STATEMENT; LUNG-CANCER; VIRAL-HEPATITIS; BREAST-CANCER
AB BACKGROUNDAnnual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers.
   METHODSCancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013.
   RESULTSAmong men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965.
   CONCLUSIONSOverall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. Cancer 2016;122:1312-1337. (c) 2016 American Cancer Society.
   The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updated information about cancer occurrence and trends in the United States. This year's report highlights the increasing burden of liver cancer and emphasizes the importance of public health efforts to prevent, identify, and treat chronic hepatitis B and C viral infections and to promote reductions in other key risk factors for liver cancer.
C1 [Ryerson, A. Blythe; Eheman, Christie R.; Henley, S. Jane] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
   [Altekruse, Sean F.; Noone, Anne-Michelle; Cronin, Kathleen A.; Penberthy, Lynne] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Ward, John W.; Holtzman, Deborah; Ly, Kathleen N.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
   [Jemal, Ahmedin; Ma, Jiemin] Amer Canc Soc, Surveillance Res Program, Atlanta, GA 30329 USA.
   [Sherman, Recinda L.; Kohler, Betsy A.] North Amer Assoc Cent Canc Registries, Springfield, IL USA.
   [Lake, Andrew] Informat Management Serv Inc, Rockville, MD USA.
   [Anderson, Robert N.] Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Hyattsville, MD USA.
RP Ryerson, AB (reprint author), Div Canc Prevent & Control, 4770 Buford Highway NE,F-76, Atlanta, GA 30341 USA.
EM aryerson@cdc.gov
FU Intramural CDC HHS [CC999999]
NR 124
TC 46
Z9 47
U1 13
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAY 1
PY 2016
VL 122
IS 9
BP 1312
EP 1337
DI 10.1002/cncr.29936
PG 26
WC Oncology
SC Oncology
GA DK1WT
UT WOS:000374706500003
PM 26959385
ER

PT J
AU Armstrong, K
   Kim, JJ
   Halm, EA
   Ballard, RM
   Schnall, MD
AF Armstrong, Katrina
   Kim, Jane J.
   Halm, Ethan A.
   Ballard, Rachel M.
   Schnall, Mitchell D.
TI Using lessons from breast, cervical, and colorectal cancer screening to
   inform the development of lung cancer screening programs
SO CANCER
LA English
DT Editorial Material
DE implementation; lung cancer; primary care; quality; screening
ID HUMAN-PAPILLOMAVIRUS; UNITED-STATES; DATA SYSTEM; IMPLEMENTATION;
   PREVENTION; SOCIETY; COLONOSCOPY; ONCOLOGY; LESIONS
AB Multiple advisory groups now recommend that high-risk smokers be screened for lung cancer by low-dose computed tomography. Given that the development of lung cancer screening programs will face many of the same issues that have challenged other cancer screening programs, the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium was used to identify lessons learned from the implementation of breast, cervical, and colorectal cancer screening that should inform the introduction of lung cancer screening. These lessons include the importance of developing systems for identifying and recruiting eligible individuals in primary care, ensuring that screening centers are qualified and performance is monitored, creating clear communication standards for reporting screening results to referring physicians and patients, ensuring follow-up is available for individuals with abnormal test results, avoiding overscreening, remembering primary prevention, and leveraging advances in cancer genetics and immunology. Overall, this experience emphasizes that effective cancer screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track each step as well as a dynamic and ongoing oversight process to revise current screening practices as new evidence regarding screening is created, new screening technologies are developed, new biological markers are identified, and new approaches to health care delivery are disseminated. Cancer 2016;122:1338-1342. (c) 2016 American Cancer Society.
   Experience with other cancer screening tests can inform the implementation of lung cancer screening programs. This experience emphasizes that screening is a multistep activity that requires robust strategies to initiate, report, follow up, and track and a dynamic oversight process to revise screening practices as information and options change over time.
C1 [Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA.
   [Kim, Jane J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
   [Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Ballard, Rachel M.] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA.
   [Schnall, Mitchell D.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Armstrong, K (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA.
EM karmstrong6@partners.org
FU NCATS NIH HHS [UL1 TR001105]; NCI NIH HHS [U54 CA163313, U54 CA163308,
   U54 CA164336]
NR 32
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAY 1
PY 2016
VL 122
IS 9
BP 1338
EP 1342
DI 10.1002/cncr.29937
PG 5
WC Oncology
SC Oncology
GA DK1WT
UT WOS:000374706500004
PM 26929386
ER

PT J
AU Dolai, S
   Sia, KCS
   Robbins, AK
   Zhong, L
   Heatley, SL
   Vincent, TL
   Hochgrafe, F
   Sutton, R
   Kurmasheva, RT
   Revesz, T
   White, DL
   Houghton, PJ
   Smith, MA
   Teachey, DT
   Daly, RJ
   Raftery, MJ
   Lock, RB
AF Dolai, Sibasish
   Sia, Keith C. S.
   Robbins, Alissa K.
   Zhong, Ling
   Heatley, Sue L.
   Vincent, Tiffaney L.
   Hochgraefe, Falko
   Sutton, Rosemary
   Kurmasheva, Raushan T.
   Revesz, Tamas
   White, Deborah L.
   Houghton, Peter J.
   Smith, Malcolm A.
   Teachey, David T.
   Daly, Roger J.
   Raftery, Mark J.
   Lock, Richard B.
TI Quantitative Phosphotyrosine Profiling of Patient-Derived Xenografts
   Identifies Therapeutic Targets in Pediatric Leukemia
SO CANCER RESEARCH
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PRECLINICAL TESTING PROGRAM; TYROSINE
   PHOSPHORYLATION; GENE-EXPRESSION; SIGNALING PATHWAY; MASS-SPECTROMETRY;
   CANCER-CELLS; KINASE; SILAC; REVEALS
AB Activating mutations in tyrosine kinases (TK) drive pediatric high-risk acute lymphoblastic leukemia (ALL) and confer resistance to standard chemotherapy. Therefore, there is urgent need to characterize dysregulated TK signaling axes in patients with ALL and identify actionable kinase targets for the development of therapeutic strategies. Here, we present the first study to quantitatively profile TK activity in xenografted patient biopsies of high-risk pediatric ALL. We integrated a quantitative phosphotyrosine profiling method with "spike-in" stable isotope labeling with amino acids in cell culture (SILAC) and quantified 1394 class I phosphorylation sites in 16 ALL xenografts. Moreover, hierarchical clustering of phosphotyrosine sites could accurately classify these leukemias into either B- or T-cell lineages with the high-risk early T-cell precursor (ETP) and Ph-like ALL clustering as a distinct group. Furthermore, we validated this approach by using specific kinase pathway inhibitors to perturb ABL1, FLT3, and JAK TK signaling in four xenografted patient samples. By quantitatively assessing the tyrosine phosphorylation status of activated kinases in xenograft models of ALL, we were able to identify and validate clinically relevant targets. Therefore, this study highlights the application and potential of phosphotyrosine profiling for identifying clinically relevant kinase targets in leukemia. (C) 2016 AACR.
C1 [Dolai, Sibasish; Sia, Keith C. S.; Robbins, Alissa K.; Sutton, Rosemary] Univ New South Wales Australia, Lowy Canc Res Ctr, Childrens Canc Inst, Sydney, NSW, Australia.
   [Zhong, Ling; Raftery, Mark J.] Univ New South Wales Australia, Bioanalyt Mass Spectrometry Facil, Mark Wainwright Analyt Ctr, Sydney, NSW, Australia.
   [Heatley, Sue L.; White, Deborah L.] South Australian Hlth & Med Res Inst SAHMRI, Adelaide, SA, Australia.
   [Heatley, Sue L.; White, Deborah L.] Univ Adelaide, Discipline Med, Adelaide, SA, Australia.
   [Vincent, Tiffaney L.; Teachey, David T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Hochgraefe, Falko] Ernst Moritz Arndt Univ Greifswald, Jr Res Grp Pathoprote, Competence Ctr Funct Genom, Greifswald, Germany.
   [Kurmasheva, Raushan T.; Houghton, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
   [Revesz, Tamas; White, Deborah L.] Univ Adelaide, Discipline Paediat, Adelaide, SA, Australia.
   [Revesz, Tamas] Womens & Childrens Hosp, SA Pathol, Adelaide, SA, Australia.
   [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Daly, Roger J.] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
RP Lock, RB (reprint author), Childrens Canc Inst, POB 81, Sydney, NSW 2031, Australia.
EM RLock@ccia.org.au
RI Lock, Richard/G-4253-2013; 
OI White, Deborah/0000-0003-4844-333X
NR 52
TC 2
Z9 2
U1 1
U2 1
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 MAY 1
PY 2016
VL 76
IS 9
BP 2766
EP 2777
DI 10.1158/0008-5472.CAN-15-2786
PG 12
WC Oncology
SC Oncology
GA DL0OM
UT WOS:000375332300026
ER

PT J
AU Wang, YF
   Bernhardy, AJ
   Cruz, C
   Krais, JJ
   Nacson, J
   Nicolas, E
   Peri, S
   van der Gulden, H
   van der Heijden, I
   O'Brien, SW
   Zhang, Y
   Harrell, MI
   Johnson, SF
   Dos Reis, FJC
   Pharoah, PDP
   Karlan, B
   Gourley, C
   Lambrechts, D
   Chenevix-Trench, G
   Olsson, H
   Benitez, JJ
   Greene, MH
   Gore, M
   Nussbaum, R
   Sadetzki, S
   Gayther, SA
   Kjaer, SK
   D'Andrea, AD
   Shapiro, GI
   Wiest, DL
   Connolly, DC
   Daly, MB
   Swisher, EM
   Bouwman, P
   Jonkers, J
   Balmana, J
   Serra, V
   Johnson, N
AF Wang, Yifan
   Bernhardy, Andrea J.
   Cruz, Cristina
   Krais, John J.
   Nacson, Joseph
   Nicolas, Emmanuelle
   Peri, Suraj
   van der Gulden, Hanneke
   van der Heijden, Ingrid
   O'Brien, Shane W.
   Zhang, Yong
   Harrell, Maribel I.
   Johnson, Shawn F.
   Candido Dos Reis, Francisco J.
   Pharoah, Paul D. P.
   Karlan, Beth
   Gourley, Charlie
   Lambrechts, Diether
   Chenevix-Trench, Georgia
   Olsson, Hakan
   Benitez, Javier J.
   Greene, Mark H.
   Gore, Martin
   Nussbaum, Robert
   Sadetzki, Siegal
   Gayther, Simon A.
   Kjaer, Susanne K.
   D'Andrea, Alan D.
   Shapiro, Geoffrey I.
   Wiest, David L.
   Connolly, Denise C.
   Daly, Mary B.
   Swisher, Elizabeth M.
   Bouwman, Peter
   Jonkers, Jos
   Balmana, Judith
   Serra, Violeta
   Johnson, Neil
CA kConFab Investigators
TI The BRCA1-Delta 11q Alternative Splice Isoform Bypasses Germline
   Mutations and Promotes Therapeutic Resistance to PARP Inhibition and
   Cisplatin
SO CANCER RESEARCH
LA English
DT Article
ID OVARIAN-CANCER; BRCA2 MUTATIONS; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS
   RECOMBINATION; BREAST-CANCER; DNA-DAMAGE; CELLS; CHEMOTHERAPY;
   ASSOCIATION; EXPRESSION
AB Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Delta 11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Delta 11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Delta 11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo. Furthermore, spliceosome inhibitors reduced BRCA1-Delta 11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. (C) 2016 AACR.
C1 [Wang, Yifan; Bernhardy, Andrea J.; Krais, John J.; Nacson, Joseph; Peri, Suraj; O'Brien, Shane W.; Connolly, Denise C.; Johnson, Neil] Fox Chase Canc Ctr, Mol Therapeut Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
   [Cruz, Cristina; Balmana, Judith] Vall dHebron Inst Oncol, High Risk & Canc Prevent Grp, Barcelona, Spain.
   [Cruz, Cristina; Serra, Violeta] Vall dHebron Inst Oncol, Expt Therapeut Grp, Barcelona, Spain.
   [Nicolas, Emmanuelle] Fox Chase Canc Ctr, Canc Biol Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
   [van der Gulden, Hanneke; van der Heijden, Ingrid; Bouwman, Peter; Jonkers, Jos] Netherlands Canc Inst, Div Pathol, Amsterdam, Netherlands.
   [Zhang, Yong; Wiest, David L.] Fox Chase Canc Ctr, Immune Cell Dev & Host Def Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
   [Harrell, Maribel I.; Swisher, Elizabeth M.] Univ Washington, Dept Obstet & Gynecol & Med, Seattle, WA 98195 USA.
   [Johnson, Shawn F.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Johnson, Shawn F.; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA USA.
   [Candido Dos Reis, Francisco J.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Sao Paulo, Brazil.
   [Candido Dos Reis, Francisco J.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England.
   [Karlan, Beth] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
   [Gourley, Charlie] Univ Edinburgh, Canc Res UK Ctr, MRC IGMM, Edinburgh, Midlothian, Scotland.
   [Lambrechts, Diether] Univ Leuven, VIB Vesalius Res Ctr, Leuven, Belgium.
   [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Herston, Qld, Australia.
   [Olsson, Hakan] Lund Univ, Dept Canc Epidemiol, Lund, Sweden.
   [Olsson, Hakan] Lund Univ, Dept Oncol, Lund, Sweden.
   [Benitez, Javier J.] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp & Human Genotyping Unit, Madrid, Spain.
   [Greene, Mark H.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Gore, Martin] Royal Marsden NHS Fdn Trust, London, England.
   [Nussbaum, Robert] Univ Calif San Francisco, Canc Risk Program, San Francisco, CA 94143 USA.
   [Sadetzki, Siegal] Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel.
   [Gayther, Simon A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Kjaer, Susanne K.] Danish Canc Soc, Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
   [kConFab Investigators] Univ Melbourne, Melbourne, Vic, Australia.
   [D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
   [D'Andrea, Alan D.] Harvard Univ, Sch Med, Boston, MA USA.
   [D'Andrea, Alan D.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA.
   [Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
   [Daly, Mary B.] Fox Chase Canc Ctr, Risk Assessment Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
RP Johnson, N (reprint author), Fox Chase Canc Ctr, Mol Therapeut Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
EM neil.johnson@fccc.edu
RI Candido dos Reis, Francisco/K-7024-2016
OI Candido dos Reis, Francisco/0000-0001-5758-5917
FU Cancer Research UK [10119, 10124]; NCI NIH HHS [P30 CA006927, P50
   CA083636, P50 CA083638, R21 CA191690]
NR 50
TC 5
Z9 5
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 MAY 1
PY 2016
VL 76
IS 9
BP 2778
EP 2790
DI 10.1158/0008-5472.CAN-16-0186
PG 13
WC Oncology
SC Oncology
GA DL0OM
UT WOS:000375332300027
PM 27197267
ER

PT J
AU Belluscio, L
AF Belluscio, Leonardo
TI Plasticity and precision in olfactory bulb circuits.
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the European-Chemoreception-Research-Organization
   (ECRO)
CY SEP 01-05, 2015
CL Bogazici Univ, Istanbul, TURKEY
SP European Chemorecept Res Org
HO Bogazici Univ
C1 [Belluscio, Leonardo] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD MAY
PY 2016
VL 41
IS 4
MA PS29
BP 399
EP 399
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
   Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
   Neurology; Physiology
GA DK2ZD
UT WOS:000374783300071
ER

PT J
AU Baranello, L
   Kouzine, F
   Sanford, S
   Levens, D
AF Baranello, Laura
   Kouzine, Fedor
   Sanford, Suzanne
   Levens, David
TI ChIP bias as a function of cross-linking time
SO CHROMOSOME RESEARCH
LA English
DT Article
DE Chromatin immunoprecipitation; DNA topoisomerase 1; Green fluorescent
   protein; Formaldehyde cross-linking
ID CHROMATIN; GENOME; IMMUNOPRECIPITATION; SCALE
AB The chromatin immunoprecipitation (ChIP) assay is widely used to capture interactions between chromatin and regulatory proteins in vivo. Formaldehyde cross-linking of DNA and proteins is a critical step required to trap their interactions inside the cells before immunoprecipitation and analysis. Yet insufficient attention has been given to variables that might give rise to artifacts in this procedure, such as the duration of cross-linking. We analyzed the dependence of the ChIP signal on the duration of formaldehyde cross-linking time for two proteins: DNA topoisomerase 1 (Top1) that is functionally associated with the double helix in vivo, especially with active chromatin, and green fluorescent protein (GFP) that has no known bona fide interactions with DNA. With short time of formaldehyde fixation, only Top1 immunoprecipation efficiently recovered DNA from active promoters, whereas prolonged fixation augmented non-specific recovery of GFP dramatizing the need to optimize ChIP protocols to minimize the time of cross-linking, especially for abundant nuclear proteins. Thus, ChIP is a powerful approach to study the localization of protein on the genome when care is taken to manage potential artifacts.
C1 [Baranello, Laura; Kouzine, Fedor; Sanford, Suzanne; Levens, David] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Baranello, L (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM baranellolf@mail.nih.gov; kouzinef@mail.nih.gov; ssanford926@gmail.com;
   levens@helix.nih.gov
FU Intramural Research Program of the US National Institutes of Health,
   Center for Cancer Research of the National Cancer Institute
FX Our research is supported by the Intramural Research Program of the US
   National Institutes of Health, Center for Cancer Research of the
   National Cancer Institute.
NR 18
TC 1
Z9 1
U1 4
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD MAY
PY 2016
VL 24
IS 2
BP 175
EP 181
DI 10.1007/s10577-015-9509-1
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DL5XQ
UT WOS:000375710800003
PM 26685864
ER

PT J
AU LeBlanc, AK
   Mazcko, CN
   Khanna, C
AF LeBlanc, Amy K.
   Mazcko, Christina N.
   Khanna, Chand
TI Defining the Value of a Comparative Approach to Cancer Drug Development
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SPONTANEOUSLY OCCURRING TUMORS; TYROSINE KINASE INHIBITOR; COMPARATIVE
   ONCOLOGY; SURGICAL EXCISION; CANINE; DOGS; PET; LYMPHOMA; MODELS;
   OSTEOSARCOMA
AB Comparative oncology as a tool in drug development requires a deeper examination of the value of the approach and examples of where this approach can satisfy unmet needs. This review seeks to demonstrate types of drug development questions that are best answered by the comparative oncology approach. We believe common perceived risks of the comparative approach relate to uncertainty of how regulatory bodies will prioritize or react to data generated from these unique studies conducted in diseased animals, and how these new data will affect ongoing human clinical trials. We contend that it is reasonable to consider these data as potentially informative and valuable to cancer drug development, but as supplementary to conventional preclinical studies and human clinical trials particularly as they relate to the identification of drug-associated adverse events. (C) 2015 AACR.
C1 [LeBlanc, Amy K.; Mazcko, Christina N.; Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP LeBlanc, AK (reprint author), NCI, NIH, Room 2144,37 Convent Dr, Bethesda, MD 20892 USA.
EM amy.leblanc@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 57
TC 2
Z9 2
U1 1
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 MAY 1
PY 2016
VL 22
IS 9
BP 2133
EP 2138
DI 10.1158/1078-0432.CCR-15-2347
PG 6
WC Oncology
SC Oncology
GA DL0NG
UT WOS:000375329100008
PM 26712689
ER

PT J
AU Rothermel, LD
   Sabesan, AC
   Stephens, DJ
   Chandran, SS
   Paria, BC
   Srivastava, AK
   Somerville, R
   Wunderlich, JR
   Lee, CCR
   Xi, LQ
   Pham, TH
   Raffeld, M
   Jailwala, P
   Kasoji, M
   Kammula, US
AF Rothermel, Luke D.
   Sabesan, Arvind C.
   Stephens, Daniel J.
   Chandran, Smita S.
   Paria, Biman C.
   Srivastava, Abhishek K.
   Somerville, Robert
   Wunderlich, John R.
   Lee, Chyi-Chia R.
   Xi, Liqiang
   Pham, Trinh H.
   Raffeld, Mark
   Jailwala, Parthav
   Kasoji, Manjula
   Kammula, Udai S.
TI Identification of an Immunogenic Subset of Metastatic Uveal Melanoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; CANDIDATE PROTEINS GP100;
   CANCER-IMMUNOTHERAPY; INTERLEUKIN-2 THERAPY; IMMUNE PRIVILEGE;
   SEQUENCING DATA; T-LYMPHOCYTES; CELLS; MUTATIONS; EXPRESSION
AB Purpose: Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma.
   Experimental Design: We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing.
   Results: Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL.
   Conclusions: The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. (C) 2015 AACR.
C1 [Rothermel, Luke D.; Sabesan, Arvind C.; Stephens, Daniel J.; Chandran, Smita S.; Paria, Biman C.; Srivastava, Abhishek K.; Somerville, Robert; Wunderlich, John R.; Kammula, Udai S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Lee, Chyi-Chia R.; Xi, Liqiang; Pham, Trinh H.; Raffeld, Mark] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Jailwala, Parthav; Kasoji, Manjula] Leidos Biomed Res Inc, FNLCR, Adv Biomed Comp Ctr, Frederick, MD USA.
RP Kammula, US (reprint author), NCI, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM udai_kammula@nih.gov
RI Srivastava, Abhishek/M-7577-2014
FU Intramural Research Program of the NCI; NIH; Department of Health and
   Human Services
FX The authors thank the Surgery Branch cell production facility and the
   immunotherapy clinical and support staff for their contributions. They
   also thank Li Jia for assistance in bioinformatics analysis. The
   Prospective Procurement of Solid Tumor Tissue to Identify Novel
   Therapeutic study was supported by the Intramural Research Program of
   the NCI, NIH, Department of Health and Human Services. Whole-exome raw
   data were uploaded to the NIH database for Genotypes and Phenotypes
   (dbGaP) under accession number phs001003.v1.p1.
NR 49
TC 1
Z9 1
U1 1
U2 1
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 MAY 1
PY 2016
VL 22
IS 9
BP 2237
EP 2249
DI 10.1158/1078-0432.CCR-15-2294
PG 13
WC Oncology
SC Oncology
GA DL0NG
UT WOS:000375329100020
PM 26712692
ER

PT J
AU Cadet, JL
   McCoy, MT
   Jayanthi, S
AF Cadet, J. L.
   McCoy, M. T.
   Jayanthi, S.
TI Epigenetics and Addiction
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID COCAINE-INDUCED PLASTICITY; SUBSTANCE USE DISORDERS; CREB-BINDING
   PROTEIN; DNA METHYLATION; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION;
   HISTONE DEACETYLASES; TRANSCRIPTIONAL RESPONSES; RAT STRIATUM;
   METHAMPHETAMINE
AB Addictions are public health menaces. However, despite advances in addiction research, the cellular or molecular mechanisms that cause transition from recreational use to addiction remain to be elucidated. We have recently suggested that addiction may be secondary to long-term epigenetic modifications that determine the clinical course of substance use disorders. A better understanding of epigenetic mechanisms in animal models that mimic human conditions should help to usher in a new area of drug development against addiction.
C1 [Cadet, J. L.; McCoy, M. T.; Jayanthi, S.] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD USA.
EM jcadet@intra.nida.nih.gov
FU Intramural Research Program of the DHHS/NIH/NIDA
FX This work was supported by funds of the Intramural Research Program of
   the DHHS/NIH/NIDA.
NR 75
TC 1
Z9 2
U1 9
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAY
PY 2016
VL 99
IS 5
BP 502
EP 511
DI 10.1002/cpt.345
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DJ8CK
UT WOS:000374439900007
PM 26841306
ER

PT J
AU Bouchelouche, K
   Choyke, PL
AF Bouchelouche, Kirsten
   Choyke, Peter L.
TI Prostate-specific membrane antigen positron emission tomography in
   prostate cancer: a step toward personalized medicine
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE personalized medicine; positron emission tomography; computed
   tomography; positron emission tomography; magnetic resonance imaging;
   prostate cancer; prostate-specific membrane antigen
ID GA-68-LABELED PSMA LIGAND; LYMPH-NODE DISSECTION; RADIATION-DOSIMETRY;
   GA-68-PSMA PET/CT; RADICAL PROSTATECTOMY; RADIOGUIDED SURGERY; ANDROGEN
   RECEPTOR; F-18-DCFBC PET/CT; TARGETED THERAPY; EAU GUIDELINES
AB Purpose of reviewIncreasing attention is being given to personalized medicine in oncology, where therapies are tailored to the particular characteristics of the individual cancer patient. In recent years, there has been greater focus on prostate-specific membrane antigen (PSMA) in prostate cancer (PCa) as a target for imaging and therapy with radionuclides. This review highlights the recent advancements in PSMA positron emission tomography (PET) in PCa during the past year.Recent findingsSeveral reports on PSMA PET/computed tomography (CT) in PCa patients are demonstrating promising results, especially for detection of biochemical recurrence. F-18-PSMA PET/CT may be superior to Ga-68-PSMA PET/CT. The detection rate of PSMA PET is influenced by prostate-specific antigen level. PSMA PET/CT may have a higher detection rate than choline PET/CT. Only a few reports have been published on PSMA PET/magnetic resonance imaging (MRI), and this modality remains to be elucidated further.SummaryMolecular imaging with PSMA PET is paving the way for personalized medicine in PCa. However, large prospective clinical studies are needed to further evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa. PSMA is an excellent target for imaging and therapy with radionuclides, and the image and treat' strategy has the potential to become a milestone in the management of PCa patients.
C1 [Bouchelouche, Kirsten] Aarhus Univ Hosp, Dept Nucl Med, Palle Juul Jensens Blvd 99, DK-8000 Aarhus, Denmark.
   [Bouchelouche, Kirsten] Aarhus Univ Hosp, PET Ctr, Palle Juul Jensens Blvd 99, DK-8000 Aarhus, Denmark.
   [Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bouchelouche, K (reprint author), Aarhus Univ Hosp, Dept Nucl Med, Palle Juul Jensens Blvd 99, DK-8000 Aarhus, Denmark.; Bouchelouche, K (reprint author), Aarhus Univ Hosp, PET Ctr, Palle Juul Jensens Blvd 99, DK-8000 Aarhus, Denmark.
EM kirsbouc@rm.dk
FU National Cancer Institute
FX P.C. receives support from the Intramural Program of the National Cancer
   Institute.
NR 57
TC 3
Z9 3
U1 3
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAY
PY 2016
VL 28
IS 3
BP 216
EP 221
DI 10.1097/CCO.0000000000000277
PG 6
WC Oncology
SC Oncology
GA DK2SK
UT WOS:000374764500006
PM 26967720
ER

PT J
AU Cordes, LM
   Gulley, JL
   Madan, RA
AF Cordes, Lisa M.
   Gulley, James L.
   Madan, Ravi A.
TI The evolving role of immunotherapy in prostate cancer
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE immunomodulating agents; immunotherapy; prostate cancer; therapeutic
   cancer vaccine
ID PHASE-II TRIAL; DOSE-ESCALATION TRIAL; SIPULEUCEL-T; ANDROGEN RECEPTOR;
   THERAPEUTIC VACCINES; ANTITUMOR EFFICACY; CLINICAL-TRIALS; DOUBLE-BLIND;
   SURVIVAL; CHEMOTHERAPY
AB Purpose of reviewIn recent clinical trials, immunotherapeutic agents have demonstrated promising results for the treatment of prostate cancer. This review discusses emerging immunotherapies for prostate cancer and their evolving role in sequencing and combination therapy.Recent findingsTherapeutic vaccines including PROSTVAC and DCVAC/PCa have completed promising phase 2 trials for the treatment of prostate cancer and phase 3 trials are underway. Recent evidence supports a synergistic relationship between immunotherapy agents themselves, antiandrogens and with cytotoxic chemotherapy. Prostate cancer patients with good prognostic factors, such as minimal disease burden, appear to achieve the optimal benefit from immunotherapy.SummaryTherapeutic cancer vaccines and immunomodulating agents have demonstrated activity in the treatment of prostate cancer. Immunotherapies may alter the prostate tumor microenvironment and ongoing studies aim to provide guidance on effective sequencing and combination strategies.
C1 [Cordes, Lisa M.] NIH, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Gulley, James L.; Madan, Ravi A.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Madan, RA (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM madanr@nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 62
TC 0
Z9 0
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAY
PY 2016
VL 28
IS 3
BP 232
EP 240
DI 10.1097/CCO.0000000000000281
PG 9
WC Oncology
SC Oncology
GA DK2SK
UT WOS:000374764500008
PM 26977847
ER

PT J
AU de Oliveira, JC
   Gomes, RM
   Miranda, RA
   Barella, LF
   Malta, A
   Martins, IP
   Franco, CCD
   Pavanello, A
   Torrezan, R
   Natali, MRM
   Lisboa, PC
   Mathias, PCD
   de Moura, EG
AF de Oliveira, Julio Cezar
   Gomes, Rodrigo Mello
   Miranda, Rosiane Aparecida
   Barella, Luiz Felipe
   Malta, Ananda
   Martins, Isabela Peixoto
   da Silva Franco, Claudineia Conationi
   Pavanello, Audrei
   Torrezan, Rosana
   Marcal Natali, Maria Raquel
   Lisboa, Patricia Cristina
   de Freitas Mathias, Paulo Cezar
   de Moura, Egberto Gaspar
TI Protein Restriction During the Last Third of Pregnancy Malprograms the
   Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat
   Offspring
SO ENDOCRINOLOGY
LA English
DT Article
ID MATERNAL PERINATAL UNDERNUTRITION; BETA-CELL MASS; THRIFTY PHENOTYPE
   HYPOTHESIS; INDUCED INSULIN-SECRETION; NERVOUS-SYSTEM CONTROL;
   GLUCOSE-TOLERANCE; FOOD-INTAKE; ADRENAL-MEDULLA; INDUCED OBESITY;
   LATE-GESTATION
AB Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-densitylipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.
C1 [de Oliveira, Julio Cezar; Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; da Silva Franco, Claudineia Conationi; Pavanello, Audrei; de Freitas Mathias, Paulo Cezar] Univ Estadual Maringa, Dept Biotechnol Cell Biol & Genet, Lab Secret Cell Biol, BR-87020900 Maringa, PR, Brazil.
   [de Oliveira, Julio Cezar; Lisboa, Patricia Cristina; de Moura, Egberto Gaspar] Univ Estado Rio De Janeiro, Roberto Alcantara Gomes Biol Inst, Dept Physiol Sci, BR-20551030 Rio De Janeiro, RJ, Brazil.
   [de Oliveira, Julio Cezar] Univ Fed Mato Grosso, Inst Hlth Sci, BR-78557267 Sinop, MT, Brazil.
   [Gomes, Rodrigo Mello; Torrezan, Rosana] Univ Estadual Maringa, Dept Physiol Sci, BR-87020900 Maringa, PR, Brazil.
   [Barella, Luiz Felipe] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Marcal Natali, Maria Raquel] Univ Estadual Maringa, Dept Morphol Sci, BR-87020900 Maringa, PR, Brazil.
RP de Oliveira, JC; Mathias, PCD (reprint author), Univ Estadual Maringa, State Univ Maringa, Dept Biotechnol Cell Biol & Genet, Lab Secret Cell Biol, Block H67,Room 19,Colombo Ave 5790, BR-87020900 Maringa, PR, Brazil.
EM biojborges@gmail.com
OI Gomes, Rodrigo/0000-0002-9012-3287; Barella, Luiz
   Felipe/0000-0003-2211-3842
FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior fellowship
   at the Institute Polytechnique LaSalle Beauvais, EGEAL-UP (Expression de
   genes et regulation epigenetique par l'aliment - Unite Prope, Beauvais
   Cedex, France); Brazilian Federal Foundation; Conselho Nacional de
   Desenvolvimento Cientifico e Tecnologico; Coordenacao de Aperfeicoamento
   de Pessoal de Nivel Superior; Parana Science Foundation (Fundacao
   Araucaria); Carlos Chagas Filho Research Foundation of the State of Rio
   de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado
   do Rio de Janeiro)
FX P.C.F.M. is a recipient of the Coordenacao de Aperfeicoamento de Pessoal
   de Nivel Superior fellowship at the Institute Polytechnique LaSalle
   Beauvais, EGEAL-UP (Expression de genes et regulation epigenetique par
   l'aliment - Unite Prope, Beauvais Cedex, France).; This work was
   supported by the Brazilian Federal Foundation, Conselho Nacional de
   Desenvolvimento Cientifico e Tecnologico, Coordenacao de Aperfeicoamento
   de Pessoal de Nivel Superior, Parana Science Foundation (Fundacao
   Araucaria), and the Carlos Chagas Filho Research Foundation of the State
   of Rio de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do
   Estado do Rio de Janeiro).
NR 65
TC 1
Z9 1
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2016
VL 157
IS 5
BP 1799
EP 1812
DI 10.1210/en.2015-1883
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL3XT
UT WOS:000375567600013
PM 27007071
ER

PT J
AU Hutchins, BI
   Kotan, LD
   Taylor-Burds, C
   Ozkan, Y
   Cheng, PJ
   Gurbuz, F
   Tiong, JDR
   Mengen, E
   Yuksel, B
   Topaloglu, AK
   Wray, S
AF Hutchins, B. Ian
   Kotan, L. Damla
   Taylor-Burds, Carol
   Ozkan, Yusuf
   Cheng, Paul J.
   Gurbuz, Fatih
   Tiong, Jean D. R.
   Mengen, Eda
   Yuksel, Bilgin
   Topaloglu, A. Kemal
   Wray, Susan
TI CCDC141 Mutation Identified in Anosmic Hypogonadotropic Hypogonadism
   (Kallmann Syndrome) Alters GnRH Neuronal Migration
SO ENDOCRINOLOGY
LA English
DT Article
ID LHRH NEURONS; CORTICAL INTERNEURONS; AXOPHILIC MIGRATION; HORMONE-1
   NEURONS; SIGNALING PROTEIN; EXPLANT CULTURES; TUBA1A MUTATIONS; LEADING
   PROCESS; GENE; SCHIZOPHRENIA
AB The first mutation in a gene associated with a neuronal migration disorder was identified in patients with Kallmann Syndrome, characterized by hypogonadotropic hypogonadism and anosmia. This pathophysiological association results from a defect in the development of the GnRH and the olfactory system. A recent genetic screening of Kallmann Syndrome patients revealed a novel mutation in CCDC141. Little is known about CCDC141, which encodes a coiled-coil domain containing protein. Here, we show that Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Our findings in human patients and mouse models predict that CCDC141 takes part in embryonic migration of GnRH neurons enabling them to form a hypothalamic neuronal network to initiate pulsatile GnRH secretion and reproductive function.
C1 [Hutchins, B. Ian; Taylor-Burds, Carol; Cheng, Paul J.; Tiong, Jean D. R.; Wray, Susan] NINDS, NIH, Bldg 35,Room 3A-1012,35 Convent Dr, Bethesda, MD 20892 USA.
   [Kotan, L. Damla; Topaloglu, A. Kemal] Cukurova Univ, Inst Sci, Dept Biotechnol, TR-01330 Adana, Turkey.
   [Ozkan, Yusuf] Firat Univ, TR-23119 Elazig, Turkey.
   [Gurbuz, Fatih; Mengen, Eda; Yuksel, Bilgin; Topaloglu, A. Kemal] Cukurova Univ, Fac Med, Div Pediat Endocrinol, TR-01330 Adana, Turkey.
RP Wray, S (reprint author), NINDS, NIH, Bldg 35,Room 3A-1012,35 Convent Dr, Bethesda, MD 20892 USA.; Topaloglu, AK (reprint author), Cukurova Univ, Inst Sci, Dept Biotechnol, TR-01330 Adana, Turkey.
EM ktopaloglu@cu.edu.tr; wrays@ninds.nih.gov
OI wray, susan/0000-0001-7670-3915
FU Scientific and Technological Research Council of Turkey Project
   [109S455]; Cukurova University Scientific Research Projects;
   International Centre for Genetic Engineering and Biotechnology Grant
   [CRP/TUR10-01]; Intramural Research Program of the National Institutes
   of Health; National Institute of Neurological Disorders and Stroke
   [NS002824-24/25]; National Institute of General Medical Sciences
   Postdoctoral Research Associate Program
FX This work was supported by the Scientific and Technological Research
   Council of Turkey Project 109S455, by the Cukurova University Scientific
   Research Projects, and by the International Centre for Genetic
   Engineering and Biotechnology Grant CRP/TUR10-01. B.I.H., P.J.C.,
   J.D.R.T., and S.W. were supported by the Intramural Research Program of
   the National Institutes of Health, National Institute of Neurological
   Disorders and Stroke Grant NS002824-24/25. B.I.H. also received funding
   through the National Institute of General Medical Sciences Postdoctoral
   Research Associate Program.
NR 44
TC 1
Z9 1
U1 4
U2 5
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2016
VL 157
IS 5
BP 1956
EP 1966
DI 10.1210/en.2015-1846
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL3XT
UT WOS:000375567600025
PM 27014940
ER

PT J
AU Klenke, U
   Constantin, S
   Wray, S
AF Klenke, Ulrike
   Constantin, Stephanie
   Wray, Susan
TI BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway
SO ENDOCRINOLOGY
LA English
DT Article
ID ESTROGEN-RELATED RECEPTORS; BISPHENOL-A EXPOSURE; GAMMA ERR-GAMMA;
   NEONATAL EXPOSURE; LHRH NEURONS; ENDOCRINE DISRUPTORS; CALCIUM-CHANNELS;
   EXPLANT CULTURES; HORMONE NEURONS; IN-VIVO
AB Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A(BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50 mu M BPA significantly decreased GnRH calcium activity. Blockage of gamma-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-beta, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-gamma, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-gamma, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons.
C1 [Klenke, Ulrike; Constantin, Stephanie; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, 35 Convent Dr MSC 3703,Bldg 35,Room 3A1012, Bethesda, MD 20892 USA.
RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, 35 Convent Dr MSC 3703,Bldg 35,Room 3A1012, Bethesda, MD 20892 USA.
EM wrays@ninds.nih.gov
OI Constantin, Stephanie/0000-0003-0596-9737; wray,
   susan/0000-0001-7670-3915
FU Intramural Research Program of the National Institutes of Health,
   National Institute of Neurological Disorders and Stroke [ZIA
   NS002824-25]
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute of Neurological
   Disorders and Stroke Grant ZIA NS002824-25.
NR 75
TC 2
Z9 2
U1 5
U2 11
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2016
VL 157
IS 5
BP 1980
EP 1990
DI 10.1210/en.2015-1924
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL3XT
UT WOS:000375567600027
PM 26934298
ER

PT J
AU Rath, MF
   Coon, SL
   Amaral, FG
   Weller, JL
   Moller, M
   Klein, DC
AF Rath, Martin F.
   Coon, Steven L.
   Amaral, Fernanda G.
   Weller, Joan L.
   Moller, Morten
   Klein, David C.
TI Melatonin Synthesis: Acetylserotonin O-Methyltransferase (ASMT) Is
   Strongly Expressed in a Subpopulation of Pinealocytes in the Male Rat
   Pineal Gland
SO ENDOCRINOLOGY
LA English
DT Article
ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; AMINO-ACID HYDROXYLASES; S-ANTIGEN;
   TRANSCRIPTION FACTOR; GENE-EXPRESSION; IMMUNOCYTOCHEMICAL DEMONSTRATION;
   MONOCLONAL-ANTIBODY; MAMMALIAN BRAIN; HOMEOBOX GENES; S-100 PROTEIN
AB The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzyme in melatonin synthesis, acetylserotonin O-methyltransferase (ASMT), and in situ hybridization techniques to study transcripts encoding ASMT and two other enzymes in melatonin synthesis, tryptophan hydroxylase (TPH)-1 and aralkylamine N-acetyltransferase. In sections of the rat pineal gland, marked cell-to-cell differences were found in ASMT immunostaining intensity and in the abundance of Tph1, Aanat, and Asmt transcripts. ASMT immunoreactivity was localized to the cytoplasm in pinealocytes in the parenchyma of the superficial pineal gland, and immunopositive pinealocytes were also detected in the pineal stalk and in the deep pineal gland. ASMT was found to inconsistently colocalize with S-antigen, a widely used pinealocyte marker; this colocalization was seen in cells throughout the pineal complex and also in displaced pinealocyte-like cells of the medial habenular nucleus. Inconsistent colocalization between ASMT and TPH protein was also detected in the pineal gland. ASMT protein was not detected in extraepithalamic parts of the central nervous system or in peripheral tissues. The findings in this report are of special interest because they provide reason to suspect that melatonin synthesis varies significantly among individual pinealocytes.
C1 [Rath, Martin F.; Moller, Morten] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark.
   [Rath, Martin F.; Coon, Steven L.; Amaral, Fernanda G.; Weller, Joan L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Rath, MF (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Panum Inst, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
EM mrath@sund.ku.dk
OI Rath, Martin/0000-0002-4047-6324
FU Novo Nordisk Foundation [NNF15OC0015988]; Lundbeck Foundation
   [R108-A10301, R2006-504]; Carlsberg Foundation [CF15-0515]; Danish
   Council for Independent Research [271-06-0754]; Brodrene Hartmanns Fond
   [A27227]; Agnes og Poul Friis Fond [1208009]; Brazilian Council for
   Science and Technology Development [200336/2007-0]; Intramural Research
   Program of the Eunice Kennedy Shriver National Institute of Child Health
   and Human Development [HD008836-09, HD008837-09, HD008838-09]
FX This work was supported by Novo Nordisk Foundation Grant NNF15OC0015988
   (to M.F.R.), Lundbeck Foundation Grants R108-A10301 (to M.F.R.) and
   R2006-504 (to M.M.), Carlsberg Foundation Grant CF15-0515 (to M.F.R.),
   Danish Council for Independent Research Grant 271-06-0754 (to M.F.R.),
   Brodrene Hartmanns Fond Grant A27227 (to M.F.R.), Agnes og Poul Friis
   Fond Grant 1208009 (to M.F.R.), Brazilian Council for Science and
   Technology Development Grant 200336/2007-0 (to F.G.A.), and the
   Intramural Research Program of the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development Projects HD008836-09,
   HD008837-09 and HD008838-09 (to S.L.C., J.L.W., and D.C.K.).
NR 70
TC 1
Z9 1
U1 2
U2 3
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2016
VL 157
IS 5
BP 2028
EP 2040
DI 10.1210/en.2015-1888
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL3XT
UT WOS:000375567600031
PM 26950199
ER

PT J
AU Boutin, A
   Neumann, S
   Gershengorn, MC
AF Boutin, Alisa
   Neumann, Susanne
   Gershengorn, Marvin C.
TI Multiple Transduction Pathways Mediate Thyrotropin Receptor Signaling in
   Preosteoblast-Like Cells
SO ENDOCRINOLOGY
LA English
DT Article
ID THYROID-STIMULATING HORMONE; ACTIVATED PROTEIN-KINASE;
   PARATHYROID-HORMONE; DEPENDENT PATHWAYS; COUPLED RECEPTORS;
   BONE-FORMATION; TSH RECEPTOR; THYROSTIMULIN; OSTEOBLAST; DIFFERENTIATION
AB It has been shown that the TSH receptor (TSHR) couples to a number of different signaling pathways, although the Gs-cAMP pathway has been considered primary. Here, we measured the effects of TSH on bone marker mRNA and protein expression in preosteoblast-like U2OS cells stably expressing TSHRs. We determined which signaling cascades are involved in the regulation of IL-11, osteopontin (OPN), and alkaline phosphatase (ALPL). We demonstrated that TSH-induced up-regulation of IL-11 is primarily mediated via the Gs pathway as IL-11 was up-regulated by forskolin (FSK), an adenylyl cyclase activator, and inhibited by protein kinase A inhibitor H-89 and by silencing of G alpha s by small interfering RNA. OPN levels were not affected by FSK, but its up-regulation was inhibited by TSHR/Gi-uncoupling by pertussis toxin. Pertussis toxin decreased p38 MAPK kinase phosphorylation, and a p38 inhibitor and small interfering RNA knockdown of p38 alpha inhibited OPN induction by TSH. Up-regulation of ALPL expression required high doses of TSH (EC50 = 395nM), whereas low doses (EC50 = 19nM) were inhibitory. FSK-stimulated cAMP production decreased basal ALPL expression, whereas protein kinase A inhibition by H-89 and silencing of G alpha s increased basal levels of ALPL. Knockdown of G alpha q/11 and a protein kinase C inhibitor decreased TSH-stimulated up-regulation of ALPL, whereas a protein kinase C activator increased ALPL levels. A MAPK inhibitor and silencing of ERK1/2 inhibited TSH-stimulated ALPL expression. We conclude that TSH regulates expression of different bone markers via distinct signaling pathways.
C1 [Boutin, Alisa; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, 50 South Dr,Room 4134, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, Lab Endocrinol & Receptor Biol, NIH, 50 South Dr,Room 4134, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, National Institutes of Health [Z01
   DK011006]
FX This work was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health Grant Z01 DK011006.
NR 37
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2016
VL 157
IS 5
BP 2173
EP 2181
DI 10.1210/en.2015-2040
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL3XT
UT WOS:000375567600042
PM 26950201
ER

PT J
AU Gonzales, FA
   Jones, RR
   Deardorff, J
   Windham, GC
   Hiatt, RA
   Kushi, LH
AF Gonzales, Felisa A.
   Jones, Rena R.
   Deardorff, Julianna
   Windham, Gayle C.
   Hiatt, Robert A.
   Kushi, Lawrence H.
TI Neighborhood deprivation, race/ethnicity, and urinary metal
   concentrations among young girls in California
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE Environmental health disparities; Metals; Vulnerability; Lead; Children
ID CUMULATIVE RISK-ASSESSMENT; TOBACCO-SMOKE EXPOSURE;
   ENVIRONMENTAL-HEALTH; LEAD-EXPOSURE; SOCIOECONOMIC-STATUS; MANGANESE
   EXPOSURE; CADMIUM EXPOSURE; CHILDRENS HEALTH; NATIONAL-HEALTH;
   LOW-INCOME
AB Background: Although metals can adversely impact children's health, the distribution of exposures to many metals, particularly among vulnerable subpopulations, is not well characterized.
   Objectives: We sought to determine whether neighborhood deprivation was associated with urinary concentrations of thirteen metals and whether observed relationships varied by race/ethnicity.
   Methods: We obtained neighborhood characteristics from the 2005-2009 American Community Survey. Demographic information and urine samples from 400 healthy young girls in Northern California were obtained during a clinical visit. Urine samples were analyzed for metals using inductively-coupled plasma-mass spectrometry and levels were corrected for creatinine. We ran analysis of variance and generalized linear regression models to estimate associations of urinary metal concentrations with neighborhood deprivation and race/ethnicity and stratified multivariable models to evaluate possible interactions among predictors on metals concentrations.
   Results: Urinary concentrations of three metals (barium, lead, antimony) varied significantly across neighborhood deprivation quartiles, and four (barium, lead, antimony, tin) varied across race/ethnicity groups. In models adjusted for family income and cotinine, both race/ethnicity (F-3,F-224 = 4.34, p = 0.01) and neighborhood deprivation (F-3,F-224 = 4.32, p = 0.01) were associated with antimony concentrations, but neither were associated with lead, barium, or tin, concentrations. Examining neighborhood deprivation within race/ethnicity groups, barium levels (p(interaction) < 0.01) decreased with neighborhood deprivation among Hispanic girls (p(trend) < 0.001) and lead levels (p(interaction) = 0.06) increased with neighborhood deprivation among Asian girls (p(trend) = 0.04).
   Conclusions: Our results indicate that children's vulnerability to some metals varies by neighborhood deprivation quartile and race/ethnicity. These differential distributions of exposures may contribute to environmental health disparities later in life. (C) 2016 Published by Elsevier Ltd.
C1 [Gonzales, Felisa A.] NCI, Hlth Syst & Intervent Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, BG 9609 RM 3E502 MSC 9712,9609 Med Ctr Dr, Rockville, MD 20850 USA.
   [Jones, Rena R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, BG 9609 RM 6E124 MSC 9771,9609 Med Ctr Dr, Rockville, MD 20850 USA.
   [Deardorff, Julianna] Univ Calif Berkeley, Sch Publ Hlth, Dept Community Hlth & Human Dev, 50 Univ Hall 7360, Berkeley, CA 94720 USA.
   [Windham, Gayle C.] Calif Dept Publ Hlth, Environm Hlth Invest Branch, 850 Marina Bay Pkwy,Bldg P,3rd Floor, Richmond, CA 94804 USA.
   [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Helen Diller Family Comprehens Canc Ctr, Box 0560, San Francisco, CA 94143 USA.
   [Kushi, Lawrence H.] Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
RP Gonzales, FA (reprint author), NCI, Hlth Syst & Intervent Res Branch, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, BG 9609 RM 3E502 MSC 9712,9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM felisa.gonzales@nih.gov; rena.jones@nih.gov; jdeardorff@berkeley.edu;
   Gayle.Windham@cdph.ca.gov; robert.hiatt@ucsf.edu; larry.kushi@kp.org
FU National Institute of Environmental Health Sciences (NIEHS)
   [U01ES012801, U01ES019435, U01FS019457]
FX This publication was made possible by the Breast Cancer and the
   Environment Research Program (BCERP) award numbers U01ES012801,
   U01ES019435 and U01FS019457 from the National Institute of Environmental
   Health Sciences (NIEHS) and the National Cancer Institute (NCI), and
   UL1RR024131 from the National Center for Research Resources (NCRR). Its
   contents are solely the responsibility of the authors and do not
   necessarily represent the official views of the NIEHS, NCI, NCCR or
   National Institutes of Health. We are grateful to the California
   Department of Public Health for storage of biospecimens and the support
   of Dr. Windham's time on the project and to the Avon Foundation for
   supporting community outreach and education activities.
NR 94
TC 0
Z9 0
U1 7
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD MAY
PY 2016
VL 91
BP 29
EP 39
DI 10.1016/j.envint.2016.02.004
PG 11
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DL4TQ
UT WOS:000375630500004
PM 26908165
ER

PT J
AU Beard, JD
   Engel, LS
   Richardson, DB
   Gammon, MD
   Baird, C
   Umbach, DM
   Allen, KD
   Stanwyck, CL
   Keller, J
   Sandler, DP
   Schmidt, S
   Kamel, F
AF Beard, John D.
   Engel, Lawrence S.
   Richardson, David B.
   Gammon, Marilie D.
   Baird, Coleen
   Umbach, David M.
   Allen, Kelli D.
   Stanwyck, Catherine L.
   Keller, Jean
   Sandler, Dale P.
   Schmidt, Silke
   Kamel, Freya
TI Military service, deployments, and exposures in relation to amyotrophic
   lateral sclerosis etiology
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE Amyotrophic lateral sclerosis; Case-control; Deployment; Etiology;
   Military
ID MARGINAL STRUCTURAL MODELS; GULF-WAR VETERANS; MOTOR-NEURON DISEASE;
   MILLENNIUM COHORT; NATIONAL REGISTRY; OCCUPATIONAL-EXPOSURE; ANTHRAX
   VACCINATION; PESTICIDE EXPOSURE; VIETNAM VETERANS; TRAUMATIC EVENTS
AB Background: Factors underlying a possible excess of amyotrophic lateral sclerosis (ALS) among military veterans remain unidentified. Limitations of previous studies on this topic include reliance on ALS mortality as a surrogate for ALS incidence, low statistical power, and sparse information on military-related factors. Objectives: We evaluated associations between military-related factors and ALS using data from a case-control study of U.S. military veterans.
   Methods: From 2005 to 2010, we identified medical record-confirmed ALS cases via the National Registry of Veterans with ALS and controls via the Veterans Benefits Administration's Beneficiary Identification and Records Locator System database. In total, we enrolled 621 cases and 958 frequency-matched controls in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study. We collected information on military service and deployments and 39 related exposures. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We used inverse probability weighting to adjust for potential bias from confounding, missing covariate data, and selection arising from a case group that disproportionately included long-term survivors and a control group that may or may not differ from U.S. military veterans at large.
   Results: The odds of ALS did not differ for veterans of the Air Force, Army, Marines, and Navy. We found higher odds of ALS for veterans whose longest deployment was World War II or the Korean War and a positive trend with total years of all deployments (OR = 1.27; 95% CI: 1.06, 1.52). ALS was positively associated with exposure to herbicides for military purposes, nasopharyngeal radium, personal pesticides, exhaust from heaters or generators, high-intensity radar waves, contaminated food, explosions within one mile, herbicides in the field, mixing and application of burning agents, burning agents in the field, and Agent Orange in the field, with ORs between 1.50 and 7.75.
   Conclusions: Although our results need confirmation, they are potentially important given the large number of U.S. military veterans, and they provide clues to potential factors underlying the apparent increase of ALS in veteran populations. Published by Elsevier Ltd
C1 [Beard, John D.; Engel, Lawrence S.; Richardson, David B.; Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
   [Beard, John D.; Sandler, Dale P.; Kamel, Freya] NIEHS, Epidemiol Branch, 111 TW Alexander Dr,A3-05, Res Triangle Pk, NC 27709 USA.
   [Baird, Coleen] US Army Publ Hlth Command, Environm Med Program, Aberdeen Proving Ground, MD USA.
   [Umbach, David M.] NIEHS, Biostat & Computat Biol Branch, 111 TW Alexander Dr,A3-05, Res Triangle Pk, NC 27709 USA.
   [Allen, Kelli D.; Stanwyck, Catherine L.] Durham VA Med Ctr, Durham, NC USA.
   [Allen, Kelli D.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
   [Allen, Kelli D.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
   [Stanwyck, Catherine L.; Schmidt, Silke] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Keller, Jean] Westat Corp, Durham, NC USA.
RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,A3-05, Res Triangle Pk, NC 27709 USA.
EM kamel@niehs.nih.gov
OI Engel, Lawrence/0000-0001-9268-4830; Kamel, Freya/0000-0001-5052-6615;
   Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the NIH; National Institute of
   Environmental Health Sciences (NIEHS) [Z01 ES049005]; NIEHS [R01
   ES13244, T32ES007018]; ALS Association [ALSA 1230]; CDC; National
   Institute for Occupational Safety and Health [T42OH00867302]; U.S.
   Department of Veterans Affairs (CSP) [500A]
FX This work was supported by the Intramural Research Program of the NIH,
   National Institute of Environmental Health Sciences (NIEHS; Z01
   ES049005), grants from the NIEHS (R01 ES13244) and the ALS Association
   (ALSA 1230), and training grants from the NIEHS (T32ES007018) and the
   CDC, National Institute for Occupational Safety and Health
   (T42OH00867302). The National Registry of Veterans with ALS was
   supported by the U.S. Department of Veterans Affairs (CSP #500A).
NR 59
TC 3
Z9 3
U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD MAY
PY 2016
VL 91
BP 104
EP 115
DI 10.1016/j.envint.2016.02.014
PG 12
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA DL4TQ
UT WOS:000375630500011
PM 26923711
ER

PT J
AU Ostroumova, E
   Hatch, M
   Brenner, A
   Nadyrov, E
   Veyalkin, I
   Polyanskaya, O
   Yauseyenka, V
   Polyakov, S
   Levin, L
   Zablotska, L
   Rozhko, A
   Mabuchi, K
AF Ostroumova, Evgenia
   Hatch, Maureen
   Brenner, Alina
   Nadyrov, Eldar
   Veyalkin, Ilya
   Polyanskaya, Olga
   Yauseyenka, Vasilina
   Polyakov, Semion
   Levin, Leonid
   Zablotska, Lydia
   Rozhko, Alexander
   Mabuchi, Kiyohiko
TI Non-thyroid cancer incidence in Belarusian residents exposed to
   Chernobyl fallout in childhood and adolescence: Standardized Incidence
   Ratio analysis, 1997-2011
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Standardized Incidence Ratio (SIR); Solid cancer; Leukemia; Lymphoma;
   Chernobyl
ID IN-UTERO EXPOSURE; THYROID-CANCER; INFANT LEUKEMIA; WEST-GERMANY;
   FOLLOW-UP; ACCIDENT; RADIATION; COHORT; CHILDREN; UKRAINE
AB Background: While an increased risk of thyroid cancer from post-Chernobyl exposure to lodine-131 (I-131) in children and adolescents has been well-documented, risks of other cancers or leukemia as a result of residence in radioactively contaminated areas remain uncertain.
   Methods: We studied non-thyroid cancer incidence in a cohort of about 12,000 individuals from Belarus exposed under age of 18 years to Chernobyl fallout (median age at the time of Chernobyl accident of 7.9 years). During 15 years of follow-up from 1997 through 2011, 54 incident cancers excluding thyroid were identified in the study cohort with 142,968 person-years at risk. We performed Standardized Incidence Ratio (SIR) analysis of all solid cancers excluding thyroid (n=42), of leukemia (n=6) and of lymphoma (n=6).
   Results: We found no significant increase in the incidence of non-thyroid solid cancer (SIR=0.83, 95% Confidence Interval [CI]: 0.61; 1.11), lymphoma (SIR=0.66, 95% CI: 0.26; 1.33) or leukemia (SIR=1.78, 95% CI: 0.71; 3.61) in the study cohort as compared with the sex-, age-and calendar-time-specific national rates. These findings may in part reflect the relatively young age of study subjects (median attained age of 33.4 years), and long latency for some radiation-related solid cancers.
   Conclusions: We found no evidence of statistically significant increases in solid cancer, lymphoma and leukemia incidence 25 years after childhood exposure in the study cohort; however, it is important to continue follow-up non -thyroid cancers in individnals exposed to low-level radiation at radiosensitive ages. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Ostroumova, Evgenia; Hatch, Maureen; Brenner, Alina; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 9609 Med Ctr Dr,MSC 9776, Bethesda, MD 20892 USA.
   [Nadyrov, Eldar; Veyalkin, Ilya; Polyanskaya, Olga; Yauseyenka, Vasilina; Rozhko, Alexander] Republican Res Ctr Radiat Med & Human Ecol, 290 Ilyicha St, Gomel 246040, Byelarus.
   [Polyakov, Semion] State Inst Republican Sci & Pract Ctr Med Technol, 7-A Petrus Brovka St, Minsk 220600, Byelarus.
   [Levin, Leonid] State Estab NN Alexandrov Natl Canc Ctr Belarus O, Canc Registry, Lesnoy 223040, Byelarus.
   [Zablotska, Lydia] Univ Calif San Francisco, 3333 Calif St, San Francisco, CA 94118 USA.
RP Ostroumova, E (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM ostroumovae@iarc.fr; hatchm@mail.nih.gov; brennera@mail.nih.gov;
   nadyrov2006@rambler.ru; veyalkin@mail.ru; polyanskaya@tut.by;
   yaus@mail.ru; spolyakov@belcmt.by; llevin@omr.med.by;
   lydia.zablotska@ucsf.edu; rcrm@tut.by; mabuchik@mail.nih.gov
FU Intramural Research Program of the U.S. National Institutes of Health
   (NIH), National Cancer Institute (NCI)
FX This research was supported by the Intramural Research Program of the
   U.S. National Institutes of Health (NIH), National Cancer Institute
   (NCI). The funding agency had no influence on study design, conduct, or
   reporting. We acknowledge the contribution of Olga Shcherbina
   (Republican Scientific and Practical Center for Medical Technologies,
   Informatization, Administration and Management of Health, Minsk,
   Belarus) to the study execution.
NR 29
TC 1
Z9 3
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD MAY
PY 2016
VL 147
BP 44
EP 49
DI 10.1016/j.envres.2016.01.025
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA DJ5UN
UT WOS:000374275700006
PM 26851723
ER

PT J
AU Velez, MP
   Arbuckle, TE
   Fraser, WD
   Mumford, SL
AF Velez, M. P.
   Arbuckle, T. E.
   Fraser, W. D.
   Mumford, S. L.
TI Perfluoroalicyl acids and Time-to-Pregnancy: The issue of
   "parity-conditioning bias"
SO ENVIRONMENTAL RESEARCH
LA English
DT Letter
ID PERFLUORINATED CHEMICALS; WOMEN; SUBFECUNDITY; EXPOSURE; PLASMA
C1 [Velez, M. P.] Queens Univ, Kingston Gen Hosp, Dept Obstet & Gynecol, Kingston, ON, Canada.
   [Arbuckle, T. E.] Hlth Canada, Populat Studies Div, Hlth Environm & Consumer Safety Branch, Ottawa, ON K1A 0L2, Canada.
   [Fraser, W. D.] Univ Montreal, St Justine Univ Hosp Res Ctr, Montreal, PQ, Canada.
   [Fraser, W. D.] Univ Sherbrooke, Dept Obstet & Gynecol, Sherbrooke, PQ J1K 2R1, Canada.
   [Mumford, S. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD USA.
RP Velez, MP (reprint author), Queens Univ, Kingston Gen Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Victory 4,76 Stuart St, Kingston, ON K7L 2V7, Canada.
EM maria.velez@queensu.ca
NR 12
TC 0
Z9 0
U1 2
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD MAY
PY 2016
VL 147
BP 572
EP 573
DI 10.1016/j.envres.2015.12.029
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA DJ5UN
UT WOS:000374275700064
PM 27040410
ER

PT J
AU Turcu, AF
   Nanba, AT
   Chomic, R
   Upadhyay, SK
   Giordano, TJ
   Shields, JJ
   Merke, DP
   Rainey, WE
   Auchus, RJ
AF Turcu, Adina F.
   Nanba, Aya T.
   Chomic, Robert
   Upadhyay, Sunil K.
   Giordano, Thomas J.
   Shields, James J.
   Merke, Deborah P.
   Rainey, William E.
   Auchus, Richard J.
TI Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant
   androgens in classic 21-hydroxylase deficiency
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID PRECOCIOUS PUBARCHE; HYPERPLASIA; WOMEN; 11-BETA-HYDROXYANDROSTENEDIONE;
   STIMULATION; MARKER; EXCESS; GENE
AB Objective: To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation.
   Design: Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex-and age-matched controls; 3 patients with 11 beta-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies.
   Methods: We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3 beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b(5) (CYB5A) within the normal and 21OHD adrenals.
   Results: Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11 beta-hydroxyandrostenedione, 11-ketoandrostenedione 11 beta-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11 beta-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals.
   Conclusions: All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess.
C1 [Turcu, Adina F.; Nanba, Aya T.; Upadhyay, Sunil K.; Rainey, William E.; Auchus, Richard J.] Univ Michigan, Div Metab Endocrinol & Diabet, 1150 W Med Ctr Dr, Ann Arbor, MI USA.
   [Chomic, Robert] Univ Michigan, Michigan Metabol & Obes Ctr, 1150 W Med Ctr Dr, Ann Arbor, MI USA.
   [Giordano, Thomas J.] Univ Michigan, Dept Pathol, 1150 W Med Ctr Dr, Ann Arbor, MI USA.
   [Shields, James J.] Univ Michigan, Dept Radiol, 1150 W Med Ctr Dr, Ann Arbor, MI USA.
   [Merke, Deborah P.] NIH, Ctr Clin, Pediatr Serv, 10 Ctr Dr, Bethesda, MD 20892 USA.
   [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 10 Ctr Dr, Bethesda, MD 20892 USA.
   [Rainey, William E.] Univ Michigan, Dept Mol & Integrat Physiol & Med, 1150 W Med Ctr, Ann Arbor, MI 48109 USA.
   [Auchus, Richard J.] Univ Michigan, Dept Pharmacol, 1150 W Med Ctr, Ann Arbor, MI 48109 USA.
RP Auchus, RJ (reprint author), Univ Michigan, Div Metab Endocrinol & Diabet, 1150 W Med Ctr Dr, Ann Arbor, MI USA.; Auchus, RJ (reprint author), Univ Michigan, Dept Pharmacol, 1150 W Med Ctr, Ann Arbor, MI 48109 USA.
EM rauchus@med.umich.edu
FU University of Michigan Reproductive Sciences Program; MICHR Pilot
   [U046500, R01GM086596, R01DK069950]; Intramural Research Program of the
   NIH; National Institutes of Health [DK089503];  [1F32DK103461]
FX This work was supported by pilot grants from the University of Michigan
   Reproductive Sciences Program and by grants MICHR Pilot U046500 to AT,
   R01GM086596 to RJA, R01DK069950 to WER, and in part by the Intramural
   Research Program of the NIH. AFT was supported by 1F32DK103461. Mass
   spectrometry used core services supported by Grant DK089503 from the
   National Institutes of Health to the University of Michigan under the
   Michigan Nutrition Obesity Center (NORC).
NR 34
TC 4
Z9 4
U1 2
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
   ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD MAY
PY 2016
VL 174
IS 5
BP 601
EP 609
DI 10.1530/EJE-15-1181
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DL5BZ
UT WOS:000375653400010
PM 26865584
ER

PT J
AU Schernthaner-Reiter, MH
   Adams, D
   Trivellin, G
   Ramnitz, MS
   Raygada, M
   Golas, G
   Faucz, FR
   Nilsson, O
   Nella, AA
   Dileepan, K
   Lodish, M
   Lee, P
   Tifft, C
   Markello, T
   Gahl, W
   Stratakis, CA
AF Schernthaner-Reiter, Marie Helene
   Adams, David
   Trivellin, Giampaolo
   Ramnitz, Mary Scott
   Raygada, Margarita
   Golas, Gretchen
   Faucz, Fabio R.
   Nilsson, Ola
   Nella, Aikaterini A.
   Dileepan, Kavitha
   Lodish, Maya
   Lee, Paul
   Tifft, Cynthia
   Markello, Thomas
   Gahl, William
   Stratakis, Constantine A.
TI A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic
   diabetes insipidus in two brothers
SO EUROPEAN JOURNAL OF PEDIATRICS
LA English
DT Article
DE X-linked nephrogenic diabetes insipidus; Arginine vasopressin receptor
   type 2; Partial nephrogenic diabetes insipidus; Pathogenic splice site
   mutation
ID UNDIAGNOSED DISEASES; GENE; INSIGHTS
AB X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A > G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain.
   Conclusion: We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis.
C1 [Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Faucz, Fabio R.; Nilsson, Ola; Nella, Aikaterini A.; Lodish, Maya; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
   [Adams, David; Golas, Gretchen; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William] NHGRI, NIH Undiagnosed Dis Program, Common Fund, Off Director,NIH, Bethesda, MD 20892 USA.
   [Adams, David; Golas, Gretchen; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Dileepan, Kavitha] Childrens Mercy Hosp, Div Endocrinol & Diabet, Kansas City, MO 64108 USA.
RP Lodish, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
EM helene@schernthaner.eu; david.adams@nih.gov;
   giampaolo.trivellin@nih.gov; maryscott.ramnitz@nih.gov; mr346j@nih.gov;
   gretchen.golas@nih.gov; Fabio.faucz@nih.gov; kdileepan@cmh.edu;
   lodishma@mail.nih.gov; paul.lee@nih.gov; cynthia.tifft@nih.gov;
   thomas.markello@nih.gov; gahlw@mail.nih.gov;
   constantine.stratakis@nih.gov
RI Trivellin, Giampaolo/J-6583-2016; 
OI Trivellin, Giampaolo/0000-0003-2384-4153; Schernthaner-Reiter, Marie
   Helene/0000-0002-7972-7610
NR 13
TC 2
Z9 2
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6199
EI 1432-1076
J9 EUR J PEDIATR
JI Eur. J. Pediatr.
PD MAY
PY 2016
VL 175
IS 5
BP 727
EP 733
DI 10.1007/s00431-015-2684-4
PG 7
WC Pediatrics
SC Pediatrics
GA DJ9UX
UT WOS:000374559600015
PM 26795631
ER

PT J
AU Cavalcante, MPV
   Brunelli, JB
   Miranda, CC
   Novak, GV
   Malle, L
   Aikawa, NE
   Jesus, AA
   Silva, CA
AF Cavalcante, Miria Paula V.
   Brunelli, Juliana B.
   Miranda, Clarissa C.
   Novak, Glaucia V.
   Malle, Louise
   Aikawa, Nadia E.
   Jesus, Adriana A.
   Silva, Clovis Artur
TI CANDLE syndrome: chronic atypical neutrophilic dermatosis with
   lipodystrophy and elevated temperature-a rare case with a novel mutation
SO EUROPEAN JOURNAL OF PEDIATRICS
LA English
DT Article
DE CANDLE syndrome; Tocilizumab; Sweet syndrome; PSMB8 gene
ID MONOGENIC AUTOINFLAMMATORY DISEASES; UPDATE
AB We described herein a patient with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and a novel mutation in PSMB8 gene. This patient had multiple visceral inflammatory involvements, including rare manifestations, such as Sweet syndrome and pericarditis. A 3-year-old male, Caucasian, was born to consanguineous healthy parents. At the age of 11 months, he presented daily fever (temperature > 40 A degrees C), irritability, hepatomegaly, splenomegaly; and tender and itching, erythematous papular and edematous plaque lesions. Echocardiogram showed mild pericarditis. Skin biopsy revealed a neutrophil infiltrate without vasculitis suggesting Sweet syndrome. Mutational screening of PSMB8 gene revealed homozygous c.280G > C, p.A94P mutation. He responded partially to high doses of oral glucorticoid and intravenous methylprednisolone. Colchicine, azathioprine, methotrexate, cyclosporine, and intravenous immunoglobulin were not efficacious. At the age of 3 years and 1 month, tocilizumab was administered resulting in remission of daily fever and irritability. However, there was no improvement of the skin tenderness and itching lesions.
   Conclusion: A new mutation in a CANDLE syndrome patient was reported with pericarditis and mimicking Sweet syndrome. The disease manifestations were refractory to immunosuppressive agents and partially responsive to tocilizumab therapy.
C1 [Cavalcante, Miria Paula V.; Silva, Clovis Artur] Hosp Geral Fortaleza, Dept Pediat, Pediat Rheumatol Unit, Fortaleza, Ceara, Brazil.
   [Cavalcante, Miria Paula V.; Brunelli, Juliana B.; Miranda, Clarissa C.; Novak, Glaucia V.; Aikawa, Nadia E.] Univ Sao Paulo, Fac Med, Dept Pediat, Pediat Rheumatol Unit, Sao Paulo, Brazil.
   [Malle, Louise; Aikawa, Nadia E.; Jesus, Adriana A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Silva, Clovis Artur] Av Dr Eneas Carvalho Aguiar 647, BR-05403000 Sao Paulo, SP, Brazil.
RP Silva, CA (reprint author), Hosp Geral Fortaleza, Dept Pediat, Pediat Rheumatol Unit, Fortaleza, Ceara, Brazil.; Silva, CA (reprint author), Av Dr Eneas Carvalho Aguiar 647, BR-05403000 Sao Paulo, SP, Brazil.
EM miria_cavalvante@hotmail.com; juju_brunelli@hotmail.com;
   clarissa-cm@hotmail.com; glaucia_novak@hotmail.com;
   louise.malle@nih.gov; nadia.aikawa@gmail.com; adriaj@uol.com.br;
   clovisaasilva@gmail.com
FU Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPQ)
   [302724/2011-7]; Federico Foundation; Nucleo de Apoio a Pesquisa "Saude
   da Crianca e do Adolescente" da USP (NAP-CriAd); NIAMS Intramural
   Research program (IRP) NIH; NIAMS
FX This study was funded by Conselho Nacional do Desenvolvimento Cientifico
   e Tecnologico (CNPQ-grant 302724/2011-7 to CAS), by Federico Foundation
   to CAS, by Nucleo de Apoio a Pesquisa "Saude da Crianca e do
   Adolescente" da USP (NAP-CriAd) and was funded by the NIAMS Intramural
   Research program (IRP) NIH, the Clinical Center, and NIAMS.
NR 13
TC 1
Z9 2
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6199
EI 1432-1076
J9 EUR J PEDIATR
JI Eur. J. Pediatr.
PD MAY
PY 2016
VL 175
IS 5
BP 735
EP 740
DI 10.1007/s00431-015-2668-4
PG 6
WC Pediatrics
SC Pediatrics
GA DJ9UX
UT WOS:000374559600016
PM 26567544
ER

PT J
AU Yoshizawa, K
   Yuki, M
   Kinoshita, Y
   Emoto, Y
   Yuri, T
   Shikata, N
   Elmore, SA
   Tsubura, A
AF Yoshizawa, Katsuhiko
   Yuki, Michiko
   Kinoshita, Yuichi
   Emoto, Yuko
   Yuri, Takashi
   Shikata, Nobuaki
   Elmore, Susan A.
   Tsubura, Airo
TI Characterization of mammary adenocarcinomas in male rats after
   N-methyl-N-nitrosourea exposure-Potential for human male breast cancer
   model
SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE Breast cancer; Immunohistochemistry; Male rat; Mammary adenocarcinoma;
   N-methyl-N-nitrosourea
ID SPRAGUE-DAWLEY RATS; PROGESTERONE-RECEPTORS; GATA-3 EXPRESSION;
   CARCINOMA; IMMUNOHISTOCHEMISTRY; ESTROGEN; SUBTYPES; LESIONS; TUMORS;
   RECOMMENDATIONS
AB The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor a (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. (C) 2016 Elsevier GmbH. All rights reserved.
C1 [Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Tsubura, Airo] Kansai Med Univ, Dept Pathol 2, 2-5-1 Shin Machi, Hirakata, Osaka 5731010, Japan.
   [Kinoshita, Yuichi; Shikata, Nobuaki] Kansai Med Univ, Takii Hosp, Div Diagnost Cytopathol & Histopathol, Fumizono 10-15, Moriguchi, Osaka 5708507, Japan.
   [Elmore, Susan A.] NIEHS, Cellular & Mol Pathol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Yoshizawa, K (reprint author), Kansai Med Univ, Dept Pathol 2, 2-5-1 Shin Machi, Hirakata, Osaka 5731010, Japan.
EM yoshizak@hirakata.kmu.ac.jp
FU MEXT-Programs for the Strategic Research Foundations at Private
   Universities (Kansai Medical University); Intramural Research Program of
   the National Institutes of Health (NIH), National Institute of
   Environmental Health Sciences (NIEHS)
FX All authors read and approved the final manuscript. The authors declare
   that we have no competing financial interests. This project was
   supported by a grant from MEXT-Supported Programs for the Strategic
   Research Foundations at Private Universities (Kansai Medical
   University). This research was supported [in part] by the Intramural
   Research Program of the National Institutes of Health (NIH), National
   Institute of Environmental Health Sciences (NIEHS).
NR 53
TC 0
Z9 0
U1 1
U2 6
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0940-2993
EI 1618-1433
J9 EXP TOXICOL PATHOL
JI Exp. Toxicol. Pathol.
PD MAY
PY 2016
VL 68
IS 5
BP 263
EP 270
DI 10.1016/j.etp.2016.01.005
PG 8
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DL3DV
UT WOS:000375515300002
PM 26852374
ER

PT J
AU Franco, PF
   Silva, NCS
   do Vale, VF
   Abreu, JF
   Santos, VC
   Gontijo, NF
   Valenzuela, JG
   Pereira, MH
   Sant'Anna, MRV
   Gomes, APS
   Araujo, RN
AF Franco, Paula F.
   Silva, Naylene C. S.
   do Vale, Vladimir Fazito
   Abreu, Jessica F.
   Santos, Vania C.
   Gontijo, Nelder F.
   Valenzuela, Jesus G.
   Pereira, Marcos H.
   Sant'Anna, Mauricio R. V.
   Gomes, Alessandra P. S.
   Araujo, Ricardo N.
TI Inhibition of the classical pathway of the complement system by saliva
   of Amblyomma cajennense (Acari: Ixodidae)
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Saliva; Amblyomma cajennense; Anti-complement; Haematophagy; Classical
   pathway
ID IXODES-SCAPULARIS; ANTICOMPLEMENT PROTEINS; BOOPHILUS-MICROPLUS; GLAND
   DEGENERATION; TICK SALIVA; AMERICANUM; RICINUS; MECHANISMS; PHYSIOLOGY;
   HEBRAEUM
AB Inhibition of the complement system during and after haematophagy is of utmost importance for tick success in feeding and tick development. The role of such inhibition is to minimise damage to the intestinal epithelium as well as avoiding inflammation and opsonisation of salivary molecules at the bite site. Despite its importance, the salivary anti-complement activity has been characterised only in species belonging to the Ixodes ricinus complex which saliva is able to inhibit the alternative and lectin pathways. Little is known about this activity in other species of the Ixodidae family. Thus, the aim of this study was to describe the inhibition of the classical pathway of the complement system by the saliva of Amblyomma cajennense at different stages of the haematophagy. The A. cajennense saliva and salivary gland extract (SGE) were able to inhibit the complement classical pathway through haemolytic assays with higher activity observed when saliva was used. The anti-complement activity is present in the salivary glands of starving females and also in females throughout the whole feeding process, with significant higher activity soon after tick detachment. The SGE activity from both females fed on mice or horses had no significant correlation (p > 0.05) with tick body weight. The pH found in the intestinal lumen of A. cajennense was 8.04 +/- 0.08 and haemolytic assays performed at pH 8.0 showed activation of the classical pathway similarly to what occurs at pH 7.4. Consequently, inhibition could be necessary to protect the tick enterocytes. Indeed, the inhibition observed by SGE was higher in pH 8.0 in comparison to pH 7.4 reinforcing the role of saliva in protecting the intestinal cells. Further studies should be carried out in order to identify the inhibitor molecule and characterise its inhibition mechanism. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Franco, Paula F.; Silva, Naylene C. S.; do Vale, Vladimir Fazito; Abreu, Jessica F.; Santos, Vania C.; Gontijo, Nelder F.; Pereira, Marcos H.; Sant'Anna, Mauricio R. V.; Araujo, Ricardo N.] Univ Fed Minas Gerais, Dept Parasitol, Lab Fisiol Insetos Hematofagos, Belo Horizonte, MG, Brazil.
   [do Vale, Vladimir Fazito] Fiocruz MS, Inst Oswaldo Cruz, Lab Simulideos & Oncocercose, BR-21045900 Rio De Janeiro, RJ, Brazil.
   [Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA.
   [Gomes, Alessandra P. S.] Pontificia Univ Catolica Minas Gerais, PUC Minas, Inst Ciencias Biol & Saude, Belo Horizonte, MG, Brazil.
RP Araujo, RN (reprint author), Univ Fed Minas Gerais, ICB, Bloco I4 Sala 177,Ave Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil.
EM rnaraujo@icb.ufmg.br
RI Pereira, Marcos/A-3774-2012
FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais; Conselho
   Nacional de Desenvolvimento Cientifico e Tecnologico
FX The authors would like to thank Mrs Marcia Gomes for her technical
   assistance and the anonymous reviewers for invaluable suggestions that
   improved the manuscript. The work was supported by Fundacao de Amparo a
   Pesquisa do Estado de Minas Gerais and Conselho Nacional de
   Desenvolvimento Cientifico e Tecnologico.
NR 44
TC 2
Z9 2
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
EI 1090-2449
J9 EXP PARASITOL
JI Exp. Parasitol.
PD MAY
PY 2016
VL 164
BP 91
EP 96
DI 10.1016/j.exppara.2016.03.002
PG 6
WC Parasitology
SC Parasitology
GA DJ8AY
UT WOS:000374435700014
PM 26948715
ER

PT J
AU Tuncbag, N
   Gursoy, A
   Keskin, O
   Nussinov, R
AF Tuncbag, Nurcan
   Gursoy, Attila
   Keskin, Ozlem
   Nussinov, Ruth
TI The potential impact of recent developments in three-dimensional
   quantitative interaction proteomics on structural biology
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Editorial Material
DE Integrative modeling; structural bioinformatics; assembly modeling;
   protein interactions
ID NATIVE MASS-SPECTROMETRY; CHEMICAL CROSS-LINKING; PROTEIN INTERACTIONS;
   MEMBRANE-PROTEINS; COMPLEXES; ARCHITECTURE; CELL
C1 [Tuncbag, Nurcan] Middle E Tech Univ, Dept Hlth Informat, Grad Sch Informat, TR-06531 Ankara, Turkey.
   [Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
   [Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, Comp Engn, Istanbul, Turkey.
   [Keskin, Ozlem] Koc Univ, Coll Engn, Chem & Biol Engn, Istanbul, Turkey.
   [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21701 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
EM nussinor@helix.nih.gov
RI Tuncbag, Nurcan/D-3383-2011; Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]
NR 26
TC 1
Z9 1
U1 4
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1478-9450
EI 1744-8387
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD MAY
PY 2016
VL 13
IS 5
BP 447
EP 449
DI 10.1080/14789450.2016.1182023
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DL7VO
UT WOS:000375848400001
PM 27104235
ER

PT J
AU Jung, O
   Patnaik, S
   Marugan, J
   Sidransky, E
   Westbroek, W
AF Jung, Olive
   Patnaik, Samarjit
   Marugan, Juan
   Sidransky, Ellen
   Westbroek, Wendy
TI Progress and potential of non-inhibitory small molecule chaperones for
   the treatment of Gaucher disease and its implications for Parkinson
   disease
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Review
DE Lysosomal storage diseases; Gaucher disease; chemical chaperone;
   glucocerebrosidase; synculeinopathies; Parkinson disease; high
   throughput screening
ID ACID BETA-GLUCOSIDASE; GLUCOCEREBROSIDASE MUTATIONS; PHARMACOLOGICAL
   CHAPERONE; MOUSE MODEL; MURINE G(M1)-GANGLIOSIDOSIS; MUTANT
   GLUCOCEREBROSIDASE; SYNUCLEIN ACCUMULATION; THERAPEUTIC STRATEGY;
   LYSOSOMAL BIOGENESIS; REPLACEMENT THERAPY
AB Gaucher disease, caused by pathological mutations GBA1, encodes the lysosome-resident enzyme glucocerebrosidase, which cleaves glucosylceramide into glucose and ceramide. In Gaucher disease, glucocerebrosidase deficiency leads to lysosomal accumulation of substrate, primarily in cells of the reticulo-endothelial system. Gaucher disease has broad clinical heterogeneity, and mutations in GBA1 are a risk factor for the development of different synucleinopathies. Insights into the cell biology and biochemistry of glucocerebrosidase have led to new therapeutic approaches for Gaucher disease including small chemical chaperones. Such chaperones facilitate proper enzyme folding and translocation to lysosomes, thereby preventing premature breakdown of the enzyme in the proteasome. This review discusses recent progress in developing chemical chaperones as a therapy for Gaucher disease, with implications for the treatment of synucleinopathies. It focuses on the development of non-inhibitory glucocerebrosidase chaperones and their therapeutic advantages over inhibitory chaperones, as well as the challenges involved in identifying and validating chemical chaperones.
C1 [Jung, Olive; Sidransky, Ellen; Westbroek, Wendy] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1E623,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
   [Patnaik, Samarjit; Marugan, Juan] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1E623,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
RI di Ronza, Alberto/H-7674-2016
OI di Ronza, Alberto/0000-0002-9813-5143
FU Intramural Research Programs of the National Human Genome Research
   Institute, National Center for Advancing Translational Sciences, and
   National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
   National Human Genome Research Institute, National Center for Advancing
   Translational Sciences, and National Institutes of Health.
NR 114
TC 5
Z9 5
U1 15
U2 24
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1478-9450
EI 1744-8387
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD MAY
PY 2016
VL 13
IS 5
BP 471
EP 479
DI 10.1080/14789450.2016.1174583
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DL7VO
UT WOS:000375848400004
PM 27098312
ER

PT J
AU Bayefsky, MJ
   DeCherney, AH
   Berkman, BE
AF Bayefsky, Michelle J.
   DeCherney, Alan H.
   Berkman, Benjamin E.
TI Compensation for egg donation: a zero-sum game
SO FERTILITY AND STERILITY
LA English
DT Review
C1 [Bayefsky, Michelle J.; Berkman, Benjamin E.] NCI, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
   [DeCherney, Alan H.] NICHHD, Bethesda, MD 20892 USA.
   [Berkman, Benjamin E.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Bayefsky, MJ (reprint author), NCI, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
OI Berkman, Benjamin/0000-0002-9098-0799
FU Intramural NIH HHS [Z99 HD999999]
NR 5
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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAY
PY 2016
VL 105
IS 5
BP 1153
EP 1154
DI 10.1016/j.fertnstert.2016.01.019
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DL8DV
UT WOS:000375871200014
PM 26854609
ER

PT J
AU Gomez-Verjan, JC
   Estrella-Parra, E
   Vazquez-Martinez, ER
   Gonzalez-Sanchez, I
   Guerrero-Magos, G
   Mendoza-Villanueva, D
   Isus, L
   Alfaro, A
   Cerbon-Cervantes, M
   Aloy, P
   Reyes-Chilpa, R
AF Gomez-Verjan, J. C.
   Estrella-Parra, E.
   Vazquez-Martinez, E. R.
   Gonzalez-Sanchez, I.
   Guerrero-Magos, G.
   Mendoza-Villanueva, D.
   Isus, L.
   Alfaro, A.
   Cerbon-Cervantes, M.
   Aloy, P.
   Reyes-Chilpa, R.
TI Risk assessment of Soulatrolide and Mammea (A/BA plus A/BB) coumarins
   from Calophyllum brasiliense by a toxicogenomic and toxicological
   approach
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Coumarins; Toxicogenomics; Mammea A/BA plus A/BB; Soulatrolide;
   Toxicology; Calophyllum brasiliense
ID TRYPANOCIDAL CONSTITUENTS; LEISHMANIA-AMAZONENSIS; NATURAL-PRODUCT;
   MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR-MECHANISMS; ACTIVE CONSTITUENTS;
   APPROACHES REVEAL; CLINICAL-TRIALS; DRUG DISCOVERY; MEXICAN PLANTS
AB Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Gomez-Verjan, J. C.; Estrella-Parra, E.; Gonzalez-Sanchez, I.; Reyes-Chilpa, R.] Univ Nacl Autonoma Mexico, Inst Quim, Dept Prod Nat, Mexico City 04510, DF, Mexico.
   [Vazquez-Martinez, E. R.; Cerbon-Cervantes, M.] Univ Nacl Autonoma Mexico, Fac Quim, Inst Nacl Perinatol, Unidad Invest Reprod Humana, Mexico City 04510, DF, Mexico.
   [Guerrero-Magos, G.] Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Lab Fitofarmacol, Mexico City 04510, DF, Mexico.
   [Mendoza-Villanueva, D.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21701 USA.
   [Isus, L.; Aloy, P.] IRB Barcelona, Joint IRB BSC CRG Program Computat Biol, Barcelona, Catalonia, Spain.
   [Alfaro, A.] Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Unidad Med Genom, Mexico City 04510, DF, Mexico.
   [Aloy, P.] ICREA, Barcelona, Catalonia, Spain.
RP Reyes-Chilpa, R (reprint author), Univ Nacl Autonoma Mexico, Inst Quim, Dept Prod Nat, Mexico City 04510, DF, Mexico.
EM carlosverjan@comunidad.unam.mx; chilpa@unam.mx
FU CONACYT [220346]; DGAPA, UNAM [IG200513]; Intramural Research Program of
   the NIH, National Cancer Institute, USA
FX Juan Carlos Gomez Verjan is grateful with CONACYT for providing a
   scholarship 220346. This work was submitted in fulfillment of the
   requirements to obtain PhD degree at Doctorado en Ciencias Biomedicas
   from UNAM. This research was supported by grant IG200513 from DGAPA,
   UNAM. Ignacio Gonzalez-Sanchez was supported by a post-doctoral grant
   (DGAPA, UNAM). This research was supported in part by the Intramural
   Research Program of the NIH, National Cancer Institute, USA (D M-V). We
   are grateful with Jorge Ivan Castillo-Arellano, Iliana
   Arellano-Bermudez, and Laura Guzman-Gutierrez, for botanicals collects,
   and laboratory assistance. We also thank Rocio Patino, Hector Rios,
   Beatriz Quiroz, Maria de los Angeles Pena, Javier Perez, and Luis
   Velasco for spectrometric recordings of tested compounds.
NR 55
TC 0
Z9 0
U1 4
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD MAY
PY 2016
VL 91
BP 117
EP 129
DI 10.1016/j.fct.2016.03.010
PG 13
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA DL4TD
UT WOS:000375629200013
PM 26995226
ER

PT J
AU Nath, A
   Conroy, E
AF Nath, Avindra
   Conroy, Elena
TI Endogenous retroviruses in amyotrophic lateral sclerosis
SO FUTURE VIROLOGY
LA English
DT Editorial Material
DE antiviral drugs; endogenous retroviruses; HIV/AIDS; mixed infections
AB Avindra Nath received his MD degree from Christian Medical College in India in 1981 and completed a residency in neurology from University of Texas Health Science Center in Houston (TX, USA), followed by a fellowship in multiple sclerosis and neurovirology at the same institution and then a fellowship in neuro-AIDS at National Institute of Neurological Disorders and Stroke. He held faculty positions at the University of Manitoba (1990-1997) (Canada) and the University of Kentucky (1997-2002) (USA). In 2002, he joined Johns Hopkins University (MD, USA) as Professor of Neurology and Director of the Division of Neuroimmunology and Neurological Infections. He joined NIH in 2011 as the Clinical Director of National Institute of Neurological Disorders and Stroke, the Director of the Translational Neuroscience Center and Chief of the Section of Infections of the Nervous System. His research focuses on understanding the pathophysiology of retroviral infections of the nervous system and the development of new diagnostic and therapeutic approaches for these diseases.
C1 [Nath, Avindra] NINDS, NIH, Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), NINDS, NIH, Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
NR 0
TC 0
Z9 0
U1 9
U2 9
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
   1QB, ENGLAND
SN 1746-0794
EI 1746-0808
J9 FUTURE VIROL
JI Future Virol.
PD MAY
PY 2016
VL 11
IS 5
BP 317
EP 320
DI 10.2217/fvl-2016-0038
PG 4
WC Virology
SC Virology
GA DL4FX
UT WOS:000375590400002
ER

PT J
AU Hjelm, BE
   Grunseich, C
   Gowing, G
   Avalos, P
   Tian, J
   Shelley, BC
   Mooney, M
   Narwani, K
   Shi, Y
   Svendsen, CN
   Wolfe, JH
   Fischbeck, KH
   Pierson, TM
AF Hjelm, B. E.
   Grunseich, C.
   Gowing, G.
   Avalos, P.
   Tian, J.
   Shelley, B. C.
   Mooney, M.
   Narwani, K.
   Shi, Y.
   Svendsen, C. N.
   Wolfe, J. H.
   Fischbeck, K. H.
   Pierson, T. M.
TI Mifepristone-inducible transgene expression in neural progenitor cells
   in vitro and in vivo
SO GENE THERAPY
LA English
DT Article
ID INACTIVATING LENTIVIRUS VECTOR; PLURIPOTENT STEM-CELLS;
   CENTRAL-NERVOUS-SYSTEM; GENE-THERAPY; RAT MODEL; PARKINSONS-DISEASE;
   GROWTH-FACTOR; SPINAL-CORD; MOUSE MODEL; BRAIN
AB Numerous gene and cell therapy strategies are being developed for the treatment of neurodegenerative disorders. Many of these strategies use constitutive expression of therapeutic transgenic proteins, and although functional in animal models of disease, this method is less likely to provide adequate flexibility for delivering therapy to humans. Ligand-inducible gene expression systems may be more appropriate for these conditions, especially within the central nervous system (CNS). Mifepristone's ability to cross the blood-brain barrier makes it an especially attractive ligand for this purpose. We describe the production of a mifepristone-inducible vector system for regulated expression of transgenes within the CNS. Our inducible system used a lentivirus-based vector platform for the ex vivo production of mifepristone-inducible murine neural progenitor cells that express our transgenes of interest. These cells were processed through a series of selection steps to ensure that the cells exhibited appropriate transgene expression in a dose-dependent and temporally controlled manner with minimal background activity. Inducible cells were then transplanted into the brains of rodents, where they exhibited appropriate mifepristone-inducible expression. These studies detail a strategy for regulated expression in the CNS for use in the development of safe and efficient gene therapy for neurological disorders.
C1 [Hjelm, B. E.; Gowing, G.; Avalos, P.; Tian, J.; Shelley, B. C.; Narwani, K.; Svendsen, C. N.; Pierson, T. M.] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA.
   [Grunseich, C.; Mooney, M.; Shi, Y.; Fischbeck, K. H.] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Wolfe, J. H.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
   [Wolfe, J. H.] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA.
   [Pierson, T. M.] Childrens Hosp, Stokes Res Inst, Philadelphia, PA 19104 USA.
   [Hjelm, B. E.; Grunseich, C.] Cedars Sinai Med Ctr, Dept Pediat & Neurol, Los Angeles, CA 90048 USA.
RP Pierson, TM (reprint author), Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA.
EM tyler.pierson@cshs.org
FU NIH [T32-HD043021-04, R01-NS08867]; Intramural Research Program of the
   NIH/NINDS; Cedars-Sinai Medical Center; Board of Governors Regenerative
   Medicine Institute institutional funding; Diana and Steve Marienhoff
   Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular
   Diseases
FX We are grateful to Trena Clarke (University of Pennsylvania), Kelli
   DeJohn, Jacalyn McHugh, Roksana Elder, Weidong Xiong and Vaithi
   Arumugaswami (CSMC) for their logistical and technical help, personal
   assistance and advice. We also appreciate the technical assistance from
   the Protein Expression Laboratory at NCI-Frederick, the Vector Core at
   the University of Pennsylvania and the Vector Core (Arumugaswami)
   laboratory of the Cedars-Sinai Regenerative Medicine Institute.
   Assistance from the members of several flow cytometry core laboratories
   was especially appreciated, including Brion Shreffler (University of
   Pennsylvania), Martha Kirby and Stacie Anderson (NHGRI/NIH) as well as
   Patricia Lin and Gillian Hultin (Cedars-Sinai Medical Center). We would
   also like to thank Barrington Burnett (NINDS/NIH) and Mark Burcin
   (Baylor College of Medine) and Soshana Svendsen (Cedars-Sinai) for
   advice and critical analysis. We also thank the NIH AIDS Reagent
   Program, Webster Cavenee (Ludwig Institute for Cancer Research), Steven
   Goldman (University of Rochester), Hansjorg Hauser (Universitat
   Oldenburg) and Tyler Jacks (MIT) for the generous gifts of plasmids.
   This research was supported in part by NIH Grant T32-HD043021-04 (to
   TMP), NIH R01-NS08867 Grant (to JHW), the Intramural Research Program of
   the NIH/NINDS (to KF) and Cedars-Sinai Medical Center and Board of
   Governors Regenerative Medicine Institute institutional funding (to CNS,
   TMP). TMP was also supported by the Diana and Steve Marienhoff Fashion
   Industries Guild Endowed Fellowship in Pediatric Neuromuscular Diseases.
NR 52
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD MAY
PY 2016
VL 23
IS 5
BP 424
EP 437
DI 10.1038/gt.2016.13
PG 14
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Research & Experimental Medicine
GA DL5TX
UT WOS:000375701000004
PM 26863047
ER

PT J
AU Hong, J
   Lunetta, KL
   Cupples, LA
   Dupuis, J
   Liu, CT
AF Hong, Jaeyoung
   Lunetta, Kathryn L.
   Cupples, L. Adrienne
   Dupuis, Josee
   Liu, Ching-Ti
TI Evaluation of a Two-Stage Approach in Trans-Ethnic Meta-Analysis in
   Genome-Wide Association Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE meta-analysis; heterogeneity; trans-ethnic meta-analysis; simulation
   study; GWAS; clustering strategy
ID TRANSETHNIC METAANALYSIS; GENETIC ARCHITECTURE; LOCI; POPULATIONS;
   CHALLENGES; IMPUTATION; RESOURCE; DISEASES; TRAITS
AB Meta-analysis of genome-wide association studies (GWAS) has achieved great success in detecting loci underlying human diseases. Incorporating GWAS results from diverse ethnic populations for meta-analysis, however, remains challenging because of the possible heterogeneity across studies. Conventional fixed-effects (FE) or random-effects (RE) methods may not be most suitable to aggregate multiethnic GWAS results because of violation of the homogeneous effect assumption across studies (FE) or low power to detect signals (RE). Three recently proposed methods, modified RE (RE-HE) model, binary-effects (BE) model and a Bayesian approach (Meta-analysis of Transethnic Association [MANTRA]), show increased power over FE and RE methods while incorporating heterogeneity of effects when meta-analyzing trans-ethnic GWAS results. We propose a two-stage approach to account for heterogeneity in trans-ethnic meta-analysis in which we clustered studies with cohort-specific ancestry information prior to meta-analysis. We compare this to a no-prior-clustering (crude) approach, evaluating type I error and power of these two strategies, in an extensive simulation study to investigate whether the two-stage approach offers any improvements over the crude approach. We find that the two-stage approach and the crude approach for all five methods (FE, RE, RE-HE, BE, MANTRA) provide well-controlled type I error. However, the two-stage approach shows increased power for BE and RE-HE, and similar power for MANTRA and FE compared to their corresponding crude approach, especially when there is heterogeneity across the multiethnic GWAS results. These results suggest that prior clustering in the two-stage approach can be an effective and efficient intermediate step in meta-analysis to account for the multiethnic heterogeneity.
C1 [Hong, Jaeyoung; Lunetta, Kathryn L.; Cupples, L. Adrienne; Dupuis, Josee; Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,Crosstown Bldg,3rd Floor, Boston, MA 02118 USA.
   [Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Hong, J (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,Crosstown Bldg,3rd Floor, Boston, MA 02118 USA.
EM jhong@bu.edu
FU NIDDK NIH HHS [NIH R01 DK078616, R01 DK078616, U01 DK078616]
NR 32
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 MAY
PY 2016
VL 40
IS 4
BP 284
EP 292
DI 10.1002/gepi.21963
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA DJ9OK
UT WOS:000374542600003
PM 27061095
ER

PT J
AU Greenspan, H
   van Ginneken, B
   Summers, RM
AF Greenspan, Hayit
   van Ginneken, Bram
   Summers, Ronald M.
TI Deep Learning in Medical Imaging: Overview and Future Promise of an
   Exciting New Technique
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Editorial Material
ID COMPUTER-AIDED DETECTION; NEURAL-NETWORK; CLASSIFICATION; GPU
C1 [Greenspan, Hayit] Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Biomed Image Comp Lab, IL-69978 Tel Aviv, Israel.
   [van Ginneken, Bram] Radboud Univ Nijmegen, Med Ctr, Diagnost Image Anal Grp, NL-6525 GA Nijmegen, Netherlands.
   [Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Greenspan, H (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Biomed Image Comp Lab, IL-69978 Tel Aviv, Israel.
NR 38
TC 13
Z9 13
U1 24
U2 66
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2016
VL 35
IS 5
SI SI
BP 1153
EP 1159
DI 10.1109/TMI.2016.2553401
PG 7
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DL3RI
UT WOS:000375550500001
ER

PT J
AU Roth, HR
   Lu, L
   Liu, JM
   Yao, JH
   Seff, A
   Cherry, K
   Kim, L
   Summers, RM
AF Roth, Holger R.
   Lu, Le
   Liu, Jiamin
   Yao, Jianhua
   Seff, Ari
   Cherry, Kevin
   Kim, Lauren
   Summers, Ronald M.
TI Improving Computer-Aided Detection Using Convolutional Neural Networks
   and Random View Aggregation
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Computer aided diagnosis; computed tomography; medical diagnostic
   imaging; machine learning; object detection; artificial neural networks;
   multi-layer neural network; deep learning
ID CT COLONOGRAPHY; BONE METASTASIS; SEGMENTATION; POLYPS; IMAGES
AB Automated computer-aided detection (CADe) has been an important tool in clinical practice and research. State-of-the-art methods often show high sensitivities at the cost of high false-positives (FP) per patient rates. We design a two-tiered coarse-to-fine cascade framework that first operates a candidate generation system at sensitivities similar to 100% of but at high FP levels. By leveraging existing CADe systems, coordinates of regions or volumes of interest (ROI or VOI) are generated and function as input for a second tier, which is our focus in this study. In this second stage, we generate 2D (two-dimensional) or 2.5D views via sampling through scale transformations, random translations and rotations. These random views are used to train deep convolutional neural network (ConvNet) classifiers. In testing, the ConvNets assign class (e.g., lesion, pathology) probabilities for a new set of random views that are then averaged to compute a final per-candidate classification probability. This second tier behaves as a highly selective process to reject difficult false positives while preserving high sensitivities. The methods are evaluated on three data sets: 59 patients for sclerotic metastasis detection, 176 patients for lymph node detection, and 1,186 patients for colonic polyp detection. Experimental results show the ability of ConvNets to generalize well to different medical imaging CADe applications and scale elegantly to various data sets. Our proposed methods improve performance markedly in all cases. Sensitivities improved from 57% to 70%, 43% to 77%, and 58% to 75% at 3 FPs per patient for sclerotic metastases, lymph nodes and colonic polyps, respectively.
C1 [Roth, Holger R.; Lu, Le; Liu, Jiamin; Yao, Jianhua; Seff, Ari; Cherry, Kevin; Kim, Lauren; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Roth, HR (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM holger.roth@nih.gov
FU Intramural Research Program of the NIH Clinical Center
FX This work was supported by the Intramural Research Program of the NIH
   Clinical Center. Asterisk indicates corresponding author.
NR 59
TC 10
Z9 10
U1 23
U2 42
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2016
VL 35
IS 5
SI SI
BP 1170
EP 1181
DI 10.1109/TMI.2015.2482920
PG 12
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DL3RI
UT WOS:000375550500003
PM 26441412
ER

PT J
AU Shin, HC
   Roth, HR
   Gao, MC
   Lu, L
   Xu, ZY
   Nogues, I
   Yao, JH
   Mollura, D
   Summers, RM
AF Shin, Hoo-Chang
   Roth, Holger R.
   Gao, Mingchen
   Lu, Le
   Xu, Ziyue
   Nogues, Isabella
   Yao, Jianhua
   Mollura, Daniel
   Summers, Ronald M.
TI Deep Convolutional Neural Networks for Computer-Aided Detection: CNN
   Architectures, Dataset Characteristics and Transfer Learning
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Biomedical imaging; computer aided diagnosis; image analysis; machine
   learning; neural networks
ID OBJECT DETECTION; LYMPH-NODES; CT DATA; SEGMENTATION; FEATURES;
   DATABASE; RECOGNITION; IMAGES; NETS
AB Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs). CNNs enable learning data-driven, highly representative, hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.
C1 [Shin, Hoo-Chang; Roth, Holger R.; Lu, Le; Nogues, Isabella; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
   [Gao, Mingchen; Xu, Ziyue; Mollura, Daniel] NIH, Ctr Infect Dis Imaging, Ctr Clin, Bethesda, MD 20892 USA.
   [Lu, Le; Yao, Jianhua; Summers, Ronald M.] NIH, Clin Image Proc Serv, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
EM hoochang.shin@nih.gov; holger.roth@nih.gov; mingchen.gao@nih.gov;
   le.lu@nih.gov; ziyue.xu@nih.gov; isabella.nogues@nih.gov; jyao@nih.gov;
   molluradj@nih.gov; rms@nih.gov
FU National Institutes of Health Clinical Center; KRIBB Research Initiative
   Program (Korean Biomedical Scientist Fellowship Program), Korea Research
   Institute of Bioscience and Biotechnology, Republic of Korea
FX This work was supported in part by the Intramural Research Program of
   the National Institutes of Health Clinical Center, and in part by a
   grant from the KRIBB Research Initiative Program (Korean Biomedical
   Scientist Fellowship Program), Korea Research Institute of Bioscience
   and Biotechnology, Republic of Korea. H. Roth and M. Gao contributed
   equally to this work. Asterisk indicates corresponding author.
NR 73
TC 21
Z9 22
U1 34
U2 75
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2016
VL 35
IS 5
SI SI
BP 1285
EP 1298
DI 10.1109/TMI.2016.2528162
PG 14
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DL3RI
UT WOS:000375550500013
PM 26886976
ER

PT J
AU Gameiro, SR
   Malamas, AS
   Bernstein, MB
   Tsang, KY
   Vassantachart, A
   Sahoo, N
   Tailor, R
   Pidikiti, R
   Guha, CP
   Hahn, SM
   Krishnan, S
   Hodge, JW
AF Gameiro, Sofia R.
   Malamas, Anthony S.
   Bernstein, Michael B.
   Tsang, Kwong Y.
   Vassantachart, April
   Sahoo, Narayan
   Tailor, Ramesh
   Pidikiti, Rajesh
   Guha, Chandan P.
   Hahn, Stephen M.
   Krishnan, Sunil
   Hodge, James W.
TI Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a
   Common Immunogenic Modulation Signature, Rendering Them More Sensitive
   to T Cell-Mediated Killing
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID CANCER STEM-CELLS; HUMAN CARCINOEMBRYONIC ANTIGEN; MESENCHYMAL
   TRANSITION; AGONIST EPITOPE; BEAM RADIATION; VACCINE; THERAPY;
   CHEMOTHERAPY; RADIOTHERAPY; LYMPHOCYTES
AB Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen-specific T cells with proton radiation therapy to exploit the activity of those T cells.
   Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences.
   Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells.
   Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options. Published by Elsevier Inc.
C1 [Gameiro, Sofia R.; Malamas, Anthony S.; Tsang, Kwong Y.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13, Bethesda, MD 20892 USA.
   [Bernstein, Michael B.; Vassantachart, April; Sahoo, Narayan; Tailor, Ramesh; Pidikiti, Rajesh; Hahn, Stephen M.; Krishnan, Sunil] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA.
   [Guha, Chandan P.] Montefiore Med Ctr, Dept Radiat Oncol, 111 E 210th St, Bronx, NY 10467 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015; 
OI Hodge, James/0000-0001-5282-3154; gameiro, sofia/0000-0002-2392-8122
FU Intramural NIH HHS [Z01 BC010661-03, Z99 CA999999]; NCI NIH HHS [Z01
   BC010975-01]
NR 35
TC 7
Z9 7
U1 0
U2 4
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 MAY 1
PY 2016
VL 95
IS 1
BP 120
EP 130
DI 10.1016/j.ijrobp.2016.02.022
PG 11
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DL1VA
UT WOS:000375419500024
PM 27084634
ER

