FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Crossey, E Amar, MJA Sampson, M Peabody, J Schiller, JT Chackerian, B Remaley, AT AF Crossey, Erin Amar, Marcelo J. A. Sampson, Maureen Peabody, Julianne Schiller, John T. Chackerian, Bryce Remaley, Alan T. TI A cholesterol-lowering VLP vaccine that targets PCSK9 SO VACCINE LA English DT Article DE PCSK9; Vaccine; Virus-like particles; LDL Cholesterol ID SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN RECEPTOR; PLASMA LDL-CHOLESTEROL; HIGH-RISK PATIENTS; IMMUNODEFICIENCY VIRUS; CARDIOVASCULAR EVENTS; NONHUMAN-PRIMATES; CHRONIC DISEASES; REDUCING LIPIDS; CELL RESPONSES AB Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the low-density lipoprotein receptor (LDL-R). Mutations that cause increased activity of PCSK9 are associated with hypercholesterolemia, atherosclerosis and early cardiovascular disease (CVD), whereas individuals with loss-of-function mutations in PCSK9 are apparently healthy but are hypocholesterolemic and have a dramatically decreased risk of CVD. In this study, we generated virus-like particle (VLP)-based vaccines targeting PCSK9. Mice and macaques vaccinated with bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG antibodies that bound to circulating PCSK9. Vaccination was associated with significant reductions in total cholesterol, free cholesterol, phospholipids, and triglycerides. A vaccine targeting PCSK9 may, therefore, be an attractive alternative to monoclonal antibody-based therapies. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Crossey, Erin; Peabody, Julianne; Chackerian, Bryce] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Amar, Marcelo J. A.; Sampson, Maureen; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA. [Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Chackerian, B (reprint author), Univ New Mexico, Dept Mol Genet & Microbiol, MSC08-4660, Albuquerque, NM 87131 USA. EM bchackerian@salud.unm.edu; aremaley1@nhlbi.nih.gov FU NIH [R01 AI083305]; Intramural Research Program of NHLBI; University of New Mexico Biology of Infectious Diseases and Inflammation Training Grant [T32 AI007538] FX This research was funded in part by NIH grant R01 AI083305 (to BC) and by the Intramural Research Program of NHLBI. EC was supported by the University of New Mexico Biology of Infectious Diseases and Inflammation Training Grant (T32 AI007538). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 11 Z9 12 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD OCT 26 PY 2015 VL 33 IS 43 BP 5747 EP 5755 DI 10.1016/j.vaccine.2015.09.044 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CU8WK UT WOS:000363824600004 PM 26413878 ER PT J AU Tatalovich, Z Zhu, L Rolin, A Lewis, DR Harlan, LC Winn, DM AF Tatalovich, Zaria Zhu, Li Rolin, Alicia Lewis, Denise R. Harlan, Linda C. Winn, Deborah M. TI Geographic disparities in late stage breast cancer incidence: results from eight states in the United States SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article DE Cancer; Late stage; Geographic disparities; Breast cancer ID SOCIOECONOMIC-STATUS; DIAGNOSIS; ACCESS; MAMMOGRAPHY; MORTALITY; ASSOCIATION; ILLINOIS; POVERTY; TIME; RISK AB Background: Late stage of cancer at diagnosis is an important predictor of cancer mortality. In many areas worldwide, cancer registry systems, available data and mapping technologies can provide information about late stage cancer by geographical regions, offering valuable opportunities to identify areas where further investigation and interventions are needed. The current study examined geographical variation in late stage breast cancer incidence across eight states in the United States with the objective to identify areas that might benefit from targeted interventions. Methods: Data from the Surveillance Epidemiology and End Results Program on late stage breast cancer incidence was used as dependent variable in regression analysis and certain factors known to contribute to high rates of late stage cancer (socioeconomic characteristics, health insurance characteristics, and the availability and utilization of cancer screening) as covariates