PT J
AU Rogers, T
   Waksman, R
AF Rogers, Toby
   Waksman, Ron
TI Role of CMR in TAVR
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE aortic stenosis; cardiovascular magnetic resonance; transcatheter aortic
   valve replacement
ID AORTIC-VALVE IMPLANTATION; CARDIOVASCULAR MAGNETIC-RESONANCE;
   PARAVALVULAR REGURGITATION; COMPUTED-TOMOGRAPHY; MYOCARDIAL INJURY;
   TRANSTHORACIC ECHOCARDIOGRAPHY; EXTRACELLULAR VOLUME; TRANSCATHETER;
   REPLACEMENT; STENOSIS
AB Multimodality imaging plays a critical role in planning, performing, and evaluating transcatheter aortic valve replacement (TAVR). Cardiovascular magnetic resonance (CMR) has been underutilized in this patient population to date, but there is increasing evidence that it can offer equivalent or even superior information to more commonly used imaging modalities, such as echocardiography or computed tomography for specific applications. In addition, CMR can provide incremental information, including advanced tissue characterization with late gadolinium enhancement and T-1 mapping. In this paper, we review the evidence for CMR in TAVR and explore whether CMR should still be considered a research tool, or whether it is now ready for implementation into clinical practice. (C) 2016 by the American College of Cardiology Foundation.
C1 [Rogers, Toby] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
   [Rogers, Toby; Waksman, Ron] MedStar Washington Hosp Ctr, Sect Intervent Cardiol, 110 Irving St Northwest,Suite 4B-1, Washington, DC 20010 USA.
RP Waksman, R (reprint author), MedStar Washington Hosp Ctr, 110 Irving St Northwest,Suite 4B-1, Washington, DC 20010 USA.
EM ron.waksman@medstar.net
FU AstraZeneca; Biotronik; Boston Scientific
FX From the <SUP>a</SUP>Cardiovascular and Pulmonary Branch, Division of
   Intramural Research, National Heart Lung and Blood Institute, Bethesda,
   Maryland; and the <SUP>b</SUP>Section of Interventional Cardiology,
   MedStar Washington Hospital Center, Washington, DC. Dr. Waksman has
   served as a consultant for Abbott Vascular, Biotronik, Boston
   Scientific, Medtronic, and St. Jude Medical; served on the Speakers
   Bureau for AstraZeneca, Boston Scientific, and Merck; and has received
   grant support from AstraZeneca, Biotronik, and Boston Scientific. Dr.
   Rogers has reported that he has no relationships relevant to the
   contents of this paper to disclose.
NR 45
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD MAY
PY 2016
VL 9
IS 5
BP 593
EP 602
DI 10.1016/j.jcmg.2016.01.011
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA DL4IN
UT WOS:000375597700015
PM 27151522
ER

PT J
AU Frances, M
AF Frances, Mary
TI Public Health Surveillance-The Integral Role of Community-Based Studies
SO JAMA OPHTHALMOLOGY
LA English
DT Editorial Material
ID MACULAR DEGENERATION; PREVALENCE; EYE
C1 [Frances, Mary] NEI, NIH, 10 Ctr Dr,Ste 3-2521, Bethesda, MD 20892 USA.
RP Frances, M (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Clin Res Ctr, 10 Ctr Dr,Ste 3-2521, Bethesda, MD 20892 USA.
EM mfc@nei.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD MAY
PY 2016
VL 134
IS 5
BP 578
EP 579
DI 10.1001/jamaophthalmol.2016.0334
PG 2
WC Ophthalmology
SC Ophthalmology
GA DL7CB
UT WOS:000375796100024
ER

PT J
AU Broccolo, F
   Din, CT
   Vigano, MG
   Rutigliano, T
   Esposito, S
   Lusso, P
   Tambussi, G
   Malnati, MS
AF Broccolo, Francesco
   Din, Chiara Tassan
   Vigano, Maria Grazia
   Rutigliano, Teresa
   Esposito, Susanna
   Lusso, Paolo
   Tambussi, Giuseppe
   Malnati, Mauro S.
TI HHV-8 DNA replication correlates with the clinical status in
   AIDS-related Kaposi's sarcoma
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Article
DE Human herpesvirus-8; Kaposi's sarcoma; Plasma viraemia; Disease
   progression
ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL
   LOAD; HUMAN-HERPESVIRUS-8 DNA; CASTLEMAN-DISEASE; INFECTED PATIENTS;
   PERIPHERAL-BLOOD; ANTIVIRAL DRUGS; HIV-INFECTION; HERPESVIRUS
AB Background: The value of plasma levels of human herpesvirus 8 (HHV-8) DNA as a marker of clinical status in acquired immunodeficiency syndrome-related Kaposi's sarcoma (AIDS-KS) remains to be elucidated.
   Objectives: To investigate the relationship between the plasma HHV-8 DNA viral load and the clinical status of AIDS-KS.
   Study Design: A total of 378 blood samples were obtained from 62 patients with AIDS-KS followed longitudinally. All patients received antiretroviral therapy (ART) or anti-neoplastic therapy. The patients were divided into four groups according to their clinical status: onset disease (OD), progressive disease (PD), stable or partial remission (S/PR) and complete remission (CR).
   Results: Plasma HHV-8 DNAaemia was detected in all samples obtained from patients with OD or PD (100%); in contrast, HHV-8 DNAaemia was found only in a minority of patients with CR (8%) and was invariably undetectable in patients with stable CR. HHV-8 DNA detection in plasma was strongly associated with an unfavourable outcome (odds ratio = 231.9; p < 0.0001). Conversely, neither the HIV-1 viral load nor peripheral CD4(+) T-cell counts were associated with the KS clinical status, though both parameters did affect HHV-8 DNAaemia levels (p < 0.0001). Multivariate analysis confirmed that HHV-8 DNAaemia was strongly and independently correlated with both clinical status (p < 0.05) and HIV-1 plasma viraemia (p = 0.027).
   Conclusions: The strong association of plasma HHV-8 DNAaemia with onset or progressive disease is compatible with an active role of replicating virus in clinically active AIDS-KS. An accurate evaluation of the plasma HHV-8 load might be useful for monitoring AIDS-KS under antiretroviral or antineoplastic therapy. (C) 2016 Published by Elsevier B.V.
C1 [Broccolo, Francesco] Univ Milano Bicocca, Dept Hlth Sci, Monza, Italy.
   [Din, Chiara Tassan; Tambussi, Giuseppe] Div Infect & Trop Dis, Milan, Italy.
   [Vigano, Maria Grazia] Div Oncol, Milan, Italy.
   [Rutigliano, Teresa; Malnati, Mauro S.] Ist Sci San Raffaele, Unit Human Virol, I-20132 Milan, Italy.
   [Esposito, Susanna] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Pediat Highly Intens Care Unit, Milan, Italy.
   [Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Lusso, P (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.; Malnati, MS (reprint author), Ist Sci San Raffaele, Unit Human Virol, Labs P2 P3, DIBIT, Via Olgettina 58, I-20132 Milan, Italy.
EM mauro.malnati@hsr.it
RI Esposito, Susanna/K-3475-2016; 
OI Esposito, Susanna/0000-0003-4103-2837; Broccolo,
   Francesco/0000-0002-9737-0459
FU Fourth National AIDS Project; First AIDS Program from Ministry of
   Health, Rome, Italy
FX This work was partially supported by grants from the Fourth National
   AIDS Project (to PL and GT) and the First AIDS Program (to MSM) from the
   Ministry of Health, Rome, Italy.
NR 39
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
EI 1873-5967
J9 J CLIN VIROL
JI J. Clin. Virol.
PD MAY
PY 2016
VL 78
BP 47
EP 52
DI 10.1016/j.jcv.2016.02.019
PG 6
WC Virology
SC Virology
GA DJ8RK
UT WOS:000374480000011
PM 26985593
ER

PT J
AU Santiana, M
   Takvorian, PM
   Altan-Bonnet, N
   Cali, A
AF Santiana, Marianita
   Takvorian, Peter M.
   Altan-Bonnet, Nihal
   Cali, Ann
TI A Novel Fluorescent Labeling Method Enables Monitoring of
   Spatio-Temporal Dynamics of Developing Microsporidia
SO JOURNAL OF EUKARYOTIC MICROBIOLOGY
LA English
DT Article
DE Anncaliia algerae; Arf-1-GFP; DRAQ5; Golgi, HeLa cells; live imaging;
   microtubules; organelle hijacking
ID BRACHIOLA-ALGERAE; ENCEPHALITOZOON-CUNICULI; PARASITOPHOROUS VACUOLE;
   CELLS; GOLGI; DISCRIMINATION; MITOCHONDRIA; VERTEBRATES; INFECTIONS;
   SPOROPLASM
AB The microsporidium, Anncaliia algerae (Brachiola algerae), is a eukaryotic obligate intracellular parasite first isolated from mosquitoes and is an important opportunistic human pathogen that can cause morbidity and mortality among immune-compromised individuals including patients with AIDS and those undergoing chemotherapy. There is little known about the Microsporidia-host cell interface in living host cells, due to current approaches being limited by the lack of fluorescent reporters for detecting the parasite lifecycle. Here, we have developed and applied novel vital fluorescent parasite labeling methodologies in conjunction with fluorescent protein-tagged reporters to track simultaneously the dynamics of both parasite and host cell specific components, including the secretory and endocytic trafficking pathways, during the entire infection time period. We have found dramatic changes in the dynamics of host secretory trafficking organelles during the course of infection. The Golgi compartment is gradually disassembled and regenerated into mini-Golgi structures in parallel with cellular microtubule depolymerization. Importantly, we find that Microsporidia progeny are associated with these de novo formed mini-Golgi structures. These host structures appear to create a membrane bound niche environment for parasite development. Our studies presented here provide novel imaging tools and methodologies that will facilitate in understanding the biology of microsporidial parasites in the living host.
C1 [Santiana, Marianita; Takvorian, Peter M.; Cali, Ann] Rutgers State Univ, Federated Dept Biol Sci, 195 Univ Ave, Newark, NJ 07102 USA.
   [Santiana, Marianita; Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Takvorian, PM; Cali, A (reprint author), Rutgers State Univ, Federated Dept Biol Sci, 195 Univ Ave, Newark, NJ 07102 USA.
EM petetak@andromeda.rutgers.edu; anncali@andromeda.rutgers.edu
FU NIH [RO1-AI31788, RO1-A1091985]
FX This research was supported by NIH grant no. RO1-AI31788 and NIH grant
   no. RO1-A1091985.
NR 25
TC 0
Z9 0
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5234
EI 1550-7408
J9 J EUKARYOT MICROBIOL
JI J. Eukaryot. Microbiol.
PD MAY-JUN
PY 2016
VL 63
IS 3
BP 318
EP 325
DI 10.1111/jeu.12281
PG 8
WC Microbiology
SC Microbiology
GA DL5HN
UT WOS:000375668100005
PM 26567000
ER

PT J
AU Portengen, L
   Linet, MS
   Li, GL
   Lan, Q
   Dores, GM
   Ji, BT
   Hayes, RB
   Yin, SN
   Rothman, N
   Vermeulen, R
AF Portengen, Lutzen
   Linet, Martha S.
   Li, Gui-Lan
   Lan, Qing
   Dores, Graa M.
   Ji, Bu-Tian
   Hayes, Richard B.
   Yin, Song-Nian
   Rothman, Nathaniel
   Vermeulen, Roel
CA US Natl Canc Inst Benzene
TI Retrospective benzene exposure assessment for a multi-center case-cohort
   study of benzene-exposed workers in China
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE benzene; hierarchical mixed modeling; Bayesian; ventilation; leukemia;
   lymphoma
ID LONG-TERM TRENDS; OCCUPATIONAL-EXPOSURE; COMPREHENSIVE EVALUATION;
   QUALITY DIMENSIONS; MORTALITY PATTERNS; PETROLEUM WORKERS; CRUDE-OIL;
   LEUKEMIA; RISK; MODELS
AB Quality of exposure assessment has been shown to be related to the ability to detect risk of lymphohematopoietic disorders in epidemiological investigations of benzene, especially at low levels of exposure. We set out to build a statistical model for reconstructing exposure levels for 2898 subjects from 501 factories that were part of a nested case-cohort study within the NCI-CAPM cohort of more than 110,000 workers. We used a hierarchical model to allow for clustering of measurements by factory, workshop, job, and date. To calibrate the model we used historical routine monitoring data. Measurements below the limit of detection were accommodated by constructing a censored data likelihood. Potential non-linear and industry-specific time-trends and predictor effects were incorporated using regression splines and random effects. A partial validation of predicted exposures in 2004/2005 was performed through comparison with full-shift measurements from an exposure survey in facilities that were still open. Median cumulative exposure to benzene at age 50 for subjects that ever held an exposed job (n = 1175) was 509 mg/m(3) years. Direct comparison of model estimates with measured full-shift personal exposure in the 2004/2005 survey showed moderate correlation and a potential downward bias at low (<1 mg/m(3)) exposure estimates. The modeling framework enabled us to deal with the data complexities generally found in studies using historical exposure data in a comprehensive way and we therefore expect to be able to investigate effects at relatively low exposure levels.
C1 [Portengen, Lutzen; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Dept Mol Epidemiol & Risk Assessment, Div Environm Epidemiol, POB 80178, NL-3508 TD Utrecht, Netherlands.
   [Linet, Martha S.; Dores, Graa M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA.
   [Li, Gui-Lan; Yin, Song-Nian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Injuries, Beijing, Peoples R China.
   [Lan, Qing; Ji, Bu-Tian; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA.
   [Dores, Graa M.] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
   [Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, 550 1St Ave, New York, NY 10016 USA.
RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Dept Mol Epidemiol & Risk Assessment, Div Environm Epidemiol, POB 80178, NL-3508 TD Utrecht, Netherlands.
EM R.C.H.Vermeulen@uu.nl
RI Vermeulen, Roel/F-8037-2011; 
OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X
NR 28
TC 0
Z9 0
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
EI 1559-064X
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD MAY-JUN
PY 2016
VL 26
IS 3
BP 334
EP 340
DI 10.1038/jes.2015.44
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA DJ7FF
UT WOS:000374376600015
PM 26264985
ER

PT J
AU Breslau, ES
   Gorin, SS
   Edwards, HM
   Schonberg, MA
   Saiontz, N
   Walter, LC
AF Breslau, Erica S.
   Gorin, Sherri Sheinfeld
   Edwards, Heather M.
   Schonberg, Mara A.
   Saiontz, Nicole
   Walter, Louise C.
TI An Individualized Approach to Cancer Screening Decisions in Older
   Adults: A Multilevel Framework
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE Individualized screening; Shared decisionmaking; Geriatric; Multilevel;
   Framework
ID SERVICES TASK-FORCE; WOMEN AGED 80; PREVENTIVE SERVICES;
   COLORECTAL-CANCER; BREAST-CANCER; RECOMMENDATION STATEMENT; LIFE
   EXPECTANCY; CHRONIC ILLNESS; NATIONAL-SURVEY; HEALTH-CARE
AB Guidelines for optimal cancer screening in older adults remain unclear, particularly for adults over the age of 75. While cancer screening in older adults may benefit some in good health, it may cause unnecessary burdens in others with limited life expectancy. Thus, a systematic approach to enable individualized cancer screening decisions in older adults is needed. We suggest a framework that guides such decisions through evidence-based approaches from multiple interactions, and that involves the patient, clinician, and healthcare system. An individualized approach considers differences in disease risk rather than the chronological age of the patient. This paper presents a comprehensive framework that depicts the independent and converging levels of influences on individualized cancer screening decisions in older adults. This Individualized Decisions for Screening (IDS) framework recognizes the reality of these interrelationships, including the tensions that arise when behaviors and outcomes are valued differently at the patient, clinician, and healthcare organization levels. Person-centered approaches are essential to advancing multilevel research of individualized cancer screening decisions among older adults.
C1 [Breslau, Erica S.] NCI, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
   [Gorin, Sherri Sheinfeld] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
   [Gorin, Sherri Sheinfeld] Herbert Irving Comprehens Canc Ctr, New York Phys Canc, New York, NY USA.
   [Edwards, Heather M.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
   [Schonberg, Mara A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Gen Med & Primary Care, Boston, MA 02215 USA.
   [Saiontz, Nicole] NCI, Off Director, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
   [Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
   [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Breslau, ES (reprint author), NCI, Healthcare Delivery Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM breslaue@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; National Institute on Aging, National Institutes of
   Health [K24AG041180]
FX Disclaimer for Drs. Edwards and Sheinfeld Gorin: This project has been
   funded in whole or in part with federal funds from the National Cancer
   Institute, National Institutes of Health, under Contract No.
   HHSN261200800001E (HME). Dr. Walter was funded by the National Institute
   on Aging, National Institutes of Health under grant number K24AG041180.
   The content of this publication does not necessarily reflect the views
   or policies of the Department of Health and Human Services, nor does the
   mention of trade names, commercial products, or organizations imply
   endorsement by the U.S. government.
NR 55
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2016
VL 31
IS 5
BP 539
EP 547
DI 10.1007/s11606-016-3629-y
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DJ8KO
UT WOS:000374461400024
PM 26941042
ER

PT J
AU Dong, MB
   Rahman, MJ
   Tarbell, KV
AF Dong, Matthew B.
   Rahman, M. Jubayer
   Tarbell, Kristin V.
TI Flow cytometric gating for spleen monocyte and DC subsets: differences
   in autoimmune NOD mice and with acute inflammation
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Dendritic cells; Immune homeostasis; Inflammation; Multicolor flow
   cytometry; Non-obese diabetic mice; Phosphoflow
ID DENDRITIC CELL SUBSETS; CD4(+) T-CELLS; STEADY-STATE;
   BACTERIAL-INFECTION; IN-VIVO; ACTIVATION; ANTIGEN; DIFFERENTIATION;
   HETEROGENEITY; MACROPHAGES
AB The role of antigen presenting cells (APCs) in the pathogenesis of autoimmune and other inflammatory diseases is now better understood due to advances in multicolor flow cytometry, gene expression analysis of APC populations, and functional correlation of mouse to human APC populations. A simple but informative nomenclature of conventional and plasmacytoid dendritic cell subsets (cDC1, cDC2, pDC) and monocyte-derived populations incorporates these advances, but accurate subset identification is critical. Ambiguous gating schemes and alterations of cell surface markers in inflammatory condition can make comparing results between studies difficult. Both acute inflammation, such as TLR-ligand stimulation, and chronic inflammation as found in mouse models of autoimmunity can alter DC subset gating. Here, we address these issues using in viva CpG stimulation as an example of acute inflammation and the non-obese diabetic (NOD) mouse as a model of chronic inflammation. We provide a flow cytometric antibody panel and gating scheme that differentiate 2 monocytic and 3 DC subsets in the spleen both at steady state and after CpG stimulation. Using this method, we observed differences in the composition of NOD DCs that have been previously reported, and newly identified increases in the number of NOD monocyte-derived DCs. Finally, we established a protocol for DC phosphoflow to measure the phosphorylation state of intracellular proteins, and use it to confirm functional differences in the identified subsets. Therefore, we present optimized methods for distinguishing monocytic and DC populations with and without inflammation and/or autoimmunity associated with NOD mice. Published by Elsevier B.V.
C1 [Dong, Matthew B.; Rahman, M. Jubayer; Tarbell, Kristin V.] NIDDK, Immune Tolerance Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Tarbell, KV (reprint author), NIDDK, DEOB, NIH, CRC, Bldg 10,West Labs 5-5940, Bethesda, MD 20892 USA.
EM tarbellk@niddk.nih.gov
OI Tarbell, Kristin/0000-0003-3738-379X
FU Intramural Research Programs of the National Institute of Diabetes and
   Digestive and Kidney Diseases
FX We would like to acknowledge Alice Franks (Diabetes, Endocrinology, and
   Obesity Branch, NIDDK) for help with mouse husbandry and the NIDDK/NHLBI
   flow core and Dr. Phil McCoy for flow cytometry support. We thank the
   member of the Tarbell Lab: Dr. Chie Iwamura, Dr. William Coley and Dr.
   Yongge Zhao for helpful discussions. This work was supported by the
   Intramural Research Programs of the National Institute of Diabetes and
   Digestive and Kidney Diseases.
NR 38
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAY
PY 2016
VL 432
SI SI
BP 4
EP 12
DI 10.1016/j.jim.2015.08.015
PG 9
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA DL8IY
UT WOS:000375886900002
PM 26344574
ER

PT J
AU Vargas, P
   Chabaud, M
   Thiam, HR
   Lankar, D
   Piel, M
   Lennon-Dumenil, AM
AF Vargas, Pablo
   Chabaud, Melanie
   Thiam, Hawa-Racine
   Lankar, Danielle
   Piel, Matthieu
   Lennon-Dumenil, Ana-Maria
TI Study of dendritic cell migration using micro-fabrication
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Cell migration; Motility; Dendritic cells; Lymphocytes; Leukocytes;
   Confinement; Micro-fabrication; Imaging; Chemokines; Gradients;
   Constrictions; Persistence; Cell polarity
ID LYMPH-NODES; MYOSIN-II; ENVIRONMENTS; HOMEOSTASIS; ACTIVATION;
   GRADIENTS; SPACE
AB Cell migration is a hallmark of dendritic cells (DCs) function. It is needed for DCs to scan their environment in search for antigens as well as to reach lymphatic organs in order to trigger T lymphocyte's activation. Such interaction leads to tolerance in the case of DCs migrating under homeostatic conditions or to immunity in the case of DCs migrating upon encounter with pathogen-associated molecular patterns. Cell migration is therefore essential for DCs to transfer information from peripheral tissues to lymphoid orgatis, thereby linking innate to adaptive immunity. This stresses the need to unravel the molecular mechanisms involved. However, the tremendous complexity of the tissue microenvironment as well as the limited spatio-temporal resolution of in vivo imaging techniques has made this task difficult. To bypass this problem, we have developed microfabrication-based experimental tools that are compatible with high-resolution imaging. Here, we will discuss how such devices can be used to study DC migration under controlled conditions that mimic their physiological environment in a robust quantitative manner. (C) 2015 Published by Elsevier B.V.
C1 [Vargas, Pablo; Thiam, Hawa-Racine; Piel, Matthieu] CNRS UMR 144, Inst Curie, 26 Rue Ulm, F-75005 Paris, France.
   [Chabaud, Melanie; Lankar, Danielle; Lennon-Dumenil, Ana-Maria] Inserm U932, Inst Curie, 26 Rue Ulm, F-75005 Paris, France.
   [Chabaud, Melanie] Univ New S Wales, Ctr Vasc Res, Sydney, NSW 2052, Australia.
   [Chabaud, Melanie] Univ New S Wales, Australian Ctr NanoMed, Sydney, NSW 2052, Australia.
   [Thiam, Hawa-Racine] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Vargas, P (reprint author), CNRS UMR 144, Inst Curie, 26 Rue Ulm, F-75005 Paris, France.
EM pablo.vargas@curie.fr
RI Lennon-Dumenil, Ana-Maria/I-6716-2016; 
OI VARGAS, Pablo/0000-0002-6475-494X
NR 23
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAY
PY 2016
VL 432
SI SI
BP 30
EP 34
DI 10.1016/j.jim.2015.12.005
PG 5
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA DL8IY
UT WOS:000375886900005
PM 26684937
ER

PT J
AU Yang, N
   Gibbs, JS
   Hickman, HD
   Reynoso, GV
   Ghosh, AK
   Bennink, JR
   Yewdell, JW
AF Yang, Ning
   Gibbs, James S.
   Hickman, Heather D.
   Reynoso, Glennys V.
   Ghosh, Arun K.
   Bennink, Jack R.
   Yewdell, Jonathan W.
TI Defining Viral Defective Ribosomal Products: Standard and Alternative
   Translation Initiation Events Generate a Common Peptide from Influenza A
   Virus M2 and M1 mRNAs
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MHC CLASS-I; CYTOTOXIC LYMPHOCYTES-T; NUCLEAR TRANSLATION; ANTIGENIC
   PEPTIDES; PROTEIN-SYNTHESIS; READING FRAMES; MAJOR SOURCE; MOLECULES;
   EXPRESSION; CELLS
AB Influenza A virus gene segment 7 encodes two proteins: the M1 protein translated from unspliced mRNA and the M2 protein produced by mRNA splicing and largely encoded by the M1 + 1 reading frame. To better understand the generation of defective ribosomal products relevant to MHC class I Ag presentation, we engineered influenza A virus gene segment 7 to encode the model H-2 K-b class I peptide ligand SIINFEKL at the M2 protein C terminus. Remarkably, after treating virus-infected cells with the RNA splicing inhibitor spliceostatin A to prevent M2 mRNA generation, K-b-SIINFEKL complexes were still presented on the cell surface at levels <= 60% of untreated cells. Three key findings indicate that SIINFEKL is produced by cytoplasmic translation of unspliced M1 mRNA initiating at CUG codons within the +1 reading frame: 1) synonymous mutation of CUG codons in the M2-reading frame reduced K-b-SIIN-FEKL generation; 2) K-b-SIINFEKL generation was not affected by drug-mediated inhibition of AUG-initiated M1 synthesis; and 3) K-b-SIINFEKL was generated in vitro and in vivo from mRNA synthesized in the cytoplasm by vaccinia virus, and hence cannot be spliced. These findings define a viral defective ribosomal product generated by cytoplasmic noncanonical translation and demonstrate the participation of CUG-codon-based translation initiation in pathogen immunosurveillance.
C1 [Yang, Ning; Gibbs, James S.; Hickman, Heather D.; Reynoso, Glennys V.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
RP Yewdell, JW (reprint author), NIAID, NIH, Room 2E13C-1,Bldg 33,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health.
NR 49
TC 0
Z9 0
U1 4
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 MAY 1
PY 2016
VL 196
IS 9
BP 3608
EP 3617
DI 10.4049/jimmunol.1502303
PG 10
WC Immunology
SC Immunology
GA DJ8GP
UT WOS:000374450900015
PM 27016602
ER

PT J
AU Wang, YM
   Sundling, C
   Wilson, R
   O'Dell, S
   Chen, YJ
   Dai, KF
   Phad, GE
   Zhu, J
   Xiao, YL
   Mascola, JR
   Hedestam, GBK
   Wyatt, RT
   Li, YX
AF Wang, Yimeng
   Sundling, Christopher
   Wilson, Richard
   O'Dell, Sijy
   Chen, Yajing
   Dai, Kaifan
   Phad, Ganesh E.
   Zhu, Jiang
   Xiao, Yongli
   Mascola, John R.
   Hedestam, Gunilla B. Karlsson
   Wyatt, Richard T.
   Li, Yuxing
TI High-Resolution Longitudinal Study of HIV-1 Env Vaccine-Elicited B Cell
   Responses to the Virus Primary Receptor Binding Site Reveals Affinity
   Maturation and Clonal Persistence
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; SINGLE-CELL;
   EFFICACY TRIAL; GP120; REPERTOIRE; EPITOPE; DESIGN; IMMUNIZATION;
   RECOGNITION
AB Because of the genetic variability of the HIV-1 envelope glycoproteins (Env), the elicitation of neutralizing Abs to conserved neutralization determinants including the primary receptor binding site, CD4 binding site (CD4bs), is a major focus of vaccine development. To gain insight into the evolution of Env-elicited Ab responses, we used single B cell analysis to interrogate the memory B cell Ig repertoires from two rhesus macaques after five serial immunizations with Env/adjuvant. We observed that the CD4bs-specific repertoire displayed unique features in the third CDR of Ig H chains with minor alterations along the immunization course. Progressive affinity maturation occurred as evidenced by elevated levels of somatic hypermutation (SHM) in Ab sequences isolated at the late immunization time point compared with the early time point. Abs with higher SHM were associated with increased binding affinity and virus neutralization capacity. Moreover, a notable portion of the CD4bs-specific repertoire was maintained between early and late immunization time points, suggesting that persistent clonal lineages were induced by Env vaccination. Furthermore, we found that the predominant persistent CD4bs-specific clonal lineages had larger population sizes and higher affinities than that from the rest of the repertoires, underscoring the critical role of Ag affinity selection in Ab maturation and clonal expansion. Genetic and functional analyses revealed that the accumulation of SHM in both framework regions and CDRs contributed to the clonal affinity and antigenicity evolution. Our longitudinal study provides high-resolution understanding of the dynamically evolving CD4bs-specific B cell response after Env immunization in primates.
C1 [Wang, Yimeng; Chen, Yajing; Dai, Kaifan; Zhu, Jiang; Wyatt, Richard T.; Li, Yuxing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Wang, Yimeng; Li, Yuxing] Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
   [Sundling, Christopher; Phad, Ganesh E.; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden.
   [Sundling, Christopher] Garvan Inst Med Res, Div Immunol, Darlinghurst, NSW 2010, Australia.
   [Wilson, Richard; Wyatt, Richard T.; Li, Yuxing] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
   [O'Dell, Sijy; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Zhu, Jiang; Wyatt, Richard T.] Scripps Ctr HIV Vaccine Immunogen Discovery, La Jolla, CA 92037 USA.
   [Xiao, Yongli] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Li, YX (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM yuxingli@umd.edu
FU National Institutes of Health, National Institute of Allergy and
   Infectious Diseases [R01 AI102766, P01 AI104722, UM1 AI100663];
   Karolinska Institutet funds; Karolinska Institutet foundations; Swedish
   Physicians against AIDS Research Foundation; Swedish Research Council
   International Postdoctoral Fellowship; Swedish Research Council;
   Intramural Research Program of the Vaccine Research Center; National
   Institute of Allergy and Infectious Diseases; National Institutes of
   Health; International AIDS Vaccine Initiative; U.S. Agency for
   International Development; Ministry of Foreign Affairs of the
   Netherlands; Bill & Melinda Gates Foundation
FX This work was supported by National Institutes of Health, National
   Institute of Allergy and Infectious Diseases Grants R01 AI102766 (to
   Y.L.), P01 AI104722 (to R.T.W., Y.L., and G.B.K.H.), and UM1 AI100663
   (to R.T.W. and J.Z.); Karolinska Institutet funds and foundations (to
   C.S.); the Swedish Physicians against AIDS Research Foundation (to
   C.S.); a Swedish Research Council International Postdoctoral Fellowship
   (to C.S.); the Swedish Research Council (to G.B.K.H.); the Intramural
   Research Program of the Vaccine Research Center, the National Institute
   of Allergy and Infectious Diseases, and the National Institutes of
   Health (to J.R.M.); and the International AIDS Vaccine Initiative (to
   R.T.W.) with generous support from the U.S. Agency for International
   Development, the Ministry of Foreign Affairs of the Netherlands, and the
   Bill & Melinda Gates Foundation (a full list of International AIDS
   Vaccine Initiative donors is available at http://www.iavi.org).
NR 54
TC 4
Z9 4
U1 1
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2016
VL 196
IS 9
BP 3729
EP 3743
DI 10.4049/jimmunol.1502543
PG 15
WC Immunology
SC Immunology
GA DJ8GP
UT WOS:000374450900026
PM 27001953
ER

PT J
AU Kong, HH
AF Kong, Heidi H.
TI Details Matter: Designing Skin Microbiome Studies
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID SEQUENCES; DIVERSITY; BACTERIA; TIME
AB The use of genomic sequencing to investigate microbes has expanded, yet it has also raised questions regarding optimal approaches to studying the skin microbiome. Meisel et al. show that while whole genome shotgun metagenomic sequences were most similar to expected microbial profiles, sequencing of the hypervariable regions V1-V3 of the 16S ribosomal RNA gene had greater accuracy than sequencing of the hypervariable region V4 in determining genus and species level classifications of prominent skin bacteria.
C1 [Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov
NR 20
TC 1
Z9 1
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2016
VL 136
IS 5
BP 900
EP 902
DI 10.1016/j.jid.2016.03.004
PG 3
WC Dermatology
SC Dermatology
GA DL9RN
UT WOS:000375980600008
PM 27107375
ER

PT J
AU Taylor, NJ
   Handorf, EA
   Mitra, N
   Avril, MF
   Azizi, E
   Bergman, W
   Bianchi-Scarra, G
   Bishop, DT
   Bressac-de Paillerets, B
   Calista, D
   Cannon-Albright, LA
   Cuellar, F
   Cust, AE
   Demenais, F
   Elder, DE
   Friedman, E
   Gerdes, AM
   Ghiorzo, P
   Goldstein, AM
   Grazziotin, TC
   Hansson, J
   Hayward, NK
   Hocevar, M
   Hoiom, V
   Holland, EA
   Ingvar, C
   Landi, MT
   Landman, G
   Larre-Borges, A
   Leachman, SA
   Mann, GJ
   Nagore, E
   Olsson, H
   Palmer, J
   Peric, B
   Pjanova, D
   Puig, S
   Schmid, H
   van der Stoep, N
   Tucker, MA
   Wadt, KAW
   Whitaker, L
   Yang, XHR
   Bishop, JAN
   Gruis, NA
   Kanetsky, PA
AF Taylor, Nicholas J.
   Handorf, Elizabeth A.
   Mitra, Nandita
   Avril, Marie-Francoise
   Azizi, Esther
   Bergman, Wilma
   Bianchi-Scarra, Giovanna
   Bishop, D. Timothy
   Bressac-de Paillerets, Brigitte
   Calista, Donato
   Cannon-Albright, Lisa A.
   Cuellar, Francisco
   Cust, Anne E.
   Demenais, Florence
   Elder, David E.
   Friedman, Eitan
   Gerdes, Anne-Marie
   Ghiorzo, Paola
   Goldstein, Alisa M.
   Grazziotin, Thais C.
   Hansson, Johan
   Hayward, Nicholas K.
   Hocevar, Marko
   Hoiom, Veronica
   Holland, Elizabeth A.
   Ingvar, Christian
   Landi, Maria Teresa
   Landman, Gilles
   Larre-Borges, Alejandra
   Leachman, Sancy A.
   Mann, Graham J.
   Nagore, Eduardo
   Olsson, Hakan
   Palmer, Jane
   Peric, Barbara
   Pjanova, Dace
   Puig, Susana
   Schmid, Helen
   van der Stoep, Nienke
   Tucker, Margaret A.
   Wadt, Karin A. W.
   Whitaker, Linda
   Yang, Xiaohong R.
   Bishop, Julia A. Newton
   Gruis, Nelleke A.
   Kanetsky, Peter A.
CA GenoMEL Consortium
TI Phenotypic and Histopathological Tumor Characteristics According to
   CDKN2A Mutation Status among Affected Members of Melanoma Families
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID GENETICS CONSORTIUM; PANCREATIC-CANCER; HIGH-RISK; POPULATION;
   PREVALENCE; GENOMEL; BREAST; RNA
C1 [Taylor, Nicholas J.; Kanetsky, Peter A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
   [Handorf, Elizabeth A.] Fox Chase Canc Ctr, Dept Biostat & Bioinformat, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
   [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Avril, Marie-Francoise] Hop Cochin, AP HP, 27 Rue Faubourg St Jacques, F-75674 Paris, France.
   [Avril, Marie-Francoise] Univ Paris 05, Paris, France.
   [Azizi, Esther] Sheba Med Ctr, Dept Dermatol, Tel Hashomer, Israel.
   [Azizi, Esther] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
   [Bergman, Wilma; van der Stoep, Nienke; Gruis, Nelleke A.] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands.
   [Bianchi-Scarra, Giovanna] Univ Genoa, Dept Internal Med & Med Specialties, I-16126 Genoa, Italy.
   [Bianchi-Scarra, Giovanna; Ghiorzo, Paola] IRCCS AOU San Martino IST Genoa, Genoa, Italy.
   [Bishop, D. Timothy; Whitaker, Linda] Univ Leeds, Sect Epidemiol & Biostat, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
   [Bressac-de Paillerets, Brigitte] Gustave Roussy, Dept Biopathol, Villejuif, France.
   [Bressac-de Paillerets, Brigitte] Gustave Roussy, INSERM, U1186, Villejuif, France.
   [Calista, Donato] Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy.
   [Cannon-Albright, Lisa A.] Univ Utah, Sch Med, Div Genet Epidemiol, Dept Internal Med, Salt Lake City, UT USA.
   [Cuellar, Francisco; Puig, Susana] IDIBAPS, Hosp Clin, Dept Dermatol, Melanoma Unit, Barcelona, Spain.
   [Cust, Anne E.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
   [Demenais, Florence] Univ Paris Diderot, INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.
   [Elder, David E.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Friedman, Eitan] Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel.
   [Gerdes, Anne-Marie; Wadt, Karin A. W.] Univ Copenhagen Hosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
   [Goldstein, Alisa M.; Landi, Maria Teresa; Tucker, Margaret A.; Yang, Xiaohong R.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Grazziotin, Thais C.] Univ Fed Ciencias Saude Porto Alegre, Porto, RS, Brazil.
   [Hansson, Johan] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
   [Hayward, Nicholas K.; Palmer, Jane] QIMR Berghofer Med Res Inst, Herston, Qld, Australia.
   [Hocevar, Marko; Peric, Barbara] Inst Oncol Ljubljana, Ljubljana, Slovenia.
   [Holland, Elizabeth A.; Mann, Graham J.; Olsson, Hakan; Schmid, Helen] Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW 2006, Australia.
   [Holland, Elizabeth A.; Mann, Graham J.; Olsson, Hakan; Schmid, Helen] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia.
   [Ingvar, Christian] Univ Lund Hosp, Dept Surg, S-22185 Lund, Sweden.
   [Landman, Gilles] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pathol, Sao Paulo, Brazil.
   [Larre-Borges, Alejandra] Univ Republica, Hosp Clin, Catedra Dermatol, Unidad Lesiones Pigmentadas, Montevideo, Uruguay.
   [Leachman, Sancy A.] Oregon Hlth & Sci Univ, Sch Med, Dept Dermatol, Portland, OR USA.
   [Nagore, Eduardo] Inst Valenciano Oncol, Dept Dermatol, Valencia, Spain.
   [Pjanova, Dace] Latvian Biomed Res & Study Ctr, Riga, Latvia.
RP Kanetsky, PA (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
EM peter.kanetsky@moffitt.org
RI Hoiom, Veronica/F-4153-2012; Demenais, Florence/G-3298-2013; 
OI Demenais, Florence/0000-0001-8361-0936; Bishop, Tim/0000-0002-8752-8785;
   albright, lisa/0000-0003-2602-3668; Newton Bishop,
   Julia/0000-0001-9147-6802; Puig, Susana/0000-0003-1337-9745
FU Medical Research Council [MR/L01629X/1]; NCI NIH HHS [R01 CA083115, P30
   CA016520, R25 CA147832, T32 CA147832]
NR 15
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAY
PY 2016
VL 136
IS 5
BP 1066
EP 1069
DI 10.1016/j.jid.2016.01.009
PG 4
WC Dermatology
SC Dermatology
GA DL9RN
UT WOS:000375980600031
PM 26827760
ER

PT J
AU Pomeraniec, IJ
   Ksendzovsky, A
   Ellis, S
   Roberts, SE
   Jane, JA
AF Pomeraniec, I. Jonathan
   Ksendzovsky, Alexander
   Ellis, Scott
   Roberts, Sarah E.
   Jane, John A., Jr.
TI Frequency and long-term follow-up of trapped fourth ventricle following
   neonatal posthemorrhagic hydrocephalus
SO JOURNAL OF NEUROSURGERY-PEDIATRICS
LA English
DT Article
DE fourth ventricle; shunt; pediatric neurosurgery; hydrocephalus
ID ISOLATED 4TH VENTRICLE; INTRAVENTRICULAR HEMORRHAGE; ENDOSCOPIC
   AQUEDUCTOPLASTY; STENT PLACEMENT; SHUNT; CHILDREN; MANAGEMENT; INFANTS;
   PATHOPHYSIOLOGY; CLASSIFICATION
AB OBJECTIVE Intraventricular hemorrhage (IVH) is a common complication of premature neonates with small birth weight, which often leads to hydrocephalus and treatment with ventriculoperitoneal (VP) shunting procedures. Trapped fourth ventricle (TFV) can be a devastating consequence of the subsequent occlusion of the cerebral aqueduct and foramina of Luschka and Magendie.
   METHODS The authors retrospectively reviewed 8 consecutive cases involving pediatric patients with TFV following VP shunting for IVH due to prematurity between 2003 and 2012. The patients ranged in gestational age from 23.0 to 32.0 weeks, with an average age at first shunting procedure of 6.1 weeks (range 3.1-12.7 weeks). Three patients were managed with surgery. Patients received long-term radiographic (mean 7.1 years; range 3.4-12.2 years) and clinical (mean 7.8 years; range 4.6-12.2 years) follow-up.
   RESULTS The frequency of TFV following VP shunting for neonatal posthemorrhagic hydrocephalus was found to be 15.4%. Three (37.5%) patients presented with symptoms of posterior fossa compression and were treated surgically. All of these patients showed signs of radiographic improvement with stable or improved clinical examinations during postoperative follow-up. Of the 5 patients treated conservatively, 80% experienced stable ventricular size and 1 patient experienced a slight increase (3 mm) on imaging. All of the nonsurgical patients showed stable to improved clinical examinations over the follow-up period.
   CONCLUSIONS The frequency of TFV among premature IVH patients is relatively high. Most patients with TFV are asymptomatic at presentation and can be managed without surgery. Symptomatic patients may be treated surgically for decompression of the fourth ventricle.
C1 [Pomeraniec, I. Jonathan; Ksendzovsky, Alexander; Ellis, Scott; Roberts, Sarah E.; Jane, John A., Jr.] Univ Virginia Hlth Syst, Dept Neurol Surg, Box 800386, Charlottesville, VA 22908 USA.
   [Ksendzovsky, Alexander] NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Jane, JA (reprint author), Univ Virginia Hlth Syst, Dept Neurol Surg, Box 800386, Charlottesville, VA 22908 USA.
EM jaj2k@virginia.edu
NR 36
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1933-0707
EI 1933-0715
J9 J NEUROSURG-PEDIATR
JI J. Neurosurg.-Pediatr.
PD MAY
PY 2016
VL 17
IS 5
BP 552
EP 557
DI 10.3171/2015.10.PEDS15398
PG 6
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA DK2CS
UT WOS:000374722800007
PM 26745647
ER

PT J
AU Good, MJ
   Hurley, P
   Woo, KM
   Szczepanek, C
   Stewart, T
   Robert, N
   Lyss, A
   Gonen, M
   Lilenbaum, R
AF Good, Marjorie J.
   Hurley, Patricia
   Woo, Kaitlin M.
   Szczepanek, Connie
   Stewart, Teresa
   Robert, Nicholas
   Lyss, Alan
   Gonen, Mithat
   Lilenbaum, Rogerio
TI Assessing Clinical Trial-Associated Workload in Community-Based Research
   Programs Using the ASCO Clinical Trial Workload Assessment Tool
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
AB Purpose
   Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings.
   Methods
   Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters.
   Results
   Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others.
   Conclusion
   The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings.
C1 NCI, 9609 Med Ctr Dr,Room 5E434,MSC 9785, Rockville, MD 20892 USA.
   Amer Soc Clin Oncol, Alexandria, VA USA.
   Virginia Canc Specialists US Oncol, Fairfax, VA USA.
   Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
   West Michigan NCI Community Oncol Res Program, Canc Res Consortium, Grand Rapids, MI USA.
   Univ New Mexico Minority, Underserved NCI Community Oncol Res Program, Albuquerque, NM USA.
   Missouri Baptist Med Ctr, Heartland Canc Res NCI Commun Oncol Res Program, St Louis, MO USA.
   Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA.
RP Good, MJ (reprint author), NCI, Canc Prevent Div, Community Oncol Prevent Trials Res Grp, 9609 Med Ctr Dr,Room 5E434,MSC 9785, Rockville, MD 20892 USA.
EM marge.good@nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD MAY
PY 2016
VL 12
IS 5
BP 457
EP +
DI 10.1200/JOP.2015.008920
PG 14
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DL6JB
UT WOS:000375744400004
ER

PT J
AU Anene, DF
   Rosenberg, AZ
   Kleiner, DE
   Cornish, TC
   Halushka, MK
AF Anene, Divine-Favour
   Rosenberg, Avi Z.
   Kleiner, David E.
   Cornish, Toby C.
   Halushka, Marc K.
TI Utilization of HPASubC for the Identification of Sinusoid-Specific
   Proteins in the Liver
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE liver; human protein atlas; Kupffer cell; endothelial cell; lymphocyte;
   HPASubC; proteome; tissue microarray
ID PHENOTYPIC HETEROGENEITY; HUMAN PROTEOME; CELL; DRAFT
AB Mass spectrometry-based proteomes of human organs and tissues are powerful tools but fail to capture protein localization and expression at the cellular level. For example, the proteome signal in liver represents the combined protein expression across diverse cellular constituents that include hepatocytes, Kupffer cells, endothelial cells, and others. We utilized HPASubC and the Human Protein Atlas (HPA) to identify the sinusoidal component of protein liver expression to further subset and organize this homogeneous signal. We evaluated 51 109 liver images covering 13 197 proteins from the HPA and discovered 1054 proteins that were exclusive to sinusoidal cells. Sinusoidal staining patterns were identified in a Kupffer cell (n = 247), endothelial cell (n = 358), or lymphocyte (n = 86) specific pattern. Two-hundred and thirty-nine of these proteins were not present in the NextProt or Human Proteome Map liver data sets, potentially expanding our knowledge of the liver proteome. We additionally demonstrate unique endothelial cell expression patterns that distinguish between portal vein, hepatic artery, capillary sinusoids, and central vein regions. These findings significantly improve our understanding of the liver proteome with insight into the endothelial complexity across the hepatic vascular network.
C1 [Anene, Divine-Favour; Cornish, Toby C.; Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Dept Pathol, 720 Rutland Ave, Baltimore, MD 21205 USA.
   [Rosenberg, Avi Z.] Childrens Natl Med Ctr, Dept Pathol, 111 Michigan Ave NW, Washington, DC 20010 USA.
   [Kleiner, David E.] NCI, Pathol Lab, Bldg 10,Room 2S235,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA.
   [Cornish, Toby C.] Univ Colorado, Sch Med, Dept Pathol, Acad Off 1,Room L15-2109,12631 East 17th Ave, Aurora, CO 80045 USA.
RP Halushka, MK (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 720 Rutland Ave, Baltimore, MD 21205 USA.
EM mhalush1@jhmi.edu
NR 18
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAY
PY 2016
VL 15
IS 5
BP 1623
EP 1629
DI 10.1021/acs.jproteome.6b00073
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DL8KP
UT WOS:000375891200021
PM 27005832
ER

PT J
AU van Sloten, TT
   Mitchell, GF
   Sigurdsson, S
   van Buchem, MA
   Jonsson, PV
   Garcia, ME
   Harris, TB
   Henry, RMA
   Levey, AS
   Stehouwer, CDA
   Gudnason, V
   Launer, LJ
AF van Sloten, Thomas T.
   Mitchell, Gary F.
   Sigurdsson, Sigurdur
   van Buchem, Mark A.
   Jonsson, Palmi V.
   Garcia, Melissa E.
   Harris, Tamara B.
   Henry, Ronald M. A.
   Levey, Andrew S.
   Stehouwer, Coen D. A.
   Gudnason, Vilmundur
   Launer, Lenore J.
TI Associations between arterial stiffness, depressive symptoms and
   cerebral small vessel disease: cross-sectional findings from the
   AGES-Reykjavik Study
SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE
LA English
DT Article
ID PULSE-WAVE VELOCITY; GENERAL ELDERLY POPULATION; WHITE-MATTER LESIONS;
   VASCULAR DEPRESSION; OLDER-ADULTS; GENE/ENVIRONMENT SUSCEPTIBILITY;
   ENDOTHELIAL DYSFUNCTION; BRAIN INFARCTS; FOLLOW-UP; MECHANISMS
AB Background Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association.
   Methods This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume.
   Results We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders ( 0.096, 95% confidence interval [CI] 0.005-0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms.
   Limitations Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire.
   Conclusion Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.
C1 [van Sloten, Thomas T.; Henry, Ronald M. A.; Stehouwer, Coen D. A.] Cardiovasc Res Inst Maastricht, Limburg, Netherlands.
   [van Sloten, Thomas T.] Maastricht Univ, Med Ctr, Sch Nutr Toxicol & Metab, NL-6200 MD Maastricht, Netherlands.
   [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
   [Sigurdsson, Sigurdur; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland.
   [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
   [Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland.
   [Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
   [Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
   [Levey, Andrew S.] Tufts Med Ctr, William B Schwartz Div Nephrol, Boston, MA USA.
RP Launer, LJ (reprint author), NIA, Intramural Res Program, Bethesda, MD 20892 USA.
EM LaunerL@nia.nih.gov
FU National Institutes of Health (NIH) [N01-AG-12100]; Intramural Research
   Program of the National Institute on Aging, USA; Icelandic Heart
   Association; Icelandic Parliament, Iceland; National Institutes of
   Health, National Heart, Lung and Blood Institute [HL094898]; National
   Institute of Diabetes and Digestive and Kidney Diseases [DK082447]
FX The AGES-Reykjavik Study was funded by National Institutes of Health
   (NIH) (contract N01-AG-12100) and the Intramural Research Program of the
   National Institute on Aging, USA; the Icelandic Heart Association and
   the Icelandic Parliament, Iceland; and by grants from the National
   Institutes of Health, National Heart, Lung and Blood Institute
   (HL094898) and the National Institute of Diabetes and Digestive and
   Kidney Diseases (DK082447).
NR 46
TC 1
Z9 1
U1 1
U2 4
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 1180-4882
EI 1488-2434
J9 J PSYCHIATR NEUROSCI
JI J. Psychiatry Neurosci.
PD MAY
PY 2016
VL 41
IS 3
BP 162
EP 168
DI 10.1503/jpn.140334
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DL8DB
UT WOS:000375868900007
PM 26505140
ER

PT J
AU Callisaya, ML
   Ayers, E
   Barzilai, N
   Ferrucci, L
   Guralnik, J
   Lipton, R
   Otahal, P
   Srikanth, V
   Verghese, J
AF Callisaya, M. L.
   Ayers, E.
   Barzilai, N.
   Ferrucci, L.
   Guralnik, J.
   Lipton, R.
   Otahal, P.
   Srikanth, V.
   Verghese, J.
TI Motoric Cognitive Risk Syndrome and Falls Risk - a multi-centre study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 19-21, 2016
CL Long Beach, CA
SP Amer Geriatr Soc
C1 [Callisaya, M. L.; Otahal, P.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia.
   [Callisaya, M. L.; Srikanth, V.] Monash Univ, Monash Med Ctr, Clayton, Vic, Australia.
   [Ayers, E.; Barzilai, N.; Verghese, J.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
   [Guralnik, J.; Lipton, R.] Univ Maryland, Baltimore, MD 21201 USA.
FU NIH [R00AG037574, 1P01AG034906, R01AG046949, 1R01AG042188, P30AG038072,
   R37AG18381, 263 MD916413, 263 MD 821336, 1ZIAAG001050]; CTSA
   [KL2TR000088]; Einstein Glenn Center; Paul Glenn Foundation; American
   Federation for Aging Research; National Institute on Aging [1P01AG03949,
   NIA U01AG009740]; Italian Ministry of Health [ICS 110.1/RS97.71];
   National Health and Medical Research Council (NHMRC) [403000, 491109];
   Perpetual Trustees; Brain Foundation; Royal Hobart Hospital Research
   Foundation [341M]; ANZ Charitable Trust; Masonic Centenary Medical
   Research Foundation
FX Supported By: The LonGenity Study was funded by NIH (R00AG037574,
   1P01AG034906, R01AG046949, 1R01AG042188, P30AG038072, and NIH
   R37AG18381), CTSA KL2TR000088, Einstein Glenn Center, Paul Glenn
   Foundation, and the American Federation for Aging Research.; The
   Einstein Aging Study was funded by the National Institute on Aging
   (1P01AG03949).; The HRS (Health and Retirement Study) is sponsored by
   the National Institute on Aging (grant number NIA U01AG009740) and is
   conducted by the University of Michigan.; The InCHIANTI Study was funded
   by the Italian Ministry of Health (grant ICS 110.1/RS97.71) and NIH
   (grants 263 MD916413, 263 MD 821336, 1ZIAAG001050).; TASCOG was funded
   by National Health and Medical Research Council (NHMRC) grants 403000
   and 491109, Perpetual Trustees, Brain Foundation, Royal Hobart Hospital
   Research Foundation (341M), ANZ Charitable Trust, Masonic Centenary
   Medical Research Foundation
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
SU 1
SI SI
MA B57
BP S106
EP S106
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK2SD
UT WOS:000374763800294
ER

PT J
AU Huisingh-Scheetz, M
   Wroblewski, K
   Hue, T
   Newman, A
   Sutherfield, S
   Harris, T
   Schoeller, D
AF Huisingh-Scheetz, M.
   Wroblewski, K.
   Hue, T.
   Newman, A.
   Sutherfield, S.
   Harris, T.
   Schoeller, D.
TI Resting Metabolic Rate and Timed Gait in the Health ABC Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 19-21, 2016
CL Long Beach, CA
SP Amer Geriatr Soc
C1 [Huisingh-Scheetz, M.; Wroblewski, K.] Univ Chicago Med, Chicago, IL USA.
   [Hue, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Newman, A.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Sutherfield, S.] Univ Tennessee, Memphis, TN USA.
   [Harris, T.] NIA, Bethesda, MD 20892 USA.
   [Schoeller, D.] Univ Wisconsin, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
SU 1
SI SI
MA C1
BP S150
EP S150
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK2SD
UT WOS:000374763800412
ER

PT J
AU Jang, S
   Chen, R
   Abbott, R
   Ross, G
   Petrovitch, H
   White, L
   Okamoto, L
   Willcox, B
   Launer, L
   Masaki, K
AF Jang, S.
   Chen, R.
   Abbott, R.
   Ross, G.
   Petrovitch, H.
   White, L.
   Okamoto, L.
   Willcox, B.
   Launer, L.
   Masaki, K.
TI Olfactory Dysfunction Predicts Twenty-Year Total Mortality: The
   Honolulu-Asia Aging Study.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 19-21, 2016
CL Long Beach, CA
SP Amer Geriatr Soc
C1 [Jang, S.; Abbott, R.; Ross, G.; Petrovitch, H.; White, L.; Okamoto, L.; Willcox, B.; Masaki, K.] Univ Hawaii, Geriatr Med, Honolulu, HI 96822 USA.
   [Chen, R.; Willcox, B.; Masaki, K.] Kuakini Med Ctr, Honolulu, HI USA.
   [Abbott, R.] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan.
   [Ross, G.; Petrovitch, H.; White, L.] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
   [Launer, L.] NIA, Bethesda, MD 20892 USA.
FU John A. Hartford Foundation Center of Excellence in Geriatrics,
   Department of Geriatric Medicine, John A. Burns School of Medicine,
   University of Hawaii; Kuakini Medical Center; National Institutes of
   Health (NIH) [N01-AG-4-2149, U01 AG019349, R01AG027060, R01AG038707,
   N01-HC-05102]; Hawaii Community Foundation [2004-0463]; Office for
   Research and Development, Department of Veterans Affairs
FX Supported By: This study was supported by the John A. Hartford
   Foundation Center of Excellence in Geriatrics, Department of Geriatric
   Medicine, John A. Burns School of Medicine, University of Hawaii; the
   Kuakini Medical Center; the National Institutes of Health (NIH)
   (Contract N01-AG-4-2149, Grants U01 AG019349, R01AG027060, and
   R01AG038707 from the National Institute on Aging, and Contract
   N01-HC-05102 from the National Heart, Lung, and Blood Institute); Hawaii
   Community Foundation grant 2004-0463; and the Office for Research and
   Development, Department of Veterans Affairs. The views expressed in this
   abstract do not necessarily represent those of the federal government.
   The funding sources had no role in the analysis.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
SU 1
SI SI
MA P27
BP S11
EP S11
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK2SD
UT WOS:000374763800027
ER

PT J
AU Naples, JG
   Marcum, Z
   Perera, S
   Newman, A
   Greenspan, SL
   Gray, S
   Bauer, D
   Simonsick, EM
   Shorr, R
   Hanlon, J
AF Naples, J. G.
   Marcum, Z.
   Perera, S.
   Newman, A.
   Greenspan, S. L.
   Gray, S.
   Bauer, D.
   Simonsick, E. M.
   Shorr, R.
   Hanlon, J.
TI Impact of Drug-Drug and Drug-Disease Interactions on Gait Speed in
   Community-Dwelling Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 19-21, 2016
CL Long Beach, CA
SP Amer Geriatr Soc
C1 [Marcum, Z.; Gray, S.] Univ Washington, Seattle, WA 98195 USA.
   [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Simonsick, E. M.] NIA, Baltimore, MD 21224 USA.
   [Shorr, R.] Malcolm Randall VAMC, Gainesville, FL USA.
   [Naples, J. G.; Perera, S.; Newman, A.; Greenspan, S. L.; Hanlon, J.] Univ Pittsburgh, Pittsburgh, PA USA.
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG024827,
   T32-AG021885, K07-AG033174, R01-AG028050, R01-AG037451]; NINR
   [R01-NR012459]; Intramural Research Program of the NIH, National
   Institute on Aging
FX Supported By: This research was supported by NIA contracts
   (N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106), grants (P30-AG024827,
   T32-AG021885, K07-AG033174, R01-AG028050, R01-AG037451), NINR grant
   (R01-NR012459), and in part by the Intramural Research Program of the
   NIH, National Institute on Aging.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
SU 1
SI SI
MA B67
BP S110
EP S110
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK2SD
UT WOS:000374763800304
ER

PT J
AU Suskind, AM
   Cawthon, PM
   Nakagawa, S
   Subak, LL
   Reinders, I
   Sutherfield, S
   Cummings, S
   Cauley, JA
   Harris, T
   Huang, AJ
AF Suskind, A. M.
   Cawthon, P. M.
   Nakagawa, S.
   Subak, L. L.
   Reinders, I.
   Sutherfield, S.
   Cummings, S.
   Cauley, J. A.
   Harris, T.
   Huang, A. J.
TI Urinary incontinence in older women: the role of body mass, body
   composition, and muscle strength from the Health, Aging, and Body
   Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 19-21, 2016
CL Long Beach, CA
SP Amer Geriatr Soc
C1 [Suskind, A. M.] UCSF, Urol, San Francisco, CA USA.
   [Cawthon, P. M.] UCSF, Epidemiol & Biostat, San Francisco, CA USA.
   [Nakagawa, S.; Subak, L. L.] UCSF, OB Gyn, San Francisco, CA USA.
   [Reinders, I.; Harris, T.] NIA, Bethesda, MD 20892 USA.
   [Reinders, I.] Vrije Univ Amsterdam, Med Ctr, Internal Med, Amsterdam, Netherlands.
   [Sutherfield, S.] UTHSC, Preventat Med, Memphis, TN USA.
   [Cummings, S.; Huang, A. J.] UCSF, Med, San Francisco, CA USA.
   [Cauley, J. A.] Univ Pittsburgh, Epidemol, Pittsburgh, PA USA.
FU American Federation for Aging Research; NIA [R01-AG028050]; NINR
   [R01-NR012459];  [K12DK83021-07];  [1K23AG038335];  [2K24DK080775-06]; 
   [N01-AG-6-2101];  [N01-AG-6-2103];  [N01-AG-6-2106]
FX Supported By: K12DK83021-07; 1K23AG038335 and the American Federation
   for Aging Research. 2K24DK080775-06, N01-AG-6-2101; N01-AG-6-2103;
   N01-AG-6-2106; NIA R01-AG028050, and NINR R01-NR012459.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2016
VL 64
SU 1
SI SI
MA B2
BP S86
EP S86
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DK2SD
UT WOS:000374763800239
ER

PT J
AU Rohr, J
   Guo, S
   Huo, J
   Bouska, A
   Lachel, C
   Li, Y
   Simone, PD
   Zhang, W
   Gong, Q
   Wang, C
   Cannon, A
   Heavican, T
   Mottok, A
   Hung, S
   Rosenwald, A
   Gascoyne, R
   Fu, K
   Greiner, TC
   Weisenburger, DD
   Vose, JM
   Staudt, LM
   Xiao, W
   Borgstahl, GEO
   Davis, S
   Steidl, C
   McKeithan, T
   Iqbal, J
   Chan, WC
AF Rohr, J.
   Guo, S.
   Huo, J.
   Bouska, A.
   Lachel, C.
   Li, Y.
   Simone, P. D.
   Zhang, W.
   Gong, Q.
   Wang, C.
   Cannon, A.
   Heavican, T.
   Mottok, A.
   Hung, S.
   Rosenwald, A.
   Gascoyne, R.
   Fu, K.
   Greiner, T. C.
   Weisenburger, D. D.
   Vose, J. M.
   Staudt, L. M.
   Xiao, W.
   Borgstahl, G. E. O.
   Davis, S.
   Steidl, C.
   McKeithan, T.
   Iqbal, J.
   Chan, W. C.
TI Recurrent activating mutations of CD28 in peripheral T-cell lymphomas
SO LEUKEMIA
LA English
DT Article
ID FOLLICULAR-HELPER; CRYSTAL-STRUCTURE; GENE-EXPRESSION; MULTIPLE-MYELOMA;
   CTLA-4 RECEPTORS; COPY NUMBER; RNA-SEQ; BINDING; COSTIMULATION;
   LANDSCAPE
AB Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation. We have identified recurrent mutations in CD28 in PTCLs. Two residues-D124 and T195-were recurrently mutated in 11.3% of cases of AITL and in one case of PTCL, not otherwise specified (PTCL-NOS). Surface plasmon resonance analysis of mutations at these residues with predicted differential partner interactions showed increased affinity for ligand CD86 (residue D124) and increased affinity for intracellular adaptor proteins GRB2 and GADS/GRAP2 (residue T195). Molecular modeling studies on each of these mutations suggested how these mutants result in increased affinities. We found increased transcription of the CD28-responsive genes CD226 and TNFA in cells expressing the T195P mutant in response to CD3 and CD86 co-stimulation and increased downstream activation of NF-kappa B by both D124V and T195P mutants, suggesting a potential therapeutic target in CD28-mutated PTCLs.
C1 [Rohr, J.; Bouska, A.; Lachel, C.; Zhang, W.; Wang, C.; Cannon, A.; Heavican, T.; Fu, K.; Greiner, T. C.; Iqbal, J.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 985900 Nebraska Med Ctr, Omaha, NE 68918 USA.
   [Rohr, J.; Li, Y.; Gong, Q.; Wang, C.; Weisenburger, D. D.; McKeithan, T.; Chan, W. C.] City Hope Natl Med Ctr, Dept Pathol, Familian Sci Bldg,Room 1013, Duarte, CA 91010 USA.
   [Guo, S.] Fourth Mil Med Univ, Xi Jing Hosp, Dept Pathol, Xian 710032, Shaan Xi Provin, Peoples R China.
   [Huo, J.; Davis, S.] Univ Oxford, Radcliffe Dept Med, Oxford, England.
   [Simone, P. D.] Florida Atlantic Univ, Internal Med Residency Program, Coll Med, Boca Raton, FL 33431 USA.
   [Wang, C.] Shandong Univ, Sch Med, Jinan 250100, Peoples R China.
   [Mottok, A.; Hung, S.; Gascoyne, R.; Steidl, C.] BC Canc Agcy, Dept Lymphoid Canc Res, Ctr Lymphoid Canc, Vancouver, BC, Canada.
   [Mottok, A.; Hung, S.; Gascoyne, R.; Steidl, C.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
   [Rosenwald, A.] Univ Wurzburg, Inst Pathol, Wurzburg, Germany.
   [Rosenwald, A.] Univ Wurzburg, Comprehens Canc Ctr Mainfranken CCC MF, D-97070 Wurzburg, Germany.
   [Vose, J. M.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA.
   [Staudt, L. M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Xiao, W.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Washington, DC 20204 USA.
   [Borgstahl, G. E. O.] Univ Nebraska Med Ctr, Eppley Inst Canc Res & Allied Dis, Omaha, NE USA.
RP Iqbal, J (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 985900 Nebraska Med Ctr, Omaha, NE 68918 USA.; Chan, WC (reprint author), City Hope Natl Med Ctr, Dept Pathol, Familian Sci Bldg,Room 1013, Duarte, CA 91010 USA.
EM jiqbal@unmc.edu; jochan@coh.org
OI Gong, Qiang/0000-0001-8502-6813
FU NCI SPECS II [5 UO1 CA157581-01]; NCI SPORE [1P50CA 136411-01 01A1
   PP-4]; City of Hope internal funds; Lymphoma Research Foundation
   [F-263549]; Leukemia and Lymphoma Society [TRP-6129-04]; UNMC
   Clinical-Translational Research Scholars Program; NCI Eppley Cancer
   Center Support Grant [P30CA036727]; Dr Mildred-Scheel Cancer Foundation;
   Michael Smith Foundation for Health Research; National Center for
   Research Resources [5P20RR016469, 1S10RR027754-01, RR018788-08];
   National Institute for General Medical Science [8P20GM103427,
   GM103471-09]; NCI; NIH [P30CA33572]; Lymphoma SPORE Developmental
   Research Award [P50 CA107399]
FX We thank R Redder and Dr A Dhar and J Eudy of the UNMC sequencing core;
   V Smith and Dr P Hexley of the UNMC flow cytometry core; and L Brown, N
   Feng and S Hsueh of the COH Analytical Cytometry Core. We would like to
   thank Elizabeth Chavez at BCCA for performing the TSCA experiment.
   Thanks to Dr Francoise Berger of Universite Lyon 1 for contributing
   several samples to this study. WCC is supported by NCI SPECS II 5 UO1
   CA157581-01, NCI SPORE 1P50CA 136411-01 01A1 PP-4 and City of Hope
   internal funds; JI is supported by the Lymphoma Research Foundation
   (F-263549), the Leukemia and Lymphoma Society (TRP-6129-04), the UNMC
   Clinical-Translational Research Scholars Program, and the NCI Eppley
   Cancer Center Support Grant P30CA036727. AM is supported by the Dr
   Mildred-Scheel Cancer Foundation and the Michael Smith Foundation for
   Health Research. Partial support is from NCI Eppley Cancer Center
   Support Grant P30CA036727, National Center for Research Resources
   5P20RR016469, and National Institute for General Medical Science
   8P20GM103427 to GB. The University of Nebraska DNA Sequencing Core
   receives partial support from the National Center for Research Resources
   (1S10RR027754-01, 5P20RR016469, RR018788-08) and the National Institute
   for General Medical Science (8P20GM103427, GM103471-09). Research
   reported in this publication included work performed in the City of Hope
   Analytical Cytometry Core supported by the NCI and NIH under award
   number P30CA33572. This publication's contents are the sole
   responsibility of the authors and do not necessarily represent the
   official views of the NIH, FDA or NIGMS. WCC is the recipient of a
   Lymphoma SPORE Developmental Research Award (P50 CA107399).
NR 60
TC 6
Z9 6
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2016
VL 30
IS 5
BP 1062
EP 1070
DI 10.1038/leu.2015.357
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA DL5QM
UT WOS:000375691800007
PM 26719098
ER

PT J
AU Lam, CJK
   Curtis, RE
   Dores, GM
   Engels, EA
   Caporaso, NE
   Polliack, A
   Warren, JL
   Young, HA
   Levine, PH
   Elmi, AF
   Fraumeni, JF
   Tucker, MA
   Morton, LM
AF Lam, C. J. K.
   Curtis, R. E.
   Dores, G. M.
   Engels, E. A.
   Caporaso, N. E.
   Polliack, A.
   Warren, J. L.
   Young, H. A.
   Levine, P. H.
   Elmi, A. F.
   Fraumeni, J. F.
   Tucker, M. A.
   Morton, L. M.
TI Risk factors for second acute myeloid leukemia/myelodysplastic syndrome
   among survivors of non-Hodgkin lymphoma
SO LEUKEMIA
LA English
DT Letter
ID LEUKEMIA; FLUDARABINE; THERAPY; MYELODYSPLASIA; AUTOIMMUNITY; DISEASES
C1 [Lam, C. J. K.; Curtis, R. E.; Dores, G. M.; Engels, E. A.; Caporaso, N. E.; Fraumeni, J. F.; Tucker, M. A.; Morton, L. M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Lam, C. J. K.; Young, H. A.; Levine, P. H.; Elmi, A. F.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC USA.
   [Polliack, A.] Hadassah Univ Hosp, Dept Hematol, POB 12000, IL-91120 Jerusalem, Israel.
   [Warren, J. L.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mortonli@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010170-11]
NR 15
TC 1
Z9 1
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2016
VL 30
IS 5
BP 1187
EP 1190
DI 10.1038/leu.2015.248
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA DL5QM
UT WOS:000375691800022
PM 26369985
ER

PT J
AU Weber, MM
   Faris, R
   McLachlan, J
   Tellez, A
   Wright, WU
   Galvan, G
   Luo, ZQ
   Samuel, JE
AF Weber, Mary M.
   Faris, Robert
   McLachlan, Juanita
   Tellez, Andres
   Wright, William U.
   Galvan, Gloria
   Luo, Zhao-Qing
   Samuel, James E.
TI Modulation of the host transcriptome by Coxiella burnetii nuclear
   effector Cbu1314
SO MICROBES AND INFECTION
LA English
DT Article
DE Coxiella burnetii; Dot/Icm; T4SS; Nuclear effector
ID GENE-EXPRESSION; ANAPLASMA-PHAGOCYTOPHILUM; INTRACELLULAR REPLICATION;
   SECRETION; PROTEINS; CELLS; CHROMATIN; IDENTIFICATION; APOPTOSIS;
   TARGETS
AB Coxiella burnetii is a Gram-negative, obligate intracellular pathogen that directs the formation of a parasitophorous vacuole derived from the host lysosomal network. Biogenesis and maintenance of this replicative compartment is dependent on bacterial protein synthesis and results in differential expression of specific host genes. However, the mechanisms by which the pathogen induces changes in the host transcriptome is poorly understood. In the current study we identified a Dot/Icm secreted effector, Cbu1314, which encodes two nuclear localization signals that are required for nuclear localization and association with host chromatin. Chromatin immunoprecipitation (ChIP) and deep sequencing revealed that Cbu1314 associated with host genes involved in transcription, cell signaling, and the immune response. RNA sequencing of cells over-expressing Cbu1314 demonstrated that Cbu1314 modulates the host transcriptome and these transcriptional changes required a functional nuclear localization signal. Of the differentially expressed genes, sixteen were also identified as Cbu1314 targets using ChIP sequencing. Collectively these results suggest that Cbu1314 associates with host chromatin and plays a role in modulating the host transcriptome. (C) 2016 Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Weber, Mary M.; Faris, Robert; McLachlan, Juanita; Tellez, Andres; Wright, William U.; Galvan, Gloria; Samuel, James E.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Microbial Pathogenesis & Immunol, Bryan, TX 77807 USA.
   [Luo, Zhao-Qing] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Weber, Mary M.] NIAID, Bacteriol Lab, NIH, Rocky Mt Labs, Hamilton, MT USA.
   [Faris, Robert] NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT USA.
   [McLachlan, Juanita] Washington State Univ, Coll Pharm, Spokane, WA USA.
   [Galvan, Gloria] Univ Texas Grad Sch Biomed Sci, Houston, TX USA.
RP Samuel, JE (reprint author), Texas A&M Hlth Sci Ctr, Coll Med, Dept Microbial Pathogenesis & Immunol, Bryan, TX 77807 USA.
EM jsamuel@medicine.tamhsc.edu
OI Galvan, Gloria/0000-0001-8398-7477; Faris, Robert/0000-0003-0855-7041
FU National Institutes of Health, National Institute of Allergy and
   Infectious Disease [AI088430, AI090142]
FX We would like to thank Elizabeth Di Russo Case and Sara Talmage for
   critical review of this manuscript. This work was supported by National
   Institutes of Health, National Institute of Allergy and Infectious
   Disease Grants AI088430 (JES) and AI090142 (JES and ZQL).
NR 38
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
EI 1769-714X
J9 MICROBES INFECT
JI Microbes Infect.
PD MAY
PY 2016
VL 18
IS 5
BP 336
EP 345
DI 10.1016/j.micinf.2016.01.003
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DL3XY
UT WOS:000375568200006
PM 26827929
ER

PT J
AU Hajishengallis, G
   Moutsopoulos, NM
AF Hajishengallis, George
   Moutsopoulos, Niki M.
TI Role of bacteria in leukocyte adhesion deficiency-associated
   periodontitis
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE Leukocyte adhesion deficiency; Periodontitis; Inflammation; Microbiota;
   IL-17; IL-23
ID INFLAMMATORY BONE LOSS; TISSUE HOMEOSTASIS; RARE DISEASES; NEUTROPHILS;
   VLA-4; HEALTH; LFA-1; MAC-1; ENDOTHELIUM; RECRUITMENT
AB Leukocyte adhesion deficiency Type I (LAD-I) associated periodontitis is an aggressive form of inflammatory bone loss that has been historically attributed to lack of neutrophil surveillance of the periodontal infection. However, this form of periodontitis has proven unresponsive to antibiotics and/or mechanical removal of the tooth-associated biofilm. Recent studies in LAD-I patients and relevant animal models have shown that the fundamental cause of LAD-I periodontitis involves dysregulation of a granulopoietic cytokine cascade. This cascade includes interleukin IL-23 (IL-23) and IL-17 that drive inflammatory bone loss in LAD-I patients and animal models and, moreover, foster a nutritionally favorable environment for bacterial growth and development of a compositionally unique microbiome. Although the lack of neutrophil surveillance in the periodontal pockets might be expected to lead to uncontrolled bacterial invasion of the underlying connective tissue, microbiological analyses of gingival biopsies from LAD-I patients did not reveal tissue-invasive infection. However, bacterial lipopolysaccharide was shown to translocate into the lesions of LAD-I periodontitis. It is concluded that the bacteria serve as initial triggers for local immunopathology through translocation of bacterial products into the underlying tissues where they unleash the dysregulated IL-23 IL-17 axis. Subsequently, the IL-23/IL-17 inflammatory response sustains and shapes a unique local microbiome which, in turn, can further exacerbate inflammation and bone loss in the susceptible host. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Hajishengallis, George] Univ Penn, Penn Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, NIH, Bethesda, MD 20892 USA.
RP Hajishengallis, G (reprint author), Univ Penn, Penn Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.; Moutsopoulos, NM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Immun & Inflammat Unit, NIH, Bethesda, MD 20892 USA.
EM geoh@upenn.edu; nmoutsopoulos@dir.nidr.nih.gov
FU NIH, NIDCR; U.S. Public Health Service from NIDCR [DE015254, DE021685,
   DE024716, AI068730]; NIAID
FX This research was supported in part by the Intramural Research Program
   of the NIH, NIDCR (N.M.M.) and by U.S. Public Health Service grants
   DE015254, DE021685, DE024716, and AI068730 from NIDCR and NIAID (G.H.).
NR 57
TC 1
Z9 1
U1 6
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0882-4010
J9 MICROB PATHOGENESIS
JI Microb. Pathog.
PD MAY
PY 2016
VL 94
BP 21
EP 26
DI 10.1016/j.micpath.2015.09.003
PG 6
WC Immunology; Microbiology
SC Immunology; Microbiology
GA DL6FN
UT WOS:000375735200004
PM 26375893
ER

PT J
AU Huebner, AR
   Cheng, L
   Somparn, P
   Knepper, MA
   Fenton, RA
   Pisitkun, T
AF Huebner, Alyssa R.
   Cheng, Lei
   Somparn, Poorichaya
   Knepper, Mark A.
   Fenton, Robert A.
   Pisitkun, Trairak
TI Deubiquitylation of Protein Cargo Is Not an Essential Step in Exosome
   Formation
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID UBIQUITINATED PROTEINS; MASS-SPECTROMETRY; DEUBIQUITINATING ENZYME;
   HUMAN URINE; PHOSPHORYLATION; IDENTIFICATION; ENDOCYTOSIS; BIOGENESIS;
   ESCRT; UBIQUITYLATION
AB Exosomes, derived from multivesicular bodies (MVBs), contain proteins and genetic materials from their cell of origin and are secreted from various cells types, including kidney epithelial cells. In general, it is thought that protein cargo is ubiquitylated but that ubiquitin is cleaved by specific deubiquitylases during the process of cargo incorporation into MVBs. Here, we provide direct evidence that, in vivo, deubiquitylation is not essential. Ubiquitin was detected within human MVBs and urinary exosomes by electron microscopy. Of the >6000 proteins identified in human urinary exosomes was mass spectrometry, 15% were ubiquitylated with various topologies (Lys63>Lys48>Lys11>Lys6>Lys29>Lys33>Lys27). A significant preference for basic amino acids upstream of ubiquitylation sites suggests specific ubiquitylation motifs. The current studies demonstrate that, in vivo, deubiquitylation of proteins is not necessary for their incorporation into MVBs and highlight that urinary exosomes are an enriched source for studying ubiquitin modifications in physiological or disease states.
C1 [Huebner, Alyssa R.; Cheng, Lei; Fenton, Robert A.; Pisitkun, Trairak] Aarhus Univ, Dept Biomed, Bldg 1233,Room 213,Wilhelm Meyers Alle 3, DK-8000 Aarhus C, Denmark.
   [Huebner, Alyssa R.; Cheng, Lei; Fenton, Robert A.; Pisitkun, Trairak] Aarhus Univ, Ctr Interact Prot Epithelial Transport, DK-8000 Aarhus C, Denmark.
   [Somparn, Poorichaya; Pisitkun, Trairak] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand.
   [Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Fenton, RA (reprint author), Aarhus Univ, Dept Biomed, Bldg 1233,Room 213,Wilhelm Meyers Alle 3, DK-8000 Aarhus C, Denmark.; Pisitkun, T (reprint author), Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand.
EM robert.a.fenton@biomed.au.dk; trairak@gmail.com
FU Danish Council for Independent Research Medical Research Council
   [4004-00043]; Natural Science Council [4002-00364]; Lundbeck Foundation;
   Novo Nordisk Foundation; Carlsberg Foundation; Aarhus University
   Research Foundation; Chulalongkorn Academic Advancement into Its 2nd
   Century Project
FX This work was supported by The Danish Council for Independent Research
   Medical Research Council (4004-00043) and Natural Science Council
   (4002-00364), the Lundbeck Foundation, the Novo Nordisk Foundation, the
   Carlsberg Foundation, and the Aarhus University Research Foundation. TP
   is supported by the Chulalongkorn Academic Advancement into Its 2nd
   Century Project.
NR 41
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD MAY
PY 2016
VL 15
IS 5
BP 1556
EP 1571
DI 10.1074/mcp.M115.054965
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DL5OI
UT WOS:000375686100006
PM 26884507
ER

PT J
AU Lal, TR
   Borger, DK
   Sidransky, E
AF Lal, Tamanna Roshan
   Borger, Daniel K.
   Sidransky, Ellen
TI Once again, rare diseases provide a spotlight
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Editorial Material
DE Multiple myeloma; Gaucher disease; Lysolipids; Monoclonal gammopathy
ID ENZYME REPLACEMENT THERAPY; GAUCHER-DISEASE; GLUCOCEREBROSIDASE;
   INFLAMMATION; MYELOMA; TYPE-1; CELLS
C1 [Lal, Tamanna Roshan; Borger, Daniel K.; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS; NIGMS NIH HHS [T32 GM007471]
NR 13
TC 0
Z9 0
U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAY
PY 2016
VL 118
IS 1
BP 1
EP 2
DI 10.1016/j.ymgme.2016.03.002
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA DL6HY
UT WOS:000375741500001
PM 27017192
ER

PT J
AU Monestime, G
   Borger, DK
   Kim, J
   Lopez, G
   Allgaeuer, M
   Jain, D
   Vortmeyer, A
   Wang, HW
   Sidransky, E
AF Monestime, Gianina
   Borger, Daniel K.
   Kim, Jenny
   Lopez, Grisel
   Allgaeuer, Michael
   Jain, Dhanpat
   Vortmeyer, Alexander
   Wang, Hao-Wei
   Sidransky, Ellen
TI Varied autopsy findings in five treated patients with Gaucher disease
   and parkinsonism include the absence of Gaucher cells
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Gaucher disease; Enzyme replacement therapy; Autopsy reports; Modifier
   genes
ID THERAPY; TYPE-3
AB Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. Published by Elsevier Inc.
C1 [Monestime, Gianina; Borger, Daniel K.; Kim, Jenny; Lopez, Grisel; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Bethesda, MD USA.
   [Allgaeuer, Michael; Wang, Hao-Wei] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Jain, Dhanpat; Vortmeyer, Alexander] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1E623,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS
NR 11
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAY
PY 2016
VL 118
IS 1
BP 55
EP 59
DI 10.1016/j.ymgme.2016.02.008
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA DL6HY
UT WOS:000375741500009
PM 26992326
ER

PT J
AU Kasianowicz, JJ
   Bezrukov, SM
AF Kasianowicz, John J.
   Bezrukov, Sergey M.
TI On 'three decades of nanopore sequencing'
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID ION-CHANNEL; DNA; MEMBRANE; DYNAMICS; BILAYERS; SITES
C1 [Kasianowicz, John J.] NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
   [Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Kasianowicz, JJ (reprint author), NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
EM jjkemail@mac.com
NR 19
TC 3
Z9 3
U1 10
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD MAY
PY 2016
VL 34
IS 5
BP 481
EP 482
DI 10.1038/nbt.3570
PG 2
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DL6FL
UT WOS:000375735000022
PM 27153275
ER

PT J
AU Brautigam, CA
   Zhao, HY
   Vargas, C
   Keller, S
   Schuck, P
AF Brautigam, Chad A.
   Zhao, Huaying
   Vargas, Carolyn
   Keller, Sandro
   Schuck, Peter
TI Integration and global analysis of isothermal titration calorimetry data
   for studying macromolecular interactions
SO NATURE PROTOCOLS
LA English
DT Article
ID HIGH-AFFINITY BINDING; PROTEIN-PROTEIN INTERACTIONS; MULTIMETHOD
   ANALYSIS; SIGNALING COMPLEXES; ITC; THERMODYNAMICS; RECOGNITION;
   MECHANISMS; CONSTANTS; SYSTEMS
AB Isothermal titration calorimetry (ITCTC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITCTC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPTPIC, SESEDPHATAT and GUSSUSSUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.
C1 [Brautigam, Chad A.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
   [Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA.
   [Vargas, Carolyn; Keller, Sandro] Univ Kaiserslautern, Mol Biophys, D-67663 Kaiserslautern, Germany.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA.; Keller, S (reprint author), Univ Kaiserslautern, Mol Biophys, D-67663 Kaiserslautern, Germany.
EM mail@sandrokeller.com; Peter.Schuck@nih.gov
RI Keller, Sandro/G-7202-2016
OI Keller, Sandro/0000-0001-5469-8772
FU Deutsche Forschungsgemeinschaft (DFG) through International Research
   Training Group [1830]; Stiftung Rheinland-Pfalz fur Innovation;
   Intramural Research Program of the National Institute of Biomedical
   Imaging and Bioengineering, US National Institutes of Health
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG)
   through International Research Training Group 1830, the Stiftung
   Rheinland-Pfalz fur Innovation and the Intramural Research Program of
   the National Institute of Biomedical Imaging and Bioengineering, US
   National Institutes of Health.
NR 60
TC 9
Z9 9
U1 5
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD MAY
PY 2016
VL 11
IS 5
BP 882
EP 894
DI 10.1038/nprot.2016.044
PG 13
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DJ8ES
UT WOS:000374445900004
PM 27055097
ER

PT J
AU Lodish, M
   Stratakis, CA
AF Lodish, Maya
   Stratakis, Constantine A.
TI A genetic and molecular update on adrenocortical causes of Cushing
   syndrome
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Review
ID MACRONODULAR ADRENAL-HYPERPLASIA; PROTEIN-KINASE-A; MCCUNE-ALBRIGHT
   SYNDROME; PKA CATALYTIC SUBUNIT; REGULATORY SUBUNIT; ARMC5 MUTATIONS;
   SIGNALING PATHWAYS; SOMATIC MUTATIONS; CARNEY COMPLEX; HEREDITARY
   LEIOMYOMATOSIS
AB Primary adrenal Cushing syndrome is the result of cortisol hypersecretion mainly by adenomas and, rarely, by bilateral micronodular or macronodular adrenocortical hyperplasia. cAMP-dependent protein kinase A (PKA) signalling is the major activator of cortisol secretion in the adrenal cortex. Many adenomas and hyperplasias associated with primary hypercortisolism carry somatic or germline mutations in genes that encode constituents of the cAMP-PKA pathway. In this Review, we discuss Cushing syndrome and its linkage to dysregulated cAMP-PKA signalling, with a focus on genetic findings in the past few years. In addition, we discuss the presence of germline inactivating mutations in ARMC5 in patients with primary bilateral macronodular adrenocortical hyperplasia. This finding has implications for genetic counselling of affected patients; hitherto, most patients with this form of adrenal hyperplasia and Cushing syndrome were thought to have a sporadic and not a familial disorder.
C1 [Lodish, Maya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA.
   [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Clin Res Ctr, 31 Ctr Dr,Bldg 31,Room 2A46,MSC2425, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Clin Res Ctr, 31 Ctr Dr,Bldg 31,Room 2A46,MSC2425, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD), NIH, Bethesda, Maryland, USA
FX This work was supported by the Intramural Research Program (IRP) of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD), NIH, Bethesda, Maryland 20892, USA.
NR 64
TC 3
Z9 4
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD MAY
PY 2016
VL 12
IS 5
BP 255
EP 262
DI 10.1038/nrendo.2016.24
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DJ8FF
UT WOS:000374447200003
PM 26965378
ER

PT J
AU Tuttle, MD
   Comellas, G
   Nieuwkoop, AJ
   Covell, DJ
   Berthold, DA
   Kloepper, KD
   Courtney, JM
   Kim, JK
   Barclay, AM
   Kendall, A
   Wan, W
   Stubbs, G
   Schwieters, CD
   Lee, VMY
   George, JM
   Rienstra, CM
AF Tuttle, Marcus D.
   Comellas, Gemma
   Nieuwkoop, Andrew J.
   Covell, Dustin J.
   Berthold, Deborah A.
   Kloepper, Kathryn D.
   Courtney, Joseph M.
   Kim, Jae K.
   Barclay, Alexander M.
   Kendall, Amy
   Wan, William
   Stubbs, Gerald
   Schwieters, Charles D.
   Lee, Virginia M. Y.
   George, Julia M.
   Rienstra, Chad M.
TI Solid-state NMR structure of a pathogenic fibril of full-length human
   alpha-synuclein
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID BETA-AMYLOID FIBRILS; ANGLE-SPINNING NMR; PARKINSONS-DISEASE;
   EXPERIMENTAL CONSTRAINTS; MOLECULAR-STRUCTURE; ALZHEIMERS-DISEASE;
   WILD-TYPE; MUTATION; PROTEIN; CORE
AB Misfolded alpha-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson's disease (PD). We present a high-resolution structure of an alpha-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by EM and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel, in-register beta-sheets and hydrophobic-core residues, and with substantial complexity arising from diverse structural features including an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a new orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as supported by the structural similarity of early-onset-PD mutants. The structure provides a framework for understanding the interactions of alpha-synuclein with other proteins and small molecules, to aid in PD diagnosis and treatment.
C1 [Tuttle, Marcus D.; Nieuwkoop, Andrew J.; Berthold, Deborah A.; Kloepper, Kathryn D.; Courtney, Joseph M.; Kim, Jae K.; Rienstra, Chad M.] Univ Illinois, Dept Chem, Urbana, IL USA.
   [Comellas, Gemma; Barclay, Alexander M.; Rienstra, Chad M.] Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL USA.
   [Covell, Dustin J.; Lee, Virginia M. Y.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Covell, Dustin J.; Lee, Virginia M. Y.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA.
   [Covell, Dustin J.; Lee, Virginia M. Y.] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
   [Kendall, Amy; Wan, William; Stubbs, Gerald] Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Kendall, Amy; Wan, William; Stubbs, Gerald] Vanderbilt Univ, Ctr Struct Biol, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
   [George, Julia M.] Queen Mary Univ London, Sch Biol & Chem Sci, Dept Biol & Expt Psychol, London, England.
   [Rienstra, Chad M.] Univ Illinois, Dept Biochem, Urbana, IL USA.
   [Tuttle, Marcus D.] Yale Univ, Dept Chem, New Haven, CT USA.
   [Nieuwkoop, Andrew J.] Leibniz Inst Mol Pharmacol, Berlin, Germany.
   [Kloepper, Kathryn D.] Mercer Univ, Dept Chem, Macon, GA 31207 USA.
   [Wan, William] European Mol Biol Lab, Struct & Computat Biol Unit, Heidelberg, Germany.
RP Rienstra, CM (reprint author), Univ Illinois, Dept Chem, Urbana, IL USA.; Rienstra, CM (reprint author), Univ Illinois, Ctr Biophys & Quantitat Biol, Urbana, IL USA.
EM rienstra@illinois.edu
RI Kendall, Amy/F-6780-2013
OI Kendall, Amy/0000-0002-6176-9177
FU US National Institutes of Health (NIH) [R01-GM073770, P50-NS053488,
   P01-AG002132]; NIH National Center for Research Resources (NCRR)
   [S10-RR025037]; NIH Molecular Biophysics Training Grant at the
   University of Illinois at Urbana-Champaign [T32-GM008276]; US National
   Science Foundation Graduate Research Fellowship; Intramural Research
   Program of the Center for Information Technology at NIH; US Department
   of Energy (DOE), Office of Biological and Environmental Research; DOE
   [DE-FG02-07ER46453, DE-FG02-07ER46471]; NIH NCRR [S10-RR011966]; NIH; 
   [T32-AG000255]
FX This study was supported by the US National Institutes of Health (NIH)
   (grants R01-GM073770 to C.M.R., P50-NS053488 to V.M.Y.L. and
   P01-AG002132 to G.S.) and used SSNMR instrumentation procured with the
   support of grant S10-RR025037 (to C.M.R.) from the NIH National Center
   for Research Resources (NCRR). M.D.T., A.J.N. and A.M.B. were supported
   as members of the NIH Molecular Biophysics Training Grant at the
   University of Illinois at Urbana-Champaign (T32-GM008276), and D.J.C. is
   supported by grant T32-AG000255. J.M.C. was supported by a US National
   Science Foundation Graduate Research Fellowship. C.D.S. is supported by
   the Intramural Research Program of the Center for Information Technology
   at NIH. The authors thank J. Wall and B. Lin. (Brookhaven National
   Laboratory) for STEM MPL sample preparation and data collection. The
   Brookhaven National Laboratory STEM was an NIH-supported Resource Center
   (P41-EB2181), and additional support was provided by the US Department
   of Energy (DOE), Office of Biological and Environmental Research. TEM
   images were collected at the Frederick Seitz Materials Research
   Laboratory Central Facilities, University of Illinois, which are
   partially supported by the DOE under grants DE-FG02-07ER46453 and
   DE-FG02-07ER46471. The Voyager-DE STR MALDI TOF mass spectrometer was
   purchased in part with a grant from the NIH NCRR (S10-RR011966). The
   Stanford Synchrotron Radiation Lightsource (SSRL) is a national user
   facility operated by Stanford University on behalf of the DOE, Office of
   Basic Energy Sciences. The SSRL Structural Molecular Biology Program is
   supported by the DOE and the NIH. The authors thank M. Tang (College of
   Staten Island) for helpful discussions.
NR 55
TC 26
Z9 26
U1 20
U2 45
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAY
PY 2016
VL 23
IS 5
BP 409
EP 415
DI 10.1038/nsmb.3194
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DL4UK
UT WOS:000375633100012
PM 27018801
ER

PT J
AU Cellmer, T
   Ferrone, FA
   Eaton, WA
AF Cellmer, Troy
   Ferrone, Frank A.
   Eaton, William A.
TI Universality of supersaturation in protein-fiber formation
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID SICKLE-CELL-DISEASE; HEMOGLOBIN POLYMERIZATION; FETAL-HEMOGLOBIN;
   TRANSITION-STATE; S GELATION; DELAY-TIME; KINETICS; MECHANISM;
   SIMULATIONS; NUCLEATION
AB The thermodynamics and kinetics of the aggregation of sickle-cell hemoglobin into fibers have been studied in great detail under a wide range of solution conditions. The stability of the fiber is measured by the solubility; the kinetics is characterized by a delay before the appearance of fibers. A review of data in the literature shows that there is no correlation of the delay time with fiber stability and only a weak correlation with the initial protein concentration. There is, however, a striking collapse of all the data onto a single universal curve when the delay time is plotted versus the supersaturation, which is the ratio of the initial protein concentration to the solubility, expressed as activities. Collapse onto the same universal curve is also obtained when using delay times calculated from the double-nucleation theoretical model.
C1 [Cellmer, Troy; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Ferrone, Frank A.] Drexel Univ, Dept Phys, Philadelphia, PA 19104 USA.
RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM eaton@helix.nih.gov
FU NIDDK, US National Institutes of Health
FX We thank A. Szabo, E. Henry and J. Hofrichter for discussions and M.
   Clore for helpful comments on the manuscript. Work by T.C. and W.A.E.
   was supported by the intramural research program of NIDDK, US National
   Institutes of Health.
NR 30
TC 1
Z9 1
U1 7
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAY
PY 2016
VL 23
IS 5
BP 459
EP 461
DI 10.1038/nsmb.3197
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DL4UK
UT WOS:000375633100019
PM 27018803
ER

PT J
AU Piknova, B
   Park, JW
   Lam, KK
   Schechter, AN
AF Piknova, Barbora
   Park, Ji Won
   Lam, Kai Kwan (Jeff)
   Schechter, Alan N.
TI Nitrate as a source of nitrite and nitric oxide during exercise
   hyperemia in rat skeletal muscle
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Nitrate; Nitrite; Nitric oxide; Functional hyperemia; Exercise; Skeletal
   muscle
ID XANTHINE-OXIDASE; BLOOD; GENERATION; REDUCTION; BACTERIA; SYNTHASE;
   RELEASE; BIOLOGY; TISSUES; SAMPLES
AB The presence of nitric oxide (NO) synthase enzymes, mainly the NOS1 isoform, in skeletal muscle had been well established; however in the last decade it has been realized that NO may also be produced by reduction of nitrate and tissue nitrite. We have recently shown that rodent skeletal muscle contains unusually high concentrations of nitrate, compared to blood and other tissues, likely produced by oxidation of NOS1-produced NO. In the present study we measured nitrate and nitrite levels in Wistar rat leg tissue before and after acute and chronic exercise of the animals on a treadmill. We found a very large decrease of muscle nitrate levels immediately after exercise accompanied by a transient increase of nitrite levels. A significant decrease in blood nitrate levels accompanied the changes in muscle levels. Using skeletal muscle tissue homogenates we established that xanthine oxidoreductase (XOR) is at least partially responsible for the generation of nitrite and/or NO from nitrate and that this effect is increased by slight lowering of pH and by other processes related to the exercise itself. We hypothesize that the skeletal muscle nitrate reservoir contributes significantly to the generation of nitrite and then, probably via formation of NO, exercise-induced functional hyperemia. A model for these metabolic interconversions in mammals is presented. These reactions could explain the muscle-generated vasodilator causing increased blood flow, with induced contraction, exercise, or hypoxia, postulated more than 100 years ago. Published by Elsevier Ltd.
C1 [Piknova, Barbora; Park, Ji Won; Lam, Kai Kwan (Jeff); Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 9N318, Bethesda, MD 20892 USA.
RP Piknova, B (reprint author), NIDDK, Mol Med Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 9N318, Bethesda, MD 20892 USA.
EM piknovab@mail.nih.gov
FU Intramural NIH HHS [Z99 DK999999]
NR 32
TC 0
Z9 0
U1 5
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
EI 1089-8611
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD MAY 1
PY 2016
VL 55-56
BP 54
EP 61
DI 10.1016/j.niox.2016.03.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DL7LM
UT WOS:000375822200007
PM 27000467
ER

PT J
AU Scott, AD
   Nielles-Vallespin, S
   Ferreira, PF
   McGill, LA
   Pennell, DJ
   Firmin, DN
AF Scott, Andrew D.
   Nielles-Vallespin, Sonia
   Ferreira, Pedro F.
   McGill, Laura-Ann
   Pennell, Dudley J.
   Firmin, David N.
TI The effects of noise in cardiac diffusion tensor imaging and the
   benefits of averaging complex data
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRI; DTI; cardiac; noise; simulations; averaging
ID CARDIOVASCULAR MAGNETIC-RESONANCE; IN-VIVO; FIBER ARCHITECTURE;
   HYPERTROPHIC CARDIOMYOPATHY; LEFT-VENTRICLE; SPIN ECHOES; MRI; MOTION;
   HEART; REPRODUCIBILITY
AB There is growing interest in cardiac diffusion tensor imaging (cDTI), but, unlike other diffusion MRI applications, there has been little investigation of the effects of noise on the parameters typically derived. One method of mitigating noise floor effects when there are multiple image averages, as in cDTI, is to average the complex rather than the magnitude data, but the phase contains contributions from bulk motion, which must be removed first. The effects of noise on the mean diffusivity (MD), fractional anisotropy (FA), helical angle (HA) and absolute secondary eigenvector angle (E2A) were simulated with various diffusion weightings (b values). The effect of averaging complex versus magnitude images was investigated. In vivo cDTI was performed in 10 healthy subjects with b=500, 1000, 1500 and 2000s/mm(2). A technique for removing the motion-induced component of the image phase present in vivo was implemented by subtracting a low-resolution copy of the phase from the original images before averaging the complex images. MD, FA, E2A and the transmural gradient in HA were compared for un-averaged, magnitude- and complex-averaged reconstructions. Simulations demonstrated an over-estimation of FA and MD at low b values and an under-estimation at high b values. The transition is relatively signal-to-noise ratio (SNR) independent and occurs at a higher b value for FA (b=1000-1250s/mm(2)) than MD (b approximate to 250s/mm(2)). E2A is under-estimated at low and high b values with a transition at b approximate to 1000s/mm(2), whereas the bias in HA is comparatively small. The under-estimation of FA and MD at high b values is caused by noise floor effects, which can be mitigated by averaging the complex data. Understanding the parameters of interest and the effects of noise informs the selection of the optimal b values. When complex data are available, they should be used to maximise the benefit from the acquisition of multiple averages. The combination of complex data is also a valuable step towards segmented acquisitions. Copyright (c) 2016 John Wiley & Sons, Ltd.
C1 [Scott, Andrew D.; Nielles-Vallespin, Sonia; Ferreira, Pedro F.; McGill, Laura-Ann; Pennell, Dudley J.; Firmin, David N.] Royal Brompton & Harefield NHS Fdn Trust, Cardiovasc Biomed Res Unit, London, England.
   [Scott, Andrew D.; Nielles-Vallespin, Sonia; Ferreira, Pedro F.; McGill, Laura-Ann; Pennell, Dudley J.; Firmin, David N.] Univ London Imperial Coll Sci Technol & Med, London, England.
   [Scott, Andrew D.; Ferreira, Pedro F.; McGill, Laura-Ann; Pennell, Dudley J.; Firmin, David N.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
   [Nielles-Vallespin, Sonia] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Scott, AD (reprint author), Royal Brompton Hosp, Cardiovasc Biomed Res Unit, Sydney St, London SW3 6NP, England.
EM a.scott@rbht.nhs.uk
OI Pennell, Dudley/0000-0001-5523-1314
FU National Institute for Health Research Cardiovascular Biomedical
   Research Unit of Royal Brompton and Harefield NHS Trust and Imperial
   College, London, UK
FX The work was supported by the National Institute for Health Research
   Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield
   NHS Trust and Imperial College, London, UK.
NR 41
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD MAY
PY 2016
VL 29
IS 5
BP 588
EP 599
DI 10.1002/nbm.3500
PG 12
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA DJ8XA
UT WOS:000374495900006
PM 26891219
ER

PT J
AU Marques, EA
   Gudnason, V
   Sigurdsson, G
   Lang, T
   Johannesdottir, F
   Siggeirsdottir, K
   Launer, L
   Eiriksdottir, G
   Harris, TB
AF Marques, E. A.
   Gudnason, V.
   Sigurdsson, G.
   Lang, T.
   Johannesdottir, F.
   Siggeirsdottir, K.
   Launer, L.
   Eiriksdottir, G.
   Harris, T. B.
TI Are bone turnover markers associated with volumetric bone density, size,
   and strength in older men and women? The AGES-Reykjavik study
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Bone turnover markers; Cortical bone; Osteoporosis; QCT; Trabecular bone
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; CORONARY-ARTERY CALCIUM;
   POSTMENOPAUSAL WOMEN; BIOCHEMICAL MARKERS; ELDERLY-WOMEN; STRUCTURAL
   BASIS; MINERAL DENSITY; CORTICAL BONE; FRACTURE RISK; OSTEOPOROSIS
AB Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density.
   The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN).
   A total of 1745 older individuals (773 men and 972 women, aged 66-92 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression.
   Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1-10 %).
   Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.
C1 [Marques, E. A.; Launer, L.; Harris, T. B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, 7201 Wisconsin Ave,3C-309 Gateway Bldg, Bethesda, MD 20814 USA.
   [Gudnason, V.; Sigurdsson, G.; Siggeirsdottir, K.; Eiriksdottir, G.] Icelandic Heart Assoc, Res Inst, Kopavogur, Iceland.
   [Gudnason, V.; Sigurdsson, G.] Univ Iceland, Reykjavik, Iceland.
   [Sigurdsson, G.] Landspitalinn Univ Hosp, Reykjavik, Iceland.
   [Lang, T.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
   [Johannesdottir, F.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England.
RP Marques, EA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, 7201 Wisconsin Ave,3C-309 Gateway Bldg, Bethesda, MD 20814 USA.
EM elisa.marques@nih.gov
OI Marques, Elisa/0000-0002-6969-6830
FU Intramural NIH HHS; NIA NIH HHS [N01-AG-012100]
NR 45
TC 1
Z9 2
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAY
PY 2016
VL 27
IS 5
BP 1765
EP 1776
DI 10.1007/s00198-015-3442-1
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DJ9WU
UT WOS:000374564800011
PM 26630978
ER

PT J
AU Emery, AC
   Alvarez, RA
   Abboud, P
   Xu, WQ
   Westover, CD
   Eiden, MV
   Eiden, LE
AF Emery, Andrew C.
   Alvarez, Ryan A.
   Abboud, Philip
   Xu, Wenqin
   Westover, Craig D.
   Eiden, Maribeth V.
   Eiden, Lee E.
TI C-terminal amidation of PACAP-38 and PACAP-27 is dispensable for
   biological activity at the PAC1 receptor
SO PEPTIDES
LA English
DT Article
DE Amidation; Cyclic AMP; Neuropeptide; PACAP; PAC1 receptor; Nervous
   system
ID CYCLASE-ACTIVATING POLYPEPTIDE; PEPTIDE ALPHA-AMIDATION;
   ADENYLATE-CYCLASE; SPLICE VARIANTS; NEUROPEPTIDE-Y; RAT-BRAIN;
   SIGNAL-TRANSDUCTION; STROKE MODELS; BLOOD-BRAIN; I RECEPTOR
AB PACAP-27 and PACAP-38 are the exclusive physiological ligands for the mammalian PAC1 receptor. The role of C-terminal amidation of these ligands at that receptor was examined in neuroendocrine cells expressing the PAC1 receptor endogenously and in non-neuroendocrine cells in which the human and rat PAC1 receptors were expressed from stable single-copy genes driven by the CMV promoter, providing stoichiometrically appropriate levels of this Gs-coupled GPCR in order to examine the potency and intrinsic activity of PACAP ligands and their des-amidated congeners. We found that replacement of the C-terminal glycine residues of PACAP-27 and -38 with a free acid; or extension of either peptide with the two to three amino acids normally found at these positions in PACAP processing intermediates in vivo following endoproteolytic cleavage and after exoproteolytic trimming and glycine-directed amidated, were equivalent in potency to the fully processed peptides in a variety of cell-based assays. These included real-time monitoring of cyclic AMP generation in both NS-1 neuroendocrine cells and non-neuroendocrine HEK293 cells; PICA-dependent gene activation in HEK293 cells; and neuritogenesis and cell growth arrest in NS-1 cells. The specific implications for the role of amidation in arming of secretin-related neuropeptides for biological function, and the general implications for neuropeptide-based delivery in the context of gene therapy, are discussed. Published by Elsevier Inc.
C1 [Emery, Andrew C.; Alvarez, Ryan A.; Abboud, Philip; Eiden, Lee E.] NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
   [Xu, Wenqin; Westover, Craig D.; Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Eiden, LE (reprint author), Sect Mol Neurosci, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
FU NIMH Intramural Research Program [ZIAMH002386, ZIAMH002592]; NARSAD from
   the Brain and Behavior Research Foundation [21356]
FX This work was supported by NIMH Intramural Research Program Projects
   ZIAMH002386 (L.E.E.) and ZIAMH002592 (M.V.E.), and by a 2014 NARSAD
   Young Investigator Grant to A.C.E. from the Brain and Behavior Research
   Foundation [Grant 21356].
NR 48
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
EI 1873-5169
J9 PEPTIDES
JI Peptides
PD MAY
PY 2016
VL 79
BP 39
EP 48
DI 10.1016/j.peptides.2016.03.003
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
   Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
   Pharmacology & Pharmacy
GA DJ8RO
UT WOS:000374480400006
PM 26976270
ER

PT J
AU Ross, A
   Yang, L
   Klagholz, SD
   Wehrlen, L
   Bevans, MF
AF Ross, A.
   Yang, L.
   Klagholz, S. D.
   Wehrlen, L.
   Bevans, M. F.
TI The relationship of health behaviors with sleep and fatigue in
   transplant caregivers
SO PSYCHO-ONCOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; TRAUMATIC BRAIN-INJURY; INVENTORY-SHORT FORM;
   OF-THE-LITERATURE; FAMILY CAREGIVERS; INFORMAL CAREGIVERS;
   CHILDHOOD-CANCER; QUALITY INDEX; CARE; SURVIVORS
AB ObjectiveThe burden and psychological impact of providing care to a loved one with cancer is significant and associated with a number of problems including sleep disturbance and fatigue. While engaging in healthy behaviors such as proper nutrition, exercise, and stress reduction may improve sleep and fatigue, few studies have focused on this relationship. The objective of this study is to examine the relationship of health behaviors with sleep quality and fatigue in transplant caregivers.
   MethodsData were analyzed from a cross-sectional survey of 78 caregivers of patients undergoing allogeneic hematopoietic stem cell transplantation. Measures included: Health-Promoting Lifestyle Profile II (HPLP-II), Brief Symptom Inventory (Distress), Caregiver Reaction Assessment (Caregiver Burden), Pittsburgh Sleep Quality Index, and the Multidimensional Fatigue Symptom Inventory Short-Form.
   ResultsControlling for age, gender, BMI, burden and distress, health behaviors predicted sleep quality (B=-0.408, p=0.021) and fatigue (B=-0.966, p<0.001). Stress management (B=-0.450, p=0.001), nutrition (B=-0.249, p=0.048), and interpersonal relationships (B=-0.319, p=0.049) were the HPLP-II subscales that significantly predicted sleep quality; nearly every HPLP-II subscale predicted fatigue.
   ConclusionsDespite the burden and distress associated with caregiving, engaging in healthy behaviors may help to improve sleep and fatigue in transplant caregivers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Ross, A.; Yang, L.; Klagholz, S. D.; Wehrlen, L.; Bevans, M. F.] NIH, Ctr Clin, Dept Nursing, 10 Ctr Dr Room 2B07, Bethesda, MD 20892 USA.
RP Ross, A (reprint author), NIH, Ctr Clin, Dept Nursing, 10 Ctr Dr Room 2B07, Bethesda, MD 20892 USA.
EM rossac@cc.nih.gov
NR 40
TC 0
Z9 0
U1 4
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD MAY
PY 2016
VL 25
IS 5
BP 506
EP 512
DI 10.1002/pon.3860
PG 7
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
   Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA DJ8WQ
UT WOS:000374494700004
PM 26179453
ER

PT J
AU Carrasquillo, JA
   Pandit-Taskar, N
   Chen, CC
AF Carrasquillo, Jorge A.
   Pandit-Taskar, Neeta
   Chen, Clara C.
TI I-131 Metaiodobenzylguanidine Therapy of Pheochromocytoma and
   Paraganglioma
SO SEMINARS IN NUCLEAR MEDICINE
LA English
DT Review
ID HIGH-DOSE I-131-METAIODOBENZYLGUANIDINE; POSITRON-EMISSION-TOMOGRAPHY;
   METASTATIC CARCINOID-TUMORS; LONG-TERM EFFICACY; MALIGNANT
   PHEOCHROMOCYTOMA; NEUROENDOCRINE TUMORS; RADIONUCLIDE THERAPY;
   CATECHOLAMINE TRANSPORTERS; REFRACTORY NEUROBLASTOMA; RESISTANT
   NEUROBLASTOMA
AB Pheochromocytomas and paragangliomas are rare tumors arising from chromaffin cells. Available therapeutic modalities consist of chemotherapy, tyrosine kinase inhibitors, and I-131 metaiodobenzylguanidine (MIBG). I-131 MIBG is taken up via specific receptors and localizes into many but not all pheochromocytomas and paragangliomas. Because these tumors are rare, most therapy studies are retrospective presentations of clinical experience. Numerous retrospective studies and a few prospective studies have shown favorable responses in this disease, including symptomatic, biochemical, and objective responses. In this report, we review the experience of using I-131 MIBG therapy for targeting pheochromocytoma and paragangliomas. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Carrasquillo, Jorge A.; Pandit-Taskar, Neeta] Mem Sloan Kettering, Dept Radiol, Mol Imaging & Therapy Serv, New York, NY USA.
   [Carrasquillo, Jorge A.; Pandit-Taskar, Neeta] Weill Cornell Med Ctr, Dept Radiol, New York, NY USA.
   [Chen, Clara C.] NIH, Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Carrasquillo, JA (reprint author), 1275 York Ave, New York, NY 10065 USA.
EM carrasj1@mskcc.org
OI Carrasquillo, Jorge/0000-0002-8513-5734
NR 119
TC 2
Z9 2
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0001-2998
EI 1558-4623
J9 SEMIN NUCL MED
JI Semin. Nucl. Med.
PD MAY
PY 2016
VL 46
IS 3
BP 203
EP 214
DI 10.1053/j.semnuclmed.2016.01.011
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK1ZH
UT WOS:000374713800004
PM 27067501
ER

PT J
AU Cerritelli, SM
   Crouch, RJ
AF Cerritelli, Susana M.
   Crouch, Robert J.
TI The Balancing Act of Ribonucleotides in DNA
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID IMMUNODEFICIENCY-VIRUS TYPE-1; YEAST REPLICATIVE POLYMERASES; RNASE H2
   COMPLEX; MITOCHONDRIAL-DNA; GENOME INTEGRITY; SACCHAROMYCES-CEREVISIAE;
   REVERSE-TRANSCRIPTASE; TOPOISOMERASE-I; MISMATCH REPAIR; EXCISION-REPAIR
AB The abundance of ribonucleotides in DNA remained undetected until recently because they are efficiently removed by the ribonucleotide excision repair (RER) pathway, a process similar to Okazaki fragment (OF) processing after incision by Ribonuclease H2 (RNase H2). All DNA polymerases incorporate ribonucleotides during DNA synthesis. How many, when, and why they are incorporated has been the focus of intense work during recent years by many labs. In this review, we discuss recent advances in ribonucleotide incorporation by eukaryotic DNA polymerases that suggest an evolutionarily conserved role for ribonucleotides in DNA. We also review the data that indicate that removal of ribonucleotides has an important role in maintaining genome stability.
C1 [Cerritelli, Susana M.; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Format RNA, Div Dev Biol, NIH, Bethesda, MD USA.
RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Format RNA, Div Dev Biol, NIH, Bethesda, MD USA.
EM crouchr@helix.nih.gov
FU NIH
FX We thank Andrei Chabes for providing comments on concentrations of dNTPs
   and rNTPs in S. cerevisiae; Baek Kim for comments on NTP concentrations
   in mammalian cells; David Clark for discussion of nucleosomes; and
   Ariadne Cerritelli for help with figures. This work was supported by the
   Intramural Program of NIH.
NR 84
TC 4
Z9 4
U1 2
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD MAY
PY 2016
VL 41
IS 5
BP 434
EP 445
DI 10.1016/j.tibs.2016.02.005
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DL7HF
UT WOS:000375811100007
PM 26996833
ER

PT J
AU Liu, YJ
   Nie, LM
   Chen, XY
AF Liu, Yajing
   Nie, Liming
   Chen, Xiaoyuan
TI Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications
   Towards Early-Stage Theranostics
SO TRENDS IN BIOTECHNOLOGY
LA English
DT Review
ID MULTISPECTRAL OPTOACOUSTIC TOMOGRAPHY; SEMICONDUCTING POLYMER
   NANOPARTICLES; IN-VIVO; FLOW-CYTOMETRY; COMPUTED-TOMOGRAPHY; SCATTERING
   MEDIA; LYMPH-NODES; MICROSCOPY; THERAPY; RESOLUTION
AB Photoacoustic imaging (PAI) has ushered in a new era of observational biotechnology and has facilitated the exploration of fundamental biological mechanisms and clinical translational applications, which has attracted tremendous attention in recent years. By converting laser into ultrasound emission, PAI combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. This evolutional technique enables multiscale and multicontrast visualization from cells to organs, anatomy to function, and molecules to metabolism with high sensitivity and specificity. The state-of-the-art developments and applications of PAI are described in this review. Future prospects for clinical use are also highlighted. Collectively, PAI holds great promise to drive biomedical applications towards early-stage theranostics.
C1 [Liu, Yajing; Nie, Liming] Xiamen Univ, Sch Publ Hlth, CMITM, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.
   [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Nie, LM (reprint author), Xiamen Univ, Sch Publ Hlth, CMITM, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China.; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM nielm@xmu.edu.cn; shawn.chen@nih.gov
FU National Basic Research Program of China (863 Program) [2015AA020502];
   National Science Foundation of China [81571744, 81301257]; Science
   Foundation of Fujian Province [2014Y2004]; Intramural Research Program
   (IRP), National Institute of Biomedical Imaging and Bioengineering
   (NIBIB), National Institutes of Health (NIH)
FX This work was supported by National Basic Research Program of China (863
   Program 2015AA020502), the National Science Foundation of China
   (81571744, 81301257), Science Foundation of Fujian Province (No.
   2014Y2004), and by the Intramural Research Program (IRP), National
   Institute of Biomedical Imaging and Bioengineering (NIBIB), National
   Institutes of Health (NIH).
NR 96
TC 9
Z9 9
U1 20
U2 62
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0167-7799
J9 TRENDS BIOTECHNOL
JI Trends Biotechnol.
PD MAY
PY 2016
VL 34
IS 5
BP 420
EP 433
DI 10.1016/j.tibtech.2016.02.001
PG 14
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DL7HD
UT WOS:000375810800010
PM 26924233
ER

PT J
AU Burnett, CJ
   Krashes, MJ
AF Burnett, C. Joseph
   Krashes, Michael J.
TI Acute Glucose Response Properties Beyond Feeding
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Editorial Material
ID EXPRESSING NEURONS; INSULIN ACTION; HOMEOSTASIS; LEPTIN
C1 [Burnett, C. Joseph; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
   [Burnett, C. Joseph; Krashes, Michael J.] NIDA, NIH, Baltimore, MD USA.
   [Burnett, C. Joseph] Brown Univ, Brown NIH Grad Partnerships Program, Providence, RI 02912 USA.
RP Krashes, MJ (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.; Krashes, MJ (reprint author), NIDA, NIH, Baltimore, MD USA.
EM michael.krashes@nih.gov
FU Intramural NIH HHS [ZIA DK075087-03, ZIA DK075089-03]
NR 10
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
EI 1471-499X
J9 TRENDS MOL MED
JI Trends Mol. Med
PD MAY
PY 2016
VL 22
IS 5
BP 356
EP 358
DI 10.1016/j.molmed.2016.03.001
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA DL7IJ
UT WOS:000375814100003
PM 27052261
ER

PT J
AU Masdeu, JC
   Dalmau, J
   Berman, KF
AF Masdeu, Joseph C.
   Dalmau, Josep
   Berman, Karen F.
TI NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism
   Uncerlying Psychosis?
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID DORSOLATERAL PREFRONTAL CORTEX; POTASSIUM CHANNEL ANTIBODIES;
   CENTRAL-NERVOUS-SYSTEM; LIMBIC ENCEPHALITIS; CASE SERIES; AUTOIMMUNE
   ENCEPHALOPATHIES; SYNAPTIC PLASTICITY; MESSENGER-RNA; AMPA RECEPTOR;
   SCHIZOPHRENIA
AB Since the early 1990s it has been postulated that hypofunction of N-methyl-D-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. In this opinion article, we review this mechanism as well as data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.
C1 [Masdeu, Joseph C.] Weill Cornell Med Coll, Houston Methodist Neurol Inst, Houston, TX 77030 USA.
   [Masdeu, Joseph C.] Weill Cornell Med Coll, Dept Neurol, Houston, TX 77030 USA.
   [Dalmau, Josep] Univ Barcelona, ICREA IDIBAPS, Hosp Clin, Serv Neurol, Barcelona, Spain.
   [Dalmau, Josep] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
   [Berman, Karen F.] NIMH, Clin & Translat Neurosci Branch, NIH, Intramural Res Program, Bethesda, MD 20892 USA.
RP Masdeu, JC (reprint author), Weill Cornell Med Coll, Houston Methodist Neurol Inst, Houston, TX 77030 USA.; Masdeu, JC (reprint author), Weill Cornell Med Coll, Dept Neurol, Houston, TX 77030 USA.
EM jcmasdeu@houstonmethodist.org
FU Houston Methodist Research Institute; National Institute of Mental
   Health (NIMH) Intramural Research Program; NIH [RO1NS077851,
   RO1MH094741]; FIS; Fundacio la Marato de TV3; McKnight Neuroscience of
   Brain Disorders award; Euroimmun Inc.;  [11/01780]
FX J.C.M. and K.F.B. were supported by the Houston Methodist Research
   Institute and by the National Institute of Mental Health (NIMH)
   Intramural Research Program, respectively; J.D. by NIH grants
   RO1NS077851, RO1MH094741, FIS, 11/01780, Fundacio la Marato de TV3, a
   McKnight Neuroscience of Brain Disorders award and a research grant from
   Euroimmun Inc. Dr Isabel Perez Otano provided valuable comments on the
   manuscript.
NR 97
TC 4
Z9 4
U1 4
U2 6
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD MAY
PY 2016
VL 39
IS 5
BP 300
EP 310
DI 10.1016/j.tins.2016.02.006
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DL6HM
UT WOS:000375740300003
ER

PT J
AU Datta, G
   Nieto, LM
   Davidson, RM
   Mehaffy, C
   Pederson, C
   Dobos, KM
   Strong, M
AF Datta, Gargi
   Nieto, Luisa M.
   Davidson, Rebecca M.
   Mehaffy, Carolina
   Pederson, Caroline
   Dobos, Karen M.
   Strong, Michael
TI Longitudinal whole genome analysis of pre and post drug treatment
   Mycobacterium tuberculosis isolates reveals progressive steps to drug
   resistance
SO TUBERCULOSIS
LA English
DT Article
DE Mycobacterium tuberculosis; Whole genome sequencing; Drug resistance
   progression; Single nucleotide polymorphism; Isoniazid; Rifampin
ID TOXIN-ANTITOXIN SYSTEMS; CATALASE-PEROXIDASE; ISONIAZID RESISTANCE;
   CONFERRING MUTATIONS; SEQUENCING DATA; KATG; DISCOVERY; STRAINS; GENE;
   DNA
AB Tuberculosis (TB) is one of the leading causes of death due to an infectious disease in the world. Understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant TB cases. We have analyzed three pairs of Mycobacterium tuberculosis strains pre-and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. In the rifampicin resistant strain, we confirmed a mutation in rpoB (S450L) that is known to confer resistance to rifampicin. We discovered a novel L101R mutation in the katG gene of an isoniazid resistant strain, which may directly contribute to isoniazid resistance due to the proximity of the mutation to the katG isoniazid-activating site. Another isoniazid resistant strain had a rare mutation in the start codon of katG. We also identified a number of mutations in each longitudinal pair, such as toxineantitoxin mutations that may influence the progression towards resistance or may play a role in compensatory fitness. These findings improve our knowledge of drug resistance progression during therapy and provide a methodology to monitor longitudinal strains using whole genome sequencing, polymorphism comparison, and functional annotation. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Datta, Gargi; Davidson, Rebecca M.; Strong, Michael] NIH, Ctr Genes Environm & Hlth, Denver, CO 80206 USA.
   [Datta, Gargi; Strong, Michael] Univ Colorado, Computat Biosci Program, Denver, CO 80045 USA.
   [Nieto, Luisa M.; Mehaffy, Carolina; Dobos, Karen M.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
   [Pederson, Caroline] ATCC, 10801 Univ Blvd, Manassas, VA 20110 USA.
RP Strong, M (reprint author), Smith Bldg,Room A651,1400 Jackson St, Denver, CO 80206 USA.
EM gargi.datta@ucdenver.edu; luisa.nieto_ramirez@colostate.edu;
   davidsonr@njhealth.org; carolina.mehaffy@colostate.edu;
   cpederson@atcc.org; karen.dobos@colostate.edu; strongm@njhealth.org
RI Dobos, Karen/D-1170-2017; 
OI Dobos, Karen/0000-0001-7115-8524; Datta, Gargi/0000-0002-1314-7824
FU Colorado Bioscience Grant; Boettcher Foundation; Colombian
   Administrative Department of Science, Technology and Innovation
   COLCIENCIAS [512]; American Type Culture Collection (ATCC) fund
   [2010-0516-0005]
FX G.D., R.D. and M.S. were supported by a Colorado Bioscience Grant and
   the Boettcher Foundation Webb Waring grant. L.N., K.D., C.M. and C.P.
   were supported by the Colombian Administrative Department of Science,
   Technology and Innovation COLCIENCIAS with the Francisco Jose de
   Caldas-512 scholarship, and the American Type Culture Collection (ATCC)
   fund #2010-0516-0005.
NR 38
TC 2
Z9 2
U1 4
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
   LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD MAY
PY 2016
VL 98
BP 50
EP 55
DI 10.1016/j.tube.2016.02.004
PG 6
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA DL4DJ
UT WOS:000375583200008
PM 27156618
ER

PT J
AU Baseler, L
   de Wit, E
   Feldmann, H
AF Baseler, L.
   de Wit, E.
   Feldmann, H.
TI A Comparative Review of Animal Models of Middle East Respiratory
   Syndrome Coronavirus Infection
SO VETERINARY PATHOLOGY
LA English
DT Review
DE animal models; common marmosets; dipeptidyl peptidase 4; mice; Middle
   East respiratory syndrome coronavirus; pathogenicity; rabbits;
   respiratory system; review; rhesus macaques; transgenic
ID MERS-COV INFECTION; DIPEPTIDYL PEPTIDASE 4; DROMEDARY CAMELS;
   SAUDI-ARABIA; RHESUS MACAQUES; FAMILY CLUSTER; MOUSE MODEL;
   CLINICAL-FEATURES; UNITED-KINGDOM; SPIKE PROTEIN
AB Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.
C1 [Baseler, L.; de Wit, E.; Feldmann, H.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
   [Baseler, L.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
   [Baseler, L.] Univ Texas MD Anderson Canc Ctr, Dept Vet Med & Surg, Houston, TX 77030 USA.
RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
OI de Wit, Emmie/0000-0002-9763-7758
FU National Institutes of Health, National Institute of Allergy and
   Infectious Diseases; National Institutes of Health Comparative
   Biomedical Scientist Training Program
FX The author( s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This work
   was supported by the Intramural Research Program of the National
   Institutes of Health, National Institute of Allergy and Infectious
   Diseases. Dr Baseler was supported in part by the National Institutes of
   Health Comparative Biomedical Scientist Training Program.
NR 76
TC 1
Z9 1
U1 2
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD MAY
PY 2016
VL 53
IS 3
BP 521
EP 531
DI 10.1177/0300985815620845
PG 11
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA DJ8WB
UT WOS:000374492800003
PM 26869154
ER

PT J
AU Andrews, C
   Operacz, M
   Maes, R
   Kiupel, M
AF Andrews, C.
   Operacz, M.
   Maes, R.
   Kiupel, M.
TI Cross Lineage Rearrangement in Feline Enteropathy-Associated T-cell
   Lymphoma
SO VETERINARY PATHOLOGY
LA English
DT Article
DE feline; gastrointestinal neoplasms; lymphoma; PARR; receptor
   rearrangement; TCRG
ID VARIABLE REGION GENES; MOLECULAR DIAGNOSIS; RECEPTOR GENES;
   IMMUNOGLOBULIN; CLONALITY
AB Feline enteropathy-associated T-cell lymphoma (EATL) type II is characterized by infiltration of the small intestinal mucosa with small T-cells with variable epitheliotropism and is often difficult to differentiate from inflammation. Polymerase chain reaction (PCR) to assess antigen receptor rearrangements (PARR) amplifies the T- (T-cell receptor gamma, TCRG) or B-cell (immunoglobulin heavy chain, IGH) antigen receptor genes and is used to differentiate EATL from inflammation. However, PARR does not determine lymphocyte phenotype, and clonal rearrangement of either or both the TCRG or IGH genes may be detected in neoplastic T-cells. The purpose of this study was to determine the incidence of cross lineage rearrangement in feline EATL type II. Using a diagnostic algorithm combining histology, immunohistochemistry, and PARR testing, 8 of 92 cases diagnosed as EATL type II at Michigan State University between January 2013 and June 2014 showed cross lineage rearrangement (8.7%). PARR for the IGH gene facilitates the diagnosis of cases histologically highly suggestive of EATL type II in which polyclonal rearrangement of the TCRG gene is detected.
C1 [Andrews, C.; Operacz, M.; Maes, R.; Kiupel, M.] Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, 4125 Beaumont Rd, Lansing, MI 48910 USA.
   [Andrews, C.] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Andrews, C (reprint author), Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, 4125 Beaumont Rd, Lansing, MI 48910 USA.
EM caroline.andrews@nih.gov
NR 10
TC 0
Z9 0
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD MAY
PY 2016
VL 53
IS 3
BP 559
EP 562
DI 10.1177/0300985815595518
PG 4
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA DJ8WB
UT WOS:000374492800006
PM 26215761
ER

PT J
AU Willson, CJ
   Flake, GP
   Sills, RC
   Kissling, GE
   Cesta, MF
AF Willson, C. J.
   Flake, G. P.
   Sills, R. C.
   Kissling, G. E.
   Cesta, M. F.
TI Immunohistochemical Expression of Cyclin D1, Cytokeratin 20, and
   Uroplakin III in Proliferative Urinary Bladder Lesions Induced by
   o-Nitroanisole in Fischer 344/N Rats
SO VETERINARY PATHOLOGY
LA English
DT Article
DE cyclin D1; cytokeratin 20; immunohistochemistry; o-nitroanisole; rats;
   urinary bladder; uroplakin III; urothelial carcinoma
ID TRANSITIONAL-CELL CARCINOMAS; UROTHELIAL TUMORS; CARCINOGENESIS; CANCER;
   OVEREXPRESSION; FEATURES; MICE; COWS
AB o-Nitroanisole is an intermediate in the manufacture of azo dyes. In a National Toxicology Program stop-exposure study, o-nitroanisole induced hyperplasia, papillomas, and papillary carcinomas in the urinary bladder of Fischer 344/N rats. o-Nitroanisole was investigated since occupational or environmental exposure to aniline and azo dyes is a risk factor for urinary bladder cancer in humans. The current study describes the morphology of urinary bladder neoplasms seen in rats with respect to those observed in humans. This study also evaluated immunohistochemical expression of the cell cycle-related proteins cyclin D1 and p53 and the differentiation markers cytokeratin 20 and uroplakin III in hyperplastic (n = 11) and neoplastic (n = 6 papillomas, n = 11 carcinomas) lesions of the urinary bladder epithelium from rats treated with o-nitroanisole and in normal (n = 6) urinary bladders from untreated rats. The tumors observed were more similar to the papillary type rather than the muscle-invasive type of urinary bladder cancer in humans. The preneoplastic and neoplastic lesions observed suggest progression from hyperplasia to papilloma to papillary carcinoma. With neoplastic progression (hyperplasia to papilloma to carcinoma), cyclin D1 immunoreactivity progressively increased in intensity, percentage of cells staining, and distribution. Overexpression of p53 was not found. Cytokeratin 20 staining decreased in superficial cells, while uroplakin III staining increased in intermediate and basal cells with progression from hyperplasia to carcinoma. The results are consistent with increased cell cycle dysregulation or proliferation (cyclin D1), decreased differentiation (cytokeratin 20), and abnormal differentiation (uroplakin III) as lesions progress toward malignancy.
C1 [Willson, C. J.; Flake, G. P.; Sills, R. C.; Cesta, M. F.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Willson, C. J.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
   [Kissling, G. E.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Cesta, MF (reprint author), NIEHS, Cellular & Mol Pathol Branch, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA.
EM cesta@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
   Health Sciences
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This
   research was supported by the National Institutes of Health, National
   Institute of Environmental Health Sciences.
NR 33
TC 0
Z9 0
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD MAY
PY 2016
VL 53
IS 3
BP 682
EP 690
DI 10.1177/0300985815603432
PG 9
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA DJ8WB
UT WOS:000374492800024
PM 26319780
ER

PT J
AU Shivva, V
   Cox, PJ
   Clarke, K
   Veech, RL
   Tucker, IG
   Duffull, SB
AF Shivva, Vittal
   Cox, Pete J.
   Clarke, Kieran
   Veech, Richard L.
   Tucker, Ian G.
   Duffull, Stephen B.
TI The Population Pharmacokinetics of D-beta-hydroxybutyrate Following
   Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate
SO AAPS JOURNAL
LA English
DT Article
DE D-beta-hydroxybutyrate; exogenous ketosis; ketone monoester;
   pharmacokinetics; population models
ID KETONE-BODY METABOLISM; XENOPUS-LAEVIS OOCYTES; ALZHEIMERS-DISEASE;
   FASTING HUMANS; KINETICS; BODIES; MODEL; DIET; QUANTIFICATION;
   KETOGENESIS
AB The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the pharmacokinetics (PK) of d-beta-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester). Healthy volunteers (n = 37) were given a single drink of the ketone monoester, following which, 833 blood BHB concentrations were measured. Two formulations and five dose levels of ketone monoester were used. A nonlinear mixed effect modelling approach was used to develop a population PK model. A one compartment disposition model with negative feedback effect on endogenous BHB production provided the best description of the data. Absorption was best described by two consecutive first-order inputs and elimination by dual processes involving first-order (CL = 10.9 L/h) and capacity limited elimination (V (max) = 4520 mg/h). Covariates identified were formulation (on relative oral bioavailable fraction and absorption rate constant) and dose (on relative oral bioavailable fraction). Lean body weight (on first-order clearance) and sex (on apparent volume of distribution) were also significant covariates. The PK of BHB is complicated by complex absorption process, endogenous production and nonlinear elimination. Formulation and dose appear to strongly influence the kinetic profile following ketone monoester administration. Further work is needed to quantify mechanisms of absorption and elimination of ketones for therapeutic use in the form of ketone monoester.
C1 [Shivva, Vittal; Tucker, Ian G.; Duffull, Stephen B.] Univ Otago, Sch Pharm, POB 56, Dunedin 9054, New Zealand.
   [Cox, Pete J.; Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England.
   [Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA.
RP Shivva, V (reprint author), Univ Otago, Sch Pharm, POB 56, Dunedin 9054, New Zealand.
EM vittal.shivva@otago.ac.nz
FU University of Otago, Dunedin, New Zealand
FX Vittal Shivva was supported by a Postgraduate Scholarship, University of
   Otago, Dunedin, New Zealand.
NR 42
TC 1
Z9 1
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAY
PY 2016
VL 18
IS 3
BP 678
EP 688
DI 10.1208/s12248-016-9879-0
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DL2IW
UT WOS:000375458700014
PM 26893218
ER

PT J
AU Cheng, H
   Xie, ZL
   Jones, WP
   Wei, XT
   Liu, ZF
   Wang, DS
   Kulp, SK
   Wang, J
   Coss, CC
   Chen, CS
   Marcucci, G
   Garzon, R
   Covey, JM
   Phelps, MA
   Chan, KK
AF Cheng, Hao
   Xie, Zhiliang
   Jones, William P.
   Wei, Xiaohui Tracey
   Liu, Zhongfa
   Wang, Dasheng
   Kulp, Samuel K.
   Wang, Jiang
   Coss, Christopher C.
   Chen, Ching-Shih
   Marcucci, Guido
   Garzon, Ramiro
   Covey, Joseph M.
   Phelps, Mitch A.
   Chan, Kenneth K.
TI Preclinical Pharmacokinetics Study of R- and S-Enantiomers of the
   Histone Deacetylase Inhibitor, AR-42 (NSC 731438), in Rodents
SO AAPS JOURNAL
LA English
DT Article
DE AR-42; histone deacetylase inhibitor; mouse; pharmacokinetics; rat
ID SUBEROYLANILIDE HYDROXAMIC ACID; ENZYME-INHIBITION; CANCER; CELLS;
   DIFFERENTIATION; MODEL; AGENTS; SAHA
AB AR-42, a new orally bioavailable, potent, hydroxamate-tethered phenylbutyrate class I/IIB histone deacetylase inhibitor currently is under evaluation in phase 1 and 2 clinical trials and has demonstrated activity in both hematologic and solid tumor malignancies. This report focuses on the preclinical characterization of the pharmacokinetics of AR-42 in mice and rats. A high-performance liquid chromatography-tandem mass spectrometry assay has been developed and applied to the pharmacokinetic study of the more active stereoisomer, S-AR-42, when administered via intravenous and oral routes in rodents, including plasma, bone marrow, and spleen pharmacokinetics (PK) in CD2F1 mice and plasma PK in F344 rats. Oral bioavailability was estimated to be 26 and 100% in mice and rats, respectively. R-AR-42 was also evaluated intravenously in rats and was shown to display different pharmacokinetics with a much shorter terminal half-life compared to that of S-AR-42. Renal clearance was a minor elimination pathway for parental S-AR-42. Oral administration of S-AR-42 to tumor-bearing mice demonstrated high uptake and exposure of the parent drug in the lymphoid tissues, spleen, and bone marrow. This is the first report of the pharmacokinetics of this novel agent, which is now in early phase clinical trials.
C1 [Cheng, Hao; Xie, Zhiliang; Jones, William P.; Liu, Zhongfa; Wang, Dasheng; Kulp, Samuel K.; Coss, Christopher C.; Chen, Ching-Shih; Marcucci, Guido; Phelps, Mitch A.; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, 500 W 12th Ave, Columbus, OH 43210 USA.
   [Wei, Xiaohui Tracey] Sanofi Aventis, Malvern, PA USA.
   [Wang, Jiang; Marcucci, Guido; Garzon, Ramiro; Phelps, Mitch A.; Chan, Kenneth K.] Ohio State Univ, Comprehens Canc, Columbus, OH 43210 USA.
   [Marcucci, Guido; Garzon, Ramiro] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
   [Covey, Joseph M.; Chan, Kenneth K.] Natl Canc Inst, Rockville, MD USA.
   [Marcucci, Guido] Gehr Family Ctr, Leukemia Res Hematologist Malignancies Inst City, Duarte, CA 90010 USA.
RP Phelps, MA; Chan, KK (reprint author), Ohio State Univ, Coll Pharm, 500 W 12th Ave, Columbus, OH 43210 USA.; Phelps, MA; Chan, KK (reprint author), Ohio State Univ, Comprehens Canc, Columbus, OH 43210 USA.; Chan, KK (reprint author), Natl Canc Inst, Rockville, MD USA.
EM phelps.32@osu.edu; chan.56@osu.edu
RI Garzon, Ramiro/E-3104-2011
FU National Cancer Institute, National Institutes of Health; 
   [NCI-N01-CM-52205];  [NCI-RO1-CA158350]
FX This study is supported by NCI-N01-CM-52205 (KKC) and NCI-RO1-CA158350
   (RG). This work has been funded in whole or in part with federal funds
   from 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 24
TC 1
Z9 1
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAY
PY 2016
VL 18
IS 3
BP 737
EP 745
DI 10.1208/s12248-016-9876-3
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DL2IW
UT WOS:000375458700019
PM 26943915
ER

PT J
AU Hosaka, M
   Fujisaki, S
   Masakane, A
   Hattori, J
   Shiino, T
   Gatanaga, H
   Shigemi, U
   Okazaki, R
   Hachiya, A
   Matsuda, M
   Ibe, S
   Iwatani, Y
   Yokomaku, Y
   Sugiura, W
AF Hosaka, Masumi
   Fujisaki, Seiichiro
   Masakane, Aki
   Hattori, Junko
   Shiino, Teiichiro
   Gatanaga, Hiroyuki
   Shigemi, Urara
   Okazaki, Reiko
   Hachiya, Atsuko
   Matsuda, Masakazu
   Ibe, Shiro
   Iwatani, Yasumasa
   Yokomaku, Yoshiyuki
   Sugiura, Wataru
CA Japanese Drug Resistance HIV-1 Sur
TI HIV-1 CRF01_AE and Subtype B Transmission Networks Crossover: A New AE/B
   Recombinant Identified in Japan
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID MODEL SELECTION; FORM; MALAYSIA; SURVEILLANCE; LIKELIHOOD; EMERGENCE;
   CRF15-01B; CRF33-01B; THAILAND; TRENDS
AB The major circulating HIV-1 strains in Japan have been subtype B (B) followed by CRF01_AE (AE) in newly diagnosed HIV/AIDS cases. These two subtypes have distinct epidemiological characteristics; B predominates in men who have sex with men, while AE is observed mostly in heterosexuals engaging in high-risk sex. However, transmission networks of these two high-risk populations appear to be crossing over and diffusing. Here we report the emergence of previously unidentified HIV-1 AE/B recombinants in Japan. We initially identified 13 cases with discordant subtyping results with AE (gag MA)/B (pol PR-RT)/AE (env C2V3) by molecular phylogenetic analysis of 1,070 cases who visited Nagoya Medical Center from 1997 to 2012. Genetic characterization of full-length sequences demonstrated that they shared an identical recombinant structure, and was designated as CRF69_01B by the Los Alamos HIV National Laboratory. By reviewing gag, pol, and env sequences collected in the Japanese Drug Resistance HIV-1 Surveillance Network, we found five other CRF69_01B probable cases from different areas in Japan, suggesting that the strain is transmitted widely throughout the country. The time of the most recent common ancestor analyses estimated that CRF69_01B emerged between 1991 and 1995, soon after AE was introduced from neighboring countries in the mid-1990s. Understanding the current epidemic strains is important for the diagnosis and treatment of HIV/AIDS, as well as for the development of globally effective HIV vaccines.
C1 [Hosaka, Masumi; Fujisaki, Seiichiro; Hattori, Junko; Shigemi, Urara; Okazaki, Reiko; Hachiya, Atsuko; Matsuda, Masakazu; Ibe, Shiro; Iwatani, Yasumasa; Yokomaku, Yoshiyuki; Sugiura, Wataru] Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan.
   [Masakane, Aki] Yamaguchi Univ, Dept Clin Lab, Yamaguchi, Japan.
   [Shiino, Teiichiro] Natl Inst Infect Dis, Infect Dis Surveillance Ctr, Tokyo, Japan.
   [Gatanaga, Hiroyuki] Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo, Japan.
   [Iwatani, Yasumasa; Sugiura, Wataru] Nagoya Univ, Grad Sch Med, Div Basic Med, Nagoya, Aichi 4648601, Japan.
   [Fujisaki, Seiichiro] Natl Inst Infect Dis, Ctr Influenza Virus Res, Lab Influenza Virus Surveillance, Tokyo, Japan.
   [Hattori, Junko] NCI, HIV Dynam & Replicat Program, NIH, Bethesda, MD 20892 USA.
   [Ibe, Shiro] Kitasato Otsuka Biomed Assay Labs Co Ltd, Dept Res & Dev, Sagamihara, Kanagawa, Japan.
   [Sugiura, Wataru] GlaxoSmithKline KK, Tokyo, Japan.
RP Sugiura, W (reprint author), GlaxoSmithKline KK, Tokyo, Japan.; Sugiura, W (reprint author), GlaxoSmithKline, GSK Bldg 4-6-15, Sendagaya, Shibuya 1518566, Japan.
EM taru1600@me.com
FU Ministry of Health, Labour, and Welfare of Japan [H25-AIDS-004]
FX We are grateful to all the patients who participated in our surveillance
   study. We thank Dr. Kiyoto Tsuchiya and Dr. Masako Nishizawa for kindly
   providing plasma/RNA samples. We also thank Dr. Brian Foley, Dr. Bette
   Korber, and editors of the Los Alamos HIV sequence database for
   discussing our data and naming the new HIV-1 circulating recombinant
   form. We greatly thank Ms. Claire Baldwin for her help in preparing the
   article. This study was supported by a Grant-in-Aid for AIDS research
   from the Ministry of Health, Labour, and Welfare of Japan
   (H25-AIDS-004). The funder had no role in the study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 34
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 2016
VL 32
IS 5
BP 412
EP 419
DI 10.1089/aid.2015.0192
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DK3PG
UT WOS:000374828900002
PM 26571151
ER

PT J
AU Townsend, K
   Meissner, EG
   Sidharthan, S
   Sampson, M
   Remaley, AT
   Tang, L
   Kohli, A
   Osinusi, A
   Masur, H
   Kottilil, S
AF Townsend, Kerry
   Meissner, Eric G.
   Sidharthan, Sreetha
   Sampson, Maureen
   Remaley, Alan T.
   Tang, Lydia
   Kohli, Anita
   Osinusi, Anu
   Masur, Henry
   Kottilil, Shyam
TI Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C
   Virus-Coinfected Subjects Results in Increased Serum Low-Density
   Lipoprotein Concentration
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; CARDIOVASCULAR RISK; CHRONIC HCV; GENOTYPE 1;
   INFECTION; SOFOSBUVIR; DISEASE; ASSOCIATION; ABNORMALITIES; LIPIDS
AB Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects.
C1 [Townsend, Kerry; Meissner, Eric G.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Meissner, Eric G.; Osinusi, Anu] Med Univ S Carolina, Dept Microbiol & Immunol, Div Infect Dis, Charleston, SC 29425 USA.
   [Meissner, Eric G.; Sidharthan, Sreetha; Kohli, Anita; Masur, Henry] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
   [Sampson, Maureen] NCI, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
   [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Tang, Lydia; Osinusi, Anu; Kottilil, Shyam] Univ Maryland, Div Infect Dis, Inst Human Virol, Baltimore, MD 21201 USA.
   [Kohli, Anita] Creighton Univ, Sch Med, Dept Hepatol, St Josephs Hosp, Phoenix, AZ USA.
   [Kohli, Anita] Creighton Univ, Sch Med, Dept Hepatol, Med Ctr, Phoenix, AZ USA.
   [Osinusi, Anu] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
RP Kottilil, S (reprint author), 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; Critical Care
   Medicine Department; Clinical Research Center of the National Institutes
   of Health
FX This study was funded by the Intramural Research Programs of the
   National Institute of Allergy and Infectious Diseases, the Critical Care
   Medicine Department, and the Clinical Research Center of the National
   Institutes of Health.
NR 41
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAY
PY 2016
VL 32
IS 5
BP 456
EP 462
DI 10.1089/aid.2015.0170
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DK3PG
UT WOS:000374828900008
PM 26559180
ER

PT J
AU Gowin, JL
   Vatsalya, V
   Westman, JG
   Schwandt, ML
   Bartlett, S
   Heilig, M
   Momenan, R
   Ramchandani, VA
AF Gowin, Joshua L.
   Vatsalya, Vatsalya
   Westman, Jonathan G.
   Schwandt, Melanie L.
   Bartlett, Selena
   Heilig, Markus
   Momenan, Reza
   Ramchandani, Vijay A.
TI The Effect of Varenicline on the Neural Processing of Fearful Faces and
   the Subjective Effects of Alcohol in Heavy Drinkers
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol; Intravenous Infusion; Heavy Drinkers; Faces Task; Amygdala
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; NATIONAL EPIDEMIOLOGIC SURVEY;
   RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; PARTIAL AGONIST;
   YOUNG-ADULTS; INTRAVENOUS ALCOHOL; AMYGDALA REACTIVITY; FACIAL
   EXPRESSIONS; RESPONSES
AB Background: Pharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an 42-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored.
   Methods: In this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2 mg/d) or placebo. After 2 weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80 mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined.
   Results: Results indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90 days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol.
   Conclusions: Our results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.
C1 [Gowin, Joshua L.; Vatsalya, Vatsalya; Westman, Jonathan G.; Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Div Intramural Clin & Biol Res, Bethesda, MD USA.
   [Schwandt, Melanie L.] NIAAA, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA.
   [Momenan, Reza] NIAAA, Clin Neuroimaging Res Core, Div Intramural Clin & Biol Res, Bethesda, MD USA.
   [Vatsalya, Vatsalya] Univ Louisville, Louisville, KY 40292 USA.
   [Vatsalya, Vatsalya] Robley Rex VAMC, Louisville, KY USA.
   [Bartlett, Selena] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Translat Res Inst, Brisbane, Qld 4001, Australia.
   [Heilig, Markus] Linkoping Univ, Dept Clin & Expt Med, Ctr Social & Affect Neurosci, Linkoping, Sweden.
RP Ramchandani, VA (reprint author), 10 Ctr Dr,Rm 2-2352, Bethesda, MD 20892 USA.
EM vijayr@mail.nih.gov
RI Bartlett, Selena/J-1345-2012; Schwandt, Melanie/L-9866-2016
OI Bartlett, Selena/0000-0002-1741-3958; 
FU NIAAA Division of Intramural Clinical and Biological Research
   [Z1AAA000466]; Indiana Alcohol Research Center [NIH P60 AA007611]
FX This study was supported by the NIAAA Division of Intramural Clinical
   and Biological Research (Z1AAA000466). Medication supply was provided by
   Pfizer Inc. under agreement with Dr. Bartlett. Development of the CAIS
   software used for the IV-ASA session was supported by Sean O'Connor, MD,
   at the Indiana Alcohol Research Center (NIH P60 AA007611).
NR 56
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAY
PY 2016
VL 40
IS 5
BP 979
EP 987
DI 10.1111/acer.13046
PG 9
WC Substance Abuse
SC Substance Abuse
GA DK5WY
UT WOS:000374993100008
PM 27062270
ER

PT J
AU Koren, G
   Hankins, GDV
   Clark, S
   Caritis, SN
   Miodovnik, M
   Umans, JG
   Mattison, DR
AF Koren, Gideon
   Hankins, Gary D. V.
   Clark, Shannon
   Caritis, Steve N.
   Miodovnik, Menachem
   Umans, Jason G.
   Mattison, Donald R.
TI Effectiveness of doxylamine-pyridoxine for morning sickness
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
C1 [Koren, Gideon] Hosp Sick Children, Motherisk Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
   [Koren, Gideon] Univ Toronto, Toronto, ON, Canada.
   [Hankins, Gary D. V.; Clark, Shannon; Caritis, Steve N.; Miodovnik, Menachem; Umans, Jason G.; Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child & Human De, Obstetr Pharmacol Res Unit Network, Bethesda, MD USA.
   [Hankins, Gary D. V.; Clark, Shannon] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
   [Caritis, Steve N.] Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA.
   [Miodovnik, Menachem; Umans, Jason G.] Washington Hosp Ctr, Dept Obstet, Washington, DC 20010 USA.
   [Miodovnik, Menachem; Umans, Jason G.] Washington Hosp Ctr, Dept Gynecol, Washington, DC 20010 USA.
   [Miodovnik, Menachem; Umans, Jason G.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
RP Koren, G (reprint author), Hosp Sick Children, Motherisk Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.; Koren, G (reprint author), Univ Toronto, Toronto, ON, Canada.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 2016
VL 214
IS 5
BP 664
EP 666
DI 10.1016/j.ajog.2016.01.186
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DL2GR
UT WOS:000375452100037
PM 26844757
ER

PT J
AU Bailit, JL
   Grobman, WA
   Rice, MM
   Wapner, RJ
   Reddy, UM
   Varner, MW
   Thorp, JM
   Caritis, SN
   Iams, JD
   Saade, G
   Rouse, DJ
   Tolosa, JE
AF Bailit, Jennifer L.
   Grobman, William A.
   Rice, Madeline Murguia
   Wapner, Ronald J.
   Reddy, Uma M.
   Varner, Michael W.
   Thorp, John M., Jr.
   Caritis, Steve N.
   Iams, Jay D.
   Saade, George
   Rouse, Dwight J.
   Tolosa, Jorge E.
CA Eunice Kennedy Shriver Natl Inst C
TI Evaluation of delivery options for second-stage events
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE forceps; operative vaginal delivery; second stage of labor; vacuum
ID NEONATAL INTRACRANIAL INJURY; SPONTANEOUS VAGINAL DELIVERY; FORCEPS
   DELIVERY; CESAREAN DELIVERY; NULLIPAROUS WOMEN; TERM PREGNANCIES;
   VACUUM; MODE; RESIDENCY; OUTCOMES
AB BACKGROUND: Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery vs cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean vs operative vaginal delivery.
   OBJECTIVE: Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps vs cesarean delivery) in patients needing second-stage assistance at a fetal station of +2 or below.
   STUDY DESIGN: We conducted secondary analysis of an observational obstetric cohort in 25 academically affiliated US hospitals over a 3-year period. A subset of >= 37 weeks, nonanomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, nonreassuring fetal status, labor dystocia, or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay >= 3 days beyond mother's, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third-and fourth-degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the 3 attempted modes of delivery. Odds ratios (OR) were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified.
   RESULTS: In all, 2531 women met inclusion criteria. No difference in the neonatal composite outcome was observed between groups. Vacuum attempt was associated with the lowest frequency of maternal complications (postpartum infection 0.2% vs 0.9% forceps vs 5.3% cesarean, postpartum hemorrhage 1.4% vs 2.8% forceps vs 3.8% cesarean), except for severe lacerations (19.1% vs 33.8% forceps vs 0% cesarean). When confounders were taken into account, both forceps (OR, 0.16; 95% confidence interval, 0.05-0.49) and vacuum (OR, 0.04; 95% confidence interval, 0.01-0.17) were associated with a significantly lower odds of postpartum infection. The neonatal composite and postpartum hemorrhage were not significantly different between modes of attempted delivery. Cesarean occurred in 6.4% and 4.4% of attempted vacuum and forceps groups (P = .04).
   CONCLUSION: In patients needing second-stage delivery assistance with a station of +2 or below, attempted operative vaginal delivery was associated with a lower frequency of postpartum infection, but higher frequency of severe lacerations.
C1 [Bailit, Jennifer L.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet, Cleveland, OH USA.
   [Bailit, Jennifer L.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Gynecol, Cleveland, OH USA.
   [Grobman, William A.] Northwestern Univ, Prentice Womens Hosp, Chicago, IL 60611 USA.
   [Rice, Madeline Murguia] George Washington Univ, Ctr Biostat, Washington, DC USA.
   [Wapner, Ronald J.] Columbia Univ, New York, NY USA.
   [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Varner, Michael W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
   [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
   [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
   [Saade, George] Univ Texas Med Branch, Galveston, TX 77555 USA.
   [Rouse, Dwight J.] Brown Univ, Providence, RI 02912 USA.
   [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Bailit, JL (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet, Cleveland, OH USA.; Bailit, JL (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Gynecol, Cleveland, OH USA.
EM jbailit@metrohealth.org
RI Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) [HD21410, HD27869, HD27915, HD27917, HD34116,
   HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485,
   HD53097, HD53118]; National Center for Research Resources [UL1 RR024989,
   5UL1 RR025764]
FX The project described was supported by grants from the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development (NICHD)
   (HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500,
   HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118) and the
   National Center for Research Resources (UL1 RR024989; 5UL1 RR025764).
   Comments and views of the authors do not necessarily represent views of
   the NICHD.
NR 16
TC 1
Z9 1
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 2016
VL 214
IS 5
AR 638.e1-e10
DI 10.1016/j.ajog.2015.11.007
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DL2GR
UT WOS:000375452100022
PM 26596236
ER

PT J
AU Korzeniewski, SJ
   Romero, R
   Chaiworapongsa, T
   Chaemsaithong, P
   Kim, CJ
   Kim, YM
   Kim, JS
   Yoon, BH
   Hassan, SS
   Yeo, L
AF Korzeniewski, Steven J.
   Romero, Roberto
   Chaiworapongsa, Tinnakorn
   Chaemsaithong, Piya
   Kim, Chong Jai
   Kim, Yeon Mee
   Kim, Jung-Sun
   Yoon, Bo Hyun
   Hassan, Sonia S.
   Yeo, Lami
TI Maternal plasma angiogenic index-1 (placental growth factor/soluble
   vascular endothelial growth factor receptor-1) is a biomarker for the
   burden of placental lesions consistent with uteroplacental
   underperfusion: a longitudinal case-cohort study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE acute atherosis; basal plate; fetal death; intervillous fibrin;
   persistent muscularization of the arteries; placental pathology;
   preeclampsia; preterm delivery; small for gestational age; soluble
   Flt-1; syncytial knot; villous infarction
ID FOR-GESTATIONAL-AGE; PRETERM PREMATURE RUPTURE; LATE-ONSET PREECLAMPSIA;
   EARLY HUMAN-PREGNANCY; FETAL-GROWTH; ACUTE ATHEROSIS; SPIRAL ARTERIES;
   SUSPECTED PREECLAMPSIA; TYROSINE KINASE-1; SOLUBLE ENDOGLIN
AB BACKGROUND: Placental lesions consistent with maternal vascular underperfusion (MVU) are thought to be pathogenically linked to preeclampsia, small-for-gestational-age newborns, fetal death, and spontaneous preterm labor and delivery; yet, these lesions cannot be diagnosed antenatally. We previously reported that patients with such conditions and lesions have an abnormal profile of the angiogenic placental growth factor (PlGF) and antiangiogenic factors (eg, soluble vascular endothelial growth factor receptor [sVEGFR]-1).
   OBJECTIVE: The objectives of this study were to: (1) examine the relationship between the maternal plasma PlGF/sVEGFR-1 concentration ratio (referred to herein as angiogenic index-1) and the burden of histologic placental features consistent with MVU; and (2) test the hypothesis that angiogenic index-1 can identify patients in the midtrimester who are destined to deliver before 34 weeks of gestation with multiple (ie, >= 3) histologic placental features consistent with MVU.
   STUDY DESIGN: A 2-stage case-cohort sampling strategy was used to select participants from among 4006 women with singleton gestations enrolled from 2006 through 2010 in a longitudinal study. Maternal plasma angiogenic index-1 ratios were determined using enzyme-linked immunosorbent assays. Placentas underwent histologic examination according to standardized protocols by experienced pediatric pathologists who were blinded to clinical diagnoses and pregnancy outcomes. The diagnosis of lesions consistent with MVU was made using criteria proposed by the Perinatal Section of the Society for Pediatric Pathology. Weighted analyses were performed to reflect the parent cohort; "n*" is used to reflect weighted frequencies.
   RESULTS: (1) Angiogenic index-1 (PlGF/sVEGFR-1) concentration ratios were determined in 7560 plasma samples collected from 1499 study participants; (2) the prevalence of lesions consistent with MVU was 21% (n* = 833.9/3904) and 27% (n* = 11.4/42.7) of women with >= 3 MVU lesions delivered before 34 weeks of gestation; (3) a low angiogenic index-1 (<2.5th quantile for gestational age) in maternal plasma samples obtained within 48 hours of delivery had a sensitivity of 73% (n* = 8.3/11.4; 95% confidence interval [CI], 47-98%), a specificity of 94% (n* = 3130.9/3316.2; 95% CI, 94-95%), a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29 in the identification of patients who delivered placentas with >= 3 MVU lesions at <34 weeks; (4) prospectively, at 20-23 weeks of gestation, a maternal plasma concentration of angiogenic index-1 <2.5th quantile identified 70% (n* = 7.2/10.3; 95% CI, 42-98%) of patients who delivered placentas with >= 3 MVU lesions before 34 weeks (specificity, 97% [n* = 2831.3/2918; 95% CI, 96-98%]; positive likelihood ratio, 23; negative likelihood ratio, 0.31); and (5) among women without obstetrical complications who delivered at term, angiogenic index-1 was lower in women with than without placental lesions consistent with MVU (P < .05).
   CONCLUSION: Maternal plasma angiogenic index-1 (PlGF/sVEGFR-1) is the first biomarker for the burden of placental lesions consistent with MVU. We propose that an accumulation of these lesions in placentas delivered before 34 weeks is a histologic counterpart of an antiangiogenic profile.
C1 [Korzeniewski, Steven J.; Romero, Roberto; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Yoon, Bo Hyun; Hassan, Sonia S.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
   [Korzeniewski, Steven J.; Romero, Roberto; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Yoon, Bo Hyun; Hassan, Sonia S.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
   [Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
   [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
   [Korzeniewski, Steven J.; Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
   [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
   [Kim, Chong Jai] Univ Ulsan, Coll Med, Dept Pathol, Seoul, South Korea.
   [Kim, Yeon Mee] Inje Univ, Coll Med, Dept Pathol, Haeundae Paik Hosp, Busan, South Korea.
   [Kim, Yeon Mee] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Daegu, South Korea.
   [Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
   [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
RP Korzeniewski, SJ; Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.; Korzeniewski, SJ; Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.; Korzeniewski, SJ (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.; Romero, R (reprint author), Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
EM skorzeni@med.wayne.edu; romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (NICHD), National Institutes of Health (NIH), Department of Health and
   Human Services; NICHD, NIH [HHSN275201300006C]
FX This research was supported, in part, by the Perinatology Research
   Branch, Division of Intramural Research, Eunice Kennedy Shriver National
   Institute of Child Health and Human Development (NICHD), National
   Institutes of Health (NIH), Department of Health and Human Services,
   and, in part, with federal funds from NICHD, NIH under contract no.
   HHSN275201300006C.
NR 183
TC 2
Z9 2
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAY
PY 2016
VL 214
IS 5
AR 629.e1-e17
DI 10.1016/j.ajog.2015.11.015
PG 17
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DL2GR
UT WOS:000375452100019
PM 26688491
ER

PT J
AU McDonnold, M
   Mele, LM
   Myatt, L
   Hauth, JC
   Leveno, KJ
   Reddy, UM
   Mercer, BM
AF McDonnold, Mollie
   Mele, Lisa M.
   Myatt, Leslie
   Hauth, John C.
   Leveno, Kenneth J.
   Reddy, Uma M.
   Mercer, Brian M.
CA Eunice Kennedy Shriver Natl Inst
TI Waist-to-Hip Ratio versus Body Mass Index as Predictor of
   Obesity-Related Pregnancy Outcomes
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE obesity; waist-to-hip ratio; cesarean delivery; large-for-gestational
   age
ID RISK-FACTORS; CARDIOVASCULAR EVENTS; NEWBORN WEIGHT; MACROSOMIA;
   CIRCUMFERENCE; WOMEN; ASSOCIATION; TRIGLYCERIDE; PREVALENCE
AB Objective In nonpregnant populations the waist-to-hip ratio (WHR) is a better predictor of obesity-related outcomes than body mass index (BMI). Our objective was to determine, in pregnancy, the relationship between these measures of obesity, and large-for-gestational age (LGA) and cesarean delivery (CD).
   Methods This is a secondary analysis of data from the Combined Antioxidant and Preeclampsia Prediction Study. Women with a WHR of >= 0.85 and 0.80 to 0.84 at 9 to 16 weeks gestation were compared with those with a WHR < 0.80. Women with early pregnancy BMI >= 30.0 kg/m(2) (obese) and 25.0 to 29.9 kg/m(2) (overweight) were compared with those < 25.0 kg/m(2). LGA was defined as > 90% by Alexander nomogram. Univariable analysis, logistic regression, and receiver operating characteristic curves were used.
   Results Data from 2,276 women were analyzed. After correcting for potential confounders, only BMI >= 30 was significantly associated with LGA (adjusted odds ratio [aOR]: 2.07, 1.35-3.16) while BMI 25.0-29.9 (aOR: 1.5, 0.98-2.28), WHR 0.8-0.84 (aOR: 1.33, 0.83-2.13), and WHR >= 0.85 (aOR: 1.05, 0.67-1.65) were not. Risk for CD was increased for women with elevated WHR and with higher BMI compared with normal.
   Conclusion WHR is not associated with LGA. While BMI performed better than WHR, neither was a strong predictor of LGA or need for CD in low-risk nulliparous women.
C1 [McDonnold, Mollie] Univ Texas Galveston, Med Ctr, Dept Obstet & Gynecol, Galveston, TX USA.
   [Mele, Lisa M.] George Washington Univ, Biostat Ctr, Washington, DC USA.
   [Myatt, Leslie] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA.
   [Hauth, John C.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
   [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
   [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA.
RP McDonnold, M (reprint author), Austin Maternal Fetal Med, 12200 Renfert Way Suite G3, Austin, TX 78758 USA.
EM mmcdonnold@gmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) [HD34208, HD27869, HD40485, HD40560, HD40544,
   HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860,
   HD53118, HD53097, HD27917, HD36801]; National Heart, Lung, and Blood
   Institute (NHLBI); National Center for Research Resources (NCRR) [M01
   RR00080, UL1 RR024153, UL1 RR024989]
FX The project described was supported by grants from the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development (NICHD)
   (HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410,
   HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917,
   and HD36801); the National Heart, Lung, and Blood Institute (NHLBI); and
   the National Center for Research Resources (NCRR) (M01 RR00080, UL1
   RR024153, UL1 RR024989) and its contents do not necessarily represent
   the official views of NICHD, NHLBI, NCRR, or National Institute of
   Health.
NR 31
TC 0
Z9 0
U1 0
U2 0
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAY
PY 2016
VL 33
IS 6
BP 618
EP 623
DI 10.1055/s-0035-1569986
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA DK7TY
UT WOS:000375129800015
PM 26788786
ER

PT J
AU Garantziotis, S
   Brezina, M
   Castelnuovo, P
   Drago, L
AF Garantziotis, Stavros
   Brezina, Martin
   Castelnuovo, Paolo
   Drago, Lorenzo
TI The role of hyaluronan in the pathobiology and treatment of respiratory
   disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Review
DE asthma; bacterial biofilm; chronic obstructive pulmonary disease; cystic
   fibrosis; hyaluronan; inflammation; respiratory tract diseases
ID MOLECULAR-WEIGHT HYALURONAN; INTER-ALPHA-INHIBITOR; PULMONARY
   ARTERIAL-HYPERTENSION; EXERCISE-INDUCED BRONCHOCONSTRICTION;
   PLASMINOGEN-ACTIVATOR INHIBITOR-1; NEBULIZED HYPERTONIC SALINE;
   CHEMOKINE GENE-EXPRESSION; LUNG ALLOGRAFT-REJECTION; ENDOSCOPIC SINUS
   SURGERY; CYSTIC-FIBROSIS PATIENTS
AB Hyaluronan, a ubiquitous naturally occurring glycosaminoglycan, is a major component of the extracellular matrix, where it participates in biological processes that include water homeostasis, cell-matrix signaling, tissue healing, inflammation, angiogenesis, and cell proliferation and migration. There are emerging data that hyaluronan and its degradation products have an important role in the pathobiology of the respiratory tract. We review the role of hyaluronan in respiratory diseases and present evidence from published literature and from clinical practice supporting hyaluronan as a novel treatment for respiratory diseases. Preliminary data show that aerosolized exogenous hyaluronan has beneficial activity against airway inflammation, protects against bronchial hyperreactivity and remodeling, and disrupts the biofilm associated with chronic infection. This suggests a role in airway diseases with a predominant inflammatory component such as rhinosinusitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis, and primary ciliary dyskinesia. The potential for hyaluronan to complement conventional therapy will become clearer when data are available from controlled trials in larger patient populations.
C1 [Garantziotis, Stavros] NIEHS, Clin Res Program, NIH, 111TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
   [Brezina, Martin] Univ Hosp Bratislava, Clin Pediat Pneumol & Phthisiol, Bratislava, Slovakia.
   [Castelnuovo, Paolo] Univ Insubria, Osped Circolo, Fdn Macchi, Dept Otorhinolaryngol Head & Neck Surg, Varese, Italy.
   [Drago, Lorenzo] Univ Milan, IRCCS Galeazzi Orthopaed Inst, Dept Biomed Sci Hlth, Lab Clin Chem & Microbiol, Milan, Italy.
RP Garantziotis, S (reprint author), NIEHS, 111TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM garantziotis@niehs.nih.gov
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
FU Division of Intramural Research, National Institute of Environmental
   Health Sciences, National Institutes of Health (NIH)
FX S. Garantziotis' research is funded by the Division of Intramural
   Research, National Institute of Environmental Health Sciences, National
   Institutes of Health (NIH).
NR 105
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Z9 1
U1 2
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD MAY 1
PY 2016
VL 310
IS 9
BP L785
EP L795
DI 10.1152/ajplung.00168.2015
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA DK7PB
UT WOS:000375117100001
PM 26747781
ER

PT J
AU Marenco, S
   Meyer, C
   Kuo, S
   van der Veen, JW
   Shen, J
   DeJong, K
   Barnett, AS
   Apud, JA
   Dickinson, D
   Weinberger, DR
   Berman, KF
AF Marenco, Stefano
   Meyer, Christian
   Kuo, Susan
   van der Veen, Jan Willem
   Shen, Jun
   DeJong, Katherine
   Barnett, Alan S.
   Apud, Jose A.
   Dickinson, Dwight
   Weinberger, Daniel R.
   Berman, Karen F.
TI Prefrontal GABA Levels Measured With Magnetic Resonance Spectroscopy in
   Patients With Psychosis and Unaffected Siblings
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID GAMMA-AMINOBUTYRIC-ACID; NEGATIVE SYNDROME SCALE; LONG-TERM TREATMENT;
   IN-VIVO; CHRONIC HALOPERIDOL; 1ST-EPISODE SCHIZOPHRENIA;
   ANTIPSYCHOTIC-DRUGS; GENE-EXPRESSION; VISUAL-CORTEX; RAT-BRAIN
AB Objective: The authors sought to compare GABA levels in treated and untreated patients with psychosis with levels in their unaffected siblings and healthy control subjects, and to assess the effects of antipsychotic medicationson GABA levels.
   Method: GABA+ levels (i.e., including signal from unrelated proteins or macromolecules) referenced to creatine or water were studied with J-edited proton spectroscopy in the dorsal anterior cingulate cortex of 289 individuals: 184 healthy control subjects, 83 treated patients with psychosis, 25 untreated patients, 31 unaffected siblings, and 17 patients studied both while off all medications and while on a single antipsychotic.
   Results: GABA+ levels in the dorsal anterior cingulate did not differ between untreated patients and healthy controls. For treated patients, levels were modestly lower for GABA+/creatine but did not differ for GABA+/water compared with healthy controls. For both GABA+ measures, unaffected siblings had significantly lower levels compared with controls. GABA+/creatine showed a modest degree of familiality (intraclass correlation=0.36). Antipsychotic dosage was negatively correlated with GABA+ levels, but the on-off medication studies indicated no difference in GABA+ levels on antipsychotics compared with off antipsychotics.
   Conclusions: GABA+/creatinein the dorsal anterior cingulate may constitute an intermediate phenotype with low effect size for psychosis, but GABA+/water measures do not fully support this conclusion. Low GABA+ levels in unaffected siblings could suggest a genetic association, but the failure to find consistent evidence of this phenotype in the patients themselves weakens genetic inference on risk for psychosis. Replication in independent samples of siblings is warranted to confirm the potential genetic risk association.
C1 [Marenco, Stefano] NIMH, Clin & Translat Neurosci Branch, IRP, Magnet Resonance Spect Core, Bethesda, MD 20892 USA.
   NICHHD, Program Pediat Imaging & Tissue Sci, IRP, Bethesda, MD 20892 USA.
   Lieber Inst Brain Dev, Baltimore, MD USA.
   Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
   Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   Johns Hopkins Univ, Inst Med Genet, Sch Med, Baltimore, MD USA.
RP Marenco, S (reprint author), NIMH, Clin & Translat Neurosci Branch, IRP, Magnet Resonance Spect Core, Bethesda, MD 20892 USA.
EM marencos@mail.nih.gov
FU NIMH Intramural Research Program [MH002942-03, MH002717-21, MH002652-23]
FX Supported by the NIMH Intramural Research Program, including projects
   ZIA MH002942-03, ZIA MH002717-21, and ZIA MH002652-23.
NR 40
TC 2
Z9 2
U1 1
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD MAY
PY 2016
VL 173
IS 5
BP 527
EP 534
DI 10.1176/appi.ajp.2015.15020190
PG 8
WC Psychiatry
SC Psychiatry
GA DK9ZS
UT WOS:000375291500016
PM 26806873
ER

PT J
AU Kane, JM
   Robinson, DG
   Schooler, NR
   Lin, HQ
   Rosenheck, RA
   Heinssen, RK
AF Kane, John M.
   Robinson, Delbert G.
   Schooler, Nina R.
   Lin, Haiqun
   Rosenheck, Robert A.
   Heinssen, Robert K.
CA RAISE-ETP Study Grp
TI Response to Amos: Addressing Purported Methodological Flaws in RAISE-ETP
   Results
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Letter
C1 [Kane, John M.] Northwell Hlth, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA.
   Feinstein Inst Med Res, Manhasset, NY USA.
   Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA.
   Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
   Yale Univ, Sch Publ Hlth, New Haven, CT USA.
   NIMH, Div Serv & Intervent Res, Rockville, MD 20857 USA.
RP Kane, JM (reprint author), Northwell Hlth, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA.
NR 2
TC 0
Z9 0
U1 2
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD MAY
PY 2016
VL 173
IS 5
BP 535
EP 536
DI 10.1176/appi.ajp.2016.15111427r
PG 2
WC Psychiatry
SC Psychiatry
GA DK9ZS
UT WOS:000375291500018
PM 27133408
ER

PT J
AU Rajaraman, P
   Doody, MM
   Yu, CL
   Preston, DL
   Miller, JS
   Sigurdson, AJ
   Freedman, DM
   Alexander, BH
   Little, MP
   Miller, DL
   Linet, MS
AF Rajaraman, Preetha
   Doody, Michele M.
   Yu, Chu Ling
   Preston, Dale L.
   Miller, Jeremy S.
   Sigurdson, Alice J.
   Freedman, D. Michal
   Alexander, Bruce H.
   Little, Mark P.
   Miller, Donald L.
   Linet, Martha S.
TI Cancer Risks in US Radiologic Technologists Working With
   Fluoroscopically Guided Interventional Procedures, 1994-2008
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE brain; breast; cancer; fluoroscopically guided interventional
   procedures; interventional radiology; radiologic procedures
ID ATOMIC-BOMB SURVIVORS; CENTRAL-NERVOUS-SYSTEM; IONIZING-RADIATION;
   UNITED-STATES; CARDIOLOGY PROCEDURES; CHILDHOOD-CANCER; POOLED ANALYSIS;
   BRAIN CANCER; SKIN-CANCER; TUMORS
AB OBJECTIVE. The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures.
   SUBJECTS AND METHODS. A nationwide prospective cohort of 90,957 radiologic technologists, who responded to a 1994-1998 survey that collected information on whether they had ever worked with fluoroscopically guided interventional procedures, was followed through completion of a subsequent cohort survey during 2003-2005 (for cancer incidence) or December 31, 2008 (for cancer mortality). Sex-adjusted hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazards models for incidence and mortality from all cancers other than nonmelanoma skin cancer and for specific cancer outcomes in participants who reported ever performing fluoroscopically guided interventional procedures compared with technologists who never performed these procedures.
   RESULTS. The analysis showed an approximately twofold increased risk of brain cancer mortality (HR, 2.55; 95% CI, 1.48-4.40) and modest elevations in incidence of melanoma (HR, 1.30; 95% CI, 1.05-1.61) and in breast cancer incidence (HR, 1.16; 95% CI, 1.02-1.32) but not mortality (HR, 1.07; 95% CI, 0.69-1.66) among technologists who performed fluoroscopically guided interventional procedures compared with those who never performed these procedures. Although there was a small suggestive increase in incidence of all cancers combined, excluding nonmelanoma skin cancers (HR, 1.08; 95% CI, 1.00-1.17), mortality from all cancers combined, excluding nonmelanoma skin cancers, was not elevated (HR, 1.00; 95% CI, 0.88-1.14). We similarly observed no elevated risk of cancers of the thyroid, skin other than melanoma, prostate, lung, or colon and rectum or of leukemia that was not chronic lymphocytic leukemia among workers who performed fluoroscopically guided interventional procedures.
   CONCLUSION. We observed elevated risks of brain cancer, breast cancer, and melanoma among technologists who performed fluoroscopically guided interventional procedures. Although exposure to low-dose radiation is one possible explanation for these increased risks, these results may also be due to chance or unmeasured confounding by nonradiation risk factors. Our results must be confirmed in other studies, preferably with individual radiation dose data.
C1 [Rajaraman, Preetha; Doody, Michele M.; Yu, Chu Ling; Sigurdson, Alice J.; Freedman, D. Michal; Little, Mark P.; Linet, Martha S.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
   [Rajaraman, Preetha] NCI, Ctr Global Hlth, NIH, US Dept HHS, Rockville, MD 20892 USA.
   [Preston, Dale L.] Hirosoft Int, Eureka, CA USA.
   [Miller, Jeremy S.] Informat Management Syst Inc, Calverton, MD USA.
   [Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
   [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, 9609 Med Ctr Dr, Rockville, MD 20892 USA.; Rajaraman, P (reprint author), NCI, Ctr Global Hlth, NIH, US Dept HHS, Rockville, MD 20892 USA.
EM rajarama@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   National Institutes of Health, U.S. Department of Health and Human
   Services
FX Funded by the intramural program of the Division of Cancer Epidemiology
   and Genetics, National Cancer Institute, National Institutes of Health,
   U.S. Department of Health and Human Services.
NR 49
TC 9
Z9 9
U1 3
U2 4
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD MAY
PY 2016
VL 206
IS 5
BP 1101
EP 1108
DI 10.2214/AJR.15.15265
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK4BD
UT WOS:000374860500035
PM 26998721
ER

PT J
AU Hancock, CN
   Liu, W
   Alvord, WG
   Phang, JM
AF Hancock, Chad N.
   Liu, Wei
   Alvord, W. Gregory
   Phang, James M.
TI Co-regulation of mitochondrial respiration by proline
   dehydrogenase/oxidase and succinate (vol 48, pg 859, 2016)
SO AMINO ACIDS
LA English
DT Correction
C1 [Hancock, Chad N.; Liu, Wei; Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.
   [Alvord, W. Gregory] NCI, Data Management Serv, Frederick, MD 21701 USA.
RP Hancock, CN; Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.
EM chad.hancock@nih.gov; phangj@mail.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD MAY
PY 2016
VL 48
IS 5
BP 1337
EP 1338
DI 10.1007/s00726-016-2184-5
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ7ES
UT WOS:000374375300020
PM 26874699
ER

PT J
AU Sandoz, KM
   Beare, PA
   Cockrell, DC
   Heinzen, RA
AF Sandoz, Kelsi M.
   Beare, Paul A.
   Cockrell, Diane C.
   Heinzen, Robert A.
TI Complementation of Arginine Auxotrophy for Genetic Transformation of
   Coxiella burnetii by Use of a Defined Axenic Medium
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID LEGIONELLA-PNEUMOPHILA GROWTH; AMINO-ACID-REQUIREMENTS;
   ESCHERICHIA-COLI; HOST-CELL; Q-FEVER; INTRACELLULAR MULTIPLICATION;
   BURKHOLDERIA-PSEUDOMALLEI; ISOLEUCINE BIOSYNTHESIS; SELECTION MARKERS;
   ABC TRANSPORTER
AB Host cell-free (axenic) culture of Coxiella burnetii in acidified citrate cysteine medium-2 (ACCM-2) has provided important opportunities for investigating the biology of this naturally obligate intracellular pathogen and enabled the development of tools for genetic manipulation. However, ACCM-2 has complex nutrient sources that preclude a detailed study of nutritional factors required for C. burnetii growth. Metabolic reconstruction of C. burnetii predicts that the bacterium cannot synthesize all amino acids and therefore must sequester some from the host. To examine C. burnetii amino acid auxotrophies, we developed a nutritionally defined medium with known amino acid concentrations, termed ACCM-D. Compared to ACCM-2, ACCM-D supported longer logarithmic growth, a more gradual transition to stationary phase, and approximately 5-to 10-fold greater overall replication. Small-cell-variant morphological forms generated in ACCM-D also showed increased viability relative to that generated in ACCM-2. Lack of growth in amino acid-deficient formulations of ACCM-D revealed C. burnetii auxotrophy for 11 amino acids, including arginine. Heterologous expression of Legionella pneumophila argGH in C. burnetii permitted growth in ACCM-D missing arginine and supplemented with citrulline, thereby providing a nonantibiotic means of selection of C. burnetii genetic transformants. Consistent with bioinformatic predictions, the elimination of glucose did not impair C. burnetii replication. Together, these results highlight the advantages of a nutritionally defined medium in investigations of C. burnetii metabolism and the development of genetic tools.
   IMPORTANCE
   Host cell-free growth and genetic manipulation of Coxiella burnetii have revolutionized research of this intracellular bacterial pathogen. Nonetheless, undefined components of growth medium have made studies of C. burnetii physiology difficult and have precluded the development of selectable markers for genetic transformation based on nutritional deficiencies. Here, we describe a medium, containing only amino acids as the sole source of carbon and energy, which supports robust growth and improved viability of C. burnetii. Growth studies confirmed that C. burnetii cannot replicate in medium lacking arginine. However, genetic transformation of the bacterium with constructs containing the last two genes in the L. pneumophila arginine biosynthesis pathway (argGH) allowed growth on defined medium missing arginine but supplemented with the arginine precursor citrulline. Our results advance the field by facilitating studies of C. burnetii metabolism and allowing non-antibiotic-based selection of C. burnetii genetic transformants, an important achievement considering that selectable makers based on antibiotic resistance are limited.
C1 [Sandoz, Kelsi M.; Beare, Paul A.; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Bacteriol Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
EM rheinzen@niaid.nih.gov
FU HHS | NIH | National Institute of Allergy and Infectious Diseases
   (NIAID) [1 ZIA AI000946 12]
FX This work, including the efforts of Robert A. Heinzen, was funded by HHS
   | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (1
   ZIA AI000946 12).
NR 74
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U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
EI 1098-5336
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD MAY
PY 2016
VL 82
IS 10
BP 3042
EP 3051
DI 10.1128/AEM.00261-16
PG 10
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA DK9EU
UT WOS:000375234400017
PM 26969695
ER

PT J
AU Batton, B
   Li, L
   Newman, NS
   Das, A
   Watterberg, KL
   Yoder, BA
   Faix, RG
   Laughon, MM
   Stoll, BJ
   Higgins, RD
   Walsh, MC
AF Batton, Beau
   Li, Lei
   Newman, Nancy S.
   Das, Abhik
   Watterberg, Kristi L.
   Yoder, Bradley A.
   Faix, Roger G.
   Laughon, Matthew M.
   Stoll, Barbara J.
   Higgins, Rosemary D.
   Walsh, Michele C.
CA Child Hlth Human Dev Neonatal Res
TI Early blood pressure, antihypotensive therapy and outcomes at
   18-22months' corrected age in extremely preterm infants
SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
LA English
DT Article
DE Neonatology; Neurodevelopment; Cardiology
ID BIRTH-WEIGHT INFANTS; 1ST 7 DAYS; VOLUME EXPANSION; HYPOTENSION;
   MANAGEMENT; FEASIBILITY; MORBIDITY; PERFUSION; DOPAMINE; NEWBORNS
AB Objective To investigate the relationships between early blood pressure (BP) changes, receipt of antihypotensive therapy and 18-22months' corrected age (CA) outcomes for extremely preterm infants.
   Design Prospective observational study of infants 23(0/7)-26(6/7)weeks' gestational age (GA). Hourly BP values and antihypotensive therapy exposure in the first 24h were recorded. Four groups were defined: infants who did or did not receive antihypotensive therapy in whom BP did or did not rise at the expected rate (defined as an increase in the mean arterial BP of 5mmHg/day). Random-intercept logistic modelling controlling for centre clustering, GA and illness severity was used to investigate the relationship between BP, antihypotensive therapies and infant outcomes.
   Setting Sixteen academic centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.
   Main outcome measures Death or neurodevelopmental impairment/developmental delay (NIDD) at 18-22months' CA.
   Results Of 367 infants, 203 (55%) received an antihypotensive therapy, 272 (74%) survived to discharge and 331 (90%) had a known outcome at 18-22months' CA. With logistic regression, there was an increased risk of death/NIDD with antihypotensive therapy versus no treatment (OR 1.836, 95% CI 1.092 to 3.086), but not NIDD alone (OR 1.53, 95% CI 0.708 to 3.307).
   Conclusions Independent of early BP changes, antihypotensive therapy exposure was associated with an increased risk of death/NIDD at 18-22months' CA when controlling for risk factors known to affect survival and neurodevelopment.
   Clinical trial registration number clinicaltrials.gov #NCT00874393.
C1 [Batton, Beau; Newman, Nancy S.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Batton, Beau] So Illinois Univ, Sch Med, Dept Pediat, Springfield, IL 62794 USA.
   [Li, Lei] RTI Int, Stat & Epidemiol Unit, Raleigh, NC USA.
   [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Watterberg, Kristi L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
   [Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
   [Laughon, Matthew M.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
   [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
   [Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Batton, B (reprint author), So Illinois Univ, Sch Med, Div Neonatol, Dept Pediat, POB 19676, Springfield, IL 62794 USA.
EM bbatton@siumed.edu
FU Best Pharmaceuticals for Children Act
FX This study was funded by the Best Pharmaceuticals for Children Act.
NR 26
TC 6
Z9 6
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1359-2998
EI 1468-2052
J9 ARCH DIS CHILD-FETAL
JI Arch. Dis. Child.-Fetal Neonatal Ed.
PD MAY
PY 2016
VL 101
IS 3
BP F201
EP F206
DI 10.1136/archdischild-2015-308899
PG 6
WC Pediatrics
SC Pediatrics
GA DK7GD
UT WOS:000375092300005
PM 26567120
ER

PT J
AU Andersson, C
   Enserro, D
   Sullivan, L
   Wang, TJ
   Januzzi, JL
   Benjamin, EJ
   Vita, JA
   Hamburg, NM
   Larson, MG
   Mitchell, GF
   Vasan, RS
AF Andersson, Charlotte
   Enserro, Danielle
   Sullivan, Lisa
   Wang, Thomas J.
   Januzzi, James L., Jr.
   Benjamin, Emelia J.
   Vita, Joseph A.
   Hamburg, Naomi M.
   Larson, Martin G.
   Mitchell, Gary F.
   Vasan, Ramachandran S.
TI Relations of circulating GDF-15, soluble ST2, and troponin-I
   concentrations with vascular function in the community: The Framingham
   Heart Study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Vascular stiffness; Endothelial function; Biomarkers; ST2; GDF-15;
   Troponin I; General population
ID GROWTH-DIFFERENTIATION FACTOR-15; FLOW-MEDIATED DILATION; ARTERIAL
   STIFFNESS; SYSTOLIC HYPERTENSION; AORTIC STIFFNESS; SENSITIVE ASSAY;
   PULSE PRESSURE; ASSOCIATION; POPULATION; MORTALITY
AB Background and aims: Growth differentiation factor-15 (GDF-15), soluble (s) ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD.
   Methods: We evaluated 1823 Framingham Study participants (mean age 61 +/- 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors.
   Results: After multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD] change per SD increase in log(e)[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in log(e)[GDF-15], p = 0.003) and inversely related to FMD (-0.051 [-0.101-0.0003] SD change per SD increase in log(e)[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in log(e)[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (-0.041 [-0.082 -0.0004] SD change per SD increase in log(e)[hs-TnI], p = 0.048).
   Conclusion: In our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Andersson, Charlotte; Wang, Thomas J.; Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
   [Andersson, Charlotte; Wang, Thomas J.; Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
   [Enserro, Danielle; Sullivan, Lisa] Boston Univ, Dept Biostat, Framingham, MA USA.
   [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
   [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
   [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
   [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA.
   [Vita, Joseph A.; Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
   [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
RP Andersson, C (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM ca@heart.dk
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
   Emelia/0000-0003-4076-2336
FU NIH Heart, Lung and Blood Institute [N01-HC-25195, R01 HL107385,
   1R01HL60040, 1RO1HL70100]; Evans Scholar award from department of
   Medicine, Boston University School of Medicine; Desanctis Clinical
   Scholar Endowment; Hutter Family Professorship; Danish Research Council
FX This study was funded by the NIH Heart, Lung and Blood Institute
   (Contract #N01-HC-25195, and R01 HL107385, PI Vasan) and (1R01HL60040;
   1RO1HL70100) with additional support from Evans Scholar award from the
   department of Medicine, Boston University School of Medicine (PI,
   Vasan). Dr. Januzzi is supported in part by the Desanctis Clinical
   Scholar Endowment and the Hutter Family Professorship. Dr. Andersson was
   supported by a grant from the Danish Research Council.
NR 31
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAY
PY 2016
VL 248
BP 245
EP 251
DI 10.1016/j.atherosclerosis.2016.02.013
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DK6MW
UT WOS:000375039200032
PM 26972631
ER

PT J
AU Dal-Re, R
   Rid, A
   Emanuel, E
   Wendler, D
AF Dal-Re, Rafael
   Rid, Annette
   Emanuel, Ezekiel
   Wendler, David
TI The potential exploitation of research participants in high income
   countries who lack access to health care
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Review
DE clinical trials regulation; drug development; ethical trial conduct;
   exploitation of participants; fair benefits framework; poor trial
   participants
ID POSTTRIAL ACCESS; PREVENTION TRIALS; CLINICAL-RESEARCH; FINANCIAL
   CRISIS; COVERAGE; COST; BENEFITS; POLICY; CANADA; DRUGS
AB There are millions of individuals living in North America and the European Union who lack access to healthcare services. When these individuals participate in research, they are at increased risk of being exposed to the risks and burdens of clinical trials without realizing the benefits that result from them. The mechanisms that have been proposed to ensure that research participants in low- and middle-income countries are not exploited are unlikely to protect participants in high-income countries. The present manuscript argues that one way to address concerns about exploitation in high-income countries would be to require sponsors to provide targeted benefits such as medical treatment during the trial, or the study drug after the trial. The latter could be achieved through extension studies, expanded access programs, or named-patient programs. Sponsors also might provide non-medical benefits, such as education or social support. Ethical and regulatory guidance should be revised to ensure that research participants in high-income countries who lack access to healthcare services receive sufficient benefits.
C1 [Dal-Re, Rafael] Univ Autonoma Madrid, Invest Clin, Programa BUC Biociencias UAM CSIC, Campus Excelencia Int, Ciudad Univ Cantoblanco,C Einstein 3, E-28049 Madrid, Spain.
   [Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England.
   [Emanuel, Ezekiel] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
   [Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Dal-Re, R (reprint author), Univ Autonoma Madrid, Invest Clin, Programa BUC Biociencias UAM CSIC, Campus Excelencia Int, Ciudad Univ Cantoblanco,C Einstein 3, E-28049 Madrid, Spain.
EM rafael.dalre@fuam.uam.es
FU People Programme (Marie Curie Actions) of the European Union's Seventh
   Framework Programme (FP7) under REA [301816]; US NIH Clinical Center
FX The opinions expressed in this article are those of the authors and may
   not reflect the opinions of the organizations that they work for.
   Annette Rid received funding from the People Programme (Marie Curie
   Actions) of the European Union's Seventh Framework Programme
   (FP7/2007-2013) under REA grant agreement no. 301816. David Wendler is a
   NIH employee. The present work was funded in part by intramural research
   funds of the US NIH Clinical Center. However, the views expressed are
   the authors' own. They do not represent the position or policy of the
   NIH, the DHHS, or the US government.
NR 49
TC 1
Z9 1
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
EI 1365-2125
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD MAY
PY 2016
VL 81
IS 5
BP 857
EP 864
DI 10.1111/bcp.12879
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK7MG
UT WOS:000375109100006
PM 26743927
ER

PT J
AU Laudisio, A
   Fontana, DO
   Rivera, C
   Ruggiero, C
   Bandinelli, S
   Gemma, A
   Ferrucci, L
   Incalzi, RA
AF Laudisio, Alice
   Fontana, Davide Onofrio
   Rivera, Chiara
   Ruggiero, Carmelinda
   Bandinelli, Stefania
   Gemma, Antonella
   Ferrucci, Luigi
   Incalzi, Raffaele Antonelli
TI Bone Mineral Density and Cognitive Decline in Elderly Women: Results
   from the InCHIANTI Study
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE Bone mineral density; Cognitive performance; Elderly; Epidemiology
ID QUANTITATIVE COMPUTED-TOMOGRAPHY; MINI-MENTAL-STATE; MEDITERRANEAN DIET;
   ALZHEIMERS-DISEASE; OLDER PATIENTS; FRACTURE RISK; POPULATION;
   OSTEOPOROSIS; ASSOCIATION; COMORBIDITY
AB Osteoporosis and cognitive impairment, which are highly prevalent conditions in elderly populations, share several risk factors. This study aims at evaluating the association of bone mineral density (BMD) with prevalent and incident cognitive impairment after a 3-year follow-up. We studied 655 community-dwelling women aged 65+ participating in the InCHIANTI study, who had been followed for 3 years. Total, trabecular, and cortical BMD were estimated by peripheral quantitative computed tomography using standard transverse scans at 4 and 38 % of the tibial length. Cognitive performance was evaluated using the Mini-Mental State Examination and the Trail Making Tests (TMT) A and B; a MMSE score <24 was adopted to define cognitive impairment. The TMT A-B score was calculated as the difference between TMT-A and TMT-B times (Delta TMT). The association of cognitive performance after 3 years with baseline indices of BMD was assessed by logistic and linear regression analyses. Cortical, but not trabecular, BMD was independently associated with incident cognitive impairment (OR 0.93, 95 % CI 0.88-0.98; P = 0.012), worsening cognitive performance (OR 0.96, 95 % CI 0.92-0.98; P = 0.039), and worsening performance in Delta TMT (OR 0.96, 95 % CI 0.92-0.99; P = 0.047). Increasing cortical BMD tertiles was associated with decreasing probability of incident cognitive impairment (P for linear trend =0.001), worsening cognitive performance (P = 0.013), and a worsening performance below the median value (P for linear trend <0.0001). In older women, low BMD might represent an independent and early marker of subsequent cognitive impairment. Physicians should assess and monitor cognitive performance in the routine management of elderly women with osteoporosis.
C1 [Laudisio, Alice; Fontana, Davide Onofrio; Rivera, Chiara; Incalzi, Raffaele Antonelli] Campus Biomed Roma Univ, Dept Med, Unit Geriatr, Via Alvaro del Portillo 21, I-00128 Rome, Italy.
   [Ruggiero, Carmelinda] Osped S Maria Misericordia, Inst Gerontol & Geriatr, Dept Med, Perugia, Italy.
   [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
   [Gemma, Antonella] Azienda Sanit Locale Roma E, Dept Homecare Serv, Rome, Italy.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Laudisio, A (reprint author), Campus Biomed Roma Univ, Dept Med, Unit Geriatr, Via Alvaro del Portillo 21, I-00128 Rome, Italy.
EM lavoralice@gmail.com
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
   on Aging [263 MD 9164, 263 MD 821336]; U.S. National Institute on Aging,
   National Institutes of Health, Baltimore, Maryland [N.1-AG-1-1,
   N.1-AG-1-2111]
FX The InCHIANTI study baseline (1998-2000) was supported as a targeted
   project (ICS110.1/RF97.71) by the Italian Ministry of Health and in part
   by the U.S. National Institute on Aging (Contracts 263 MD 9164 and 263
   MD 821336); the InCHIANTI Follow-Up 1 (2001-2003) was funded by the U.S.
   National Institute on Aging, National Institutes of Health, Baltimore,
   Maryland (Contracts N.1-AG-1-1 and N.1-AG-1-2111). None of the
   sponsoring institutions interfered with the design, methods, subject
   recruitment, data collections, analysis, and preparation of paper.
NR 42
TC 1
Z9 1
U1 4
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-967X
EI 1432-0827
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD MAY
PY 2016
VL 98
IS 5
BP 479
EP 488
DI 10.1007/s00223-015-0102-6
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK5NN
UT WOS:000374966700008
PM 26713334
ER

PT J
AU Zhao, ZG
   Wen, WQ
   Michailidou, K
   Bolla, MK
   Wang, Q
   Zhang, B
   Long, JR
   Shu, XO
   Schmidt, MK
   Milne, RL
   Garcia-Closas, M
   Chang-Claude, J
   Lindstrom, S
   Bojesen, SE
   Ahsan, H
   Aittomaki, K
   Andrulis, IL
   Anton-Culver, H
   Arndt, V
   Beckmann, MW
   Beeghly-Fadiel, A
   Benitez, J
   Blomqvist, C
   Bogdanova, NV
   Borresen-Dale, AL
   Brand, J
   Brauch, H
   Brenner, H
   Burwinkel, B
   Cai, QY
   Casey, G
   Chenevix-Trench, G
   Couch, FJ
   Cox, A
   Cross, SS
   Czene, K
   Dork, T
   Dumont, M
   Fasching, PA
   Figueroa, J
   Flesch-Janys, D
   Fletcher, O
   Flyger, H
   Fostira, F
   Gammon, M
   Giles, GG
   Guenel, P
   Haiman, CA
   Hamann, U
   Harrington, P
   Hartman, M
   Hooning, MJ
   Hopper, JL
   Jakubowska, A
   Jasmine, F
   John, EM
   Johnson, N
   Kabisch, M
   Khan, S
   Kibriya, M
   Knight, JA
   Kosma, VM
   Kriege, M
   Kristensen, V
   Le Marchand, L
   Lee, E
   Li, JM
   Lindblom, A
   Lophatananon, A
   Luben, R
   Lubinski, J
   Malone, KE
   Mannermaa, A
   Manoukian, S
   Margolin, S
   Marme, F
   McLean, C
   Meijers-Heijboer, H
   Meindl, A
   Miao, H
   Muir, K
   Neuhausen, SL
   Nevanlinna, H
   Neven, P
   Olson, JE
   Perkins, B
   Peterlongo, P
   Phillips, KA
   Pylkas, K
   Rudolph, A
   Santella, R
   Sawyer, EJ
   Schmutzler, RK
   Schoemaker, M
   Shah, M
   Shrubsole, M
   Southey, MC
   Swerdlow, AJ
   Toland, AE
   Tomlinson, I
   Torres, D
   Truong, T
   Ursin, G
   Van Der Luijt, RB
   Verhoef, S
   Wang-Gohrke, S
   Whittemore, AS
   Winqvist, R
   Zamora, MP
   Zhao, H
   Dunning, AM
   Simard, J
   Hall, P
   Kraft, P
   Pharoah, P
   Hunter, D
   Easton, DF
   Zheng, W
AF Zhao, Zhiguo
   Wen, Wanqing
   Michailidou, Kyriaki
   Bolla, Manjeet K.
   Wang, Qin
   Zhang, Ben
   Long, Jirong
   Shu, Xiao-Ou
   Schmidt, Marjanka K.
   Milne, Roger L.
   Garcia-Closas, Montserrat
   Chang-Claude, Jenny
   Lindstrom, Sara
   Bojesen, Stig E.
   Ahsan, Habibul
   Aittomaki, Kristiina
   Andrulis, Irene L.
   Anton-Culver, Hoda
   Arndt, Volker
   Beckmann, Matthias W.
   Beeghly-Fadiel, Alicia
   Benitez, Javier
   Blomqvist, Carl
   Bogdanova, Natalia V.
   Borresen-Dale, Anne-Lise
   Brand, Judith
   Brauch, Hiltrud
   Brenner, Hermann
   Burwinkel, Barbara
   Cai, Qiuyin
   Casey, Graham
   Chenevix-Trench, Georgia
   Couch, Fergus J.
   Cox, Angela
   Cross, Simon S.
   Czene, Kamila
   Doerk, Thilo
   Dumont, Martine
   Fasching, Peter A.
   Figueroa, Jonine
   Flesch-Janys, Dieter
   Fletcher, Olivia
   Flyger, Henrik
   Fostira, Florentia
   Gammon, Marilie
   Giles, Graham G.
   Guenel, Pascal
   Haiman, Christopher A.
   Hamann, Ute
   Harrington, Patricia
   Hartman, Mikael
   Hooning, Maartje J.
   Hopper, John L.
   Jakubowska, Anna
   Jasmine, Farzana
   John, Esther M.
   Johnson, Nichola
   Kabisch, Maria
   Khan, Sofia
   Kibriya, Muhammad
   Knight, Julia A.
   Kosma, Veli-Matti
   Kriege, Mieke
   Kristensen, Vessela
   Le Marchand, Loic
   Lee, Eunjung
   Li, Jingmei
   Lindblom, Annika
   Lophatananon, Artitaya
   Luben, Robert
   Lubinski, Jan
   Malone, Kathleen E.
   Mannermaa, Arto
   Manoukian, Siranoush
   Margolin, Sara
   Marme, Frederik
   McLean, Catriona
   Meijers-Heijboer, Hanne
   Meindl, Alfons
   Miao, Hui
   Muir, Kenneth
   Neuhausen, Susan L.
   Nevanlinna, Heli
   Neven, Patrick
   Olson, Janet E.
   Perkins, Barbara
   Peterlongo, Paolo
   Phillips, Kelly-Anne
   Pylkas, Katri
   Rudolph, Anja
   Santella, Regina
   Sawyer, Elinor J.
   Schmutzler, Rita K.
   Schoemaker, Minouk
   Shah, Mitul
   Shrubsole, Martha
   Southey, Melissa C.
   Swerdlow, Anthony J.
   Toland, Amanda E.
   Tomlinson, Ian
   Torres, Diana
   Therese Truong
   Ursin, Giske
   Van Der Luijt, Rob B.
   Verhoef, Senno
   Wang-Gohrke, Shan
   Whittemore, Alice S.
   Winqvist, Robert
   Zamora, M. Pilar
   Zhao, Hui
   Dunning, Alison M.
   Simard, Jacques
   Hall, Per
   Kraft, Peter
   Pharoah, Paul
   Hunter, David
   Easton, Douglas F.
   Zheng, Wei
TI Association of genetic susceptibility variants for type 2 diabetes with
   breast cancer risk in women of European ancestry
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Type 2 diabetes; Genetic susceptibility; GWAS; Breast cancer;
   Epidemiology
ID GENOME-WIDE ASSOCIATION; POPULATION-BASED COHORT; MULTIETHNIC COHORT;
   CONSENSUS REPORT; LOCI; MELLITUS; METAANALYSIS; OBESITY; PAGE
AB Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors.
   We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies.
   The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04).
   We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.
C1 [Zhao, Zhiguo; Wen, Wanqing; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Beeghly-Fadiel, Alicia; Borresen-Dale, Anne-Lise; Cai, Qiuyin; Shrubsole, Martha; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
   [Zhao, Zhiguo] Vanderbilt Univ, Sch Med, Dept Biostat, Div Canc Biostat, Nashville, TN 37212 USA.
   [Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Pharoah, Paul; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Schmidt, Marjanka K.; Verhoef, Senno] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
   [Milne, Roger L.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
   [Milne, Roger L.; Giles, Graham G.; Hopper, John L.] Univ Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
   [Garcia-Closas, Montserrat; Schoemaker, Minouk; Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
   [Garcia-Closas, Montserrat; Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England.
   [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
   [Chang-Claude, Jenny; Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany.
   [Lindstrom, Sara; Kraft, Peter; Hunter, David] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA.
   [Lindstrom, Sara; Kraft, Peter; Hunter, David] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA.
   [Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
   [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
   [Ahsan, Habibul; Jasmine, Farzana; Kibriya, Muhammad] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
   [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
   [Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
   [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
   [Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
   [Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
   [Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Obstet & Gynaecol, D-91054 Erlangen, Germany.
   [Benitez, Javier; Brand, Judith] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
   [Benitez, Javier; Brand, Judith] Ctr Invest Red Enfermedades Raras, Valencia, Spain.
   [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
   [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
   [Kristensen, Vessela] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway.
   [Kristensen, Vessela] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Oslo, Norway.
   [Czene, Kamila; Li, Jingmei; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany.
   [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
   [Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany.
   [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
   [Burwinkel, Barbara] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
   [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
   [Casey, Graham; Haiman, Christopher A.; Lee, Eunjung] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
   [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
   [Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
   [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
   [Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
   [Dumont, Martine; Simard, Jacques] Univ Laval, CHU Quebec, Res Ctr, Quebec City, PQ, Canada.
   [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Figueroa, Jonine] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Flesch-Janys, Dieter] Univ Med Ctr Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
   [Flesch-Janys, Dieter] Univ Med Ctr Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany.
   [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark.
   [Fostira, Florentia] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece.
   [Gammon, Marilie] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
   [Guenel, Pascal; Therese Truong] INSERM, Natl Inst Hlth & Med Res, Ctr Res Epidemiol & Populat Hlth, CESP,Environm Epidemiol Canc,U1018, F-94807 Villejuif, France.
   [Guenel, Pascal; Therese Truong] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
   [Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
   [Harrington, Patricia] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England.
   [Hartman, Mikael; Miao, Hui] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
   [Hooning, Maartje J.; Kriege, Mieke] Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands.
   [Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
   [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
   [John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
   [Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
   [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
   [Kosma, Veli-Matti; Lophatananon, Artitaya; Mannermaa, Arto] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, SF-70210 Kuopio, Finland.
   [Kosma, Veli-Matti; Lophatananon, Artitaya; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
   [Kosma, Veli-Matti; Lophatananon, Artitaya; Mannermaa, Arto] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland.
   [Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
   [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
   [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
   [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
   [Luben, Robert] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England.
   [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
   [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
   [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
   [Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
   [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
   [McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic, Australia.
   [Meijers-Heijboer, Hanne] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
   [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-80290 Munich, Germany.
   [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
   [Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
   [Neven, Patrick] Univ Leuven, KU Leuven, Univ Hosp Leuven, Dept Oncol,Multidisciplinary Breast Ctr & Gynaeco, B-3000 Louvain, Belgium.
   [Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
   [Perkins, Barbara; Shah, Mitul; Dunning, Alison M.; Pharoah, Paul; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
   [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
   [Phillips, Kelly-Anne] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
   [Phillips, Kelly-Anne] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
   [Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia.
   [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland.
   [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Bioctr Oulu, Oulu, Finland.
   [Santella, Regina] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
   [Santella, Regina] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
   [Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London WC2R 2LS, England.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med, Cologne, Germany.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
   [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
   [Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
   [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
   [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
   [Ursin, Giske] Canc Registry Norway, Oslo, Norway.
   [Van Der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
   [Winqvist, Robert] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
   [Zamora, M. Pilar] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain.
   [Zhao, Hui] Vesalius Res Ctr, Louvain, Belgium.
   [Zhao, Hui] Univ Leuven, Dept Oncol, Lab Translat Genet, Louvain, Belgium.
   [Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, 2525 West End Ave,8th Floor, Nashville, TN 37203 USA.
EM wei.zheng@vanderbilt.edu
RI Shrubsole, Martha/K-5052-2015; Dork, Thilo/J-8620-2012; Li,
   Jingmei/I-2904-2012; Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013;
   Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; 
OI Arndt, Volker/0000-0001-9320-8684; Shrubsole,
   Martha/0000-0002-5591-7575; Li, Jingmei/0000-0001-8587-7511; Zheng,
   Wei/0000-0003-1226-070X; Brenner, Hermann/0000-0002-6129-1572;
   manoukian, siranoush/0000-0002-6034-7562; Schoemaker,
   Minouk/0000-0001-8403-2234; Phillips, Kelly-Anne/0000-0002-0475-1771;
   Khan, Sofia/0000-0003-4185-8882; Dunning, Alison
   Margaret/0000-0001-6651-7166
FU NIH [R37CA070867, CA122340, CA128978, CA63464, CA54281, CA098758,
   CA132839, R01CA100374, P30 CA016056]; endowment funds for the Ingram
   Professorship; Anne Potter Wilson Chair in Medicine; Cancer Research UK
   [C1287/A10118, C1287/A12014, C8197/A16565, C1287/A10710, C490/A10124];
   European Community [223175 (HEALTH-F2-2009-223175)]; European Union COST
   programme [BM0606]; European Union [HEALTH-F2-2009-223175]; Canadian
   Institutes of Health Research; Ministry of Economic Development,
   Innovation and Export Trade of Quebec [PSR-SIIRI-701]; National Cancer
   Institute (USA) [UM1 CA164920]; National Health and Medical Research
   Council of Australia; New South Wales Cancer Council; Victorian Health
   Promotion Foundation (Australia); Victorian Breast Cancer Research
   Consortium; Dutch Cancer Society [NKI 2007-3839, 2009 4363, RUL
   1997-1505, DDHK 2004-3124, DDHK 2009-4318]; BBMRI-NL - Dutch government
   [NWO 184.021.007]; ELAN-Fond of the University Hospital of Erlangen;
   Cancer Research UK; Breakthrough Breast Cancer; NHS; NIHR Comprehensive
   Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust;
   King's College London, UK; Wellcome Trust [090532/Z/09/Z]; Oxford
   Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society;
   German Cancer Research Center (DKFZ); Fondation de France; Institut
   National du Cancer (INCa); Ligue Nationale contre le Cancer; Agence
   Nationale de Securite Sanitaire (ANSES); Agence Nationale de la
   Recherche (ANR); Chief Physician Johan Boserup and Lise Boserup Fund;
   Danish Medical Research Council; Herlev Hospital; Genome Spain
   Foundation; Red Tematica de Investigacion Cooperativa en Cancer;
   Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario
   [PI11/00923, PI081120]; Instituto de Salud Carlos III; California Breast
   Cancer Act; California Breast Cancer Research Fund [97-10500]; National
   Institutes of Health [R01 CA77398]; Lon V Smith Foundation [LVS39420];
   Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer
   Aid (Deutsche Krebshilfe); Federal Ministry of Education and Research
   (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402];
   Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum
   (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine
   of the German Social Accident Insurance; Institute of the Ruhr
   University Bochum (IPA); Department of Internal Medicine; Evangelische
   Kliniken Bonn gGmbH; Johanniter Krankenhaus Bonn, Germany; Helsinki
   University Central Hospital Research Fund; Academy of Finland [266528,
   250083, 122715]; Finnish Cancer Society; Nordic Cancer Union; Sigrid
   Juselius Foundation; Rudolf Bartling Foundation; Stockholm County
   Council; Karolinska Institute; Stockholm Cancer Foundation; Swedish
   Cancer Society; Kuopio University Hospital; Cancer Fund of North Savo;
   Finnish Cancer Organizations; Academy of Finland; University of Eastern
   Finland; National Breast Cancer Foundation; NHMRC; Queensland Cancer
   Fund; Cancer Council of New South Wales; Cancer Council of Victoria;
   Cancer Council of Tasmania; Cancer Council of South Australia; Cancer
   Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600];
   United States Army Medical Research and Materiel Command
   [DAMD17-01-1-0729]; Stichting tegen Kanker [232-2008, 196-2010]; FWO;
   ERC; Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419];
   Hamburg Cancer Society; German Cancer Research Center; Italian
   Association for Cancer Research (AIRC); Specialized Program of Research
   Excellence (SPORE) in Breast Cancer [CA116201]; Breast Cancer Research
   Foundation; Ting Tsung and Wei Fong Chao Foundation; VicHealth; Cancer
   Council Victoria; Australian NHMRC [209057, 251553, 504711]; Quebec
   Breast Cancer Foundation; Canadian Institutes of Health Research
   [CRN-87521]; Ministry of Economic Development, Innovation and Export
   Trade [PSR-SIIRI-701]; Norwegian Research council [155218/V40,
   175240/S10, FUGE-NFR 181600/V11]; Academy of Finland (Center of
   Excellence) [251314]; Finnish Cancer Foundation; University of Oulu;
   University of Oulu Support Foundation; special Governmental EVO funds
   for Oulu University Hospital-based research activities; National Cancer
   Institute [UM1 CA164920]; National Cancer Institute, Department of
   Health and Human Services, USA; Marit and Hans Rausings Initiative
   Against Breast Cancer; Agency for Science, Technology and Research of
   Singapore (A*STAR); US National Institute of Health (NIH); Susan G.
   Komen Breast Cancer Foundation; Swedish Cancer Society [5128-B07-01PAF];
   Yorkshire Cancer Research [S305PA, S299, S295]; UK National Institute
   for Health Research Biomedical Research Centre at the University of
   Cambridge; DKFZ; Stefanie Spielman Breast Cancer fund; OSU Comprehensive
   Cancer Center, DBBR; Hellenic Cooperative Oncology Group research Grant
   [HR R_BG/04]; Greek General Secretary for Research and Technology (GSRT)
   Program, Research Excellence II; European Union (European Social
   Fund-ESF); Greek national funds through the Operational Program
   'Education and Lifelong Learning' of the National Strategic Reference
   Framework (NSRF)-ARISTEIA; Institute of Cancer Research (ICR);
   Netherlands Organisation for Scientific Research (NWO) as part of a
   ZonMw/VIDI [91756341]; Netherlands Organisation of Scientific Research
   NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for
   Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative
   (NGI)/Netherlands Organisation for Scientific Research (NWO)
   [050-060-810];  [KULPFV/10/016-SymBioSysII];  [PBZ_KBN_122/P05/2004]
FX The work conducted for this project at the Vanderbilt Epidemiology
   Center is supported in part by NIH Grant R37CA070867 and endowment funds
   for the Ingram Professorship and Anne Potter Wilson Chair in Medicine.
   BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by
   the European Community's Seventh Framework Programme under Grant
   agreement no 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC
   have been funded by the European Union COST programme (BM0606).
   Genotyping of the iCOGS array was funded by the European Union
   (HEALTH-F2-2009-223175), Cancer Research UK (C8197/A16565 and
   C1287/A10710), the Canadian Institutes of Health Research for the 'CIHR
   Team in Familial Risks of Breast Cancer' program and the Ministry of
   Economic Development, Innovation and Export Trade of Quebec
   (PSR-SIIRI-701). Additional support for the iCOGS infrastructure was
   provided by the National Institutes of Health (CA128978) and Post-Cancer
   GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112-the
   GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), Komen
   Foundation for the Cure, the Breast Cancer Research Foundation, and the
   Ovarian Cancer Research Fund. The Australia, California, and Ontario
   sites of the Breast Cancer Family Registry were supported by Grant UM1
   CA164920 from the National Cancer Institute (USA). The content of this
   manuscript does not necessarily reflect the views or policies of the
   National Cancer Institute or any of the collaborating centers in the
   Breast Cancer Family Registry (BCFR), nor does mention of trade names,
   commercial products, or organizations imply endorsement by the USA
   Government or the BCFR. The ABCFS (Australia site of the BCFR) was also
   supported by the National Health and Medical Research Council of
   Australia, the New South Wales Cancer Council, the Victorian Health
   Promotion Foundation (Australia) and the Victorian Breast Cancer
   Research Consortium. John L. Hopper is a National Health and Medical
   Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is
   a NHMRC Senior Research Fellow. Work at the OFBCR (Ontario site of the
   BCFR) was also supported by the Canadian Institutes of Health Research
   'CIHR Team in Familial Risks of Breast Cancer' program. The ABCS study
   was supported by the Dutch Cancer Society [Grants NKI 2007-3839; 2009
   4363] and BBMRI-NL, which is a Research Infrastructure financed by the
   Dutch government (NWO 184.021.007). The work of the BBCC was partly
   funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is
   funded by Cancer Research UK and Breakthrough Breast Cancer and
   acknowledges NHS funding to the NIHR Biomedical Research Centre, and the
   National Cancer Research Network (NCRN). Elinor J. Sawyer is supported
   by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas'
   NHS Foundation Trust in partnership with King's College London, UK. Core
   funding to the Wellcome Trust Centre for Human Genetics was provided by
   the Wellcome Trust (090532/Z/09/Z). Ian Tomlinson is supported by the
   Oxford Biomedical Research Centre. The BSUCH study was supported by the
   Dietmar-Hopp Foundation, the Helmholtz Society, and the German Cancer
   Research Center (DKFZ). The CECILE study was funded by Fondation de
   France, Institut National du Cancer (INCa), Ligue Nationale contre le
   Cancer, Agence Nationale de Securite Sanitaire (ANSES), and Agence
   Nationale de la Recherche (ANR). The CGPS was supported by the Chief
   Physician Johan Boserup and Lise Boserup Fund, the Danish Medical
   Research Council, and Herlev Hospital.; The CNIO-BCS was supported by
   the Genome Spain Foundation, the Red Tematica de Investigacion
   Cooperativa en Cancer, and grants from the Asociacion Espanola Contra el
   Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and
   PI081120). The Human Genotyping-CEGEN Unit, CNIO is supported by the
   Instituto de Salud Carlos III. The CTS was initially supported by the
   California Breast Cancer Act of 1993 and the California Breast Cancer
   Research Fund (contract 97-10500) and is currently funded through the
   National Institutes of Health (R01 CA77398). Collection of cancer
   incidence data was supported by the California Department of Public
   Health as part of the statewide cancer reporting program mandated by
   California Health and Safety Code Section 103885. HAC receives support
   from the Lon V Smith Foundation (LVS39420). The ESTHER study was
   supported by a grant from the Baden Wurttemberg Ministry of Science,
   Research and Arts. Additional cases were recruited in the context of the
   VERDI study, which was supported by a grant from the German Cancer Aid
   (Deutsche Krebshilfe). The GENICA was funded by the Federal Ministry of
   Education and Research (BMBF) Germany Grants 01KW9975/5, 01KW9976/8,
   01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart,
   Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for
   Prevention and Occupational Medicine of the German Social Accident
   Insurance, Institute of the Ruhr University Bochum (IPA), as well as the
   Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH,
   Johanniter Krankenhaus Bonn, Germany. The HEBCS was supported by the
   Helsinki University Central Hospital Research Fund, Academy of Finland
   (266528), the Finnish Cancer Society, the Nordic Cancer Union, and the
   Sigrid Juselius Foundation. The HMBCS was supported by the Rudolf
   Bartling Foundation. Financial support for KARBAC was provided through
   the regional agreement on medical training and clinical research (ALF)
   between Stockholm County Council and Karolinska Institute, the Stockholm
   Cancer Foundation, and the Swedish Cancer Society. The KBCP was
   financially supported by the special Government Funding (EVO) of Kuopio
   University Hospital grants, Cancer Fund of North Savo, the Finnish
   Cancer Organizations, the Academy of Finland, and by the strategic
   funding of the University of Eastern Finland. kConFab is supported by
   grants from the National Breast Cancer Foundation, the NHMRC, the
   Queensland Cancer Fund, the Cancer Councils of New South Wales,
   Victoria, Tasmania and South Australia, and the Cancer Foundation of
   Western Australia. The kConFab Clinical Follow Up Study was funded by
   the NHMRC (145684, 288704, 454508). Kelly-Anne Phillips is a National
   Breast Cancer Foundation Fellow (Australia). Financial support for the
   AOCS was provided by the United States Army Medical Research and
   Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and
   Cancer Foundation of Western Australia, and the NHMRC (199600). Georgia
   Chenevix-Trench and P.W. are supported by the NHMRC. LMBC is supported
   by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether
   Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII and
   by a ERC consolidator grant. The MARIE study was supported by the
   Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], the
   Hamburg Cancer Society, the German Cancer Research Center, and the
   Federal Ministry of Education and Research (BMBF) Germany [01KH0402].;
   MBCSG is supported by grants from the Italian Association for Cancer
   Research (AIRC) and by funds from the Italian citizens who allocated a
   5/1000 share of their tax payment in support of the Fondazione IRCCS
   Istituto Nazionale Tumori, according to Italian laws (INT-Institutional
   strategic projects '5 x 1,000'). The MCBCS was supported by the NIH
   Grants (CA122340, CA128978) and a Specialized Program of Research
   Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer
   Research Foundation, and a generous gift from the David F. and Margaret
   T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao
   Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer
   Council Victoria. The MCCS was further supported by Australian NHMRC
   Grants 209057, 251553, and 504711 and by infrastructure provided by
   Cancer Council Victoria. The MEC was supported by NIH Grants CA63464,
   CA54281, CA098758, and CA132839. The work of MTLGEBCS was supported by
   the Quebec Breast Cancer Foundation, the Canadian Institutes of Health
   Research for the 'CIHR Team in Familial Risks of Breast Cancer'
   program-Grant No CRN-87521 and the Ministry of Economic Development,
   Innovation and Export Trade-Grant No PSR-SIIRI-701. The NBCS was
   supported by grants from the Norwegian Research council (155218/V40,
   175240/S10 to A.L.B.D., FUGE-NFR 181600/V11 to V.N.K. and a Swizz Bridge
   Award to A.L.B.D.). The NBHS was supported by NIH Grant R01CA100374.
   Biological sample preparation was conducted the Survey and Biospecimen
   Shared Resource, which is supported by P30 CA68485. OBCS was supported
   by the Academy of Finland (Grant Number 250083, 122715 and Center of
   Excellence Grant Number 251314), the Finnish Cancer Foundation, the
   Sigrid Juselius Foundation, the University of Oulu, the University of
   Oulu Support Foundation and the special Governmental EVO funds for Oulu
   University Hospital-based research activities. This OFBCR was supported
   by grant UM1 CA164920 from the National Cancer Institute. The content of
   this manuscript does not necessarily reflect the views or policies of
   the National Cancer Institute or any of the collaborating centers in the
   Breast Cancer Family Registry (BCFR), nor does mention of trade names,
   commercial products, or organizations imply endorsement by the US
   Government or the BCFR. The ORIGO study was supported by the Dutch
   Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular
   Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded
   by Intramural Research Funds of the National Cancer Institute,
   Department of Health and Human Services, USA. The pKARMA study was
   supported by Marit and Hans Rausings Initiative Against Breast Cancer.
   The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK
   2009-4318). The SASBAC was supported by funding from the Agency for
   Science, Technology and Research of Singapore (A*STAR), the US National
   Institute of Health (NIH), and the Susan G. Komen Breast Cancer
   Foundation. KC was financed by the Swedish Cancer Society
   (5128-B07-01PAF). The SBCS was supported by Yorkshire Cancer Research
   S305PA, S299, and S295. SEARCH is funded by a programme grant from
   Cancer Research UK (C490/A10124) and supported by the UK National
   Institute for Health Research Biomedical Research Centre at the
   University of Cambridge. SKKDKFZS is supported by the DKFZ. The SZBCS
   was supported by Grant PBZ_KBN_122/P05/2004.; The TNBCC was supported
   by: a Specialized Program of Research Excellence (SPORE) in Breast
   Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a
   generous gift from the David F. and Margaret T. Grohne Family Foundation
   and the Ting Tsung and Wei Fong Chao Foundation, the Stefanie Spielman
   Breast Cancer fund and the OSU Comprehensive Cancer Center, DBBR (a CCSG
   Share Resource by National Institutes of Health Grant P30 CA016056), the
   Hellenic Cooperative Oncology Group research Grant (HR R_BG/04) and the
   Greek General Secretary for Research and Technology (GSRT) Program,
   Research Excellence II, the European Union (European Social Fund-ESF),
   and Greek national funds through the Operational Program 'Education and
   Lifelong Learning' of the National Strategic Reference Framework
   (NSRF)-ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and
   the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to
   the NIHR Biomedical Research Centre. The DFBBCS GWAS was funded by the
   Netherlands Organisation for Scientific Research (NWO) as part of a
   ZonMw/VIDI Grant number 91756341. The generation and management of GWAS
   genotype data for the Rotterdam Study (control samples) are supported by
   the Netherlands Organisation of Scientific Research NWO Investments (nr.
   175.010.2005.011, 911-03-012). This study is funded by the Research
   Institute for Diseases in the Elderly (014-93-015; RIDE2), the
   Netherlands Genomics Initiative (NGI)/Netherlands Organisation for
   Scientific Research (NWO) project nr. 050-060-810.
NR 37
TC 1
Z9 2
U1 5
U2 14
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAY
PY 2016
VL 27
IS 5
BP 679
EP 693
DI 10.1007/s10552-016-0741-6
PG 15
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DK3YC
UT WOS:000374852300009
PM 27053251
ER

PT J
AU Gabrielson, A
   Wu, YN
   Wang, HK
   Jiang, JJ
   Kallakury, B
   Gatalica, Z
   Reddy, S
   Kleiner, D
   Fishbein, T
   Johnson, L
   Island, E
   Satoskar, R
   Banovac, F
   Jha, R
   Kachhela, J
   Feng, P
   Zhang, T
   Tesfaye, A
   Prins, P
   Loffredo, C
   Marshall, J
   Weiner, L
   Atkins, M
   He, AR
AF Gabrielson, Andrew
   Wu, Yunan
   Wang, Hongkun
   Jiang, Jiji
   Kallakury, Bhaskar
   Gatalica, Zoran
   Reddy, Sandeep
   Kleiner, David
   Fishbein, Thomas
   Johnson, Lynt
   Island, Eddie
   Satoskar, Rohit
   Banovac, Filip
   Jha, Reena
   Kachhela, Jaydeep
   Feng, Perry
   Zhang, Tiger
   Tesfaye, Anteneh
   Prins, Petra
   Loffredo, Christopher
   Marshall, John
   Weiner, Louis
   Atkins, Michael
   He, Aiwu Ruth
TI Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free
   Survival in HCC
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; HEPATOCELLULAR-CARCINOMA;
   COLORECTAL-CANCER; VASCULAR INVASION; IMMUNE CELLS; IMMUNOSCORE;
   RECURRENCE; EXPRESSION; APOPTOSIS; RESECTION
AB Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+). Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. (C) 2016 AACR.
C1 [Gabrielson, Andrew; Wang, Hongkun; Jiang, Jiji; Kachhela, Jaydeep; Feng, Perry; Zhang, Tiger; Tesfaye, Anteneh; Prins, Petra; Loffredo, Christopher; Marshall, John; Weiner, Louis; Atkins, Michael; He, Aiwu Ruth] Georgetown Lombardi Comprehens Canc Ctr, Div Hematol & Oncol, Washington, DC USA.
   [Wu, Yunan] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.
   [Kallakury, Bhaskar] Georgetown Univ Hosp, Dept Pathol, Washington, DC 20007 USA.
   [Gatalica, Zoran; Reddy, Sandeep] Caris Life Sci, Irving, TX USA.
   [Kleiner, David] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Fishbein, Thomas; Island, Eddie; Satoskar, Rohit] Georgetown Univ Hosp, Medstar Transplant Inst, Washington, DC 20007 USA.
   [Johnson, Lynt] Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA.
   [Banovac, Filip; Jha, Reena] Georgetown Univ Hosp, Dept Radiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
RP He, AR (reprint author), Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.; He, AR (reprint author), MedStar Georgetown Univ Hosp, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM arh29@georgetown.edu
FU American Cancer Society [118525-MRSG-10-068-01-TBE]; NIH-P30 [CA51008];
   NCATS [8 UL1 TR000101]
FX This work was supported by American Cancer Society grant
   118525-MRSG-10-068-01-TBE (A.R. He). The experiments were carried out
   with the help of Georgetown University Medical Center's (GUMC) Shared
   Resources (including histopathology, microscopy and imaging, genomics
   and epigenomics, and flow cytometry), which was supported by NIH-P30
   CA51008 and NCATS 8 UL1 TR000101.
NR 44
TC 5
Z9 6
U1 3
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD MAY
PY 2016
VL 4
IS 5
BP 419
EP 430
DI 10.1158/2326-6066.CIR-15-0110
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA DL1RV
UT WOS:000375410600006
PM 26968206
ER

PT J
AU Vandeveer, AJ
   Fallon, JK
   Tighe, R
   Sabzevari, H
   Schlom, J
   Greiner, JW
AF Vandeveer, Amanda J.
   Fallon, Jonathan K.
   Tighe, Robert
   Sabzevari, Helen
   Schlom, Jeffrey
   Greiner, John W.
TI Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with
   Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID BACILLUS-CALMETTE-GUERIN; TISSUE INFILTRATING LYMPHOCYTES; ANTITUMOR
   IMMUNITY; ADAPTIVE IMMUNITY; RESPONSES; MELANOMA; ANTIBODY; SAFETY;
   TUMORS; ACTIVATION
AB Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non-muscle invasive, nonmetastatic human urothelial carcinoma. Although the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49(luc)), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49(luc) murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non-muscle invasive, nonmetastatic urothelial carcinomas. MB49(luc) bladder tumors are highly positive for the expression of PD-L1, and avelumab administration induced significant (P < 0.05) antitumor effects. These antitumor effects were more dependent on the presence of CD4 than CD8 T cells, as determined by in vivo immune cell depletions. The findings suggest that in this bladder tumor model, interruption of the immune-suppressive PD-1/PD-L1 complex releases a local adaptive immune response that, in turn, reduces tumor growth. This bladder tumor model can be used to further identify host antitumor immune mechanisms and evaluate combinations of immune-based therapies for carcinoma in situ and non-muscle invasive, nonmetastatic urothelial carcinoma, to provide the rationale for subsequent clinical studies. (C) 2016 AACR.
C1 [Vandeveer, Amanda J.; Fallon, Jonathan K.; Schlom, Jeffrey; Greiner, John W.] NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA.
   [Tighe, Robert; Sabzevari, Helen] EMD Serono Res & Dev Inst, Billerica, MA USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
EM js141c@nih.gov
FU Center for Cancer Research, NCI, NIH [ZIA BC 010970]; EMD Serono; NCI
FX This research was supported by the Intramural Research Program of the
   Center for Cancer Research, NCI, NIH (ZIA BC 010970), as well as through
   a Cooperative Research and Development Agreement (CRADA) between EMD
   Serono and the NCI.
NR 35
TC 5
Z9 5
U1 2
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD MAY
PY 2016
VL 4
IS 5
BP 452
EP 462
DI 10.1158/2326-6066.CIR-15-0176
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA DL1RV
UT WOS:000375410600009
PM 26921031
ER

PT J
AU Gao, B
AF Gao, Bin
TI Basic liver immunology
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Editorial Material
ID ORGAN; IMMUNITY; CELLS
C1 [Gao, Bin] NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
NR 17
TC 1
Z9 1
U1 0
U2 0
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD MAY
PY 2016
VL 13
IS 3
SI SI
BP 265
EP 266
DI 10.1038/cmi.2016.9
PG 2
WC Immunology
SC Immunology
GA DL1TX
UT WOS:000375416500001
PM 27041634
ER

PT J
AU Zhou, Z
   Xu, MJ
   Gao, B
AF Zhou, Zhou
   Xu, Ming-Jiang
   Gao, Bin
TI Hepatocytes: a key cell type for innate immunity
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Review
DE Liver; acute phase protein; cytokine; infection; transcription factor
ID SERUM-AMYLOID-P; LIPOPOLYSACCHARIDE-BINDING PROTEIN; C-REACTIVE PROTEIN;
   ACUTE-PHASE RESPONSE; NF-KAPPA-B; GRAM-NEGATIVE BACTERIA; FC-GAMMA
   RECEPTORS; A GENE-EXPRESSION; SOLUBLE CD14; C/EBP-BETA
AB Hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. Hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. These proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide signaling, and the coagulation factor fibrinogen that activates innate immunity. In this review, we summarize the wide variety of innate immunity proteins produced by hepatocytes and discuss liver-enriched transcription factors (e.g. hepatocyte nuclear factors and CCAAT/enhancer-binding proteins), pro-inflammatory mediators (e.g. interleukin (IL)-6, IL-22, IL-1 beta and tumor necrosis factor-alpha), and downstream signaling pathways (e.g. signal transducer and activator of transcription factor 3 and nuclear factor-kappa B) that regulate the expression of these innate immunity proteins. We also briefly discuss the dysregulation of these innate immunity proteins in chronic liver disease, which may contribute to an increased susceptibility to bacterial infection in patients with cirrhosis.
C1 [Zhou, Zhou; Xu, Ming-Jiang; Gao, Bin] NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Zhou, Zhou/R-7788-2016
FU intramural program of NIAAA, NIH
FX The work from the authors' lab described in the current review was
   supported by the intramural program of NIAAA, NIH (B.G.)
NR 173
TC 6
Z9 6
U1 3
U2 8
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD MAY
PY 2016
VL 13
IS 3
SI SI
BP 301
EP 315
DI 10.1038/cmi.2015.97
PG 15
WC Immunology
SC Immunology
GA DL1TX
UT WOS:000375416500005
PM 26685902
ER

PT J
AU Janssen, I
   Xekouki, P
   Nambuba, J
   Chen, CC
   Herscovitch, P
   Millo, CM
   Schrump, DS
   Pacak, K
AF Janssen, Ingo
   Xekouki, Paraskevi
   Nambuba, Joan
   Chen, Clara C.
   Herscovitch, Peter
   Millo, Corina M.
   Schrump, David S.
   Pacak, Karel
TI Rapidly Growing Chest Wall Mass in a Case of Sporadic Metastatic
   Paraganglioma: Imaging With 4 Different PET Radiopharmaceuticals
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE pheochromocytoma; paraganglioma; metastatic; PET
ID POSITRON-EMISSION-TOMOGRAPHY; PHEOCHROMOCYTOMA; LOCALIZATION;
   SUPERIORITY; SST1-SST5
AB Pheochromocytomas/paragangliomas (PGLs) are rare tumors and mostly benign. We report on a 32-year-old woman with metastatic PGL who was first diagnosed with an abdominal PGL at the age of 12 years. She soon developed metastatic disease and received several treatments including external beam radiation and chemotherapy. When she was referred to our institution in 2014, her major complaint was a rapidly growing chest wall mass on the left side. The patient was imaged at our institution with 4 different PET radiopharmaceuticals.
C1 [Janssen, Ingo; Xekouki, Paraskevi; Nambuba, Joan; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA.
   [Chen, Clara C.] NIH, Div Nucl Med, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr,Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Herscovitch, Peter; Millo, Corina M.] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Schrump, David S.] NCI, Ctr Canc Res, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008735-15]
NR 15
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 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD MAY
PY 2016
VL 41
IS 5
BP 399
EP 400
DI 10.1097/RLU.0000000000001116
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK4GY
UT WOS:000374876600027
PM 26828140
ER

PT J
AU Kleiner, DE
   Makhlouf, HR
AF Kleiner, David E.
   Makhlouf, Hala R.
TI Histology of Nonalcoholic Fatty Liver Disease and Nonalcoholic
   Steatohepatitis in Adults and Children
SO CLINICS IN LIVER DISEASE
LA English
DT Article
DE Steatohepatitis; Liver biopsy; Steatosis; Histology; Scoring; Staging
ID PLACEBO-CONTROLLED-TRIAL; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-RESEARCH
   NETWORK; CRYPTOGENIC CIRRHOSIS; NATURAL-HISTORY; UNITED-STATES;
   FOLLOW-UP; VITAMIN-E; URSODEOXYCHOLIC ACID; RISK-FACTORS
AB Nonalcoholic fatty liver disease (NAFLD) is the liver disease associated with obesity, diabetes, and the metabolic syndrome. Although steatosis is a key histologic feature, liver biopsies of patients with NAFLD can show a wide range of findings. Nonalcoholic steatohepatitis (NASH) is a progressive subtype of NAFLD first defined by analogy to alcoholic hepatitis. Young children may have an alternate pattern of progressive NAFLD characterized by a zone 1 distribution of steatosis, inflammation, and fibrosis. Several grading and staging systems exist, but all require adequate biopsies. Although NASH generally shows fibrosis progression over time, some patients show regression of disease.
C1 [Kleiner, David E.] NCI, Pathol Lab, Ctr Canc Res, Bldg 10,Room 2S235,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA.
   [Makhlouf, Hala R.] NCI, Canc Diag Program, Pathol Invest & Resources Branch, Div Canc Treatment & Diag, 9609 Med Ctr Dr,Room 4W438, Bethesda, MD 20892 USA.
   [Makhlouf, Hala R.] Ain Shams Univ, Fac Med, Dept Pathol, 38 Al Abbassyah, Cairo 11566, Greater Cairo, Egypt.
RP Kleiner, DE (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10,Room 2S235,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kleinerd@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010685-03]
NR 95
TC 0
Z9 0
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1089-3261
EI 1557-8224
J9 CLIN LIVER DIS
JI Clin. Liver Dis.
PD MAY
PY 2016
VL 20
IS 2
BP 293
EP +
DI 10.1016/j.cld.2015.10.011
PG 21
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DL2YV
UT WOS:000375502000008
PM 27063270
ER

PT J
AU McLaughlin, T
   Craig, C
   Liu, LF
   Perelman, D
   Allister, C
   Spielman, D
   Cushman, SW
AF McLaughlin, Tracey
   Craig, Colleen
   Liu, Li-Fen
   Perelman, Dalia
   Allister, Candice
   Spielman, Daniel
   Cushman, Samuel W.
TI Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic
   Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive
   Humans
SO DIABETES
LA English
DT Article
ID BODY-MASS INDEX; MEDIATED GLUCOSE-UPTAKE; IMPAIRED ADIPOGENESIS; OBESE
   INDIVIDUALS; SUPPRESSION TEST; WEIGHT-GAIN; US ADULTS; TISSUE;
   PREVALENCE; PIOGLITAZONE
AB Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 +/- 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance.
C1 [McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Cushman, Samuel W.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP McLaughlin, T (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM tmclaugh@stanford.edu
FU American Diabetes Association [1-11-CT-35]
FX This work was supported by American Diabetes Association grant
   1-11-CT-35.
NR 32
TC 5
Z9 5
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAY
PY 2016
VL 65
IS 5
BP 1245
EP 1254
DI 10.2337/db15-1213
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK6JA
UT WOS:000375028000015
PM 26884438
ER

PT J
AU Nathan, DM
   Bebu, I
   Braffett, BH
   Lachin, JM
   Orchard, TJ
   Cowie, CC
   Lopes-Virella, M
   Schutta, M
AF Nathan, David M.
   Bebu, Ionut
   Braffett, Barbara H.
   Lachin, John M.
   Orchard, Trevor J.
   Cowie, Catherine C.
   Lopes-Virella, Maria
   Schutta, Mark
CA Diabet Control & Complications
TI Risk Factors for Cardiovascular Disease in Type 1 Diabetes
SO DIABETES
LA English
DT Article
ID CORONARY-HEART-DISEASE; TERM-FOLLOW-UP; PITTSBURGH EPIDEMIOLOGY;
   COMPLICATIONS TRIAL; ARTERY-DISEASE; INSULIN-RESISTANCE; GLYCEMIC
   CONTROL; 64 COHORTS; INTERVENTIONS; METAANALYSIS
AB Risk factors for cardiovascular disease (CVD) are well-established in type 2 but not type 1 diabetes (T1DM). We assessed risk factors in the long-term (mean 27 years) follow-up of the Diabetes Control and Complications Trial (DCCT) cohort with T1DM. Cox proportional hazards multivariate models assessed the association of traditional and novel risk factors, including HbA(1c), with major atherosclerotic cardiovascular events (MACE) (fatal or nonfatal myocardial infarction [MI] or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Age and mean HbA(1c) were strongly associated with any-CVD and with MACE. For each percentage point increase in mean HbA(1c), the risk for any-CVD and for MACE increased by 31 and 42%, respectively. CVD and MACE were associated with seven other conventional factors, such as blood pressure, lipids, and lack of ACE inhibitor use, but not with sex. The areas under the receiver operating characteristics curves for the association of age and HbA(1c), taken together with any-CVD and for MACE, were 0.70 and 0.77, respectively, and for the final models, including all significant risk factors, were 0.75 and 0.82. Although many conventional CVD risk factors apply in T1DM, hyperglycemia is an important risk factor second only to age.
C1 [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
   [Bebu, Ionut; Braffett, Barbara H.; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
   [Orchard, Trevor J.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
   [Cowie, Catherine C.] NIDDK, Bethesda, MD 20892 USA.
   [Lopes-Virella, Maria] Med Univ S Carolina, Charleston, SC 29425 USA.
   [Schutta, Mark] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA.
RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD USA.
EM jml@bsc.gwu.edu
OI orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841
FU Division of Diabetes, Endocrinology, and Metabolic Diseases of the
   National Institute of Diabetes and Digestive and Kidney Diseases
   [U01-DK-094176, U01-DK-094157]; National Eye Institute; National
   Institute of Neurological Disorders and Stroke; General Clinical
   Research Centers Program; Clinical and Translational Science Center
   Program, Bethesda, MD
FX DCCT/EDIC has been supported by cooperative agreement grants (1982-1993,
   2012-2017) and contracts (1982-2012) with the Division of Diabetes,
   Endocrinology, and Metabolic Diseases of the National Institute of
   Diabetes and Digestive and Kidney Diseases (current grant numbers
   U01-DK-094176 and U01-DK-094157) and through support from the National
   Eye Institute, the National Institute of Neurological Disorders and
   Stroke, the General Clinical Research Centers Program (1993-2007), and
   the Clinical and Translational Science Center Program (2006-present),
   Bethesda, MD. Industry contributors have had no role in DCCT/EDIC but
   have provided free or discounted supplies or equipment to support
   participants' adherence to the study: Abbott Diabetes Care (Alameda,
   CA), Animas (Westchester, PA), Bayer Diabetes Care (North America
   Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), Eli
   Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet
   Corporation (Bedford, MA), LifeScan (Milpitas, CA), Medtronic Diabetes
   (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova
   Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes
   Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi
   (Bridgewater, NJ).
NR 43
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Z9 1
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAY
PY 2016
VL 65
IS 5
BP 1370
EP 1379
DI 10.2337/db15-1517
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK6JA
UT WOS:000375028000026
ER

PT J
AU Yun, JS
   Ahn, YB
   Song, KH
   Yoo, KD
   Park, YM
   Kim, HW
   Ko, SH
AF Yun, J. -S.
   Ahn, Y. -B.
   Song, K. -H.
   Yoo, K. -D.
   Park, Y. -M.
   Kim, H. -W.
   Ko, S. -H.
TI Lipoprotein(a) predicts a new onset of chronic kidney disease in people
   with Type2 diabetes mellitus
SO DIABETIC MEDICINE
LA English
DT Article
ID RISK-FACTOR
AB AimsWe investigated the association between lipoprotein(a) [Lp(a)] level and new-onset chronic kidney disease (CKD) in patients with Type2 diabetes.
   MethodsWe conducted a prospective cohort study from March 2003 to December 2004 with a median follow-up time of 10.1years. Patients aged 25-75years with Type2 diabetes and without CKD [estimated glomerular filtration rate (eGFR) 90ml/min/1.73m(2)) were consecutively enrolled. The eGFR was measured at least twice every year , and new-onset CKD was defined as a decreased eGFR status of <60ml/min/1.73m(2) using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
   ResultsOf the 862 patients who were enrolled, 560 (65.0%) completed the follow-up and 125 (22.3%) progressed to CKD. The mean age and duration of diabetes were 53.39.6 and 7.56.0 years, respectively. The baseline eGFR was 101.811.3ml/min/1.73m(2). After adjusting for multiple confounding factors, a Cox hazard regression analysis revealed that the third tertile of Lp(a) was significantly associated with the development of CKD during the observation period when compared with the first tertile [hazard ratio 2.12 (95% confidence interval 1.33-3.36); P=0.001).
   ConclusionsIn this prospective, longitudinal, observational cohort study, we demonstrated that the Lp(a) level was an independent prognostic factor for the future development of CKD in patients with Type2 diabetes.
   What's new?
   Our study confirms that an elevated lipoprotein(a) level is an independent predictable risk factor for the future development of new-onset chronic kidney disease in Type2 diabetes. The median calculated estimated glomerular filtration rate reduction showed an increasing trend as the lipoprotein(a) level increased. We suggest that cardiovascular risk factors in patients with diabetes who have high lipoprotein(a) should be treated more aggressively to prevent the future development of chronic kidney disease.
C1 [Yun, J. -S.; Ahn, Y. -B.; Ko, S. -H.] Catholic Univ Korea, St Vincents Hosp, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea.
   [Song, K. -H.] Catholic Univ Korea, Yeouido St Marys Hosp, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea.
   [Yoo, K. -D.] Catholic Univ Korea, St Vincents Hosp, Dept Internal Med, Div Cardiol, Seoul, South Korea.
   [Park, Y. -M.] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Kim, H. -W.] Catholic Univ Korea, St Vincents Hosp, Dept Internal Med, Div Nephrol, Seoul, South Korea.
RP Ko, SH (reprint author), Catholic Univ Korea, St Vincents Hosp, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea.
EM kosh@catholic.ac.kr
NR 20
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-3071
EI 1464-5491
J9 DIABETIC MED
JI Diabetic Med.
PD MAY
PY 2016
VL 33
IS 5
BP 639
EP 643
DI 10.1111/dme.12862
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK7PZ
UT WOS:000375119500009
PM 26202453
ER

PT J
AU Niehoff, NM
   Nichols, HB
   White, AJ
   Parks, CG
   D'Aloisio, AA
   Sandler, DP
AF Niehoff, Nicole M.
   Nichols, Hazel B.
   White, Alexandra J.
   Parks, Christine G.
   D'Aloisio, Aimee A.
   Sandler, Dale P.
TI Childhood and Adolescent Pesticide Exposure and Breast Cancer Risk
SO EPIDEMIOLOGY
LA English
DT Article
ID CURRENTLY USED PESTICIDES; RECEPTOR STATUS; EPIDEMIOLOGIC EVIDENCE;
   AGRICULTURAL HEALTH; BODY BURDEN; ESTROGEN; ORGANOCHLORINES;
   RELIABILITY; WOMEN; LIFE
AB Background: To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype.
   Methods: During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression.
   Results: HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0-18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7).
   Conclusion: These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women.
C1 [Niehoff, Nicole M.; Nichols, Hazel B.; White, Alexandra J.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2102A McGavran Greenberg Hall,135 Dauer Dr, Chapel Hill, NC 27516 USA.
   [Parks, Christine G.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
   [D'Aloisio, Aimee A.] Social & Sci Syst Inc, Durham, NC USA.
RP Nichols, HB (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2102A McGavran Greenberg Hall,135 Dauer Dr, Chapel Hill, NC 27516 USA.
EM hazel.nichols@unc.edu
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018
FU Intramural and Extramural Research Programs of the National Institutes
   of Health, National Institute of Environmental Health Sciences
   [Z01-ES044005, T32-ES007018]; National Center for Advancing
   Translational Sciences [KL2-TR001109]; UNC Lineberger Cancer Control
   Education Program [R25 CA57726]
FX This research was supported in part by the Intramural and Extramural
   Research Programs of the National Institutes of Health, National
   Institute of Environmental Health Sciences (Z01-ES044005, T32-ES007018),
   by the National Center for Advancing Translational Sciences
   (KL2-TR001109), and by the UNC Lineberger Cancer Control Education
   Program (R25 CA57726).
NR 44
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U1 4
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2016
VL 27
IS 3
BP 326
EP 333
DI 10.1097/EDE.0000000000000451
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DK2XI
UT WOS:000374777300020
PM 26808595
ER

PT J
AU Lubin, JH
   Couper, D
   Lutsey, PL
   Woodward, M
   Yatsuya, H
   Huxley, RR
AF Lubin, Jay H.
   Couper, David
   Lutsey, Pamela L.
   Woodward, Mark
   Yatsuya, Hiroshi
   Huxley, Rachel R.
TI Risk of Cardiovascular Disease from Cumulative Cigarette Use and the
   Impact of Smoking Intensity
SO EPIDEMIOLOGY
LA English
DT Article
ID CORONARY-HEART-DISEASE; LUNG-CANCER; PACK-YEARS; COTININE LEVELS;
   EXPOSURE; CONSUMPTION; SMOKERS; PATHOPHYSIOLOGY; TIME; ATHEROSCLEROSIS
AB Background: Relative risks (RRs) for cardiovascular disease (CVD) by smoking rate exhibit a concave pattern, with RRs in low rate smokers exceeding a linear extrapolation from higher rate smokers. However, cigarettes/day does not by itself fully characterize smoking-related risks. A reexamination of the concave pattern using a comprehensive representation of smoking may enhance insights.
   Methods: Data were from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort enrolled in four areas of the US in 1987-1989. Follow-up was through 2008. Analyses included 14,233 participants, 245,915 person-years, and 3,411 CVD events.
   Results: The concave RRs with cigarettes/day were consistent with cigarettes/day modifying a linear RR association of pack-years with CVD (i.e., strength of the pack-years association depended on cigarettes/day, indicating that the manner of pack-years accrual impacted risk). Smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration (P < 0.01). For 50 pack-years (365,000 cigarettes), estimated RRs of CVD were 2.1 for accrual at 20 cigarettes/day and 1.6 for accrual at 50 cigarettes/day. Years since smoking cessation did not alter the diminishing strength of association with increasing cigarettes/day. Analyses that accounted for competing risks did not affect findings.
   Conclusion: Pack-years remained the primary determinant of smoking-related CVD risk; however, accrual influenced RRs. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. This observation provides clues to better understanding the biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CVD risk.
C1 [Lubin, Jay H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Couper, David] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
   [Lutsey, Pamela L.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
   [Woodward, Mark] Univ Oxford, George Inst Global Hlth, Nuffield Dept Populat Hlth, Biostat, Oxford, England.
   [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia.
   [Woodward, Mark] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
   [Yatsuya, Hiroshi] Fujita Hlth Univ, Sch Med, Dept Publ Hlth, Toyoake, Aichi 47011, Japan.
   [Huxley, Rachel R.] Curtin Univ, Sch Publ Hlth, Perth, WA 6845, Australia.
RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM lubinj@mail.nih.gov
RI Huxley, Rachel/C-7032-2013; Woodward, Mark/D-8492-2015
OI Huxley, Rachel/0000-0002-2705-6616; 
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
   HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
   HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
   HHSN268201100012C]; Intramural Research Program of the National
   Institutes of Health, National Cancer Institute, Division of Cancer
   Epidemiology and Genetics
FX The Atherosclerosis Risk in Communities 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). Dr. Lubin
   was supported by the Intramural Research Program of the National
   Institutes of Health, National Cancer Institute, Division of Cancer
   Epidemiology and Genetics. The authors maintained full control over the
   management, analysis, and interpretation of the data; the preparation,
   review, and approval of the manuscript; and were independent of funders.
NR 41
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U1 6
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2016
VL 27
IS 3
BP 395
EP 404
DI 10.1097/EDE.0000000000000437
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DK2XI
UT WOS:000374777300030
PM 26745609
ER

PT J
AU Goldenholz, DM
   Goldenholz, SR
AF Goldenholz, Daniel M.
   Goldenholz, Shira R.
TI Response to placebo in clinical epilepsy trials-Old ideas and new
   insights
SO EPILEPSY RESEARCH
LA English
DT Review
DE Placebo effect; Epilepsy; Clinical trial
ID RANDOMIZED CONTROLLED-TRIAL; DRUG-RESISTANT EPILEPSY; ANTIEPILEPTIC
   DRUGS; REFRACTORY EPILEPSY; POWERFUL PLACEBO; NATURAL-HISTORY;
   DOUBLE-BLIND; METAANALYSIS; STIMULATION; POPULATION
AB Randomized placebo-controlled trials are a mainstay of modern clinical epilepsy research; the success or failure of innovative therapies depends on proving superiority to a placebo. Consequently, understanding what drives response to placebo (including the "placebo effect") may facilitate evaluation of new therapies. In this review, part one will explore observations about placebos specific to epilepsy, including the relatively higher placebo response in children, apparent increase in placebo response over the past several decades, geographic variation in placebo effect, relationship to baseline epilepsy characteristics, influence of nocebo on clinical trials, the possible increase in (SUDEP) in placebo arms of trials, and patterns that placebo responses appear to follow in individual patients. Part two will discuss the principal causes of placebo responses, including regression to the mean, anticipation, classical conditioning, the Hawthorne effect, expectations from symbols, and the natural history of disease. Included in part two will be a brief overview of recent advances using simulations from large datasets that have afforded new insights into causes of epilepsy-related placebo responses. In part three, new developments in study design will be explored, including sequential parallel comparison, two-way enriched design, time to pre-randomization, delayed start, and cohort reduction techniques. Published by Elsevier B.V.
C1 [Goldenholz, Daniel M.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
RP Goldenholz, DM (reprint author), NINDS, NIH, Clin Epilepsy Sect, CNP,DIR, 10 Ctr Dr,10 CRC,Room 5S-217,MSC 1408, Bethesda, MD 20892 USA.
EM daniel.goldenholz@nih.gov
OI Goldenholz, Daniel/0000-0002-8370-2758
FU NIH
FX The authors would like to acknowledge the guidance from Dr. William
   Theodore and Dr. Sara Inati. This work was supported by the Intramural
   Research Program of the NIH:.
NR 64
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U1 3
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-1211
EI 1872-6844
J9 EPILEPSY RES
JI Epilepsy Res.
PD MAY
PY 2016
VL 122
BP 15
EP 25
DI 10.1016/j.eplepsyres.2016.02.002
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA DK3GM
UT WOS:000374805100003
PM 26921852
ER

PT J
AU Hannan, R
   Tumati, V
   Xie, XJ
   Cho, LC
   Kavanagh, BD
   Brindle, J
   Raben, D
   Nanda, A
   Cooley, S
   Kim, DWN
   Pistenmaa, D
   Lotan, Y
   Timmerman, R
AF Hannan, Raquibul
   Tumati, Vasu
   Xie, Xian-Jin
   Cho, L. Chinsoo
   Kavanagh, Brian D.
   Brindle, Jeffrey
   Raben, David
   Nanda, Akash
   Cooley, Susan
   Kim, D. W. Nathan
   Pistenmaa, David
   Lotan, Yair
   Timmerman, Robert
TI Stereotactic body radiation therapy for low and intermediate risk
   prostate cancer-Results from a multi-institutional clinical trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Stereotactic body radiation therapy; SBRT; Prostate cancer; Dose
   constraints
ID RADICAL RETROPUBIC PROSTATECTOMY; RANDOMIZED CONTROLLED-TRIAL; DOSE-RATE
   BRACHYTHERAPY; QUALITY-OF-LIFE; SEXUAL FUNCTION; RADIOTHERAPY;
   EXPERIENCE; MONOTHERAPY; TOXICITY; POTENCY
AB Background: We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR) prostate cancer (PCa) patients.
   Patients and methods: Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA <= 20 or Gleason 7 with PSA <= 15 and clinical stage <= T2b. For the phase I portion of the study patients in cohorts of 15 received 45, 47.5, or 50 Gray (Gy) in five fractions. Since the maximally tolerated dose was not met in the phase I study, an additional 47 patients received 50 Gy in five fractions in the phase II study. Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0, quality of life, and outcome data was collected.
   Results: A total of 91 patients are included for analysis; 63.7% had NCCN IR and 36.3% had LR PCa. At a median follow up of 54 months the actuarial freedom from biochemical failure was 100% at 3 years and 98.6% at 5 years. Actuarial distant metastasis free survival was 100% at 3 and 5 years. Overall survival was 94% at 3 years and 89.7% at 5 years with no deaths attributed to PCa. Acute and late urinary grade >= III toxicity occurred in 0% and 5.5% of patients, respectively. Gastrointestinal (GI) acute and late toxicity of grade >= III occurred in 2% and 7% of patients, respectively. A total of four men experienced grade IV toxicity (three GI, one genitourinary).
   Conclusion: SBRT treatment results in excellent biochemical control rates at 5 years for LR and IR PCa patients although doses greater than 47.5 Gy in five fractions led to increased severe late toxicity. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Hannan, Raquibul; Tumati, Vasu; Cooley, Susan; Timmerman, Robert] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, 5801 Forest Pk Rd, Dallas, TX 75390 USA.
   [Xie, Xian-Jin] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Cho, L. Chinsoo] Univ Minnesota, Dept Radiat Oncol, Minneapolis, MN 55455 USA.
   [Kavanagh, Brian D.; Raben, David] Univ Colorado, Dept Radiat Oncol, Boulder, CO 80309 USA.
   [Brindle, Jeffrey] Prairie Lakes Hosp, Dept Radiat Oncol, Watertown, SD USA.
   [Nanda, Akash] Orlando Hlth, Dept Radiat Oncol, Orlando, FL USA.
   [Lotan, Yair] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
   [Kim, D. W. Nathan] Texas Oncol Waco, Waco, TX USA.
   [Pistenmaa, David] NCI, Radiat Res Program, Bethesda, MD 20892 USA.
RP Timmerman, R (reprint author), Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, 5801 Forest Pk Rd, Dallas, TX 75390 USA.
EM Robert.Timmerman@utsouthwestern.edu
OI Tumati, Vasu/0000-0003-3908-6166
FU US Department of Defense
FX The funding agency (US Department of Defense) was involved establishing
   guidelines for monitoring and received periodic progress reports.
NR 42
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U1 2
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAY
PY 2016
VL 59
BP 142
EP 151
DI 10.1016/j.ejca.2016.02.014
PG 10
WC Oncology
SC Oncology
GA DK7WT
UT WOS:000375138200016
PM 27035363
ER

PT J
AU Herrera, JJ
   Fedynska, S
   Ghasem, PR
   Wieman, T
   Clark, PJ
   Gray, N
   Loetz, E
   Campeau, S
   Fleshner, M
   Greenwood, BN
AF Herrera, Jonathan J.
   Fedynska, Sofiya
   Ghasem, Parsa R.
   Wieman, Tyler
   Clark, Peter J.
   Gray, Nathan
   Loetz, Esteban
   Campeau, Serge
   Fleshner, Monika
   Greenwood, Benjamin N.
TI Neurochemical and behavioural indices of exercise reward are independent
   of exercise controllability
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dopamine; immediate early genes; rat; striatum; ventral tegmental area
ID CONDITIONED PLACE PREFERENCE; MESSENGER-RNA EXPRESSION; DELTA-FOSB
   INDUCTION; ANTIDEPRESSANT RESPONSES; UNCONTROLLABLE STRESS; VOLUNTARY
   EXERCISE; STRIATAL NEURONS; GENE-EXPRESSION; BRAIN; RATS
AB Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety-like and depression-like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward-related plasticity marker Delta FosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct-pathway (dynorphin-positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase-positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance.
C1 [Herrera, Jonathan J.; Ghasem, Parsa R.; Wieman, Tyler; Clark, Peter J.; Fleshner, Monika; Greenwood, Benjamin N.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA.
   [Fedynska, Sofiya; Gray, Nathan; Loetz, Esteban] Univ Colorado, Dept Psychol, CB 173,POB 173364, Denver, CO 80217 USA.
   [Campeau, Serge] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
   [Campeau, Serge; Fleshner, Monika; Greenwood, Benjamin N.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
   [Clark, Peter J.] NIA, 253 Bayview Blvd, Baltimore, MD 21224 USA.
RP Greenwood, BN (reprint author), Univ Colorado, Dept Psychol, CB 173,POB 173364, Denver, CO 80217 USA.
EM benjamin.greenwood@ucdenver.edu
FU NIH [R01-MH068283-06A1, R03-MH086665-01]
FX This work was funded by NIH R01-MH068283-06A1 and NIH R03-MH086665-01.
NR 56
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U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAY
PY 2016
VL 43
IS 9
BP 1190
EP 1202
DI 10.1111/ejn.13193
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DK7VO
UT WOS:000375134800009
PM 26833814
ER

PT J
AU Ivy, SP
   Liu, JF
   Lee, JM
   Matulonis, UA
   Kohn, EC
AF Ivy, S. Percy
   Liu, Joyce F.
   Lee, Jung-Min
   Matulonis, Ursula A.
   Kohn, Elise C.
TI Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in
   combination therapy for high grade serous ovarian cancer
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Article
DE Germline deleterious BRCA1; 2 mutation; chemical and contextual
   synthetic lethality; poly(adenosine diphosphate-ribose) polymerase
   inhibitor; DNA repair defect; homologous recombination repair; high
   grade serous ovarian cancer; vascular endothelial growth factor receptor
   inhibitor
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; RECURRENT
   EPITHELIAL OVARIAN; RANDOMIZED PHASE-2 TRIAL; PEGYLATED LIPOSOMAL
   DOXORUBICIN; VASCULAR-PERMEABILITY FACTOR; NEGATIVE BREAST-CANCER;
   FALLOPIAN-TUBE CANCER; NONSMALL CELL LUNG; POLY(ADP-RIBOSE) POLYMERASE
AB Introduction: An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill similar to 14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC.Areas covered: Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts.Expert opinion: Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality.
C1 [Ivy, S. Percy; Kohn, Elise C.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA.
   [Liu, Joyce F.; Matulonis, Ursula A.] Dana Farber Canc Inst, Gynecol Oncol Program, Boston, MA 02115 USA.
   [Lee, Jung-Min] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Ivy, SP (reprint author), NCI, Canc Therapy Evaluat Program, Bethesda, MD USA.
EM ivyp@ctep.nci.nih.gov
FU National Cancer Institute, Bethesda; Harvard Medical School, Boston;
   AstraZeneca; Genentech; Merrimack Pharmaceuticals; Boston Biomedical;
   Atara Pharmaceuticals
FX This paper has been supported by the National Cancer Institute,
   Bethesda, and Harvard Medical School, Boston. JD Liu is a consultant for
   AstraZeneca and Genentech, and has acted as principal investigator for
   clinical trials sponsored by AstraZeneca, Genentech, Merrimack
   Pharmaceuticals, Boston Biomedical and Atara Pharmaceuticals. U
   Matulonis has participated in advisory boards for AstraZeneca and
   Tesaro. 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. This includes employment, consultancies, honoraria,
   stock ownership or options, expert testimony, grants or patents received
   or pending, or royalties.
NR 88
TC 4
Z9 4
U1 3
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1354-3784
EI 1744-7658
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD MAY
PY 2016
VL 25
IS 5
BP 597
EP 611
DI 10.1517/13543784.2016.1156857
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK2XR
UT WOS:000374778200009
PM 26899229
ER

PT J
AU Hollestelle, A
   van der Baan, FH
   Berchuck, A
   Johnatty, SE
   Aben, KK
   Agnarsson, BA
   Aittomaki, K
   Alducci, E
   Andrulis, IL
   Anton-Culver, H
   Antonenkova, NN
   Antoniou, AC
   Apicella, C
   Arndt, V
   Arnold, N
   Arun, BK
   Arver, B
   Ashworth, A
   Baglietto, L
   Balleine, R
   Bandera, EV
   Barrowdale, D
   Bean, YT
   Beckmann, L
   Beckmann, MW
   Benitez, J
   Berger, A
   Berger, R
   Beuselinck, B
   Bisogna, M
   Bjorge, L
   Blomqvist, C
   Bogdanova, NV
   Bojesen, A
   Bojesen, SE
   Bolla, MK
   Bonanni, B
   Brand, JS
   Brauch, H
   Brenner, H
   Brinton, L
   Brooks-Wilson, A
   Bruinsma, F
   Brunet, J
   Bruning, T
   Budzilowska, A
   Bunker, CH
   Burwinkel, B
   Butzow, R
   Buys, SS
   Caligo, MA
   Campbell, I
   Carter, J
   Chang-Claude, J
   Chanock, SJ
   Claes, KBM
   Collee, JM
   Cook, LS
   Couch, FJ
   Cox, A
   Cramer, D
   Cross, SS
   Cunningham, JM
   Cybulski, C
   Czene, K
   Damiola, F
   Dansonka-Mieszkowska, A
   Darabi, H
   de la Hoya, M
   Defazio, A
   Dennis, J
   Devilee, P
   Dicks, EM
   Diez, O
   Doherty, JA
   Domchek, SM
   Dorfling, CM
   Dork, T
   Silva, ID
   du Bois, A
   Dumont, M
   Dunning, AM
   Duran, M
   Easton, DF
   Eccles, D
   Edwards, RP
   Ehrencrona, H
   Ejlertsen, B
   Ekici, AB
   Ellis, SD
   Engel, C
   Eriksson, M
   Fasching, PA
   Feliubadalo, L
   Figueroa, J
   Flesch-Janys, D
   Fletcher, O
   Fontaine, A
   Fortuzzi, S
   Fostira, F
   Fridley, BL
   Friebel, T
   Friedman, E
   Friel, G
   Frost, D
   Garber, J
   Garcia-Closas, M
   Gayther, SA
   Gentry-Maharaj, A
   Gerdes, AM
   Giles, GG
   Glasspool, R
   Glendon, G
   Godwin, AK
   Goodman, MT
   Gore, M
   Greene, MH
   Grip, M
   Gronwald, J
   Kaulich, DG
   Guenel, P
   Guzman, SR
   Haeberle, L
   Haiman, CA
   Hall, P
   Halverson, SL
   Hamann, U
   Hansen, TVO
   Harter, P
   Hartikainen, JM
   Healey, S
   Hein, A
   Heitz, F
   Henderson, BE
   Herzog, J
   Hildebrandt, MAT
   Bogdan, CK
   Hogdall, E
   Hogervorst, FBL
   Hopper, JL
   Humphreys, K
   Huzarski, T
   Imyanitov, EN
   Isaacs, C
   Jakubowska, A
   Janavicius, R
   Jaworska, K
   Jensen, A
   Jensen, UB
   Johnson, N
   Jukkola-Vuorinen, A
   Kabisch, M
   Karlan, BY
   Kataja, V
   Kauff, N
   Kelemen, LE
   Kerin, MJ
   Kiemeney, LA
   Kjaer, SK
   Knight, JA
   Knol-Bout, JP
   Konstantopoulou, I
   Kosma, VM
   Krakstad, C
   Kristensen, V
   Kuchenbaecker, KB
   Kupryjanczyk, J
   Laitman, Y
   Lambrechts, D
   Lambrechts, S
   Larson, MC
   Lasa, A
   Laurent-Puig, P
   Lazaro, C
   Le, ND
   Le Marchand, L
   Leminen, A
   Lester, J
   Levine, DA
   Li, JM
   Liang, D
   Lindblom, A
   Lindor, N
   Lissowska, J
   Long, JR
   Lu, KH
   Lubinski, J
   Lundvall, L
   Lurie, G
   Mai, PL
   Mannermaa, A
   Margolin, S
   Mariette, F
   Marme, F
   Martens, JWM
   Massuger, LFAG
   Maugard, C
   Mazoyer, S
   McGuffog, L
   McGuire, V
   McLean, C
   McNeish, L
   Meindi, A
   Menegaux, F
   Menendez, P
   Menkiszak, J
   Menon, U
   Mensenkamp, AR
   Miller, N
   Milne, RL
   Modugno, F
   Montagna, M
   Moysich, KB
   Muller, H
   Mulligan, AM
   Muranen, TA
   Narod, SA
   Nathanson, KL
   Ness, RB
   Neuhausen, SL
   Nevanlinna, H
   Neven, P
   Nielsen, FC
   Nielsen, SF
   Nordestgaard, BG
   Nussbaum, RL
   Odunsi, K
   Offit, K
   Olah, E
   Olopade, OI
   Olson, JE
   Olson, SH
   Oosterwijk, JC
   Orlow, I
   Orr, N
   Orsulic, S
   Osorio, A
   Ottini, L
   Paul, J
   Pearce, CL
   Pedersen, IS
   Peissel, B
   Pejovic, T
   Pelttari, LM
   Perkins, J
   Permuth-Wey, J
   Peterlongo, P
   Peto, J
   Phelan, CM
   Phillips, KA
   Piedmonte, M
   Pike, MC
   Platte, R
   Plisiecka-Halasa, J
   Poole, EM
   Poppe, B
   Pylkas, K
   Radice, P
   Ramus, SJ
   Rebbeck, TR
   Reed, MWR
   Rennert, G
   Risch, HA
   Robson, M
   Rodriguez, GC
   Romero, A
   Rossing, MA
   Rothstein, JH
   Rudolph, A
   Runnebaum, I
   Salani, R
   Salvesen, HB
   Sawyer, EJ
   Schildkraut, JM
   Schmidt, MK
   Schmutzler, RK
   Schneeweiss, A
   Schoemaker, MJ
   Schrauder, MG
   Schumacher, F
   Schwaab, I
   Scuvera, G
   Sellers, TA
   Severi, G
   Seynaeve, CM
   Shah, M
   Shrubsole, M
   Siddiqui, N
   Sieh, W
   Simard, J
   Singer, CF
   Sinilnikova, OM
   Smeets, D
   Sohn, C
   Soller, M
   Song, H
   Soucy, P
   Southey, MC
   Stegmaier, C
   Stoppa-Lyonnet, D
   Sucheston, L
   Swerdlow, A
   Tangen, IL
   Tea, MK
   Teixeira, MR
   Terry, KL
   Terry, MB
   Thomassen, M
   Thompson, PJ
   Tihomirova, L
   Tischkowitz, M
   Toland, AE
   Tollenaar, RAEM
   Tomlinson, I
   Torres, D
   Truong, T
   Tsimiklis, H
   Tung, N
   Tworoger, SS
   Tyrer, JP
   Vachon, CM
   Van 't Veer, LJ
   van Altena, AM
   Van Asperen, CJ
   van den Berg, D
   van den Ouweland, AMW
   van Doom, HC
   Van Nieuwenhuysen, E
   van Rensburg, EJ
   Vergote, I
   Verhoef, S
   Vierkant, RA
   Vijai, J
   Vitonis, AF
   von Wachenfeldt, A
   Walsh, C
   Wang, Q
   Wang-Gohrke, S
   Wappenschmidt, B
   Weischer, M
   Weitzel, JN
   Weltens, C
   Wentzensen, N
   Whittemore, AS
   Wilkens, LR
   Winqvist, R
   Wu, AH
   Wu, XF
   Yang, HP
   Zaffaroni, D
   Zamora, MP
   Zheng, W
   Ziogas, A
   Chenevix-Trench, G
   Pharoah, PDP
   Rookus, MA
   Hooning, MJ
   Goode, EL
AF Hollestelle, Antoinette
   van der Baan, Frederieke H.
   Berchuck, Andrew
   Johnatty, Sharon E.
   Aben, Katja K.
   Agnarsson, Bjarni A.
   Aittomaki, Kristiina
   Alducci, Elisa
   Andrulis, Irene L.
   Anton-Culver, Hoda
   Antonenkova, Natalia N.
   Antoniou, Antonis C.
   Apicella, Carmel
   Arndt, Volker
   Arnold, Norbert
   Arun, Banu K.
   Arver, Brita
   Ashworth, Alan
   Baglietto, Laura
   Balleine, Rosemary
   Bandera, Elisa V.
   Barrowdale, Daniel
   Bean, Yukie T.
   Beckmann, Lars
   Beckmann, Matthias W.
   Benitez, Javier
   Berger, Andreas
   Berger, Raanan
   Beuselinck, Benoit
   Bisogna, Maria
   Bjorge, Line
   Blomqvist, Carl
   Bogdanova, Natalia V.
   Bojesen, Anders
   Bojesen, Stig E.
   Bolla, Manjeet K.
   Bonanni, Bernardo
   Brand, Judith S.
   Brauch, Hiltrud
   Brenner, Hermann
   Brinton, Louise
   Brooks-Wilson, Angela
   Bruinsma, Fiona
   Brunet, Joan
   Bruning, Thomas
   Budzilowska, Agnieszka
   Bunker, Clareann H.
   Burwinkel, Barbara
   Butzow, Ralf
   Buys, Saundra S.
   Caligo, Maria A.
   Campbell, Ian
   Carter, Jonathan
   Chang-Claude, Jenny
   Chanock, Stephen J.
   Claes, Kathleen B. M.
   Collee, J. Margriet
   Cook, Linda S.
   Couch, Fergus J.
   Cox, Angela
   Cramer, Daniel
   Cross, Simon S.
   Cunningham, Julie M.
   Cybulski, Cezary
   Czene, Kamila
   Damiola, Francesca
   Dansonka-Mieszkowska, Agnieszka
   Darabi, Hatef
   de la Hoya, Miguel
   deFazio, Anna
   Dennis, Joseph
   Devilee, Peter
   Dicks, Ed M.
   Diez, Orland
   Doherty, Jennifer A.
   Domchek, Susan M.
   Dorfling, Cecilia M.
   Dork, Thilo
   Dos Santos Silva, Isabel
   du Bois, Andreas
   Dumont, Martine
   Dunning, Alison M.
   Duran, Mercedes
   Easton, Douglas F.
   Eccles, Diana
   Edwards, Robert P.
   Ehrencrona, Hans
   Ejlertsen, Bent
   Ekici, Arif B.
   Ellis, Steve D.
   Engel, Christoph
   Eriksson, Mikael
   Fasching, Peter A.
   Feliubadalo, Lidia
   Figueroa, Jonine
   Flesch-Janys, Dieter
   Fletcher, Olivia
   Fontaine, Annette
   Fortuzzi, Stefano
   Fostira, Florentia
   Fridley, Brooke L.
   Friebel, Tara
   Friedman, Eitan
   Friel, Grace
   Frost, Debra
   Garber, Judy
   Garcia-Closas, Montserrat
   Gayther, Simon A.
   Gentry-Maharaj, Aleksandra
   Gerdes, Anne-Marie
   Giles, Graham G.
   Glasspool, Rosalind
   Glendon, Gord
   Godwin, Andrew K.
   Goodman, Marc T.
   Gore, Martin
   Greene, Mark H.
   Grip, Mervi
   Gronwald, Jacek
   Kaulich, Daphne Gschwantler
   Guenel, Pascal
   Guzman, Starr R.
   Haeberle, Lothar
   Haiman, Christopher A.
   Hall, Per
   Halverson, Sandra L.
   Hamann, Ute
   Hansen, Thomas V. O.
   Harter, Philipp
   Hartikainen, Jaana M.
   Healey, Sue
   Hein, Alexander
   Heitz, Florian
   Henderson, Brian E.
   Herzog, Josef
   Hildebrandt, Michelle A. T.
   Bogdan, Claus K.
   Hogdall, Estrid
   Hogervorst, Frans B. L.
   Hopper, John L.
   Humphreys, Keith
   Huzarski, Tomasz
   Imyanitov, Evgeny N.
   Isaacs, Claudine
   Jakubowska, Anna
   Janavicius, Ramunas
   Jaworska, Katarzyna
   Jensen, Allan
   Jensen, Uffe Birk
   Johnson, Nichola
   Jukkola-Vuorinen, Arja
   Kabisch, Maria
   Karlan, Beth Y.
   Kataja, Vesa
   Kauff, Noah
   Kelemen, Linda E.
   Kerin, Michael J.
   Kiemeney, Lambertus A.
   Kjaer, Susanne K.
   Knight, Julia A.
   Knol-Bout, Jacoba P.
   Konstantopoulou, Irene
   Kosma, Veli-Matti
   Krakstad, Camilla
   Kristensen, Vessela
   Kuchenbaecker, Karoline B.
   Kupryjanczyk, Jolanta
   Laitman, Yael
   Lambrechts, Diether
   Lambrechts, Sandrina
   Larson, Melissa C.
   Lasa, Adriana
   Laurent-Puig, Pierre
   Lazaro, Conxi
   Le, Nhu D.
   Le Marchand, Loic
   Leminen, Arto
   Lester, Jenny
   Levine, Douglas A.
   Li, Jingmei
   Liang, Dong
   Lindblom, Annika
   Lindor, Noralane
   Lissowska, Jolanta
   Long, Jirong
   Lu, Karen H.
   Lubinski, Jan
   Lundvall, Lene
   Lurie, Galina
   Mai, Phuong L.
   Mannermaa, Arto
   Margolin, Sara
   Mariette, Frederique
   Marme, Frederik
   Martens, John W. M.
   Massuger, Leon F. A. G.
   Maugard, Christine
   Mazoyer, Sylvie
   McGuffog, Lesley
   McGuire, Valerie
   McLean, Catriona
   McNeish, Lain
   Meindi, Alfons
   Menegaux, Florence
   Menendez, Primitiva
   Menkiszak, Janusz
   Menon, Usha
   Mensenkamp, Arjen R.
   Miller, Nicola
   Milne, Roger L.
   Modugno, Francesmary
   Montagna, Marco
   Moysich, Kirsten B.
   Mueller, Heiko
   Mulligan, Anna Marie
   Muranen, Taru A.
   Narod, Steven A.
   Nathanson, Katherine L.
   Ness, Roberta B.
   Neuhausen, Susan L.
   Nevanlinna, Heli
   Neven, Patrick
   Nielsen, Finn C.
   Nielsen, Sune F.
   Nordestgaard, Berge G.
   Nussbaum, Robert L.
   Odunsi, Kunle
   Offit, Kenneth
   Olah, Edith
   Olopade, Olufunmilayo I.
   Olson, Janet E.
   Olson, Sara H.
   Oosterwijk, Jan C.
   Orlow, Irene
   Orr, Nick
   Orsulic, Sandra
   Osorio, Ana
   Ottini, Laura
   Paul, James
   Pearce, Celeste L.
   Pedersen, Inge Sokilde
   Peissel, Bernard
   Pejovic, Tanja
   Pelttari, Liisa M.
   Perkins, Jo
   Permuth-Wey, Jenny
   Peterlongo, Paolo
   Peto, Julian
   Phelan, Catherine M.
   Phillips, Kelly-Anne
   Piedmonte, Marion
   Pike, Malcolm C.
   Platte, Radka
   Plisiecka-Halasa, Joanna
   Poole, Elizabeth M.
   Poppe, Bruce
   Pylkas, Katri
   Radice, Paolo
   Ramus, Susan J.
   Rebbeck, Timothy R.
   Reed, Malcolm W. R.
   Rennert, Gad
   Risch, Harvey A.
   Robson, Mark
   Rodriguez, Gustavo C.
   Romero, Atocha
   Rossing, Mary Anne
   Rothstein, Joseph H.
   Rudolph, Anja
   Runnebaum, Ingo
   Salani, Ritu
   Salvesen, Helga B.
   Sawyer, Elinor J.
   Schildkraut, Joellen M.
   Schmidt, Marjanka K.
   Schmutzler, Rita K.
   Schneeweiss, Andreas
   Schoemaker, Minouk J.
   Schrauder, Michael G.
   Schumacher, Fredrick
   Schwaab, Ira
   Scuvera, Giulietta
   Sellers, Thomas A.
   Severi, Gianluca
   Seynaeve, Caroline M.
   Shah, Mitul
   Shrubsole, Martha
   Siddiqui, Nadeem
   Sieh, Weiva
   Simard, Jacques
   Singer, Christian F.
   Sinilnikova, Olga M.
   Smeets, Dominiek
   Sohn, Christof
   Soller, Maria
   Song, Honglin
   Soucy, Penny
   Southey, Melissa C.
   Stegmaier, Christa
   Stoppa-Lyonnet, Dominique
   Sucheston, Lara
   Swerdlow, Anthony
   Tangen, Ingvild L.
   Tea, Muy-Kheng
   Teixeira, Manuel R.
   Terry, Kathryn L.
   Terry, Mary Beth
   Thomassen, Mads
   Thompson, Pamela J.
   Tihomirova, Laima
   Tischkowitz, Marc
   Toland, Amanda Ewart
   Tollenaar, Rob A. E. M.
   Tomlinson, Ian
   Torres, Diana
   Truong, Therese
   Tsimiklis, Helen
   Tung, Nadine
   Tworoger, Shelley S.
   Tyrer, Jonathan P.
   Vachon, Celine M.
   Van 't Veer, Laura J.
   van Altena, Anne M.
   Van Asperen, C. J.
   van den Berg, David
   van den Ouweland, Ans M. W.
   van Doom, Helena C.
   Van Nieuwenhuysen, Els
   van Rensburg, Elizabeth J.
   Vergote, Ignace
   Verhoef, Senno
   Vierkant, Robert A.
   Vijai, Joseph
   Vitonis, Allison F.
   von Wachenfeldt, Anna
   Walsh, Christine
   Wang, Qin
   Wang-Gohrke, Shan
   Wappenschmidt, Barbara
   Weischer, Maren
   Weitzel, Jeffrey N.
   Weltens, Caroline
   Wentzensen, Nicolas
   Whittemore, Alice S.
   Wilkens, Lynne R.
   Winqvist, Robert
   Wu, Anna H.
   Wu, Xifeng
   Yang, Hannah P.
   Zaffaroni, Daniela
   Zamora, M. Pilar
   Zheng, Wei
   Ziogas, Argyrios
   Chenevix-Trench, Georgia
   Pharoah, Paul D. P.
   Rookus, Matti A.
   Hooning, Maartje J.
   Goode, Ellen L.
CA Ovarian Canc Assoc Consortium
   Breast Canc Assoc Consortium
   Consortium Modifiers BRCA1 & BRCA2
   Australian Ovarian Canc Study Grp
   Breast Cancer Family Register
   EMBRACE
   GEMO Study Collaborators
   GENICA Network
   HEBON
   KConFab Investigators
   SWE-BRCA
TI No clinical utility of KRAS variant rs61764370 for ovarian or breast
   cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Review
DE KRAS variant; Breast cancer; Ovarian cancer; Genetic association;
   Clinical outcome
ID GENOME-WIDE ASSOCIATION; MICRORNA-BINDING-SITE; SUSCEPTIBILITY LOCI;
   RISK; PROSTATE; IDENTIFICATION; POLYMORPHISMS; ENDOMETRIOSIS; WOMEN
AB Objective. Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.
   Methods. Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers).
   Results. We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 034, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations.
   Conclusions. rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Box 3079, Durham, NC 27710 USA.
   [Hollestelle, Antoinette; Martens, John W. M.; Seynaeve, Caroline M.; Hooning, Maartje J.] Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands.
   [van der Baan, Frederieke H.; Knol-Bout, Jacoba P.] Netherlands Canc Inst, Amsterdam, Netherlands.
   [Johnatty, Sharon E.; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
   [Aben, Katja K.] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands.
   [Aben, Katja K.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
   [Agnarsson, Bjarni A.] Landspitali Univ Hosp, Reykjavik, Iceland.
   [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
   [Alducci, Elisa] Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy.
   [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
   [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
   [Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
   [Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
   [Antoniou, Antonis C.; Barrowdale, Daniel; Bolla, Manjeet K.; Dennis, Joseph; Easton, Douglas F.; Ellis, Steve D.; Frost, Debra; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Perkins, Jo; Poole, Elizabeth M.; Wang, Qin] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Apicella, Carmel; Baglietto, Laura; Bruinsma, Fiona; Garcia-Closas, Montserrat; Giles, Graham G.; Hopper, John L.; Milne, Roger L.; Orr, Nick; Phillips, Kelly-Anne; Severi, Gianluca] Univ Melbourne, Ctr Epidemiol & Biostat, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
   [Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
   [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany.
   [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
   [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Clin Canc Genet, Houston, TX 77030 USA.
   [Arver, Brita; von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
   [Ashworth, Alan; Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Breast Canc Res, London SW3 6JB, England.
   QIMR Berghofer Med Res Inst, Canc Div, Herston, Qld, Australia.
   Peter MacCallum Canc Inst, 481 Little Lonsdale St, Melbourne, Vic 3000, Australia.
   [deFazio, Anna] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Sydney, NSW 2006, Australia.
   [Baglietto, Laura; Bruinsma, Fiona; Giles, Graham G.; Milne, Roger L.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
   [Baglietto, Laura; Bruinsma, Fiona; Giles, Graham G.; Severi, Gianluca] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
   [Balleine, Rosemary] Univ Sydney, Westmead Millennium Inst Med Res, Western Sydney & Nepean Blue Mt Local Hlth Dist, Sydney, NSW 2006, Australia.
   [Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
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   [Bean, Yukie T.; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
   [Beckmann, Lars] Inst Qual & Efficiency Hlth Care IQWiG, Cologne, Germany.
   [Beckmann, Matthias W.; Benitez, Javier; Fasching, Peter A.; Haeberle, Lothar; Schrauder, Michael G.] Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Erlangen, Germany.
   [Benitez, Javier] CNIO, Spanish Natl Canc Res Ctr, Ctr Natl Genotipac, Human Canc Genet Program, Madrid, Spain.
   [Osorio, Ana] CNIO, Spanish Natl Canc Res Ctr, Human Genet Grp, Madrid, Spain.
   [Benitez, Javier; Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid, Spain.
   [Berger, Andreas; Kaulich, Daphne Gschwantler; Singer, Christian F.; Tea, Muy-Kheng] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria.
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   [Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
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   [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
   [Bogdanova, Natalia V.; Dork, Thilo] Hannover Med Sch, Dept Obstet & Gynaecol, Hannover, Germany.
   [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
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   [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Berge G.; Weischer, Maren] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
   [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Berge G.; Weischer, Maren] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
   [Bonanni, Bernardo] Ist Europeo Oncol IEO, Div Canc Prevent & Genet, Milan, Italy.
   [Brand, Judith S.; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Humphreys, Keith; Li, Jingmei] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
   [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
   [Brauch, Hiltrud] German Canc Consortium DKTK, Heidelberg, Germany.
   Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
   [Brinton, Louise; Chanock, Stephen J.; Figueroa, Jonine; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
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   [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
   [Brunet, Joan] IDIBGI Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain.
   [Bruning, Thomas] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany.
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   [Bunker, Clareann H.; Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
   [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
   [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
   [Butzow, Ralf; Leminen, Arto; Muranen, Taru A.; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
   [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
   [Caligo, Maria A.] Univ Pisa, Univ Hosp Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy.
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   [Campbell, Ian; Phillips, Kelly-Anne] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia.
   [Campbell, Ian] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
   [Carter, Jonathan] Chris OBrien Lifehouse, Gynaecol Oncol, Sydney, NSW, Australia.
   [Carter, Jonathan] Univ Sydney, Sydney, NSW 2006, Australia.
   [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
   [Claes, Kathleen B. M.] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
   [Collee, J. Margriet; van den Ouweland, Ans M. W.] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
   [Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
   [Couch, Fergus J.; Guzman, Starr R.; Olson, Janet E.; Vachon, Celine M.; Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
   [Couch, Fergus J.; Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN USA.
   [Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England.
   [Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
   [Cramer, Daniel; Poppe, Bruce; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
   [Cybulski, Cezary] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
   [Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.] Univ Lyon 1, CNRS UMR5286, INSERM U1052, Ctr Rech Cancerol Lyon, F-69365 Lyon, France.
   [de la Hoya, Miguel; Romero, Atocha] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
   [deFazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia.
   [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
   [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
   [Dicks, Ed M.; Dunning, Alison M.; Easton, Douglas F.; Shah, Mitul; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
   [Diez, Orland] Univ Hosp Vail dHebron, Vali Dhebron Inst Oncol VHIO, Oncogenet Lab, Barcelona, Spain.
   [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Lebanon, NH USA.
   [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Basser Res Ctr, Philadelphia, PA 19104 USA.
   [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa.
   [Dos Santos Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England.
   [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Klin Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany.
   [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, Essen, Germany.
   [Dumont, Martine; Simard, Jacques; Soucy, Penny] Univ Laval, Ctr Hosp Univ, Quebec Res Ctr, Quebec City, PQ, Canada.
   [Duran, Mercedes] Univ Valladolid, IBGM UVA, Valladolid, Spain.
   [Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, Southampton SO9 5NH, Hants, England.
   [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA.
   [Ehrencrona, Hans] Lund Univ, Dept Clin Genet, Lund, Sweden.
   [Ejlertsen, Bent] Rigshosp, Copenhagen Univ Hosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
   [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
   [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
   [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Feliubadalo, Lidia; Lazaro, Conxi] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain.
   [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany.
   [Fontaine, Annette; Herzog, Josef; Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet, 1500 E Duarte Rd, Duarte, CA 91010 USA.
   [Fontaine, Annette] New Mexico Canc Ctr, Albuquerque, NM USA.
   [Fortuzzi, Stefano; Mariette, Frederique; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol IFOM, Milan, Italy.
   [Fortuzzi, Stefano; Mariette, Frederique] Cogentech Canc Genet Test Lab, Milan, Italy.
   [Fostira, Florentia; Konstantopoulou, Irene] Natl Ctr Sci Res Demokritos, Inst Nucl & Radiol Sci & Technol Energy & Safety, Mol Diagnost Lab, Athens, Greece.
   [Fridley, Brooke L.] Univ Kansas, Ctr Canc, Kansas IDeA Network Biomed Res Excellence Bioinfo, Kansas City, KS USA.
   [Friebel, Tara] Univ Penn, Philadelphia, PA 19104 USA.
   [Friedman, Eitan; Laitman, Yael] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
   [Friedman, Eitan; Laitman, Yael] Sheba Med Ctr, Inst Oncol, Tel Hashomer, Israel.
   [Friel, Grace; Odunsi, Kunle; Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
   [Garber, Judy] Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA 02115 USA.
   [Gayther, Simon A.; Haiman, Christopher A.; Henderson, Brian E.; Pearce, Celeste L.; Pike, Malcolm C.; Plisiecka-Halasa, Joanna; Ramus, Susan J.; Schumacher, Fredrick; van den Berg, David; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   UNICANCER Genet Grp, GEMO Study Natl Canc Genet Network, Paris, France.
   Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany.
   Univ Bonn, Fac Med, Inst Pathol, Bonn, Germany.
   Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, Hamburg, Germany.
   [Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
   [Gentry-Maharaj, Aleksandra; Menon, Usha; Montagna, Marco] UCL, Inst Womens Hlth, Gynaecol Canc Res Ctr, Dept Womens Canc, London, England.
   [Gerdes, Anne-Marie] Rigshosp, Copenhagen Univ Hosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
   [Glasspool, Rosalind; Paul, James] Beason West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland.
   [Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
   [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
   [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
   [Gore, Martin] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
   [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
   [Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland.
   [Gronwald, Jacek; Huzarski, Tomasz; Jakubowska, Anna; Jaworska, Katarzyna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
   [Guenel, Pascal; Menegaux, Florence; Truong, Therese] INSERM, CESP, Ctr Res Epidemiol & Populat Hlth, U1018,Environm Epidemiol Canc, Villejuif, France.
   [Guenel, Pascal; Menegaux, Florence; Truong, Therese] Univ Paris 11, UMRS 1018, Villejuif, France.
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   [Hansen, Thomas V. O.; Nielsen, Finn C.] Rigshosp, Copenhagen Univ Hosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark.
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   Netherlands Canc Inst, Coordinating Ctr, Hereditary Breast & Ovarian Canc Res Grp Netherla, Amsterdam, Netherlands.
   [Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Ctr Comprehens Canc, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
   [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Bogdan, Claus K.; Kjaer, Susanne K.; Lundvall, Lene] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark.
   [Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark.
   [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
   [Hogervorst, Frans B. L.; Schmidt, Marjanka K.; Van 't Veer, Laura J.; Verhoef, Senno] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
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   [Jaworska, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland.
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   [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
   [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
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   Peter MacCallum Canc Ctr, KConFab Kathleen Cuningham Consortium Res Familil, Melbourne, Australia.
   [Kelemen, Linda E.] Alberta Hlth Serv Cancer Care, Dept Populat Hlth Res, Calgary, AB, Canada.
   [Kelemen, Linda E.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada.
   [Kelemen, Linda E.] Univ Calgary, Dept Oncol, Calgary, AB, Canada.
   [Kerin, Michael J.; Miller, Nicola] Natl Univ Ireland Univ Coll Galway, Sch Med, Galway, Ireland.
   [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
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   [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
   [Kristensen, Vessela] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway.
   [Kristensen, Vessela] Univ Oslo, Fac Med, Fac Div Ahus, N-0316 Oslo, Norway.
   [Lambrechts, Diether; Smeets, Dominiek] Univ Leuven, Dept Oncol, Lab Translat Genet, Louvain, Belgium.
   [Lambrechts, Diether; Smeets, Dominiek] VIB, VRC, Leuven, Belgium.
   [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium.
   [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium.
   [Larson, Melissa C.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
   [Lasa, Adriana; Osorio, Ana] CNIO, Spanish Natl Canc Res Ctr, Human Canc Genet Program, Genet & Mol Epidemiol Grp, Madrid, Spain.
   [Laurent-Puig, Pierre] Univ Paris, Sorbonne Paris Cite, UMR S775, F-75252 Paris, France.
   [Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 4E6, Canada.
   [Le Marchand, Loic; Lurie, Galina; Wilkens, Lynne R.] Univ Hawaii, Canc Res Ctr, Canc Epidemiol Program, Honolulu, HI 96813 USA.
   [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
   [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
   [Lindor, Noralane] Mayo Clin, Ctr Individualized Med, Scottsdale, AZ USA.
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   [Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
   [Margolin, Sara] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden.
   [Marme, Frederik; Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
   [Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Med Ctr, Dept Gynecol, NL-6525 ED Nijmegen, Netherlands.
   [Maugard, Christine] CHRU Nouvel Hop Civil, Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France.
   [Maugard, Christine] CHRU Nouvel Hop Civil, Hop Univ Strasbourg, Serv Oncohematol, Strasbourg, France.
   [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA USA.
   [McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic, Australia.
   [McNeish, Lain] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Inst Canc Sci, Glasgow, Lanark, Scotland.
   [Meindi, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Dept Gynecol & Obstet, Div Tumor Genet, D-80290 Munich, Germany.
   [Menendez, Primitiva] Hosp Monte Naranco, Serv Anat Patol, Oviedo, Spain.
   [Menkiszak, Janusz] Pomeranian Med Univ, Dept Surg Gynecol & Gynecol Oncol Adults & Adolsc, Szczecin, Poland.
   [Mensenkamp, Arjen R.; Moysich, Kirsten B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
   [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA.
   [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
   [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
   [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
   Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
   [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
   [Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
   [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA USA.
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   [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
   [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
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   [Oosterwijk, Jan C.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
   [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
   [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Clin Biochem, Sect Mol Diagnost, Aalborg, Denmark.
   [Peissel, Bernard; Scuvera, Giulietta; Zaffaroni, Daniela] Fdn Ist Ricovero & Cura Carattere Sci, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
   [Permuth-Wey, Jenny; Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
   [Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia.
   [Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia.
   [Piedmonte, Marion; Platte, Radka] NRG Oncol Stat & Data Management Ctr, Buffalo, NY USA.
   [Poppe, Bruce; Tworoger, Shelley S.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA.
   [Poppe, Bruce; Tworoger, Shelley S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
   [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Lab Canc Genet & Tumor Biol, Oulu, Finland.
   [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Bioctr Oulu, Oulu, Finland.
   [Radice, Paolo] Fdn Ist Ricovero & Cura Carattere Sci, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
   [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel.
   [Rennert, Gad] Technion Israel Inst Technol, Carmel Med Ctr, Dept Community Med & Epidemiol, Haifa, Israel.
   [Rennert, Gad] Technion Israel Inst Technol, B Rappaport Fac Med, Haifa, Israel.
   [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
   [Rodriguez, Gustavo C.] Univ Chicago, NorthShore Univ Hlth Syst, Evanston, IL USA.
   [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
   [Runnebaum, Ingo] Jena Univ Hosp, Dept Gynecol, Jena, Germany.
   [Salani, Ritu] Ohio State Univ, Columbus, OH 43210 USA.
   [Sawyer, Elinor J.] Kings Coll London, Guys & St Thomas NHS Fdn Trust, NIHR Comprehens Biomed Res Ctr, Div Canc Studies, London, England.
   [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
   [Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA.
   [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany.
   [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CMMC, Cologne, Germany.
   [Schoemaker, Minouk J.; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
   [Schwaab, Ira] Inst Humangenet Wiesbaden, Wiesbaden, Germany.
   [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynecol Oncol, Glasgow G4 0SF, Lanark, Scotland.
   [Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France.
   [Soller, Maria] Univ Lund Hosp, Dept Clin Genet, Univ & Reg Labs, S-22185 Lund, Sweden.
   [Southey, Melissa C.; Tsimiklis, Helen] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
   [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
   [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France.
   [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, U830, Paris, France.
   [Stoppa-Lyonnet, Dominique] Univ Paris 07, Sorbonne Paris Cite, F-75221 Paris 05, France.
   Lund Univ, Dept Oncol, Lund, Sweden.
   [Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, Sutton, Surrey, England.
   [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
   [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
   [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA.
   [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
   [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
   [Tischkowitz, Marc] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada.
   [Tischkowitz, Marc] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada.
   [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Human Canc Genet, Columbus, OH 43210 USA.
   [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Div Human Canc Genet, Columbus, OH 43210 USA.
   [Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands.
   [Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
   [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX1 2JD, England.
   [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia.
   [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
   [Van Asperen, C. J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
   [van Doom, Helena C.] Erasmus MC Canc Inst, Dept Gynecol, Rotterdam, Netherlands.
   [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany.
   [Zamora, M. Pilar] Hosp Univ La Paz, Serv Oncol Med, Madrid, Spain.
   [Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92717 USA.
   [Rookus, Matti A.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
   [Agnarsson, Bjarni A.] Univ Iceland, Sch Med, Reykjavik, Iceland.
   [Brauch, Hiltrud] Canc Res Ctr DKFZ, Heidelberg, Germany.
   [Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hollestelle, A (reprint author), Duke Univ, Med Ctr, Duke Canc Inst, Box 3079, Durham, NC 27710 USA.
EM berch001@mc.duke.edu
RI Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; Bjorge,
   Line/C-1307-2017; salvesen, Helga/C-1187-2017; Peissel,
   Bernard/E-8187-2017; montagna, marco/E-2225-2012; Feliubadalo,
   Lidia/G-4577-2016; Johnatty, Sharon/R-8890-2016; Hein,
   Alexander/F-6999-2010; Bruning, Thomas/G-8120-2015; Hartikainen,
   Jaana/E-6256-2015; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011;
   Osorio, Ana/I-4324-2014; Shrubsole, Martha/K-5052-2015; Dork,
   Thilo/J-8620-2012; Li, Jingmei/I-2904-2012; Menkiszak,
   Janusz/I-4036-2014; Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013
OI Muranen, Taru/0000-0002-5895-1808; Brunet, Joan/0000-0003-1945-3512;
   Kauff, Noah/0000-0001-7242-6156; Dunning, Alison
   Margaret/0000-0001-6651-7166; Krakstad, Camilla/0000-0002-0174-8139;
   Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684;
   Gronwald, Jacek/0000-0002-3643-2871; Brenner,
   Hermann/0000-0002-6129-1572; Bjorge, Line/0000-0002-0240-2770; salvesen,
   Helga/0000-0002-4438-8831; Peissel, Bernard/0000-0001-9233-3571;
   montagna, marco/0000-0002-4929-2150; Phillips,
   Kelly-Anne/0000-0002-0475-1771; Teixeira, Manuel/0000-0002-4896-5982;
   Ramus, Susan/0000-0003-0005-7798; Menon, Usha/0000-0003-3708-1732;
   Feliubadalo, Lidia/0000-0002-1736-0112; Ehrencrona,
   Hans/0000-0002-5589-3622; Johnatty, Sharon/0000-0002-7888-1966; Hein,
   Alexander/0000-0003-2601-3398; Bruning, Thomas/0000-0001-9560-5464;
   Osorio, Ana/0000-0001-8124-3984; Shrubsole, Martha/0000-0002-5591-7575;
   Li, Jingmei/0000-0001-8587-7511; Zheng, Wei/0000-0003-1226-070X
FU European Commission [223175 HEALTH-F2-2009-223175]; Ovarian Cancer
   Research Fund [PPD/RPCI.07]; US National Cancer Institute GAME-ON
   Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113]; National
   Health and Medical Research Council; Deutsche Krebshilfe; American
   Cancer Society [SIOP-06-258-01-COUN]; Barbara Thomason Ovarian Cancer
   Research Professorship from the American Cancer Society
   [SIOP-06-090-06]; California Cancer Research Program [00-01389V-20170,
   N01-CN25403, 2110200]; Canadian Institutes for Health Research; Cancer
   Council Victoria; Cancer Council Queensland; Cancer Council New South
   Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer
   Foundation of Western Australia; Cancer Institute of New Jersey; Cancer
   Research UK [C490/A6187, C490/A10119, C490/A10124, C536/A13086,
   C536/A6689]; Celma Mastry Ovarian Cancer Foundation the Danish Cancer
   Society [94-222-52]; ELAN Funds of the University of Erlangen-Nuremberg;
   Eve Appeal; Helsinki University Central Hospital Research Fund; Imperial
   Experimental Cancer Research Centre [C1312/A15589]; Ovarian Cancer
   Research Fund; Nationaal Kankerplan of Belgium; L AMP; S Milken
   Foundation; Polish Ministry of Science and Higher Education [4 PO5C 028
   14, 2 PO5A 068 27]; Roswell Park Cancer Institute Alliance Foundation;
   US National Cancer Institute [K07-CA095666, K07-CA143047, K22-CA138563,
   N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696,
   P3O-CA15083, P5O-CA105009, P50-CA136393]; US Army Medical Research and
   Material Command [DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666,
   DAMD17-02-1-0669, W81XWH-07-0449]; National Health and Medical Research
   Council of Australia [199600, 400281]; German Federal Ministry of
   Education and Research of Germany Programme of Clinical Biomedical
   Research [01 GB 9401]; state of Baden-Wurttemberg through Medical
   Faculty of the University of Ulm [P.685]; Minnesota Ovarian Cancer
   Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation;
   Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU Foundation;
   Mermaid I project; Rudolf-Bartling Foundation; UK National Institute for
   Health Research Biomedical Research Centres at the University of
   Cambridge; Imperial College London; University College Hospital "Women's
   Health Theme"; Royal Marsden Hospital; WorkSafeBC; The US National
   Cancer Institute [R01-CA014089, R01-CA016056, R01-CA017054,
   R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860,
   R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277,
   R01-CA067262, R01-CA071766, R01-CA076016, R01-CA080978, R01-CA087538,
   R01-CA092044]; A US National Cancer Institute [R01-095023, R01-CA106414,
   R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429,
   R01CA83918, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867,
   U01-CA069417, U01-CA071966]
FX The COGS project is funded through a European Commission's Seventh
   Framework Programme grant (agreement number 223175
   HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is
   supported by a grant from the Ovarian Cancer Research Fund thanks to
   donations by the family and friends of Kathryn Sladek Smith
   (PPD/RPCI.07). The scientific development and funding for this project
   were in part supported by the US National Cancer Institute GAME-ON
   Post-GWAS Initiative (U19-CA148112). This study made use of data
   generated by the Wellcome Trust Case Control consortium. A full list of
   the investigators who contributed to the generation of the data is
   available from http://www.wtccc.org.uk/. Funding for the project was
   provided by the Wellcome Trust under award 076113.r G.C.-T. and P.M.W.
   are supported by the National Health and Medical Research Council;
   P.A.F. is supported by the Deutsche Krebshilfe; B.K. holds an American
   Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN);
   K.-A.P. is an Australian National Breast Cancer Foundation Fellow; and
   A.B. holds the Barbara Thomason Ovarian Cancer Research Professorship
   from the American Cancer Society (SIOP-06-090-06). R. Balleine was a
   Cancer Institute NSW Clinical Research Fellow.r OCAC, in particular,
   acknowledges D. Bowtell, A. deFazio, D. Gertig, A. Green, P. Parsons, N.
   Hayward and D. Whiteman (AUS); G. Peuteman, T. Van Brussel and D. Smeets
   (BEL); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schtirmann,
   F. Kramer, W. Zheng, T.-W. Park Simon, K. Beer-Grondke and D. Schmidt
   (HJO); Sharon Windebank, Christopher Hilker and Jason Vollenweider
   (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL,
   GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH,
   OK OR, PA, RI, SC, TN, TX, VA, WA, and WY (NHS); L. Paddock, M. King, U.
   Chandran, A. Samoila, and Y. Bensman (NJO); L. Brinton, M. Sherman, A.
   Hutchinson, N. SzeszeniaDabrowska, B. Peplonska, W. Zatonski, A. Soni,
   P. Chao and M. Stagner (POL); C. Luccarini, P. Harrington, the SEARCH
   team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group
   and SCOTROCI investigators (SRO); W -H. Chow and Y -T. Gao (SWH); I.
   Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford
   (UKO); and Carole Pye (UKR).; Funding of the constituent OCAC studies
   was provided by the American Cancer Society (CRTG-00-196-01-CCE); the
   California Cancer Research Program (00-01389V-20170, N01-CN25403,
   2110200); the Canadian Institutes for Health Research; Cancer Council
   Victoria; Cancer Council Queensland; Cancer Council New South Wales;
   Cancer Council South Australia; Cancer Council Tasmania; Cancer
   Foundation of Western Australia; the Cancer Institute of New Jersey;
   Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086,
   C536/A6689); the Celma Mastry Ovarian Cancer Foundation the Danish
   Cancer Society (94-222-52); ELAN Funds of the University of
   Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central
   Hospital Research Fund; Imperial Experimental Cancer Research Centre
   (C1312/A15589); the Ovarian Cancer Research Fund; Nationaal Kankerplan
   of Belgium; the L & S Milken Foundation; the Polish Ministry of Science
   and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park
   Cancer Institute Alliance Foundation; the US National Cancer Institute
   (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010,
   N01-PC035137, P01-CA017054, P01-CA087696, P3O-CA15083, P5O-CA105009,
   P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449,
   R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107,
   R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262,
   R01-CA071766, R01-CA076016, R01-CA080978, R01-CA087538, R01-CA092044,
   R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343,
   R01-CA126841, R01-CA149429, R01CA83918, R03-CA113148, R03-CA115195,
   R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966 and Intramural
   research funds); the US Army Medical Research and Material Command
   (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669,
   W81XWH-07-0449); the National Health and Medical Research Council of
   Australia (199600 and 400281); the German Federal Ministry of Education
   and Research of Germany Programme of Clinical Biomedical Research (01 GB
   9401); the state of Baden-Wurttemberg through Medical Faculty of the
   University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the
   Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the
   Lon V.r Smith Foundation (LVS-39420); the Oak Foundation; the OHSU
   Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the
   UK National Institute for Health Research Biomedical Research Centres at
   the University of Cambridge, Imperial College London, University College
   Hospital "Women's Health Theme" and the Royal Marsden Hospital; and
   WorkSafeBC.
NR 39
TC 2
Z9 3
U1 87
U2 104
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAY
PY 2016
VL 141
IS 2
BP 386
EP 401
DI 10.1016/j.ygyno.2015.04.034
PG 16
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DL0YJ
UT WOS:000375358200032
ER

PT J
AU Lathrop, DA
   Rosen, MR
AF Lathrop, David A.
   Rosen, Michael R.
TI Peter M. Spooner, November 11, 1942-January 30, 2016
SO HEART RHYTHM
LA English
DT Biographical-Item
C1 [Lathrop, David A.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
   [Rosen, Michael R.] Columbia Univ, Med Ctr, Dept Pharmacol, New York, NY USA.
   [Rosen, Michael R.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY USA.
RP Rosen, MR (reprint author), Columbia Univ, Med Ctr, Pharmacol, P&S7-444,630 W 168 St, New York, NY 10032 USA.; Rosen, MR (reprint author), Columbia Univ, Med Ctr, Pediat, P&S7-444,630 W 168 St, New York, NY 10032 USA.
EM mrr1@cumc.columbia.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD MAY
PY 2016
VL 13
IS 5
BP 187
EP 187
DI 10.1016/j.hrthm.2016.02.011
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DL2LL
UT WOS:000375466200034
PM 27131073
ER

PT J
AU Maric-Bilkan, C
   Arnold, AP
   Taylor, DA
   Dwinell, M
   Howlett, SE
   Wenger, N
   Reckelhoff, JF
   Sandberg, K
   Churchill, G
   Levin, E
   Lundberg, MS
AF Maric-Bilkan, Christine
   Arnold, Arthur P.
   Taylor, Doris A.
   Dwinell, Melinda
   Howlett, Susan E.
   Wenger, Nanette
   Reckelhoff, Jane F.
   Sandberg, Kathryn
   Churchill, Gary
   Levin, Ellis
   Lundberg, Martha S.
TI Report of the National Heart, Lung, and Blood Institute Working Group on
   Sex Differences Research in Cardiovascular Disease Scientific Questions
   and Challenges
SO HYPERTENSION
LA English
DT Review
ID ENDOTHELIAL PROGENITOR CELLS; ESTROGEN-RECEPTOR-ALPHA; II-INDUCED
   HYPERTENSION; DAHL-S RATS; REPERFUSION INJURY; DNA METHYLATION; T-CELL;
   EXPRESSION; GENDER; GROWTH
C1 [Maric-Bilkan, Christine; Lundberg, Martha S.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Arnold, Arthur P.] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90024 USA.
   [Taylor, Doris A.] Texas Heart Inst, Dept Regenerat Med, Houston, TX 77025 USA.
   [Dwinell, Melinda] Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
   [Howlett, Susan E.] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada.
   [Howlett, Susan E.] Univ Manchester, Cardiovasc Physiol, Manchester, Lancs, England.
   [Wenger, Nanette] Emory Univ, Dept Med, Sch Med, Atlanta, GA 30322 USA.
   [Reckelhoff, Jane F.] Univ Mississippi, Dept Physiol, Med Ctr, Jackson, MS USA.
   [Sandberg, Kathryn] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
   [Churchill, Gary] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
   [Levin, Ellis] Univ Calif Irvine, Dept Diabet Endocrinol & Metab, Irvine, CA USA.
RP Maric-Bilkan, C (reprint author), NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, Room 8110,6701 Rockledge Dr, Bethesda, MD 20892 USA.; Lundberg, MS (reprint author), NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, Room 8210,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM christine.maric-bilkan@nih.gov; lundberm@nhlbi.nih.gov
OI Howlett, Susan/0000-0001-5351-6308
FU National Institutes of Health/National Heart, Lung, and Blood Institute,
   Bethesda, MD
FX Funding for the Working Group meeting was provided by the National
   Institutes of Health/National Heart, Lung, and Blood Institute,
   Bethesda, MD.
NR 51
TC 8
Z9 8
U1 3
U2 4
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 MAY
PY 2016
VL 67
IS 5
BP 802
EP 807
DI 10.1161/HYPERTENSIONAHA.115.06967
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DK2WZ
UT WOS:000374776400055
PM 26975706
ER

PT J
AU Pingili, AK
   Thirunavukkarasu, S
   Kara, M
   Brand, DD
   Katsurada, A
   Majid, DSA
   Navar, LG
   Gonzalez, FJ
   Malik, KU
AF Pingili, Ajeeth K.
   Thirunavukkarasu, Shyamala
   Kara, Mehmet
   Brand, David D.
   Katsurada, Akemi
   Majid, Dewan S. A.
   Navar, L. Gabriel
   Gonzalez, Frank J.
   Malik, Kafait U.
TI 6 beta-Hydroxytestosterone, a Cytochrome P450
   1B1-Testosterone-Metabolite, Mediates Angiotensin II-Induced Renal
   Dysfunction in Male Mice
SO HYPERTENSION
LA English
DT Article
DE 6 beta-hydroxytestosterone; angiotensinogen; cytochrome P450 1B1;
   fibrosis
ID SALT-SENSITIVE HYPERTENSION; OBESE ZUCKER RATS; MONOCYTE CHEMOATTRACTANT
   PROTEIN-1; TYPE-2 RECEPTOR STIMULATION; OXIDATIVE STRESS; URINARY
   ALBUMIN; AT(2) RECEPTOR; THERAPEUTIC IMPLICATIONS; FRACTIONAL EXCRETION;
   DIABETIC-NEPHROPATHY
AB 6 beta-Hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension, and end-organ damage, this study was conducted to determine the contribution of 6 beta-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1+/+ and Cyp1b1-/-mice. Castration of Cyp1b1+/+ mice or Cyp1b1-/gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6 beta-Hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1+/+ mice, but restored these effects of angiotensin II in Cyp1b1-/-or castrated Cyp1b1+/+ mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin-converting enzyme. 6 beta-Hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin-converting enzyme in Cyp1b1+/+ mice. However, in Cyp1b1-/-or castrated Cyp1b1+/+ mice, it restored these effects of angiotensin II. These data indicate that 6 beta-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end-organ injury associated with angiotensin IIinduced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in male mice.
C1 [Pingili, Ajeeth K.; Thirunavukkarasu, Shyamala; Kara, Mehmet; Malik, Kafait U.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA.
   [Brand, David D.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Med & Microbiol,Immunol & Biochem, Memphis, TN 38163 USA.
   [Brand, David D.] Vet Affairs Med Ctr, Memphis, TN USA.
   [Katsurada, Akemi; Majid, Dewan S. A.; Navar, L. Gabriel] Tulane Univ, Sch Med, Dept Physiol, Tulane Hypertens & Renal Ctr Excellence, New Orleans, LA 70112 USA.
   [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, 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
FU National Institutes of Health; National Heart, Lung, and Blood Institute
   [R01HL-19134-40, R01HL-079109-09, R01HL-66432, R01HL26371]; Department
   of Veterans Affairs [BX001193-02]; Tulane Bridge Fund; National
   Institute of General Medical Sciences IDeA Program (COBRE)
   [P30GM103337]; Department of Pharmacology, Faculty of Medicine, Erciyes
   University, Kayseri, Turkey
FX This work was supported by the National Institutes of Health and
   National Heart, Lung, and Blood Institute grants R01HL-19134-40 and
   R01HL-079109-09 (Dr Malik); and the Department of Veterans Affairs
   BX001193-02 (Dr Brand); the National Heart, Lung, and Blood Institute
   (R01HL-66432) and the Tulane Bridge Fund (Dr Majid); the National
   Institute of General Medical Sciences IDeA Program (COBRE, P30GM103337),
   and by the National Institutes of Health and National Heart, Lung, and
   Blood Institute grant R01HL26371 (Dr Navar). Dr Kara was supported by a
   fellowship from the Department of Pharmacology, Faculty of Medicine,
   Erciyes University, Kayseri, Turkey 38039. The contents of this article
   are solely the responsibility of us and do not necessarily represent the
   official views of the National Heart, Lung, and Blood Institute.
NR 67
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Z9 1
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 MAY
PY 2016
VL 67
IS 5
BP 916
EP 926
DI 10.1161/HYPERTENSIONAHA.115.06936
PG 11
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DK2WZ
UT WOS:000374776400075
PM 26928804
ER

PT J
AU Fleshner, M
   Olivier, KN
   Shaw, PA
   Adjemian, J
   Strollo, S
   Claypool, RJ
   Folio, L
   Zelazny, A
   Holland, SM
   Prevots, DR
AF Fleshner, M.
   Olivier, K. N.
   Shaw, P. A.
   Adjemian, J.
   Strollo, S.
   Claypool, R. J.
   Folio, L.
   Zelazny, A.
   Holland, S. M.
   Prevots, D. R.
TI Mortality among patients with pulmonary non-tuberculous mycobacteria
   disease
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE epidemiology; non-tuberculous mycobacteria; lung infection; mortality
ID HIV-NEGATIVE PATIENTS; COMPLEX LUNG-DISEASE; AVIUM-COMPLEX;
   PROGNOSTIC-FACTORS; RISK-FACTORS; FOLLOW-UP; PREVALENCE; INTRACELLULARE;
   INFECTIONS; JAPAN
AB SETTING: Tertiary referral center, National Institutes of Health (NIH), USA.
   OBJECTIVE: To estimate the mortality rate and its correlates among persons with pulmonary non-tuberculous mycobacteria (PNTM) disease.
   DESIGN: A retrospective review of 106 patients who were treated at the NIH Clinical Center and met American Thoracic Society/Infectious Diseases Society of America criteria for PNTM. Eligible patients were aged 18 years and did not have cystic fibrosis or human immunodeficiency virus (HIV) infection.
   RESULTS: Of 106 patients followed for a median of 4.9 years, 27 (25%) died during follow-up, for a mortality rate of 4.2 per 100 person-years. The population was predominantly female (88%) and White (88%), with infrequent comorbidities. Fibrocavitary disease (adjusted hazard ratio [aHR] 3.3, 95% confidence interval [CI] 1.3-8.3) and pulmonary hypertension (aHR 2.1, 95 %CI 0.9-5.1) were associated with a significantly elevated risk of mortality in survival analysis.
   CONCLUSIONS: PNTM remains a serious public health concern, with a consistently elevated mortality rate across multiple populations. Significant risk factors for death include fibrocavitary disease and pulmonary hypertension. Further research is needed to more specifically identify clinical and microbiologic factors that jointly influence disease outcome.
C1 [Fleshner, M.; Adjemian, J.; Strollo, S.; Prevots, D. R.] NIAID, Epidemiol Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Fleshner, M.; Adjemian, J.; Strollo, S.; Claypool, R. J.; Holland, S. M.; Prevots, D. R.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Olivier, K. N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Shaw, P. A.] Univ Penn, Perelman Sch Med, Div Clin Res, Biostat Res Branch, Philadelphia, PA 19104 USA.
   [Shaw, P. A.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Folio, L.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Zelazny, A.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Prevots, DR (reprint author), NIAID, NIH, 8 West Dr MSC 2665, Bethesda, MD 20892 USA.
EM rprevots@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
   Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
FX This research was supported in part by the Intramural Research Program
   of the National Institute of Allergy and Infectious Diseases, National
   Institutes of Health, Bethesda, MD, USA.
NR 33
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U1 0
U2 3
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD MAY
PY 2016
VL 20
IS 5
BP 582
EP 587
DI 10.5588/ijtld.15.0807
PG 6
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA DK9GR
UT WOS:000375239400005
PM 27084809
ER

PT J
AU Olwenyi, OA
   Naluyima, P
   Cham, F
   Quinn, TC
   Serwadda, D
   Sewankambo, NK
   Gray, RH
   Sandberg, JK
   Michael, NL
   Wabwire-Mangen, F
   Robb, ML
   Eller, MA
AF Olwenyi, Omalla A.
   Naluyima, Prossy
   Cham, Fatim
   Quinn, Thomas C.
   Serwadda, David
   Sewankambo, Nelson K.
   Gray, Ronald H.
   Sandberg, Johan K.
   Michael, Nelson L.
   Wabwire-Mangen, Fred
   Robb, Merlin L.
   Eller, Michael A.
TI Differential Associations of Interleukin 6 and Intestinal Fatty
   Acid-Binding Protein With Progressive Untreated HIV-1 Infection in
   Rakai, Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1; AIDS; immune activation; inflammation; IL-6; IFABP
ID C-REACTIVE PROTEIN; IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION;
   SYSTEMIC IMMUNE ACTIVATION; DISEASE PROGRESSION; MICROBIAL
   TRANSLOCATION; GASTROINTESTINAL-TRACT; VIRAL LOAD; ANTIRETROVIRAL
   THERAPY; PREDICT MORTALITY
AB The significance of HIV-associated immune activation and microbial translocation in Sub-Saharan African population remains poorly defined. We assessed biomarkers of inflammation, microbial translocation, and cellular activation and found most factors elevated in Ugandan HIV-1 seroconverters compared with community-matched controls. In contrast to previous findings in Western cohorts, C-reactive protein, neopterin, and intestinal fatty acid binding protein were not elevated. Higher T-cell activation and IL-6 were associated with faster disease progression. Surprisingly, intestinal fatty acid binding protein, indicative of enterocyte turnover, was higher in slow than in fast progressors. These data suggest differential relationships among biomarkers of intestinal barrier integrity and innate immune activation between developed countries and Sub-Saharan Africa.
C1 [Olwenyi, Omalla A.; Naluyima, Prossy; Cham, Fatim; Wabwire-Mangen, Fred] Makerere Univ Walter Reed Project, Kampala, Uganda.
   [Naluyima, Prossy; Sandberg, Johan K.] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Ctr Infect Med,Dept Med, Stockholm, Sweden.
   [Cham, Fatim] Henry M Jackson Fdn Adv of Mil Med, Bethesda, MD USA.
   [Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Serwadda, David; Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
   [Serwadda, David; Sewankambo, Nelson K.] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda.
   [Sewankambo, Nelson K.] Makerere Univ, Coll Hlth Sci, Fac Med, Kampala, Uganda.
   [Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
RP Eller, MA (reprint author), Walter Reed Army Inst, HJF, US Mil HIV Res Program MHRP, 503 Robert Grant Ave,1N11, Silver Spring, MD 20910 USA.
EM meller@hivresearch.org
FU Henry M. Jackson Foundation for the Advancement of Military Medicine,
   Inc. [W81XWH-11-2-0174]; U.S. Army Medical Research and Materiel Command
   [W81XWH-11-2-0174]
FX Supported by a cooperative agreement (W81XWH-11-2-0174) between the
   Henry M. Jackson Foundation for the Advancement of Military Medicine,
   Inc., and the U.S. Army Medical Research and Materiel Command.
NR 46
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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 MAY 1
PY 2016
VL 72
IS 1
BP 15
EP 20
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DK6WY
UT WOS:000375067600012
PM 26630672
ER

PT J
AU Barr, RD
   Ferrari, A
   Ries, L
   Whelan, J
   Bleyer, WA
AF Barr, Ronald D.
   Ferrari, Andrea
   Ries, Lynn
   Whelan, Jeremy
   Bleyer, W. Archie
TI Cancer in Adolescents and Young Adults A Narrative Review of the Current
   Status and a View of the Future
SO JAMA PEDIATRICS
LA English
DT Review
ID QUALITY-OF-LIFE; CHILDHOOD-CANCER; INTERNATIONAL PERSPECTIVES;
   UNITED-STATES; PHYSICAL-ACTIVITY; 5-YEAR SURVIVORS; HEALTH OUTCOMES;
   PALLIATIVE CARE; LATE MORTALITY; FOLLOW-UP
AB IMPORTANCE Although cancer remains the most common cause of disease-related death in adolescents and young adults (AYAs) in high-income countries, their overall survival rates continue to increase and now exceed 80% at 5 years in several high-income countries. This has been accomplished through progressive improvements in active treatment and supportive care, although accrual rates to therapeutic clinical trials remain disappointing. Recognition of the unique distribution of diseases in the AYA population with cancer and further understanding of the distinctive biology of cancers in AYAs will lead to continuing gains in clinical outcomes.
   OBSERVATIONS Many of the challenges faced by AYAs with a diagnosis of malignant disease are shared by others with chronic medical conditions and even their healthy peers, such as a sense of invulnerability that may contribute to delays in diagnosis. A particular need for psychological support has been identified for AYAs with cancer, even after active therapy has been completed and especially in the context of palliative care. Notable needs also include fertility preservation and navigation through the multiple transitions in the cancer journey. Additionally, there is a "cost of cure." This is not only in the form of short-term, treatment-related morbidity and mortality but also in the burden of "late effects," including second cancers, that compromise quality of life and limit life expectancy. Establishing clinical programs devoted to AYAs with cancer, with complementary educational initiatives, will strengthen the advances made. It is anticipated that clinical trial accrual will increase substantially, providing further gains in survival. Likewise, addressing the challenges of survivorship, including secondary prevention of long-term morbidity and mortality, will lead to additional improvements in clinical outcomes.
   CONCLUSIONS AND RELEVANCE Transferring this knowledge to the care of an estimated 1 million incident cases of cancer in AYAs worldwide, most of whom do not live in high-income countries, remains a considerable challenge.
C1 [Barr, Ronald D.] McMaster Univ, Dept Pediat, Hamilton, ON L8S 4J9, Canada.
   [Ferrari, Andrea] Natl Canc Inst, Dept Pediat, I-20133 Milan, Italy.
   [Ries, Lynn] NCI, Surveillance Epidemiol & End Results Program, Bethesda, MD 20892 USA.
   [Whelan, Jeremy] Univ Coll London Hosp, Natl Inst Hlth Res, Biomed Res Ctr, London, England.
   [Bleyer, W. Archie] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA.
RP Barr, RD (reprint author), McMaster Univ, Hlth Sci Ctr, 1200 Main St W,Room 3N27, Hamilton, ON L8S 4J9, Canada.
EM rbarr@mcmaster.ca
OI Ferrari, Andrea/0000-0002-4724-0517
NR 73
TC 8
Z9 8
U1 3
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD MAY
PY 2016
VL 170
IS 5
BP 495
EP 501
DI 10.1001/jamapediatrics.2015.4689
PG 7
WC Pediatrics
SC Pediatrics
GA DK9YJ
UT WOS:000375287800021
PM 26999630
ER

PT J
AU Manuck, TA
   Levy, PT
   Gyamfi-Bannerman, C
   Jobe, AH
   Blaisdell, CJ
AF Manuck, Tracy A.
   Levy, Philip T.
   Gyamfi-Bannerman, Cynthia
   Jobe, Alan H.
   Blaisdell, Carol J.
TI Prenatal and Perinatal Determinants of Lung Health and Disease in Early
   Life A National Heart, Lung, and Blood Institute Workshop Report
SO JAMA PEDIATRICS
LA English
DT Article
ID FETAL-GROWTH RESTRICTION; VITAMIN-D DEFICIENCY; BRONCHOPULMONARY
   DYSPLASIA; RESPIRATORY OUTCOMES; PULMONARY-FUNCTION; PRETERM INFANTS;
   UNITED-STATES; CHORIOAMNIONITIS; PREMATURITY; ASTHMA
AB Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome.
C1 [Blaisdell, Carol J.] NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Two Rockledge Ctr,Ste 10042, Bethesda, MD 20892 USA.
   [Manuck, Tracy A.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27515 USA.
   [Levy, Philip T.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Levy, Philip T.] Atlantic Hlth Syst, Goryeb Childrens Hosp, Morristown, NJ USA.
   [Gyamfi-Bannerman, Cynthia] Columbia Univ, Med Ctr, Div Maternal Fetal Med, New York, NY USA.
   [Jobe, Alan H.] Univ Cincinnati, Sch Med, Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH USA.
RP Blaisdell, CJ (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Two Rockledge Ctr,Ste 10042, Bethesda, MD 20892 USA.
EM blaisdellcj@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute of the National Institutes of
   Health
FX Funding for the workshop was provided by the National Heart, Lung, and
   Blood Institute of the National Institutes of Health. The institute
   provided travel expenses for the workshop and administrative support for
   subcommittee conference calls.
NR 37
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U1 2
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD MAY
PY 2016
VL 170
IS 5
AR e154577
DI 10.1001/jamapediatrics.2015.4577
PG 6
WC Pediatrics
SC Pediatrics
GA DK9YJ
UT WOS:000375287800002
PM 26953657
ER

PT J
AU Shaw, P
AF Shaw, Philip
TI Maps of the Development of the Brain's Functional Architecture Could
   They Provide Growth Charts for Psychiatry?
SO JAMA PSYCHIATRY
LA English
DT Editorial Material
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
C1 [Shaw, Philip] NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI,Intramural Program, Bldg 31,B1 B37, Bethesda, MD 20892 USA.
RP Shaw, P (reprint author), NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI,Intramural Program, Bldg 31,B1 B37, Bethesda, MD 20892 USA.
EM shawp@mail.nih.gov
FU Intramural Programs of the National Human Genome Research Institute;
   National Institute of Mental Health
FX Dr Shaw is funded by the Intramural Programs of the National Human
   Genome Research Institute and National Institute of Mental Health.
NR 8
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U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2016
VL 73
IS 5
BP 445
EP 446
DI 10.1001/jamapsychiatry.2016.0140
PG 2
WC Psychiatry
SC Psychiatry
GA DL2KD
UT WOS:000375462600008
PM 27074120
ER

PT J
AU Kaup, AR
   Byers, AL
   Falvey, C
   Simonsick, EM
   Satterfield, S
   Ayonayon, HN
   Smagula, SF
   Rubin, SM
   Yaffe, K
AF Kaup, Allison R.
   Byers, Amy L.
   Falvey, Cherie
   Simonsick, Eleanor M.
   Satterfield, Suzanne
   Ayonayon, Hilsa N.
   Smagula, Stephen F.
   Rubin, Susan M.
   Yaffe, Kristine
TI Trajectories of Depressive Symptoms in Older Adults and Risk of Dementia
SO JAMA PSYCHIATRY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; ALZHEIMERS-DISEASE;
   BODY-COMPOSITION; PRIMARY-CARE; HEALTH ABC; DECLINE; WOMEN; ASSOCIATION;
   PREDICTORS
AB IMPORTANCE Depression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.
   OBJECTIVE To investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.
   DESIGN, SETTING, AND PARTICIPANTS This was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.
   MAIN OUTCOMES AND MEASURES Incident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (>= 1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).
   RESULTS The analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2%[n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.
   CONCLUSIONS AND RELEVANCE Older adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.
C1 [Kaup, Allison R.; Byers, Amy L.] San Francisco VA Med Ctr, Res Serv, 4150 Clement St,Mail Code 116H, San Francisco, CA 94121 USA.
   [Kaup, Allison R.; Byers, Amy L.; Falvey, Cherie; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
   [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
   [Ayonayon, Hilsa N.; Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Smagula, Stephen F.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
   [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
   [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Kaup, AR (reprint author), San Francisco VA Med Ctr, Res Serv, 4150 Clement St,Mail Code 116H, San Francisco, CA 94121 USA.
EM allison.kaup@ucsf.edu
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
   N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute for
   Nursing Research [R01-NR012459]; Intramural Research Program of the
   National Institute on Aging; US Department of Veterans Affairs,
   Rehabilitation Research and Development Service [1IK2RX001629]; National
   Institute of Mental Health [T32 MH019986]; Department of Veterans
   Affairs Office of Academic Affiliations Advanced Fellowship Program in
   Mental Illness Research and Treatment; Medical Research Service of the
   San Francisco Veterans Affairs Medical Center; Department of Veterans
   Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical
   Center
FX This research was supported by contracts N01-AG-6-2101, N01-AG-6-2103,
   and N01-AG-6-2106 from the National Institute on Aging; by grant
   R01-AG028050 from the National Institute on Aging; by grant R01-NR012459
   from the National Institute for Nursing Research; and in part by the
   Intramural Research Program of the National Institute on Aging. The
   research described herein was also supported in part by Career
   Development Award 1IK2RX001629 from the US Department of Veterans
   Affairs, Rehabilitation Research and Development Service (Dr Kaup); by
   research training grant T32 MH019986 from the National Institute of
   Mental Health (Dr Smagula); by grant K24AG031155 from the National
   Institute on Aging (Dr Yaffe); and by the Department of Veterans Affairs
   Office of Academic Affiliations Advanced Fellowship Program in Mental
   Illness Research and Treatment, the Medical Research Service of the San
   Francisco Veterans Affairs Medical Center, and the Department of
   Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and
   Clinical Center.
NR 35
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U1 3
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PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2016
VL 73
IS 5
BP 525
EP 531
DI 10.1001/jamapsychiatry.2016.0004
PG 7
WC Psychiatry
SC Psychiatry
GA DL2KD
UT WOS:000375462600018
PM 26982217
ER

PT J
AU Hasin, DS
   Grant, B
AF Hasin, Deborah S.
   Grant, Bridget
TI NESARC Findings on Increased Prevalence of Marijuana Use
   Disorders-Consistent With Other Sources of Information
SO JAMA PSYCHIATRY
LA English
DT Letter
ID UNITED-STATES
C1 [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
   [Grant, Bridget] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA.
RP Hasin, DS (reprint author), Columbia Univ, Med Ctr, Dept Psychiat, 1051 Riverside Dr,123, New York, NY 10032 USA.
EM dsh2@cumc.columbia.edu
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
   Institute on Drug Abuse (NIDA); NIAAA; New York State Psychiatric
   Institute; NIDA [R01DA034244]
FX The National Epidemiologic Survey of Alcohol and Related Conditions was
   sponsored by the National Institute on Alcohol Abuse and Alcoholism
   (NIAAA), with supplemental support from the National Institute on Drug
   Abuse (NIDA). This work was supported by the intramural program, NIAAA,
   the New York State Psychiatric Institute, and by grant R01DA034244 from
   the NIDA (Dr Hasin).
NR 5
TC 5
Z9 5
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2016
VL 73
IS 5
BP 532
EP 532
DI 10.1001/jamapsychiatry.2015.3158
PG 1
WC Psychiatry
SC Psychiatry
GA DL2KD
UT WOS:000375462600019
PM 27008098
ER

PT J
AU Tucker-Seeley, RD
   Yabroff, KR
AF Tucker-Seeley, Reginald D.
   Yabroff, K. Robin
TI Minimizing the "Financial Toxicity" Associated With Cancer Care:
   Advancing the Research Agenda
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID BREAST-CANCER; OLDER-ADULTS; HARDSHIP; HEALTH; CHEMOTHERAPY; EXPERIENCE;
   MORTALITY; SURVIVORS; STRESS; STRAIN
C1 [Tucker-Seeley, Reginald D.] Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW743, Boston, MA 02115 USA.
   [Tucker-Seeley, Reginald D.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
   [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW743, Boston, MA 02115 USA.
EM retucker@hsph.harvard.edu
NR 25
TC 1
Z9 1
U1 3
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY
PY 2016
VL 108
IS 5
AR djv410
DI 10.1093/jnci/djv410
PG 3
WC Oncology
SC Oncology
GA DL1PQ
UT WOS:000375404600014
ER

PT J
AU Zheng, ZY
   Yabroff, KR
   Guy, GP
   Han, XS
   Li, CY
   Banegas, MP
   Ekwueme, DU
   Jemal, A
AF Zheng, Zhiyuan
   Yabroff, K. Robin
   Guy, Gery P., Jr.
   Han, Xuesong
   Li, Chunyu
   Banegas, Matthew P.
   Ekwueme, Donatus U.
   Jemal, Ahmedin
TI Annual Medical Expenditure and Productivity Loss Among Colorectal,
   Female Breast, and Prostate Cancer Survivors in the United States
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID ECONOMIC BURDEN; HEALTH-CARE; COSTS; PROJECTIONS; STATISTICS; AGREEMENT;
   OUTCOMES; IMPACT; ADULTS; COLON
AB Background: There are limited nationally representative estimates of the annual economic burden among survivors of the three most prevalent cancers (colorectal, female breast, and prostate) in both nonelderly and elderly populations in the United States.
   Methods: The 2008 to 2012 Medical Expenditure Panel Survey data were used to identify colorectal (n = 540), female breast (n = 1568), and prostate (n = 1170) cancer survivors and individuals without a cancer history (n = 109 423). Excess economic burden attributable to cancer included per-person excess annual medical expenditures and productivity losses (employment disability, missed work days, and days stayed in bed). All analyses were stratified by cancer site and age (nonelderly: 18-64 years vs elderly: = 65 years). Multivariable analyses controlled for age, sex, race/ethnicity, marital status, education, number of comorbidities, and geographic region. All statistical tests were two-sided.
   Results: Compared with individuals without a cancer history, cancer survivors experienced annual excess medical expenditures (for the nonelderly population, colorectal: $8647, 95% confidence interval [CI] = $4932 to $13 974, P<.001; breast: $5119, 95% CI = $3439 to $7158, P<.001; prostate: $3586, 95% CI = $1792 to $6076, P<.001; for the elderly population, colorectal: $4913, 95% CI = $2768 to $7470, P<.001; breast: $2288, 95% CI = $814 to $3995, P=.002; prostate: $3524, 95% CI = $1539 to $5909, P<.001). Nonelderly colorectal and breast cancer survivors experienced statistically significant annual excess employment disability (13.6%, P<.001, and 4.8%, P=.001) and productivity loss at work (7.2 days, P<.001, and 3.3 days, P=.002) and at home (4.5 days, P<.001, and 3.3 days, P=.003). In contrast, elderly survivors of all three cancer sites had comparable productivity losses as those without a cancer history.
   Conclusions: Colorectal, breast, and prostate cancer survivors experienced statistically significantly higher economic burden compared with individuals without a cancer history; however, excess economic burden varies by cancer site and age. Targeted efforts will be important in reducing the economic burden of colorectal, breast, and prostate cancer.
C1 [Zheng, Zhiyuan; Han, Xuesong; Jemal, Ahmedin] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Atlanta, GA 30329 USA.
   [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Guy, Gery P., Jr.; Li, Chunyu; Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
   [Banegas, Matthew P.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA.
RP Zheng, ZY (reprint author), Amer Canc Soc Inc, Surveillance & Hlth Serv Res, 250 Williams St, Atlanta, GA 30303 USA.
EM jason.zheng@cancer.org
NR 42
TC 2
Z9 2
U1 3
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD MAY
PY 2016
VL 108
IS 5
AR djv382
DI 10.1093/jnci/djv382
PG 9
WC Oncology
SC Oncology
GA DL1PQ
UT WOS:000375404600019
ER

PT J
AU Aiello, CM
   Nussear, KE
   Esque, TC
   Emblidge, PG
   Sah, P
   Bansal, S
   Hudson, PJ
AF Aiello, Christina M.
   Nussear, Kenneth E.
   Esque, Todd C.
   Emblidge, Patrick G.
   Sah, Pratha
   Bansal, Shweta
   Hudson, Peter J.
TI Host contact and shedding patterns clarify variation in pathogen
   exposure and transmission in threatened tortoise Gopherus agassizii:
   implications for disease modelling and management
SO JOURNAL OF ANIMAL ECOLOGY
LA English
DT Article
DE contact heterogeneity; detecting infection; infectiousness; per-contact
   transmission probability; social behaviour; upper respiratory tract
   disease; wildlife disease ecology
ID RESPIRATORY-TRACT DISEASE; MYCOPLASMA-AGASSIZII; DESERT TORTOISES;
   SOCIAL NETWORKS; INFECTIOUS-DISEASES; MOJAVE DESERT; WILDLIFE;
   PREVALENCE; DYNAMICS; GALLISEPTICUM
AB Most directly transmitted infections require some form of close contact between infectious and susceptible hosts to spread. Often disease models assume contacts are equal and use mean field estimates of transmission probability for all interactions with infectious hosts. Such methods may inaccurately describe transmission when interactions differ substantially in their ability to cause infection. Understanding this variation in transmission risk may be critical to properly model and manage some infectious diseases. In this study, we investigate how varying exposure and transmission may be key to understanding disease dynamics in the threatened desert tortoise Gopherus agassizii. We created heterogeneity in Mycoplasma agassizii exposure (the putative bacterial agent of a respiratory disease) by varying the duration of interactions between naturally infected and uninfected captive desert tortoises. Using qPCR, we identified new infections and compared models of transmission probability as a function of contact duration and pathogen load. We then examined the contact patterns of a wild tortoise population using proximity loggers to identify heterogeneity in contact duration. The top-ranked model predicting M.agassizii transmission included a dose term defined as the product of the number of days in proximity to an infected host and the infection level of that host. Models predicted low transmission probability for short interactions, unless the infectious host had a high load of M.agassizii: such hosts were predicted to transmit infection at higher rates with any amount of contact. We observed predominantly short-lived interactions in a free-ranging tortoise population and thus, expect transmission patterns in this population to vary considerably with the frequency and duration of high infection levels. Mean field models may misrepresent natural transmission patterns in this and other populations depending on the distribution of high-risk contact and shedding events. Rapid outbreaks in generally solitary species may result from changes to their naturally low-risk contact patterns or due to increases in the frequency of severe infections or super-shedding events - population characteristics that should be further investigated to develop effective management strategies.
C1 [Aiello, Christina M.; Emblidge, Patrick G.; Hudson, Peter J.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [Aiello, Christina M.; Esque, Todd C.] US Geol Survey, Western Ecol Res Ctr, Las Vegas Field Stn, 160 N Stephanie St, Henderson, NV 89074 USA.
   [Nussear, Kenneth E.] Univ Nevada, Dept Geog, Reno, NV 89557 USA.
   [Sah, Pratha; Bansal, Shweta] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
   [Bansal, Shweta] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Aiello, CM (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.; Aiello, CM (reprint author), US Geol Survey, Western Ecol Res Ctr, Las Vegas Field Stn, 160 N Stephanie St, Henderson, NV 89074 USA.
EM caiello@usgs.gov
OI Bansal, Shweta/0000-0002-1740-5421; Sah, Pratha/0000-0001-8936-5871;
   Aiello, Christina/0000-0002-2399-5464
FU National Science Foundation EID grant [1216054]; BLM grant [L11AC20382]
FX We thank our research assistants: A. Berger, J. Jozkowski, J. Lopez, R.
   Moylan and M. Walden as well as numerous SCA interns and volunteers;
   Fort Irwin NTC for use of lands to collect wild tortoise contact data;
   the BLM for use of DTCC facilities and San Diego Zoo Global for
   logistical support; K. Drake, R. Averill-Murray, K. Fields and C. Everly
   for collaboration and support. The content of this paper was stimulated
   by the collaboration and discussions of members of the desert tortoise
   disease assessment workgroup including N. Lamberski, B. Rideout, J.
   Simecka, R. Swaisgood, C. R. Tracy, and several others. This research
   was funded by the National Science Foundation EID grant # 1216054 and
   BLM grant L11AC20382. All activities were performed under federal
   wildlife permits TE102235-5 and TE030659-9, state wildlife permits
   S36421 (NV) and 9383 (CA) and Pennsylvania State University IACUC #
   38532. Any use of trade, product, or firm names is for descriptive
   purposes only and does not imply endorsement by the U.S. Government.
NR 58
TC 1
Z9 1
U1 6
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-8790
EI 1365-2656
J9 J ANIM ECOL
JI J. Anim. Ecol.
PD MAY
PY 2016
VL 85
IS 3
BP 829
EP 842
DI 10.1111/1365-2656.12511
PG 14
WC Ecology; Zoology
SC Environmental Sciences & Ecology; Zoology
GA DK7QS
UT WOS:000375121400023
PM 26935482
ER

PT J
AU Jones, M
   Bisht, K
   Savage, SA
   Nandakumar, J
   Keegan, CE
   Maillard, I
AF Jones, Morgan
   Bisht, Kamlesh
   Savage, Sharon A.
   Nandakumar, Jayakrishnan
   Keegan, Catherine E.
   Maillard, Ivan
TI The shelterin complex and hematopoiesis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID BONE-MARROW FAILURE; HOYERAAL-HREIDARSSON-SYNDROME; CHRONIC
   LYMPHOCYTIC-LEUKEMIA; TELOMERE LENGTH REGULATOR; CAUSES
   DYSKERATOSIS-CONGENITA; DOUBLE-STRAND BREAKS; CELL-CYCLE CONTROL;
   DNA-DAMAGE; DYSFUNCTIONAL TELOMERES; MAMMALIAN TELOMERES
AB Mammalian chromosomes terminate in stretches of repetitive telomeric DNA that act as buffers to avoid loss of essential genetic information during end-replication. A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. Telomere erosion contributes to human diseases ranging from BM failure to premature aging syndromes and cancer. The role of shelterin telomere protection is less understood. Mutations in genes encoding the shelterin proteins TRF1-interacting nuclear factor 2 (TIN2) and adrenocortical dysplasia homolog (ACD) were identified in dyskeratosis congenita, a syndrome characterized by somatic stem cell dysfunction in multiple organs leading to BM failure and other pleiotropic manifestations. Here, we introduce the biochemical features and in vivo effects of individual shelterin proteins, discuss shelterin functions in hematopoiesis, and review emerging knowledge implicating the shelterin complex in hematological disorders.
C1 [Jones, Morgan] Univ Michigan, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA.
   [Jones, Morgan] Univ Michigan, Med Scientist Training Program, Ann Arbor, MI 48109 USA.
   [Bisht, Kamlesh; Nandakumar, Jayakrishnan] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
   [Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Keegan, Catherine E.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Keegan, Catherine E.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
   [Maillard, Ivan] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA.
   [Maillard, Ivan] Univ Michigan, Div Hematol Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Maillard, Ivan] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
RP Maillard, I (reprint author), Univ Michigan, Life Sci Inst 6382A, 210 Washtenaw Ave, Ann Arbor, MI 48109 USA.
EM imaillar@umich.edu
FU Leukemia and Lymphoma Society [1227-14]; D. Dan and Betty Kahn
   Foundation; intramural research program of the Division of Cancer
   Epidemiology and Genetics, National Cancer Institute of the NIH;  [NIH:
   R01-AG-050509];  [R00-CA-167644];  [P30-AG-013283];  [R01-HD-058606]; 
   [R01-AI-091627];  [T32-GM007315];  [T32-GM007863]
FX Experimental work in the Nandakumar, Keegan, and Maillard laboratories
   has been supported by the NIH: R01-AG-050509 (to J. Nandakumar, C. E.
   Keegan, and I. Maillard); R00-CA-167644 and P30-AG-013283 (to J.
   Nandakumar); R01-HD-058606 (to C. E. Keegan); and R01-AI-091627 (to I.
   Maillard). M. Jones was supported by T32-GM007315 and T32-GM007863. I.
   Maillard is the recipient of a career development award from the
   Leukemia and Lymphoma Society (grant 1227-14) and an award from the D.
   Dan and Betty Kahn Foundation. Research in the Savage laboratory has
   been supported by the intramural research program of the Division of
   Cancer Epidemiology and Genetics, National Cancer Institute of the NIH.
NR 140
TC 2
Z9 2
U1 3
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAY
PY 2016
VL 126
IS 5
BP 1621
EP 1629
DI 10.1172/JCI84547
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DK8MX
UT WOS:000375182100003
PM 27135879
ER

PT J
AU Blosser, SJ
   Drake, SK
   Andrasko, JL
   Henderson, CM
   Kamboj, K
   Antonara, S
   Mijares, L
   Conville, P
   Frank, KM
   Harrington, SM
   Balada-Llasat, JM
   Zelazny, AM
AF Blosser, Sara J.
   Drake, Steven K.
   Andrasko, Jennifer L.
   Henderson, Christina M.
   Kamboj, Kamal
   Antonara, Stella
   Mijares, Lilia
   Conville, Patricia
   Frank, Karen M.
   Harrington, Susan M.
   Balada-Llasat, Joan-Miquel
   Zelazny, Adrian M.
TI Multicenter Matrix-Assisted Laser Desorption Ionization-Time of Flight
   Mass Spectrometry Study for Identification of Clinically Relevant
   Nocardia spp.
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID ANTIMICROBIAL SUSCEPTIBILITY; MYCOBACTERIA; TAXONOMY; MEDIA
AB This multicenter study analyzed Nocardia spp., including extraction, spectral acquisition, Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification, and score interpretation, using three Nocardia libraries, the Bruker, National Institutes of Health (NIH), and The Ohio State University (OSU) libraries, and compared the results obtained by each center. A standardized study protocol, 150 Nocardia isolates, and NIH and OSU Nocardia MALDI-TOF MS libraries were distributed to three centers. Following standardized culture, extraction, and MALDI-TOF MS analysis, isolates were identified using score cutoffs of >= 2.0 for species/species complex-level identification and >= 1.8 for genus-level identification. Isolates yielding a score of < 2.0 underwent a single repeat extraction and analysis. The overall score range for all centers was 1.3 to 2.7 (average, 2.2 +/- 0.3), with common species generally producing higher average scores than less common ones. Score categorization and isolate identification demonstrated 86% agreement between centers; 118 of 150 isolates were correctly identified to the species/species complex level by all centers. Nine strains (6.0%) were not identified by any center, and six (4.0%) of these were uncommon species with limited library representation. A categorical score discrepancy among centers occurred for 21 isolates (14.0%). There was an overall benefit of 21.2% from repeat extraction of low-scoring isolates and a center-dependent benefit for duplicate spotting (range, 2 to 8.7%). Finally, supplementation of the Bruker Nocardia MALDI-TOF MS library with both the OSU and NIH libraries increased the genus-level and species-level identification by 18.2% and 36.9%, respectively. Overall, this study demonstrates the ability of diverse clinical microbiology laboratories to utilize MALDI-TOF MS for the rapid identification of clinically relevant Nocardia spp. and to implement MALDI-TOF MS libraries developed by single laboratories across institutions.
C1 [Blosser, Sara J.; Henderson, Christina M.; Antonara, Stella; Mijares, Lilia; Conville, Patricia; Frank, Karen M.; Zelazny, Adrian M.] NIH, Dept Lab Med, Microbiol Serv, Bldg 10, Bethesda, MD 20892 USA.
   [Drake, Steven K.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
   [Andrasko, Jennifer L.; Harrington, Susan M.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
   [Kamboj, Kamal; Balada-Llasat, Joan-Miquel] Ohio State Univ, Dept Pathol, Wexner Med Ctr, Columbus, OH 43210 USA.
   [Blosser, Sara J.] Indiana State Dept Hlth, Div Clin Microbiol & Virol, Indianapolis, IN 46202 USA.
   [Antonara, Stella] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA.
   [Mijares, Lilia] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
   [Conville, Patricia] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Zelazny, AM (reprint author), NIH, Dept Lab Med, Microbiol Serv, Bldg 10, Bethesda, MD 20892 USA.
EM azelazny@mail.nih.gov
FU Intramural Research Program of the NIH Clinical Center, Department of
   Laboratory Medicine
FX The Intramural Research Program of the NIH Clinical Center, Department
   of Laboratory Medicine, supported this research.
NR 18
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2016
VL 54
IS 5
BP 1251
EP 1258
DI 10.1128/JCM.02942-15
PG 8
WC Microbiology
SC Microbiology
GA DK5JH
UT WOS:000374955700015
PM 26912758
ER

PT J
AU Masujin, K
   Orru, CD
   Miyazawa, K
   Groveman, BR
   Raymond, LD
   Hughson, AG
   Caughey, B
AF Masujin, Kentaro
   Orru, Christina D.
   Miyazawa, Kohtaro
   Groveman, Bradley R.
   Raymond, Lynne D.
   Hughson, Andrew G.
   Caughey, Byron
TI Detection of Atypical H-Type Bovine Spongiform Encephalopathy and
   Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced
   Conversion (vol 54, pg 677, 2016)
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Correction
C1 [Masujin, Kentaro; Orru, Christina D.; Groveman, Bradley R.; Raymond, Lynne D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
   [Masujin, Kentaro; Miyazawa, Kohtaro] Natl Agr & Food Res Org, Natl Inst Anim Hlth, Influenza & Prion Dis Res Ctr, Tsukuba, Ibaraki, Japan.
RP Masujin, K (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.; Masujin, K (reprint author), Natl Agr & Food Res Org, Natl Inst Anim Hlth, Influenza & Prion Dis Res Ctr, Tsukuba, Ibaraki, Japan.
NR 1
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2016
VL 54
IS 5
BP 1407
EP 1407
DI 10.1128/JCM.00472-16
PG 1
WC Microbiology
SC Microbiology
GA DK5JH
UT WOS:000374955700043
PM 27114566
ER

PT J
AU Chiou, VL
   Burotto, M
AF Chiou, Victoria L.
   Burotto, Mauricio
TI Integration of Immuno-Oncology and Palliative Care Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID SOLID TUMORS
C1 [Chiou, Victoria L.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Burotto, Mauricio] Univ Desarrollo, Clin Alemana Santiago, Santiago, Chile.
RP Chiou, VL (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 1
PY 2016
VL 34
IS 13
DI 10.1200/JCO.2015.66.2031
PG 2
WC Oncology
SC Oncology
GA DK6SM
UT WOS:000375055500026
PM 26926687
ER

PT J
AU Kos, A
   Wanke, KA
   Gioio, A
   Martens, GJ
   Kaplan, BB
   Aschrafi, A
AF Kos, Aron
   Wanke, Kai A.
   Gioio, Anthony
   Martens, Gerard J.
   Kaplan, Barry B.
   Aschrafi, Armaz
TI Monitoring mRNA Translation in Neuronal Processes Using Fluorescent
   Non-Canonical Amino Acid Tagging
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE neurons; axon; synapse; local protein synthesis; click assay;
   microfluidic chambers; FUNCAT
ID NEWLY SYNTHESIZED PROTEINS; MICROFLUIDIC CULTURE PLATFORM;
   FRAGILE-X-SYNDROME; SQUID GIANT-AXON; LOCAL TRANSLATION; SYMPATHETIC
   NEURONS; VISUALIZATION; INITIATION; GROWTH
AB A steady accumulation of experimental data argues that protein synthesis in neurons is not merely restricted to the somatic compartment, but also occurs in several discrete cellular micro-domains. Local protein synthesis is critical for the establishment of synaptic plasticity in mature dendrites and in directing the growth cones of immature axons, and has been associated with cognitive impairment in mice and humans. Although in recent years a number of important mechanisms governing this process have been described, it remains technically challenging to precisely monitor local protein synthesis in individual neuronal cell parts independent from the soma. This report presents the utility of employing microfluidic chambers for the isolation and treatment of single neuronal cellular compartments. Furthermore, it is demonstrated that a protein synthesis assay, based on fluorescent non-canonical amino acid tagging (FUNCAT), can be combined with this cell culture system to label nascent proteins within a discrete structural and functional domain of the neuron. Together, these techniques could be employed for the detection of protein synthesis within developing and mature neurites, offering an effective approach to elucidate novel mechanisms controlling synaptic maintenance and plasticity.
C1 [Kos, Aron] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands.
   [Kos, Aron; Wanke, Kai A.] Ctr Neurosci, Donders Inst Brain Cognit & Behav, NL-6525 AJ Nijmegen, Netherlands.
   [Wanke, Kai A.] Max Planck Inst Psycholinguist, Language & Genet Dept, NL-6525 XD Nijmegen, Netherlands.
   [Gioio, Anthony; Kaplan, Barry B.; Aschrafi, Armaz] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Martens, Gerard J.] Radboud Univ Nijmegen, Dept Mol Anim Physiol, NL-6525 ED Nijmegen, Netherlands.
RP Aschrafi, A (reprint author), NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM Armaz.aschrafi@gmail.com
FU Donders Center for Neuroscience fellowship award of the Radboudumc;
   FP7-Marie Curie International Reintegration Grant [276868]; Division of
   Intramural Research Programs of the National Institute of Mental Health
   [MH002768]
FX The authors disclosed receipt of the following financial support for the
   research, authorship, and/or publication of this article: The research
   of the authors is supported by grants from the Donders Center for
   Neuroscience fellowship award of the Radboudumc (to AA); the FP7-Marie
   Curie International Reintegration Grant (Grant 276868 to AA). This work
   was supported by the Division of Intramural Research Programs of the
   National Institute of Mental Health (MH002768).
NR 34
TC 1
Z9 1
U1 2
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
EI 1551-5044
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD MAY
PY 2016
VL 64
IS 5
BP 323
EP 333
DI 10.1369/0022155416641604
PG 11
WC Cell Biology
SC Cell Biology
GA DK7TH
UT WOS:000375128100004
PM 27026294
ER

PT J
AU Vigneault, DM
   te Riele, ASJM
   James, CA
   Zimmerman, SL
   Selwaness, M
   Murray, B
   Tichnell, C
   Tee, M
   Noble, JA
   Calkins, H
   Tandri, H
   Bluemke, DA
AF Vigneault, Davis M.
   te Riele, Anneline S. J. M.
   James, Cynthia A.
   Zimmerman, Stefan L.
   Selwaness, Mariana
   Murray, Brittney
   Tichnell, Crystal
   Tee, Michael
   Noble, J. Alison
   Calkins, Hugh
   Tandri, Harikrishna
   Bluemke, David A.
TI Right ventricular strain by MR quantitatively identifies regional
   dysfunction in patients with arrhythmogenic right ventricular
   cardiomyopathy
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE magnetic resonance imaging (MRI); strain; feature tracking;
   arrhythmogenic right ventricular cardiomyopathy (ARVC); cardiac magnetic
   resonance (MR)
ID RESONANCE-IMAGING FINDINGS; TASK-FORCE CRITERIA;
   DYSPLASIA/CARDIOMYOPATHY; DYSPLASIA; TRACKING; ECHOCARDIOGRAPHY
AB BackgroundAnalysis of regional wall motion of the right ventricle (RV) is primarily qualitative with large interobserver variation in clinical practice. Thus, the purpose of this study was to use feature tracking to analyze regional wall motion abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).
   MethodsWe enrolled 110 subjects (39 overt ARVC [mutation+/phenotype+] (35.5%), 40 preclinical ARVC [mutation+/phenotype-] (36.3%), and 31 control subjects (28.2%)). Cine steady state free precession cardiac MR was performed with temporal resolution 40 ms in the horizontal long axis (HLA), axial, and short axis directions. Regional strain was analyzed using feature tracking software and reproducibility was assessed by means of intraclass correlation coefficient. Dunnett's test was used in univariate analysis for comparisons to control subjects; cumulative odds logistic regression was used for minimally and fully adjusted multivariate models.
   ResultsStrain was significantly impaired in overt ARVC compared with control subjects both globally (P < 0.01) and regionally (all segments of HLA view, P < 0.01). In the HLA view, regional reproducibility was excellent within (intraclass correlation coefficient [ICC] = 0.81) and moderate between (ICC = 0.62) observers. Using a threshold of -31% subtricuspid strain in the HLA view, the sensitivity and specificity for overt ARVC were 75.0% and 78.2%, respectively. In multivariable analysis involving all three groups, subtricuspid strain less than -31% (beta = 1.38; P = 0.014) and RV end diastolic volume index (beta = 0.06; P = 0.001) were significant predictors of disease presence.
   ConclusionRV strain can be reproducibly assessed with MR feature tracking, and regional strain is abnormal in overt ARVC compared with control subjects. J. Magn. Reson. Imaging 2016;43:1132-1139.
C1 [Vigneault, Davis M.; Selwaness, Mariana; Tee, Michael; Bluemke, David A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Vigneault, Davis M.; Tee, Michael; Noble, J. Alison] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Parks Rd, Oxford OX1 3PJ, England.
   [Vigneault, Davis M.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA.
   [te Riele, Anneline S. J. M.; James, Cynthia A.; Murray, Brittney; Tichnell, Crystal; Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA.
   [te Riele, Anneline S. J. M.] Univ Med Ctr Utrecht, Div Cardiol, Dept Med, Utrecht, Netherlands.
   [Zimmerman, Stefan L.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA.
   [Selwaness, Mariana] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bluemked@cc.nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU NIH; Oxford-Cambridge NIH Training Program; Leyla Erkan Family Fund for
   ARVD Research; Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns
   Hopkins; Bogle Foundation; Dr. Francis P. Chiaramonte Private
   Foundation; Healing Hearts Foundation; Campanella family; Patrick J.
   Harrison Family; Peter French Memorial Foundation; Wilmerding Endowments
FX The authors thank the study participants, without whom this work would
   not have been possible. Davis Vigneault's contributions were funded by
   the NIH intramural research program and the Oxford-Cambridge NIH
   Training Program. This work was performed during Anneline te Riele's
   tenure as the Mark Josephson and Hein Wellens research fellow of the
   Heart Rhythm Society. The Johns Hopkins ARVD/C Program is supported by
   the Leyla Erkan Family Fund for ARVD Research, the Dr. Satish, Rupal,
   and Robin Shah ARVD Fund at Johns Hopkins, the Bogle Foundation, the Dr.
   Francis P. Chiaramonte Private Foundation, the Healing Hearts
   Foundation, the Campanella family, the Patrick J. Harrison Family, the
   Peter French Memorial Foundation, and the Wilmerding Endowments.
NR 18
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAY
PY 2016
VL 43
IS 5
BP 1132
EP 1139
DI 10.1002/jmri.25068
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK7PO
UT WOS:000375118400011
PM 26497822
ER

PT J
AU Gai, ND
   Malayeri, A
   Agarwal, H
   Evers, R
   Bluemke, D
AF Gai, Neville D.
   Malayeri, Ashkan
   Agarwal, Harsh
   Evers, Robert
   Bluemke, David
TI Evaluation of optimized breath-hold and free-breathing 3D ultrashort
   echo time contrast agent-free MRI of the human lung
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE 3D stack of radials; lung parenchyma; breath-hold; free-breathing
ID ARBITRARY K-SPACE; RECONSTRUCTION; GRADIENTS; IMAGES
AB PurposeTo evaluate an optimized stack of radials ultrashort echo time (UTE) 3D magnetic resonance imaging (MRI) sequence for breath-hold and free-breathing imaging of the human lung.
   Materials and MethodsA 3D stack of ultrashort echo time radials trajectory was optimized for coronal and axial lower-resolution breath-hold and higher-resolution free-breathing scans using Bloch simulations. The sequence was evaluated in 10 volunteers, without the use of contrast agents. Signal-to-noise ratio (SNR) mean and 95% confidence interval (CI) were determined from separate signal and noise images in a semiautomated fashion. The four scanning schemes were evaluated for significant differences in image quality using Student's t-test. Ten clinical patients were scanned with the sequence and findings were compared with concomitant computed tomography (CT) in nine patients. Breath-hold 3D spokes images were compared with 3D stack of radials in five volunteers. A Mann-Whitney U-test was performed to test significance in both cases.
   ResultsBreath-hold imaging of the entire lung in volunteers was performed with SNR (mean=42.5 [CI]: 35.5-49.5; mean=34.3 [CI]: 28.6-40) in lung parenchyma for coronal and axial scans, respectively, which can be used as a quick scout scan. Longer respiratory triggered free-breathing scan enabled high-resolution UTE scanning with mean SNR of 14.2 ([CI]: 12.9-15.5) and 9.2 ([CI]: 8.2-10.2) for coronal and axial scans, respectively. Axial free-breathing scans showed significantly higher image quality (P=0.008) than the three other scanning schemes. The mean score for comparison with CT was 1.67 (score 0: n=0; 1: n=3; 2: n=6). There was no significant difference between CT and MRI (P=0.25). 3D stack of radials images were significantly better than 3D spokes images (P < 0.001).
   ConclusionThe optimized 3D stack of radials trajectory was shown to provide high-quality MR images of the lung parenchyma without the use of MRI contrast agents. The sequence may offer the possibility of breath-hold imaging and provides greater flexibility in trading off slice thickness and parallel imaging for scan time. J. Magn. Reson. Imaging 2016;43:1230-1238.
C1 [Gai, Neville D.; Malayeri, Ashkan; Evers, Robert; Bluemke, David] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
   [Agarwal, Harsh] Philips Res NA, Briarcliff Manor, NY USA.
RP Gai, ND (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10,Rm 1C502, Bethesda, MD 20892 USA.
EM gaind@cc.nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU Intramural Research Program of the NIH Clinical Center
FX Contract grant sponsor: Intramural Research Program of the NIH Clinical
   Center.
NR 32
TC 1
Z9 1
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAY
PY 2016
VL 43
IS 5
BP 1230
EP 1238
DI 10.1002/jmri.25073
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DK7PO
UT WOS:000375118400022
PM 26458867
ER

PT J
AU Easton, DF
   Lesueur, F
   Decker, B
   Michailidou, K
   Li, J
   Allen, J
   Luccarini, C
   Pooley, KA
   Shah, M
   Bolla, MK
   Wang, Q
   Dennis, J
   Ahmad, J
   Thompson, ER
   Damiola, F
   Pertesi, M
   Voegele, C
   Mebirouk, N
   Robinot, N
   Durand, G
   Forey, N
   Luben, RN
   Ahmed, S
   Aittomaki, K
   Anton-Culver, H
   Arndt, V
   Baynes, C
   Beckman, MW
   Benitez, J
   Van Den Berg, D
   Blot, WJ
   Bogdanova, NV
   Bojesen, SE
   Brenner, H
   Chang-Claude, J
   Chia, KS
   Choi, JY
   Conroy, DM
   Cox, A
   Cross, SS
   Czene, K
   Darabi, H
   Devilee, P
   Eriksson, M
   Fasching, PA
   Figueroa, J
   Flyger, H
   Fostira, F
   Garcia-Closas, M
   Giles, GG
   Glendon, G
   Gonzalez-Neira, A
   Guenel, P
   Haiman, CA
   Hall, P
   Hart, SN
   Hartman, M
   Hooning, MJ
   Hsiung, CN
   Ito, H
   Jakubowska, A
   James, PA
   John, EM
   Johnson, N
   Jones, M
   Kabisch, M
   Kang, D
   Kosma, VM
   Kristensen, V
   Lambrechts, D
   Li, N
   Lindblom, A
   Long, J
   Lophatananon, A
   Lubinski, J
   Mannermaa, A
   Manoukian, S
   Margolin, S
   Matsuo, K
   Meindl, A
   Mitchell, G
   Muir, K
   Nevelsteen, I
   van den Ouweland, A
   Peterlongo, P
   Phuah, SY
   Pylkas, K
   Rowley, SM
   Sangrajrang, S
   Schmutzler, RK
   Shen, CY
   Shu, XO
   Southey, MC
   Surowy, H
   Swerdlow, A
   Teo, SH
   Tollenaar, RAEM
   Tomlinson, I
   Torres, D
   Truong, T
   Vachon, C
   Verhoef, S
   Wong-Brown, M
   Zheng, W
   Zheng, Y
   Nevanlinna, H
   Scott, RJ
   Andrulis, IL
   Wu, AH
   Hopper, JL
   Couch, FJ
   Winqvist, R
   Burwinkel, B
   Sawyer, EJ
   Schmidt, MK
   Rudolph, A
   Dork, T
   Brauch, H
   Hamann, U
   Neuhausen, SL
   Milne, RL
   Fletcher, O
   Pharoah, PDP
   Campbell, IG
   Dunning, AM
   Le Calvez-Kelm, F
   Goldgar, DE
   Tavtigian, SV
   Chenevix-Trench, G
AF Easton, Douglas F.
   Lesueur, Fabienne
   Decker, Brennan
   Michailidou, Kyriaki
   Li, Jun
   Allen, Jamie
   Luccarini, Craig
   Pooley, Karen A.
   Shah, Mitul
   Bolla, Manjeet K.
   Wang, Qin
   Dennis, Joe
   Ahmad, Jamil
   Thompson, Ella R.
   Damiola, Francesca
   Pertesi, Maroulio
   Voegele, Catherine
   Mebirouk, Noura
   Robinot, Nivonirina
   Durand, Geoffroy
   Forey, Nathalie
   Luben, Robert N.
   Ahmed, Shahana
   Aittomaki, Kristiina
   Anton-Culver, Hoda
   Arndt, Volker
   Baynes, Caroline
   Beckman, Matthias W.
   Benitez, Javier
   Van Den Berg, David
   Blot, William J.
   Bogdanova, Natalia V.
   Bojesen, Stig E.
   Brenner, Hermann
   Chang-Claude, Jenny
   Chia, Kee Seng
   Choi, Ji-Yeob
   Conroy, Don M.
   Cox, Angela
   Cross, Simon S.
   Czene, Kamila
   Darabi, Hatef
   Devilee, Peter
   Eriksson, Mikael
   Fasching, Peter A.
   Figueroa, Jonine
   Flyger, Henrik
   Fostira, Florentia
   Garcia-Closas, Montserrat
   Giles, Graham G.
   Glendon, Gord
   Gonzalez-Neira, Anna
   Guenel, Pascal
   Haiman, Christopher A.
   Hall, Per
   Hart, Steven N.
   Hartman, Mikael
   Hooning, Maartje J.
   Hsiung, Chia-Ni
   Ito, Hidemi
   Jakubowska, Anna
   James, Paul A.
   John, Esther M.
   Johnson, Nichola
   Jones, Michael
   Kabisch, Maria
   Kang, Daehee
   Kosma, Veli-Matti
   Kristensen, Vessela
   Lambrechts, Diether
   Li, Na
   Lindblom, Annika
   Long, Jirong
   Lophatananon, Artitaya
   Lubinski, Jan
   Mannermaa, Arto
   Manoukian, Siranoush
   Margolin, Sara
   Matsuo, Keitaro
   Meindl, Alfons
   Mitchell, Gillian
   Muir, Kenneth
   Nevelsteen, Ines
   van den Ouweland, Ans
   Peterlongo, Paolo
   Phuah, Sze Yee
   Pylkas, Katri
   Rowley, Simone M.
   Sangrajrang, Suleeporn
   Schmutzler, Rita K.
   Shen, Chen-Yang
   Shu, Xiao-Ou
   Southey, Melissa C.
   Surowy, Harald
   Swerdlow, Anthony
   Teo, Soo H.
   Tollenaar, Rob A. E. M.
   Tomlinson, Ian
   Torres, Diana
   Truong, Therese
   Vachon, Celine
   Verhoef, Senno
   Wong-Brown, Michelle
   Zheng, Wei
   Zheng, Ying
   Nevanlinna, Heli
   Scott, Rodney J.
   Andrulis, Irene L.
   Wu, Anna H.
   Hopper, John L.
   Couch, Fergus J.
   Winqvist, Robert
   Burwinkel, Barbara
   Sawyer, Elinor J.
   Schmidt, Marjanka K.
   Rudolph, Anja
   Doerk, Thilo
   Brauch, Hiltrud
   Hamann, Ute
   Neuhausen, Susan L.
   Milne, Roger L.
   Fletcher, Olivia
   Pharoah, Paul D. P.
   Campbell, Ian G.
   Dunning, Alison M.
   Le Calvez-Kelm, Florence
   Goldgar, David E.
   Tavtigian, Sean V.
   Chenevix-Trench, Georgia
CA Australian Ovarian Canc Study Grp
   kConFab Investigators
   Lifepool Investigators
   NBCS Investigators
TI No evidence that protein truncating variants in BRIP1 are associated
   with breast cancer risk: implications for gene panel testing
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID DNA-SEQUENCING DATA; FAMILY REGISTRY; SUSCEPTIBILITY ALLELES;
   ATAXIA-TELANGIECTASIA; MUTATION ANALYSIS; RARE MUTATIONS; ATM MUTATIONS;
   FRAMEWORK; PALB2; CARRIERS
AB Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.
   Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48144 cases and 43607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.
   Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).
   Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
C1 [Easton, Douglas F.; Luccarini, Craig; Shah, Mitul; Ahmed, Shahana; Baynes, Caroline; Conroy, Don M.; Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
   [Easton, Douglas F.; Decker, Brennan; Michailidou, Kyriaki; Allen, Jamie; Pooley, Karen A.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Lesueur, Fabienne; Mebirouk, Noura] Mines ParisTech, Inst Curie, INSERM, Genet Epidemiol Canc Team,U900, Paris, France.
   [Decker, Brennan] NHGRI, Canc Genet & Comparat Genom Sect, NIH, Bethesda, MD 20892 USA.
   [Michailidou, Kyriaki] Cyprus Inst Neurol & Genet, Dept Elect Microscopy Mol Pathol, Nicosia, Cyprus.
   [Li, Jun; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
   [Ahmad, Jamil; Pertesi, Maroulio; Voegele, Catherine; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Le Calvez-Kelm, Florence] Int Agcy Res Canc, Genet Canc Susceptibil Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
   [Thompson, Ella R.; Li, Na; Rowley, Simone M.; Campbell, Ian G.; Lifepool Investigators] Peter MacCallum Canc Ctr, Div Res, East Melbourne, Vic, Australia.
   [Thompson, Ella R.; Mitchell, Gillian; Campbell, Ian G.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
   [Damiola, Francesca] Ctr Leon Berard, Canc Res Ctr Lyon, Genet Breast Canc Team, F-69373 Lyon, France.
   Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England.
   [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland.
   [Aittomaki, Kristiina] Helsinki Univ Hosp, Helsinki, Finland.
   [Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
   [Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
   [Australian Ovarian Canc Study Grp] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
   [Beckman, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Obstet & Gynaecol, D-91054 Erlangen, Germany.
   [Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain.
   [Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain.
   Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
   [Blot, William J.; Long, Jirong; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Epidemiol, Nashville, TN USA.
   [Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
   [Bojesen, Stig E.] Copenhagen Gen Populat Study, Herlev, Denmark.
   [Bojesen, Stig E.] Copenhagen Univ Hosp, Gentofte Hosp, Herlev, Denmark.
   [Bojesen, Stig E.] Dept Clin Biochem, Herlev, Denmark.
   [Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
   [Brenner, Hermann; Brauch, Hiltrud] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
   [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
   [Brenner, Hermann] Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
   [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
   [Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
   [Chia, Kee Seng; Hartman, Mikael] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
   [Chia, Kee Seng; Hartman, Mikael] Natl Univ Hlth Syst, Singapore, Singapore.
   [Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Inst Canc Res, Seoul, South Korea.
   [Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.
   [Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
   [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
   [Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
   [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
   [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Figueroa, Jonine; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Figueroa, Jonine] Univ Edinburgh, Sch Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
   [Flyger, Henrik] Dept Breast Surg, Herlev, Denmark.
   [Flyger, Henrik] Copenhagen Univ Hosp, Gentofte Hosp, Herlev, Denmark.
   [Fostira, Florentia] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece.
   [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 Biostat & Epidemiol, Melbourne, Vic, Australia.
   [Glendon, Gord; Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
   [Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, Villejuif, France.
   [Guenel, Pascal; Truong, Therese] CESP Ctr Res Epidemiol & Populat Hlth, Inserm, Canc & Environm Grp, U1018, Villejuif, France.
   [Hart, Steven N.; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
   [Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore.
   [Hooning, Maartje J.] Erasmus Univ, Med Ctr, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
   [Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
   [Ito, Hidemi] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
   [Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
   [James, Paul A.; Southey, Melissa C.; Campbell, Ian G.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
   [James, Paul A.; Mitchell, Gillian] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia.
   [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
   [John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
   [John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
   [Johnson, Nichola; Fletcher, Olivia] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
   [Johnson, Nichola; Swerdlow, Anthony; Fletcher, Olivia] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
   [Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
   [Kabisch, Maria; Torres, Diana; Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
   [Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
   [kConFab Investigators] Peter MacCallum Canc Ctr, kConFab Kathleen Cuningham Consortium Res Familia, Melbourne, Vic, Australia.
   [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med, Pathol & Forens Med, Kuopio, Finland.
   [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, SF-70210 Kuopio, Finland.
   [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland.
   [Kristensen, Vessela] Oslo Univ Hosp, Radiumhospitalet, Inst Canc Res, Dept Genet, Oslo, Norway.
   [Kristensen, Vessela] Univ Oslo, Fac Med, KG Jebsen Ctr Breast Canc Res, Inst Clin Med, Oslo, Norway.
   [Kristensen, Vessela] Univ Oslo, Dept Clin Mol Biol EpiGen, Oslo, Norway.
   [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
   [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
   [Li, Na] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Canc Biol Res Ctr, Wuhan 430074, Hubei, Peoples R China.
   [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
   [Lophatananon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
   [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
   [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
   [Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
   [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-80290 Munich, Germany.
   [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
   [NBCS Investigators] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet,Norwegian Breast Canc Study, Oslo, Norway.
   [Nevelsteen, Ines] Univ Hosp Gashuisberg, Leuven, Belgium.
   [van den Ouweland, Ans] Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands.
   [Peterlongo, Paolo] FIRC Italian Fdn Canc Res, IFOM, Inst Mol Oncol, Milan, Italy.
   [Phuah, Sze Yee; Teo, Soo H.] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia.
   [Phuah, Sze Yee; Teo, Soo H.] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya, Malaysia.
   [Pylkas, Katri; Winqvist, Robert] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
   [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Bioctr Oulu, Lab Canc Genet & Tumor Biol Canc Res & Translat M, Oulu, Finland.
   [Sangrajrang, Suleeporn] NCI, Bangkok, Thailand.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, CIO, Cologne, Germany.
   [Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany.
   [Schmutzler, Rita K.] Univ Cologne, CMMC, Cologne, Germany.
   [Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung, Taiwan.
   [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei 115, Taiwan.
   [Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
   [Surowy, Harald; Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
   [Surowy, Harald; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
   [Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands.
   [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
   [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
   [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia.
   [Verhoef, Senno; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
   [Wong-Brown, Michelle; Scott, Rodney J.] John Hunter Hosp, Div Genet, Hunter Area Pathol Serv, Newcastle, NSW, Australia.
   [Zheng, Ying] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China.
   [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
   [Nevanlinna, Heli] Helsinki Univ Hosp, Helsinki, Finland.
   [Scott, Rodney J.] John Hunter Hosp, Div Mol Med, Pathol North, Newcastle, NSW, Australia.
   [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
   [Hopper, John L.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
   [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
   [Sawyer, Elinor J.] Guys Hosp, Kings Coll London, Div Canc Studies, Res Oncol, London SE1 9RT, England.
   [Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
   [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
   [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
   [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
   [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
   [Goldgar, David E.] Huntsman Canc Inst, Canc Control & Populat Sci, Salt Lake City, UT USA.
   [Tavtigian, Sean V.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
RP Chenevix-Trench, G (reprint author), QIMR Berghofer, Dept Genet & Computat Biol, Locked Bag 2000,RBH Post Off, Herston, Qld 4029, Australia.
EM georgiaT@qimr.edu.au
RI Dork, Thilo/J-8620-2012; Teo,  Soo-hwang/H-2353-2014; Zheng,
   Wei/O-3351-2013; Brenner, Hermann/B-4627-2017; manoukian,
   siranoush/E-7132-2017; 
OI Arndt, Volker/0000-0001-9320-8684; Zheng, Wei/0000-0003-1226-070X;
   Brenner, Hermann/0000-0002-6129-1572; manoukian,
   siranoush/0000-0002-6034-7562; Decker, Brennan/0000-0003-4516-7421;
   Dunning, Alison Margaret/0000-0001-6651-7166; Giles,
   Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314
FU European Commission [223175-HEALTH-F2-2009-223175]; Cancer Research UK
   [C1287/A10118, C1287/A12014, C1287/A 10710, C12292/A11174, C1281/A12014,
   C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C490/A10124,
   C1287/A16563]; European Community [223175, HEALTH-F2-2009-223175];
   National Institutes of Health [CA128978, R01 CA77398, R01 CA092447];
   Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19
   CA148112]; Department of Defense [W81XWH-10-1-0341]; Canadian Institutes
   of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
   Cancer; Komen Foundation for the Cure; Breast Cancer Research
   Foundation; Ovarian Cancer Research Fund; Wellcome Trust [076113]; Susan
   S. Komen Foundation; National Cancer Institute (USA) [UM1 CA164920];
   National Health and Medical Research Council of Australia; New South
   Wales Cancer Council; Victorian Health Promotion Foundation (Australia);
   Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI
   2007-3839, 2009 4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318];
   Breast Cancer Research Trust, UK; ELAN-Fond of the University Hospital
   of Erlangen; Breakthrough Breast Cancer; NIHR Comprehensive Biomedical
   Research Centre; Guy's & St. Thomas' NHS Foundation Trust; King's
   College London, UK; Oxford Biomedical Research Centre; Dietmar-Hopp
   Foundation; Helmholtz Society; German Cancer Research Center; Fondation
   de France; Institut National du Cancer (INCa); Ligue Nationale contre le
   Cancer; Ligue contre le Cancer Grand Ouest; Agence Nationale de Securite
   Sanitaire (ANSES); Agence Nationale de la Recherche (ANR); Chief
   Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research
   Council; Herlev Hospital; Instituto de Salud Carlos III; Red Tematica de
   Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el
   Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI12/00070];
   California Breast Cancer Act; California Breast Cancer Research Fund
   [97-10500]; California Department of Public Health [103885]; Lon V Smith
   Foundation [LVS39420]; Baden Wurttemberg Ministry of Science, Research
   and Arts; German Cancer Aid (Deutsche Krebshilfe); Deutsche Krebshilfe
   [107 352]; Federal Ministry of Education and Research (BMBF) Germany
   [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]; Robert Bosch
   Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ),
   Heidelberg; Institute for Prevention and Occupational Medicine of the
   German Social Accident Insurance; Institute of the Ruhr University
   Bochum (IPA), Bochum; Department of Internal Medicine, Evangelische
   Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Helsinki
   University Central Hospital Research Fund; Academy of Finland [266528,
   250083, 122715]; Finnish Cancer Society; Nordic Cancer Union; Sigrid
   Juselius Foundation; Ministry of Education, Science, Sports, Culture and
   Technology of Japan; Ministry Health, Labour and Welfare of Japan;
   Health and Labour Sciences Research Grants for Research on Applying
   Health Technology from Ministry Health, Labour and Welfare of Japan;
   National Cancer Center Research and Development Fund; Takeda Health
   Foundation; Friends of Hannover Medical School; Rudolf Bartling
   Foundation; Stockholm County Council; Karolinska Institutet; Swedish
   Cancer Society; Gustav V Jubilee foundation; Bert von Kantzows
   foundation; special Government Funding (EVO) of Kuopio University
   Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations;
   University of Eastern Finland; National Breast Cancer Foundation;
   National Health and Medical Research Council (NHMRC); Queensland Cancer
   Fund; Cancer Councils of New South Wales; Cancer Councils of Victoria;
   Cancer Councils of Tasmania; Cancer Councils of South Australia; Cancer
   Foundation of Western Australia; United States Army Medical Research and
   Materiel Command [DAMD17-01-1-0729]; Cancer Council Victoria; Cancer
   Council New South Wales; Cancer Council South Australia; Cancer Council
   Tasmania; National Health and Medical Research Council of Australia
   (NHMRC) [400413, 400281, 199600]; California Breast Cancer Research
   Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098]; California Department
   of Health; National Cancer Institute's Division of Cancer Prevention and
   Control Surveillance, Epidemiology, and End Results Program
   [N01CN25403]; Stichting tegen Kanker [232-2008, 196-2010]; FWO; Deutsche
   Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419]; Hamburg Cancer
   Society; German Cancer Research Center (DKFZ); Italian Association for
   Cancer Research (AIRC); Fondazione IRCCS Istituto Nazionale Tumori; NIH
   [CA128978, CA116167, CA192393, CA176785, CA63464, CA54281, CA098758,
   CA132839, R01CA100374, R01CA64277, R01CA148667, R37CA70867]; NIH
   Specialized Program of Research Excellence (SPORE) in Breast Cancer
   [CA116201]; VicHealth; Australian NHMRC [209057, 251553, 504711];
   Malaysian Ministry of Science, Technology and Innovation (MOSTI);
   Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer
   Research Initiatives Foundation (CARIF); Biomedical Research Council
   [BMRC08/1/35/19/550, 05/1/21/19/425]; Singapore and the National medical
   Research Council, Singapore [NMRC/CG/SERI/2010]; K.G. Jebsen Centre for
   Breast Cancer Research; Research Council of Norway [193387/V50,
   193387/H10]; South Eastern Norway Health Authority [39346]; Norwegian
   Cancer Society; Finnish Cancer Foundation; Academy of Finland (Center of
   Excellence) [251314]; University of Oulu; University of Oulu Support
   Foundation; special Governmental EVO funds for Oulu University
   Hospital-based research activities; Biobanking and Biomolecular
   Resources Research Infrastructure [BBMRI-NL CP16]; Intramural Research
   Funds of the National Cancer Institute, Department of Health and Human
   Services, USA; Marit and Hans Rausings Initiative Against Breast Cancer;
   Agency for Science, Technology and Research of Singapore (A*STAR); US
   National Institute of Health (NIH); Susan G. Komen Breast Cancer
   Foundation; Genetic Associations and Mechanisms in Oncology (GAME-ON)
   Network [U19 CA148065]; Yorkshire Cancer Research [S295, S299, S305PA];
   Sheffield Experimental Cancer Medicine Centre; National Program of
   Cancer Registries; Centers for Disease Control and Prevention (CDC); UK
   National Institute for Health Research Biomedical Research Centre at the
   University of Cambridge; BRL (Basic Research Laboratory) programme
   through the National Research Foundation of Korea - Ministry of
   Education, Science and Technology [2012-0000347]; NUS start-up Grant;
   National University Cancer Institute Singapore (NCIS) Centre Grant; NMRC
   Clinician Scientist Award; DKFZ; National Cancer Institute Thailand;
   Specialized Program of Research Excellence (SPORE) in Breast Cancer
   [CA116201]; Hellenic Cooperative Oncology Group [HR R_BG/04]; Taiwan
   Biobank project of the Institute of Biomedical Sciences, Academia
   Sinica, Taiwan; Institute of Cancer Research (ICR), London; NHS; Greek
   General Secretary for Research and Technology (GSRT) Program, Research
   Excellence II; European Union (European Social Fund-ESF); Greek national
   funds through the Operational Program 'Education and Lifelong Learning'
   of the National Strategic Reference Framework (NSRF)-ARISTEIA; 
   [KULPFV/10/016-SymBioSysII];  [P30 CA68485];  [PBZ_KBN_122/P05/2004]
FX Higher-level funding: The COGS project is funded through a European
   Commission's Seventh Framework Programme grant (agreement number
   223175-HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK
   (C1287/A10118, C1287/A12014) and by the European Community's Seventh
   Framework Programme under grant agreement number 223175 (grant number
   HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came
   from: the European Community's Seventh Framework Programme under grant
   agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK
   (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
   C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of
   Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19
   CA148065 and 1U19 CA148112-the GAME-ON initiative), the Department of
   Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research
   (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen
   Foundation for the Cure, the Breast Cancer Research Foundation, and the
   Ovarian Cancer Research Fund. This study made use of data generated by
   the Wellcome Trust Case Control consortium. Funding for the project was
   provided by the Wellcome Trust under award 076113. The results published
   here are in part based upon data generated by The Cancer Genome Atlas
   Project established by the National Cancer Institute and National Human
   Genome Research Institute. Personal support: GC-T is a National Health
   and Medical Research (NHMRC) Senior Principal Research Fellow. IGC is a
   National Health and Medical Research (NHMRC) Principal Research Fellow.
   ERT is a National Breast Cancer Foundation Postdoctoral Fellow. JL is
   supported by the Susan S. Komen Foundation. Funding of constituent
   studies: BCAC-The Australian Breast Cancer Family Study (ABCFS) was
   supported by grant UM1 CA164920 from the National Cancer Institute
   (USA). The content of this manuscript does not necessarily reflect the
   views or policies of the National Cancer Institute or any of the
   collaborating centres in the Breast Cancer Family Registry (BCFR), nor
   does mention of trade names, commercial products or organisations imply
   endorsement by the US government or the BCFR. The ABCFS was also
   supported by the National Health and Medical Research Council of
   Australia, the New South Wales Cancer Council, the Victorian Health
   Promotion Foundation (Australia) and the Victorian Breast Cancer
   Research Consortium. JLH is an NHMRC Senior Principal Research Fellow.
   MCS. is an NHMRC Senior Research Fellow. The ABCS study was supported by
   the Dutch Cancer Society (grants NKI 2007-3839; 2009 4363). The ACP
   study is funded by the Breast Cancer Research Trust, UK. The work of the
   BBCC was partly funded by ELAN-Fond of the University Hospital of
   Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough
   Breast Cancer (recently merged with Breast Cancer Campaign forming
   Breast Cancer Now) and acknowledges NHS funding to the NIHR Biomedical
   Research Centre, and the National Cancer Research Network (NCRN).
   (BIGGS) ES is supported by NIHR Comprehensive Biomedical Research
   Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with
   King's College London, UK. IT is supported by the Oxford Biomedical
   Research Centre. The BSUCH study was supported by the Dietmar-Hopp
   Foundation, the Helmholtz Society and the German Cancer Research Center
   (DKFZ).; The CECILE study was funded by Fondation de France, Institut
   National du Cancer (INCa), Ligue Nationale contre le Cancer, Ligue
   contre le Cancer Grand Ouest, Agence Nationale de Securite Sanitaire
   (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported
   by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish
   Medical Research Council and Herlev Hospital. The CNIO-BCS was supported
   by the Instituto de Salud Carlos III, the Red Tematica de Investigacion
   Cooperativa en Cancer and grants from the Asociacion Espanola Contra el
   Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and
   PI12/00070). The CTS was initially supported by the California Breast
   Cancer Act of 1993 and the California Breast Cancer Research Fund
   (contract 97-10500) and is currently funded through the National
   Institutes of Health (R01 CA77398). Collection of cancer incidence data
   was supported by the California Department of Public Health as part of
   the statewide cancer reporting programme mandated by California Health
   and Safety Code Section 103885. HAC receives support from the Lon V
   Smith Foundation (LVS39420). The ESTHER study was supported by a grant
   from the Baden Wurttemberg Ministry of Science, Research and Arts.
   Additional cases were recruited in the context of the VERDI study, which
   was supported by a grant from the German Cancer Aid (Deutsche
   Krebshilfe). The GC-HBOC was supported by Deutsche Krebshilfe (107 352).
   The GENICA was funded by the Federal Ministry of Education and Research
   (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114,
   the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum
   (DKFZ), Heidelberg, the Institute for Prevention and Occupational
   Medicine of the German Social Accident Insurance, Institute of the Ruhr
   University Bochum (IPA), Bochum, as well as the Department of Internal
   Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus,
   Bonn, Germany. The HEBCS was financially supported by the Helsinki
   University Central Hospital Research Fund, Academy of Finland (266528),
   the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid
   Juselius Foundation. The HERPACC was supported by a Grant-in-Aid for
   Scientific Research on Priority Areas from the Ministry of Education,
   Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for
   the Third Term Comprehensive 10-Year Strategy for Cancer Control from
   Ministry Health, Labour and Welfare of Japan, by Health and Labour
   Sciences Research Grants for Research on Applying Health Technology from
   Ministry Health, Labour and Welfare of Japan, National Cancer Center
   Research and Development Fund and Grant form Takeda Health Foundation.
   The HMBCS was supported by a grant from the Friends of Hannover Medical
   School and by the Rudolf Bartling Foundation. Financial support for
   KARBAC was provided through the regional agreement on medical training
   and clinical research (ALF) between Stockholm County Council and
   Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee
   foundation and Bert von Kantzows foundation. The KBCP was financially
   supported by the special Government Funding (EVO) of Kuopio University
   Hospital grants, Cancer Fund of North Savo, the Finnish Cancer
   Organizations, and by the strategic funding of the University of Eastern
   Finland.; kConFab is supported by a grant from the National Breast
   Cancer Foundation, and previously by the National Health and Medical
   Research Council (NHMRC), the Queensland Cancer Fund, the Cancer
   Councils of New South Wales, Victoria, Tasmania and South Australia, and
   the Cancer Foundation of Western Australia. Financial support for the
   AOCS was provided by the United States Army Medical Research and
   Materiel Command (DAMD17-01-1-0729), Cancer Council Victoria, Queensland
   Cancer Fund, Cancer Council New South Wales, Cancer Council South
   Australia, The Cancer Foundation of Western Australia, Cancer Council
   Tasmania and the National Health and Medical Research Council of
   Australia (NHMRC; 400413, 400281, 199600). LAABC is supported by grants
   (1RB-0287, 3PB-0102, 5PB-0018,10PB-0098) from the California Breast
   Cancer Research Program. Incident breast cancer cases were collected by
   the USC Cancer Surveillance Program (CSP), which is supported under
   subcontract by the California Department of Health. The CSP is also part
   of the National Cancer Institute's Division of Cancer Prevention and
   Control Surveillance, Epidemiology, and End Results Program, under
   contract number N01CN25403. LMBC is supported by the 'Stichting tegen
   Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the
   FWO and the KULPFV/10/016-SymBioSysII. The MARIE study was supported by
   the Deutsche Krebshilfe e.V. (70-2892-BR I, 106332, 108253, 108419), the
   Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the
   Federal Ministry of Education and Research (BMBF) Germany (01KH0402).
   (MBCSG) is supported by grants from the Italian Association for Cancer
   Research (AIRC) and by funds from the Italian citizens who allocated the
   5/1000 share of their tax payment in support of the Fondazione IRCCS
   Istituto Nazionale Tumori, according to Italian laws (INT-Institutional
   strategic projects "5x1000"). The MCBCS was supported by the NIH grants
   CA128978, CA116167, CA192393, CA176785 an NIH Specialized Program of
   Research Excellence (SPORE) in Breast Cancer (CA116201), and the Breast
   Cancer Research Foundation and a generous gift from the David F. and
   Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded
   by VicHealth and Cancer Council Victoria. The MCCS was further supported
   by Australian NHMRC grants 209057, 251553 and 504711 and by
   infrastructure provided by Cancer Council Victoria. Cases and their
   vital status were ascertained through the Victorian Cancer Registry
   (VCR). The MEC was support by NIH grants CA63464, CA54281, CA098758 and
   CA132839. MYBRCA is funded by research grants from the Malaysian
   Ministry of Science, Technology and Innovation (MOSTI), Malaysian
   Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research
   Initiatives Foundation (CARIF). Additional controls were recruited by
   the Singapore Eye Research Institute, which was supported by a grant
   from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and
   the National medical Research Council, Singapore (NMRC/CG/SERI/2010).
   The NBCS has received funding from the K.G. Jebsen Centre for Breast
   Cancer Research; the Research Council of Norway grant 193387/V50 (to A-L
   Borresen-Dale and VNK) and grant 193387/H10 (to A-L Borresen-Dale and
   VNK), South Eastern Norway Health Authority (grant 39346 to A-L
   Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale
   and VN K). The NBHS was supported by NIH grant R01CA100374. Biological
   sample preparation was conducted the Survey and Biospecimen Shared
   Resource, which is supported by P30 CA68485.; The OBCS was supported by
   research grants from the Finnish Cancer Foundation, the Academy of
   Finland (grant number 250083, 122715 and Center of Excellence grant
   number 251314), the Finnish Cancer Foundation, the Sigrid Juselius
   Foundation, the University of Oulu, the University of Oulu Support
   Foundation and the special Governmental EVO funds for Oulu University
   Hospital-based research activities. The Ontario Familial Breast Cancer
   Registry (OFBCR) was supported by grant UM1 CA164920 from the National
   Cancer Institute (USA). The content of this manuscript does not
   necessarily reflect the views or policies of the National Cancer
   Institute or any of the collaborating centres in the Breast Cancer
   Family Registry (BCFR), nor does mention of trade names, commercial
   products, or organisations imply endorsement by the USA Government or
   the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL
   1997-1505) and the Biobanking and Biomolecular Resources Research
   Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural
   Research Funds of the National Cancer Institute, Department of Health
   and Human Services, USA. The pKARMA study was supported by Marit and
   Hans Rausings Initiative Against Breast Cancer. The RBCS was funded by
   the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC
   study was supported by funding from the Agency for Science, Technology
   and Research of Singapore (A*STAR), the US National Institute of Health
   (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was
   supported primarily by NIH grants R01CA64277, R01CA148667, and
   R37CA70867. Biological sample preparation was conducted the Survey and
   Biospecimen Shared Resource, which is supported by P30 CA68485. The
   scientific development and funding of this project were, in part,
   supported by the Genetic Associations and Mechanisms in Oncology
   (GAME-ON) Network U19 CA148065. The SBCS was supported by Yorkshire
   Cancer Research S295, S299, S305PA and Sheffield Experimental Cancer
   Medicine Centre. The SCCS is supported by a grant from the National
   Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in
   this publication were provided by the Alabama Statewide Cancer Registry;
   Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health,
   Office of Cancer Surveillance; Florida Cancer Data System; North
   Carolina Central Cancer Registry, North Carolina Division of Public
   Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry;
   Mississippi Cancer Registry; South Carolina Central Cancer Registry;
   Virginia Department of Health, Virginia Cancer Registry; Arkansas
   Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR
   72205. The Arkansas Central Cancer Registry is fully funded by a grant
   from National Program of Cancer Registries, Centers for Disease Control
   and Prevention (CDC). Data on SCCS cancer cases from Mississippi were
   collected by the Mississippi Cancer Registry which participates in the
   National Program of Cancer Registries (NPCR) of the Centers for Disease
   Control and Prevention (CDC). The contents of this publication are
   solely the responsibility of the authors and do not necessarily
   represent the official views of the CDC or the Mississippi Cancer
   Registry. SEARCH is funded by a programme grant from Cancer Research UK
   (C490/A10124) and supported by the UK National Institute for Health
   Research Biomedical Research Centre at the University of Cambridge.
   Targeted sequencing in SEARCH was supported by Cancer Research UK grants
   C1287/A16563 to DFE and C8197/A16565 to AMD.; SEBCS was supported by the
   BRL (Basic Research Laboratory) programme through the National Research
   Foundation of Korea funded by the Ministry of Education, Science and
   Technology (2012-0000347). SGBCC is funded by the NUS start-up Grant,
   National University Cancer Institute Singapore (NCIS) Centre Grant and
   the NMRC Clinician Scientist Award. Additional controls were recruited
   by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort
   (SCCS-MEC), which was funded by the Biomedical Research Council, grant
   number: 05/1/21/19/425. SKKDKFZS is supported by the DKFZ. The SZBCS was
   supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The
   National Cancer Institute Thailand. TNBCC was supported by: a
   Specialized Program of Research Excellence (SPORE) in Breast Cancer
   (CA116201), a grant from the Breast Cancer Research Foundation, a
   generous gift from the David F. and Margaret T. Grohne Family
   Foundation, the Hellenic Cooperative Oncology Group research grant (HR
   R_BG/04) and the Greek General Secretary for Research and Technology
   (GSRT) Program, Research Excellence II, the European Union (European
   Social Fund-ESF), and Greek national funds through the Operational
   Program 'Education and Lifelong Learning' of the National Strategic
   Reference Framework (NSRF)-ARISTEIA. The TWBCS is supported by the
   Taiwan Biobank project of the Institute of Biomedical Sciences, Academia
   Sinica, Taiwan. The UKBGS is funded by Breakthrough Breast Cancer and
   the Institute of Cancer Research (ICR), London. ICR acknowledges NHS
   funding to the NIHR Biomedical Research Centre.
NR 43
TC 8
Z9 9
U1 4
U2 12
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 MAY
PY 2016
VL 53
IS 5
BP 298
EP 309
DI 10.1136/jmedgenet-2015-103529
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DK9TR
UT WOS:000375274900003
PM 26921362
ER

PT J
AU Vilboux, T
   Malicdan, MCV
   Chang, YM
   Guo, J
   Zerfas, PM
   Stephen, J
   Cullinane, AR
   Bryant, J
   Fischer, R
   Brooks, BP
   Zein, WM
   Wiggs, EA
   Zalewski, CK
   Poretti, A
   Bryan, MM
   Vemulapalli, M
   Mullikin, JC
   Kirby, M
   Anderson, SM
   Huizing, M
   Toro, C
   Gahl, WA
   Gunay-Aygun, M
AF Vilboux, Thierry
   Malicdan, May Christine V.
   Chang, Yun Min
   Guo, Jennifer
   Zerfas, Patricia M.
   Stephen, Joshi
   Cullinane, Andrew R.
   Bryant, Joy
   Fischer, Roxanne
   Brooks, Brian P.
   Zein, Wadih M.
   Wiggs, Edythe A.
   Zalewski, Christopher K.
   Poretti, Andrea
   Bryan, Melanie M.
   Vemulapalli, Meghana
   Mullikin, James C.
   Kirby, Martha
   Anderson, Stacie M.
   Huizing, Marjan
   Toro, Camilo
   Gahl, William A.
   Gunay-Aygun, Meral
CA NISC Comparative Sequencing Progra
TI Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a
   lamininopathy associated with tics, obsessive compulsive traits and
   myopia due to cell adhesion and migration defects
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; UNDIAGNOSED DISEASES; NEURITE
   OUTGROWTH; GENE; EXPRESSION; HERLITZ; IDENTIFICATION; POLARIZATION;
   DYSTROPHY; ZEBRAFISH
AB Background Laminins are heterotrimeric complexes, consisting of , and subunits that form a major component of basement membranes and extracellular matrix. Laminin complexes have different, but often overlapping, distributions and functions.
   Methods Under our clinical protocol, NCT00068224, we have performed extensive clinical and neuropsychiatric phenotyping, neuroimaging and molecular analysis in patients with laminin 1 (LAMA1)-associated lamininopathy. We investigated the consequence of mutations in LAMA1 using patient-derived fibroblasts and neuronal cells derived from neuronal stem cells.
   Results In this paper we describe individuals with biallelic mutations in LAMA1, all of whom had the cerebellar dysplasia, myopia and retinal dystrophy, in addition to obsessive compulsive traits, tics and anxiety. Patient-derived fibroblasts have impaired adhesion, reduced migration, abnormal morphology and increased apoptosis due to impaired activation of Cdc42, a member of the Rho family of GTPases that is involved in cytoskeletal dynamics. LAMA1 knockdown in human neuronal cells also showed abnormal morphology and filopodia formation, supporting the importance of LAMA1 in neuronal migration, and marking these cells potentially useful tools for disease modelling and therapeutic target discovery.
   Conclusion This paper broadens the phenotypes associated with LAMA1 mutations. We demonstrate that LAMA1 deficiency can lead to alteration in cytoskeletal dynamics, which may invariably lead to alteration in dendrite growth and axonal formation. Estimation of disease prevalence based on population studies in LAMA1 reveals a prevalence of 1-20 in 1000000.
C1 [Gahl, William A.; Gunay-Aygun, Meral] NHGRI, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
   [Vilboux, Thierry; Malicdan, May Christine V.; Chang, Yun Min; Guo, Jennifer; Stephen, Joshi; Cullinane, Andrew R.; Bryant, Joy; Fischer, Roxanne; Bryan, Melanie M.; Huizing, Marjan; Gahl, William A.; Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
   [Vilboux, Thierry] Inova Translat Med Inst, Div Med Genom, Falls Church, VA USA.
   [Malicdan, May Christine V.; Toro, Camilo; Gahl, William A.] NIH, Common Fund, NIH Undiagnosed Dis Program, Bethesda, MD USA.
   [Zerfas, Patricia M.] NIH, Off Res Serv, Diagnost & Res Serv Branch, Bethesda, MD USA.
   [Cullinane, Andrew R.] Howard Univ, Coll Med, Dept Anat, Washington, DC 20059 USA.
   [Brooks, Brian P.; Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD USA.
   [Wiggs, Edythe A.] NINCDS, NIH, Bethesda, MD 20892 USA.
   [Zalewski, Christopher K.] Natl Inst Deaf & Other Commun Disorders, Audiol Unit, Otolaryngol Branch, NIH, Bethesda, MD USA.
   [Poretti, Andrea] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Div Pediat Radiol, Sect Pediat Neuroradiol, Baltimore, MD USA.
   [Vemulapalli, Meghana; Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
   [Kirby, Martha; Anderson, Stacie M.] NHGRI, Flow Cytometry Core, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
RP Malicdan, MCV (reprint author), NHGRI, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
EM malicdanm@mail.nih.gov
OI Poretti, Andrea/0000-0002-9594-3858; Chang, Yun Min/0000-0002-8766-3768
FU Intramural Research Programs of the National Human Genome Research
   Institute; National Institute on Deafness and Other Communication
   Disorders, National Institutes of Health, Bethesda, Maryland, USA
FX This research was supported by the Intramural Research Programs of the
   National Human Genome Research Institute and the National Institute on
   Deafness and Other Communication Disorders, National Institutes of
   Health, Bethesda, Maryland, USA.
NR 45
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD MAY
PY 2016
VL 53
IS 5
BP 318
EP 329
DI 10.1136/jmedgenet-2015-103416
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DK9TR
UT WOS:000375274900005
PM 27095636
ER

PT J
AU Sims, DJ
   Harrington, RD
   Polley, EC
   Forbes, TD
   Mehaffey, MG
   McGregor, PM
   Camalier, CE
   Harper, KN
   Bouk, CH
   Das, B
   Conley, BA
   Doroshow, JH
   Williams, PM
   Lih, CJ
AF Sims, David J.
   Harrington, Robin D.
   Polley, Eric C.
   Forbes, Thomas D.
   Mehaffey, Michele G.
   McGregor, Paul M., III
   Camalier, Corinne E.
   Harper, Kneshay N.
   Bouk, Courtney H.
   Das, Biswajit
   Conley, Barbara A.
   Doroshow, James H.
   Williams, P. Mickey
   Lih, Chih-Jian
TI Plasmid-Based Materials as Multiplex Quality Controls and Calibrators
   for Clinical Next-Generation Sequencing Assays
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID CANCER MEDICINE; VALIDATION; CHALLENGES
AB Although next-generation sequencing technologies have been widely adapted for clinical diagnostic applications, an urgent need exists for multianalyte calibrator materials and controls to evaluate the performance of these assays. Control materials will also play a major role in the assessment, development, and selection of appropriate alignment and variant calling pipelines. We report an approach to provide effective multianalyte controls for next-generation sequencing assays, referred to as the control plasmid spiked-in genome (CPSG). Control plasmids that contain approximately 1000 bases of human genomic sequence with a specific mutation of interest positioned near the middle of the insert and a nearby 6-bp molecular barcode were synthesized, linearized, quantitated, and spiked into genomic DNA derived from formalin-fixed, paraffin-embedded prepared hapmap cell Lines at defined copy number ratios. Serial titration experiments demonstrated the CPSGs performed with similar efficiency of variant detection as formalin-fixed, paraffin-embedded cell line genomic DNA. Repetitive analyses of one lot of CPSGs 90 times during 18 months revealed that the reagents were stable with consistent detection of each of the plasmids at similar variant allele frequencies. CPSGs are designed to work across most next-generation sequencing methods, platforms, and data analysis pipelines. CPSGs are robust controls and can be used to evaluate the performance of different next-generation sequencing diagnostic assays, assess data analysis pipelines, and ensure robust assay performance metrics.
C1 [Sims, David J.; Harrington, Robin D.; Forbes, Thomas D.; Mehaffey, Michele G.; McGregor, Paul M., III; Camalier, Corinne E.; Harper, Kneshay N.; Bouk, Courtney H.; Das, Biswajit; Williams, P. Mickey; Lih, Chih-Jian] Frederick Natl Lab Canc Res, Mol Characterizat & Clin Assay Dev Lab, Frederick, MD USA.
   [Polley, Eric C.; Conley, Barbara A.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Lih, CJ (reprint author), Frederick Natl Lab Canc Res, Bldg 320,Room 5,1050 Boyles St, Frederick, MD 21702 USA.
EM jason.lih@nih.gov
FU National Cancer Institute, NIH [HHSN261200800001E, NO1-CO-2008-00001]
FX Supported by National Cancer Institute, NIH, grants HHSN261200800001E
   and NO1-CO-2008-00001.
NR 22
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAY
PY 2016
VL 18
IS 3
BP 336
EP 349
DI 10.1016/j.jmoldx.2015.11.008
PG 14
WC Pathology
SC Pathology
GA DL3BR
UT WOS:000375509700004
PM 27105923
ER

PT J
AU Luo, YP
   Pan, QQ
   Yao, SB
   Yu, M
   Wu, WM
   Xue, HD
   Kiesewetter, DO
   Zhu, ZH
   Li, F
   Zhao, YP
   Chen, XY
AF Luo, Yaping
   Pan, Qingqing
   Yao, Shaobo
   Yu, Miao
   Wu, Wenming
   Xue, Huadan
   Kiesewetter, Dale O.
   Zhu, Zhaohui
   Li, Fang
   Zhao, Yupei
   Chen, Xiaoyuan
TI Glucagon-Like Peptide-1 Receptor PET/CT with Ga-68-NOTA-Exendin-4 for
   Detecting Localized Insulinoma: A Prospective Cohort Study
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE glucagon-like peptide-1 receptor (GLP-1R); exendin-4; PET/CT; insulinoma
ID GLP-1 RECEPTOR; PANCREATIC INSULINOMAS; TRANSPLANTED ISLETS; EXENDIN-4;
   ANALOG; SCINTIGRAPHY; MANAGEMENT
AB Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with Ga-68-NOTA-MAL-cys(40)-exendin-4 (Ga-68-NOTA-exendin-4) is efficient in detecting insulinoma. Methods: In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and Tc-99m-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30-60 min after the injection of Ga-68-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery. Results: Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. Ga-68-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg +/- SD, 10.2 +/- 4.9; mean SUVmax +/- SD, 23.6 +/- 11.7), resulting in sensitivity of 97.7%. In contrast, Tc-99m-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively. Conclusion: 68Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization of insulinoma.
C1 [Luo, Yaping; Pan, Qingqing; Yao, Shaobo; Zhu, Zhaohui; Li, Fang; Zhao, Yupei] Chinese Acad Med Sci, Dept Nucl Med, Beijing 100730, Peoples R China.
   [Luo, Yaping; Pan, Qingqing; Yao, Shaobo; Yu, Miao; Wu, Wenming; Xue, Huadan; Zhu, Zhaohui; Li, Fang; Zhao, Yupei] Beijing Union Med Coll Hosp, Beijing 100730, Peoples R China.
   [Yu, Miao] Chinese Acad Med Sci, Dept Endocrinol, Beijing 100730, Peoples R China.
   [Wu, Wenming; Zhao, Yupei] Chinese Acad Med Sci, Dept Gen Surg, Beijing 100730, Peoples R China.
   [Xue, Huadan] Chinese Acad Med Sci, Dept Radiol, Beijing 100730, Peoples R China.
   [Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Zhao, YP (reprint author), Chinese Acad Med Sci, Dept Nucl Med, Beijing 100730, Peoples R China.; Zhao, YP (reprint author), Beijing Union Med Coll Hosp, Beijing 100730, Peoples R China.; Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM zhaoyp_pumch@163.com; shawn.chen@nih.gov
FU Special Scientific Research Fund for Public Welfare Professions of China
   [201402001]; Intramural Research Program, National Institute of
   Biomedical Imaging and Bioengineering, National Institutes of Health
FX The costs of publication of this article were defrayed in part by the
   payment of page charges. Therefore, and solely to indicate this fact,
   this article is hereby marked "advertisement" in accordance with 18 USC
   section 1734. This work was supported in part by a Special Scientific
   Research Fund for Public Welfare Professions of China (grant 201402001)
   and the Intramural Research Program, National Institute of Biomedical
   Imaging and Bioengineering, National Institutes of Health. No other
   potential conflict of interest relevant to this article was reported.
NR 32
TC 4
Z9 4
U1 3
U2 8
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD MAY
PY 2016
VL 57
IS 5
BP 715
EP 720
DI 10.2967/jnumed.115.167445
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DL1DP
UT WOS:000375372700039
PM 26795291
ER

PT J
AU Hyun, OJ
   Luber, BS
   Leal, JP
   Wang, H
   Bolejack, V
   Schuetze, SM
   Schwartz, LH
   Helman, LJ
   Reinke, D
   Baker, LH
   Wahl, RL
AF Hyun, Joo O.
   Luber, Brandon S.
   Leal, Jeffiey P.
   Wang, Hao
   Bolejack, Vanessa
   Schuetze, Scott M.
   Schwartz, Lawrence H.
   Helman, Lee J.
   Reinke, Denise
   Baker, Laurence H.
   Wahl, Richard L.
TI Response to Early Treatment Evaluated with F-18-FDG PET and PERCIST 1.0
   Predicts Survival in Patients with Ewing Sarcoma Family of Tumors
   Treated with a Monoclonal Antibody to the Insulinlike Growth Factor 1
   Receptor
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE sarcoma; insulin-like growth factor; F-18-FDG PET
ID POSITRON-EMISSION-TOMOGRAPHY; NEOADJUVANT CHEMOTHERAPY
AB The aim of this study was to assess the prognostic and predictive value of early quantitative F-18-FDG PET to monitor therapy with an antibody to the insulinlike growth factor 1 receptor (IGF-1R antibody) in patients with Ewing sarcoma family of tumors (ESFT). Methods: F-18-FDG PET images at baseline and approximately 9 d after initiation of IGF-1R antibody therapy in 115 patients with refractory or relapsed ESFT were prospectively obtained as part of the Sarcoma Alliance for Research through Collaboration trial. Responses were centrally evaluated by PERCIST 1.0 in 93 patients. The 9-d PET responses were correlated to overall survival (OS), progression-free survival (PFS), and clinical benefit after 6 wk of therapy based on clinical observation and CT response by World Health Organization anatomic criteria. Results: The median OS was 8.1 mo (95% confidence interval, 6.4-10.0 mo). When PERCIST was used, patients with progressive metabolic disease showed shorter OS (median, 4.7 mo) than patients without progression (median, 10.0 mo; P = 0.001). Progressive metabolic disease on day-9 PET was associated with a significantly higher risk of death (hazard ratio, 2.8; 95% confidence interval, 1.5-5.5). Changes in F-18-FDG uptake after 9 d of therapy had an area under the curve of receiver operating characteristic of 0.71 to predict 1-y OS. The area under the curve was 0.63 to predict progression at 3 mo and 0.79 to predict clinical benefit after 6 wk of therapy. Conclusion: Treatment response by quantitative F-18-FDG PET assessed by PERCIST 1.0 as early as 9 d into IGF-1R antibody therapy in patients with ESFT can predict the OS, PFS, and clinical response to therapy.
C1 [Hyun, Joo O.; Leal, Jeffiey P.; Wahl, Richard L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med, Baltimore, MD USA.
   [Luber, Brandon S.; Wang, Hao] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat & Bioinformat, Baltimore, MD 21205 USA.
   [Bolejack, Vanessa] Canc Res & Biostat, Seattle, WA USA.
   [Schuetze, Scott M.; Baker, Laurence H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Schwartz, Lawrence H.] Columbia Univ, Dept Radiol, New York, NY USA.
   [Helman, Lee J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
   [Reinke, Denise] SARC, Ann Arbor, MI USA.
RP Wahl, RL (reprint author), Washington Univ, Sch Med, Dept Radiol, Campus Box 8131,660 S Euclid Ave, St Louis, MO 63110 USA.
EM wahlr@mir.wustl.edu
FU Radiological Society of North America; Quantitative Imaging Biomarker
   Alliance; Department of Health and Human Services [HHSN268201000050C];
   NCI [U01 CA140204]; Sarcoma Alliance for Research through Collaboration;
   F. Hoffman-La Roche; federal funds from National Institute of Biomedical
   Imaging and Bioengineering, National Institutes of Health [U54CA168512]
FX The costs of publication of this article were defrayed in part by the
   payment of page charges. Therefore, and solely to indicate this fact,
   this article is hereby marked "advertisement" in accordance with 18 USC
   section 1734. This study was made possible by funding from the
   Radiological Society of North America, the Quantitative Imaging
   Biomarker Alliance, and funded in part with federal funds from the
   National Institute of Biomedical Imaging and Bioengineering, the
   National Institutes of Health under award number U54CA168512, Department
   of Health and Human Services under contract no. HHSN268201000050C, NCI
   contract no. U01 CA140204, and funds from the Sarcoma Alliance for
   Research through Collaboration, supported by F. Hoffman-La Roche.
   Laurence Baker reports a consulting or advisory role at Ascenta
   Therapeutics, Inc., The Hope Foundation, NCCN Guidelines Committee, and
   SARC, for which he receives no compensation. Richard Wahl is a
   consultant for Nihon Medi Physics. No other potential conflict of
   interest relevant to this article was reported.
NR 19
TC 0
Z9 0
U1 0
U2 0
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD MAY
PY 2016
VL 57
IS 5
BP 735
EP 740
DI 10.2967/jnumed.115.162412
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DL1DP
UT WOS:000375372700042
ER

PT J
AU Schleicher, RL
   Sternberg, MR
   Looker, AC
   Yetley, EA
   Lacher, DA
   Sempos, CT
   Taylor, CL
   Durazo-Arvizu, RA
   Maw, KL
   Chaudhary-Webb, M
   Johnson, CL
   Pfeiffer, CM
AF Schleicher, Rosemary L.
   Sternberg, Maya R.
   Looker, Anne C.
   Yetley, Elizabeth A.
   Lacher, David A.
   Sempos, Christopher T.
   Taylor, Christine L.
   Durazo-Arvizu, Ramon A.
   Maw, Khin L.
   Chaudhary-Webb, Madhulika
   Johnson, Clifford L.
   Pfeiffer, Christine M.
TI National Estimates of Serum Total 25-Hydroxyvitamin D and Metabolite
   Concentrations Measured by Liquid Chromatography-Tandem Mass
   Spectrometry in the US Population during 2007-2010
SO JOURNAL OF NUTRITION
LA English
DT Article
DE NHANES; 25-hydroxyvitamin D-3; 25-hydroxyvitamin D-2; C3-epimer of
   25-hydroxyvitamin D-3; LC-MS/MS
ID VITAMIN-D STATUS; C-3 EPIMER; 3-EPI-25-HYDROXYVITAMIN D-3;
   REPRESENTATIVE SAMPLE; STANDARD REFERENCE; CLINICAL-PRACTICE; NUTRITION
   SURVEY; WHITE AMERICANS; D DEFICIENCY; ADULTS
AB Background: The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D [25(OH)D] concentrations measured by standardized liquid chromatography-tandem mass spectrometry.
   Objective: We describe patterns for total 25(OH)D and individual metabolites in persons aged >= 1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables.
   Methods: We measured 25-hydroxycholecalciferol [25(OH)D-3], 25-hydroxyergocalciferol [25(OH)D-2], and C3-epimer of 25(OH)D-3 [C3-epi-25(OH)D-3] in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES [total 25(OH)D = 25(OH)D-3 + 25(OH)D-2].
   Results: Concentrations (median, detection rate) of 25(OH)D-3 (63.6 nmol/L, 100%) and C3-epi-25(OH)D-3 (3.40 nmol/L, 86%) were generally detectable; 25(OH)D-2 was detectable in 19% of the population. Total 25(OH)D, 25(OH)D-3, and C3-epi-25(OH)D-3 displayed similar demographic patterns and were strongly correlated (Spearman's r > 0.70). Concentrations of 25(OH)D-2 (90th percentile) were much higher in persons aged >= 60 y (17.3 nmol/L) than in younger age groups (<= 4.88 nmol/L). We noted significant race-ethnicity differences in mean total 25(OH)D [non-Hispanic blacks (NHBs), Hispanics, and non-Hispanic whites (NHWs): 46.6, 57.2, and 75.2 nmol/L, respectively] and in the prevalence of total 25(OH)D <30 nmol/L overall (24% of NHBs, 6.4% of Hispanics, and 2.3% of NHWs) as well as stratified by season (winter months: 30% of NHBs, 7.5% of Hispanics, and 3.8% of NHWs; summer months: 17% of NHBs, 4.4% of Hispanics, and 1.6% of NHWs). Persons with higher vitamin D intakes (diet, supplements, or both) and those examined during May-October had significantly higher total 25(OH)D. Significant race-ethnicity interactions in a multiple linear regression model confirmed the necessity of providing race-ethnicity-specific estimates of total 25(OH)D.
   Conclusions: Race-ethnicity differences in the prevalence of low total 25(OH)D remained strong even after adjustment for season to account for the NHANES design imbalance between season, latitude, and race-ethnicity. The strong correlation between C3-epi-25(OH)D-3 and 25(OH)D-3 may be because the epimer is a metabolite of 25(OH)D-3 The presence of 25(OH)D-2 mainly in older persons is likely a result of high-dose prescription vitamin D-2.
C1 [Schleicher, Rosemary L.; Sternberg, Maya R.; Maw, Khin L.; Chaudhary-Webb, Madhulika; Pfeiffer, Christine M.] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
   [Looker, Anne C.; Lacher, David A.; Johnson, Clifford L.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
   [Yetley, Elizabeth A.; Sempos, Christopher T.; Taylor, Christine L.] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
   [Durazo-Arvizu, Ramon A.] Loyola Univ, Dept Epidemiol & Prevent Med, Chicago, IL 60611 USA.
RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
EM cpfeiffer@cdc.gov
FU Office of Dietary Supplements, NIH
FX Data collection and laboratory analyses of vitamin D were supported by
   funding from the Office of Dietary Supplements, NIH.
NR 63
TC 4
Z9 4
U1 4
U2 9
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2016
VL 146
IS 5
BP 1051
EP 1061
DI 10.3945/jn.115.227728
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DL0VA
UT WOS:000375349500017
PM 27052537
ER

PT J
AU Subar, AF
   Freedman, LS
   Kirkpatrick, SI
   Boushey, C
   Potischman, N
   Guenther, PM
   Krebs-Smith, SM
AF Subar, Amy F.
   Freedman, Laurence S.
   Kirkpatrick, Sharon I.
   Boushey, Carol
   Potischman, Nancy
   Guenther, Patricia M.
   Krebs-Smith, Susan M.
TI We Agree That Self-Reported Energy Intake Should Not Be Used as a Basis
   for Conclusions about Energy Intake in Scientific Research Reply
SO JOURNAL OF NUTRITION
LA English
DT Letter
C1 [Subar, Amy F.; Krebs-Smith, Susan M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, Tel Hashomer, Israel.
   [Kirkpatrick, Sharon I.] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada.
   [Boushey, Carol] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
   [Potischman, Nancy] NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
   [Guenther, Patricia M.] Univ Utah, Dept Nutr & Integrat Physiol, Salt Lake City, UT USA.
RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM subara@mail.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2016
VL 146
IS 5
BP 1142
EP 1143
DI 10.3945/jn.116.230854
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DL0VA
UT WOS:000375349500029
PM 27138890
ER

PT J
AU Glod, J
   Rahme, GJ
   Kaur, H
   Raabe, EH
   Hwang, EI
   Israel, MA
AF Glod, John
   Rahme, Gilbert J.
   Kaur, Harpreet
   Raabe, Eric H.
   Hwang, Eugene I.
   Israel, Mark A.
TI Pediatric Brain Tumors: Current Knowledge and Therapeutic Opportunities
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Review
DE pediatric glioma; medulloblastoma; diffuse intrinsic pontine glioma;
   ependymoma; SEGA
ID LOW-GRADE GLIOMAS; INTRINSIC PONTINE GLIOMA; CHILDRENS ONCOLOGY GROUP;
   GIANT-CELL ASTROCYTOMA; NEWLY-DIAGNOSED GLIOBLASTOMA; CONFORMAL
   RADIATION-THERAPY; MAPK PATHWAY ACTIVATION; TUBEROUS SCLEROSIS;
   PHASE-II; MYXOPAPILLARY EPENDYMOMA
AB Great progress has been made in many areas of pediatric oncology. However, tumors of the central nervous system (CNS) remain a significant challenge. A recent explosion of data has led to an opportunity to understand better the molecular basis of these diseases and is already providing a foundation for the pursuit of rationally chosen therapeutics targeting relevant molecular pathways. The molecular biology of pediatric brain tumors is shifting from a singular focus on basic scientific discovery to a platform upon which insights are being translated into therapies.
C1 [Rahme, Gilbert J.; Israel, Mark A.] Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03756 USA.
   [Israel, Mark A.] Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Pediat, Hanover, NH 03756 USA.
   [Rahme, Gilbert J.; Israel, Mark A.] Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Geisel Sch Med Dartmouth, Hanover, NH 03756 USA.
   [Glod, John] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Kaur, Harpreet; Raabe, Eric H.] Johns Hopkins Sch Med, Div Neuropathol, Bloomberg Childrens Hosp, Baltimore, MD USA.
   [Kaur, Harpreet; Raabe, Eric H.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Bloomberg Childrens Hosp, Baltimore, MD USA.
   [Kaur, Harpreet; Raabe, Eric H.] Johns Hopkins Sch Med, Div Pediat Oncol, Bloomberg Childrens Hosp, Baltimore, MD USA.
   [Hwang, Eugene I.] Childrens Natl Med Ctr, Brain Tumor Inst, Washington, DC 20010 USA.
   [Hwang, Eugene I.] Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA.
RP Glod, J (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03756 USA.
EM john.glod@nih.gov
OI Rahme, Gilbert/0000-0001-6060-1279
FU Hitchcock Foundation; Jordan and Kyra Memorial Foundation; Theodora B.
   Betz Foundation; Intramural Research Program of the National Cancer
   Institute, National Institutes of Health
FX Supported by the Hitchcock Foundation (G.J.R.), the Jordan and Kyra
   Memorial Foundation (M.A.I.), and the Theodora B. Betz Foundation
   (M.A.I.). Supported in part, by the Intramural Research Program of the
   National Cancer Institute, National Institutes of Health (J.G.).
NR 161
TC 1
Z9 1
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1077-4114
EI 1536-3678
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD MAY
PY 2016
VL 38
IS 4
BP 249
EP 260
PG 12
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DK7ZF
UT WOS:000375145200003
PM 26989915
ER

PT J
AU Suderman, M
   Stene, LC
   Bohlin, J
   Page, CM
   Holvik, K
   Parr, CL
   Magnus, MC
   Haberg, SE
   Joubert, BR
   Wu, MC
   London, SJ
   Relton, C
   Nystad, W
AF Suderman, M.
   Stene, L. C.
   Bohlin, J.
   Page, C. M.
   Holvik, K.
   Parr, C. L.
   Magnus, M. C.
   Haberg, S. E.
   Joubert, B. R.
   Wu, M. C.
   London, S. J.
   Relton, C.
   Nystad, W.
TI 25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA
   methylation in two pregnancy cohorts (MoBa and ALSPAC)
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE DNA methylation; Epigenetics; Vitamin D; 2-Hydroxyvitamin D; Maternal
   vitamin D; Methylome; Offspring
ID VITAMIN-D STATUS; RANDOMIZED CLINICAL-TRIAL; QUANTILE NORMALIZATION;
   NORWEGIAN MOTHER; CHILD COHORT; EPIGENOME; HEALTH; SUPPLEMENTATION;
   ASSOCIATION; PROFILE
AB The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin. D concentrations are associated with cord blood DNA methylation.
   DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC).
   Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR> 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR < 0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points. (C) 2016 The Authors. Published by Elsevier Ltd.
C1 [Suderman, M.; Relton, C.] Univ Bristol, MRC, Integrat Epidemiol Unit, Oakfield House, Bristol BS8 2BN, Avon, England.
   [Stene, L. C.; Page, C. M.; Holvik, K.; Parr, C. L.; Magnus, M. C.; Haberg, S. E.; Nystad, W.] Norwegian Inst Publ Hlth, Div Epidemiol, Marcus Thrones Gate 6,POB 4404, N-0403 Oslo, Norway.
   [Bohlin, J.] Norwegian Inst Publ Hlth Infect Control & Environ, Lovisenbergata 8,POB 4404, N-0403 Oslo, Norway.
   [Joubert, B. R.; London, S. J.] NIEHS, NIH, US Dept HHS, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
   [Wu, M. C.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
RP Suderman, M (reprint author), Univ Bristol, MRC, Integrat Epidemiol Unit, Oakfield House, Bristol BS8 2BN, Avon, England.
EM matthew.suderman@bristol.ac.uk
OI London, Stephanie/0000-0003-4911-5290; Relton,
   Caroline/0000-0003-2052-4840; Bohlin, Jon/0000-0002-0992-1311
FU Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences [Z01-ES-49019]; Norwegian Ministry of
   Health; Ministry of Education and Research, NIH/NIEHS [N01-ES-75558];
   NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE
   [151918/S10]; Norwegian Research Council/Human Biobanks and Health
   [221097]; BBSRC [BBI025751/1, BB/1025263/1]; Medical Research Council
   (MRC); Wellcome Trust [102215/2/13/1]; University of Bristol; MRC
   Integrative Epidemiology Unit at the University of Bristol
   [MC_UU_12013/2, MC_UU_12013/8]
FX For MoBa this research was supported [in part] by the Intramural
   Research Program of the NIH, National Institute of Environmental Health
   Sciences (Z01-ES-49019). The Norwegian Mother and Child Cohort Study is
   supported by the Norwegian Ministry of Health and the Ministry of
   Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS
   (grant no. 1 UO1 NS 047537-01) and the Norwegian Research Council/FUGE
   (grant no. 151918/S10), and the present study by the Norwegian Research
   Council/Human Biobanks and Health (grant number 221097). We are grateful
   to all families participating in the Norwegian Mother and Child Cohort
   Study.; ARIES was funded by the BBSRC (BBI025751/1 and BB/1025263/1).
   Core programme support for ALSPAC is provided by the Medical Research
   Council (MRC) and the Wellcome Trust (Grant ref: 102215/2/13/1) and the
   University of Bristol. ARIES is maintained under the auspices of the MRC
   Integrative Epidemiology Unit at the University of Bristol
   (MC_UU_12013/2 and MC_UU_12013/8). We are grateful to all the families
   who took part in the ALSPAC study, the midwives for their help in
   recruiting them, and the whole ALSPAC team, which includes interviewers,
   computer and laboratory technicians, clerical workers, research
   scientists, volunteers, managers, receptionists and nurses.
NR 46
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD MAY
PY 2016
VL 159
BP 102
EP 109
DI 10.1016/j.jsbmb.2016.03.005
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DK4UT
UT WOS:000374916500014
PM 26953979
ER

PT J
AU Enoch, MA
   Kitzman, H
   Smith, JA
   Anson, E
   Hodgkinson, CA
   Goldman, D
   Olds, DL
AF Enoch, Mary-Anne
   Kitzman, Harriet
   Smith, Joyce A.
   Anson, Elizabeth
   Hodgkinson, Colin A.
   Goldman, David
   Olds, David L.
TI A Prospective Cohort Study of Influences on Externalizing Behaviors
   Across Childhood: Results From a Nurse Home Visiting Randomized
   Controlled Trial
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE Achenbach Child Behavior Checklist; nurse home visiting; 5-HTTLPR;
   FKBP5; DRD2/ANKK1
ID SUBSTANCE USE DISORDERS; MATERNAL LIFE-COURSE; FOLLOW-UP;
   ANTISOCIAL-BEHAVIOR; SELF-EFFICACY; DEPRESSION; CHILDREN; ADOLESCENCE;
   VISITATION; SYMPTOMS
AB Objective: This study investigated genetic and environmental influences on behavior in a cohort of 600 children followed prenatally to 18 years.
   Method: A randomized controlled trial of prenatal/infancy nurse home visits (NHV) was conducted in 600 predominantly African American mothers and their firstborn children from Memphis, TN. Mothers were assessed in pregnancy for mental health (MH), self-efficacy, and mastery. Mothers reported longitudinally on smoking and alcohol/drug use. The functional polymorphisms SLC6A4 5-HTTLPR, FKBP5 rs1360780 and DRD2/ANKK1 rs1800497 were genotyped together with 186 ancestry informative markers. Composite externalizing disorders (ED) continuous total scores from the mother-report Achenbach Child Behavior Checklist were included as dependent variables in regression analyses for time points 2, 6, 12, and 18 years.
   Results: Behaviors at younger ages strongly predicted later behaviors (p<.0001). Children whose mothers had high self-efficacy and had received NHV were better behaved at age 2 years. Poorer maternal MH adversely influenced ED up to 12 years, but at age 18 years, maternal mastery exerted a strong, positive effect (p=.0001). Maternal smoking was associated with worse ED at 6 and 18 years. Main and interactive effects of genetic polymorphisms varied across childhood: FKBP5 rs1360780 up to age 6, 5-HTTLPR from 6 to 12, and DRD2/ANKK1 rs1800497 from 2 to 18 years.
   Conclusion: Our study suggests that maternal MH and resilience measured in pregnancy have long-lasting effects on child behavior. Maternal smoking across childhood and genetic factors also play a role. NHV had a positive effect on early behavior. Our findings have implications for prevention of pathological behaviors in adulthood.
C1 [Enoch, Mary-Anne; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Kitzman, Harriet; Smith, Joyce A.; Anson, Elizabeth] Univ Rochester, Sch Nursing, Rochester, NY USA.
   [Olds, David L.] Univ Colorado, Aurora, CO USA.
RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, ING, Room 3S32,MSC 9412,5625 Fishers Lane, Bethesda, MD 20892 USA.
EM maenoch@niaaa.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Robert Wood Johnson Foundation [017934, 11084, 027901]; Carnegie
   Corporation of New York [B 5492]; Pew Charitable Trusts [88-0211-000,
   93-02363-000]; William T Grant Foundation [88-1246-88, 91-1246-88];
   Senior Research Scientist Award [1-K05-MH01382-01]; National Institute
   of Mental Health (NIMH) [1R01MH68790-01, R01-MH61428-01]; National
   Institute of Child Health and Human Development [R01-HD-043492];
   National Institute of Nursing Research (NINR) [NR01-01691-05];
   Department of Health and Human Services (DHHS); National Center for
   Child Abuse and Neglect, through a transfer of funds; Office of Juvenile
   Justice and Delinquency Prevention grant [2004-52854-CO-JSO];
   Administration for Children and Families, DHHS [90PD0215/01, 90PJ0003];
   Bureau of Maternal and Child Health [MCJ 360579]; Hearst Foundation;
   National Institute on Alcohol Abuse and Alcoholism, NIH
FX The research was supported by the Robert Wood Johnson Foundation
   (017934, 11084, 027901); the Carnegie Corporation of New York (B 5492);
   the Pew Charitable Trusts (88-0211-000, 93-02363-000); the William T
   Grant Foundation (88-1246-88, 91-1246-88); and a Senior Research
   Scientist Award (1-K05-MH01382-01) to David Olds. Further grants:
   National Institute of Mental Health (NIMH) 1R01MH68790-01
   R01-MH61428-01; National Institute of Child Health and Human
   Development. R01-HD-043492; National Institute of Nursing Research
   (NINR): NR01-01691-05; Department of Health and Human Services (DHHS)
   and the National Center for Child Abuse and Neglect, through a transfer
   of funds to the NINR; Office of Juvenile Justice and Delinquency
   Prevention grant 2004-52854-CO-JSO; the Administration for Children and
   Families, DHHS, 90PD0215/01, 90PJ0003; the Bureau of Maternal and Child
   Health MCJ 360579; and the Hearst Foundation. This research was funded
   in part by the intramural program of the National Institute on Alcohol
   Abuse and Alcoholism, NIH.
NR 44
TC 1
Z9 1
U1 2
U2 8
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 MAY
PY 2016
VL 55
IS 5
BP 376
EP 382
DI 10.1016/j.jaac.2016.02.007
PG 7
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DL1AA
UT WOS:000375363100009
PM 27126851
ER

PT J
AU Scahill, L
   Jeon, S
   Boorin, SJ
   McDougle, CJ
   Aman, MG
   Dziura, J
   McCracken, JT
   Caprio, S
   Arnold, LE
   Nicol, G
   Deng, YH
   Challa, SA
   Vitiello, B
AF Scahill, Lawrence
   Jeon, Sangchoon
   Boorin, Susan J.
   McDougle, Christopher J.
   Aman, Michael G.
   Dziura, James
   McCracken, James T.
   Caprio, Sonia
   Arnold, L. Eugene
   Nicol, Ginger
   Deng, Yanhong
   Challa, Saankari A.
   Vitiello, Benedetto
TI Weight Gain and Metabolic Consequences of Risperidone in Young Children
   With Autism Spectrum Disorder
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE autism spectrum disorder; risperidone; weight gain; metabolic syndrome;
   insulin resistance
ID PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT BEHAVIOR CHECKLIST;
   RANDOMIZED CLINICAL-TRIAL; CARDIOVASCULAR RISK; CARDIOMETABOLIC RISK;
   INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; CHOLESTEROL RATIO; OBESE
   CHILDREN; ADOLESCENTS
AB Objective: We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD).
   Method: This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 +/- 2.35 years; 105 boys and 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained before treatment and at week 16.
   Results: In 97 children with a mean of 22.9 +/- 2.8 weeks of risperidone exposure, there was a 5.4 +/- 3.4 kg weight gain over 24 weeks (p<.0001); waist circumference increased from 60.7 +/- 10.4 cm to 66.8 +/- 11.3 cm (p<.0001). At baseline, 59 of 97 children (60.8%) were classified as having normal weight; by week 24, only 25 of 85 (29.4%) remained in that group. Growth curve analysis showed a significant change in body mass index (BMI) z scores from pretreatment to week 24 (p<.0001). This effect was significantly greater for children with reported increased appetite in the first 8 weeks. From before treatment to week 16, there were significant increases in glucose (p=.02), hemoglobin Alc (p=.01), insulin (p<.0001), homeostatic model assessment insulin resistance (HOMA-IR; p<.001), alanine aminotransferase (p=.01), and leptin (p<.0001). Adiponectin declined (p=.003). At baseline, 7 children met conventional criteria for metabolic syndrome; by week 16, 12 additional children were so classified.
   Conclusion: Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring.
C1 [Scahill, Lawrence; Challa, Saankari A.] Emory Univ, Sch Med, Atlanta, GA USA.
   [Scahill, Lawrence] Marcus Autism Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
   [Jeon, Sangchoon; Boorin, Susan J.] Yale Univ, Sch Nursing, West Haven, CT USA.
   [McDougle, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
   [McDougle, Christopher J.] Lurie Ctr Autism, Boston, MA USA.
   [Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA.
   [Dziura, James; Caprio, Sonia] Yale Univ, Sch Med, New Haven, CT USA.
   [McCracken, James T.] Univ Calif Los Angeles, Div Child Psychiat, Los Angeles, CA USA.
   [Nicol, Ginger] Washington Univ, St Louis, MO 63130 USA.
   [Deng, Yanhong] Yale Univ, New Haven, CT 06520 USA.
   [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
RP Scahill, L (reprint author), Marcus Autism Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
EM lawrence.scahill@emory.edu
FU NIMH, Yale [U10MH66764]; NIMH, Indiana University [U10MH66766]; NIMH,
   Ohio State University [U10MH66768]; Yale CTSA [UL1 RR024139]; IU CTSA
   [UL1 RR025761]; OSU CTSA [UL1 RR025755]; Atlanta Clinical and
   Translational Science Institute at Emory University from the National
   Center for Research Resources [UL1TR000454]; Marcus Foundation;
   Children's Hospital of Atlanta Trust Fund
FX This work was funded by NIMH by the following RUPP grants: Yale,
   U10MH66764; Indiana University, U10MH66766, Ohio State University,
   U10MH66768; and Janssen/Johnson and Johnson Pharmaceutical Research and
   Development provided active risperidone for the study. This publication
   was also supported by the Yale CTSA UL1 RR024139, IU CTSA UL1 RR025761,
   OSU CTSA UL1 RR025755, and Atlanta Clinical and Translational Science
   Institute UL1TR000454 at Emory University from the National Center for
   Research Resources. Dr. Scahill also received support from the Marcus
   Foundation and the Children's Hospital of Atlanta Trust Fund.
NR 47
TC 2
Z9 2
U1 4
U2 5
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 MAY
PY 2016
VL 55
IS 5
BP 415
EP 423
DI 10.1016/j.jaac.2016.02.016
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DL1AA
UT WOS:000375363100014
PM 27126856
ER

PT J
AU Ye, H
   Wang, XF
   Sussman, CR
   Hopp, K
   Lrazabal, MV
   Bakeberg, JL
   LaRiviere, WB
   Manganiello, VC
   Vorhees, CV
   Zhao, HQ
   Harris, PC
   van Deursen, J
   Ward, CJ
   Torres, VE
AF Ye, Hong
   Wang, Xiaofang
   Sussman, Caroline R.
   Hopp, Katharina
   Lrazabal, Maria V.
   Bakeberg, Jason L.
   LaRiviere, Wells B.
   Manganiello, Vincent C.
   Vorhees, Charles V.
   Zhao, Haiqing
   Harris, Peter C.
   van Deursen, Jan
   Ward, Christopher J.
   Torres, Vicente E.
TI Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1
   and 3 Subfamilies
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; MICE; CAMP; VASOPRESSIN; MODEL;
   CGMP; COMPARTMENTALIZATION; LOCALIZATION; CYSTOGENESIS; INHIBITION
AB Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR)-driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A-phosphorylated (Ser133) cAMP-responsive binding protein (P-CREB), activating transcription factor-1, and CREB-induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2(-/WS25);Pde1a(-/-), Pkd2(-/WS25);Pde1c(-/-), and Pkd2(-/WS25);Pde3a(-/-) kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR-driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.
C1 [Ye, Hong; Wang, Xiaofang; Sussman, Caroline R.; Hopp, Katharina; Lrazabal, Maria V.; LaRiviere, Wells B.; Harris, Peter C.; Torres, Vicente E.] Mayo Clin, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55905 USA.
   [van Deursen, Jan] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [Bakeberg, Jason L.; Ward, Christopher J.] Univ Kansas, Med Ctr, Div Nephrol & Hypertens, Kidney Inst, Kansas City, KS 66103 USA.
   [Vorhees, Charles V.] NHLBI, Cardiovasc & Pulm Branch, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
   [Vorhees, Charles V.] Cincinnati Childrens Res Fdn, Dept Pediat, Div Neurol, Cincinnati, OH USA.
   [Vorhees, Charles V.] Univ Cincinnati, Cincinnati, OH USA.
   [Zhao, Haiqing] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
RP Torres, VE (reprint author), Mayo Clin, Div Nephrol & Hypertens, 200 First St SW, Rochester, MN 55905 USA.
EM torres.vicente@mayo.edu
FU National Institutes of Health [DK44863, DK090728]; Polycystic Kidney
   Disease Foundation; American Society of Nephrology Ben J. Lipps
   Fellowship; National Heart, Lung, and Blood Institute Intramural
   Research Program
FX This work was supported by National Institutes of Health Grants DK44863
   and DK090728, a Polycystic Kidney Disease Foundation Grant (to C.R.S.),
   and an American Society of Nephrology Ben J. Lipps Fellowship (to K.H.).
   V.C.M. is supported by the National Heart, Lung, and Blood Institute
   Intramural Research Program.
NR 39
TC 1
Z9 1
U1 3
U2 4
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2016
VL 27
IS 5
BP 1312
EP 1320
DI 10.1681/ASN.2015010057
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA DK9FR
UT WOS:000375236700011
PM 26374610
ER

PT J
AU Wang, XXX
   Edelstein, MH
   Gafter, U
   Qiu, LR
   Luo, YH
   Dobrinskikh, E
   Lucia, S
   Adorini, L
   D'Agati, VD
   Levi, J
   Rosenberg, A
   Kopp, JB
   Gius, DR
   Saleem, MA
   Levi, M
AF Wang, Xiaoxin X.
   Edelstein, Michel Herman
   Gafter, Uzi
   Qiu, Liru
   Luo, Yuhuan
   Dobrinskikh, Evgenia
   Lucia, Scott
   Adorini, Luciano
   D'Agati, Vivette D.
   Levi, Jonathan
   Rosenberg, Avi
   Kopp, Jeffrey B.
   Gius, David R.
   Saleem, Moin A.
   Levi, Moshe
TI G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney
   Disease in Obesity and Diabetes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID RENAL LIPID-METABOLISM; FARNESOID-X RECEPTOR; ELEMENT-BINDING PROTEINS;
   GROWTH-FACTOR-BETA; OXIDATIVE STRESS; CHOLESTEROL CRYSTALS;
   ENERGY-METABOLISM; MOUSE PODOCYTES; GENE-EXPRESSION; SIRTUIN 1
AB Obesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid beta-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondria! superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondria! biogenesis, decreased oxidative stress, and increased fatty acid beta-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.
C1 [Wang, Xiaoxin X.; Qiu, Liru; Luo, Yuhuan; Dobrinskikh, Evgenia; Lucia, Scott; Levi, Moshe] Univ Colorado Anschutz Med Campus, Dept Med, Div Renal Dis & Hypertens, Aurora, CO USA.
   [Edelstein, Michel Herman; Gafter, Uzi] Tel Aviv Univ, Rabin Med Ctr, Dept Nephrol & Hypertens, Felsenstein Med Res Ctr,Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Adorini, Luciano] Intercept, New York, NY USA.
   [D'Agati, Vivette D.] Columbia Univ, Dept Pathol, Coll Phys & Surg, New York, NY USA.
   [Levi, Jonathan; Rosenberg, Avi; Kopp, Jeffrey B.] NIDDK, NIH, Bethesda, MD 20892 USA.
   [Gius, David R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Saleem, Moin A.] Univ Bristol, Southmead Hosp, Bristol, Avon, England.
RP Levi, M (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, 12700 East 19th Ave,Res 2,Room 7002,Box C281, Aurora, CO 80045 USA.; Wang, XXX (reprint author), Univ Colorado Denver, Dept Med, 12700 East 19th Ave,Res 2,Room 7450,Box C281, Aurora, CO 80045 USA.
EM Xiaoxin.Wang@ucdenver.edu; Moshe.Levi@ucdenver.edu
FU NIH [1R01-DK098336, U24-DK076169]; VA [1I01BX001954]; Intercept
FX These studies were supported by grants from NIH (1R01-DK098336, to M.
   Levi, X. Wang, Y. Luo, and E. Dobrinskikh), VA (1I01BX001954, to M.
   Levi, X. Wang, Y. Luo, and E. Dobrinskikh), NIH (U24-DK076169, to M.
   Herman Edelstein, V. D. D'Agati, and M. Levi), and Intercept (to M.
   Levi).
NR 81
TC 7
Z9 7
U1 10
U2 14
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2016
VL 27
IS 5
BP 1362
EP 1378
DI 10.1681/ASN.2014121271
PG 17
WC Urology & Nephrology
SC Urology & Nephrology
GA DK9FR
UT WOS:000375236700015
PM 26424786
ER

PT J
AU Yanik, EL
   Clarke, CA
   Snyder, JJ
   Pfeiffer, RM
   Engels, EA
AF Yanik, Elizabeth L.
   Clarke, Christina A.
   Snyder, Jon J.
   Pfeiffer, Ruth M.
   Engels, Eric A.
TI Variation in Cancer Incidence among Patients with ESRD during Kidney
   Function and Nonfunction Intervals
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID STAGE RENAL-DISEASE; COMBINATION ANTIRETROVIRAL THERAPY; TRANSPLANT
   RECIPIENTS; RISK-FACTORS; RETROSPECTIVE COHORT; NATURAL-HISTORY;
   LUNG-CANCER; HIV; IMMUNOSUPPRESSION; WOMEN
AB Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.
C1 [Yanik, Elizabeth L.; Pfeiffer, Ruth M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
   [Clarke, Christina A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
   [Clarke, Christina A.] Stanford Canc Inst, Palo Alto, CA USA.
   [Snyder, Jon J.] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA.
   [Snyder, Jon J.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Yanik, EL (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E-216, Bethesda, MD 20892 USA.
EM elizabeth.yanik@nih.gov
FU Intramural Research Program of the National Cancer Institute; Arbor
   Research Collaborative for Health in Ann Arbor, Michigan
   [HHSH234200537009C]; National Program of Cancer Registries of the
   Centers for Disease Control and Prevention: California [1U58
   DP000807-01]; National Program of Cancer Registries of the Centers for
   Disease Control and Prevention: Colorado [U58 DP000848-04]; National
   Program of Cancer Registries of the Centers for Disease Control and
   Prevention: Georgia [5U58DP003875-01]; National Program of Cancer
   Registries of the Centers for Disease Control and Prevention: Illinois
   [5U58DP003883-03]; National Program of Cancer Registries of the Centers
   for Disease Control and Prevention: Michigan [5U58DP003921-03]; National
   Program of Cancer Registries of the Centers for Disease Control and
   Prevention: New Jersey [5U58/DP003931-02]; National Program of Cancer
   Registries of the Centers for Disease Control and Prevention: New York
   [U58DP003879]; National Program of Cancer Registries of the Centers for
   Disease Control and Prevention: North Carolina [U58DP000832]; National
   Program of Cancer Registries of the Centers for Disease Control and
   Prevention: Texas [5U58DP000824-04]; SEER Program of the National Cancer
   Institute: California [HHSN261201000036C, HHSN261201000035C,
   HHSN261201000034C]; SEER Program of the National Cancer Institute:
   Connecticut [HHSN261201000024C]; SEER Program of the National Cancer
   Institute: Hawaii [HHSN261201000037C, N01-PC-35137, N01-PC-35139]; SEER
   Program of the National Cancer Institute: Iowa [HSN261201000032C,
   N01-PC-35143]; SEER Program of the National Cancer Institute: New Jersey
   [HHSN261201300021I, N01-PC-2013-00021]; SEER Program of the National
   Cancer Institute: Seattle-Puget Sound [N01-PC-35142]; SEER Program of
   the National Cancer Institute: Utah [HHSN261201000026C]; state of
   California; state of Colorado; state of Connecticut; state of Illinois;
   state of Iowa; state of New Jersey; state of New York; Cancer
   Surveillance Initiative; state of Texas; state of Washington; Fred
   Hutchinson Cancer Research Center in Seattle, Washington
FX This research was supported by the Intramural Research Program of the
   National Cancer Institute.; During the initial period when registry
   linkages were performed, the SRTR was managed by Arbor Research
   Collaborative for Health in Ann Arbor, Michigan (contract
   HHSH234200537009C), beginning in September 2010, the SRTR was managed by
   Minneapolis Medical Research Foundation in Minneapolis, Minnesota
   (HHSH250201000018C).; The following cancer registries were supported by
   the National Program of Cancer Registries of the Centers for Disease
   Control and Prevention: California (agreement 1U58 DP000807-01),
   Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois
   (5U58DP003883-03), Michigan (5U58DP003921-03), New Jersey
   (5U58/DP003931-02), New York (U58DP003879), North Carolina
   (U58DP000832), and Texas (5U58DP000824-04).; The following cancer
   registries were supported by the SEER Program of the National Cancer
   Institute: California (contracts HHSN261201000036C, HHSN261201000035C,
   and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii
   (HHSN261201000037C, N01-PC-35137, and N01-PC-35139), Iowa
   (HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201300021I,
   N01-PC-2013-00021), Seattle-Puget Sound (N01-PC-35142), and Utah
   (HHSN261201000026C).; Additional support was provided by the states of
   California, Colorado, Connecticut, Illinois, Iowa, New Jersey, New York
   (including the Cancer Surveillance Initiative), Texas, and Washington,
   as well as the Fred Hutchinson Cancer Research Center in Seattle,
   Washington.
NR 31
TC 7
Z9 7
U1 3
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2016
VL 27
IS 5
BP 1495
EP 1504
DI 10.1681/ASN.2015040373
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA DK9FR
UT WOS:000375236700027
PM 26563384
ER

PT J
AU Mendez-Rios, JD
   Yang, ZL
   Erlandson, KJ
   Cohen, JI
   Martens, CA
   Bruno, DP
   Porcella, SF
   Moss, B
AF Mendez-Rios, Jorge D.
   Yang, Zhilong
   Erlandson, Karl J.
   Cohen, Jeffrey I.
   Martens, Craig A.
   Bruno, Daniel P.
   Porcella, Stephen F.
   Moss, Bernard
TI Molluscum Contagiosum Virus Transcriptome in Abortively Infected
   Cultured Cells and a Human Skin Lesion
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID KAPPA-B ACTIVATION; VACCINIA VIRUS; AUTOINTEGRATION FACTOR;
   DERMATOTROPIC POXVIRUS; DNA-REPLICATION; GENE-EXPRESSION; KINASE
   COMPLEX; MC159 PROTEIN; MC160 PROTEIN; HOST-DEFENSE
AB Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model or a cell culture replication system. We used next-generation sequencing to analyze and compare polyadenylated RNAs from abortive MOCV infections of several cell lines and a human skin lesion. Viral RNAs were detected for 14 days after MOCV infection of cultured cells; however, there was little change in the RNA species during this time and a similar pattern occurred in the presence of an inhibitor of protein synthesis, indicating a block preventing postreplicative gene expression. Moreover, a considerable number of MOCV RNAs mapped to homologs of orthopoxvirus early genes, but few did so to homologs of intermediate or late genes. The RNAs made during in vitro infections represent a subset of RNAs detected in human skin lesions which mapped to homologs of numerous postreplicative as well as early orthopoxvirus genes. Transfection experiments using fluorescent protein and luciferase reporters demonstrated that vaccinia virus recognized MOCV intermediate and late promoters, indicating similar gene regulation. The specific recognition of the intermediate promoter in MOCV-infected cells provided evidence for the synthesis of intermediate transcription factors, which are products of early genes, but not for late transcription factors. Transcriptome sequencing (RNA-seq) and reporter gene assays may be useful for testing engineered cell lines and conditions that ultimately could provide an in vitro replication system.
C1 [Mendez-Rios, Jorge D.; Yang, Zhilong; Erlandson, Karl J.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Yang, Zhilong] Kansas State Univ, Div Biol, Ackert Hall, Manhattan, KS 66506 USA.
   [Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Martens, Craig A.; Bruno, Daniel P.; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
   (NIAID) [Ai00030733]
FX This work, including the efforts of Bernard Moss, Jorge D. Mendez-Rios,
   Zhilong Yang, and Karl Erlandson, was funded by HHS vertical bar NIH
   vertical bar National Institute of Allergy and Infectious Diseases
   (NIAID) (Ai00030733).
NR 45
TC 0
Z9 0
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 9
BP 4469
EP 4480
DI 10.1128/JVI.02911-15
PG 12
WC Virology
SC Virology
GA DK7SG
UT WOS:000375125400020
PM 26889040
ER

PT J
AU Kaplan, G
   Roitburd-Berman, A
   Lewis, GK
   Gershoni, JM
AF Kaplan, Gilad
   Roitburd-Berman, Anna
   Lewis, George K.
   Gershoni, Jonathan M.
TI Range of CD4-Bound Conformations of HIV-1 gp120, as Defined Using
   Conditional CD4-Induced Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; HUMAN
   MONOCLONAL-ANTIBODY; CORECEPTOR-BINDING-SITE; NEUTRALIZING ANTIBODIES;
   STRUCTURAL DEFINITION; OLIGOMERIC STRUCTURE; EFFECTOR FUNCTION;
   CROSS-LINKING; CD4 RECEPTOR
AB The HIV envelope binds cellular CD4 and undergoes a range of conformational changes that lead to membrane fusion and delivery of the viral nucleocapsid into the cellular cytoplasm. This binding to CD4 reveals cryptic and highly conserved epitopes, the molecular nature of which is still not fully understood. The atomic structures of CD4 complexed with gp120 core molecules (a form of gp120 in which the V1, V2, and V3 loops and N and C termini have been truncated) have indicated that a hallmark feature of the CD4-bound conformation is the bridging sheet minidomain. Variations in the orientation of the bridging sheet hairpins have been revealed when CD4-liganded gp120 was compared to CD4-unliganded trimeric envelope structures. Hence, there appears to be a number of conformational transitions possible in HIV-1 monomeric gp120 that are affected by CD4 binding. The spectrum of CD4-bound conformations has been interrogated in this study by using a well-characterized panel of conditional, CD4-induced (CD4i) monoclonal antibodies (MAbs) that bind HIV-1 gp120 and its mutations under various conditions. Two distinct CD4i epitopes of the outer domain were studied: the first comprises the bridging sheet, while the second contains elements of the V2 loop. Furthermore, we show that the unliganded extended monomeric core of gp120 (core(e)) assumes an intermediate CD4i conformation in solution that further undergoes detectable rearrangements upon association with CD4. These discoveries impact both accepted paradigms concerning gp120 structure and the field of HIV immunogen design.
C1 [Kaplan, Gilad; Roitburd-Berman, Anna; Gershoni, Jonathan M.] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel.
   [Lewis, George K.] Univ Maryland, Sch Med, Inst Human Virol, Div Vaccine Res, Baltimore, MD 21201 USA.
   [Kaplan, Gilad] NCI, NIH, Bethesda, MD 20892 USA.
RP Gershoni, JM (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel.
EM gershoni@tauex.tau.ac.il
FU HHS \ National Institutes of Health (NIH) [R01 AI087181]; Bill and
   Melinda Gates Foundation; Israel Science Foundation (ISF); Frankel
   Family Foundation
FX This work, including the efforts of George K. Lewis, was funded by HHS
   vertical bar National Institutes of Health (NIH) (R01 AI087181). This
   work, including the efforts of George K. Lewis, was funded by Bill and
   Melinda Gates Foundation. This work, including the efforts of Gilad
   Kaplan, Anna Roitburd-Berman, and Jonathan M. Gershoni, was funded by
   Israel Science Foundation (ISF). This work, including the efforts of
   Gilad Kaplan, Anna Roitburd-Berman, and Jonathan M. Gershoni, was funded
   by Frankel Family Foundation.
NR 84
TC 1
Z9 1
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 9
BP 4481
EP 4493
DI 10.1128/JVI.03206-15
PG 13
WC Virology
SC Virology
GA DK7SG
UT WOS:000375125400021
PM 26889042
ER

PT J
AU Vinton, C
   Wu, F
   Rossjohn, J
   Matsuda, K
   McCluskey, J
   Hirsch, V
   Price, DA
   Brenchley, JM
AF Vinton, Carol
   Wu, Fan
   Rossjohn, Jamie
   Matsuda, Kenta
   McCluskey, James
   Hirsch, Vanessa
   Price, David A.
   Brenchley, Jason M.
TI Mucosa-Associated Invariant T Cells Are Systemically Depleted in Simian
   Immunodeficiency Virus-Infected Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VITAMIN-B METABOLITES; MAIT CELLS; MICROBIAL TRANSLOCATION; IMMUNE
   ACTIVATION; SIV INFECTION; HIV-INFECTION; RECEPTOR HETEROGENEITY;
   GASTROINTESTINAL-TRACT; MR1 TETRAMERS; RECOGNITION
AB Mucosa-associated invariant T (MAIT) cells contribute to host immune protection against a wide range of potential pathogens via the recognition of bacterial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although bacterial products translocate systemically in human immunodeficiency virus (HIV)-infected individuals and simian immunodeficiency virus (SIV)-infected Asian macaques, several studies have shown that MAIT cell frequencies actually decrease in peripheral blood during the course of HIV/SIV disease. However, the mechanisms underlying this proportional decline remain unclear. In this study, we characterized the phenotype, activation status, functionality, distribution, and clonotypic structure of MAIT cell populations in the peripheral blood, liver, mesenteric lymph nodes (MLNs), jejunum, and bronchoalveolar lavage (BAL) fluid of healthy and SIV-infected rhesus macaques (RMs). Low frequencies of MAIT cells were observed in the peripheral blood, MLNs, and BAL fluid of SIV-infected RMs. These numerical changes were coupled with increased proliferation and a highly public T cell receptor alpha (TCR alpha) repertoire in the MAIT cell compartment without redistribution to other anatomical sites. Collectively, our data show systemically decreased frequencies of MAIT cells likely attributable to enhanced turnover in SIV-infected RMs. This process may impair protective immunity against certain opportunistic infections with progression to AIDS.
C1 [Vinton, Carol; Wu, Fan; Matsuda, Kenta; Hirsch, Vanessa; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Rossjohn, Jamie] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Infect & Immun Program, Clayton, Vic, Australia.
   [Rossjohn, Jamie] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
   [Rossjohn, Jamie; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Heath Pk, Cardiff CF10 3AX, S Glam, Wales.
   [McCluskey, James] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia.
   [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Vinton, Carol; Brenchley, Jason M.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.; Brenchley, JM (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
EM jbrenchl@niaid.nih.gov
RI Price, David/C-7876-2013; McCluskey, James/A-1291-2007; 
OI Price, David/0000-0001-9416-2737; McCluskey, James/0000-0002-8597-815X;
   Rossjohn, Jamie/0000-0002-2020-7522
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health; Australian Research
   Council; National Health and Medical Research Council; Wellcome Trust
FX Funding for this study was provided in part by the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases, National Institutes of Health. Additional funding was provided
   by the Australian Research Council, the National Health and Medical
   Research Council, and the Wellcome Trust.
NR 38
TC 4
Z9 4
U1 2
U2 6
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 MAY
PY 2016
VL 90
IS 9
BP 4520
EP 4529
DI 10.1128/JVI.02876-15
PG 10
WC Virology
SC Virology
GA DK7SG
UT WOS:000375125400024
PM 26912615
ER

PT J
AU Barros, M
   Heinrich, F
   Datta, SAK
   Rein, A
   Karageorgos, I
   Nanda, H
   Losche, M
AF Barros, Marilia
   Heinrich, Frank
   Datta, Siddhartha A. K.
   Rein, Alan
   Karageorgos, Ioannis
   Nanda, Hirsh
   Loesche, Mathias
TI Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer
   Composition and Protein Lipidation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; PLASMA-MEMBRANE;
   TYPE-1 GAG; ELECTROSTATIC INTERACTIONS; RETROVIRAL MATRIX; FATTY-ACIDS;
   CHOLESTEROL; DOMAIN; LIPIDS
AB By assembling in a protein lattice on the host's plasma membrane, the retroviral Gag polyprotein triggers formation of the viral protein/membrane shell. The MA domain of Gag employs multiple signals-electrostatic, hydrophobic, and lipid-specific-to bring the protein to the plasma membrane, thereby complementing protein-protein interactions, located in full-length Gag, in lattice formation. We report the interaction of myristoylated and unmyristoylated HIV-1 Gag MA domains with bilayers composed of purified lipid components to dissect these complex membrane signals and quantify their contributions to the overall interaction. Surface plasmon resonance on well-defined planar membrane models is used to quantify binding affinities and amounts of protein and yields free binding energy contributions, Delta G, of the various signals. Charge-charge interactions in the absence of the phosphatidylinositide PI(4,5)P-2 attract the protein to acidic membrane surfaces, and myristoylation increases the affinity by a factor of 10; thus, our data do not provide evidence for a PI(4,5)P-2 trigger of myristate exposure. Lipid-specific interactions with PI(4,5)P-2, the major signal lipid in the inner plasma membrane, increase membrane attraction at a level similar to that of protein lipidation. While cholesterol does not directly engage in interactions, it augments protein affinity strongly by facilitating efficient myristate insertion and PI(4,5)P-2 binding. We thus observe that the isolated MA protein, in the absence of protein-protein interaction conferred by the full-length Gag, binds the membrane with submicromolar affinities.
C1 [Barros, Marilia; Heinrich, Frank; Nanda, Hirsh; Loesche, Mathias] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
   [Loesche, Mathias] Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA.
   [Heinrich, Frank; Nanda, Hirsh; Loesche, Mathias] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21701 USA.
   [Karageorgos, Ioannis] Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
   [Karageorgos, Ioannis] Inst Biosci & Biotechnol Res, Rockville, MD USA.
   [Nanda, Hirsh] Janssen LLC, Spring House, PA USA.
RP Losche, M (reprint author), Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.; Losche, M (reprint author), Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA.; Losche, M (reprint author), Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.; Rein, A (reprint author), NCI, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM reina@mail.nih.gov; quench@cmu.edu
RI Heinrich, Frank/A-5339-2010; 
OI Heinrich, Frank/0000-0002-8579-553X; Losche,
   Mathias/0000-0001-6666-916X; Datta, Siddhartha/0000-0002-4098-7490
FU HHS \ NIH \ National Cancer Institute (NCI); HHS \ NIH \ National
   Institute of General Medical Sciences (NIGMS) [R01GM101647]
FX This work, including the efforts of Alan Rein, was funded by HHS
   vertical bar NIH vertical bar National Cancer Institute (NCI). This
   work, including the efforts of Marilia Barros and Mathias Losche, was
   funded by HHS vertical bar NIH vertical bar National Institute of
   General Medical Sciences (NIGMS) (R01GM101647).
NR 80
TC 3
Z9 3
U1 1
U2 6
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 MAY
PY 2016
VL 90
IS 9
BP 4544
EP 4555
DI 10.1128/JVI.02820-15
PG 12
WC Virology
SC Virology
GA DK7SG
UT WOS:000375125400026
PM 26912608
ER

PT J
AU Kailasan, S
   Garrison, J
   Ilyas, M
   Chipman, P
   McKenna, R
   Kantola, K
   Soderlund-Venermo, M
   Kucinskaite-Kodze, I
   Zvirbliene, A
   Agbandje-McKenna, M
AF Kailasan, Shweta
   Garrison, Jamie
   Ilyas, Maria
   Chipman, Paul
   McKenna, Robert
   Kantola, Kalle
   Soderlund-Venermo, Maria
   Kucinskaite-Kodze, Indre
   Zvirbliene, Aurelija
   Agbandje-McKenna, Mavis
TI Mapping Antigenic Epitopes on the Human Bocavirus Capsid
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY-TRACT INFECTIONS; MINK DISEASE PARVOVIRUS; VIRUS-LIKE
   PARTICLES; ACUTE GASTROENTERITIS; CANINE PARVOVIRUS; MINUTE VIRUS;
   NEUTRALIZING EPITOPES; MONOCLONAL-ANTIBODY; ELECTRON-MICROSCOPY; PEPTIDE
   VACCINE
AB Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0-to 8.5-angstrom resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae. The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses.
C1 [Kailasan, Shweta; Garrison, Jamie; Ilyas, Maria; Chipman, Paul; McKenna, Robert; Agbandje-McKenna, Mavis] Univ Florida, Dept Biochem & Mol Biol, McKnight Brain Inst, Gainesville, FL 32610 USA.
   [Kantola, Kalle; Soderlund-Venermo, Maria] Univ Helsinki, Dept Virol, Helsinki, Finland.
   [Kucinskaite-Kodze, Indre; Zvirbliene, Aurelija] Vilnius State Univ, Inst Biotechnol, Dept Immunol & Cell Biol, Vilnius, Lithuania.
   [Kailasan, Shweta] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Agbandje-McKenna, M (reprint author), Univ Florida, Dept Biochem & Mol Biol, McKnight Brain Inst, Gainesville, FL 32610 USA.
EM mckenna@ufl.edu
FU UF College of Medicine; UF Division of Sponsored Programs; Beckman
   Scholars Undergraduate Fellowship; McKnight Brain Institute; Finnish
   Medical Foundation; Sigrid Juselius Foundation; Medical Association Liv
   och Halsa; Helsinki University
FX We thank the UF Interdisciplinary Center for Biotechnology Research
   Electron Microscopy core for cryo-electron microscopy access (funded by
   the UF College of Medicine and UF Division of Sponsored Programs).; This
   project was funded in part by the Beckman Scholars Undergraduate
   Fellowship (to M.I.), the UF College of Medicine and McKnight Brain
   Institute (to M.A.-M.), the Finnish Medical Foundation (to M.S.-V.), the
   Sigrid Juselius Foundation (to M.S.-V.), the Medical Association Liv och
   Halsa (to M.S.-V.), and a Helsinki University 375-year celebration grant
   (to M.S.-V.).
NR 81
TC 3
Z9 3
U1 4
U2 7
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 MAY
PY 2016
VL 90
IS 9
BP 4670
EP 4680
DI 10.1128/JVI.02998-15
PG 11
WC Virology
SC Virology
GA DK7SG
UT WOS:000375125400037
PM 26912619
ER

PT J
AU Saijo, E
   Hughson, AG
   Raymond, GJ
   Suzuki, A
   Horiuchi, M
   Caughey, B
AF Saijo, Eri
   Hughson, Andrew G.
   Raymond, Gregory J.
   Suzuki, Akio
   Horiuchi, Motohiro
   Caughey, Byron
TI PrPSc-Specific Antibody Reveals C-Terminal Conformational Differences
   between Prion Strains
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TRANSMISSIBLE MINK ENCEPHALOPATHY; MONOCLONAL-ANTIBODY; SCRAPIE
   INCUBATION; PROTEIN; AGENT; MICE; ISOFORM; DISEASE; IDENTIFICATION;
   TRANSITION
AB Understanding the structure of PrPSc and its strain variation has been one of the major challenges in prion disease biology. To study the strain-dependent conformations of PrPSc, we purified proteinase-resistant PrPSc (PrPRES) from mouse brains with three different murine-adapted scrapie strains (Chandler, 22L, and Me7) and systematically tested the accessibility of epitopes of a wide range of anti-PrP and anti-PrPSc specific antibodies by indirect enzyme-linked immunosorbent assay (ELISA). We found that epitopes of most anti-PrP antibodies were hidden in the folded structure of PrPRES, even though these epitopes are revealed with guanidine denaturation. However, reactivities to a PrPSc-specific conformational C-terminal antibody showed significant differences among the three different prion strains. Our results provide evidence for strain-dependent conformational variation near the C termini of molecules within PrPSc multimers.
   IMPORTANCE
   It has long been apparent that prion strains can have different conformations near the N terminus of the PrPSc protease-resistant core. Here, we show that a C-terminal conformational PrPSc-specific antibody reacts differently to three murine-adapted scrapie strains. These results suggest, in turn, that conformational differences in the C terminus of PrPSc also contribute to the phenotypic distinction between prion strains.
C1 [Saijo, Eri; Hughson, Andrew G.; Raymond, Gregory J.; Caughey, Byron] NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
   [Suzuki, Akio; Horiuchi, Motohiro] Hokkaido Univ, Grad Sch Vet Med, Lab Vet Hyg, Sapporo, Hokkaido, Japan.
RP Caughey, B (reprint author), NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
EM BCAUGHEY@nih.gov
FU HHS \ National Institutes of Health (NIH); Ministry of Education,
   Culture, Sports, Science and Technology (MEXT); Japan Society for the
   Promotion of Science (JSPS); Ministry of Health, Labour and Welfare
   (MHLW) [H26-Shokuhin-Ippan-003]; Intramural Research Program of the
   NIAID
FX This work, including the efforts of Byron Caughey, was funded by HHS
   vertical bar National Institutes of Health (NIH). This work, including
   the efforts of Motohiro Horiuchi, was funded by Ministry of Education,
   Culture, Sports, Science and Technology (MEXT) (F01). This work,
   including the efforts of Eri Saijo, was funded by Japan Society for the
   Promotion of Science (JSPS). This work, including the efforts of
   Motohiro Horiuchi, was funded by Ministry of Health, Labour and Welfare
   (MHLW) (H26-Shokuhin-Ippan-003).; The Intramural Research Program of the
   NIAID provided the NIH funding.
NR 65
TC 1
Z9 1
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 10
BP 4905
EP 4913
DI 10.1128/JVI.00088-16
PG 9
WC Virology
SC Virology
GA DK7SN
UT WOS:000375126100006
PM 26937029
ER

PT J
AU Swanstrom, AE
   Haggarty, B
   Jordan, APO
   Romano, J
   Leslie, GJ
   Aye, PP
   Marx, PA
   Lackner, AA
   Del Prete, GQ
   Robinson, JE
   Betts, MR
   Montefiori, DC
   LaBranche, CC
   Hoxie, JA
AF Swanstrom, Adrienne E.
   Haggarty, Beth
   Jordan, Andrea P. O.
   Romano, Josephine
   Leslie, George J.
   Aye, Pyone P.
   Marx, Preston A.
   Lackner, Andrew A.
   Del Prete, Gregory Q.
   Robinson, James E.
   Betts, Michael R.
   Montefiori, David C.
   LaBranche, Celia C.
   Hoxie, James A.
TI Derivation and Characterization of a CD4-Independent, Non-CD4-Tropic
   Simian Immunodeficiency Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; CORECEPTOR-BINDING-SITE; NONPATHOGENIC MOLECULAR CLONES;
   RHESUS MONOCLONAL-ANTIBODIES; FOLLICULAR HELPER-CELLS; HIV-1 ENVELOPE
   TRIMER; TROPISM IN-VIVO; MACROPHAGE TROPISM; SIV INFECTION;
   NEUTRALIZATION SENSITIVITY
AB CD4 tropism is conserved among all primate lentiviruses and likely contributes to viral pathogenesis by targeting cells that are critical for adaptive antiviral immune responses. Although CD4-independent variants of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have been described that can utilize the coreceptor CCR5 or CXCR4 in the absence of CD4, these viruses typically retain their CD4 binding sites and still can interact with CD4. We describe the derivation of a novel CD4-independent variant of pathogenic SIVmac239, termed iMac239, that was used to derive an infectious R5-tropic SIV lacking a CD4 binding site. Of the seven mutations that differentiate iMac239 from wild-type SIVmac239, a single change (D178G) in the V1/V2 region was sufficient to confer CD4 independence in cell-cell fusion assays, although other mutations were required for replication competence. Like other CD4-independent viruses, iMac239 was highly neutralization sensitive, although mutations were identified that could confer CD4-independent infection without increasing its neutralization sensitivity. Strikingly, iMac239 retained the ability to replicate in cell lines and primary cells even when its CD4 binding site had been ablated by deletion of a highly conserved aspartic acid at position 385, which, for HIV-1, plays a critical role in CD4 binding. iMac239, with and without the D385 deletion, exhibited an expanded host range in primary rhesus peripheral blood mononuclear cells that included CCR5(+) CD8(+) T cells. As the first non-CD4-tropic SIV, iMac239-Delta D385 will afford the opportunity to directly assess the in vivo role of CD4 targeting on pathogenesis and host immune responses.
   IMPORTANCE
   CD4 tropism is an invariant feature of primate lentiviruses and likely plays a key role in pathogenesis by focusing viral infection onto cells that mediate adaptive immune responses and in protecting virions attached to cells from neutralizing antibodies. Although CD4-independent viruses are well described for HIV and SIV, these viruses characteristically retain their CD4 binding site and can engage CD4 if available. We derived a novel CD4-independent, CCR5-tropic variant of the pathogenic molecular clone SIVmac239, termed iMac239. The genetic determinants of iMac239's CD4 independence provide new insights into mechanisms that underlie this phenotype. This virus remained replication competent even after its CD4 binding site had been ablated by mutagenesis. As the first truly non-CD4-tropic SIV, lacking the capacity to interact with CD4, iMac239 will provide the unique opportunity to evaluate SIV pathogenesis and host immune responses in the absence of the immunomodulatory effects of CD4(+) T cell targeting and infection.
C1 [Swanstrom, Adrienne E.; Haggarty, Beth; Jordan, Andrea P. O.; Romano, Josephine; Leslie, George J.; Betts, Michael R.; Hoxie, James A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Aye, Pyone P.; Marx, Preston A.; Lackner, Andrew A.] Tulane Natl Primate Res Ctr, Covington, LA USA.
   [Aye, Pyone P.; Marx, Preston A.; Lackner, Andrew A.] Tulane Univ, Dept Trop Med, New Orleans, LA 70118 USA.
   [Del Prete, Gregory Q.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
   [Robinson, James E.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70118 USA.
   [Montefiori, David C.; LaBranche, Celia C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
RP Hoxie, JA (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM hoxie@mail.med.upenn.edu
FU HHS \ National Institutes of Health (NIH) [T32-AI07632, R01-AI112456,
   RO1-AI074362, P30-AI045008]; HHS \ NIH \ National Cancer Institute (NCI)
   [HHSN261200800001E]; HHS \ NIH \ National Institute of Allergy and
   Infectious Diseases (NIAID) [HHSN27201100016C]; National Institute of
   Allergy and Infectious Diseases [HHSN27201100016C]
FX This work, including the efforts of Adrienne E. Swanstrom, was funded by
   HHS vertical bar National Institutes of Health (NIH) (T32-AI07632). This
   work, including the efforts of James A. Hoxie, was funded by HHS
   vertical bar National Institutes of Health (NIH) (R01-AI112456,
   RO1-AI074362, and P30-AI045008). This work, including the efforts of
   Gregory Q. Del Prete, was funded by HHS vertical bar NIH vertical bar
   National Cancer Institute (NCI) (HHSN261200800001E). This work,
   including the efforts of David Montefiori, was funded by HHS vertical
   bar NIH vertical bar National Institute of Allergy and Infectious
   Diseases (NIAID) (HHSN27201100016C).; The Nonhuman Primate Humoral
   Immunology Core Laboratory also received funds through National
   Institute of Allergy and Infectious Diseases contract HHSN27201100016C.
   Extensive assistance was provided by the Viral/Molecular and Nonhuman
   Primate Cores of the Penn Center for AIDS Research (P30-AI045008).
NR 121
TC 1
Z9 1
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 10
BP 4966
EP 4980
DI 10.1128/JVI.02851-15
PG 15
WC Virology
SC Virology
GA DK7SN
UT WOS:000375126100011
PM 26937037
ER

PT J
AU Singh, K
   Gittis, AG
   Gitti, RK
   Ostazeski, SA
   Su, HP
   Garboczi, DN
AF Singh, Kavita
   Gittis, Apostolos G.
   Gitti, Rossitza K.
   Ostazeski, Stanley A.
   Su, Hua-Poo
   Garboczi, David N.
TI The Vaccinia Virus H3 Envelope Protein, a Major Target of Neutralizing
   Antibodies, Exhibits a Glycosyltransferase Fold and Binds UDP-Glucose
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID N-ACETYLGLUCOSAMINYLTRANSFERASE-I; INTRACELLULAR MATURE VIRION; SURFACE
   HEPARAN-SULFATE; TRANSFER DIFFERENCE NMR; CRYSTAL-STRUCTURE;
   CHONDROITIN-SULFATE; SMALLPOX VACCINE; A27L PROTEIN; COMPLEX; INFECTION
AB The highly conserved H3 poxvirus protein is a major target of the human antibody response against poxviruses and is likely a key contributor to protection against infection. Here, we present the crystal structure of H3 from vaccinia virus at a 1.9-angstrom resolution. H3 looks like a glycosyltransferase, a family of enzymes that transfer carbohydrate molecules to a variety of acceptor substrates. Like glycosyltransferases, H3 binds UDP-glucose, as shown by saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, and this binding requires Mg2+. Mutation of the glycosyltransferase-like metal ion binding motif in H3 greatly diminished its binding to UDP-glucose. We found by flow cytometry that H3 binds to the surface of human cells but does not bind well to cells that are deficient in surface glycosaminoglycans. STD NMR experiments using a heparin sulfate decasaccharide confirmed that H3 binds heparin sulfate. We propose that a surface of H3 with an excess positive charge may be the binding site for heparin. Heparin binding and glycosyltransferase activity may be involved in the function of H3 in the poxvirus life cycle.
   IMPORTANCE
   Poxviruses are under intense research because of bioterrorism concerns, zoonotic infections, and the side effects of existing smallpox vaccines. The smallpox vaccine using vaccinia virus has been highly successful, but it is still unclear why the vaccine is so effective. Studying the antigens that the immune system recognizes may allow a better understanding of how the vaccine elicits immunity and how improved vaccines can be developed. Poxvirus protein H3 is a major target of the immune system. The H3 crystal structure shows that it has a glycosyltransferase protein fold. We demonstrate that H3 binds the sugar nucleotide UDPglucose, as do glycosyltransferases. Our experiments also reveal that H3 binds cell surface molecules that are involved in the attachment of poxviruses to cells. These structural and functional studies of H3 will help in designing better vaccines and therapeutics.
C1 [Singh, Kavita; Gittis, Apostolos G.; Su, Hua-Poo; Garboczi, David N.] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD USA.
   [Gitti, Rossitza K.; Ostazeski, Stanley A.] Edgewood Chem Biol Ctr, Forens Analyt Branch, Aberdeen Proving Ground, MD USA.
RP Singh, K; Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD USA.
EM ksingh@niaid.nih.gov; dgarboczi@niaid.nih.gov
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
   Sciences [W-31-109-Eng-38]; Intramural Research Program of the NIH,
   NIAID
FX X-ray data were collected at the Southeast Regional Collaborative Access
   Team (22-ID and 22-BM) and Structural Biology Center (19ID) beam lines
   at the Advanced Photon Source, which is supported by the U.S. Department
   of Energy, Office of Science, Office of Basic Energy Sciences, under
   contract W-31-109-Eng-38. This research was supported by the Intramural
   Research Program of the NIH, NIAID.
NR 68
TC 0
Z9 0
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 10
BP 5020
EP 5030
DI 10.1128/JVI.02933-15
PG 11
WC Virology
SC Virology
GA DK7SN
UT WOS:000375126100015
PM 26937025
ER

PT J
AU Wu, WM
   Newcomb, WW
   Cheng, NQ
   Aksyuk, A
   Winkler, DC
   Steven, AC
AF Wu, Weimin
   Newcomb, William W.
   Cheng, Naiqian
   Aksyuk, Anastasia
   Winkler, Dennis C.
   Steven, Alasdair C.
TI Internal Proteins of the Procapsid and Mature Capsids of Herpes Simplex
   Virus 1 Mapped by Bubblegram Imaging
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RADIATION-DAMAGE; CRYOELECTRON MICROSCOPY; BACTERIOPHAGE T7; HSV-1
   CAPSIDS; DNA; MATURATION; HERPESVIRUSES; RESOLUTION; PROTEASE; VIRIONS
AB The herpes simplex virus 1 (HSV-1) capsid is a huge assembly, similar to 1,250 angstrom in diameter, and is composed of thousands of protein subunits with a combined mass of similar to 200 MDa, housing a 100-MDa genome. First, a procapsid is formed through coassembly of the surface shell with an inner scaffolding shell; then the procapsid matures via a major structural transformation, triggered by limited proteolysis of the scaffolding proteins. Three mature capsids are found in the nuclei of infected cells. A capsids are empty, B capsids retain a shrunken scaffolding shell, and C capsids-which develop into infectious virions-are filled with DNA and ostensibly have expelled the scaffolding shell. The possible presence of other internal proteins in C capsids has been moot as, in cryo-electron microscopy (cryo-EM), they would be camouflaged by the surrounding DNA. We have used bubblegram imaging to map internal proteins in all four capsids, aided by the discovery that the scaffolding protein is exceptionally prone to radiation-induced bubbling. We confirmed that this protein forms thick-walled inner shells in the procapsid and the B capsid. C capsids generate two classes of bubbles: one occupies positions beneath the vertices of the icosahedral surface shell, and the other is distributed throughout its interior. A likely candidate is the viral protease. A subpopulation of C capsids bubbles particularly profusely and may represent particles in which expulsion of scaffold and DNA packaging are incomplete. Based on the procapsid structure, we propose that the axial channels of hexameric capsomers afford the pathway via which the scaffolding protein is expelled.
   IMPORTANCE
   In addition to DNA, capsids of tailed bacteriophages and their distant relatives, herpesviruses, contain internal proteins. These proteins are often essential for infectivity but are difficult to locate within the virion. A novel adaptation of cryo-EM based on detecting gas bubbles generated by radiation damage was used to localize internal proteins of HSV-1, yielding insights into how capsid maturation is regulated. The scaffolding protein, which forms inner shells in the procapsid and B capsid, is exceptionally bubbling-prone. In the mature DNA-filled C capsid, a previously undetected protein was found to underlie the icosahedral vertices: this is tentatively assigned as a storage form of the viral protease. We also observed a capsid species that appears to contain substantial amounts of scaffolding protein as well as DNA, suggesting that DNA packaging and expulsion of the scaffolding protein are coupled processes.
C1 [Wu, Weimin; Newcomb, William W.; Cheng, Naiqian; Aksyuk, Anastasia; Winkler, Dennis C.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
   [Aksyuk, Anastasia] Meso Scale Discovery, Rockville, MD USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
   Intramural Research Program [AR027002-37]
FX This work was funded by National Institute of Arthritis and
   Musculoskeletal and Skin Diseases Intramural Research Program
   (AR027002-37).
NR 34
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2016
VL 90
IS 10
BP 5176
EP 5186
DI 10.1128/JVI.03224-15
PG 11
WC Virology
SC Virology
GA DK7SN
UT WOS:000375126100029
PM 26984725
ER

PT J
AU Patz, EF
   Greco, E
   Gatsonis, C
   Pinsky, P
   Kramer, BS
   Aberle, DR
AF Patz, Edward F., Jr.
   Greco, Erin
   Gatsonis, Constantine
   Pinsky, Paul
   Kramer, Barnett S.
   Aberle, Denise R.
TI Lung cancer incidence and mortality in National Lung Screening Trial
   participants who underwent low-dose CT prevalence screening: a
   retrospective cohort analysis of a randomised, multicentre, diagnostic
   screening trial
SO LANCET ONCOLOGY
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; PULMONARY NODULES; BIOMARKERS; MANAGEMENT
AB Background Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations.
   Methods We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385.
   Findings Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371.88 [95% CI 337.97-408.26] per 100 000 person-years vs 661.23 [622.07-702.21]) and had lower lung cancer-related mortality (185.82 [95% CI 162.17-211.93] per 100 000 person-years vs 277.20 [252.28-303.90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0.34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1.0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185.82 [95% CI 162.17-211.93] per 100 000 person-years to 212.14 [186.80-239.96]) over the course of the trial.
   Interpretation Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted.
C1 [Patz, Edward F., Jr.] Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA.
   [Patz, Edward F., Jr.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Greco, Erin; Gatsonis, Constantine] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA.
   [Gatsonis, Constantine] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA.
   [Pinsky, Paul; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Aberle, Denise R.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA.
RP Patz, EF (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA.
EM patz0002@mc.duke.edu
OI Aberle, Denise/0000-0002-8858-3401
FU National Institutes of Health [U01CA079778, U01 CA080098, N01-CN-25511,
   N01-CN-25512, N01-CN-25513, N01-CN-25514, N01-CN-25515, N01-CN-25516,
   N01-CN-25518, N01-CN-25522, N01-CN-25524, N01-CN-75022, N01-CN-25476,
   N02-CN-63300]
FX The National Lung Screening Trial was supported by the National
   Institutes of Health (grants U01CA079778 and U01 CA080098 and contracts
   N01-CN-25511, N01-CN-25512, N01-CN-25513, N01-CN-25514, N01-CN-25515,
   N01-CN-25516, N01-CN-25518, N01-CN-25522, N01-CN-25524, N01-CN-75022,
   N01-CN-25476, and N02-CN-63300).
NR 20
TC 16
Z9 16
U1 7
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAY
PY 2016
VL 17
IS 5
BP 590
EP 599
DI 10.1016/S1470-2045(15)00621-X
PG 10
WC Oncology
SC Oncology
GA DK3PO
UT WOS:000374829800050
PM 27009070
ER

PT J
AU Yanik, EL
   Chinnakotla, S
   Gustafson, SK
   Snyder, JJ
   Israni, AK
   Segev, DL
   Engels, EA
AF Yanik, Elizabeth L.
   Chinnakotla, Srinath
   Gustafson, Sally K.
   Snyder, Jon J.
   Israni, Ajay K.
   Segev, Dorry L.
   Engels, Eric A.
TI Effects of Maintenance Immunosuppression With Sirolimus After Liver
   Transplant for Hepatocellular Carcinoma
SO LIVER TRANSPLANTATION
LA English
DT Article
ID SCIENTIFIC REGISTRY; RECURRENCE; RECIPIENTS; SURVIVAL; PATHWAY; TRIAL;
   THERAPY; IMPACT; TARGET
AB For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients <= 55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation.
C1 [Yanik, Elizabeth L.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E-216, Rockville, MD 20850 USA.
   [Chinnakotla, Srinath] Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN 55455 USA.
   [Snyder, Jon J.; Israni, Ajay K.] Univ Minnesota, Sch Med, Dept Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
   [Israni, Ajay K.] Univ Minnesota, Sch Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA.
   [Gustafson, Sally K.; Snyder, Jon J.; Israni, Ajay K.; Segev, Dorry L.] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA.
   [Segev, Dorry L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Yanik, EL (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E-216, Rockville, MD 20850 USA.
EM elizabeth.yanik@nih.gov
OI Yanik, Elizabeth/0000-0002-5835-0201
FU Intramural Research Program of the National Cancer Institute;
   Minneapolis Medical Research Foundation (MMRF) in Minneapolis, MN
   [HHSH250201000018C]; Pfizer
FX Elizabeth L. Yanik and Eric A. Engels were supported by the Intramural
   Research Program of the National Cancer Institute. The Scientific
   Registry of Transplant Recipients (SRTR) was managed by Minneapolis
   Medical Research Foundation (MMRF) in Minneapolis, MN (contract
   HHSH250201000018C). Research support for the linkage between the
   Scientific Registry of Transplant Recipients and IMS Health pharmacy
   claims was provided by Pfizer.
NR 27
TC 5
Z9 5
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6465
EI 1527-6473
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD MAY
PY 2016
VL 22
IS 5
BP 627
EP 634
DI 10.1002/lt.24395
PG 8
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA DK8CV
UT WOS:000375155700008
PM 26784951
ER

PT J
AU Bradley, CJ
   Yabroff, KR
   Warren, JL
   Zeruto, C
   Chawla, N
   Lamont, EB
AF Bradley, Cathy J.
   Yabroff, K. Robin
   Warren, Joan L.
   Zeruto, Christopher
   Chawla, Neetu
   Lamont, Elizabeth B.
TI Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly
   Patients
SO MEDICAL CARE
LA English
DT Article
DE colorectal cancer; treatment costs; chemotherapy use; antineoplastic
   agents; survival
ID CETUXIMAB PLUS IRINOTECAN; COLORECTAL-CANCER; UNITED-STATES;
   CHEMOTHERAPY REGIMENS; 1ST-LINE TREATMENT; CLINICAL ONCOLOGY; AMERICAN
   SOCIETY; YOUNGER PATIENTS; PHASE-II; OXALIPLATIN
AB Background: Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65-74 and 75+.
   Methods: We used Surveillance, Epidemiology, and End Results-Medicare data for persons diagnosed with metastatic colon (N = 16117) or rectal cancer (N = 4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment.
   Results: The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65-74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65-74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+.
   Conclusions: Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64-75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit.
C1 [Bradley, Cathy J.] Univ Colorado, Colorado Comprehens Canc Ctr, Dept Hlth Syst Management & Policy, Aurora, CO 80045 USA.
   [Yabroff, K. Robin; Warren, Joan L.; Chawla, Neetu] NCI, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA.
   [Zeruto, Christopher] Informat Management Serv Inc, Rockville, MD USA.
   [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA.
   [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Dept Hlth Care Policy, Boston, MA 02114 USA.
   [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Bradley, CJ (reprint author), Univ Colorado, Colorado Comprehens Canc Ctr, Dept Hlth Syst Management & Policy, Aurora, CO 80045 USA.
EM cathy.bradley@ucdenver.edu
FU National Cancer Institute
FX Financial support for this study was provided partially by a contract
   between C.J.B. and the National Cancer Institute.
NR 49
TC 3
Z9 3
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD MAY
PY 2016
VL 54
IS 5
BP 490
EP 497
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
   Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA DK4OL
UT WOS:000374897800012
PM 26900834
ER

PT J
AU Alabanza, LM
   Pegues, MA
   Geldres, C
   Shi, V
   Kochenderfer, JN
AF Alabanza, Leah M.
   Pegues, Melissa A.
   Geldres, Claudia
   Shi, Victoria
   Kochenderfer, James N.
TI The Impact of Different Hinge and Transmembrane Components on the
   Function of a Novel Fully-Human Anti-CD19 Chimeric Antigen Receptor
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Alabanza, Leah M.; Pegues, Melissa A.; Geldres, Claudia; Shi, Victoria; Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 74
BP S32
EP S33
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200075
ER

PT J
AU Arnold, M
   Sloan, JL
   Achilly, NP
   Elliot, G
   Onojafe, IF
   Brooks, BP
   Venditti, CP
AF Arnold, Madeline
   Sloan, Jennifer L.
   Achilly, Nathan P.
   Elliot, Gene
   Onojafe, Ighovie F.
   Brooks, Brian P.
   Venditti, Charles P.
TI The First Viable Mouse Model of cblC Type Combined Methylmalonic
   Acidemia and Homocysteinemia: AAV Gene Therapy Rescues Neonatal
   Lethality and Provides Insight into Disease-Associated Retinal
   Degeneration
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Arnold, Madeline; Sloan, Jennifer L.; Achilly, Nathan P.; Elliot, Gene; Brooks, Brian P.; Venditti, Charles P.] NHGRI, Bethesda, MD 20892 USA.
   [Onojafe, Ighovie F.; Brooks, Brian P.] NEI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 46
BP S20
EP S21
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200047
ER

PT J
AU Ashtari, M
   Cook, P
   Zhang, H
   Cyckowski, L
   Nikonova, E
   Young, G
   Marshall, K
   Gee, J
   Leopold, D
   Baker, C
   Maguire, A
   Bennett, J
AF Ashtari, Manzar
   Cook, Philip
   Zhang, Hui
   Cyckowski, Laura
   Nikonova, Elena
   Young, Gloria
   Marshall, Kathleen
   Gee, James
   Leopold, David
   Baker, Chris
   Maguire, Albert
   Bennett, Jean
TI Brain Pathways Enabling Vision in LCA Patients Before and After Gene
   Therapy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Ashtari, Manzar; Cook, Philip; Young, Gloria; Gee, James; Maguire, Albert; Bennett, Jean] Univ Penn, Perelman Sch Med, CAROT, Philadelphia, PA 19104 USA.
   [Zhang, Hui] UCL, London, England.
   [Cyckowski, Laura; Marshall, Kathleen] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Nikonova, Elena] Univ Pittsburgh, Pittsburgh, PA USA.
   [Leopold, David; Baker, Chris] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 265
BP S105
EP S105
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200262
ER

PT J
AU Bharucha-Goebel, D
   Jain, M
   Waite, M
   Lehky, T
   Foley, R
   Marra, JD
   Zein, W
   Bonnemann, CG
AF Bharucha-Goebel, Diana
   Jain, Minal
   Waite, Melissa
   Lehky, Tanya
   Foley, Reghan
   Marra, Jonathan D.
   Zein, Wadih
   Bonnemann, Carsten G.
TI Giant Axonal Neuropathy - The Role of Natural History Studies in Gene
   Transfer Therapy Trial Design
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Bharucha-Goebel, Diana; Foley, Reghan; Bonnemann, Carsten G.] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Bharucha-Goebel, Diana] Childrens Natl Hlth Syst, Washington, DC USA.
   [Jain, Minal; Waite, Melissa; Zein, Wadih] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Lehky, Tanya] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Marra, Jonathan D.] Columbia Univ, Med Ctr, New York, NY USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 715
BP S282
EP S282
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200704
ER

PT J
AU Bofill-De Ros, X
   Dai, LS
   Gu, S
AF Bofill-De Ros, Xavier
   Dai, Lisheng
   Gu, Shuo
TI Applying Insights from Pri-miRNA Processing to shRNA Design
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Bofill-De Ros, Xavier; Dai, Lisheng; Gu, Shuo] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RI Gu, Shuo/K-5404-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 154
BP S61
EP S61
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200153
ER

PT J
AU Bolduc, V
   Sizov, K
   Sarathy, A
   Zou, YQ
   Bonnemann, CG
AF Bolduc, Veronique
   Sizov, Katherine
   Sarathy, Apurva
   Zou, Yaqun
   Bonnemann, Carsten G.
TI Further Development of an Allele-Specific Gene Silencing Strategy to
   Correct a Dominant-Negative Mutation Causing Collagen VI-Related
   Muscular Dystrophy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Bolduc, Veronique; Sizov, Katherine; Sarathy, Apurva; Zou, Yaqun; Bonnemann, Carsten G.] NINDS, NIH, Porter Neurosci Res Ctr, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 150
BP S60
EP S60
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200150
ER

PT J
AU Castiello, MC
   Pala, F
   Morbach, H
   Schickel, JN
   Scaramuzza, S
   Chamberlain, N
   Romberg, N
   Ferrua, F
   Candotti, F
   van der Burg, M
   Naldini, L
   Aiuti, A
   Meffre, E
   Bosticardo, M
   Villa, A
AF Castiello, Maria Carmina
   Pala, Francesca
   Morbach, Henner
   Schickel, Jean-Nicolas
   Scaramuzza, Samantha
   Chamberlain, Nicolas
   Romberg, Neil
   Ferrua, Francesca
   Candotti, Fabio
   van der Burg, Mirjam
   Naldini, Luigi
   Aiuti, Alessandro
   Meffre, Eric
   Bosticardo, Marita
   Villa, Anna
TI Lentiviral-Mediated Gene Therapy Restores B Cell Homeostasis and
   Tolerance in Wiskott-Aldrich Syndrome Patients
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Castiello, Maria Carmina; Pala, Francesca; Scaramuzza, Samantha; Ferrua, Francesca; Naldini, Luigi; Aiuti, Alessandro; Bosticardo, Marita; Villa, Anna] IRCCS San Raffaele Sci Inst, San Raffaele Telethon Inst Gene Therapy SR TIGET, Milan, Italy.
   [Morbach, Henner; Schickel, Jean-Nicolas; Chamberlain, Nicolas; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
   [Romberg, Neil] Yale Univ, Sch Med, Dept Pediat, Div Allergy & Clin Immunol, New Haven, CT 06510 USA.
   [Ferrua, Francesca; Aiuti, Alessandro] IRCCS San Raffaele Sci Inst, Pediat Immunohematol & Bone Marrow Transplantat U, Milan, Italy.
   [Ferrua, Francesca; Naldini, Luigi; Aiuti, Alessandro] Univ Vita Salute San Raffaele, Milan, Italy.
   [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
   [van der Burg, Mirjam] Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands.
   [Villa, Anna] IRGB CNR, Milan Unit, Milan, Italy.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 280
BP S112
EP S112
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200277
ER

PT J
AU Chandler, RJ
   Barzel, A
   Kay, MA
   Venditti, CP
AF Chandler, Randy J.
   Barzel, Adi
   Kay, Mark A.
   Venditti, Charles P.
TI Treatment of Methylmalonic Acidemia by Promoterless Gene-Targeting Using
   Adeno-Associated Viral (AAV) Mediated Homologous Recombination
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Chandler, Randy J.; Venditti, Charles P.] NIH, MGMMGB, Bldg 10, Bethesda, MD 20892 USA.
   [Barzel, Adi; Kay, Mark A.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
   [Barzel, Adi; Kay, Mark A.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 48
BP S21
EP S22
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200049
ER

PT J
AU Choi, EY
   Kan, SH
   Le, SQ
   Dickson, PI
   Kaler, SG
AF Choi, Eun-Young
   Kan, Shih-hsin
   Le, S. Q.
   Dickson, Patricia I.
   Kaler, Stephen G.
TI Choroid Plexus-Targeted Viral Gene Therapy for Lysosomal Storage
   Diseases
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Choi, Eun-Young; Kaler, Stephen G.] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Kan, Shih-hsin; Le, S. Q.; Dickson, Patricia I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 615
BP S244
EP S244
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200606
ER

PT J
AU Dai, M
   Wang, XH
   Liou, B
   Inskeep, V
   Grabowski, G
   Sun, Y
   Brady, R
   Pan, D
AF Dai, Mei
   Wang, Xiaohong
   Liou, Benjamin
   Inskeep, Venette
   Grabowski, Gregory
   Sun, Ying
   Brady, Roscoe
   Pan, Dao
TI Platelets Transfusion New Role as Brain Therapeutics for Acute
   Neuronopathic Gaucher Disease
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Dai, Mei; Wang, Xiaohong; Liou, Benjamin; Inskeep, Venette; Grabowski, Gregory; Sun, Ying; Pan, Dao] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
   [Grabowski, Gregory; Sun, Ying; Pan, Dao] Univ Cincinnati, Sch Med, Dept Pediat, Cincinnati, OH USA.
   [Brady, Roscoe] NINDS, NIH, Bethesd, MD USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 521
BP S208
EP S208
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200515
ER

PT J
AU Deniger, DC
   Pasetto, A
   Prickett, TD
   Gartner, JJ
   Bharathan, M
   Tran, E
   Robbins, PF
   Rosenberg, SA
AF Deniger, Drew C.
   Pasetto, Anna
   Prickett, Todd D.
   Gartner, Jared J.
   Bharathan, Mini
   Tran, Eric
   Robbins, Paul F.
   Rosenberg, Steven A.
TI Mutated Tumor Neoantigens Are Recognized by Tumor Infiltrating
   Lymphocytes from Metastatic Ovarian Cancer
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Deniger, Drew C.; Pasetto, Anna; Prickett, Todd D.; Gartner, Jared J.; Bharathan, Mini; Tran, Eric; Robbins, Paul F.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 391
BP S155
EP S155
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200387
ER

PT J
AU Epping, M
   Manoli, I
   Wang, C
   Zerfas, P
   Hoffmann, V
   Elliott, G
   Li, LL
   Venditti, C
AF Epping, Madeline
   Manoli, Irini
   Wang, Cindy
   Zerfas, Pat
   Hoffmann, Victoria
   Elliott, Gene
   Li, Lingli
   Venditti, Chuck
TI A Mouse Model of Cobalamin A (cblA) Class Isolated Methymalonic Academy
   (MMA) Provides Unique Platform for Testing Gene and Cell Therapies
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Epping, Madeline; Manoli, Irini; Wang, Cindy; Zerfas, Pat; Hoffmann, Victoria; Elliott, Gene; Venditti, Chuck] NHGRI, Bethesda, MD 20892 USA.
   [Li, Lingli] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 357
BP S143
EP S143
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200354
ER

PT J
AU Gagne, J
   Manoli, I
   Harrington, E
   Smyth, S
   Hattenbach, JD
   Sloan, JL
   Chen, KY
   Venditti, CP
AF Gagne, Jack
   Manoli, Irini
   Harrington, Elizabeth
   Smyth, Sarah
   Hattenbach, Jacob D.
   Sloan, Jennifer L.
   Chen, Kong Y.
   Venditti, Charles P.
TI 1-C-13-Propionate Oxidation as a Measure of Methylmalonyl-CoA Mutase
   (MUT) Activity in Methylmalonic Acidemia
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Gagne, Jack; Manoli, Irini; Harrington, Elizabeth; Sloan, Jennifer L.; Venditti, Charles P.] NHGRI, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA.
   [Smyth, Sarah; Hattenbach, Jacob D.; Chen, Kong Y.] NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 353
BP S141
EP S141
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200350
ER

PT J
AU Gibson, AL
   Chandler, RJ
   Williams, IM
   Incao, AA
   Porter, FD
   Pavan, WJ
   Venditti, CP
AF Gibson, Alana L.
   Chandler, Randy J.
   Williams, Ian M.
   Incao, Arturo A.
   Porter, Forbes D.
   Pavan, William J.
   Venditti, Charles P.
TI A Comparison of CNS Transduction After Systemic versus Cranial Delivery
   of an AAV2/9 CamKII Promoter-eGFP Vector in Mice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Gibson, Alana L.; Chandler, Randy J.; Incao, Arturo A.; Pavan, William J.; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Williams, Ian M.; Porter, Forbes D.] NICHHD, NIH, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 613
BP S243
EP S243
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200604
ER

PT J
AU Haddad, MR
   Ralle, M
   Vine, DJ
   Zerfas, PM
   Kaler, SG
AF Haddad, Marie Reine
   Ralle, Martina
   Vine, David J.
   Zerfas, Patricia M.
   Kaler, Stephen G.
TI High-Resolution X-Ray Fluorescence Microscopy (XFM) Indicates Enhanced
   Brain Copper Delivery in AAV9-Treated Menkes Disease Mice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Haddad, Marie Reine; Kaler, Stephen G.] NICHD, Sect Translat Neurosci, NIH, Bethesda, MD USA.
   [Ralle, Martina] OHSU, Dept Mol & Med Genet, Portland, OR USA.
   [Vine, David J.] Argonne Natl Lab, X Ray Sci Div, Adv Photon Source, 9700 S Cass Ave, Argonne, IL 60439 USA.
   [Zerfas, Patricia M.] NIH, Div Vet Resources, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 356
BP S142
EP S143
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200353
ER

PT J
AU Hallwirth, CV
   Smith, RH
   Westerman, M
   Hetherington, NA
   Tseng, YS
   Cecchini, S
   Virag, T
   Ziegler, ML
   Rogozin, IB
   Koonin, EV
   Agbandje-McKenna, M
   Alexander, IE
   Kotin, RM
AF Hallwirth, Claus V.
   Smith, Richard H.
   Westerman, Michael
   Hetherington, Nicola A.
   Tseng, Yu-Shan
   Cecchini, Sylvain
   Virag, Tamas
   Ziegler, Mona-Larissa
   Rogozin, Igor B.
   Koonin, Eugene V.
   Agbandje-McKenna, Mavis
   Alexander, Ian E.
   Kotin, Robert M.
TI Use of Endogenous Viral Elements to Deduce the Sequence of an Ancient
   Adeno-Associated Virus That Circulated Amongst Australian Marsupials
   similar to 30 Million Years Ago
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Hallwirth, Claus V.; Hetherington, Nicola A.; Ziegler, Mona-Larissa; Alexander, Ian E.] Childrens Med Res Inst, Gene Therapy Res Unit, Westmead, NSW, Australia.
   [Hallwirth, Claus V.; Hetherington, Nicola A.; Ziegler, Mona-Larissa; Alexander, Ian E.] Childrens Hosp Westmead, Westmead, NSW, Australia.
   [Smith, Richard H.; Cecchini, Sylvain; Virag, Tamas; Kotin, Robert M.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
   [Westerman, Michael] La Trobe Univ, Bundoora, Vic, Australia.
   [Tseng, Yu-Shan; Agbandje-McKenna, Mavis] Univ Florida, Gainesville, FL USA.
   [Rogozin, Igor B.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 541
BP S216
EP S216
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200534
ER

PT J
AU Heathward, EJ
   Sun, G
   Domingo, RU
   Thomas, CA
   Richie, CT
   Harvey, B
AF Heathward, Emily J.
   Sun, Giun
   Domingo, Ron U.
   Thomas, Calvin A.
   Richie, Christopher T.
   Harvey, Brandon
TI The OTTC Plasmid Manager: A Comprehensive Database for Archiving Plasmid
   DNA Sequence
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Heathward, Emily J.; Richie, Christopher T.; Harvey, Brandon] NIDA, Optogenet & Transgen Technol Core, Baltimore, MD USA.
   [Sun, Giun; Domingo, Ron U.; Thomas, Calvin A.] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 591
BP S234
EP S234
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200582
ER

PT J
AU Heathward, EJ
   Sun, G
   Domingo, RU
   Johnson, CA
   Richie, CT
   Harvey, BK
AF Heathward, Emily J.
   Sun, Giun
   Domingo, Ron U.
   Johnson, Calvin A.
   Richie, Christopher T.
   Harvey, Brandon K.
TI A Plasmid Manager, a Comprehensive Database for Archiving Plasmid DNA
   Sequence
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Heathward, Emily J.; Richie, Christopher T.; Harvey, Brandon K.] NIDA, Baltimore, MD USA.
   [Sun, Giun; Domingo, Ron U.; Johnson, Calvin A.] NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 156
BP S61
EP S61
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200155
ER

PT J
AU Hubbard, BT
   Chandler, RJ
   Venditti, CP
AF Hubbard, Brandon T.
   Chandler, Randy J.
   Venditti, Charles P.
TI Assaying Hepatic Correction Mediated by Varied AAV Vectors in a
   Knock-Out Transgenic Mouse Model of Methylmalonic Acidemia (MMA)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Hubbard, Brandon T.; Chandler, Randy J.; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 168
BP S65
EP S66
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200167
ER

PT J
AU Kawai, T
   Okamura, K
   Yagita, M
   Goto, F
   Nakazawa, Y
   Uchiyama, T
   Nakabayashi, K
   Nunoi, H
   Malech, H
   Onodera, M
AF Kawai, Toshinao
   Okamura, Kohji
   Yagita, Mari
   Goto, Fumihiro
   Nakazawa, Yumiko
   Uchiyama, Toru
   Nakabayashi, Kazuhiko
   Nunoi, Hiroyuki
   Malech, Harry
   Onodera, Masafumi
TI A Gene Therapy Clinical Study of a Patient with X-Linked Chronic
   Granulomatous Disease
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Kawai, Toshinao; Yagita, Mari; Goto, Fumihiro; Nakazawa, Yumiko; Uchiyama, Toru; Onodera, Masafumi] Natl Ctr Child Hlth & Dev, Dept Human Genet, Tokyo, Japan.
   [Okamura, Kohji] Natl Ctr Child Hlth & Dev, Dept Syst BioMed, Tokyo, Japan.
   [Nakabayashi, Kazuhiko] Natl Ctr Child Hlth & Dev, Div Dev Genom, Tokyo, Japan.
   [Nunoi, Hiroyuki] Miyazaki Univ, Dept Pediat, Miyazaki, Japan.
   [Malech, Harry] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 224
BP S87
EP S88
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200222
ER

PT J
AU Kwon, J
   Cho, JH
   Lee, YM
   Kim, GY
   Anduaga, J
   Chou, J
AF Kwon, Joonhyun
   Cho, Jun-Ho
   Lee, Young Mok
   Kim, Goo-Young
   Anduaga, Javier
   Chou, Janice
TI Liver-Directed Gene Therapy for Murine Glycogen Storage Disease Type IB
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Kwon, Joonhyun; Cho, Jun-Ho; Kim, Goo-Young; Anduaga, Javier; Chou, Janice] NICHD, NIH, Bethesda, MD USA.
   [Lee, Young Mok] Univ Florida, Gainesville, FL USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 165
BP S64
EP S65
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200164
ER

PT J
AU Lee, Y
   Bae, S
   Rocca, CJ
   Cherqui, S
   Weinstein, DA
   Chou, JY
AF Lee, Youngmok
   Bae, Seongho
   Rocca, Celine J.
   Cherqui, Stephanie
   Weinstein, David A.
   Chou, Janice Y.
TI Kidney-Directed Gene Therapy for Murine Glycogen Storage Disease Type IA
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Lee, Youngmok; Weinstein, David A.] Univ Florida, Dept Pediat, Div Pediat Endocrinol, Glycogen Storage Dis Program, Gainesville, FL USA.
   [Bae, Seongho; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Div Translat Medidine, NIH, Bethesda, MD USA.
   [Rocca, Celine J.; Cherqui, Stephanie] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 350
BP S140
EP S140
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200347
ER

PT J
AU Li, LH
   De Ravin, SS
   Allen, C
   Choi, U
   Koontz, S
   Theobald, N
   Lee, J
   Viley, A
   Natarajan, P
   NewCombe, H
   McMichael, A
   Wu, XL
   Malech, HL
   Peshwa, MV
AF Li, Linhong
   De Ravin, Suk See
   Allen, Cornell
   Choi, Uimook
   Koontz, Sherry
   Theobald, Narda
   Lee, Janet
   Viley, Angelia
   Natarajan, Pachai
   NewCombe, Hannah
   McMichael, Ashley
   Wu, Xiaolin
   Malech, Harry L.
   Peshwa, Madhusudan V.
TI Therapeutic Level CRISPR-Oligomer-Mediated Correction of X-CGD Patient
   Hematopoietic Stem Cells Using Non-Viral, cGMP Compliant, Scalable, and
   Closed System
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Li, Linhong; Allen, Cornell; Viley, Angelia; Natarajan, Pachai; Peshwa, Madhusudan V.] MaxCyte, Gaithersburg, MD USA.
   [De Ravin, Suk See; Choi, Uimook; Koontz, Sherry; Theobald, Narda; Lee, Janet; NewCombe, Hannah; McMichael, Ashley; Wu, Xiaolin; Malech, Harry L.] NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 41
BP S18
EP S18
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200042
ER

PT J
AU Li, PJ
   Zou, JZ
   Morreale, MT
   Marino, MP
   Reiser, J
AF Li, Pingjuan
   Zou, Jizhong
   Morreale, Michael T.
   Marino, Michael P.
   Reiser, Jakob
TI Targeted Lentiviral Vector Integration Mediated by the AAV Rep78 Protein
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Li, Pingjuan; Morreale, Michael T.; Marino, Michael P.; Reiser, Jakob] US FDA, CBER, Silver Spring, MD USA.
   [Zou, Jizhong] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 566
BP S226
EP S226
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200559
ER

PT J
AU Melchiori, L
   Lowther, DE
   Binder-Scholl, GK
   Williams, DD
   Peretz, Y
   Fortin, M
   Tap, WD
   Rapoport, AP
   Mackall, CL
   Jakobsen, BK
AF Melchiori, Luca
   Lowther, Daniel E.
   Binder-Scholl, Gwendolyn K.
   Williams, Daniel D.
   Peretz, Yoav
   Fortin, Marylene
   Tap, Willian D.
   Rapoport, Aaron P.
   Mackall, Crystal L.
   Jakobsen, Bent K.
TI Deep Phenotyping of Manufactured Enhanced-Affinity NY-ESO-1-Specific T
   Cells Reveals a Pattern of Effector and Memory Programming That
   Correlates with Clinical Outcome in Observed Cancer Indications
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Melchiori, Luca; Lowther, Daniel E.; Binder-Scholl, Gwendolyn K.; Williams, Daniel D.; Jakobsen, Bent K.] Adaptimmune Therapeut, Abingdon, Oxon, England.
   [Peretz, Yoav; Fortin, Marylene] ImmuneCarta, Montreal, PQ, Canada.
   [Tap, Willian D.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
   [Rapoport, Aaron P.] Univ Maryland, Baltimore, MD 21201 USA.
   [Mackall, Crystal L.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 192
BP S75
EP S75
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200190
ER

PT J
AU Panch, SR
   Yabe, I
   Espinoza, D
   Wu, C
   Hong, SG
   Sellers, S
   Krouse, A
   Bonifacino, A
   Donahue, R
   Dunbar, C
AF Panch, Sandhya R.
   Yabe, Idalia
   Espinoza, Diego
   Wu, Chuanfeng
   Hong, So Gun
   Sellers, Stephanie
   Krouse, Allen
   Bonifacino, Aylin
   Donahue, Robert
   Dunbar, Cynthia
TI Human Umbilical Vein Endothelial Cell, HUVEC, Co-Culture Promotes Robust
   Expansion and Maintains Phenotypic Integrity of Rhesus Hematopoietic
   Stem and Progenitor Cells, HSPC, Prior to Autologous Transplantation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Panch, Sandhya R.] NIH, Transfus Med, Bldg 10, Bethesda, MD 20892 USA.
   [Yabe, Idalia] NHLBI, Hematol, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Espinoza, Diego; Wu, Chuanfeng; Hong, So Gun; Sellers, Stephanie; Krouse, Allen; Bonifacino, Aylin; Donahue, Robert; Dunbar, Cynthia] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 523
BP S209
EP S209
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200517
ER

PT J
AU Pasetto, A
   Gros, A
   Robbins, PF
   Deniger, DC
   Prickett, TD
   Parkhurst, MR
   Matus-Nicodemos, R
   Douek, DC
   Gartner, J
   Trebska-McGowan, K
   Crystal, J
   Rosenberg, SA
AF Pasetto, Anna
   Gros, Alena
   Robbins, Paul F.
   Deniger, Drew C.
   Prickett, Todd D.
   Parkhurst, Maria R.
   Matus-Nicodemos, Rodrigo
   Douek, Daniel C.
   Gartner, Jared
   Trebska-McGowan, Katarzyna
   Crystal, Jessica
   Rosenberg, Steven A.
TI Rapid Identification of Tumor- and Neoantigen-Reactive T-Cell Receptors
   for Personalized Immunotherapy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Pasetto, Anna; Gros, Alena; Robbins, Paul F.; Deniger, Drew C.; Prickett, Todd D.; Parkhurst, Maria R.; Gartner, Jared; Trebska-McGowan, Katarzyna; Crystal, Jessica; Rosenberg, Steven A.] NIH, CRC, Surg Branch, Bldg 10, Bethesda, MD 20892 USA.
   [Matus-Nicodemos, Rodrigo; Douek, Daniel C.] NIAID, NIH, VRC, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 272
BP S108
EP S108
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200269
ER

PT J
AU Reuschel, EL
   Muthumani, K
   Kraynyak, K
   Tingey, C
   Kudchodkar, SB
   Khan, AS
   Sardesai, NY
   Kim, JJ
   Maslow, J
   Park, YK
   Kobinger, G
   Falzarano, D
   Feldman, H
   Weiner, DB
AF Reuschel, Emma L.
   Muthumani, Karrupiah
   Kraynyak, Kim
   Tingey, Colleen
   Kudchodkar, Sagar B.
   Khan, Amir S.
   Sardesai, Niranjan Y.
   Kim, J. Joseph
   Maslow, Joel
   Park, Young K.
   Kobinger, Gary
   Falzarano, Darryl
   Feldman, Heinrich
   Weiner, David B.
TI Developing a Synthetic DNA Vaccine for an Emerging Pathogen - Middle
   East Respiratory Syndrome
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Reuschel, Emma L.; Muthumani, Karrupiah; Tingey, Colleen; Kudchodkar, Sagar B.; Weiner, David B.] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Kraynyak, Kim; Khan, Amir S.; Sardesai, Niranjan Y.; Kim, J. Joseph] Inovio Pharmaceut Inc, Blue Bell, PA USA.
   [Maslow, Joel; Park, Young K.] GeneOne Life Sci, Seoul, South Korea.
   [Kobinger, Gary] Univ Manitoba, Special Pathogens Program, Winnipeg, MB, Canada.
   [Kobinger, Gary] Publ Hlth Agcy Canada, Winnipeg, MB, Canada.
   [Falzarano, Darryl] Univ Saskatchewan, Vaccine & Infect Dis Org, Int Vaccine Ctr, Saskatoon, SK, Canada.
   [Feldman, Heinrich] NIAID, Lab Virol, Div Intramural Resesarch, Rocky Mt Labs,NIH, Hamilton, MT USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 436
BP S172
EP S173
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200432
ER

PT J
AU Schneller, JL
   Chandler, RJ
   Venditti, CP
AF Schneller, Jessica L.
   Chandler, Randy J.
   Venditti, Charles P.
TI Targeted Genome Editing Using TALENs to Correct a Mouse Model of
   Methylmalonic Acidemia (MMA)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Schneller, Jessica L.; Chandler, Randy J.; Venditti, Charles P.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 359
BP S144
EP S144
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200356
ER

PT J
AU Shivaprasad, N
   Xiong, Y
   Yohe, M
   Schneider, D
   Shern, J
   Baskar, S
   Dimitrov, D
   Sorenson, P
   Orentas, R
   Khan, J
AF Shivaprasad, Nityashree
   Xiong, Ying
   Yohe, Marielle
   Schneider, Dina
   Shern, Jack
   Baskar, Sivasubramanian
   Dimitrov, Dimiter
   Sorenson, Paul
   Orentas, Rimas
   Khan, Javed
TI Developing FGFR4 Chimeric Antigen Receptor CAR T Cell Therapy Against
   Rhabdomyosarcoma
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Shivaprasad, Nityashree; Yohe, Marielle; Shern, Jack; Baskar, Sivasubramanian; Dimitrov, Dimiter; Khan, Javed] NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Xiong, Ying; Schneider, Dina; Orentas, Rimas] Lentigen Technol Inc, Gaithersburg, MD USA.
   [Sorenson, Paul] BC Canc Agcy, Vancouver, BC, Canada.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 649
BP S257
EP S258
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200639
ER

PT J
AU Smith, RH
   Nasimuzzaman, M
   Dutta, R
   Uzel, G
   Bauer, TR
   Holland, SM
   Russell, DW
   Hickstein, DD
   Malik, P
   van der Loo, JCM
   Larochelle, A
AF Smith, Richard H.
   Nasimuzzaman, Md
   Dutta, Roop
   Uzel, Gulbu
   Bauer, Thomas R.
   Holland, Steven M.
   Russell, David W.
   Hickstein, Dennis D.
   Malik, Punam
   van der Loo, Johannes C. M.
   Larochelle, Andre
TI Foamy Viral Vector Expressing Human CD18 Results in High Levels of
   Transduction and Multilineage Engraftment with CD18+LAD-1 Cells in NSG
   Mice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Smith, Richard H.; Dutta, Roop; Larochelle, Andre] NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA.
   [Nasimuzzaman, Md; Malik, Punam] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
   [Uzel, Gulbu; Holland, Steven M.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Bauer, Thomas R.; Hickstein, Dennis D.] NCI, NIH, Bethesda, MD 20892 USA.
   [Russell, David W.] Univ Washington, Div Hematol, Seattle, WA 98195 USA.
   [van der Loo, Johannes C. M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 285
BP S114
EP S115
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200282
ER

PT J
AU Sweeney, CL
   Choi, U
   Zou, JZ
   Merling, RK
   De Ravin, SS
   Malech, HL
AF Sweeney, Colin L.
   Choi, Uimook
   Zou, Jizhong
   Merling, Randall K.
   De Ravin, Suk See
   Malech, Harry L.
TI Targeted CYBB Minigene Insertion into the CYBB Locus for Correction of
   X-CGD iPSCs Requires Intronic Elements for Expression
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Sweeney, Colin L.; Choi, Uimook; Merling, Randall K.; De Ravin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, Genet Immunotherapy Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Zou, Jizhong] NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 557
BP S223
EP S223
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200550
ER

PT J
AU Tsuchiya, M
   Kumar, P
   Bhattacharyya, S
   Kalurupalle, S
   Vasudevan, S
   Martindale, J
   Gorospe, M
   Biswas, R
AF Tsuchiya, Motohiro
   Kumar, Parameet
   Bhattacharyya, Sharmistha
   Kalurupalle, Swathi
   Vasudevan, Shobha
   Martindale, Jennifer
   Gorospe, Myriam
   Biswas, Roopa
TI Regulation of Inflammation in Cystic Fibrosis Lung Epithelial Cells by
   miR-155
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Tsuchiya, Motohiro; Kumar, Parameet; Bhattacharyya, Sharmistha; Kalurupalle, Swathi; Biswas, Roopa] Uniformed Serv Univ Hlth Sci, Anat Physiol & Genet, Bethesda, MD 20814 USA.
   [Vasudevan, Shobha] Massachusetts Gen Hosp, Genet, Boston, MA 02114 USA.
   [Martindale, Jennifer; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 146
BP S59
EP S59
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200147
ER

PT J
AU Uchida, N
   Shvygin, A
   Skala, L
   Raines, L
   Ballantine, J
   Tisdale, J
AF Uchida, Naoya
   Shvygin, Anna
   Skala, Luke
   Raines, Lydia
   Ballantine, Josiah
   Tisdale, John
TI Development of a Cas9 Protein Delivery System with Lentiviral Vectors
   for RNA-Guided Genome Editing
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Uchida, Naoya; Shvygin, Anna; Skala, Luke; Raines, Lydia; Ballantine, Josiah; Tisdale, John] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 3
BP S2
EP S2
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200004
ER

PT J
AU Valdmanis, PN
   Gu, S
   Chu, K
   Jin, L
   Zhang, FJ
   Munding, EM
   Zhang, Y
   Huang, Y
   Kutay, H
   Ghoshal, K
   Lisowski, L
   Kay, MA
AF Valdmanis, Paul N.
   Gu, Shuo
   Chu, Kirk
   Jin, Lan
   Zhang, Feijie
   Munding, Elizabeth M.
   Zhang, Yue
   Huang, Yong
   Kutay, Huban
   Ghoshal, Kalpana
   Lisowski, Leszek
   Kay, Mark A.
TI RNAi Induced Hepatotoxicity Results from a Functional Depletion of the
   First Synthesized Isoform of miR-122
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Valdmanis, Paul N.; Chu, Kirk; Zhang, Feijie; Munding, Elizabeth M.; Zhang, Yue; Huang, Yong; Lisowski, Leszek; Kay, Mark A.] Stanford Univ, Pediat, Stanford, CA 94305 USA.
   [Gu, Shuo; Jin, Lan] NCI, GRCBL, Ctr Canc Res, Frederick, MD USA.
   [Kutay, Huban; Ghoshal, Kalpana] Ohio State Univ, Pathol, Columbus, OH 43210 USA.
RI Gu, Shuo/K-5404-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 737
BP S290
EP S291
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200725
ER

PT J
AU Wires, ES
   Howard, D
   Henderson, MJ
   Yan, XK
   Trychta, KA
   Heathward, EJ
   Zhang, YJ
   Lutrey, M
   Richie, C
   Harvey, BK
AF Wires, Emily S.
   Howard, Doug
   Henderson, Mark J.
   Yan, Xiaokang
   Trychta, Kathleen A.
   Heathward, Emily J.
   Zhang, Yajun
   Lutrey, Molly
   Richie, Christopher
   Harvey, Brandon K.
TI Monitoring ER Stress Activation of the ATF6 Pathway Using Nanoluciferase
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Wires, Emily S.; Howard, Doug; Henderson, Mark J.; Yan, Xiaokang; Trychta, Kathleen A.; Heathward, Emily J.; Zhang, Yajun; Lutrey, Molly; Richie, Christopher; Harvey, Brandon K.] NIDA, OTTC, NIH, Baltimore, MD USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 218
BP S85
EP S85
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200216
ER

PT J
AU Yada, RC
   Hong, SG
   Zou, JZ
   Choi, K
   Carpentier, A
   Liang, TJ
   Merling, R
   Sweeney, C
   Malech, H
   Jung, M
   Corat, M
   Lin, YS
   Tunc, I
   Wang, XJ
   Palisoc, M
   Pittaluga, S
   Winkler, T
   Dunbar, C
AF Yada, Ravi Chandra
   Hong, So Gun
   Zou, Jizhong
   Choi, Kyujoo
   Carpentier, Arnaud
   Liang, T. Jake
   Merling, Randall
   Sweeney, Colin
   Malech, Harry
   Jung, Moonjung
   Corat, Marcus
   Lin, Youngshun
   Tunc, Ilker
   Wang, Xujing
   Palisoc, Maryknoll
   Pittaluga, Stefania
   Winkler, Thomas
   Dunbar, Cynthia
TI Improvement of Pre-Clinical Non-Human Primate Model for Pluripotent Stem
   Cell Based Therapies by Introducing Marker Genes in Safe Harbor Locus
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Yada, Ravi Chandra; Hong, So Gun; Zou, Jizhong; Choi, Kyujoo; Carpentier, Arnaud; Liang, T. Jake; Merling, Randall; Sweeney, Colin; Malech, Harry; Jung, Moonjung; Corat, Marcus; Lin, Youngshun; Tunc, Ilker; Wang, Xujing; Palisoc, Maryknoll; Pittaluga, Stefania; Winkler, Thomas; Dunbar, Cynthia] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 527
BP S210
EP S211
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200521
ER

PT J
AU Yu, KR
   Corat, MAF
   Metais, JY
   Dunbar, CE
AF Yu, Kyung-Rok
   Corat, Marcus A. F.
   Metais, Jean-Yves
   Dunbar, Cynthia E.
TI The Cytotoxic Effect of RNA-Guided Endonuclease Cas9 on Human
   Hematopoietic Stem and Progenitor Cells (HSPCs)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Yu, Kyung-Rok; Corat, Marcus A. F.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Corat, Marcus A. F.] Univ Estadual Campinas, Multidisciplinar Ctr Biol Res, Campinas, SP, Brazil.
   [Metais, Jean-Yves] St Jude Childrens Res Hosp, Hematol, Memphis, TN USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 564
BP S225
EP S226
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200557
ER

PT J
AU Yu, WH
   Mookherjee, S
   Kim, JW
   Hiriyanna, S
   Ataeijannati, Y
   Sun, X
   Dong, LJ
   Li, TS
   Swaroop, A
   Wu, ZJ
AF Yu, Wenhan
   Mookherjee, Suddhasil
   Kim, Jung-Woong
   Hiriyanna, Suja
   Ataeijannati, Yasaman
   Sun, Xun
   Dong, Lijin
   Li, Tiansen
   Swaroop, Anand
   Wu, Zhijian
TI In Vivo Rod Photoreceptor Reprogramming Using AAV-Delivered CRISPR/Cas9
   Rescues Retinal Degeneration
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
   (ASGCT)
CY MAY 04-07, 2016
CL Washington, DC
SP Amer Soc Gene & Cell Therapy
C1 [Yu, Wenhan; Mookherjee, Suddhasil; Kim, Jung-Woong; Hiriyanna, Suja; Ataeijannati, Yasaman; Sun, Xun; Dong, Lijin; Li, Tiansen; Swaroop, Anand; Wu, Zhijian] NEI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2016
VL 24
SU 1
MA 266
BP S105
EP S106
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK9PT
UT WOS:000375264200263
ER

PT J
AU Dai, C
   Yao, X
   Gordon, EM
   Barochia, A
   Cuento, RA
   Kaler, M
   Meyer, KS
   Keeran, KJ
   Nugent, GZ
   Jeffries, KR
   Qu, X
   Yu, ZX
   Aponte, A
   Gucek, M
   Dagur, PK
   Mccoy, JP
   Levine, SJ
AF Dai, C.
   Yao, X.
   Gordon, E. M.
   Barochia, A.
   Cuento, R. A.
   Kaler, M.
   Meyer, K. S.
   Keeran, K. J.
   Nugent, G. Z.
   Jeffries, K. R.
   Qu, X.
   Yu, Z-X
   Aponte, A.
   Gucek, M.
   Dagur, P. K.
   Mccoy, J. P.
   Levine, S. J.
TI A CCL24-dependent pathway augments eosinophilic airway inflammation in
   house dust mite-challenged Cd163(-/-) mice
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID SCAVENGER RECEPTOR CD163; ALLERGEN DER-P-1; EPITHELIAL-CELLS; DENDRITIC
   CELLS; HUMAN MONOCYTES; SEVERE ASTHMA; EXPRESSION; LUNG; IDENTIFICATION;
   MECHANISM
AB CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMUs) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(-/-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages(BMMUs) from Cd163(-/-) mice, but not BMMUs from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMU's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.
C1 [Dai, C.; Yao, X.; Gordon, E. M.; Barochia, A.; Cuento, R. A.; Kaler, M.; Meyer, K. S.; Levine, S. J.] NHLBI, Lab Asthma & Lung Inflammat, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Keeran, K. J.; Nugent, G. Z.; Jeffries, K. R.] NHLBI, Anim Surg & Resources Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Qu, X.; Yu, Z-X] NHLBI, Pathol Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Aponte, A.; Gucek, M.] NHLBI, Prote Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Dagur, P. K.; Mccoy, J. P.] NHLBI, Flow Cytometry Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Lab Asthma & Lung Inflammat, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov
FU Division of Intramural Research, NHLBI
FX We thank Dr Grzegorz Piszczek from the NHLBI Biophysics Core Facility,
   Dr Christian A. Combs and Dr Daniela Malide, from the NHLBI Light
   Microscopy Core Facility, for their advice and support, and Dr Martha
   Vaughan and Dr Joel Moss for their helpful discussions. This work was
   funded by the Division of Intramural Research, NHLBI.
NR 50
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2016
VL 9
IS 3
BP 702
EP 717
DI 10.1038/mi.2015.94
PG 16
WC Immunology
SC Immunology
GA DK9TV
UT WOS:000375275300012
PM 26376364
ER

PT J
AU Miller, DM
   Bethoux, F
   Victorson, D
   Nowinski, CJ
   Buono, S
   Lai, JS
   Wortman, K
   Burns, JL
   Moy, C
   Cella, D
AF Miller, Deborah M.
   Bethoux, Francois
   Victorson, David
   Nowinski, Cindy J.
   Buono, Sarah
   Lai, Jin-Shei
   Wortman, Katy
   Burns, James L.
   Moy, Claudia
   Cella, David
TI Validating Neuro-QoL short forms and targeted scales with people who
   have multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE Neuro-QOL; multiple sclerosis; health-related quality of life;
   patient-reported outcomes
ID QUALITY-OF-LIFE; HEALTH-STATUS; ITEM BANKS; DISABILITY; DISORDERS;
   COGNITION; FATIGUE; SCORES; EQ-5D
AB Background: Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses.
   Objective: The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS.
   Methods: We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients.
   Results: Internal consistency was high for all measures ( = 0.81-0.95) and ICCs were within the acceptable range (0.76-0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group.
   Conclusions: The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS.
C1 [Miller, Deborah M.; Bethoux, Francois] Cleveland Clin, Mellen Ctr, 9500 Euclid Ave,Mail Stop U10, Cleveland, OH 44195 USA.
   [Victorson, David; Nowinski, Cindy J.; Buono, Sarah; Lai, Jin-Shei; Wortman, Katy; Burns, James L.; Cella, David] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Evanston, IL 60208 USA.
   [Moy, Claudia] NINDS, Off Clin Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Miller, DM (reprint author), Cleveland Clin, Mellen Ctr, 9500 Euclid Ave,Mail Stop U10, Cleveland, OH 44195 USA.
EM millerd@ccf.org
FU National Institute for Neurological Disorders and Stroke [HHSN
   2652004236-01C, HHSN 271201200036C-0-0-1]
FX Supported by the National Institute for Neurological Disorders and
   Stroke contracts HHSN 2652004236-01C and HHSN 271201200036C-0-0-1. The
   contents represent original work and have not been published elsewhere.
   No commercial party having a direct financial interest in the results of
   the research supporting this article has or will confer a benefit upon
   the author(s) or upon any organization with which the author(s) is/are
   associated.
NR 26
TC 1
Z9 1
U1 4
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD MAY
PY 2016
VL 22
IS 6
BP 830
EP 841
DI 10.1177/1352458515599450
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DK2VS
UT WOS:000374773100082
PM 26238464
ER

PT J
AU Swaminathan, V
   Waterman, CM
AF Swaminathan, Vinay
   Waterman, Clare M.
TI The molecular clutch model for mechanotransduction evolves
SO NATURE CELL BIOLOGY
LA English
DT Editorial Material
ID CELL-MIGRATION; TALIN; ADHESION; ACTIN; TRACTION; KINDLINS; DYNAMICS;
   GROWTH
AB Many biological processes are influenced by the mechanical rigidity of surrounding tissues. Now, a combination of experiments and mathematical modelling has been used to describe the precise molecular and physical mechanism by which cells sense and respond to the mechanical properties of their extracellular environment through integrin-based adhesions.
C1 [Swaminathan, Vinay; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM watermancm@nhlbi.nih.gov
NR 16
TC 2
Z9 2
U1 4
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD MAY
PY 2016
VL 18
IS 5
BP 459
EP 461
PG 3
WC Cell Biology
SC Cell Biology
GA DK3RH
UT WOS:000374834600001
PM 27117328
ER

PT J
AU Dooley, J
   Tian, L
   Schonefeldt, S
   Delghingaro-Augusto, V
   Garcia-Perez, JE
   Pasciuto, E
   Di Marino, D
   Carr, EJ
   Oskolkov, N
   Lyssenko, V
   Franckaert, D
   Lagou, V
   Overbergh, L
   Vandenbussche, J
   Allemeersch, J
   Chabot-Roy, G
   Dahlstrom, JE
   Laybutt, DR
   Petrovsky, N
   Socha, L
   Gevaert, K
   Jetten, AM
   Lambrechts, D
   Linterman, MA
   Goodnow, CC
   Nolan, CJ
   Lesage, S
   Schlenner, SM
   Liston, A
AF Dooley, James
   Tian, Lei
   Schonefeldt, Susann
   Delghingaro-Augusto, Viviane
   Garcia-Perez, Josselyn E.
   Pasciuto, Emanuela
   Di Marino, Daniele
   Carr, Edward J.
   Oskolkov, Nikolay
   Lyssenko, Valeriya
   Franckaert, Dean
   Lagou, Vasiliki
   Overbergh, Lut
   Vandenbussche, Jonathan
   Allemeersch, Joke
   Chabot-Roy, Genevieve
   Dahlstrom, Jane E.
   Laybutt, D. Ross
   Petrovsky, Nikolai
   Socha, Luis
   Gevaert, Kris
   Jetten, Anton M.
   Lambrechts, Diether
   Linterman, Michelle A.
   Goodnow, Chris C.
   Nolan, Christopher J.
   Lesage, Sylvie
   Schlenner, Susan M.
   Liston, Adrian
TI Genetic predisposition for beta cell fragility underlies type 1 and type
   2 diabetes
SO NATURE GENETICS
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; HUMAN
   PANCREATIC-ISLETS; TRANSGENIC MOUSE MODEL; DNA-SEQUENCING DATA;
   MOLECULAR-DYNAMICS; NOD MOUSE; T-CELLS; RNA-SEQ; MICE
AB Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes.
C1 [Dooley, James; Tian, Lei; Schonefeldt, Susann; Garcia-Perez, Josselyn E.; Pasciuto, Emanuela; Franckaert, Dean; Lagou, Vasiliki; Schlenner, Susan M.; Liston, Adrian] VIB, Ctr Biol Dis, Leuven, Belgium.
   [Dooley, James; Tian, Lei; Schonefeldt, Susann; Garcia-Perez, Josselyn E.; Pasciuto, Emanuela; Franckaert, Dean; Lagou, Vasiliki; Schlenner, Susan M.; Liston, Adrian] Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium.
   [Delghingaro-Augusto, Viviane; Dahlstrom, Jane E.; Nolan, Christopher J.] Australian Natl Univ, Sch Med, Canberra, ACT, Australia.
   [Di Marino, Daniele] Univ Svizzera Italiana, Dept Informat, Lugano, Switzerland.
   [Carr, Edward J.; Linterman, Michelle A.] Babraham Inst, Lymphocyte Signaling & Dev Inst Strateg Programme, Cambridge, England.
   [Oskolkov, Nikolay; Lyssenko, Valeriya] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
   [Lyssenko, Valeriya] Steno Diabet Ctr, Dept Translat Pathophysiol, DK-2820 Gentofte, Denmark.
   [Lagou, Vasiliki] Univ Leuven, Dept Neurosci, Leuven, Belgium.
   [Overbergh, Lut] Univ Leuven, Dept Clin & Expt Med, Leuven, Belgium.
   [Vandenbussche, Jonathan; Gevaert, Kris] VIB, Dept Med Prot Res, Ghent, Belgium.
   [Vandenbussche, Jonathan; Gevaert, Kris] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Allemeersch, Joke] Univ Leuven, VIB Nucle Core, Leuven, Belgium.
   [Chabot-Roy, Genevieve; Lesage, Sylvie] Hop Maison Neuve Rosemont, Immunol Oncol Sect, Montreal, PQ H1T 2M4, Canada.
   [Chabot-Roy, Genevieve; Lesage, Sylvie] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada.
   [Dahlstrom, Jane E.] Canberra Hosp, Dept Anat Pathol, Garran, ACT, Australia.
   [Laybutt, D. Ross; Goodnow, Chris C.] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW, Australia.
   [Petrovsky, Nikolai] Flinders Univ S Australia, Dept Endocrinol, Adelaide, SA 5001, Australia.
   [Socha, Luis] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
   [Jetten, Anton M.] NIEHS, Immun Inflammat & Dis Lab, US Natl Inst Hlth, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
   [Lambrechts, Diether] Univ Leuven, Dept Oncol, Leuven, Belgium.
   [Nolan, Christopher J.] Canberra Hosp, Dept Endocrinol, Garran, ACT, Australia.
RP Liston, A (reprint author), VIB, Ctr Biol Dis, Leuven, Belgium.; Liston, A (reprint author), Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium.
EM adrian.liston@vib.be
RI Liston, Adrian/G-8606-2013; Gevaert, Kris/D-6489-2017; 
OI Liston, Adrian/0000-0002-6272-4085; Gevaert, Kris/0000-0002-4237-0283;
   Linterman, Michelle/0000-0001-6047-1996; Carr,
   Edward/0000-0001-9343-4593; Petrovsky, Nikolai/0000-0002-1580-5245
FU VIB; European Research Council (ERC); Juvenile Diabetes Research
   Foundation (JDRF); National Health and Medical Research Council of
   Australia [1028108]; Swedish Research Council [2009-1039]
FX This work was supported by the VIB, European Research Council (ERC) and
   a Juvenile Diabetes Research Foundation (JDRF) Career Development Award
   (A.L.) and by the National Health and Medical Research Council of
   Australia (project grant 1028108; C.J.N.). N.O. and V. Lyssenko
   acknowledge support by a Strategic Research Grant from the Swedish
   Research Council (2009-1039).
NR 76
TC 10
Z9 10
U1 9
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2016
VL 48
IS 5
BP 519
EP +
DI 10.1038/ng.3531
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA DK3RC
UT WOS:000374834100011
PM 26998692
ER

PT J
AU Zhou, WY
   Machiela, MJ
   Freedman, ND
   Rothman, N
   Malats, N
   Dagnall, C
   Caporaso, N
   Teras, LT
   Gaudet, MM
   Gapstur, SM
   Stevens, VL
   Jacobs, KB
   Sampson, J
   Albanes, D
   Weinstein, S
   Virtamo, J
   Berndt, S
   Hoover, RN
   Black, A
   Silverman, D
   Figueroa, J
   Garcia-Closas, M
   Real, FX
   Earl, J
   Marenne, G
   Rodriguez-Santiago, B
   Karagas, M
   Johnson, A
   Schwenn, M
   Wu, XF
   Gu, J
   Ye, YQ
   Hutchinson, A
   Tucker, M
   Perez-Jurado, LA
   Dean, M
   Yeager, M
   Chanock, SJ
AF Zhou, Weiyin
   Machiela, Mitchell J.
   Freedman, Neal D.
   Rothman, Nathaniel
   Malats, Nuria
   Dagnall, Casey
   Caporaso, Neil
   Teras, Lauren T.
   Gaudet, Mia M.
   Gapstur, Susan M.
   Stevens, Victoria L.
   Jacobs, Kevin B.
   Sampson, Joshua
   Albanes, Demetrius
   Weinstein, Stephanie
   Virtamo, Jarmo
   Berndt, Sonja
   Hoover, Robert N.
   Black, Amanda
   Silverman, Debra
   Figueroa, Jonine
   Garcia-Closas, Montserrat
   Real, Francisco X.
   Earl, Julie
   Marenne, Gaelle
   Rodriguez-Santiago, Benjamin
   Karagas, Margaret
   Johnson, Alison
   Schwenn, Molly
   Wu, Xifeng
   Gu, Jian
   Ye, Yuanqing
   Hutchinson, Amy
   Tucker, Margaret
   Perez-Jurado, Luis A.
   Dean, Michael
   Yeager, Meredith
   Chanock, Stephen J.
TI Mosaic loss of chromosome Y is associated with common variation near
   TCL1A
SO NATURE GENETICS
LA English
DT Article
ID DETECTABLE CLONAL MOSAICISM; BONE-MARROW-CELLS; MYELOPROLIFERATIVE
   NEOPLASMS; CONFERS SUSCEPTIBILITY; BLADDER-CANCER; JAK2 HAPLOTYPE; AGE;
   GENOME; RISK; HEMATOPOIESIS
AB Mosaic loss of chromosome Y (mLOY) leading to gonosomal XY/XO commonly occurs during aging, particularly in smokers. We investigated whether mLOY was associated with non-hematological cancer in three prospective cohorts (8,679 cancer cases and 5,110 cancer-free controls) and genetic susceptibility to mLOY. Overall, mLOY was observed in 7% of men, and its prevalence increased with age (per-year odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.12-1.15; P < 2 x 10(-16)), reaching 18.7% among men over 80 years old. mLOY was associated with current smoking (OR = 2.35, 95% CI = 1.82-3.03; P = 5.55 x 10(-11)), but the association weakened with years after cessation. mLOY was not consistently associated with overall or specific cancer risk (for example, bladder, lung or prostate cancer) nor with cancer survival after diagnosis (multivariate-adjusted hazard ratio = 0.87, 95% CI = 0.73-1.04; P = 0.12). In a genome-wide association study, we observed the first example of a common susceptibility locus for genetic mosaicism, specifically mLOY, which maps to TCL1A at 14q32.13, marked by rs2887399 (OR = 1.55, 95% CI = 1.36-1.78; P = 1.37 x 10(-10)).
C1 [Zhou, Weiyin; Machiela, Mitchell J.; Freedman, Neal D.; Rothman, Nathaniel; Dagnall, Casey; Caporaso, Neil; Sampson, Joshua; Albanes, Demetrius; Weinstein, Stephanie; Berndt, Sonja; Hoover, Robert N.; Black, Amanda; Silverman, Debra; Figueroa, Jonine; Garcia-Closas, Montserrat; Hutchinson, Amy; Tucker, Margaret; Dean, Michael; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA.
   [Zhou, Weiyin; Dagnall, Casey; Jacobs, Kevin B.; Hutchinson, Amy; Yeager, Meredith] Leidos Biomed Res Inc, Canc Genom Res Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
   [Malats, Nuria; Real, Francisco X.; Earl, Julie; Marenne, Gaelle] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
   [Teras, Lauren T.; Gaudet, Mia M.; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
   [Jacobs, Kevin B.] Bioinformed LLC, Gaithersburg, MD USA.
   [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
   [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
   [Real, Francisco X.; Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
   [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain.
   [Rodriguez-Santiago, Benjamin] QGenomics, Quantitat Genom Med Lab, Barcelona, Spain.
   [Karagas, Margaret] Dartmouth Med Sch, Biostat & Epidemiol Sect, Lebanon, NH USA.
   [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
   [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
   [Wu, Xifeng; Gu, Jian; Ye, Yuanqing] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Perez-Jurado, Luis A.] Hosp del Mar Res Inst IMIM, Barcelona, Spain.
   [Dean, Michael] NCI, Lab Expt Immunol, Ctr Canc Res, Frederick, MD 21701 USA.
RP Yeager, M; Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA.; Yeager, M (reprint author), Leidos Biomed Res Inc, Canc Genom Res Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM yeagerm@mail.nih.gov; chanocks@mail.nih.gov
RI Real, Francisco X/H-5275-2015; 
OI Machiela, Mitchell/0000-0001-6538-9705; Real, Francisco
   X/0000-0001-9501-498X; Dagnall, Casey/0000-0001-7334-4718; Malats,
   Nuria/0000-0003-2538-3784
FU National Cancer Institute, US National Institutes of Health
   [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, US National Institutes of Health, under
   contract HHSN261200800001E. The content of this publication does not
   necessarily reflect the views or policies of the US Department of Health
   and Human Services nor does mention of trade names, commercial products
   or organizations imply endorsement by the US government.
NR 35
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U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2016
VL 48
IS 5
BP 563
EP +
DI 10.1038/ng.3545
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DK3RC
UT WOS:000374834100017
PM 27064253
ER

PT J
AU Siu, LL
   Lawler, M
   Haussler, D
   Knoppers, BM
   Lewin, J
   Vis, DJ
   Liao, RG
   Andre, F
   Banks, I
   Barrett, JC
   Caldas, C
   Camargo, AA
   Fitzgerald, RC
   Mao, M
   Mattison, JE
   Pao, W
   Sellers, WR
   Sullivan, P
   Teh, BT
   Ward, RL
   ZenKlusen, JC
   Sawyers, CL
   Voest, EE
AF Siu, Lillian L.
   Lawler, Mark
   Haussler, David
   Knoppers, Bartha Maria
   Lewin, Jeremy
   Vis, Daniel J.
   Liao, Rachel G.
   Andre, Fabrice
   Banks, Ian
   Barrett, J. Carl
   Caldas, Carlos
   Camargo, Anamaria Aranha
   Fitzgerald, Rebecca C.
   Mao, Mao
   Mattison, John E.
   Pao, William
   Sellers, William R.
   Sullivan, Patrick
   Teh, Bin Tean
   Ward, Robyn L.
   ZenKlusen, Jean Claude
   Sawyers, Charles L.
   Voest, Emile E.
TI Facilitating a culture of responsible and effective sharing of cancer
   genome data
SO NATURE MEDICINE
LA English
DT Article
ID BILL-OF-RIGHTS; GENETIC PRIVACY; GLOBAL ALLIANCE; MEDICINE; CONSENT;
   CARE; EUROPE; HEALTH; LEGAL; INFORMATION
AB Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precision cancer care. Information systems must be harmonized to overcome the multiple technical and logistical barriers to data sharing. Against this backdrop, the Global Alliance for Genomic Health (GA4GH) was established in 2013 to create a common framework that enables responsible, voluntary and secure sharing of clinical and genomic data. This Perspective from the GA4GH Clinical Working Group Cancer Task Team highlights the data-aggregation challenges faced by the field, suggests potential collaborative solutions and describes how GA4GH can catalyze a harmonized data-sharing culture.
C1 [Siu, Lillian L.; Lewin, Jeremy] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada.
   [Lawler, Mark] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland.
   [Haussler, David] Univ Calif Santa Cruz, UC Santa Cruz Genom Inst, Santa Cruz, CA 95064 USA.
   [Knoppers, Bartha Maria] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada.
   [Vis, Daniel J.; Voest, Emile E.] Netherlands Canc Inst, Amsterdam, Netherlands.
   [Liao, Rachel G.] Global Alliance Genom & Hlth, Toronto, ON, Canada.
   [Andre, Fabrice] Gustave Roussy, Villejuif, France.
   [Andre, Fabrice] Univ Paris 11, Villejuif, France.
   [Banks, Ian] European Canc Org, Patients Advocacy Comm, Brussels, Belgium.
   [Barrett, J. Carl] AstraZeneca, Oncol IMED, Translat Sci, Waltham, MA USA.
   [Caldas, Carlos; Fitzgerald, Rebecca C.] Univ Cambridge, Dept Oncol, Cambridge, England.
   [Camargo, Anamaria Aranha] Hosp Sirio Libanes, Sao Paulo, Brazil.
   [Mao, Mao] Yonsei Univ, Coll Med, Yonsei Canc Res Inst, Seoul, South Korea.
   [Mattison, John E.] Kaiser Permanente, Pasadena, CA USA.
   [Pao, William] Roche, Pharma Res & Early Dev, Roche Innovat Ctr Basel, Basel, Switzerland.
   [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA USA.
   [Sullivan, Patrick] Advocacy Canadian Children Oncol Network, Vancouver, BC, Canada.
   [Teh, Bin Tean] Natl Canc Ctr Singapore, Singapore, Singapore.
   [Ward, Robyn L.] Univ Queensland, St Lucia, Qld, Australia.
   [ZenKlusen, Jean Claude] NCI, Canc Genome Atlas, NIH, Bethesda, MD 20892 USA.
   [Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
RP Lawler, M (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland.
EM mark.lawler@qub.ac.uk
RI Camargo, Anamaria/E-9388-2012; Ward, Robyn/I-2313-2013; 
OI Camargo, Anamaria/0000-0002-6076-9597; Ward, Robyn/0000-0002-6877-8906;
   Caldas, Carlos/0000-0003-3547-1489
FU Cancer Care Ontario Research Chair and Applied Cancer Research Units
   Grant; Cancer Research UK; US National Institutes of Health
   [U54HG007990]; Quebec Breast Cancer Foundation; Howard Hughes Medical
   Institute; US National Cancer Institute [CA008748]; Barcode for Life
   Foundation; Hartwig Medical Foundation
FX This manuscript is written on behalf of the GA4GH Clinical Working Group
   (WG). We thank the Data WG, Regulatory and Ethics WG and Security WG for
   their important contributions. L.L.S. is supported by the Cancer Care
   Ontario Research Chair and Applied Cancer Research Units Grant; M.L.,
   C.C. and R.C.F. are supported by Cancer Research UK; D.H. is funded by
   the US National Institutes of Health (award #U54HG007990). B.M.K. is
   supported by the Quebec Breast Cancer Foundation; C.L.S. is supported by
   the Howard Hughes Medical Institute and US National Cancer Institute
   (Grant #CA008748); E.E.V. is supported by the Barcode for Life
   Foundation and the Hartwig Medical Foundation.
NR 68
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD MAY
PY 2016
VL 22
IS 5
BP 464
EP 471
DI 10.1038/nm.4089
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA DL3DI
UT WOS:000375514000008
PM 27149219
ER

PT J
AU Marakalala, MJ
   Raju, RM
   Sharma, K
   Zhang, YJJ
   Eugenin, EA
   Prideaux, B
   Daudelin, IB
   Chen, PY
   Booty, MG
   Kim, JH
   Eum, SY
   Via, LE
   Behar, SM
   Barry, CE
   Mann, M
   Dartois, V
   Rubin, EJ
AF Marakalala, Mohlopheni J.
   Raju, Ravikiran M.
   Sharma, Kirti
   Zhang, Yanjia J.
   Eugenin, Eliseo A.
   Prideaux, Brendan
   Daudelin, Isaac B.
   Chen, Pei-Yu
   Booty, Matthew G.
   Kim, Jin Hee
   Eum, Seok Yong
   Via, Laura E.
   Behar, Samuel M.
   Barry, Clifton E., III
   Mann, Matthias
   Dartois, Veronique
   Rubin, Eric J.
TI Inflammatory signaling in human tuberculosis granulomas is spatially
   organized
SO NATURE MEDICINE
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; LIPID MEDIATORS; MACROPHAGE DEATH; HOST
   IMMUNITY; INFECTION; SUSCEPTIBILITY; RESISTANCE; INDUCTION; CASEATION;
   DISEASE
AB Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner. Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas. We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature. These findings are consistent across a set of six human subjects and in rabbits. Although the balance between systemic pro and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma. From the protein and lipid snapshots of-human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.
C1 [Marakalala, Mohlopheni J.; Raju, Ravikiran M.; Zhang, Yanjia J.; Rubin, Eric J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Sharma, Kirti; Mann, Matthias] Max Planck Inst Biochem, Dept Prote & Signal Transduct, Klopferspitz 18A, D-82152 Martinsried, Germany.
   [Eugenin, Eliseo A.; Prideaux, Brendan; Daudelin, Isaac B.; Chen, Pei-Yu; Dartois, Veronique] Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst, 185 S Orange Ave, Newark, NJ 07103 USA.
   [Eugenin, Eliseo A.; Dartois, Veronique] Rutgers State Univ, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07102 USA.
   [Booty, Matthew G.; Behar, Samuel M.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA USA.
   [Booty, Matthew G.] Harvard Univ, Sch Med, Program Immunol, Div Med Sci, Boston, MA USA.
   [Kim, Jin Hee] Natl Masan TB Hosp, Chang Won, South Korea.
   [Eum, Seok Yong] Int TB Res Ctr, Chang Won, South Korea.
   [Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa.
   [Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Dept Clin Lab Sci, ZA-7700 Rondebosch, South Africa.
RP Rubin, EJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.; Dartois, V (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst, 185 S Orange Ave, Newark, NJ 07103 USA.; Dartois, V (reprint author), Rutgers State Univ, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07102 USA.
EM dartoiva@nims.rutgers.edu; erubin@hsph.harvard.edu
RI Sharma, Kirti/C-5944-2011; 
OI Sharma, Kirti/0000-0003-3704-1466; Booty, Matthew/0000-0002-0835-3439;
   Behar, Samuel/0000-0002-3374-6699; MARAKALALA, MOHLOPHENI
   /0000-0001-7476-1652
FU HHMI-K-RITH; US National Institutes of Health (NIH) [1S10OD018072-01A1,
   R01AI098637]; National Institute of Mental Health [MH096625]; US Bill
   and Melinda Gates Foundation TB Drug Accelerator grant [OPP 1066499]; US
   Public Health Research Institute (New Jersey Medical School) central
   grant; Division of Intramural Research, National Institute of Allergy
   and Infectious Disease, NIH; Korean Centers of Disease Control, Ministry
   of Health, Welfare and Family Affairs
FX We thank the patients and staff of National Masan TB Hospital, as well
   as the technical staff from the International Tuberculosis Research
   Center, for their participation in our studies. We acknowledge A.
   Martinot for generating some of the H&E-stained images and for useful
   advice on the pathology studies, and thank members of the Rubin and
   Fortune laboratories for useful discussions. This work was supported by
   a Visiting Science Award from HHMI-K-RITH (E.J.R.), the US National
   Institutes of Health (NIH) grants 1S10OD018072-01A1 (shared
   instrumentation grant for the MALDI orbitrap; V.D.) and R01AI098637
   (S.M.B.), the National Institute of Mental Health grant MH096625
   (E.A.E.), the US Bill and Melinda Gates Foundation TB Drug Accelerator
   grant OPP 1066499 (V.D.), a US Public Health Research Institute (New
   Jersey Medical School) central grant (E.A.E.), the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Disease, NIH (C.E.B.) and the Korean Centers of Disease Control,
   Ministry of Health, Welfare and Family Affairs (C.E.B.). We would like
   to acknowledge the PRIDE Team for upload of proteomics raw data.
NR 40
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD MAY
PY 2016
VL 22
IS 5
BP 531
EP 538
DI 10.1038/nm.4073
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA DL3DI
UT WOS:000375514000016
PM 27043495
ER

PT J
AU Valdmanis, PN
   Gu, S
   Chu, K
   Jin, L
   Zhang, FJ
   Munding, EM
   Zhang, Y
   Huang, Y
   Kutay, H
   Ghoshal, K
   Lisowski, L
   Kay, MA
AF Valdmanis, Paul N.
   Gu, Shuo
   Chu, Kirk
   Jin, Lan
   Zhang, Feijie
   Munding, Elizabeth M.
   Zhang, Yue
   Huang, Yong
   Kutay, Huban
   Ghoshal, Kalpana
   Lisowski, Leszek
   Kay, Mark A.
TI RNA interference-induced hepatotoxicity results from loss of the first
   synthesized isoform of microRNA-122 in mice
SO NATURE MEDICINE
LA English
DT Article
ID GENE-EXPRESSION; MESSENGER-RNAS; RAT-LIVER; IN-VIVO; MIR-122;
   HEPATOCARCINOGENESIS; BINDING; MOUSE
AB Small RNAs can be engineered to target and eliminate expression of disease-causing genes or infectious viruses, resulting in the preclinical and clinical development of RNA interference (RNAi) therapeutics using these small RNAs1. To ensure the success of RNAi therapeutics, small hairpin RNAs (shRNAs) must co-opt sufficient quantities of the endogenous microRNA machinery to elicit efficient gene knockdown without impeding normal cellular function. We previously observed liver toxicity-including hepatocyte turnover, loss of gene repression and lethality(2)-in mice receiving high doses of a recombinant adeno-associated virus (rAAV) vector expressing shRNAs (rAAV-shRNAs); however the mechanism by which toxicity ensues has not been elucidated. Using rAAV-shRNAs we have now determined that hepatotoxicity arises when exogenous shRNAs exceed 12% of the total amount of liver microRNAs. After this threshold was surpassed, shRNAs specifically reduced the initially synthesized 22-nucleotide isoform of microRNA (miR)-122-5p without substantially affecting other microRNAs, resulting in functional de-repression of miR-122 target mRNAs. Delivery of a rAAV-shRNA vector expressing mature miR-122-5p could circumvent toxicity, despite the exogenous shRNA accounting for 70% of microRNAs. Toxicity was also not observed in Mir122-knockout mice regardless of the level or sequence of the shRNA. Our study establishes limits to the microRNA machinery that is available for therapeutic siRNAs and suggests new paradigms for the role of miR-122 in liver homeostasis in mice.
C1 [Valdmanis, Paul N.; Gu, Shuo; Chu, Kirk; Jin, Lan; Zhang, Feijie; Munding, Elizabeth M.; Zhang, Yue; Huang, Yong; Lisowski, Leszek; Kay, Mark A.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
   [Valdmanis, Paul N.; Gu, Shuo; Chu, Kirk; Jin, Lan; Zhang, Feijie; Munding, Elizabeth M.; Zhang, Yue; Huang, Yong; Lisowski, Leszek; Kay, Mark A.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Kutay, Huban; Ghoshal, Kalpana] Ohio State Univ, Dept Pathol, Ctr Comprehens Canc, Columbus, OH 43210 USA.
   [Gu, Shuo] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
   [Lisowski, Leszek] Childrens Med Res Inst, Sydney, NSW, Australia.
RP Kay, MA (reprint author), Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.; Kay, MA (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
EM markay@stanford.edu
RI Gu, Shuo/K-5404-2016
FU NIH [R01DK078424, R01AI071068, R01CA193244]; Canadian Institutes of
   Health Research
FX This work was supported by NIH grants R01DK078424 (M.A.K.), R01AI071068
   (M.A.K.) and R01CA193244 (K.G.) and a Banting Postdoctoral Fellowship
   from the Canadian Institutes of Health Research (P.N.V.). We would like
   to thank all members of the Kay laboratory for input and suggestions,
   and H. Vogel for EM image analysis. Dicer1-knockout cells were kindly
   provided by B. Cullen (Duke University). We would like to thank the
   Stanford Functional Genomics Facility and the Stanford Center for
   Genomics and Personalized Medicine for high-throughput sequencing
   services.
NR 31
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD MAY
PY 2016
VL 22
IS 5
BP 557
EP 562
DI 10.1038/nm.4079
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA DL3DI
UT WOS:000375514000019
PM 27064447
ER

PT J
AU Fang, EF
   Scheibye-Knudsen, M
   Chua, KF
   Mattson, MP
   Croteau, DL
   Bohr, VA
AF Fang, Evandro Fei
   Scheibye-Knudsen, Morten
   Chua, Katrin F.
   Mattson, Mark P.
   Croteau, Deborah L.
   Bohr, Vilhelm A.
TI Nuclear DNA damage signalling to mitochondria in ageing
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID HISTONE DEACETYLASE SIRT6; GILFORD-PROGERIA-SYNDROME; BASE
   EXCISION-REPAIR; EXTENDS LIFE-SPAN; CALORIE RESTRICTION; PROTEIN-KINASE;
   CELL-SURVIVAL; CAENORHABDITIS-ELEGANS; ATAXIA-TELANGIECTASIA; ALLOSTERIC
   ACTIVATORS
AB Mitochondrial dysfunction is a hallmark of ageing, and mitochondrial maintenance may lead to increased healthspan. Emerging evidence suggests a crucial role for signalling from the nucleus to mitochondria (NM signalling) in regulating mitochondrial function and ageing. An important initiator of NM signalling is nuclear DNA damage, which accumulates with age and may contribute to the development of age-associated diseases. DNA damage-dependent NM signalling constitutes a network that includes nuclear sirtuins and controls genomic stability and mitochondrial integrity. Pharmacological modulation of NM signalling is a promising novel approach for the prevention and treatment of age-associated diseases.
C1 [Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
   [Chua, Katrin F.] Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Sch Med, Stanford, CA 94305 USA.
   [Chua, Katrin F.] VA Palo Alto Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Palo Alto, CA 94304 USA.
   [Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
   [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280
FU US National Institutes of Health (NIH) National Institute on Ageing
   (NIA); Department of Veterans Affairs; Glenn Foundation for Medical
   Research; NIH/NIA [R56AG050997]
FX The authors acknowledge the valuable work of the many investigators
   whose published articles they were unable to cite owing to space
   limitations. They thank Prabhat Khadka and Anne Tseng for critical
   reading of the manuscript. This research was supported entirely by the
   Intramural Research Program of the US National Institutes of Health
   (NIH) National Institute on Ageing (NIA). K.F.C. was supported by the
   Department of Veterans Affairs (Merit Award), research awards from the
   Glenn Foundation for Medical Research and the NIH/NIA (R56AG050997).
NR 151
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U1 9
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
EI 1471-0080
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD MAY
PY 2016
VL 17
IS 5
BP 308
EP 321
DI 10.1038/nrm.2016.14
PG 14
WC Cell Biology
SC Cell Biology
GA DJ9MG
UT WOS:000374537000009
PM 26956196
ER

PT J
AU Sidhu, VK
   Huang, BX
   Desai, A
   Kevala, K
   Kim, HY
AF Sidhu, Vishaldeep K.
   Huang, Bill X.
   Desai, Abhishek
   Kevala, Karl
   Kim, Hee-Yong
TI Role of DHA in aging-related changes in mouse brain synaptic plasma
   membrane proteome
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Aging-related changes; Synaptic plasma membrane proteins; DHA;
   Neurotransmission; MS-based protein quantitation; Mass spectrometry;
   Recognition memory
ID FATTY-ACID-COMPOSITION; AGE-RELATED DECREASES; DOCOSAHEXAENOIC ACID;
   COGNITIVE IMPAIRMENT; SPINE APPARATUS; RAT HIPPOCAMPUS;
   N-DOCOSAHEXAENOYLETHANOLAMINE; VESICULAR TRANSPORT; RECEPTOR SUBUNITS;
   MASS-SPECTROMETRY
AB Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-alpha, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-a, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. Published by Elsevier Inc.
C1 [Sidhu, Vishaldeep K.; Huang, Bill X.; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, DICBR, NIH, Bethesda, MD USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
EM hykim@nih.gov
FU National Institute of Alcohol Abuse and Alcoholism, National Institutes
   of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Alcohol Abuse and Alcoholism, National Institutes
   of Health.
NR 81
TC 2
Z9 2
U1 6
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2016
VL 41
BP 73
EP 85
DI 10.1016/j.neurobiolaging.2016.02.007
PG 13
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DK7TU
UT WOS:000375129400008
PM 27103520
ER

PT J
AU Muller, M
   Sigurdsson, S
   Kjartansson, O
   Gunnarsdottir, I
   Thorsdottir, I
   Harris, TB
   van Buchem, M
   Gudnason, V
   Launer, LJ
AF Muller, Majon
   Sigurdsson, Sigurdur
   Kjartansson, Olafur
   Gunnarsdottir, Ingibjorg
   Thorsdottir, Inga
   Harris, Tamara B.
   van Buchem, Mark
   Gudnason, Vilmundur
   Launer, Lenore J.
CA Age Gene Environm Susceptibility
TI Late-life brain volume: a life-course approach. The AGES-Reykjavik study
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Brain volume; Life-course; Birth size; Cardiovascular risk factors
ID HIGH-BIRTH-WEIGHT; COGNITIVE FUNCTION; TISSUE VOLUMES; POPULATION;
   DISEASE; FETAL; SIZE; RISK; MRI
AB The "fetal-origins-of-adult-disease" hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Midlife cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low ponderal index [PI]) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Muller, Majon; Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
   [Muller, Majon] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands.
   [Sigurdsson, Sigurdur; Kjartansson, Olafur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
   [Kjartansson, Olafur] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland.
   [Kjartansson, Olafur] Landspitali Univ Hosp, Dept Radiol, Reykjavik, Iceland.
   [Gunnarsdottir, Ingibjorg; Thorsdottir, Inga] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland.
   [Gunnarsdottir, Ingibjorg; Thorsdottir, Inga] Landspitali Univ Hosp, Reykjavik, Iceland.
   [van Buchem, Mark] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Launer, LJ (reprint author), NIA, Lab Epidemiol & Populat Sci, Suite 3C309,Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM launerl@nia.nih.gov
NR 26
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 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAY
PY 2016
VL 41
BP 86
EP 92
DI 10.1016/j.neurobiolaging.2016.02.012
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA DK7TU
UT WOS:000375129400009
PM 27103521
ER

PT J
AU Callahan, A
   Ames, NJ
   Manning, ML
   Touchton-Leonard, K
   Yang, L
   Wallen, GR
AF Callahan, Amy
   Ames, Nancy J.
   Manning, Mary Lou
   Touchton-Leonard, Kate
   Yang, Li
   Wallen, Gwenyth R.
TI Factors Influencing Nurses' Use of Hazardous Drug Safe-Handling
   Precautions
SO ONCOLOGY NURSING FORUM
LA English
DT Article
DE oncology nurses; hazardous drugs; safe handling; occupational exposure
ID ANTINEOPLASTIC DRUGS; DERMAL EXPOSURE; AGENTS
AB Purpose/Objectives: To identify factors associated with oncology nurses' use of hazardous drug (HD) safe-handling precautions in inpatient clinical research units.
   Design: Descriptive, cross-sectional.
   Setting: The National Institutes of Health Clinical Center in Bethesda, Maryland.
   Sample: 115 RNs working on high-volume HD administration units.
   Methods: Survey data were collected online using the Hazardous Drug Handling Questionnaire. Data were analyzed using descriptive statistics and multiple regression analysis.
   Main Research Variables: Exposure knowledge, self-efficacy, barriers to personal protective equipment use, perceived risk, conflict of interest, interpersonal influences, workplace safety climate, and total mean HD precaution use.
   Findings: Participants demonstrated high exposure knowledge, self-efficacy, perceived risk, interpersonal influences, and workplace safety climate. Participants demonstrated moderate barriers and conflict of interest. Total mean HD precaution use proved highest during HD administration and lowest for handling excreta at 48 hours. Average patients per day significantly influenced total HD precaution: nurses exhibited more HD precaution use when assigned fewer patients.
   Conclusions: Despite high exposure knowledge, barriers to personal protective equipment use and conflict of interest may contribute to reduced adoption of personal protective practices among oncology nurses.
   Implications for Nursing: Hospital and unit-specific factors captured by the predictor variables could contribute to institutional HD policy.
C1 [Callahan, Amy] Thomas Jefferson Univ Hosp, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
   [Ames, Nancy J.] NIH, Dept Nursing, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
   [Manning, Mary Lou] Thomas Jefferson Univ, Sch Nursing, Philadelphia, PA 19107 USA.
   [Touchton-Leonard, Kate; Yang, Li; Wallen, Gwenyth R.] NIH, Dept Nursing, Ctr Clin, Bethesda, MD USA.
RP Callahan, A (reprint author), Thomas Jefferson Univ Hosp, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
EM amy.callahan@jefferson.edu
FU Intramural NIH HHS [Z99 CL999999]
NR 30
TC 0
Z9 0
U1 5
U2 10
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
EI 1538-0688
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAY
PY 2016
VL 43
IS 3
BP 342
EP 349
DI 10.1188/16.ONF.43-03AP
PG 8
WC Oncology; Nursing
SC Oncology; Nursing
GA DK7YP
UT WOS:000375143400015
PM 27105195
ER

PT J
AU Gruchalla, RS
   Sampson, HA
   Liu, AH
   Shreffler, W
   Wallace, PK
   Togias, A
   David, G
   Calatroni, A
   LeBeau, P
AF Gruchalla, R. S.
   Sampson, H. A.
   Liu, A. H.
   Shreffler, W.
   Wallace, P. K.
   Togias, A.
   David, G.
   Calatroni, A.
   LeBeau, P.
CA Inner-city Asthma Consortium
TI Effects of omalizumab on T lymphocyte function in inner-city children
   with asthma
SO PEDIATRIC ALLERGY AND IMMUNOLOGY
LA English
DT Letter
ID GRASS-POLLEN IMMUNOTHERAPY; ALLERGIC-ASTHMA; ANTIBODY; CELLS
C1 [Gruchalla, R. S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Sampson, H. A.] Mt Sinai Sch Med, New York, NY USA.
   [Liu, A. H.] Univ Colorado, Sch Med, Natl Jewish Hlth, Denver, CO USA.
   [Shreffler, W.] Harvard Univ, Sch Med, Boston, MA USA.
   [Wallace, P. K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
   [Togias, A.] NIH, Div Allergy Immunol & Transplantat, Bldg 10, Bethesda, MD 20892 USA.
   [David, G.; Calatroni, A.; LeBeau, P.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
RP Gruchalla, RS (reprint author), Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
EM Rebecca.gruchalla@utsouthwestern.edu
FU NCATS NIH HHS [UL1 TR001105, UL1 TR000448]; NCRR NIH HHS [M01 RR000052,
   M01 RR000071, M01 RR000533, M01 RR020359, UL1 RR024982, UL1 RR024992];
   NIAID NIH HHS [N01 AI025496, N01AI25482, N01AI25496, UM1 AI114271, UM2
   AI117870]
NR 8
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0905-6157
EI 1399-3038
J9 PEDIAT ALLERG IMM-UK
JI Pediatr. Allergy Immunol.
PD MAY
PY 2016
VL 27
IS 3
BP 328
EP 331
DI 10.1111/pai.12508
PG 4
WC Allergy; Immunology; Pediatrics
SC Allergy; Immunology; Pediatrics
GA DK6QN
UT WOS:000375049900016
PM 26573086
ER

PT J
AU Setse, RW
   Siberry, GK
   Moss, WJ
   Wheeling, J
   Bohannon, BA
   Dominguez, KL
AF Setse, Rosanna W.
   Siberry, George K.
   Moss, William J.
   Wheeling, John
   Bohannon, Beverly A.
   Dominguez, Kenneth L.
CA LEGACY Consortium
TI Meningococcal Conjugate and Tetanus Toxoid, Reduced Diphtheria Toxoid
   and Acellular Pertussis Vaccination Among HIV-infected Youth
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE HIV; MCV4; Tdap; vaccine coverage
ID AGED 13-17 YEARS; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNIZATION PRACTICES
   ACIP; UNITED-STATES; INFLUENZA VACCINATION; HUMAN-PAPILLOMAVIRUS;
   ADVISORY-COMMITTEE; ADOLESCENT IMMUNIZATION; ANTIBODY-RESPONSE;
   MULTILEVEL MODELS
AB Background: The meningococcal conjugate vaccine (MCV4) and the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) were first recommended for adolescents in the US in 2005. The goal of our study was to determine MCV4 and Tdap vaccines coverage among perinatally and behaviorally HIV-infected adolescents in 2006 and to compare coverage estimates in our study population to similarly aged healthy youth in 2006.
   Methods: Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is a retrospective cohort study of HIV-infected youth in 22 HIV specialty clinics across the US. Among LEGACY participants 11 years of age in 2006, we conducted a cross-sectional analysis to determine MCV4, Tdap and MCV4/Tdap vaccine coverage. We compared vaccine coverage among our study population to coverage among similarly aged youth in the 2006 National Immunization Survey for Teens (NIS-Teen Survey). Multivariable mixed effects logistic regression modeling was used to examine associations between MCV4/Tdap vaccination and mode of HIV transmission.
   Results: MCV4 and Tdap coverage rates among 326 eligible participants were 31.6% and 28.8%, respectively. Among adolescents 13-17 years of age, MCV4 and Tdap coverage was significantly higher among HIV-infected youth than among youth in the 2006 NIS-Teen Survey (P <0.01). In multivariable analysis, perinatally HIV-infected youth were significantly more likely to have received MCV4/Tdap vaccination compared with their behaviorally infected counterparts (adjusted odds ratio: 5.1; 95% confidence interval: 2.0, 12.7). HIV-infected youth with CD4 cell counts of 200-499 cells/L were more likely to have had MCV4/Tdap vaccination compared with those with CD4 counts 500 cells/L (adjusted odds ratio: 2.2; 95% confidence interval: 1.2, 4.3). Participants with plasma HIV RNA viral loads of >400 copies/mL were significantly less likely to have received MCV4/Tdap vaccination (P < 0.05).
   Conclusions: MCV4 and Tdap coverage among HIV-infected youth was suboptimal but higher than for healthy adolescents in the 2006 NIS-Teen Survey. Perinatal HIV infection was associated with increased likelihood of vaccination. Specific measures are needed to improve vaccine coverage among adolescents in the US.
C1 [Setse, Rosanna W.; Moss, William J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent Maternal AIDS Branch, NIH, Bethesda, MD USA.
   [Wheeling, John] Northrop Grumman Inc, Atlanta, GA USA.
   [Bohannon, Beverly A.; Dominguez, Kenneth L.; LEGACY Consortium] Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA USA.
   [Setse, Rosanna W.] US FDA, Silver Spring, MD USA.
RP Setse, RW (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
EM rsetse@hotmail.com
FU Centers for Disease Control and Prevention, Atlanta, GA [200-2004-09976]
FX The LEGACY project was funded by the Centers for Disease Control and
   Prevention, Atlanta, GA, contract number 200-2004-09976. This study was
   approved by the Institutional Review Board (IRB) of the Johns Hopkins
   School of Medicine, IRB No. NA_00011187.
NR 39
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD MAY
PY 2016
VL 35
IS 5
BP e152
EP e157
DI 10.1097/INF.0000000000001078
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA DK6PC
UT WOS:000375045200004
PM 26855409
ER

PT J
AU Justinova, Z
   Le Foll, B
   Redhi, GH
   Markou, A
   Goldberg, SR
AF Justinova, Zuzana
   Le Foll, Bernard
   Redhi, Godfrey H.
   Markou, Athina
   Goldberg, Steven R.
TI Differential effects of the metabotropic glutamate 2/3 receptor agonist
   LY379268 on nicotine versus cocaine self-administration and relapse in
   squirrel monkeys
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Cocaine; Glutamate; Nicotine; Reinstatement; Relapse;
   Self-administration; Smoking cessation; Squirrel monkey
ID NUCLEUS-ACCUMBENS SHELL; VENTRAL TEGMENTAL AREA; CUE-INDUCED
   REINSTATEMENT; DRUG-SEEKING BEHAVIOR; HEROIN SEEKING; REINFORCING
   EFFICACY; 2ND-ORDER SCHEDULES; ALCOHOL-SEEKING; MESSENGER-RNA; RAT-BRAIN
AB Rationale Group II metabotropic glutamate receptors (mGluR2 and mGluR3) have been suggested to play an important role in mediation of drug-reinforced behaviors, as well as in the mechanisms underlying relapse in abstinent subjects. The prototypical mGluR2/3 agonist, LY379268, has been shown to attenuate nicotine reinforcement and cue-induced reinstatement of drug seeking in rats, as well as reinstatement induced by drug-associated stimuli and contexts across different drugs of abuse (i.e., cocaine, heroin, and methamphetamine). However, in primates, LY379268 has been shown to produce conflicting results on abuse-related effects of cocaine, and there are no data available for nicotine.
   Objectives To explore the therapeutic potential of mGluR2/3 agonists, we compared the effects of LY379268 (0.03-1.0 mg/kg) on nicotine, cocaine, and food self-administration under a fixed-ratio (FR10) schedule in three separate groups of squirrel monkeys. Moreover, we studied the effects of LY379268 on nicotine/cocaine priming-induced and cue-induced reinstatement of drug-seeking behavior in nicotine- and cocaine-experienced groups of animals.
   Results LY379268 blocked nicotine, but not cocaine, self-administration in monkeys. There was a partial overlap between doses that affected nicotine and food self-administration. In abstinent monkeys, LY379268 dose-dependently blocked nicotine, but not cocaine, priming-induced reinstatement of drug seeking. In both cocaine-experienced and nicotine- experienced groups of animals, LY379268 potently reduced cue-induced reinstatement of drug-seeking behavior.
   Conclusions The present findings provide strong support for the potential utility of mGlu2/3 receptor agonists for the treatment of nicotine dependence and suggest their utility for prevention of relapse induced by environmental cues associated with drug taking.
C1 [Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
   [Le Foll, Bernard] Univ Toronto, Translat Addict Res Lab, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
   [Le Foll, Bernard] Ctr Addict & Mental Hlth, Alcohol Res & Treatment Clin, Addict Med Serv, Ambulatory Care & Structured Treatments, Toronto, ON, Canada.
   [Le Foll, Bernard] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada.
   [Le Foll, Bernard] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Dept Psychiat, Div Brain & Therapeut, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Toronto, ON, Canada.
   [Markou, Athina] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA.
RP Justinova, Z (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
EM zjustino@intra.nida.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU NIDA grant [DA011946]; Intramural Research Program, National Institute
   on Drug Abuse, NIH; DHHS
FX This work was supported in part by the Intramural Research Program,
   National Institute on Drug Abuse, NIH, DHHS, and in part by NIDA grant
   DA011946 to Dr. Markou.
NR 46
TC 3
Z9 3
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1791
EP 1800
DI 10.1007/s00213-015-3994-y
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400004
PM 26149611
ER

PT J
AU Forget, B
   Guranda, M
   Gamaleddin, I
   Goldberg, SR
   Le Foll, B
AF Forget, Benoit
   Guranda, Mihail
   Gamaleddin, Islam
   Goldberg, Steven R.
   Le Foll, Bernard
TI Attenuation of cue-induced reinstatement of nicotine seeking by URB597
   through cannabinoid CB1 receptor in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Nicotine; Intravenous self-administration; Rats; Relapse; Rimonabant;
   URB597
ID AMIDE HYDROLASE INHIBITION; ALPHA NUCLEAR RECEPTORS; ENDOCANNABINOID
   SYSTEM; ANANDAMIDE HYDROLYSIS; DRUG RELAPSE; FAAH; ACTIVATION;
   ADDICTION; SMOKING; ABUSE
AB Rationale The endocannabinoid system is composed of endocannabinoids (such as anandamide), their target receptors (CB1 and CB2 receptors, CB(1)Rs and CB(2)Rs), the enzymes that degrade them (fatty-acid-amide-hydrolase (FAAH) for anandamide), and an endocannabinoid transporter. FAAH inhibition has been recently identified as having a critical involvement in behaviors related to nicotine addiction and has been shown to reduce the effect of nicotine on the mesolimbic dopaminergic system via CB1R and peroxisome proliferator-activated receptor alpha (PPAR alpha). Thus, inhibition of FAAH may represent a novel strategy for smoking cessation, but its mechanism of action on relapse to nicotine seeking is still unknown.
   Objective The study aims to explore the mechanism of action of the inhibitor of FAAH activity, URB597, on relapse to nicotine seeking by evaluating the effect of the CB1R, CB2R, and PPAR alpha antagonists on the attenuating effect of URB597 on cue-induced reinstatement of nicotine seeking in rats.
   Results URB597 reduced cue-induced reinstatement of nicotine seeking, an effect that was reversed by the CB1R antagonist rimonabant, but not by the CB2R or PPAR alpha antagonists AM630 and MK886, respectively.
   Conclusions These results indicate that URB597 reduces cue-induced reinstatement in rats through a CB1 receptor-dependent mechanism, and not via CB2R or PPAR alpha. Since FAAH inhibition represent a novel and promising strategy for tobacco smoking cessation, dissecting how it produces its action may lead to a better understanding of the neurobiological mechanisms underlying nicotine addiction.
C1 [Forget, Benoit; Guranda, Mihail; Gamaleddin, Islam; Le Foll, Bernard] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, 33 Russell St, Toronto, ON M5S 2S1, Canada.
   [Forget, Benoit] Inst Pasteur, Unite Neurobiol Integrat Syst, Cholinerg, CNRS UMR 3571, F-75724 Paris 15, France.
   [Gamaleddin, Islam] Ain Shams Univ, Inst Environm Studies & Res, Cairo, Egypt.
   [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD USA.
   [Le Foll, Bernard] CAMH, Alcohol Res & Treatment Clin, Addict Med Serv, Ambulatory Care & Structured Treatments, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Pharmacol, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON, Canada.
RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, 33 Russell St, Toronto, ON M5S 2S1, Canada.; Le Foll, B (reprint author), CAMH, Alcohol Res & Treatment Clin, Addict Med Serv, Ambulatory Care & Structured Treatments, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Pharmacol, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON, Canada.
EM bernard.lefoll@camh.ca
FU Heart and Stroke Foundation [NA 6901]
FX This work was supported by a grant from the Heart and Stroke Foundation
   no. NA 6901.
NR 38
TC 3
Z9 3
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1823
EP 1828
DI 10.1007/s00213-016-4232-y
PG 6
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400007
PM 26864774
ER

PT J
AU Le Foll, B
   Chefer, SI
   Kimes, AS
   Stein, EA
   Goldberg, SR
   Mukhin, AG
AF Le Foll, Bernard
   Chefer, Svetlana I.
   Kimes, Alane S.
   Stein, Elliot A.
   Goldberg, Steven R.
   Mukhin, Alexey G.
TI Impact of short access nicotine self-administration on expression of
   alpha 4 beta 2*nicotinic acetylcholine receptors in non-human primates
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Positron emission tomography; Nicotine self-administration; In vivo
   binding; Non-human primates
ID BINDING-SITES; PHARMACOLOGICAL CHAPERONE; CHOLINERGIC-RECEPTOR;
   UP-REGULATION; HUMAN-BRAIN; RAT-BRAIN; PET; SMOKING; SMOKERS; ADDICTION
AB Rationale Although nicotine exposure upregulates the alpha 4 beta 2* subtype of nicotinic acetylcholine receptors (nAChRs), the upregulation of nAChRs in non-human primates voluntarily self-administering nicotine has never been demonstrated.
   Objectives The objective of the study is to determine if short access to nicotine in a non-human primate model of nicotine self-administration is sufficient to induce nAChRs upregulation.
   Methods We combined a nicotine self-administration paradigm with in vivo measure of alpha 4 beta 2* nAChRs using 2-[F-18]fluoro-A-85380 (2-FA) and positron emission tomography (PET) in six squirrel monkeys. PET measurement was performed before and after intravenous nicotine self-administration (unit dose 10 mu g/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (1 h daily per weekday) to nicotine was allowed for 4 weeks and levels of alpha 4 beta 2* nAChRs were measured 4 days later.
   Results This intermittent access was sufficient to induce upregulation of alpha 4 beta 2* receptors in the whole brain (31 % upregulation) and in specific brain areas (+36 % in amygdala and +62 % in putamen).
   Conclusions These results indicate that intermittent nicotine exposure is sufficient to produce change in nAChRs expression.
C1 [Le Foll, Bernard] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, 33 Russell St, Toronto, ON M5S 2S1, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Pharmacol, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON, Canada.
   [Le Foll, Bernard] Ctr Addict & Mental Hlth, Ambulatory Care & Structured Treatment Program, Toronto, ON M5S 2S1, Canada.
   [Le Foll, Bernard; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
   [Chefer, Svetlana I.; Kimes, Alane S.; Stein, Elliot A.; Mukhin, Alexey G.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
   [Chefer, Svetlana I.] NIAID, Integrated Res Facil, Div Clin Res, NIH, Frederick, MD 21702 USA.
   [Kimes, Alane S.] NIDA, Off Clin Director, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
   [Mukhin, Alexey G.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 2424 Erwin Rd,Suite 201, Durham, NC 27705 USA.
   [Mukhin, Alexey G.] Duke Univ, Med Ctr, Ctr Smoking Cessat, 2424 Erwin Rd,Suite 201, Durham, NC 27705 USA.
RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, 33 Russell St, Toronto, ON M5S 2S1, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Family & Community Med, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Pharmacol, Toronto, ON, Canada.; Le Foll, B (reprint author), Univ Toronto, Inst Med Sci, Dept Psychiat, Toronto, ON, Canada.; Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Ambulatory Care & Structured Treatment Program, Toronto, ON M5S 2S1, Canada.; Le Foll, B (reprint author), NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
EM bernard.lefoll@camh.ca
FU Intramural Research Program of the National Institute on Drug Abuse,
   NIH, DHHS
FX This study was supported by the Intramural Research Program of the
   National Institute on Drug Abuse, NIH, DHHS.
NR 46
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1829
EP 1835
DI 10.1007/s00213-016-4250-9
PG 7
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400008
PM 26911381
ER

PT J
AU Tanda, G
AF Tanda, Gianluigi
TI Preclinical studies on the reinforcing effects of cannabinoids. A
   tribute to the scientific research of Dr. Steve Goldberg
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Cannabis; Delta-9-THC; Dopamine neurochemistry; Marijuana substance use
   disorders; Addiction; Self-administration; Drug discrimination; Place
   conditioning; Spice
ID CONDITIONED PLACE PREFERENCE; INTRACRANIAL SELF-STIMULATION; ACID AMIDE
   HYDROLASE; DISCRIMINATIVE STIMULUS PROPERTIES; MEDIAL-PREFRONTAL CORTEX;
   NUCLEUS-ACCUMBENS SHELL; FREELY-MOVING RATS; HIPPOCAMPAL
   ACETYLCHOLINE-RELEASE; RECEPTOR AGONIST CP-55,940; RHESUS-MONKEYS
AB Rationale The reinforcing effects of most abused drugs have been consistently demonstrated and studied in animal models, although those of marijuana were not, until the demonstration 15 years ago that delta-9-tetrahydrocannabinol (THC) could serve as a reinforcer in self-administration (SA) procedures in squirrel monkeys. Until then, those effects were inferred using indirect assessments.
   Objectives The aim of this manuscript is to review the primary preclinical procedures used to indirectly and directly infer reinforcing effects of cannabinoid drugs.
   Methods Results will be reviewed from studies of cannabinoid discrimination, intracranial self-stimulation (ICSS), conditioned place preference (CPP), as well as change in levels of dopamine assessed in brain areas related to reinforcement, and finally from self-administration procedures. For each procedure, an evaluation will be made of the predictive validity in detecting the potential abuse liability of cannabinoids based on seminal papers, with the addition of selected reports from more recent years especially those from Dr. Goldberg's research group.
   Raesults and conclusions ICSS and CPP do not provide consistent results for the assessment of potential for abuse of cannabinoids. However, drug discrimination and neurochemistry procedures appear to detect potential for abuse of cannabinoids, as well as several novel "designer cannabinoid drugs." Though after 15 years transfer of the self-administration model of marijuana abuse from squirrel monkeys to other species remains somewhat problematic, studies with the former species have substantially advanced the field, and several reports have been published with consistent self-administration of cannabinoid agonists in rodents.
C1 [Tanda, Gianluigi] NIDA, Medicat Dev Program, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 333 Cassell Dr,Triad Bldg,NIDA Suite 3301, Baltimore, MD 21224 USA.
RP Tanda, G (reprint author), NIDA, Medicat Dev Program, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 333 Cassell Dr,Triad Bldg,NIDA Suite 3301, Baltimore, MD 21224 USA.
EM gtanda@mail.nih.gov
RI Tanda, Gianluigi/B-3318-2009
OI Tanda, Gianluigi/0000-0001-9526-9878
FU Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS
FX This study was supported by the Intramural Research Program, National
   Institute on Drug Abuse, NIH/DHHS.
NR 221
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U1 8
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1845
EP 1866
DI 10.1007/s00213-016-4244-7
PG 22
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400010
PM 27026633
ER

PT J
AU Schindler, CW
   Scherma, M
   Redhi, GH
   Vadivel, SK
   Makriyannis, A
   Goldberg, SR
   Justinova, Z
AF Schindler, Charles W.
   Scherma, Maria
   Redhi, Godfrey H.
   Vadivel, Subramanian K.
   Makriyannis, Alexandros
   Goldberg, Steven R.
   Justinova, Zuzana
TI Self-administration of the anandamide transport inhibitor AM404 by
   squirrel monkeys
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Anandamide; AM404; Self-administration; Reinstatement; Rimonabant;
   Squirrel monkeys
ID ACID AMIDE HYDROLASE; ENDOGENOUS CANNABINOID ANANDAMIDE; ENDOCANNABINOID
   LEVELS; SELECTIVE-INHIBITION; NUCLEUS-ACCUMBENS; RIMONABANT; RECEPTORS;
   NICOTINE; BEHAVIOR; AGONIST
AB Rationale N-(4-hydroxyphenyl)-arachidonamide (AM404) is an anandamide transport inhibitor shown to reduce rewarding and relapse-inducing effects of nicotine in several animal models of tobacco dependence. However, the reinforcing/rewarding effects of AM404 are not clear.
   Objectives We investigated whether AM404 maintains self-administration behavior or reinstates extinguished drug seeking in squirrel monkeys.
   Methods and results In monkeys with a history of anandamide or cocaine self-administration, we substituted injections of AM404 (1-100 mu g/kg/injection). Using a 10-response, fixed-ratio schedule, self-administration behavior was maintained by AM404. Dose-response curves had inverted U shapes, with peak response rates occurring at a dose of 10 mu g/kg/injection. In anandamide-experienced monkeys, we also demonstrated self-administration of another anandamide transport inhibitor VDM11. In addition to supporting self-administration, priming injections of AM404 (0.03-0.3 mg/kg) reinstated drug-seeking behavior previously reinforced by cannabinoids (Delta(9)-tetrahydrocannabinol (THC) or anandamide) or cocaine. Both AM404 self-administration behavior and reinstatement of drug seeking by AM404 were reduced by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (0.3 mg/kg). Moreover, the reinforcing effects of AM404 were potentiated by the treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg) suggesting a major role of anandamide in these effects. Finally, AM404 (0.3 mg/kg) potentiated the reinforcing effects of anandamide but not those of cocaine.
   Conclusions In non-human primates, AM404 effectively reinforced self-administration behavior and induced reinstatement of drug-seeking behavior in abstinent monkeys. These effects appeared to be mediated by cannabinoid CB1 receptors. Therefore, compounds that promote actions of endocannabinoids throughout the brain by inhibiting their membrane transport may have a potential for abuse.
C1 [Schindler, Charles W.; Redhi, Godfrey H.; Goldberg, Steven R.; Justinova, Zuzana] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
   [Scherma, Maria] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Monserrato, Italy.
   [Vadivel, Subramanian K.; Makriyannis, Alexandros] Northeastern Univ, Dept Pharmaceut Sci, Ctr Drug Discovery, Boston, MA 02115 USA.
   [Makriyannis, Alexandros] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM cschind@helix.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of NIDA, NIH; NIDA [R01DA003801,
   R01DA007215]
FX This research was supported by the Intramural Research Program of NIDA,
   NIH and by NIDA grants R01DA003801 and R01DA007215 (to Dr. Makriyannis).
   We thank Dr. Daniele Piomelli for providing URB597 and NIDA Drug Supply
   Program for providing THC and rimonabant.
NR 50
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1867
EP 1877
DI 10.1007/s00213-016-4211-3
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400011
PM 26803499
ER

PT J
AU Panlilio, LV
   Thorndike, EB
   Nikas, SP
   Alapafuja, SO
   Bandiera, T
   Cravatt, BF
   Makriyannis, A
   Piomelli, D
   Goldberg, SR
   Justinova, Z
AF Panlilio, Leigh V.
   Thorndike, Eric B.
   Nikas, Spyros P.
   Alapafuja, Shakiru O.
   Bandiera, Tiziano
   Cravatt, Benjamin F.
   Makriyannis, Alexandros
   Piomelli, Daniele
   Goldberg, Steven R.
   Justinova, Zuzana
TI Effects of fatty acid amide hydrolase (FAAH) inhibitors on working
   memory in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Delayed spatial matching; Working memory; Endocannabinoids; FAAH
   inhibition; Monoacylglycerol lipase inhibition
ID SHORT-TERM-MEMORY; ENDOGENOUS CANNABINOID ANANDAMIDE; SQUIRREL-MONKEYS;
   ENDOCANNABINOID SYSTEM; SPATIAL MEMORY; URB597; MICE;
   DELTA(9)-TETRAHYDROCANNABINOL; MODULATION; BLOCKADE
AB Rationale Manipulations of the endocannabinoid system could potentially produce therapeutic effects with minimal risk of adverse cannabis-like side effects. Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of the cannabinoid-receptor agonist, anandamide, and show promise for treating a wide range of disorders. However, their effects on learning and memory have not been fully characterized.
   Objectives We determined the effects of five structurally different FAAH inhibitors in an animal model of working memory known to be sensitive to impairment by delta-9 tetrahydrocannabinol (THC).
   Methods A delayed nonmatching-to-position procedure was used in rats. Illuminated nosepoke holes were used to provide sample cues (left versus right) and record responses (correct versus incorrect) after delays ranging from 0 to 28 s. Various test drugs were given acutely up to two times per week before daily sessions.
   Results One FAAH inhibitor, AM3506 (3 mg/kg), decreased accuracy in the memory task. Four other FAAH inhibitors (URB597, URB694, PF-04457845, and ARN14633) and a monoacylglycerol lipase inhibitor (JZL184, which blocks the degradation of the endocannabinoid 2-arachidonoylglycerol) had no effect. Testing of AM3506 in combination with antagonists for receptors known to be affected by anandamide and other fatty acid amides indicated that the impairment induced by AM3506 was mediated by cannabinoid CB1 receptors, and not by alpha-type peroxisome proliferator-activated receptors (PPAR-alpha) or vanilloid transient receptor potential cation channels (TRPV1).
   Conclusions FAAH inhibitors differ with respect to their potential for memory impairment, abuse liability, and probably other cannabis-like effects, and they should be evaluated individually for specific therapeutic and adverse effects.
C1 [Panlilio, Leigh V.; Thorndike, Eric B.; Goldberg, Steven R.; Justinova, Zuzana] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
   [Nikas, Spyros P.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA.
   [Nikas, Spyros P.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA.
   [Alapafuja, Shakiru O.] MAKScientific LLC, Boston, MA USA.
   [Cravatt, Benjamin F.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Cravatt, Benjamin F.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Bandiera, Tiziano; Piomelli, Daniele] Ist Italiano Tecnol, Drug Discovery & Dev, Genoa, Italy.
   [Makriyannis, Alexandros] Northeastern Univ, Ctr Drug Discovery, Dept Pharmaceut Sci & Chem & Chem Biol, Boston, MA 02115 USA.
   [Makriyannis, Alexandros] Northeastern Univ, Ctr Drug Discovery, Chem & Chem Biol, Boston, MA 02115 USA.
   [Piomelli, Daniele] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA.
RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM lpanlili@mail.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the NIH, National Institute on Drug
   Abuse;  [5 DP1 DA031387];  [DA031020];  [DA09158];  [DA3801]
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute on Drug Abuse (LVP, EBT, SRG, ZJ), by grant 5
   DP1 DA031387 (DP) and by grants DA031020, DA09158, and DA3801 (AM).
NR 50
TC 3
Z9 3
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1879
EP 1888
DI 10.1007/s00213-015-4140-6
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400012
PM 26558620
ER

PT J
AU Aliczki, M
   Barna, I
   Till, I
   Baranyi, M
   Sperlagh, B
   Goldberg, SR
   Haller, J
AF Aliczki, Mano
   Barna, Istvan
   Till, Ibolya
   Baranyi, Maria
   Sperlagh, Beata
   Goldberg, Steven R.
   Haller, Jozsef
TI The effects anandamide signaling in the prelimbic cortex and basolateral
   amygdala on coping with environmental stimuli in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Amygdala; Basolateral amygdala; Anandamide; Coping; Emotional
   homeostasis; Medial prefrontal cortex; Prelimbic cortex; URB597
ID ACID AMIDE HYDROLASE; ELEVATED PLUS-MAZE; CENTRAL-NERVOUS-SYSTEM;
   ENDOCANNABINOID SYSTEM; PREFRONTAL CORTEX; INHIBITOR URB597; CONDITIONED
   FEAR; ANXIETY; BEHAVIOR; STRESS
AB Rationale Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding.
   Objectives Here, we investigated the brain mechanisms underlying this phenomenon in rats.
   Methods The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter, we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests.
   Results URB597 concentration was similar to 30 mu g/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol. High levels of illumination halved the time spent by controls in the open arms of the plus-maze. No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30 % in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness.
   Conclusions Our findings show that elevated prelimbic anandamide signaling leads to less environment-dependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping.".
C1 [Aliczki, Mano; Barna, Istvan; Till, Ibolya; Haller, Jozsef] Hungarian Acad Sci, Inst Expt Med, Dept Behav Neurobiol, POB 67, H-1450 Budapest, Hungary.
   [Baranyi, Maria; Sperlagh, Beata] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1450 Budapest, Hungary.
   [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD USA.
RP Haller, J (reprint author), Hungarian Acad Sci, Inst Expt Med, Dept Behav Neurobiol, POB 67, H-1450 Budapest, Hungary.
EM haller@koki.hu
FU National Research, Development and Innovation Office (NKFIH) [PD112787,
   K101645]; Janos Bolyai Research Scholarship of the Hungarian Academy of
   Sciences; European Research Council [294313-SERRACO]; Intramural
   Research Program of the National Institute on Drug Abuse, NIH, DHHS
FX The authors dedicate this paper to the memory of Steven R. Goldberg, an
   eminent scientist and good friend, who played an important role in
   shaping the coping concept of endocannabinoid action and in designing
   the studies presented here. Funding for this study was provided by the
   National Research, Development and Innovation Office (NKFIH) grants No.
   PD112787 (to M.A.) and K101645 (to J.H.), Janos Bolyai Research
   Scholarship of the Hungarian Academy of Sciences (M.A.), European
   Research Council grant No. 294313-SERRACO (to J.H.), and the Intramural
   Research Program of the National Institute on Drug Abuse, NIH, DHHS (to
   S.R.G.). The authors declare no conflicts of interest.
NR 53
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U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1889
EP 1899
DI 10.1007/s00213-016-4219-8
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400013
PM 26809457
ER

PT J
AU Katz, JL
AF Katz, Jonathan L.
TI Contributions to drug abuse research of Steven R. Goldberg's behavioral
   analysis of stimulus-stimulus contingencies
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Drug self-administration; Stimulus-stimulus contingencies; Opioid
   withdrawal; Second-order schedules; Respondent conditioning; Drug abuse;
   Conditioned reinforcement
ID MORPHINE-DEPENDENT MONKEYS; 2ND-ORDER SCHEDULES; RHESUS-MONKEYS; COCAINE
   INJECTION; FOOD PRESENTATION; SQUIRREL-MONKEYS; SEEKING BEHAVIOR;
   ELECTRIC-SHOCK; FIXED-RATIO; ADDICTION
AB By the mid-1960s, the concept that drugs can function as reinforcing stimuli through response-reinforcer contingencies had created a paradigm shift in drug abuse science. Steve Goldberg's first several publications focused instead on stimulus-stimulus contingencies (respondent conditioning) in examining Abraham Wikler's two-factor hypothesis of relapse involving conditioned withdrawal and reinforcing effects of drugs. Goldberg provided a compelling demonstration that histories of contingencies among stimuli could produce lasting withdrawal reactions in primates formerly dependent on opioids. Other studies conducted by Goldberg extended the analysis of effects of stimulus-stimulus contingencies on behavior maintained by opioid reinforcing effects and showed that withdrawal-inducing antagonist administration can produce conditioned increases in self-administration. Subsequent studies of the effects of stimuli associated with cocaine injection under second-order schedules showed that the maintenance of behavior with drug injections was in most important aspects similar to the maintenance of behavior with more conventional reinforcers when the behavior-disrupting pharmacological effects of the drugs were minimized. Studies on second-order schedules demonstrated a wide array of conditions under which behavior could be maintained by drug injection and further influenced by stimulus-stimulus contingencies. These schedules present opportunities to produce in the laboratory complex situations involving response- and stimulus-stimulus contingencies, which go beyond simplistic pairings of stimuli and more closely approximate those found with human drug abusers. A focus on the response- and stimulus-stimulus contingencies, and resulting quantifiable changes in objective and quantifiable behavioral endpoints exemplified by the studies by Steve Goldberg, remains the most promising way forward for studying problems of drug dependence.
C1 [Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, Baltimore, MD USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, Baltimore, MD USA.
EM jkatz@intra.nida.nih.gov
FU NIDA-IRP
FX Thanks are due to the organizers of the NIDA-IRP Steve Goldberg
   Symposium, including Antonello Bonci for funding, and particularly
   Zuzana Justinova, for bringing all of us together to pay tribute to a
   remarkable scientist and Laboratory Chief. I also thank Dr. Gianluigi
   Tanda and Daniela Useli for their sublime hospitality after the
   symposium. Jason Eaton and Marc Raley were extremely helpful in
   capturing figures from papers published years ago and rendering their
   fidelity suitable for republishing. Thanks are also due Gianluigi Tanda
   for comments during the preparation of my presentation for the NIDA-IRP
   symposium, and Drs. W.H. Morse and C-.E. Johanson for helpful comments
   on a previous draft of this paper. Lastly, I owe an immeasurable amount
   to Dr. James H. Woods for checks on my perceptions of a uniquely
   exciting and productive time in drug abuse science and behavioral
   pharmacology, for many enjoyable discussions of the materials conveyed
   here, as well as other topics often further afield.
NR 52
TC 0
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U1 4
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1921
EP 1932
DI 10.1007/s00213-015-4149-x
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400016
PM 26564234
ER

PT J
AU Lamb, RJ
   Schindler, CW
   Pinkston, JW
AF Lamb, R. J.
   Schindler, Charles W.
   Pinkston, Jonathan W.
TI Conditioned stimuli's role in relapse: preclinical research on
   Pavlovian-Instrumental-Transfer
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Conditioned Response; Sign-Tracking; Goal-Tracking; Motivation;
   Alcoholism; self-administration; discriminative stimulus; conditioned
   reinforcement; conditioned approach; incentive salience
ID DRUG-SEEKING BEHAVIOR; INCENTIVE SALIENCE; RHESUS-MONKEYS;
   SIGN-TRACKING; DISCRIMINATIVE STIMULUS; 2ND-ORDER SCHEDULES; COCAINE
   SEEKING; ETHANOL; RATS; ALCOHOL
AB Rationale and objective Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become conditioned stimuli (CS) and subsequently elicit drug-seeking and drug-taking. However, in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT.
   Findings We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition, six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug-taking. Both failed to find CS-elicited increases, i.e., no study shows CS-elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived.
   Conclusions These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug-paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful.
C1 [Lamb, R. J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
   [Lamb, R. J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
   [Schindler, Charles W.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
   [Pinkston, Jonathan W.] Univ N Texas, Dept Behav Anal, 360 G Chilton Hall,Ave C, Denton, TX 76208 USA.
RP Lamb, RJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Lamb, RJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM lamb@uthscsa.edu
FU NIAAA NIH HHS [R01 AA012337]
NR 67
TC 2
Z9 2
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1933
EP 1944
DI 10.1007/s00213-016-4216-y
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400017
PM 26800688
ER

PT J
AU Krasnova, IN
   Justinova, Z
   Cadet, JL
AF Krasnova, Irina N.
   Justinova, Zuzana
   Cadet, Jean Lud
TI Methamphetamine addiction: involvement of CREB and neuroinflammatory
   signaling pathways
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Self-administration; Striatum; Cortex; Dopamine; Neurotoxicity; Gene
   expression; Neuroinflammation
ID VENTRAL TEGMENTAL AREA; HYPOTHALAMIC OREXIN NEURONS; MESSENGER-RNA
   EXPRESSION; SUBSTANCE USE DISORDERS; GLIAL-CELL MODULATORS; MICROGLIAL
   ACTIVATION; INDUCED NEUROTOXICITY; NEUROTROPHIC FACTOR; GENE-EXPRESSION;
   TRANSCRIPTIONAL RESPONSES
AB Rationale and objectives Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models are also helping to decipher the neurobiological substrates of associated neuropsychiatric complications. This review summarizes our work on the influence of METH self-administration on dopamine systems, transcription and immune responses in the brain.
   Methods We used the rat model of METH self-administration with extended access (15 h/day for eight consecutive days) to investigate the effects of voluntary METH intake on the markers of dopamine system integrity and changes in gene expression observed in the brain at 2 h-1 month after cessation of drug exposure.
   Results Extended access to METH self-administration caused changes in the rat brain that are consistent with clinical findings reported in neuroimaging and postmortem studies of human METH addicts. In addition, gene expression studies using striatal tissues from METH self-administering rats revealed increased expression of genes involved in cAMP response element binding protein (CREB) signaling pathway and in the activation of neuroinflammatory response in the brain.
   Conclusion These data show an association of METH exposure with activation of neuroplastic and neuroinflammatory cascades in the brain. The neuroplastic changes may be involved in promoting METH addiction. Neuroinflammatory processes in the striatum may underlie cognitive deficits, depression, and parkinsonism reported in METH addicts. Therapeutic approaches that include suppression of neuroinflammation may be beneficial to addicted patients.
C1 [Krasnova, Irina N.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
   [Justinova, Zuzana] NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Krasnova, IN; Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM ikrasnov@intra.nida.nih.gov; JCADET@intra.nida.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the National Institute on Drug Abuse,
   NIH, DHHS
FX This research was supported by the Intramural Research Program of the
   National Institute on Drug Abuse, NIH, DHHS.
NR 157
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U1 8
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1945
EP 1962
DI 10.1007/s00213-016-4235-8
PG 18
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400018
PM 26873080
ER

PT J
AU Ferre, S
AF Ferre, Sergi
TI Mechanisms of the psychostimulant effects of caffeine: implications for
   substance use disorders
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Caffeine; Psychostimulants; Adenosine; Dopamine; Receptor heteromer;
   Drug abuse; Alcohol
ID ADENOSINE A(2A) RECEPTORS; ELECTRICAL BRAIN-STIMULATION;
   DOPAMINE-DEFICIENT MICE; COCAINE-TAKING BEHAVIOR; TERM RESERPINIZED
   MICE; CENTRAL-NERVOUS-SYSTEM; METHYL-D-ASPARTATE;
   6-HYDROXYDOPAMINE-LESIONED RATS; NUCLEUS-ACCUMBENS; PARKINSONS-DISEASE
AB Background The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforcing, and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems.
   Objectives A model that considers the striatal adenosine A(2A)-dopamine D-2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine.
   Highlights The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally, the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives, synthetic cathinones, and energy drinks with alcohol, and the higher sensitivity of children and adolescents to the psychostimulant effects of caffeine and its potential to increase vulnerability to SUD.
   Conclusions The striatal A(2A)-D-2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.
C1 [Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Triad Technol Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
FU National Institute on Drug Abuse
FX This work was supported by the intramural funds of the National
   Institute on Drug Abuse. The author thanks Dr. Roy A. Wise for his
   critical review of the manuscript.
NR 209
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U1 17
U2 26
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1963
EP 1979
DI 10.1007/s00213-016-4212-2
PG 17
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400019
PM 26786412
ER

PT J
AU Schindler, CW
   Thorndike, EB
   Goldberg, SR
   Lehner, KR
   Cozzi, NV
   Brandt, SD
   Baumann, MH
AF Schindler, Charles W.
   Thorndike, Eric B.
   Goldberg, Steven R.
   Lehner, Kurt R.
   Cozzi, Nicholas V.
   Brandt, Simon D.
   Baumann, Michael H.
TI Reinforcing and neurochemical effects of the "bath salts" constituents
   3,4-methylenedioxypyrovalerone (MDPV) and
   3,4-methylenedioxy-N-methylcathinone (methylone) in male rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE 3,4-Methylenedioxypyrovalerone (MDPV); Methylone; Cocaine;
   Self-administration; Microdialysis; Rats
ID INTRACRANIAL SELF-STIMULATION; METHYLENEDIOXYPYROVALERONE MDPV;
   LOCOMOTOR-ACTIVITY; MEPHEDRONE; MDMA; DOPAMINE; DRUG; ACQUISITION;
   SEROTONIN; TRANSPORTER
AB Rationale 3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT).
   Objectives We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV.
   Methods To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats.
   Results MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT.
   Conclusions Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.
C1 [Schindler, Charles W.; Thorndike, Eric B.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Lehner, Kurt R.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Cozzi, Nicholas V.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI 53706 USA.
   [Brandt, Simon D.] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Byrom St, Liverpool L3 3AF, Merseyside, England.
RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM cschind@helix.nih.gov
OI Brandt, Simon/0000-0001-8632-5372
FU Intramural Research Program of NIH, NIDA
FX This research was supported by the Intramural Research Program of NIH,
   NIDA. The authors have no conflicts of interest to report. We dedicate
   this paper to our colleague and friend Steven R. Goldberg who passed
   away suddenly on November 25, 2014.
NR 41
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U1 3
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1981
EP 1990
DI 10.1007/s00213-015-4057-0
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400020
PM 26319160
ER

PT J
AU Bossert, JM
   Adhikary, S
   St Laurent, R
   Marchant, NJ
   Wang, HL
   Morales, M
   Shaham, Y
AF Bossert, Jennifer M.
   Adhikary, Sweta
   St Laurent, Robyn
   Marchant, Nathan J.
   Wang, Hui-Ling
   Morales, Marisela
   Shaham, Yavin
TI Role of projections from ventral subiculum to nucleus accumbens shell in
   context-induced reinstatement of heroin seeking in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Baclofen; Conditioned cues; Dopamine; Drug environment; Extinction;
   Fluoro-Gold; Fos; GABA; Glutamate; Heroin self-administration;
   Hippocampus; Muscimol; Opiates; Relapse; SCH 23390
ID MEDIAL PREFRONTAL CORTEX; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; DOPAMINE
   D-1-FAMILY RECEPTORS; BASOLATERAL AMYGDALA; COCAINE-SEEKING; TEGMENTAL
   AREA; DRUG-SEEKING; INDUCED RELAPSE; DORSOLATERAL STRIATUM;
   ALCOHOL-SEEKING
AB Rationale and objective In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement.
   Methods We trained rats to self-administer heroin (0.05-0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone-light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub -> NAc shell and vSub -> vmPFC projections are functionally involved in this reinstatement.
   Results Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub -> NAc shell projection, but not the vSub -> vmPFC projection, decreased this reinstatement.
   Conclusion Our data indicate that the vSub -> NAc shell glutamatergic projection, but not the vSub -> vmPFC projection, contributes to context-induced reinstatement of heroin seeking.
C1 [Bossert, Jennifer M.; Adhikary, Sweta; St Laurent, Robyn; Marchant, Nathan J.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD USA.
   [Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
   [Wang, Hui-Ling; Morales, Marisela] NIDA, Integrat Neurosci Branch, IRP, NIH, Baltimore, MD USA.
RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD USA.
EM jbossert@intra.nida.nih.gov
FU National Institute on Drug Abuse, Intramural Research Program
FX This research was supported by the National Institute on Drug Abuse,
   Intramural Research Program. This paper is part of a special issue
   entitled "Addiction research and the legacy of Steven R. Goldberg" and
   is dedicated to Dr. Steven Goldberg, a valued friend, colleague, and a
   pioneer in addiction research.
NR 80
TC 3
Z9 3
U1 3
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 1991
EP 2004
DI 10.1007/s00213-015-4060-5
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400021
PM 26344108
ER

PT J
AU Zanettini, C
   Pressly, JD
   Ibarra, MH
   Smith, KR
   Gerak, LR
AF Zanettini, Claudio
   Pressly, Jeffrey D.
   Ibarra, Miguel H.
   Smith, Kelsey R.
   Gerak, Lisa R.
TI Comparing the discriminative stimulus effects of modulators of GABA(A)
   receptors containing alpha(4)-delta subunits with those of gaboxadol in
   rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Gaboxadol; Ethanol; Neuroactive steroids; GABA(A) receptors; Drug
   discrimination; Rats; Flumazenil
ID NEUROACTIVE STEROID PREGNANOLONE; AMINOBUTYRIC ACID(A) RECEPTORS;
   ALCOHOL ANTAGONIST RO15-4513; DELTA-SUBUNIT; PRIMARY INSOMNIA;
   RHESUS-MONKEYS; DRUG DISCRIMINATION; ALTERED EXPRESSION; TONIC
   INHIBITION; DEFICIENT MICE
AB Rationale Gaboxadol is a selective agonist at gamma-aminobutyric acid(A) (GABA(A)) receptors that contain alpha(4)-delta subunits, and it produces anxiolytic and sedative effects. Although adverse effects preclude its clinical use, its mechanism of action suggests that those receptors might provide novel therapeutic targets, particularly for modulators of those GABA(A) receptor subtypes, by retaining therapeutic effects of gaboxadol and not adverse effects.
   Objectives The current study compared discriminative stimulus effects of gaboxadol with those of modulators acting at GABA(A) receptors containing alpha(4)-delta subunits.
   Materials Eight rats discriminated 5.6 mg/kg gaboxadol from vehicle while responding under a fixed - ratio 10 schedule for food. Modulators acting at GABA(A) receptors containing alpha(4)-delta subunits (pregnanolone, ethanol, and flumazenil) and receptors that do not contain those subunits (midazolam) were studied alone; pregnanolone and ethanol were also combined with gaboxadol. In addition, gaboxadol was studied in separate groups discriminating 0.32 mg/kg midazolam, 3.2 mg/kg pregnanolone, or 0.75 g/kg ethanol from vehicle.
   Results Gaboxadol produced >= 80 % gaboxadol-lever responding and did not alter rates. No other drug produced, on average, >= 80 % drug-lever responding up to doses that decreased rates, although 1.78 mg/kg midazolam produced 32 % gaboxadol-lever responding. Ethanol and pregnanolone did not enhance the effects of gaboxadol. Rats discriminating midazolam, pregnanolone, or ethanol from vehicle responded predominantly on the vehicle lever after receiving gaboxadol.
   Conclusions Drugs that modulate GABA(A) receptors containing alpha(4)-delta subunits neither mimicked nor enhanced the discriminative stimulus effects of gaboxadol, indicating that at least some effects of gaboxadol are not shared with modulators of that GABA(A) receptor subtype.
C1 [Zanettini, Claudio; Pressly, Jeffrey D.; Ibarra, Miguel H.; Smith, Kelsey R.; Gerak, Lisa R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA.
   [Zanettini, Claudio] NIDA, Medicat Dev Program, Mol Targets & Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD USA.
RP Gerak, LR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA.
EM gerak@uthscsa.edu
FU US Public Health Service Grant [DA017240]
FX These studies were supported by US Public Health Service Grant DA017240.
   The authors wish to thank T. Bentley, A. Hernandez, A. Mensah, and C.
   Moreno for their excellent technical assistance. This work is dedicated
   to the memory of Dr Steven R. Goldberg, a mentor and a friend.
NR 50
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U1 1
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PU SPRINGER
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PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2016
VL 233
IS 10
BP 2005
EP 2013
DI 10.1007/s00213-016-4243-8
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DK5RK
UT WOS:000374977400022
PM 26900079
ER

PT J
AU Callier, V
AF Callier, Viviane
TI Making the Most of School
SO SCIENTIST
LA English
DT Editorial Material
C1 [Callier, Viviane] Arizona State Univ, Tempe, AZ 85287 USA.
   [Callier, Viviane] NCI, Bethesda, MD 20892 USA.
   [Callier, Viviane] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Callier, V (reprint author), NCI, Bethesda, MD 20892 USA.; Callier, V (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LABX MEDIA GROUP
PI MIDLAND
PA PO BOX 216, 478 BAY ST, MIDLAND, ONTARIO L4R 1K9, CANADA
SN 0890-3670
EI 1547-0806
J9 SCIENTIST
JI Scientist
PD MAY
PY 2016
VL 30
IS 5
BP 63
EP 65
PG 3
WC Information Science & Library Science; Multidisciplinary Sciences
SC Information Science & Library Science; Science & Technology - Other
   Topics
GA DL0RO
UT WOS:000375340500018
ER

PT J
AU Spira, AP
   Gonzalez, CE
   Venkatraman, VK
   Wu, MN
   Pacheco, J
   Simonsick, EM
   Ferrucci, L
   Resnick, SM
AF Spira, Adam P.
   Gonzalez, Christopher E.
   Venkatraman, Vijay K.
   Wu, Mark N.
   Pacheco, Jennifer
   Simonsick, Eleanor M.
   Ferrucci, Luigi
   Resnick, Susan M.
TI Sleep Duration and Subsequent Cortical Thinning in Cognitively Normal
   Older Adults
SO SLEEP
LA English
DT Article
DE aging; atrophy; cortical thinning; gray matter; neuroimaging; sleep
   duration
ID LONGITUDINAL NEUROIMAGE DATA; MAGNETIC-RESONANCE IMAGES; CHRONIC PRIMARY
   INSOMNIA; HUMAN CEREBRAL-CORTEX; SURFACE RECONSTRUCTION; GEOMETRICALLY
   ACCURATE; HIPPOCAMPAL VOLUME; ALZHEIMERS-DISEASE; SLOW WAVES; BRAIN
AB Study Objectives: To determine the association between self-reported sleep duration and cortical thinning among older adults.
   Methods: We studied 122 cognitively normal participants in the Baltimore Longitudinal Study of Aging with a mean age = 66.6 y (range, 51-84) at baseline sleep assessment and 69.5 y (range, 56-86) at initial magnetic resonance imaging (MRI) scan. Participants reported average sleep duration and completed a mean of 7.6 1.5-T MRI scans (range, 3-11), with mean follow-up from initial scan of 8.0 y (range, 2.0-11.8).
   Results: In analyses adjusted for age, sex, education, race, and interval between sleep assessment and initial MRI scan, participants reporting > 7 h sleep at baseline had thinner cortex in the inferior occipital gyrus and sulcus of the left hemisphere at initial MRI scan than those reporting 7 h (cluster P < 0.05). In adjusted longitudinal analyses, compared to those reporting 7 h of sleep, participants reporting < 7 h exhibited higher rates of subsequent thinning in the superior temporal sulcus and gyrus, inferior and middle frontal gyrus, and superior frontal sulcus of the left hemisphere, and in the superior frontal gyrus of the right hemisphere; those reporting > 7 h of sleep had higher rates of thinning in the superior frontal and middle frontal gyrus of the left hemisphere (cluster P < 0.05 for all). In sensitivity analyses, adjustment for apolipoprotein E (APOE) e4 genotype reduced or eliminated some effects but revealed others. When reports of < 7 h of sleep were compared to reports of 7 or 8 h combined, there were no significant associations with cortical thinning.
   Conclusions: Among cognitively normal older adults, sleep durations of < 7 h and > 7 h may increase the rate of subsequent frontotemporal gray matter atrophy. Additional studies, including those that use objective sleep measures and investigate mechanisms linking sleep duration to gray matter loss, are needed.
C1 [Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
   [Spira, Adam P.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Gonzalez, Christopher E.; Venkatraman, Vijay K.; Pacheco, Jennifer; Simonsick, Eleanor M.; Ferrucci, Luigi; Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Wu, Mark N.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
   [Wu, Mark N.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Pacheco, Jennifer] NIMH, Off Director, NIH, Bethesda, MD 20892 USA.
RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Room 794, Baltimore, MD 21205 USA.
EM aspira@jhu.edu
FU Intramural Research Program (IRP), National Institute on Aging (NIA),
   National Institutes of Health (NIH); National Institute on Aging
   [1K01AG033195, 1R01AG050507]; William and Ella Owens Medical Research
   Foundation; Takeda; Roche; Pfizer; Lundbeck; Johnson Johnson;
   Intracellular; GE Healthcare; DART Neuroscience; Avid/Lilly; Piramal
   Imaging;  [HHSN-260-2004-00012C]
FX This study was supported in part by the Intramural Research Program
   (IRP), National Institute on Aging (NIA), National Institutes of Health
   (NIH) and by Research and Development Contract HHSN-260-2004-00012C. Dr.
   Spira was supported in part by 1K01AG033195 and by 1R01AG050507 from the
   National Institute on Aging and has received funding from the William
   and Ella Owens Medical Research Foundation. Investigators from the NIH,
   NIA, and IRP were involved in all aspects of this manuscript, including
   the design and conduct of the study; collection, management, analysis,
   and interpretation of the data; and preparation, review, or approval of
   the manuscript; and decision to submit the manuscript for publication.
   Dr. Resnick has an immediate family member who has received
   grant/research support from Takeda, Roche, Pfizer, Lundbeck, Johnson &
   Johnson, Intracellular, GE Healthcare, DART Neuroscience, Avid/Lilly,
   and Piramal Imaging. The other authors report no conflicts of interest.
   Results from this study were presented at the 2015 Annual Meeting of the
   Gerontological Society of America.
NR 54
TC 1
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U1 0
U2 2
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD MAY 1
PY 2016
VL 39
IS 5
BP 1121
EP 1128
AR PII sp-00308-15
DI 10.5665/sleep.5768
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DK8PE
UT WOS:000375188400020
PM 26951390
ER

PT J
AU Thorne, N
   Malik, N
   Shah, S
   Zhao, J
   Class, B
   Aguisanda, F
   Southall, N
   Xia, MH
   McKew, JC
   Rao, M
   Zheng, W
AF Thorne, Natasha
   Malik, Nasir
   Shah, Sonia
   Zhao, Jean
   Class, Bradley
   Aguisanda, Francis
   Southall, Noel
   Xia, Menghang
   McKew, John C.
   Rao, Mahendra
   Zheng, Wei
TI High-Throughput Phenotypic Screening of Human Astrocytes to Identify
   Compounds That Protect Against Oxidative Stress
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Astrocytes; Neurodegenerative disease; High-throughput screening;
   Oxidative stress; Stem cells
ID PLURIPOTENT STEM-CELLS; FACTOR-KAPPA-B; ANTIOXIDANT RESPONSE; SIGNALING
   PATHWAY; INDUCED APOPTOSIS; PYRROLIDINE DITHIOCARBAMATE;
   NEURODEGENERATIVE DISEASES; NEUROLOGICAL DISEASE; CORTICAL ASTROCYTES;
   NEURONAL DAMAGE
AB Astrocytes are the predominant cell type in the nervous system and play a significant role in maintaining neuronal health and homeostasis. Recently, astrocyte dysfunction has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an attractive new target for drug discovery for neurological disorders. Using astrocytes differentiated from human embryonic stem cells, we have developed an assay to identify compounds that protect against oxidative stress, a condition associated with many neurodegenerative diseases. This phenotypic oxidative stress assay has been optimized for high-throughput screening in a 1,536-well plate format. From a screen of approximately 4,100 bloactive tool compounds and approved drugs, we identified a set of 22 that acutely protect human astrocytes from the consequences of hydrogen peroxide-induced oxidative stress. Nine of these compounds were also found to be protective of induced pluripotent stem cell-differentiated astrocytes in a related assay. These compounds are thought to confer protection through hormesis, activating stress-response pathways and preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In fact, four of these compounds were found to activate the antioxidant response element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced by toxic insults. Our results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development.
C1 [Thorne, Natasha; Zhao, Jean; Class, Bradley; Aguisanda, Francis; Southall, Noel; Xia, Menghang; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
   [Malik, Nasir; Shah, Sonia] NIAMSD, Lab Stem Cell Biol, NIH, Bethesda, MD 20892 USA.
   [Rao, Mahendra] NIH, Ctr Regenerat Med, Bldg 10, Bethesda, MD 20892 USA.
RP Thorne, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 66,Room 5551, Silver Spring, MD 20993 USA.; Zheng, W (reprint author), NIH, NCATS, 9800 Med Ctr Dr,MSC 3375, Bethesda, MD 20892 USA.
EM Natasha.Thorne@fda.hhs.gov; wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU NIH Common Fund; Intramural Research Program of the Therapeutics for
   Rare and Neglected Diseases/NIH Center for Advancing Translational
   Sciences; Center for Regenerative Medicine/National Institute of
   Arthritis, Musculoskeletal and Skin Diseases, NIH
FX We thank Steve Titus for expert guidance in analyzing data acquired by
   the InCell2000, Eric Jones for his assistance with robotics used for
   screening and immunostaining in 1536-well plate format, and Paul Shinn
   for generating follow-up compound plates. This work was supported by the
   NIH Common Fund and the Intramural Research Program of the Therapeutics
   for Rare and Neglected Diseases/NIH Center for Advancing Translational
   Sciences and the Center for Regenerative Medicine/National Institute of
   Arthritis, Musculoskeletal and Skin Diseases, NIH.
NR 97
TC 1
Z9 1
U1 12
U2 29
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD MAY
PY 2016
VL 5
IS 5
BP 613
EP 627
DI 10.5966/sctm.2015-0170
PG 15
WC Cell & Tissue Engineering
SC Cell Biology
GA DK8KS
UT WOS:000375176200011
PM 27034412
ER

PT J
AU Warach, SJ
   Luby, M
   Albers, GW
   Bammer, R
   Bivard, A
   Campbell, BCV
   Derdeyn, C
   Heit, JJ
   Khatri, P
   Lansberg, MG
   Liebeskind, DS
   Majoie, CBLM
   Marks, MP
   Menon, BK
   Muir, KW
   Parsons, MW
   Vagal, A
   Yoo, AJ
   Alexandrov, AV
   Baron, JC
   Fiorella, DJ
   Furlan, AJ
   Puig, J
   Schellinger, PD
   Wintermark, M
AF Warach, Steven J.
   Luby, Marie
   Albers, Gregory W.
   Bammer, Roland
   Bivard, Andrew
   Campbell, Bruce C. V.
   Derdeyn, Colin
   Heit, Jeremy J.
   Khatri, Pooja
   Lansberg, Maarten G.
   Liebeskind, David S.
   Majoie, Charles B. L. M.
   Marks, Michael P.
   Menon, Bijoy K.
   Muir, Keith W.
   Parsons, Mark W.
   Vagal, Achala
   Yoo, Albert J.
   Alexandrov, Andrei V.
   Baron, Jean-Claude
   Fiorella, David J.
   Furlan, Anthony J.
   Puig, Josep
   Schellinger, Peter D.
   Wintermark, Max
CA Stroke Imaging Res STIR Investigat
   VISTA-Imaging Investigator
TI Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes
   in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations
   and Further Research Priorities
SO STROKE
LA English
DT Article
DE angiography; clinical trial; ischemia; reperfusion; stroke
ID ACUTE ISCHEMIC-STROKE; INTRAVENOUS T-PA; ENDOVASCULAR TREATMENT;
   RECANALIZATION; THROMBECTOMY; THERAPY; PREDICTION
AB Background and Purpose-The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.
   Methods-This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.
   Results-The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.
   Conclusions-Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.
C1 [Warach, Steven J.] Univ Texas Austin, Dell Med Sch, Dept Neurol, Austin, TX 78712 USA.
   [Luby, Marie] NINDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
   [Albers, Gregory W.; Lansberg, Maarten G.] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Bammer, Roland] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA.
   [Heit, Jeremy J.; Marks, Michael P.; Wintermark, Max] Stanford Univ, Sch Med, Dept Radiol, Neuroradiol Sect, Stanford, CA 94305 USA.
   [Bivard, Andrew; Parsons, Mark W.] Univ Newcastle, Hunter Med Res Inst, John Hunter Hosp, Dept Neurol, Callaghan, NSW 2308, Australia.
   [Campbell, Bruce C. V.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Med, Parkville, Vic, Australia.
   [Campbell, Bruce C. V.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Neurol, Parkville, Vic, Australia.
   [Derdeyn, Colin] Univ Iowa Hosp & Clin, Dept Radiol, Iowa City, IA 52242 USA.
   [Khatri, Pooja] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA.
   [Vagal, Achala] Univ Cincinnati, Dept Neuroadiol, Cincinnati, OH 45221 USA.
   [Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, Neurovasc Imaging Res Core, Los Angeles, CA 90024 USA.
   [Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, UCLA Stroke Ctr, Los Angeles, CA 90024 USA.
   [Majoie, Charles B. L. M.] AMC, Dept Radiol, Amsterdam, Netherlands.
   [Menon, Bijoy K.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
   [Menon, Bijoy K.] Univ Calgary, Hotchkiss Brain Inst, Dept Radiol, Calgary, AB, Canada.
   [Muir, Keith W.] Univ Glasgow, So Gen Hosp, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland.
   [Yoo, Albert J.] Texas Stroke Inst, Plano, TX USA.
   [Alexandrov, Andrei V.] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN USA.
   [Baron, Jean-Claude] Sorbonne Paris Cite, Ctr Hosp St Anne, INSERM, U894, Paris, France.
   [Baron, Jean-Claude] Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
   [Fiorella, David J.] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY USA.
   [Furlan, Anthony J.] Univ Hosp Cleveland, Dept Neurol, Case Med Ctr, 2074 Abington Rd, Cleveland, OH 44106 USA.
   [Furlan, Anthony J.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Puig, Josep] Hosp Josep Trueta, Dept Radiol, Girona, Spain.
   [Schellinger, Peter D.] Johannes Wesling Klinikum Minden, Dept Neurol & Geriatr, Minden, Germany.
RP Wintermark, M (reprint author), Stanford Univ, Dept Radiol, Neuroradiol Div, 300 Pasteur Dr,Room S047, Stanford, CA 94305 USA.
EM Max.Wintermark@gmail.com
RI Thijs, Vincent/C-3647-2009; 
OI Thijs, Vincent/0000-0002-6614-8417; Derdeyn, Colin/0000-0002-5932-2683;
   baron, jean-claude/0000-0002-5264-2588
FU Stroke Imaging Research (STIR) group; Virtual International Stroke
   Trials Archive (VISTA); American Society of Neuroradiology (ASNR);
   Foundation of the American Society of Neuroradiology; NIH [RO1 EB002711,
   NS086872]; National Institutes of Health (NIH)- National Institute of
   Neurological Disorders and Stroke grant [K24NS072272]; GE-NFL
FX This article, and the efforts that led to it, were supported by the
   Stroke Imaging Research (STIR) group, by Virtual International Stroke
   Trials Archive (VISTA), by the American Society of Neuroradiology (ASNR)
   and the Foundation of the American Society of Neuroradiology, as well as
   by generous donations from General Electric Healthcare, Siemens
   Healthcare, Bayer, and Toshiba Medical Systems. Additional sources of
   funding included Dr Bammer-NIH RO1 EB002711, Dr Derdeyn-NIH NS086872, Dr
   Liebeskind-National Institutes of Health (NIH)- National Institute of
   Neurological Disorders and Stroke grant: K24NS072272, and Dr
   Wintermark-GE-NFL advisory board for TBI.
NR 28
TC 4
Z9 4
U1 5
U2 9
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 MAY
PY 2016
VL 47
IS 5
BP 1389
EP 1398
DI 10.1161/STROKEAHA.115.012364
PG 10
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DK6QM
UT WOS:000375049700044
PM 27073243
ER

PT J
AU Shin, YW
   Choi, YM
   Kim, HS
   Kim, DJ
   Jo, HJ
   O'Donnell, BF
   Jang, EK
   Kim, TY
   Shong, YK
   Hong, JP
   Kim, WB
AF Shin, Yong-Wook
   Choi, Yun Mi
   Kim, Ho Sung
   Kim, Dae-Jin
   Jo, Hang Joon
   O'Donnell, Brian F.
   Jang, Eun Kyung
   Kim, Tae Yong
   Shong, Young Kee
   Hong, Jin Pyo
   Kim, Won Bae
TI Diminished Quality of Life and Increased Brain Functional Connectivity
   in Patients with Hypothyroidism After Total Thyroidectomy
SO THYROID
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; REGIONAL HOMOGENEITY; RAT-BRAIN;
   CARDIOVASCULAR-SYSTEM; REPLACEMENT THERAPY; GLUCOSE-METABOLISM; FMRI;
   HORMONE; DEPRESSION; CORTEX
AB Background: Acute hypothyroidism induced by thyroid hormone withdrawal (THW) in patients with thyroid cancer after total thyroidectomy can affect mood and quality of life (QoL). While loss or dysregulation of thyroid hormone (TH) has these well-known behavioral consequences, the effects of TH alterations on brain function are not well understood. Resting state functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI) allows non-invasive evaluation of human brain function. This study therefore examined whether THW affects resting state FC and whether changes in FC correlate with the mood or QoL of the patients with THW status.
   Methods: Twenty-one patients who had undergone total thyroidectomy for thyroid cancer were recruited. Resting state fMRI scanning of the brain, thyroid function tests, and administration of the 12-Item Short Form Health Survey (SF-12) and the Patient Health Questionnaire-9 (PHQ-9) were performed before and after two weeks of THW. Regional homogeneity (ReHo), one of the measures of resting state FC, was calculated, and each voxel was compared between before and after THW in 19 patients. The ReHo values were extracted from the regions of interest showing within-group differences in ReHo values after THW, and correlations of ReHo values with thyrotropin (TSH) levels, total score of the PHQ-9, and composite scores of the SF-12 were statistically evaluated.
   Results: Higher ReHo was observed after THW in the brain cortical regions across primary motor and sensory, visual, and association cortices. Among the regions, the ReHo values in the bilateral pre- and postcentral gyri, bilateral middle occipito-temporal cortices, the left precuneus, and the left lingual gyrus showed positive correlations with serum TSH levels after THW. Higher ReHo values in the bilateral pre- and postcentral gyri, the left middle temporo-occipital cortices, and the left ligual gyrus correlated with the lower mental component summary score from the SF-12, while higher ReHo values in the bilateral pre- and postcentral gyri correlated with higher total scores in the PHQ-9.
   Conclusions: Local brain FC is increased in the acute hypothyroid state. Higher FC correlates with a poorer mental QoL and increased depression in the hypothyroid state.
C1 [Shin, Yong-Wook] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Seoul, South Korea.
   [Choi, Yun Mi; Jang, Eun Kyung; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae] Univ Ulsan, Coll Med, Asan Med Ctr, Internal Med, Seoul, South Korea.
   [Kim, Ho Sung] Univ Ulsan, Coll Med, Asan Med Ctr, Radiol, Seoul, South Korea.
   [Kim, Dae-Jin; O'Donnell, Brian F.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
   [Jo, Hang Joon] NIMH, NIH, Sci & Stat Comp Core, Bethesda, MD 20892 USA.
   [Hong, Jin Pyo] Sungkyunkwan Univ, Sch Med, Dept Psychiat, Samsung Med Ctr, Seoul, South Korea.
RP Kim, WB (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Internal Med, 88 Olymp Ro,43-Gil, Seoul 05505, South Korea.; Hong, JP (reprint author), Sungkyunkwan Univ, Sch Med, Dept Psychiat, Samsung Med Ctr, 81 Irwon Ro, Seoul 06351, South Korea.
EM suhurhong@gmail.com; kimwb@amc.seoul.kr
RI Kim, Tae Yong/C-1272-2009; 
OI Kim, Tae Yong/0000-0003-4982-4441; Shin, Yong-Wook/0000-0002-0360-6118;
   Shong, Young Kee/0000-0002-7911-9471; Jo, Hang Joon/0000-0002-9180-3831
FU Genzyme Korea Co. Ltd., Seoul, Korea [GZ-RES12-RF003]
FX This study was supported by a Research Grant (# GZ-RES12-RF003) from
   Genzyme Korea Co. Ltd., Seoul, Korea. The funders had no role in study
   design, data collection and analysis, or preparation of the manuscript.
NR 68
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Z9 1
U1 2
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD MAY
PY 2016
VL 26
IS 5
BP 641
EP 649
DI 10.1089/thy.2015.0452
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK7RN
UT WOS:000375123500005
PM 26976233
ER

PT J
AU Sanders, JM
   Coulter, SJ
   Knudsen, GA
   Dunnick, JK
   Kissling, GE
   Birnbaum, LS
AF Sanders, J. Michael
   Coulter, Sherry J.
   Knudsen, Gabriel A.
   Dunnick, June K.
   Kissling, Grace E.
   Birnbaum, Linda S.
TI Disruption of estrogen homeostasis as a mechanism for uterine toxicity
   in Wistar Han rats treated with tetrabromobisphenol A
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Tetrabromobisphenol A; TBBPA; Uterine toxicity; Rats; Gene expression;
   Estrogen homeostasis
ID BROMINATED FLAME RETARDANTS; IN-VITRO; BISPHENOL-A; RECEPTOR-ALPHA;
   METABOLISM; ENDOMETRIAL; EXPRESSION; EXPOSURE; DISPOSITION; ACTIVATION
AB Chronic oral treatment of tetrabromobisphenol A (TBBPA) to female Wistar Han rats resulted in increased incidence of cell proliferation at 250 mg/kg and tumor formation in the uterus at higher doses. The present study was designed to test the hypothesis that disruption of estrogen homeostasis was a major mode-of-action for the observed effects. Biological changes were assessed in serum, liver, and the proximal (nearest the cervix) and distal (nearest the ovaries) sections of the uterine horn of Wistar Han rats 24 h following administration of the last of five daily oral doses of 250 mg/kg. Expression of genes associated with receptors, biosynthesis, and metabolism of estrogen was altered in the liver and uterus. TBBPA treatment also resulted in changes in expression of genes associated with cell division and growth. Changes were also observed in the concentration of thyroxine in serum and in expression of genes in the liver and uterus associated with thyroid hormone receptors. Differential expression of some genes was tissue-dependent or specific to tissue location in the uterus. The biological responses observed in the present study support the hypothesis that perturbation of estrogen homeostasis is a major mode-of-action for TBBPA-mediated cell proliferation and tumorigenesis previously observed in the uterus of TBBPA-treated Wistar Han rats. Published by Elsevier Inc.
C1 [Sanders, J. Michael; Coulter, Sherry J.; Knudsen, Gabriel A.; Birnbaum, Linda S.] NIEHS, Lab Toxicol & Toxicokinet, NCI, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Dunnick, June K.; Kissling, Grace E.] NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Sanders, JM (reprint author), NIEHS, POB 12233,Maildrop C2-02, Res Triangle Pk, NC 27709 USA.
EM sander10@mail.nih.gov
OI Coulter, Sherry/0000-0002-2732-3470
FU Intramural Research Program of the National Cancer Institute of the
   National Institutes of Health [ZIA BC 011476]
FX The authors thank Mr. Ralph Wilson (NIEHS) for serum analysis. This work
   was supported by the Intramural Research Program of the National Cancer
   Institute of the National Institutes of Health [Project: ZIA BC 011476].
NR 49
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Z9 2
U1 6
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAY 1
PY 2016
VL 298
BP 31
EP 39
DI 10.1016/j.taap.2016.03.007
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DJ7YN
UT WOS:000374429200004
PM 26988606
ER

PT J
AU Chertow, DS
   Kindrachuk, J
   Sheng, ZM
   Pujanauski, LM
   Cooper, K
   Nogee, D
   St Claire, M
   Solomon, J
   Perry, D
   Sayre, P
   Janosko, KB
   Lackemeyer, MG
   Bohannon, JK
   Kash, JC
   Jahrling, PB
   Taubenberger, JK
AF Chertow, Daniel S.
   Kindrachuk, Jason
   Sheng, Zong-Mei
   Pujanauski, Lindsey M.
   Cooper, Kurt
   Nogee, Daniel
   St Claire, Marisa
   Solomon, Jeffrey
   Perry, Donna
   Sayre, Philip
   Janosko, Krisztina B.
   Lackemeyer, Matthew G.
   Bohannon, Jordan K.
   Kash, John C.
   Jahrling, Peter B.
   Taubenberger, Jeffery K.
TI Influenza A and methicillin-resistant Staphylococcus aureus co-infection
   in rhesus macaques - A model of severe pneumonia
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Influenza; Co-infection; Pneumonia; Vaccines; Therapies
ID RESPIRATORY-TRACT INFECTION; BACTERIAL COINFECTION; PANDEMIC INFLUENZA;
   NONHUMAN-PRIMATES; AVIAN INFLUENZA; UNITED-STATES; VIRUS
AB Background: Influenza results in up to 500,000 deaths annually. Seasonal influenza vaccines have an estimated 60% effectiveness, but provide little or no protection against novel subtypes, and may be less protective in high-risk groups. Neuraminidase inhibitors are recommended for the treatment of severe influenza infection, but are not proven to reduce mortality in severe disease. Preclinical models of severe influenza infection that closely correlate to human disease are needed to assess efficacy of new vaccines and therapeutics.
   Methods: We developed a nonhuman primate model of influenza and bacterial co-infection that recapitulates severe pneumonia in humans. Animals were infected with influenza A virus via intrabronchial or small-particle aerosol inoculation, methicillin-resistant Staphylococcus aureus, or co infected with influenza and methicillin-resistant S. aureus combined. We assessed the severity of disease in animals over the course of our study using tools available to evaluate critically ill human patients including high-resolution computed tomography imaging of the lungs, arterial blood gas analyses, and bronchoalveolar lavage.
   Results: Using an intra-bronchial route of inoculation we successfully induced severe pneumonia following influenza infection alone and following influenza and bacterial co-infection. Peak illness was observed at day 6 post-influenza infection, manifested by bilateral pulmonary infiltrates and hypoxemia. The timing of radiographic and physiologic manifestations of disease in our model closely match those observed in severe human influenza infection.
   Discussion: This was the first nonhuman primate study of influenza and bacterial co-infection where high-resolution computed tomography scanning of the lungs was used to quantitatively assess pneumonia over the course of illness and where hypoxemia was correlated with pneumonia severity. With additional validation this model may serve as a pathway for regulatory approval of vaccines and therapeutics for the prevention and treatment of severe influenza pneumonia. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
C1 [Chertow, Daniel S.; Kindrachuk, Jason; Nogee, Daniel] NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C-145, Bethesda, MD 20892 USA.
   [Kindrachuk, Jason; Cooper, Kurt; St Claire, Marisa; Perry, Donna; Sayre, Philip; Janosko, Krisztina B.; Lackemeyer, Matthew G.; Bohannon, Jordan K.; Jahrling, Peter B.] NIH, Integrated Res Facil Frederick, Frederick, MD USA.
   [Chertow, Daniel S.; Sheng, Zong-Mei; Pujanauski, Lindsey M.; Nogee, Daniel; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Solomon, Jeffrey] NIH, Ctr Infect Dis Imaging, RAD&IS, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
RP Chertow, DS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C-145, Bethesda, MD 20892 USA.
EM chertowd@cc.nih.gov
OI Cooper, Kurt/0000-0003-2941-8008; Kindrachuk, Jason/0000-0002-3305-7084;
   Pujanandez, Lindsey/0000-0002-2982-3700
FU Intramural Research Program of NIAID, NIH; Battelle Memorial Institute's
   prime contract with NIAID [HHSN272200700016I]
FX The Intramural Research Program of NIAID, NIH supported this work. We
   are grateful to Lisa E. Hensley, Russell Byrum, Dan Ragland, Dawn
   Traynor, Catherine Jett and the entire IRF team for their contributions
   to these studies. The content of this publication does not necessarily
   reflect the views or policies of the US Department of Health and Human
   Services (DHHS) or of the institutions and companies affiliated with the
   authors. This work was funded in part through Battelle Memorial
   Institute's prime contract with NIAID under Contract no.
   HHSN272200700016I. J.K.B. and K.B.J. performed this work as employees of
   Battelle Memorial Institute. Subcontractors to Battelle Memorial
   Institute who performed this work are: M.G.L., an employee of Lovelace
   Respiratory Research Institute; and P.S., an employee of MEDRelief.
NR 21
TC 0
Z9 0
U1 2
U2 6
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 MAY
PY 2016
VL 129
BP 120
EP 129
DI 10.1016/j.antiviral.2016.02.013
PG 10
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA DK0PH
UT WOS:000374614200015
PM 26923881
ER

PT J
AU Gao, ZG
   Jacobson, KA
AF Gao, Zhan-Guo
   Jacobson, Kenneth A.
TI On the selectivity of the G alpha(q) inhibitor UBO-QIC: A comparison
   with the G alpha(i) inhibitor pertussis toxin
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE G protein; G alpha(q) inhibitor; GPCR; GB gamma subunits; FR900359;
   UBO-QIC
ID BETA-GAMMA-SUBUNITS; HETEROTRIMERIC G-PROTEINS; ADENOSINE RECEPTOR;
   PHOSPHOLIPASE-C; CELLS; ACTIVATION; STIMULATION; PHOSPHORYLATION;
   MOBILIZATION; ARRESTINS
AB G alpha(q) inhibitor UBO-QIC (FR900359) is becoming an important pharmacological tool, but its selectivity against other G proteins and their subunits, especially beta gamma, has not been well characterized. We examined UBO-QIC's effect on diverse signaling pathways mediated via various G protein-coupled receptors (GPCRs) and G protein subunits by comparison with known Got; inhibitor pertussis toxin. As expected, UBO-QIC inhibited G alpha(q), signaling in all assay systems examined. However, other non-G alpha(q)-events, e.g. G beta gamma-mediated intracellular calcium release and inositol phosphate production, following activation of G(1)-coupled A(1) adenosine and M-2 muscarinic acetylcholine receptors, were also blocked by low concentrations of UBO-QIC, indicating that its effect is not limited to Gag. Thus, UBO-QIC also inhibits G beta gamma-mediated signaling similarly to pertussis toxin, although UBO-QIC does not affect G alpha(i)-mediated inhibition or G alpha(s)-mediated stimulation of adenylyl cyclase activity. However, the blockade by UBO-QIC of GPCR signaling, such as carbachol- or adenosine-mediated calcium or inositol phosphate increases, does not always indicate inhibition of G alpha(q)-mediated events, as the beta gamma subunits released from G(i) proteins following the activation of G(i)-coupled receptors, e.g. M-2 and A(1)Rs, may produce similar signaling events. Furthermore, UBO-QIC completely inhibited Akt signaling, but only partially blocked ERK1/2 activity stimulated by the Gq-coupled P2Y(1)R. Thus, we have revealed new aspects of the pharmacological interactions of UBO-QIC. Published by Elsevier Inc.
C1 [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Gao, ZG; Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zg21o@nih.gov; kennethj@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, National Institutes of Health, Bethesda,
   MD
FX Supported by the Intramural Research Program of the National Institute
   of Diabetes and Digestive and Kidney Diseases, National Institutes of
   Health, Bethesda, MD. We thank Jianxin Hu and Jurgen Wess (NIDDK,
   Bethesda, MD) for helpful discussions and supplying cell lines. We thank
   T.K. Harden (Univ. of North Carolina, Chapel Hill, NC) for cell lines.
NR 38
TC 1
Z9 1
U1 4
U2 5
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 MAY 1
PY 2016
VL 107
BP 59
EP 66
DI 10.1016/j.bcp.2016.03.003
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DK0SG
UT WOS:000374621900005
PM 26954502
ER

PT J
AU Murphy, MP
   Corriveau, RA
   Wilcock, DM
AF Murphy, M. Paul
   Corriveau, Roderick A.
   Wilcock, Donna M.
TI Vascular contributions to cognitive impairment and dementia (VCID)
   Preface
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Editorial Material
ID ALZHEIMERS-DISEASE; NUN
C1 [Murphy, M. Paul] Univ Kentucky, Dept Mol & Cellular Biochem, 800 South Limestone St, Lexington, KY USA.
   [Murphy, M. Paul] Univ Kentucky, Sanders Brown Ctr Aging, 800 South Limestone St, Lexington, KY USA.
   [Corriveau, Roderick A.] NIH, Div Extramural Res, NINDS, Neurosci Ctr, Room 2153,6001 Execut Blvd,MSC 9525, Bethesda, MD USA.
   [Wilcock, Donna M.] Univ Kentucky, Dept Physiol, 800 South Limestone St, Lexington, KY USA.
   [Wilcock, Donna M.] Univ Kentucky, Sanders Rown Ctr Aging, 800 South Limestone St, Lexington, KY USA.
RP Murphy, MP (reprint author), Univ Kentucky, Dept Mol & Cellular Biochem, 800 South Limestone St, Lexington, KY USA.; Murphy, MP (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, 800 South Limestone St, Lexington, KY USA.
EM mpmurp3@email.uky.edu
RI Wilcock, Donna/J-7517-2016
NR 31
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 0006-3002
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD MAY
PY 2016
VL 1862
IS 5
SI SI
BP 857
EP 859
DI 10.1016/j.bbadis.2016.02.010
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DK0NJ
UT WOS:000374609200001
PM 26921818
ER

PT J
AU Dong, J
   Li, S
   Mo, JL
   Cai, HB
   Le, WD
AF Dong, Jie
   Li, Song
   Mo, Jing-Lin
   Cai, Huai-Bin
   Le, Wei-Dong
TI Nurr1-Based Therapies for Parkinson's Disease
SO CNS NEUROSCIENCE & THERAPEUTICS
LA English
DT Review
DE Inflammation; Neuroprotection; Nurr1; Parkinson's disease; Treatment
ID NUCLEAR RECEPTOR NURR1; NEURAL STEM-CELLS; PROTEIN-KINASE-A;
   MESENCEPHALIC DOPAMINERGIC-NEURONS; PANCREATIC-CANCER CELLS;
   LIGAND-BINDING DOMAIN; NERVE GROWTH-FACTOR; ALPHA-SYNUCLEIN;
   GENE-EXPRESSION; NEUROTROPHIC FACTOR
AB Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR4A2) plays important roles in the midbrain dopamine (DA) neuron development, differentiation, and survival. Furthermore, it has been reported that the defects in Nurr1 are associated with Parkinson's disease (PD). Thus, Nurr1 might be a potential therapeutic target for PD. Emerging evidence from in vitro and in vivo studies has recently demonstrated that Nurr1-activating compounds and Nurr1 gene therapy are able not only to enhance DA neurotransmission but also to protect DA neurons from cell injury induced by environmental toxin or microglia-mediated neuroinflammation. Moreover, modulators that interact with Nurr1 or regulate its function, such as retinoid X receptor, cyclic AMP-responsive element-binding protein, glial cell line-derived neurotrophic factor, and Wnt/-catenin pathway, have the potential to enhance the effects of Nurr1-based therapies in PD. This review highlights the recent progress in preclinical studies of Nurr1-based therapies and discusses the outlook of this emerging therapy as a promising new generation of PD medication.
C1 [Dong, Jie; Li, Song; Mo, Jing-Lin; Le, Wei-Dong] Dalian Med Univ, Affiliated Hosp 1, Ctr Translat Res Neurol Dis, Dalian 116021, Peoples R China.
   [Cai, Huai-Bin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Le, Wei-Dong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China.
RP Le, WD (reprint author), Dalian Med Univ, Affiliated Hosp 1, Dalian 116021, Peoples R China.
EM wdle@sibs.ac.cn
RI Li, Song/C-6701-2014
OI Li, Song/0000-0003-2713-9136
FU Chinese National Sciences Foundation [81370470, 81430021]; Collaborative
   Innovation Center for Brain Science; Program for Liaoning Innovative
   Research Team in University [LT2015009]; NIA [AG000928]
FX The authors are supported in part by Chinese National Sciences
   Foundation (NO. 81370470 and 81430021), the Collaborative Innovation
   Center for Brain Science, the Program for Liaoning Innovative Research
   Team in University (LT2015009), and the intramural research program of
   NIA (AG000928).
NR 120
TC 3
Z9 4
U1 5
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-5930
EI 1755-5949
J9 CNS NEUROSCI THER
JI CNS Neurosci. Ther.
PD MAY
PY 2016
VL 22
IS 5
BP 351
EP 359
DI 10.1111/cns.12536
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DJ7FP
UT WOS:000374377600003
PM 27012974
ER

PT J
AU Huang, MX
   Parker, AM
   Bienvenu, OJ
   Dinglas, VD
   Colantuoni, E
   Hopkins, RO
   Needham, DM
AF Huang, Minxuan
   Parker, Ann M.
   Bienvenu, O. Joseph
   Dinglas, Victor D.
   Colantuoni, Elizabeth
   Hopkins, Ramona O.
   Needham, Dale M.
TI Psychiatric Symptoms in Acute Respiratory Distress Syndrome Survivors: A
   1-Year National Multicenter Study
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE anxiety; critical illness; depression; posttraumatic; stress disorder;
   prospective studies
ID POSTTRAUMATIC-STRESS-DISORDER; ACUTE LUNG INJURY; GENERAL
   INTENSIVE-CARE; QUALITY-OF-LIFE; ALCOHOL-USE DISORDERS; CRITICAL
   ILLNESS; RISK-FACTORS; MECHANICAL VENTILATION; ANXIETY DISORDERS; UNIT
   SURVIVORS
AB Objective: To evaluate prevalence, severity, and co-occurrence of and risk factors for depression, anxiety, and posttraumatic stress disorder symptoms over the first year after acute respiratory distress syndrome.
   Design: Prospective longitudinal cohort study.
   Settings: Forty-one Acute Respiratory Distress Syndrome Network hospitals across the United States.
   Patients: Six hundred ninety-eight acute respiratory distress syndrome survivors.
   Interventions: None.
   Measurements and Main Results: Psychiatric symptoms were evaluated by using the Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised at 6 and 12 months. Adjusted prevalence ratios for substantial symptoms (binary outcome) and severity scores were calculated by using Poisson and linear regression, respectively. During 12 months, a total of 416 of 629 patients (66%) with at least one psychiatric outcome measure had substantial symptoms in at least one domain. There was a high and almost identical prevalence of substantial symptoms (36%, 42%, and 24% for depression, anxiety, and posttraumatic stress disorder) at 6 and 12 months. The most common pattern of co-occurrence was having symptoms of all three psychiatric domains simultaneously. Younger age, female sex, unemployment, alcohol misuse, and greater opioid use in the ICU were significantly associated with psychiatric symptoms, whereas greater severity of illness and ICU length of stay were not associated.
   Conclusions: Psychiatric symptoms occurred in two thirds of acute respiratory distress syndrome survivors with frequent co-occurrence. Sociodemographic characteristics and in-ICU opioid administration, rather than traditional measures of critical illness severity, should be considered in identifying the patients at highest risk for psychiatric symptoms during recovery. Given high co-occurrence, acute respiratory distress syndrome survivors should be simultaneously evaluated for a full spectrum of psychiatric sequelae to maximize recovery.
C1 [Huang, Minxuan; Parker, Ann M.; Bienvenu, O. Joseph; Dinglas, Victor D.; Colantuoni, Elizabeth; Hopkins, Ramona O.; Needham, Dale M.] NHLBI, NIH, Acute Resp Distress Syndrome Network, Bethesda, MD 20892 USA.
   [Huang, Minxuan; Parker, Ann M.; Bienvenu, O. Joseph; Dinglas, Victor D.; Colantuoni, Elizabeth; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA.
   [Huang, Minxuan; Parker, Ann M.; Dinglas, Victor D.; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
   [Bienvenu, O. Joseph] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Colantuoni, Elizabeth] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
   [Hopkins, Ramona O.] Intermt Med Ctr, Dept Med, Div Pulm & Crit Care, Murray, UT USA.
   [Hopkins, Ramona O.] Intermt Healthcare, Ctr Humanizing Crit Care, Murray, UT USA.
   [Hopkins, Ramona O.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
   [Hopkins, Ramona O.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA.
   [Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA.
RP Needham, DM (reprint author), NHLBI, NIH, Acute Resp Distress Syndrome Network, Bethesda, MD 20892 USA.; Needham, DM (reprint author), Johns Hopkins Univ, Sch Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA.; Needham, DM (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.; Needham, DM (reprint author), Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA.
EM dale.needham@jhmi.edu
FU National Heart, Lung, and Blood Institute [N01HR56170, R01HL091760,
   3R01HL091760-02S1]; Albuterol for the Treatment of ALI and Early vs.
   Delayed Enteral Nutrition trials [HHSN268200536165C, HHSN268200536166C,
   HHSN268200536167C, HHSN268200536168C, HHSN268200536169C,
   HHSN268200536170C, HHSN268200536171C, HHSN268200536172C]; 
   [5T32HL00753432];  [HHSN268200536173C];  [HHSN268200536174C]; 
   [HHSN268200536175C];  [HHSN268200536176C];  [HHSN268200536177C]; 
   [HHSN268200536178C];  [HHSN268200536179C]
FX National Heart, Lung, and Blood Institute funded this follow-up study
   (grants N01HR56170, R01HL091760, and 3R01HL091760-02S1) and the
   Albuterol for the Treatment of ALI and Early vs. Delayed Enteral
   Nutrition trials (contracts HHSN268200536165C to HHSN268200536175C and
   HHSN268200536179C) as well as provided support via grant 5T32HL00753432.
NR 50
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Z9 6
U1 0
U2 3
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 MAY
PY 2016
VL 44
IS 5
BP 954
EP 965
DI 10.1097/CCM.0000000000001621
PG 12
WC Critical Care Medicine
SC General & Internal Medicine
GA DJ7BF
UT WOS:000374366200013
PM 26807686
ER

PT J
AU Gerstein, HC
   Beavers, DP
   Bertoni, AG
   Bigger, JT
   Buse, JB
   Craven, TE
   Cushman, WC
   Fonseca, V
   Geller, NL
   Giddings, SJ
   Grimm, RH
   Genuth, S
   Hramiak, I
   Ismail-Beigi, F
   Jimenez, CRL
   Kirby, R
   Probstfield, J
   Riddle, MC
   Seaquist, ER
   Friedewald, WT
AF Gerstein, Hertzel C.
   Beavers, Daniel P.
   Bertoni, Alain G.
   Bigger, J. Thomas
   Buse, John B.
   Craven, Timothy E.
   Cushman, William C.
   Fonseca, Vivian
   Geller, Nancy L.
   Giddings, Stephen J.
   Grimm, Richard H., Jr.
   Genuth, Saul
   Hramiak, Irene
   Ismail-Beigi, Faramarz
   Jimenez, Carlos R. Lopez
   Kirby, Ruth
   Probstfield, Jeffrey
   Riddle, Matthew C.
   Seaquist, Elizabeth R.
   Friedewald, William T.
CA ACCORD Study Grp
TI Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on
   Cardiovascular Outcomes
SO DIABETES CARE
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; ACCORD TRIAL; GLUCOSE CONTROL; FOLLOW-UP;
   MORTALITY; METAANALYSIS; RISK
AB OBJECTIVE
   In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, similar to 4 years of intensive versus standard glycemic control in participants with type 2 diabetes and other cardiovascular risk factors had a neutral effect on the composite cardiovascular outcome, increased cardiovascular and total mortality, and reduced nonfatal myocardial infarction. Effects of the intervention during prolonged follow-up were analyzed.
   RESEARCH DESIGN AND METHODS
   All surviving ACCORD participants were invited to participate in the ACCORD Follow-on (ACCORDION) study, during which participants were treated according to their health care provider's judgment. Cardiovascular and other health-related outcomes were prospectively collected and analyzed using an intention-to-treat approach according to the group to which participants were originally allocated.
   RESULTS
   A total of 8,601 people, representing 98% of those who did not suffer a primary outcome or death during the ACCORD trial, were monitored for a median of 8.8 years and a mean of 7.7 years from randomization. Intensive glucose lowering for a mean of 3.7 years had a neutral long-term effect on the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), death from any cause, and an expanded composite outcome that included all-cause death. Moreover, the risk of cardiovascular mortality noted during the active phase (hazard ratio 1.49; 95% CI 1.19, 1.87; P < 0.0001) decreased (HR 1.20; 95% CI 1.03, 1.39; P = 0.02).
   CONCLUSIONS
   In high-risk people with type 2 diabetes monitored for 9 years, a mean of 3.7 years of intensive glycemic control had a neutral effect on death and nonfatal cardiovascular events but increased cardiovascular-related death.
C1 [Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
   [Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
   [Gerstein, Hertzel C.] Hamilton Hlth Sci, Hamilton, ON, Canada.
   [Beavers, Daniel P.; Craven, Timothy E.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Bertoni, Alain G.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
   [Bigger, J. Thomas; Jimenez, Carlos R. Lopez] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA.
   [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
   [Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA.
   [Fonseca, Vivian] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
   [Geller, Nancy L.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
   [Giddings, Stephen J.] VA St Louis Hlth Care Syst, St Louis, MO USA.
   [Grimm, Richard H., Jr.] Univ Minnesota, Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
   [Genuth, Saul; Ismail-Beigi, Faramarz] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Hramiak, Irene] Univ Western Ontario, St Josephs Hlth Care, London, ON, Canada.
   [Ismail-Beigi, Faramarz] VA Med Ctr, Cleveland, OH USA.
   [Kirby, Ruth] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
   [Probstfield, Jeffrey] Univ Washington, Dept Med, Seattle, WA USA.
   [Riddle, Matthew C.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA.
   [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Div Diabet & Endocrinol, Box 736 UMHC, Minneapolis, MN 55455 USA.
   [Friedewald, William T.] Columbia Univ, New York, NY USA.
RP Gerstein, HC (reprint author), McMaster Univ, Dept Med, Hamilton, ON, Canada.; Gerstein, HC (reprint author), McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.; Gerstein, HC (reprint author), Hamilton Hlth Sci, Hamilton, ON, Canada.
EM gerstein@mcmaster.ca
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
   N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
   HHSN268201100027C, Y1-HC-9035, Y1-HC-1010]; National Institute of
   Diabetes and Digestive and Kidney Diseases; National Institute on Aging;
   National Eye Institute; Centers for Disease Control and Prevention;
   General Clinical Research Centers; Veterans Affairs medical centers
FX ACCORD was supported by National Heart, Lung, and Blood Institute
   contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181,
   N01-HC-95182, N01-HC-95183, N01-HC-95184; IAA #Y1-HC-9035; and IAA
   #Y1-HC-1010. Other components of the National Institutes of Health,
   including the National Institute of Diabetes and Digestive and Kidney
   Diseases, the National Institute on Aging, and the National Eye
   Institute, contributed funding. The Centers for Disease Control and
   Prevention funded substudies within ACCORD on cost-effectiveness and
   health-related quality of life. General Clinical Research Centers
   provided support at many sites. This material is also the result of work
   supported with resources and the use of facilities at the Veterans
   Affairs medical centers, as listed previously. ACCORDION activities were
   supported by National Heart, Lung, and Blood Institute contract
   HHSN268201100027C. The contents do not represent the views of the
   National Institutes of Health, the U.S. Department of Veterans Affairs,
   or the U.S. Government.
NR 29
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAY
PY 2016
VL 39
IS 5
BP 701
EP 708
DI 10.2337/dc15-2283
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK6MU
UT WOS:000375039000010
ER

PT J
AU Callaghan, BC
   Xia, R
   Banerjee, M
   de Rekeneire, N
   Harris, TB
   Newman, AB
   Satterfield, S
   Schwartz, AV
   Vinik, AI
   Feldman, EL
   Strotmeyer, ES
AF Callaghan, Brian C.
   Xia, Rong
   Banerjee, Mousumi
   de Rekeneire, Nathalie
   Harris, Tamara B.
   Newman, Anne B.
   Satterfield, Suzanne
   Schwartz, Ann V.
   Vinik, Aaron I.
   Feldman, Eva L.
   Strotmeyer, Elsa S.
CA Hlth ABC Study
TI Metabolic Syndrome Components Are Associated With Symptomatic
   Polyneuropathy Independent of Glycemic Status
SO DIABETES CARE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE;
   PERIPHERAL-NERVE FUNCTION; SENSORY NEUROPATHY; CHRONIC COMPLICATIONS;
   INCREASED PREVALENCE; DIABETES-MELLITUS; NATIONAL-HEALTH; RISK;
   DIAGNOSIS
AB OBJECTIVE
   Previous studies demonstrate that the metabolic syndrome is associated with distal symmetric polyneuropathy (DSP). We aimed to determine the magnitude of this effect and the precise components involved.
   RESEARCH DESIGN AND METHODS
   We determined the symptomatic DSP prevalence in the Health, Aging, and Body Composition (Health ABC) study (prospective cohort study, with subjects aged 7079 years at baseline), stratified by glycemic status (glucose tolerance test) and the number of additional metabolic syndrome components (updated National Cholesterol Education Program/Adult Treatment Panel III definition). DSP was defined as neuropathic symptoms (questionnaire) plus at least one of three confirmatory tests (heavy monofilament, peroneal conduction velocity, and vibration threshold). Multivariable logistic and linear regression evaluated the association of metabolic syndrome components with DSP in cross-sectional and longitudinal analyses.
   RESULTS
   Of 2,382 participants with neuropathy measures (mean age 73.5 +/- 2.9 years, 38.2% black, 51.7% women), 21.0% had diabetes, 29.9% prediabetes, 52.8% metabolic syndrome, and 11.1% DSP. Stratified by glycemic status, DSP prevalence increased as the number of metabolic syndrome components increased (P = 0.03). Diabetes (cross-sectional model, odds ratio [OR] 1.65 [95% CI 1.18-2.31]) and baseline hemoglobin A(1C) (longitudinal model, OR 1.42 [95% CI 1.15-1.75]) were the only metabolic syndrome measures significantly associated with DSP. Waist circumference and HDL were significantly associated with multiple secondary neuropathy outcomes.
   CONCLUSIONS
   Independent of glycemic status, symptomatic DSP is more common in those with additional metabolic syndrome components. However, the issue of which metabolic syndrome components drive this association, in addition to hyperglycemia, remains unclear. Larger waist circumference and low HDL may be associated with DSP, but larger studies with more precise metabolic measures are needed.
C1 [Callaghan, Brian C.; Feldman, Eva L.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA.
   [Xia, Rong; Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
   [de Rekeneire, Nathalie] Univ Bordeaux, ISPED, Ctr INSERM U1219 Epidemiol Biostat, Bordeaux, France.
   [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
   [Newman, Anne B.; Strotmeyer, Elsa S.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA.
   [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Preventat Med, Memphis, TN 38163 USA.
   [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Vinik, Aaron I.] Strelitz Diabet Res Inst, Norfolk, VA USA.
RP Callaghan, BC (reprint author), Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA.
EM bcallagh@med.umich.edu
RI Newman, Anne B./C-6408-2013; 
OI Newman, Anne B./0000-0002-0106-1150; Strotmeyer,
   Elsa/0000-0002-4093-6036
FU Taubman Medical Institute; National Institute of Neurological Disorders
   and Stroke, National Institutes of Health (NIH), K23 grant [NS079417];
   National Institute of Diabetes and Digestive and Kidney Diseases
   [DP3DK094292, R24082841]; National Institute on Aging (NIA)
   [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA grant [R01-AG028050];
   National Institute of Nursing Research grant [R01-NR12459]; Intramural
   Research Program of the NIH, the National Institute on Aging; University
   of Pittsburgh Claude D. Pepper Older Americans Independence Center Pilot
   grant [P30-AG024827]
FX B.C.C. and E.L.F. are supported by the Taubman Medical Institute. B.C.C.
   is supported by a National Institute of Neurological Disorders and
   Stroke, National Institutes of Health (NIH), K23 grant (NS079417).
   E.L.F. is supported by National Institute of Diabetes and Digestive and
   Kidney Diseases grants DP3DK094292 and R24082841. This research was
   supported by the National Institute on Aging (NIA) contracts
   N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050
   (to E.S.S.); and National Institute of Nursing Research grant
   R01-NR12459. This research was also supported in part by the Intramural
   Research Program of the NIH, the National Institute on Aging, and the
   University of Pittsburgh Claude D. Pepper Older Americans Independence
   Center Pilot grant P30-AG024827 (to E.S.S.).
NR 34
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Z9 3
U1 2
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAY
PY 2016
VL 39
IS 5
BP 801
EP 807
DI 10.2337/dc16-0081
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK6MU
UT WOS:000375039000024
PM 26965720
ER

PT J
AU Farombi, EO
   Adedara, IA
   Forcados, GE
   Anao, OO
   Agbowo, A
   Patlolla, AK
AF Farombi, Ebenezer O.
   Adedara, Isaac A.
   Forcados, Gilead E.
   Anao, Osemudiamen O.
   Agbowo, Agatha
   Patlolla, Anita K.
TI Responses of testis, epididymis, and sperm of pubertal rats exposed to
   functionalized multiwalled carbon nanotubes
SO ENVIRONMENTAL TOXICOLOGY
LA English
DT Article
DE functionalized multiwalled carbon nanotubes; testicular toxicity;
   oxidative stress; nanotoxicology; rats
ID OXIDATIVE STRESS; DRUG-DELIVERY; NANOPARTICLES; MICE; HEPATOTOXICITY;
   GLUTATHIONE; TOXICITY; LUNG; SPERMATOZOA; DISEASE
AB The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg(-1) functionalized multi-walled carbon nanotubes (f-MWCNTs) for 5 days. The results showed that administration of (f-MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione-S-transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f-MWCNTs)-treated rats. The spermiogram of (f-MWCNTs)-treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f-MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f-MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction. (c) 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 543-551, 2016.
C1 [Farombi, Ebenezer O.; Adedara, Isaac A.; Forcados, Gilead E.; Anao, Osemudiamen O.; Agbowo, Agatha] Univ Ibadan, Coll Med, Dept Biochem, Drug Metab & Toxicol Res Labs, Ibadan, Nigeria.
   [Patlolla, Anita K.] Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Jackson, MS USA.
RP Farombi, EO (reprint author), Univ Ibadan, Coll Med, Dept Biochem, Drug Metab & Toxicol Res Labs, Ibadan, Nigeria.
EM olatunde_farombi@yahoo.com
OI Forcados, Gilead/0000-0001-6353-0015
FU NIH-NIMHD [G12MD007581]
FX Contract grant sponsor: NIH-NIMHD.; Contract grant number: G12MD007581.
NR 37
TC 2
Z9 2
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1520-4081
EI 1522-7278
J9 ENVIRON TOXICOL
JI Environ. Toxicol.
PD MAY
PY 2016
VL 31
IS 5
BP 543
EP 551
DI 10.1002/tox.22067
PG 9
WC Environmental Sciences; Toxicology; Water Resources
SC Environmental Sciences & Ecology; Toxicology; Water Resources
GA DJ6OM
UT WOS:000374332800004
PM 25410135
ER

PT J
AU Jia, J
   Davis, CM
   Zhang, WR
   Edin, ML
   Jouihan, S
   Jia, TP
   Bradbury, JA
   Graves, JP
   DeGraff, LM
   Lee, CR
   Ronnekleiv, O
   Wang, RK
   Xu, Y
   Zeldin, DC
   Alkayed, NJ
AF Jia, Jia
   Davis, Catherine M.
   Zhang, Wenri
   Edin, Matthew L.
   Jouihan, Sari
   Jia, Taiping
   Bradbury, J. Alyce
   Graves, Joan P.
   DeGraff, Laura M.
   Lee, Craig R.
   Ronnekleiv, Oline
   Wang, Ruikang
   Xu, Yun
   Zeldin, Darryl C.
   Alkayed, Nabil J.
TI Sex- and isoform-specific mechanism of neuroprotection by transgenic
   expression of P450 epoxygenase in vascular endothelium
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Stroke; Eicosanoids; Vasodilation; Inflammation; Cerebral blood flow
ID SOLUBLE EPOXIDE HYDROLASE; ARACHIDONIC-ACID EPOXYGENASE;
   CEREBRAL-BLOOD-FLOW; EPOXYEICOSATRIENOIC ACIDS; GENDER-DIFFERENCE;
   MOLECULAR-CLONING; LIVER-MICROSOMES; CYTOCHROMES P450; GENE-EXPRESSION;
   NITRIC-OXIDE
AB Objective: Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice.
   Approach and results: Male and female wild-type and transgenic mice overexpressing either human CYP2J2 or CYP2C8 epoxygenases in vascular endothelium under control of the Tie2 promoter (Tie2-CYP2J2 and Tie2-CYP2C8) were subjected to 60-min middle cerebral artery occlusion (MCAO). Microvascular cortical perfusion was monitored during vascular occlusion and reperfusion using laser-Doppler flowmetry and optical imaging. Infarct size and inflammatory cytokines were measured at 24h of reperfusion by TTC and real-time quantitative PCR, respectively. Infarct size was significantly reduced in both Tie2-CYP2J2 and Tie2-CYP2C8 transgenic male mice compared to corresponding WT male mice (n = 10 per group, p < 0.05). Tie2-CYP2J2, but not Tie2-CYP2C8 male mice maintained higher blood flow during MCAO; however, both Tie2-CYP2J2 and Tie2-CYP2C8 had lower inflammatory cytokine expression after ischemia compared to corresponding WT males (n = 10 per group for CBF and n = 3 for cytokines, p < 0.05). In females, a reduction in infarct was observed in the caudate-putamen, but not in the cortex or hemisphere as a whole and no differences were observed in blood flow between female transgenic and WT mice (n = 10 per group).
   Conclusions: Overexpression of CYP epoxygenases in vascular endothelial cells protects against experimental cerebral ischemia in male mice. The mechanism of protection is in part linked to enhanced blood flow and suppression of inflammation, and is both sex- and CYP isoform-specific. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Davis, Catherine M.; Zhang, Wenri; Jouihan, Sari; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
   [Edin, Matthew L.; Bradbury, J. Alyce; Graves, Joan P.; DeGraff, Laura M.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
   [Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
   [Wang, Ruikang] Univ Washington, Dept Biomed Engn, Seattle, WA 98195 USA.
   [Jia, Jia] Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou, Jiangsu, Peoples R China.
   [Jia, Jia] Soochow Univ, Coll Pharmaceut Sci, Suzhou, Jiangsu, Peoples R China.
   [Jia, Taiping; Ronnekleiv, Oline] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
   [Xu, Yun] Nanjing Univ, Sch Med, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China.
RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM alkayedn@ohsu.edu
OI Lee, Craig/0000-0003-3595-5301
FU National Institute of Health (NIH) [R01NS070837, P01NS049210,
   R01HL093140, R01GM088199]; Intramural Research Program of the National
   Institute of Environmental Health Sciences (NIEHS) [Z01 ES025034]
FX This work was supported by the National Institute of Health (NIH)
   R01NS070837 to NJA, P01NS049210 to NJA and OKR, R01HL093140 to RKW,
   R01GM088199 to CRL and the Intramural Research Program of the National
   Institute of Environmental Health Sciences (NIEHS) Z01 ES025034 to DCZ.
NR 45
TC 0
Z9 0
U1 2
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD MAY
PY 2016
VL 279
BP 75
EP 85
DI 10.1016/j.expneurol.2016.02.016
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DK0OU
UT WOS:000374612900006
PM 26902473
ER

PT J
AU Uehara, H
   Luo, S
   Aryal, B
   Levine, RL
   Rao, VA
AF Uehara, Hiroshi
   Luo, Shen
   Aryal, Baikuntha
   Levine, Rodney L.
   Rao, V. Ashutosh
TI Distinct oxidative cleavage and modification of bovine [Cu- Zn]-SOD by
   an ascorbic acid/Cu(II) system: Identification of novel copper binding
   site on SOD molecule
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE SOD; Metal catalyzed oxidation; Copper; Ascorbic acid; Carbonylation;
   Mass spectrometry
ID AMYOTROPHIC-LATERAL-SCLEROSIS; METAL-CATALYZED OXIDATION;
   AMINO-ACID-RESIDUES; SUPEROXIDE-DISMUTASE; CU,ZN-SUPEROXIDE DISMUTASE;
   AFFINITY CLEAVAGE; PROTEIN OXIDATION; BIOLOGICAL CONSEQUENCES;
   METHIONINE OXIDATION; HYDROGEN-PEROXIDE
AB We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2 kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and alpha-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5 angstrom from the alpha-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. Published by Elsevier Inc.
C1 [Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Rao, V. Ashutosh] US FDA, Lab Appl Biochem, Div Biotechnol Review & Res 3, Off Biotechnol Prod,Off Pharmaceut Qual,Ctr Drug, White Oak, MD 20993 USA.
   [Levine, Rodney L.] NHLBI, Biochem Lab, Bldg 10, Bethesda, MD 20892 USA.
RP Rao, VA (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Rm 2212, Silver Spring, MD 20993 USA.
EM ashutosh.rao@fda.hhs.gov
RI Levine, Rodney/D-9885-2011
FU FDA CDER Critical Path Initiative; Intramural Research Program of the
   National Heart, Lung, and Blood Institute
FX This research was supported by the FDA CDER Critical Path Initiative.
   R.L.L. was supported by the Intramural Research Program of the National
   Heart, Lung, and Blood Institute.
NR 54
TC 2
Z9 2
U1 5
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAY
PY 2016
VL 94
BP 161
EP 173
DI 10.1016/j.freeradbiomed.2016.01.020
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DK1AK
UT WOS:000374644100016
PM 26872685
ER

PT J
AU Harrington, EA
   Sloan, JL
   Manoli, I
   Chandler, RJ
   Schneider, M
   McGuire, PJ
   Calcedo, R
   Wilson, JM
   Venditti, CP
AF Harrington, Elizabeth A.
   Sloan, Jennifer L.
   Manoli, Irini
   Chandler, Randy J.
   Schneider, Mark
   McGuire, Peter J.
   Calcedo, Roberto
   Wilson, James M.
   Venditti, Charles P.
TI Neutralizing Antibodies Against Adeno-Associated Viral Capsids in
   Patients with mut Methylmalonic Acidemia
SO HUMAN GENE THERAPY
LA English
DT Article
ID LIVER-KIDNEY TRANSPLANTATION; GENE DELIVERY RESCUES; COA MUTASE; MURINE
   MODEL; METABOLIC-DISORDERS; PEDIATRIC-PATIENTS; IMMUNE-RESPONSE; AAV;
   THERAPY; IDENTIFICATION
AB Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut(0) MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study (clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut(-) and 34 mut(0); 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n=35), AAV8 (n=41), and AAV9 (n=42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers 1:20) in the pediatric MMA patients (2-18 years) for both AAV2 (p<0.05) and AAV8 (p<0.01) neutralizing antibodies (NAbs) compared with historical controls. Those with positive NAb titers were typically older than 18 years (p<0.05 all serotypes) or had received solid organ transplantation (p<0.01 AAV8, AAV9). The mut(0) patients who had not been transplanted (n=24)that is, the subset with the greatest need for improved treatmentsrepresented the seronegative majority, with 21 out of 24 patients lacking Abs against all AAV capsids tested. The unexpected lack of NAbs against AAV in this patient population has encouraging implications for systemic gene delivery as a treatment for mut MMA.
C1 [Harrington, Elizabeth A.; Sloan, Jennifer L.; Manoli, Irini; Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA.
   [McGuire, Peter J.] NHGRI, Metab, Infect & Immun Unit, Med Genom & Metab Genet Branch,NIH, Bethesda, MD 20892 USA.
   [Schneider, Mark; Calcedo, Roberto; Wilson, James M.] Univ Penn, Gene Therapy Program, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
   Institute
FX We thank all patients and their families for their participation, Isa
   Bernardini and Roxanne Fischer for processing patient samples, and Jean
   Gagne for assistance with data collection. This work was supported by
   the Intramural Research Program of the National Human Genome Research
   Institute.
NR 47
TC 2
Z9 2
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD MAY
PY 2016
VL 27
IS 5
BP 345
EP 353
DI 10.1089/hum.2015.092
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK1CH
UT WOS:000374649600003
PM 26790480
ER

PT J
AU Bush, RA
   Zeng, Y
   Colosi, P
   Kjellstrom, S
   Hiriyanna, S
   Vijayasarathy, C
   Santos, M
   Li, JB
   Wu, ZJ
   Sieving, PA
AF Bush, Ronald A.
   Zeng, Yong
   Colosi, Peter
   Kjellstrom, Sten
   Hiriyanna, Suja
   Vijayasarathy, Camasamudram
   Santos, Maria
   Li, Jinbo
   Wu, Zhijian
   Sieving, Paul A.
TI Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy
   in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression
   and Improved Retinal Structure and Function
SO HUMAN GENE THERAPY
LA English
DT Article
ID LEBERS CONGENITAL AMAUROSIS; ERG B-WAVE; JUVENILE RETINOSCHISIS;
   MOLECULAR-MECHANISMS; SYNAPTIC PATHOLOGY; PHOTORECEPTOR; CELLS; RS1;
   DELIVERY; PROTEIN
AB Gene therapy for inherited retinal diseases has been shown to ameliorate functional and structural defects in both animal models and in human clinical trials. X-linked retinoschisis (XLRS) is an early-age onset macular dystrophy resulting from loss of an extracellular matrix protein (RS1). In preparation for a human clinical gene therapy trial, we conducted a dose-range efficacy study of the clinical vector, a self-complementary AAV delivering a human retinoschisin (RS1) gene under control of the RS1 promoter and an interphotoreceptor binding protein enhancer (AAV8-scRS/IRBPhRS), in the retinoschisin knockout (Rs1-KO) mouse. The therapeutic vector at 1x10(6) to 2.5x10(9) (1E6-2.5E9) vector genomes (vg)/eye or vehicle was administered to one eye of 229 male Rs1-KO mice by intravitreal injection at 22 +/- 3 days postnatal age (PN). Analysis of retinal function (dark-adapted electroretinogram, ERG), structure (cavities and outer nuclear layer thickness) by in vivo retinal imaging using optical coherence tomography, and retinal immunohistochemistry (IHC) for RS1 was done 3-4 months and/or 6-9 months postinjection (PI). RS1 IHC staining was dose dependent across doses 1E7 vg/eye, and the threshold for significant improvement in all measures of retinal structure and function was 1E8 vg/eye. Higher doses, however, did not produce additional improvement. At all doses showing efficacy, RS1 staining in Rs1-KO mouse was less than that in wild-type mice. Improvement in the ERG and RS1 staining was unchanged or greater at 6-9 months than at 3-4 months PI. This study demonstrates that vitreal administration of AAV8 scRS/IRBPhRS produces significant improvement in retinal structure and function in the mouse model of XLRS over a vector dose range that can be extended to a human trial. It indicates that a fully normal level of RS1 expression is not necessary for a therapeutic effect.
C1 [Bush, Ronald A.; Zeng, Yong; Kjellstrom, Sten; Vijayasarathy, Camasamudram; Li, Jinbo; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
   [Colosi, Peter; Hiriyanna, Suja; Santos, Maria; Wu, Zhijian; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
   [Kjellstrom, Sten] Lund Univ, Dept Ophthalmol, Lund, Sweden.
RP Bush, RA (reprint author), 50 South Dr, Bethesda, MD 20892 USA.
EM bushr@nidcd.nih.gov
FU National Institute on Deafness and Other Communication Disorders;
   National Eye Institute; National Institutes of Health
FX This study was supported by the intramural research program of the
   National Institute on Deafness and Other Communication Disorders, the
   National Eye Institute, and the National Institutes of Health. We would
   like to acknowledge Dr. Lisa Wei for helpful comments on the manuscript.
NR 43
TC 2
Z9 2
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD MAY
PY 2016
VL 27
IS 5
BP 376
EP 389
DI 10.1089/hum.2015.142
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA DK1CH
UT WOS:000374649600006
PM 27036983
ER

PT J
AU Donovan, FX
   Kimble, DC
   Kim, Y
   Lach, FP
   Harper, U
   Kamat, A
   Jones, M
   Sanborn, EM
   Tryon, R
   Wagner, JE
   MacMillan, ML
   Ostrander, EA
   Auerbach, AD
   Smogorzewska, A
   Chandrasekharappa, SC
AF Donovan, Frank X.
   Kimble, Danielle C.
   Kim, Yonghwan
   Lach, Francis P.
   Harper, Ursula
   Kamat, Aparna
   Jones, MaryPat
   Sanborn, Erica M.
   Tryon, Rebecca
   Wagner, John E.
   MacMillan, Margaret L.
   Ostrander, Elaine A.
   Auerbach, Arleen D.
   Smogorzewska, Agata
   Chandrasekharappa, Settara C.
TI Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in
   Homozygosity of a Mutant Allele Causes Fanconi Anemia
SO HUMAN MUTATION
LA English
DT Article
DE Uniparental disomy; UPD16; Fanconi anemia; Recurrence risk; FANCA; FANCP
ID GENES; POPULATION; MUTATIONS; REPAIR; UBE2T
AB Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and SNP arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis.
C1 [Donovan, Frank X.; Kimble, Danielle C.; Harper, Ursula; Kamat, Aparna; Jones, MaryPat; Ostrander, Elaine A.; Chandrasekharappa, Settara C.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, 50 South Dr,Bldg 50,Room 5232, Bethesda, MD 20892 USA.
   [Kim, Yonghwan; Lach, Francis P.; Sanborn, Erica M.; Smogorzewska, Agata] Rockefeller Univ, Lab Genome Maintenance, 1230 York Ave, New York, NY 10021 USA.
   [Tryon, Rebecca; Wagner, John E.; MacMillan, Margaret L.] Univ Minnesota, Dept Pediat, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA.
   [Auerbach, Arleen D.] Rockefeller Univ, Human Genet & Hematol Program, 1230 York Ave, New York, NY 10021 USA.
   [Kim, Yonghwan] Sookmyung Womens Univ, Dept Life Syst, Seoul 04310, South Korea.
RP Chandrasekharappa, SC (reprint author), NHGRI, Canc Genet & Comparat Genom Branch, NIH, 50 South Dr,Bldg 50,Room 5232, Bethesda, MD 20892 USA.
EM chandra@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU NIH [R01 HL120922, UL1 TR000043]; Intramural Research Program of the
   National Human Genome Research Institute, NIH; Rita Allen Foundation;
   Starr Cancer Consortium; Vilcek Foundation
FX Contract grant sponsors: NIH (R01 HL120922, #UL1 TR000043); Intramural
   Research Program of the National Human Genome Research Institute, NIH;
   Rita Allen Foundation (AS); Starr Cancer Consortium (AS); Vilcek
   Foundation (ADA).
NR 15
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD MAY
PY 2016
VL 37
IS 5
BP 465
EP 468
DI 10.1002/humu.22962
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA DJ6PK
UT WOS:000374335200006
PM 26841305
ER

PT J
AU Chen, KQ
   Wang, JM
   Yuan, RX
   Yi, X
   Li, LZ
   Gong, WH
   Yang, TS
   Li, LW
   Su, SB
AF Chen, Keqiang
   Wang, Ji Ming
   Yuan, Ruoxi
   Yi, Xiang
   Li, Liangzhu
   Gong, Wanghua
   Yang, Tianshu
   Li, Liwu
   Su, Shaobo
TI Tissue-resident dendritic cells and diseases involving dendritic cell
   malfunction
SO INTERNATIONAL IMMUNOPHARMACOLOGY
LA English
DT Review
DE Dendritic cells; Resident DCs; DC-related diseases; Autoimmunity; Cancer
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ACTIVATED RECEPTOR-GAMMA; CD4(+) T-CELLS;
   ALLERGIC AIRWAY INFLAMMATION; PROSTATE-CANCER PATIENTS; HEPATITIS-B
   INFECTION; BRONCHIAL LYMPH-NODE; TUMOR-ANTIGEN MUC1; PHASE-I/II TRIAL;
   RESPIRATORY-TRACT
AB Dendritic cells (DCs) control immune responses and are central to the development of immune memory and tolerance. DCs initiate and orchestrate immune responses in a manner that depends on signals they receive from microbes and cellular environment. Although DCs consist mainly of bone marrow-derived and resident populations, a third tissue-derived population resides the spleen and lymph nodes (LNs), different subsets of tissue derived DCs have been identified in the blood, spleen, lymph nodes, skin, lung, liver, gut and kidney to maintain the tolerance and control immune responses. Tissue-resident DCs express different receptors for microbe associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs), which were activated to promote the production of pro- or anti-inflammatory cytokines. Malfunction of DCs contributes to diseases such as autoimmunity, allergy, and cancer. It is therefore important to update the knowledge about resident DC subsets and diseases associated with DC malfunction. Published by Elsevier B.V.
C1 [Chen, Keqiang; Yang, Tianshu; Su, Shaobo] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China.
   [Chen, Keqiang; Wang, Ji Ming; Yi, Xiang; Li, Liangzhu; Gong, Wanghua] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Chen, Keqiang; Yuan, Ruoxi; Li, Liwu] Virginia Polytech Inst & State Univ, Dept Biol Sci, Lab Inflammat Biol, Blacksburg, VA 24061 USA.
   [Gong, Wanghua] Leidos Biomed Res Inc, Basic Res Program, Frederick, MD 21702 USA.
RP Chen, KQ (reprint author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China.; Wang, JM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM keqiangc8@gmail.com; wangji@mail.nih.gov
FU federal funds from the National Cancer Institute, National Institutes of
   Health [HHSN261200800001E]; NCI, NIH; National Natural Science
   Foundation of China [31470844]
FX This project was funded in part by federal funds from the National
   Cancer Institute, National Institutes of Health, under Contract No.
   HHSN261200800001E and was supported in part by the Intramural Research
   Program of the NCI, NIH. This project was also supported in part by the
   grants from the National Natural Science Foundation of China (31470844).
NR 197
TC 4
Z9 4
U1 4
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-5769
EI 1878-1705
J9 INT IMMUNOPHARMACOL
JI Int. Immunopharmacol.
PD MAY
PY 2016
VL 34
BP 1
EP 15
DI 10.1016/j.intimp.2016.02.007
PG 15
WC Immunology; Pharmacology & Pharmacy
SC Immunology; Pharmacology & Pharmacy
GA DK0LN
UT WOS:000374604400001
PM 26906720
ER

PT J
AU Kerkar, SP
   Wang, ZF
   Lasota, J
   Park, T
   Patel, K
   Groh, E
   Rosenberg, SA
   Miettinen, MM
AF Kerkar, Sid P.
   Wang, Zeng-Feng
   Lasota, Jerzy
   Park, Tristen
   Patel, Krishna
   Groh, Eric
   Rosenberg, Steven A.
   Miettinen, Markku M.
TI MAGE-A is More Highly Expressed Than NY-ESO-1 in a Systematic
   Immunohistochemical Analysis of 3668 Cases
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE cancer; immunotherapy; immunohistochemistry; NY-ESO; MAGE-A;
   cancer-testis antigens; tissue-arrays; immune-escape;
   prognostic-markers; predictive-markers
ID CANCER-TESTIS ANTIGENS; CANCER/TESTIS ANTIGENS; ESOPHAGEAL CANCER; CELL;
   IMMUNOTHERAPY; LYMPHOCYTES; MELANOMA; TARGETS
AB Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NY-ESO-1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (> 50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1% < 1%), bladder urothelial CA (40.4%/8.3%), cervical/anal SCC (37.5%/0%), lung SCC (34%/3.8%), lung adenocarcinomas (27.6%/3.9%), ovarian CA (26.4%/3.6%), endometrial CA (26.3%/1.3%), lung small cell CA (24.4%/2.4%), gastric adenocarcinomas (20%/4%), breast mucinous CA (19.3%/0%), hepatocellular CA (18.8%/1.2%), breast infiltrating ductal CA (16.4%/1.8%), colorectal adenocarcinomas (10.7%/ < 1%), cholangiocarcinomas (9.8%/0%), thymic CA (9%/4.5%), and mesotheliomas (7.9%/ < 1%). Furthermore, high expression of MAGE-A, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.
C1 [Kerkar, Sid P.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
   [Wang, Zeng-Feng; Lasota, Jerzy; Miettinen, Markku M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
   [Park, Tristen; Patel, Krishna; Groh, Eric; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Kerkar, SP (reprint author), Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
EM spkerkar@yahoo.com
FU Intramural NIH HHS [Z99 CA999999]
NR 27
TC 1
Z9 1
U1 0
U2 5
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 MAY
PY 2016
VL 39
IS 4
BP 181
EP 187
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA DK2CX
UT WOS:000374723300004
PM 27070449
ER

PT J
AU Goldberg, RB
   Temprosa, M
   Mele, L
   Orchard, T
   Mather, K
   Bray, G
   Horton, E
   Kitabchi, A
   Krakoff, J
   Marcovina, S
   Perreault, L
   White, N
AF Goldberg, Ronald B.
   Temprosa, Marinella
   Mele, Lisa
   Orchard, Trevor
   Mather, Kieren
   Bray, George
   Horton, Edward
   Kitabchi, Abbas
   Krakoff, Jonathan
   Marcovina, Santica
   Perreault, Leigh
   White, Neil
CA Diabet Prevention Program Res Grp
TI Change in adiponectin explains most of the change in HDL particles
   induced by lifestyle intervention but not metformin treatment in the
   Diabetes Prevention Program
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Adiponectin; HDL; Lifestyle change; Metformin
ID CARDIOVASCULAR RISK-FACTORS; LOW-DENSITY-LIPOPROTEIN;
   CORONARY-HEART-DISEASE; INSULIN SENSITIVITY; ANTIGEN
AB Objective. In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDLC) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP.
   Methods. The effects of a 1 year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850 mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis.
   Results. After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect.
   Conclusion. While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease. (C) 2016 Published by Elsevier Inc.
C1 [Goldberg, Ronald B.] Univ Miami, Diabet Res Inst, 1450 NW 10th Ave,Suite 2054, Miami, FL 33136 USA.
   [Temprosa, Marinella; Mele, Lisa] George Washington Univ, Biostat Ctr, 6110 Executive Blvd,Suite 750, Rockville, MD 20852 USA.
   [Orchard, Trevor] Univ Pittsburgh, 3512 Fifth Ave, Pittsburgh, PA 15213 USA.
   [Mather, Kieren] Indiana Univ, Dept Med, 541 Clin Dr CL 365, Indianapolis, IN 46202 USA.
   [Bray, George] Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
   [Horton, Edward] Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, One Joslin Pl, Boston, MA 02215 USA.
   [Horton, Edward] Harvard Univ, Sch Med, Dept Med, 25 Shattuck St, Boston, MA 02115 USA.
   [Kitabchi, Abbas] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol, 920 Madison Ave Suite 300A, Memphis, TN 38163 USA.
   [Krakoff, Jonathan] NIDDKD, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
   [Marcovina, Santica] Univ Washington, Northwest Lipid Res Labs, 401 Queen Anne Ave, North Seattle, WA 98109 USA.
   [Perreault, Leigh] Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Anschutz Med Campus,12801 E 17th Ave, Aurora, CO 80045 USA.
   [White, Neil] Washington Univ, Sch Med, 660 South Euclid Aye, St Louis, MO 63110 USA.
RP Goldberg, RB (reprint author), George Washington Univ, Diabet Prevent Program, Coordinating Ctr, Biostat Ctr, 6110 Executive Blvd,Suite 750, Rockville, MD 20852 USA.
EM dppmail@bsc.gwu.edu
OI orchard, trevor/0000-0001-9552-3215
FU National Institute of Diabetes and Digestive and Kidney Diseases
   [DK048489]
FX National Institute of Diabetes and Digestive and Kidney Diseases
   (DK048489)
NR 31
TC 3
Z9 3
U1 1
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD MAY
PY 2016
VL 65
IS 5
BP 764
EP 775
DI 10.1016/j.metabol.2015.11.011
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DK1ZI
UT WOS:000374714000015
PM 27085783
ER

PT J
AU Jenkins, AK
   Paterson, C
   Wang, Y
   Hyde, TM
   Kleinman, JE
   Law, AJ
AF Jenkins, A. K.
   Paterson, C.
   Wang, Y.
   Hyde, T. M.
   Kleinman, J. E.
   Law, A. J.
TI Neurexin 1 (NRXN1) splice isoform expression during human neocortical
   development and aging
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID COPY NUMBER VARIATION; CLOZAPINE RESPONSE; ALPHA-NEUREXINS;
   SCHIZOPHRENIA; GENES; NEUROLIGINS; DELETIONS; AUTISM; DISORDER; SPECTRUM
AB Neurexin 1 (NRXN1), a presynaptic cell adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including autism, intellectual disability and schizophrenia. To gain insight into NRXN1's involvement in human cortical development we used quantitative real-time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms, NRXN1-alpha and NRXN1-beta, in prefrontal cortex from fetal stages to aging. In addition, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison with non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, markedly increasing with gestational age. In the postnatal dorsolateral prefrontal cortex, expression levels were negatively correlated with age, peaking at birth until similar to 3 years of age, after which levels declined markedly to be stable across the lifespan. NRXN1-beta expression was modestly but significantly elevated in the brains of patients with schizophrenia compared with non-psychiatric controls, whereas NRXN1-alpha expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human dorsolateral prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders.
C1 [Jenkins, A. K.; Paterson, C.; Wang, Y.; Law, A. J.] NIH, Clin Brain Disorder Branch, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
   [Jenkins, A. K.] Univ Kentucky, Coll Med, Lexington, KY USA.
   [Paterson, C.; Law, A. J.] Univ Colorado, Sch Med, Dept Psychiat & Cell & Dev Biol, Mailstop 8619,RC2,RM 4100C, Aurora, CO 80045 USA.
   [Wang, Y.; Hyde, T. M.; Kleinman, J. E.] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA.
RP Law, AJ (reprint author), Univ Colorado, Sch Med, Dept Psychiat & Cell & Dev Biol, Mailstop 8619,RC2,RM 4100C, Aurora, CO 80045 USA.
EM amanda.law@ucdenver.edu
OI Law, Amanda/0000-0002-2574-1564
FU National Institutes of Health, National Institute of Mental Health
   intramural program; NIH [R01MH103716]; Clinical Brain Disorders Branch;
   Amy Deep-Soboslay of the National Institutes of Health, National
   Institute of Mental Health; Lieber Institute
FX This research was supported primarily by funds from the National
   Institutes of Health, National Institute of Mental Health intramural
   program to the Law lab and Clinical Brain Disorders Branch, and in part
   by NIH, R01MH103716 (Law PI). We would like to acknowledge Dr Daniel
   Weinberger, for additional research support from the Clinical Brain
   Disorders Branch and Amy Deep-Soboslay of the National Institutes of
   Health, National Institute of Mental Health and Lieber Institute for
   Brain Development for NRXN1 expression during human neocortical
   development and aging AK Jenkins et al
NR 50
TC 4
Z9 4
U1 3
U2 3
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 MAY
PY 2016
VL 21
IS 5
BP 701
EP 706
DI 10.1038/mp.2015.107
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA DJ6LH
UT WOS:000374324000017
PM 26216298
ER

PT J
AU Leonard, WJ
   Mitra, S
   Lin, JX
AF Leonard, Warren J.
   Mitra, Suman
   Lin, Jian-Xin
TI JAK3 inhibition-is it sufficient?
SO NATURE CHEMICAL BIOLOGY
LA English
DT News Item
ID ALLOGRAFT-REJECTION; INTERLEUKIN-2; PREVENTION; MUTATION
C1 [Leonard, Warren J.; Mitra, Suman; Lin, Jian-Xin] NHLBI, Lab Mol Immunol, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
   [Leonard, Warren J.; Mitra, Suman; Lin, Jian-Xin] NHLBI, Ctr Immunol, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.; Leonard, WJ (reprint author), NHLBI, Ctr Immunol, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
EM leonardw@nhlbi.nih.gov
NR 10
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD MAY
PY 2016
VL 12
IS 5
BP 308
EP 310
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ6KY
UT WOS:000374322800003
PM 27556128
ER

PT J
AU Starokadomskyy, P
   Gemelli, T
   Rios, JJ
   Xing, C
   Wang, RC
   Li, HY
   Pokatayev, V
   Dozmorov, I
   Khan, S
   Miyata, N
   Fraile, G
   Raj, P
   Xu, Z
   Xu, ZG
   Ma, L
   Lin, ZM
   Wang, HJ
   Yang, Y
   Ben-Amitai, D
   Orenstein, N
   Mussaffi, H
   Baselga, E
   Tadini, G
   Grunebaum, E
   Sarajlija, A
   Krzewski, K
   Wakeland, EK
   Yan, N
   de la Morena, MT
   Zinn, AR
   Burstein, E
AF Starokadomskyy, Petro
   Gemelli, Terry
   Rios, Jonathan J.
   Xing, Chao
   Wang, Richard C.
   Li, Haiying
   Pokatayev, Vladislav
   Dozmorov, Igor
   Khan, Shaheen
   Miyata, Naoteru
   Fraile, Guadalupe
   Raj, Prithvi
   Xu, Zhe
   Xu, Zigang
   Ma, Lin
   Lin, Zhimiao
   Wang, Huijun
   Yang, Yong
   Ben-Amitai, Dan
   Orenstein, Naama
   Mussaffi, Huda
   Baselga, Eulalia
   Tadini, Gianluca
   Grunebaum, Eyal
   Sarajlija, Adrijan
   Krzewski, Konrad
   Wakeland, Edward K.
   Yan, Nan
   de la Morena, Maria Teresa
   Zinn, Andrew R.
   Burstein, Ezra
TI DNA polymerase-alpha regulates the activation of type I interferons
   through cytosolic RNA:DNA synthesis
SO NATURE IMMUNOLOGY
LA English
DT Article
ID RETICULATE PIGMENTARY DISORDER; NF-KAPPA-B; SYSTEMIC MANIFESTATIONS;
   CUTANEOUS AMYLOIDOSIS; DEFICIENCY; DISEASE; HUMANS; FAMILY;
   ENCEPHALITIS; REPLICATION
AB Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-alpha. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA: DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA: DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.
C1 [Starokadomskyy, Petro; Li, Haiying; Pokatayev, Vladislav; Miyata, Naoteru; Yan, Nan; de la Morena, Maria Teresa; Zinn, Andrew R.; Burstein, Ezra] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Gemelli, Terry; Rios, Jonathan J.; Xing, Chao; Zinn, Andrew R.] Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
   [Rios, Jonathan J.] Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA.
   [Rios, Jonathan J.; de la Morena, Maria Teresa] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Xing, Chao] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Wang, Richard C.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA.
   [Dozmorov, Igor; Khan, Shaheen; Raj, Prithvi; Wakeland, Edward K.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
   [Fraile, Guadalupe] Ramon y Cajal Univ Hosp, Dept Internal Med, Madrid, Spain.
   [Xu, Zhe; Xu, Zigang; Ma, Lin] Capital Med Univ, Beijing Childrens Hosp, Dept Dermatol, Beijing, Peoples R China.
   [Lin, Zhimiao; Wang, Huijun; Yang, Yong] Peking Univ, Hosp 1, Dept Dermatol, Beijing 100871, Peoples R China.
   [Wang, Huijun; Yang, Yong] Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China.
   [Wang, Huijun] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China.
   [Ben-Amitai, Dan] Schneider Childrens Med Ctr Israel, Unit Pediat Dermatol, Petah Tiqwa, Israel.
   [Ben-Amitai, Dan; Mussaffi, Huda] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
   [Orenstein, Naama] Schneider Childrens Med Ctr Israel, Genet Unit, Petah Tiqwa, Israel.
   [Mussaffi, Huda] Schneider Childrens Med Ctr, Pulmonol Inst, Petah Tiqwa, Israel.
   [Baselga, Eulalia] Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain.
   [Tadini, Gianluca] Univ Milan, Dept Pathophysiol & Transplantat, Pediat Dermatol Unit, Milan, Italy.
   [Tadini, Gianluca] Univ Milan, Dept Pathophysiol & Transplantat, Pediat Highly Intens Care Unit, Milan, Italy.
   [Tadini, Gianluca] IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy.
   [Grunebaum, Eyal] Hosp Sick Children, Dev & Stem Cell Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
   [Grunebaum, Eyal] Univ Toronto, Hosp Sick Children, Div Immunol & Allergy, Toronto, ON M5G 1X8, Canada.
   [Sarajlija, Adrijan] Mother & Child Hlth Care Inst Serbia, Belgrade, Serbia.
   [Sarajlija, Adrijan] Univ Belgrade, Sch Med, Belgrade, Serbia.
   [Krzewski, Konrad] NIAID, Immunogenet Lab, Receptor Cell Biol Sect, NIH, Rockville, MD USA.
   [Yan, Nan] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [de la Morena, Maria Teresa] Childrens Hlth, Dallas, TX USA.
   [Burstein, Ezra] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
RP Zinn, AR; Burstein, E (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.; Zinn, AR (reprint author), Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.; Burstein, E (reprint author), Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
EM andrew.zinn@utsouthwestern.edu; ezra.burstein@utsouthwestern.edu
FU US National Institutes of Health [R01DK073639, R56AI113274, UL1TR001105,
   T32AI005284, R01AI098569, P30CA142543]; Children's Medical Center
   Foundation; National Natural Science Foundation of China [81271744];
   XLPDR International Association
FX We thank the patients and their families for their participation in this
   research project and, in particular, the XLPDR International Association
   for support for the study of this disease; T. Hyatt for technical
   assistance with allelic discrimination assays; D. Baltimore (Caltech)
   for the lentiviral packaging plasmids pHCMV-VSV-G, pMDLg/pRRE and
   pRSV-Rev; Y. Pavlov (University of Nebraska) for the plasmid
   pcDNA3-POLA1; L. Schmitz (Justus-Liebig-University) for the HeLa
   fluorescent ubiquitination-based cell cycle indicator; J. Shay
   (University of Texas Southwestern Medical Center) for the gene encoding
   human telomerase; and H. Hobbs, J. Cohen, M. Attanasio and Z. (J.) Chen
   for comments and suggestions. Supported by the US National Institutes of
   Health (R01DK073639 to Ez.B.; R56AI113274 to Ez.B. and A.R.Z.;
   UL1TR001105 to J.J.R.; T32AI005284 to V.P.; R01AI098569 to N.Y.; and
   P30CA142543 for the UT Southwestern Live Cell Imaging Facility), the
   Children's Medical Center Foundation (A.R.Z.) and the National Natural
   Science Foundation of China (81271744 to Y.Y.).
NR 50
TC 7
Z9 7
U1 0
U2 5
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 MAY
PY 2016
VL 17
IS 5
BP 495
EP +
DI 10.1038/ni.3409
PG 13
WC Immunology
SC Immunology
GA DJ6LA
UT WOS:000374323100008
PM 27019227
ER

PT J
AU Vannella, KM
   Ramalingam, TR
   Hart, KM
   Prado, RD
   Sciurba, J
   Barron, L
   Borthwick, LA
   Smith, AD
   Mentink-Kane, M
   White, S
   Thompson, RW
   Cheever, AW
   Bock, K
   Moore, I
   Fitz, LJ
   Urban, JF
   Wynn, TA
AF Vannella, Kevin M.
   Ramalingam, Thirumalai R.
   Hart, Kevin M.
   Prado, Rafael de Queiroz
   Sciurba, Joshua
   Barron, Luke
   Borthwick, Lee A.
   Smith, Allen D.
   Mentink-Kane, Margaret
   White, Sandra
   Thompson, Robert W.
   Cheever, Allen W.
   Bock, Kevin
   Moore, Ian
   Fitz, Lori J.
   Urban, Joseph F., Jr.
   Wynn, Thomas A.
TI Acidic chitinase primes the protective immune response to
   gastrointestinal nematodes
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CD103(+) DENDRITIC CELLS; GENE-EXPRESSION PROFILES; MAMMALIAN CHITINASE;
   NIPPOSTRONGYLUS-BRASILIENSIS; LYMPHOID-CELLS; CHITOTRIOSIDASE; DISTINCT;
   TISSUE; ROLES; IL-13
AB Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.
C1 [Vannella, Kevin M.; Ramalingam, Thirumalai R.; Hart, Kevin M.; Prado, Rafael de Queiroz; Sciurba, Joshua; Barron, Luke; Borthwick, Lee A.; Mentink-Kane, Margaret; White, Sandra; Thompson, Robert W.; Cheever, Allen W.; Wynn, Thomas A.] NIAID, Program Tissue Immun & Repair, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Borthwick, Lee A.] Newcastle Univ, Inst Cellular Med, Tissue Fibrosis & Repair Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Smith, Allen D.; Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Ctr, Beltsville, MD USA.
   [Bock, Kevin; Moore, Ian] NIAID, Infect Dis Pathogenesis Sect, NIH, Rockville, MD USA.
   [Fitz, Lori J.] Pfizer Worldwide R&D, Inflammat & Immun, Cambridge, MA USA.
RP Wynn, TA (reprint author), NIAID, Program Tissue Immun & Repair, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
   National Institute of Allergy and Infectious Disease
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute of Allergy and
   Infectious Disease. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript. We thank MedImmune for generating the anti-AMCase rabbit
   sera, C. Mainhart for genotyping, T. Gieseck and K. Kindrachuk for
   discussions, and the animal care staffs of Buildings 50 and 14BS at the
   US National Institutes of Health's Bethesda, Maryland campus for the
   conscientious care of mice.
NR 32
TC 3
Z9 4
U1 8
U2 15
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 MAY
PY 2016
VL 17
IS 5
BP 538
EP +
DI 10.1038/ni.3417
PG 9
WC Immunology
SC Immunology
GA DJ6LA
UT WOS:000374323100013
PM 27043413
ER

PT J
AU Li, C
   Krashes, MJ
AF Li, Chia
   Krashes, Michael J.
TI Foraging and flight trump defense and fight
SO NATURE NEUROSCIENCE
LA English
DT Editorial Material
ID NEURAL BASIS; AGRP; BEHAVIORS; CIRCUITRY; NEURONS; MICE
AB Hypothalamic Agouti-related peptide (AgRP)-expressing neurons promote feeding via inhibitory mechanisms. A downstream target in the medial amygdala both mediates feeding and modulates risk-taking and defensive behaviors in the face of starvation.
C1 [Li, Chia; Krashes, Michael J.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Diabet Endocrinol & Obes Branch, US Natl Inst Hlth, Bethesda, MD USA.
   [Li, Chia; Krashes, Michael J.] NIDA, US Natl Inst Hlth, Baltimore, MD USA.
RP Krashes, MJ (reprint author), Natl Inst Diabet & Digest & Kidney Dis NIDDK, Diabet Endocrinol & Obes Branch, US Natl Inst Hlth, Bethesda, MD USA.; Krashes, MJ (reprint author), NIDA, US Natl Inst Hlth, Baltimore, MD USA.
EM michael.krashes@nih.gov
NR 14
TC 0
Z9 0
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAY
PY 2016
VL 19
IS 5
BP 645
EP 646
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA DK2RM
UT WOS:000374762100002
PM 27116388
ER

PT J
AU Vivar, C
   Peterson, BD
   van Praag, H
AF Vivar, Carmen
   Peterson, Benjamin D.
   van Praag, Henriette
TI Running rewires the neuronal network of adult-born dentate granule cells
SO NEUROIMAGE
LA English
DT Article
DE Adult neurogenesis; Entorhinal cortex; Exercise; Hippocampus; Neural
   circuitry; Rabies virus; Retrograde tracing; Retrovirus
ID MEDIAL ENTORHINAL CORTEX; SPATIAL-PATTERN SEPARATION; HIPPOCAMPAL
   NEUROGENESIS; THETA-RHYTHM; IN-VIVO; SUPRAMAMMILLARY NUCLEUS; FEEDBACK
   INHIBITION; ALZHEIMERS-DISEASE; MEMORY SEQUENCES; IMPROVES MEMORY
AB Exercise improves cognition in humans and animals. Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain area important for learning and memory. It is unclear how running modifies the circuitry of new dentate gyrus neurons to support their role in memory function. Here we combine retroviral labeling with rabies virus mediated trans-synaptic retrograde tracing to define and quantify new neuron afferent inputs in young adult male C57Bl/6 mice, housed with or without a running wheel for one month. Exercise resulted in a shift in new neuron networks that may promote sparse encoding and pattern separation. Neurogenesis increased in the dorsal, but not the ventral, dentate gyrus by three-fold, whereas afferent traced cell labeling doubled in number. Regional analysis indicated that running differentially affected specific inputs. Within the hippocampus the ratio of innervation from inhibitory interneurons and glutamatergic mossy cells to new neurons was reduced. Distal traced cells were located in sub-cortical and cortical regions, including perirhinal, entorhinal and sensory cortices. Innervation from entorhinal cortex (EC) was augmented, in proportion to the running-induced enhancement of adult neurogenesis. Within EC afferent input and short-term synaptic plasticity from lateral entorhinal cortex, considered to convey contextual information to the hippocampus was increased. Furthermore, running upregulated innervation from regions important for spatial memory and theta rhythm generation, including caudo-medial entorhinal cortex and subcortical medial septum, supra-and medial mammillary nuclei. Altogether, running may facilitate contextual, spatial and temporal information encoding by increasing adult hippocampal neurogenesis and by reorganization of new neuron circuitry. Published by Elsevier Inc.
C1 [Vivar, Carmen; Peterson, Benjamin D.; van Praag, Henriette] NIA, Neuroplast & Behav Unit, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
   [Vivar, Carmen] IPN, Ctr Invest & Estudios Avanzados, Dept Physiol Biophys & Neurosci, Lab Neurogenesis & Neuroplast, Mexico City 07738, DF, Mexico.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Lab Neurosci, NIH,Biomed Res Ctr, Suite 100,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM vanpraagh@mail.nih.gov
RI Meijer, Anna/K-5118-2016; van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU National Institute on Aging, Intramural Research Program
FX This work was supported by the National Institute on Aging, Intramural
   Research Program. We are most grateful to Linda R. Kitabayashi for her
   help with preparation of photomicrographs, Galit Benoni for help with
   the graphical abstract, Jason Boulter for technical assistance and Drs.
   Peter Clark, Jim Knierim, Hyo Youl Moon and Nirnath Sah for comments on
   the manuscript.
NR 93
TC 10
Z9 10
U1 2
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2016
VL 131
BP 29
EP 41
DI 10.1016/j.neuroimage.2015.11.031
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DK0XH
UT WOS:000374635200004
PM 26589333
ER

PT J
AU Thomas, AG
   Dennis, A
   Rawlings, NB
   Stagg, CJ
   Matthews, L
   Morris, M
   Kolind, SH
   Foxley, S
   Jenkinson, M
   Nichols, TE
   Dawes, H
   Bandettini, PA
   Johansen-Berg, H
AF Thomas, Adam G.
   Dennis, Andrea
   Rawlings, Nancy B.
   Stagg, Charlotte J.
   Matthews, Lucy
   Morris, Martyn
   Kolind, Shannon H.
   Foxley, Sean
   Jenkinson, Mark
   Nichols, Thomas E.
   Dawes, Helen
   Bandettini, Peter A.
   Johansen-Berg, Heidi
TI Multi-modal characterization of rapid anterior hippocampal volume
   increase associated with aerobic exercise
SO NEUROIMAGE
LA English
DT Article
DE Neurogenesis; Angiogenesis; Dentate gyrus; Hippocampus; Fitness;
   Exercise; Aging; Environmental enrichment; Myelin; Plasticity
ID CEREBRAL BLOOD-VOLUME; HUMAN BRAIN; MAGNETIC-SUSCEPTIBILITY;
   WHITE-MATTER; FIELD INHOMOGENEITY; CELL-PROLIFERATION;
   PHYSICAL-EXERCISE; T-2 RELAXATION; DENTATE GYRUS; HEART-RATE
AB The hippocampus has been shown to demonstrate a remarkable degree of plasticity in response to a variety of tasks and experiences. For example, the size of the human hippocampus has been shown to increase in response to aerobic exercise. However, it is currently unknown what underlies these changes. Here we scanned sedentary, young to middle-aged human adults before and after a six-week exercise intervention using nine different neuroimaging measures of brain structure, vasculature, and diffusion. We then tested two different hypotheses regarding the nature of the underlying changes in the tissue. Surprisingly, we found no evidence of a vascular change as has been previously reported. Rather, the pattern of changes is better explained by an increase in myelination. Finally, we show that hippocampal volume increase is temporary, returning to baseline after an additional six weeks without aerobic exercise. This is the first demonstration of a change in hippocampal volume in early to middle adulthood suggesting that hippocampal volume is modulated by aerobic exercise throughout the lifespan rather than only in the presence of age related atrophy. It is also the first demonstration of hippocampal volume change over a period of only six weeks, suggesting that gross morphometric hippocampal plasticity occurs faster than previously thought. Published by Elsevier Inc.
C1 [Thomas, Adam G.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, NIH, DHHS, Bethesda, MD 20892 USA.
   [Thomas, Adam G.; Dennis, Andrea; Rawlings, Nancy B.; Stagg, Charlotte J.; Matthews, Lucy; Foxley, Sean; Jenkinson, Mark; Johansen-Berg, Heidi] Univ Oxford, Nuffield Dept Clin Neurosci, FMRIB, Oxford, England.
   [Morris, Martyn] Oxford Brookes Univ, Movement Sci Grp, Oxford OX3 0BP, England.
   [Kolind, Shannon H.] Kings Coll London, Ctr Neuroimaging Sci, London, ON, Canada.
   [Nichols, Thomas E.; Dawes, Helen] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England.
RP Thomas, AG (reprint author), NIMH, Sect Funct Imaging Methods, NIH, DHHS, Bethesda, MD 20892 USA.
EM adamt@nih.gov
RI Dey, Kamalesh/E-6568-2017; 
OI Stagg, Charlotte/0000-0002-5542-5036; Thomas, Adam/0000-0002-2850-1419
FU NIMH intramural program; UK National Institutes of Health Research
   (NIHR) Oxford Biomedical Research Centre based at the Oxford University
   Hospital NHS Trust; University of Oxford
FX The authors have no conflicts of interest to declare. We would like to
   acknowledge the financial support of the NIMH intramural program and the
   UK National Institutes of Health Research (NIHR) Oxford Biomedical
   Research Centre based at the Oxford University Hospital NHS Trust and
   the University of Oxford. HJB is a Wellcome Trust Senior Research
   Fellow. HD is the Elizabeth Casson Trust Chair in Rehabilitation. We
   would also like to thank Sam Wharton and Tianyou Xu for assisting with
   the QSM analysis, Cameron Holloway for providing medical assistance with
   contrast agent administration, James Bateman (Oxford Brookes University)
   who organized and delivered the exercise training, Anderson Winkler who
   assisted with statistical design, and Gwen Douaud and James Kolasinski
   who provided helpful comments on the manuscript. This study utilized the
   high-performance computational capabilities of the Biowulf Linux cluster
   at the National Institutes of Health, Bethesda, MD (http://hpc.nih.gov).
NR 88
TC 7
Z9 7
U1 5
U2 10
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 MAY 1
PY 2016
VL 131
BP 162
EP 170
DI 10.1016/j.neuroimage.2015.10.090
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DK0XH
UT WOS:000374635200017
PM 26654786
ER

PT J
AU Harris-Love, ML
   Chan, E
   Dromerick, AW
   Cohen, LG
AF Harris-Love, Michelle L.
   Chan, Evan
   Dromerick, Alexander W.
   Cohen, Leonardo G.
TI Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients
   With Hand Paralysis
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE stroke; transcranial magnetic stimulation; upper extremity paresis;
   cerebrovascular accident; rehabilitation; arm; interhemispheric
   inhibition
ID TRANSCRANIAL MAGNETIC STIMULATION; INDUCED MOVEMENT THERAPY; SILENT
   PERIOD; INTERHEMISPHERIC INHIBITION; CORTEX EXCITABILITY; CORTICAL
   EXCITABILITY; BRAIN-STIMULATION; TRANSCALLOSAL INHIBITION;
   RETICULAR-FORMATION; SUBCORTICAL STROKE
AB In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 +/- 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.
C1 [Harris-Love, Michelle L.; Dromerick, Alexander W.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
   [Harris-Love, Michelle L.; Chan, Evan; Dromerick, Alexander W.] MedStar Natl Rehabil Hosp, Washington, DC USA.
   [Dromerick, Alexander W.] District Columbia VA Med Ctr, Washington, DC USA.
   [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Harris-Love, ML (reprint author), 102 Irving St NW,Room 1058, Washington, DC 20010 USA.
EM Mh672@georgetown.edu
FU NIH [K01HD060886]; NIH/NINDS; National Capital Area Rehabilitation
   Research Network (NCARRN) via NICHD/NINDS [HD050845]
FX The authors disclosed receipt of the following financial support for the
   research, authorship, and/or publication of this article: NIH
   K01HD060886 (MHL); NIH/NINDS Competitive Intramural Postdoctoral
   Fellowship (MHL); National Capital Area Rehabilitation Research Network
   (NCARRN) pilot award to MHL via NICHD/NINDS HD050845 (Barbara S.
   Bregman, PI).
NR 60
TC 4
Z9 4
U1 3
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
EI 1552-6844
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD MAY
PY 2016
VL 30
IS 4
BP 328
EP 338
DI 10.1177/1545968315594886
PG 11
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA DJ6VI
UT WOS:000374350900004
PM 26163204
ER

PT J
AU Gorka, AX
   LaBar, KS
   Hariri, AR
AF Gorka, Adam X.
   LaBar, Kevin S.
   Hariri, Ahmad R.
TI Variability in emotional responsiveness and coping style during active
   avoidance as a window onto psychological vulnerability to stress
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Active avoidance; Coping style; Anxiety; Individual differences; Stress
   vulnerability
ID SALIVARY ALPHA-AMYLASE; ROMAN HIGH-AVOIDANCE; RATS; AGGRESSION;
   BEHAVIOR; ANXIETY; FEAR; AMYGDALA; NEUROENDOCRINE; NUCLEUS
AB Individual differences in coping styles are associated with psychological vulnerability to stress. Recent animal research suggests that coping styles reflect trade-offs between proactive and reactive threat responses during active avoidance paradigms, with proactive responses associated with better stress tolerance. Based on these preclinical findings, we developed a novel instructed active avoidance paradigm to characterize patterns of proactive and reactive responses using behavioral, motoric, and autonomic measures in humans. Analyses revealed significant inter-individual variability not only in the magnitude of general emotional responsiveness but also the likelihood to specifically express proactive or reactive responses. In men but not women, individual differences in general emotional responsiveness were linked to increased trait anxiety while proactive coping style was linked to increased trait aggression. These patterns are consistent with preclinical findings and suggest that instructed active avoidance paradigms may be useful in assessing psychological vulnerability to stress using objective behavioral measures. (C) 2016 Published by Elsevier Inc.
C1 [Gorka, Adam X.] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA.
   [LaBar, Kevin S.; Hariri, Ahmad R.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA.
RP Gorka, AX (reprint author), 15K North Dr Rm 300-F, Bethesda, MD 20892 USA.
EM axgorka@gmail.com
FU Duke University; Transdisciplinary Prevention Research Center [P30
   DA023026]; National Institute on Drug Abuse [R01-DA033369]; National
   Institute of Aging [R01AG049789]
FX We thank Bartholomew Brigidi, Spenser Radtke, and Annchen Knodt for
   their assistance in DNS data collection and analysis. This work was
   supported by internal support from Duke University, the
   Transdisciplinary Prevention Research Center (P30 DA023026), and
   research grants from the National Institute on Drug Abuse (R01-DA033369
   to ARH). ARH also receives support from the National Institute of Aging
   (R01AG049789).
NR 61
TC 0
Z9 0
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD MAY 1
PY 2016
VL 158
BP 90
EP 99
DI 10.1016/j.physbeh.2016.02.036
PG 10
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA DK0MU
UT WOS:000374607700013
PM 26922874
ER

PT J
AU Zhang, TW
   Dutton-Regester, K
   Brown, KM
   Hayward, NK
AF Zhang, Tongwu
   Dutton-Regester, Ken
   Brown, Kevin M.
   Hayward, Nicholas K.
TI The genomic landscape of cutaneous melanoma
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE exome sequencing; genomics; melanoma; mutation; ultraviolet radiation;
   driver gene
ID TERT PROMOTER MUTATIONS; BASAL-CELL CARCINOMA; MALIGNANT-MELANOMA;
   SOMATIC MUTATIONS; FAMILIAL MELANOMA; WIDE ASSOCIATION; METASTATIC
   MELANOMA; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; UVEAL MELANOMA
AB Somatic mutation analysis of melanoma has been performed at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last 5yr, next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multigene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer.
C1 [Zhang, Tongwu; Brown, Kevin M.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Dutton-Regester, Ken] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA.
   [Dutton-Regester, Ken] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Dutton-Regester, Ken; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Oncogen Lab, Herston, Qld, Australia.
RP Hayward, NK (reprint author), QIMR Berghofer Med Res Inst, Oncogen Lab, Herston, Qld, Australia.
EM nick.hayward@qimrberghofer.edu.au
NR 122
TC 11
Z9 11
U1 4
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD MAY
PY 2016
VL 29
IS 3
BP 266
EP 283
DI 10.1111/pcmr.12459
PG 18
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA DK1TH
UT WOS:000374696700006
PM 26833684
ER

PT J
AU Kishimoto, T
   Chawla, JM
   Hagi, K
   Zarate, CA
   Kane, JM
   Bauer, M
   Correll, CU
AF Kishimoto, T.
   Chawla, J. M.
   Hagi, K.
   Zarate, C. A., Jr.
   Kane, J. M.
   Bauer, M.
   Correll, C. U.
TI Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate
   receptor antagonists for unipolar and bipolar depression: a
   meta-analysis of efficacy, safety and time trajectories
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Bipolar depression; depression; ketamine; meta-analyses;
   N-methyl-D-aspartate receptor antagonists; trajectories
ID TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIAL;
   PROOF-OF-CONCEPT; ADD-ON TRIAL; MAJOR DEPRESSION; ANTIDEPRESSANT
   EFFICACY; INTRAVENOUS KETAMINE; CHANNEL BLOCKER; RATING-SCALE; IV
   KETAMINE
AB Background. Ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear.
   Method. We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.
   Results. A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD= 554, BD = 34), lasting 10.0 +/- 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g =-1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g =-0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.
   Conclusions. A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance.
C1 [Kishimoto, T.] Keio Univ, Sch Med, Tokyo, Japan.
   [Kishimoto, T.; Chawla, J. M.; Hagi, K.; Kane, J. M.; Correll, C. U.] Zucker Hillside Hosp, Northwell Hlth Syst, Psychiat Res, Glen Oaks, NY USA.
   [Kishimoto, T.; Kane, J. M.; Correll, C. U.] Hofstra Northwell Sch Med, Hempstead, NY USA.
   [Kishimoto, T.; Kane, J. M.; Correll, C. U.] Feinstein Inst Med Res, Manhasset, NY USA.
   [Hagi, K.] Sumitomo Dainippon Pharma Co Ltd, Med Affairs, Tokyo, Japan.
   [Zarate, C. A., Jr.] NIMH, Northwell Hlth Syst, Bethesda, MD 20892 USA.
   [Bauer, M.] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Klin & Poliklin Psychiat & Psychotherapie, D-01062 Dresden, Germany.
RP Correll, CU (reprint author), Zucker Hillside Hosp, Psychiat, 75-59 263rd St, Glen Oaks, NY 11004 USA.
EM ccorrell@lij.edu
FU Zucker Hillside Hospital Mental Advanced Center for Intervention and
   Services Research for the Study of Schizophrenia from the NIMH,
   Bethesda, MD [P30MH090590]
FX Funding for this study was supported in part by The Zucker Hillside
   Hospital Mental Advanced Center for Intervention and Services Research
   for the Study of Schizophrenia (P30MH090590) from the NIMH, Bethesda,
   MD. The NIMH had no further role in study design; in the collection,
   analysis and interpretation of data; in the writing of the report; and
   in the decision to submit the paper for publication.
NR 54
TC 12
Z9 12
U1 12
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 MAY
PY 2016
VL 46
IS 7
BP 1459
EP 1472
DI 10.1017/S0033291716000064
PG 14
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DJ4IN
UT WOS:000374168700011
PM 26867988
ER

PT J
AU Hwang, S
   Nolan, ZT
   White, SF
   Williams, WC
   Sinclair, S
   Blair, RJR
AF Hwang, S.
   Nolan, Z. T.
   White, S. F.
   Williams, W. C.
   Sinclair, S.
   Blair, R. J. R.
TI Dual neurocircuitry dysfunctions in disruptive behavior disorders:
   emotional responding and response inhibition
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Amygdala; callous-unemotional trait; disruptive behavior disorder;
   emotional responding; response inhibition
ID CALLOUS-UNEMOTIONAL TRAITS; CONDUCT PROBLEMS; PSYCHOPATHIC TRAITS;
   AMYGDALA RESPONSE; NEURAL RESPONSES; EXPECTED VALUE; CHILDREN; YOUTHS;
   CONNECTIVITY; ADOLESCENTS
AB Background. To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits.
   Method. Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (groupxemotion by task) was conducted on the BOLD response data.
   Results. Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD.
   Conclusions. These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.
C1 [Hwang, S.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
   [Nolan, Z. T.] Penn State Coll Med, MD PhD Program, Hershey, PA USA.
   [White, S. F.] Boystown Natl Res Hosp, Boystown, NE USA.
   [Williams, W. C.] Stanford Univ, Dept Psychol, Stanford, CA USA.
   [Sinclair, S.; Blair, R. J. R.] NIMH, Dept Hlth & Human Serv, Sect Affect Cognit Neurosci, NIH, Bethesda, MD 20892 USA.
RP Hwang, S (reprint author), Univ Nebraska Med Ctr, Dept Psychiat, 987830 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM soonjo.hwang@unmc.edu
FU National Institute of Mental Health, National Institutes of Health
   [1-ZIA-MH002860-08]
FX Drs Hwang, White, Sinclair, and Blair are with the Intramural Research
   Program at the National Institute of Mental Health, National Institutes
   of Health. This work was supported by the Intramural Research Program at
   the National Institute of Mental Health, National Institutes of Health
   under grant number 1-ZIA-MH002860-08 to Dr Blair. Ethics approval for
   this study was granted by the NIH Combined Neuroscience Institutional
   Review Board under protocol number 05-M-0105.
NR 57
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 MAY
PY 2016
VL 46
IS 7
BP 1485
EP 1496
DI 10.1017/S0033291716000118
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DJ4IN
UT WOS:000374168700013
PM 26875722
ER

PT J
AU Stoddard, J
   Gotts, SJ
   Brotman, MA
   Lever, S
   Hsu, D
   Zarate, C
   Ernst, M
   Pine, DS
   Leibenluft, E
AF Stoddard, J.
   Gotts, S. J.
   Brotman, M. A.
   Lever, S.
   Hsu, D.
   Zarate, C., Jr.
   Ernst, M.
   Pine, D. S.
   Leibenluft, E.
TI Aberrant intrinsic functional connectivity within and between
   corticostriatal and temporal-parietal networks in adults and youth with
   bipolar disorder
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Bipolar disorder; children; functional connectivity; imaging; resting
   state
ID RESTING-STATE FMRI; INDEPENDENT COMPONENT ANALYSIS; GLOBAL ASSESSMENT
   SCALE; WORKING-MEMORY TASK; LINE BRAIN ACTIVITY; 1ST-DEGREE RELATIVES;
   UNIPOLAR DEPRESSION; PSYCHOSIS HISTORY; EUTHYMIC PATIENTS; RATING-SCALE
AB Background. Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas.
   Method. We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks.
   Results. Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group x diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation.
   Conclusions. These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.
C1 [Stoddard, J.; Brotman, M. A.; Lever, S.; Leibenluft, E.] NIMH, Dept Hlth & Human Serv, Sect Bipolar Spectrum Disorders, Emot & Dev Branch,NIH, 9000 Rockville Pike MSC 2670,Bldg 15K, Bethesda, MD 20892 USA.
   [Gotts, S. J.] NIMH, Dept Hlth & Human Serv, Sect Cognit Neuropsychol, NIH, Bethesda, MD 20892 USA.
   [Hsu, D.] Emory Univ, Sch Med, Atlanta, GA USA.
   [Zarate, C., Jr.] NIMH, Dept Hlth & Human Serv, Sect Neurobiol & Treatment Mood Disorders, NIH, Bethesda, MD 20892 USA.
   [Ernst, M.; Pine, D. S.] NIMH, Dept Hlth & Human Serv, Sect Dev & Affect Neurosci, Emot & Dev Branch,NIH, Bethesda, MD 20892 USA.
RP Stoddard, J (reprint author), NIMH, Dept Hlth & Human Serv, Sect Bipolar Spectrum Disorders, Emot & Dev Branch,NIH, 9000 Rockville Pike MSC 2670,Bldg 15K, Bethesda, MD 20892 USA.
EM joel.stoddard@nih.gov
RI Brotman, Melissa/H-7409-2013
FU NIMH;  [ZIA-MH002778];  [ZIA-MH002786]
FX This research was supported by the Intramural Research Program of the
   NIMH, and it was conducted under projects ZIA-MH002778 (clinical
   protocol NCT00006177) and ZIA-MH002786 (clinical protocol NCT00025935).
NR 71
TC 1
Z9 1
U1 4
U2 6
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 MAY
PY 2016
VL 46
IS 7
BP 1509
EP 1522
DI 10.1017/S0033291716000143
PG 14
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DJ4IN
UT WOS:000374168700015
PM 26924633
ER

PT J
AU Paksarian, D
   Merikangas, KR
   Calkins, ME
   Gur, RE
AF Paksarian, Diana
   Merikangas, Kathleen R.
   Calkins, Monica E.
   Gur, Raquel E.
TI Racial-ethnic disparities in empirically-derived subtypes of subclinical
   psychosis among a U.S. sample of youths (vol 170, pg 205, 2016)
SO SCHIZOPHRENIA RESEARCH
LA English
DT Correction
C1 [Paksarian, Diana; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, 35A Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
   [Calkins, Monica E.; Gur, Raquel E.] Univ Penn, Neuropsychiat Sect, Dept Psychiat, Perelman Sch Med, 3400 Spruce St,10th Floor,Gates Bldg, Philadelphia, PA 19104 USA.
RP Paksarian, D (reprint author), NIMH, Genet Epidemiol Res Branch, Intramural Res Program, 35A Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM diana.paksarian@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAY
PY 2016
VL 173
IS 1-2
BP 119
EP 119
DI 10.1016/j.schres.2016.02.030
PG 1
WC Psychiatry
SC Psychiatry
GA DK6SN
UT WOS:000375055600019
PM 27087272
ER

PT J
AU Cannon, RO
AF Cannon, Richard O., III
TI MY APPROACH to chest pain with normal coronary arteries
SO TRENDS IN CARDIOVASCULAR MEDICINE
LA English
DT Editorial Material
C1 [Cannon, Richard O., III] NHLBI, Inst Review Board, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Cannon, RO (reprint author), NHLBI, Inst Review Board, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM cannonr@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1050-1738
J9 TRENDS CARDIOVAS MED
JI Trends Cardiovasc. Med.
PD MAY
PY 2016
VL 26
IS 4
BP 391
EP 392
DI 10.1016/j.tcm.2015.06.010
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DK0RN
UT WOS:000374620000016
PM 26944230
ER

PT J
AU Filler, K
   Lyon, D
   McCain, N
   Bennett, J
   Fernandez-Martinez, JL
   deAndres-Galiana, EJ
   Elswick, RK
   Lukkahatai, N
   Saligan, L
AF Filler, Kristin
   Lyon, Debra
   McCain, Nancy
   Bennett, James, Jr.
   Luis Fernandez-Martinez, Juan
   Juan deAndres-Galiana, Enrique
   Elswick, R. K., Jr.
   Lukkahatai, Nada
   Saligan, Leorey
TI Relationship of Mitochondrial Enzymes to Fatigue Intensity in Men With
   Prostate Cancer Receiving External Beam Radiation Therapy
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE fatigue; mitochondria; radiation therapy
ID QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; MECHANISMS; ANEMIA; SCALES
AB Purpose: Mitochondrial dysfunction is a plausible biological mechanism for cancer-related fatigue. Specific aims of this study were to (1) describe the levels of mitochondrial oxidative phosphorylation complex (MOPC) enzymes, fatigue, and health-related quality of life (HRQOL) before and at completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (PC); (2) examine relationships over time among levels of MOPC enzymes, fatigue, and HRQOL; and (3) compare levels of MOPC enzymes in men with clinically significant and nonsignificant fatigue intensification during EBRT.
   Methods: Fatigue was measured by the revised Piper Fatigue Scale and the Functional Assessment of Cancer Therapy-Fatigue subscale (FACT-F). MOPC enzymes (Complexes I-V) and mitochondrial antioxidant superoxide dismutase 2 were measured in peripheral blood using enzyme-linked immunosorbent assay at baseline and completion of EBRT. Participants were categorized into high or low fatigue (HF vs. LF) intensification groups based on amount of change in FACT-F scores during EBRT.
   Results: Fatigue reported by the 22 participants with PC significantly worsened and HRQOL significantly declined from baseline to EBRT completion. The HF group comprised 12 men with clinically significant change in fatigue (HF) during EBRT. Although no significant changes were observed in MOPC enzymes from baseline to EBRT completion, there were important differences in the patterns in the levels of MOPC enzymes between HF and LF groups.
   Conclusion: Distinct patterns of changes in the absorbance of MOPC enzymes delineated fatigue intensification among participants. Further investigation using a larger sample is warranted.
C1 [Filler, Kristin; Saligan, Leorey] NINR, NIH, 9000 Rockville Pike,Bldg 3,Room 5E14, Bethesda, MD 20892 USA.
   [Lyon, Debra] Univ Florida, Gainesville, FL USA.
   [McCain, Nancy; Elswick, R. K., Jr.] Virginia Commonwealth Univ, Richmond, VA USA.
   [Bennett, James, Jr.] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA 23298 USA.
   [Luis Fernandez-Martinez, Juan; Juan deAndres-Galiana, Enrique] Univ Oviedo, Dept Math, Oviedo, Spain.
   [Lukkahatai, Nada] Univ Nevada, Las Vegas, NV 89154 USA.
RP Saligan, L (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 3,Room 5E14, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
OI deAndres-Galiana, Enrique J/0000-0001-8555-3832
FU Jonas Nurse Leaders Scholar Program; Jonas Center for Nursing
   Excellence/AACN; Doctoral Degree Scholarship in Cancer Nursing from the
   American Cancer Society [122565-DSCN-12-204-01-SCN]; Graduate
   Partnership Program of the National Institutes of Health, National
   Institute of Nursing Research
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This
   research was supported by grants from the Jonas Nurse Leaders Scholar
   Program, the Jonas Center for Nursing Excellence/AACN, the Doctoral
   Degree Scholarship in Cancer Nursing (122565-DSCN-12-204-01-SCN) from
   the American Cancer Society, and the Graduate Partnership Program of the
   National Institutes of Health, National Institute of Nursing Research.
NR 29
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
EI 1552-4175
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD MAY
PY 2016
VL 18
IS 3
BP 274
EP 280
DI 10.1177/1099800415617848
PG 7
WC Nursing
SC Nursing
GA DJ5LA
UT WOS:000374248300003
PM 26584846
ER

PT J
AU Hsiao, CP
   Reddy, SY
   Chen, MK
   Saligan, LN
AF Hsiao, Chao-Pin
   Reddy, Swarnalatha Y.
   Chen, Mei-Kuang
   Saligan, Leorey N.
TI Genomic Profile of Fatigued Men Receiving Localized Radiation Therapy
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE microarray; gene expression; fatigue; radiation therapy; prostate
   cancer; membrane-spanning four domains; subfamily A; member (MS4A1
ID CANCER-RELATED FATIGUE; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE;
   PROSTATE-CANCER; GENE-EXPRESSION; NECK-CANCER; ASSOCIATION; SYSTEM;
   DEPRESSION; PATHWAYS
AB Purpose: The purpose of this study was to explore gene expression changes in fatigued men with nonmetastatic prostate cancer receiving localized external beam radiation therapy (EBRT).
   Methods: Fatigue was measured in 40 men with prostate cancer (20 receiving EBRT and 20 controls on active surveillance) using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F). EBRT subjects were followed from baseline to midpoint and end point of EBRT, while controls were seen at one time point. EBRT subjects were categorized into high- and low-fatigue groups based on change in FACT-F scores from baseline to EBRT completion. Full genome microarray was performed from peripheral leukocyte RNA to determine gene expression changes related to fatigue phenotypes. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay confirmed the most differentially expressed gene in the microarray experiment.
   Results: At baseline, mean FACT-F scores were not different between EBRT subjects (44.3 7.16) and controls (46.7 +/- 4.32, p = .24). Fatigue scores of EBRT subjects decreased at treatment midpoint (38.6 +/- 9.17, p = .01) and completion (37.6 +/- 9.9, p = .06), indicating worsening fatigue. Differential expression of 42 genes was observed between fatigue groups when EBRT time points were controlled. Membrane-spanning four domains, subfamily A, member (MS4A1) was the most differentially expressed gene and was associated with fatigue at treatment end point (r = -.46, p = .04).
   Conclusion: Fatigue intensification was associated with MS4A1 downregulation, suggesting that fatigue during EBRT may be related to impairment in B-cell immune response. The 42 differentially expressed fatigue-related genes are associated with glutathione biosynthesis, -glutamyl cycle, and antigen presentation pathways.
C1 [Hsiao, Chao-Pin; Reddy, Swarnalatha Y.; Saligan, Leorey N.] NINR, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Hsiao, Chao-Pin] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
   [Chen, Mei-Kuang] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
RP Saligan, LN (reprint author), NINR, NIH, 3 Ctr Dr,Bldg 3,Room 5E14, Bethesda, MD 20892 USA.
EM saliganl@mail.nih.gov
OI Chen, Mei-kuang/0000-0002-0407-6788
FU Division of Intramural Research of the National Institute of Nursing
   Research of the National Institutes of Health, Bethesda, MD [09-NR-0088]
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: This study
   is fully supported by the Division of Intramural Research of the
   National Institute of Nursing Research of the National Institutes of
   Health, Bethesda, MD (Protocol # 09-NR-0088).
NR 44
TC 0
Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
EI 1552-4175
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD MAY
PY 2016
VL 18
IS 3
BP 281
EP 289
DI 10.1177/1099800415618786
PG 9
WC Nursing
SC Nursing
GA DJ5LA
UT WOS:000374248300004
PM 26620220
ER

PT J
AU Mathur, MB
   Epel, E
   Kind, S
   Desai, M
   Parks, CG
   Sandler, DP
   Khazeni, N
AF Mathur, Maya B.
   Epel, Elissa
   Kind, Shelley
   Desai, Manisha
   Parks, Christine G.
   Sandler, Dale P.
   Khazeni, Nayer
TI Perceived stress and telomere length: A systematic review,
   meta-analysis, and methodologic considerations for advancing the field
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Review
DE Telomere; Stress; Cellular damage; Meta-analysis
ID CORONARY-HEART-DISEASE; LIFE STRESS; PSYCHOLOGICAL STRESS;
   CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; DEPRESSION; ASSOCIATION;
   CANCER; ADULTS; HEALTH
AB Importance: Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes.
   Objective: We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL).
   Data sources: We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data.
   Study selection: Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed.
   Data extraction and synthesis: We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study).
   Main outcomes and measures: We conducted random-effects meta-analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression.
   Results: Increased PS was associated with a very small decrease in TL (n = 8724 total; r = -0.06; 95% CI: -0.10, -0.008; p = 0.01; alpha = 0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r = -0.13; vs. general samples: b = -0.11; 95% CI: -027, 0.01; p = 0.05; alpha = 0.013). Publication bias may exist; correcting for its effects attenuated the relationship.
   Conclusions and relevance: Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample-size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress. (C) 2016 The Authors. Published by Elsevier Inc.
C1 [Mathur, Maya B.; Desai, Manisha] Stanford Univ, Quantitat Sci Unit, 1070 Arastradero Rd, Palo Alto, CA 94305 USA.
   [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
   [Kind, Shelley] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA.
   [Parks, Christine G.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
   [Khazeni, Nayer] Stanford Univ, Div Pulm & Crit Care Med, Stanford, CA 94305 USA.
   [Khazeni, Nayer] Stanford Univ, Ctr Hlth Policy, Stanford, CA 94305 USA.
   [Khazeni, Nayer] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA.
RP Mathur, MB (reprint author), Stanford Univ, Quantitat Sci Unit, 1070 Arastradero Rd, Palo Alto, CA 94305 USA.
EM mmathur@stanford.edu
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018
FU Agency for Healthcare Research and Policy [1 K08 HS019816]; Wisconsin
   Partnership Program PERC Award [233 PRJ 25DJ]; National Institutes of
   Health's Clinical and Translational Science Award [5UL1RR025011];
   National Heart, Lung, and Blood Institute [1 RC2 HL101468]; Intramural
   Research Program of the NIH, National Institute of Environmental Health
   Sciences [ZO1 ES044005]; Department of Defense Breast Cancer Research
   Concept Award [BC045286]
FX This research was supported by the Agency for Healthcare Research and
   Policy (1 K08 HS019816, Dr. Khazeni). The Survey of the Health of
   Wisconsin, from which we obtained raw data, was funded by the Wisconsin
   Partnership Program PERC Award (233 PRJ 25DJ), the National Institutes
   of Health's Clinical and Translational Science Award (5UL1RR025011), and
   the National Heart, Lung, and Blood Institute (1 RC2 HL101468). The
   Sister Study was supported by the Intramural Research Program of the
   NIH, National Institute of Environmental Health Sciences (ZO1 ES044005),
   and telomere assays supported in part through by Department of Defense
   Breast Cancer Research Concept Award (BC045286, Dr. Parks). The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 92
TC 7
Z9 9
U1 4
U2 18
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 MAY
PY 2016
VL 54
BP 158
EP 169
DI 10.1016/j.bbi.2016.02.002
PG 12
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA DJ4VW
UT WOS:000374207200016
PM 26853993
ER

PT J
AU Simon, CD
   Adam, EK
   McKinney, CO
   Krohn, JB
   Shalowitz, MU
AF Simon, Clarissa D.
   Adam, Emma K.
   McKinney, Chelsea O.
   Krohn, Julie B.
   Shalowitz, Madeleine U.
TI Breastfeeding, Bed-Sharing, and Maternal Cortisol
SO CLINICAL PEDIATRICS
LA English
DT Article
DE cortisol; breastfeeding; bed-sharing; stress; cosleeping; postpartum
   health
ID PITUITARY-ADRENAL AXIS; INFANT-DEATH-SYNDROME; SALIVARY CORTISOL;
   POSTPARTUM MOTHERS; LACTATING WOMEN; STRESS; SLEEP; PREGNANCY;
   RESPONSES; RHYTHM
AB Prior studies have found that close mother-child sleep proximity helps increase rates of breastfeeding, and breastfeeding itself is linked to better maternal and infant health. In this study, we examine whether breastfeeding and infant bed-sharing are related to daily rhythms of the stress-responsive hormone cortisol. We found that bed-sharing was related to flatter diurnal cortisol slopes, and there was a marginal effect for breastfeeding to predict steeper cortisol slopes. Furthermore, mothers who breastfeed but do not bed-share had the steepest diurnal cortisol slopes, whereas mothers who bed-shared and did not breastfeed had the flattest slopes (P < .05). These results were significant after controlling for subjective sleep quality, perceived stress, depression, socioeconomic status, race, and maternal age. Findings from this study indicate that infant parenting choices recommended for infants (breastfeeding and separate sleep surfaces for babies) may also be associated with more optimal stress hormone profiles for mothers.
C1 [Simon, Clarissa D.; Adam, Emma K.] Northwestern Univ, Sch Educ & Social Policy, 2120 Campus Dr, Evanston, IL 60201 USA.
   [Simon, Clarissa D.; Adam, Emma K.; McKinney, Chelsea O.; Krohn, Julie B.; Shalowitz, Madeleine U.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Baltimore, MD USA.
   [Adam, Emma K.] Inst Policy Res, Evanston, IL USA.
   [McKinney, Chelsea O.; Shalowitz, Madeleine U.] NorthShore Univ, Hlth Syst Res Inst, Evanston, IL USA.
   [Krohn, Julie B.] Lake Cty Hlth Dept & Community Hlth Ctr, Waukegan, IL USA.
RP Simon, CD (reprint author), Northwestern Univ, Sch Educ & Social Policy, 2120 Campus Dr, Evanston, IL 60201 USA.
EM clarissa.simon@northwestern.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [U HD44207, U HD44219, U HD44226, U HD44245, U HD44253, U
   HD54791, U HD54019, U HD44226-05S1, U HD44245-06S1, R03 HD59584];
   National Institute for Nursing Research [U NR008929]
FX The author(s) disclosed receipt of the following financial support for
   the research, authorship, and/or publication of this article: The CCHN
   is supported through cooperative agreements with the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development (U
   HD44207, U HD44219, U HD44226, U HD44245, U HD44253, U HD54791, U
   HD54019, U HD44226-05S1, U HD44245-06S1, R03 HD59584) and the National
   Institute for Nursing Research (U NR008929).
NR 52
TC 0
Z9 0
U1 2
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
EI 1938-2707
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD MAY
PY 2016
VL 55
IS 5
BP 470
EP 478
DI 10.1177/0009922815601981
PG 9
WC Pediatrics
SC Pediatrics
GA DJ5FM
UT WOS:000374232200011
PM 26330120
ER

PT J
AU Seam, N
   Suffredini, AF
AF Seam, Nitin
   Suffredini, Anthony F.
TI Steroids are part of rescue therapy in ARDS patients with refractory
   hypoxemia: we are not sure
SO INTENSIVE CARE MEDICINE
LA English
DT Editorial Material
ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; INFLAMMATORY
   CYTOKINES; PERSISTENT ELEVATION; BERLIN DEFINITION; CORTICOSTEROIDS;
   INFUSION; PREDICTS; TIME
C1 [Seam, Nitin; Suffredini, Anthony F.] Ctr Clin, Dept Crit Care Med, NIH, Bldg 10,Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Suffredini, AF (reprint author), Ctr Clin, Dept Crit Care Med, NIH, Bldg 10,Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA.
EM asuffredini@cc.nih.gov
FU Intramural NIH HHS
NR 23
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
EI 1432-1238
J9 INTENS CARE MED
JI Intensive Care Med.
PD MAY
PY 2016
VL 42
IS 5
BP 924
EP 927
DI 10.1007/s00134-015-4160-z
PG 4
WC Critical Care Medicine
SC General & Internal Medicine
GA DJ4LJ
UT WOS:000374176700049
PM 26883255
ER

PT J
AU Simonsen, L
   Viboud, C
AF Simonsen, Lone
   Viboud, Cecile
TI The power of historical data for assessment of childhood vaccine
   benefits
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
C1 [Simonsen, Lone] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
   [Simonsen, Lone] Univ Copenhagen, Inst Folkesundhedsvidenskab, DK-1353 Copenhagen K, Denmark.
   [Viboud, Cecile] NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Simonsen, L (reprint author), Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.; Simonsen, L (reprint author), Univ Copenhagen, Inst Folkesundhedsvidenskab, DK-1353 Copenhagen K, Denmark.
EM simonsen@sund.ku.dk
OI Simonsen, Lone/0000-0003-1535-8526
NR 8
TC 0
Z9 0
U1 0
U2 1
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 MAY
PY 2016
VL 16
IS 5
BP 516
EP 518
DI 10.1016/S1473-3099(16)00060-8
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA DJ5TL
UT WOS:000374272900010
PM 26873664
ER

PT J
AU Keutgen, XM
   Nilubol, N
   Kebebew, E
AF Keutgen, Xavier M.
   Nilubol, Naris
   Kebebew, Electron
TI Malignant-functioning neuroendocrine tumors of the pancreas: A survival
   analysis
SO SURGERY
LA English
DT Article
ID ISLET-CELL CARCINOMA; CONTEMPORARY-SERIES; ENDOCRINE CARCINOMA; FEATURES
AB Background. Malignant functioning pancreatic neuroendocrine tumors (mFpNETs) are rare. Research analyzing the presentation, biological behavior, and patient outcomes of these tumors is limited.
   Methods. We used the Surveillance, Epidemiology, and End Results database to identify patients with malignant insulinomas, gastrinomas, glucagonomas, vasoactive intestinal peptide secreting tumors (VIPomas), somastatinomas, and mixed islet cell tumors (MICTs). The primary endpoint of this study was to identify factors affecting survival.
   Results. We identified 401 patients with mFpNETs. Between histologic subtypes, there were significant differences in sex and age, and in tumor size, grade, location, and stage. Median survival time for insulinomas was 12.7 years; gastrinomas, 10.2 years; glucagonomas, 7.7 years; VIPomas, 7.9 years; and MICTs, 3.4 years. Multivariable analysis showed that histology (insulinoma, gastrinoma, and VIPoma; P = .009), absence of distant metastases (P = .002), age < 50 years (P = .001), surgical intervention (P = .001), and stage I/II disease (P = .011) were independently associated with prolonged survival. Subgroup analysis demonstrated that removal of the primary tumor in stage IV mFpNETs was associated with significantly prolonged survival (P = .01).
   Conclusion. inFpNETs are rare tumors that commonly present at an advanced stage despite hormonal secretion. Primary tumor resection is associated with longer survival in stages as well as stage IV tumors.
C1 [Keutgen, Xavier M.; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Keutgen, XM (reprint author), NCI, Endocrine Oncol Branch, NIH, 10 Ctr Dr,3W-5840, Bethesda, MD 20892 USA.
EM xavier.keutgen@nih.gov
NR 17
TC 2
Z9 2
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 MAY
PY 2016
VL 159
IS 5
BP 1382
EP 1389
DI 10.1016/j.surg.2015.11.010
PG 8
WC Surgery
SC Surgery
GA DJ4WI
UT WOS:000374208400017
PM 26704781
ER

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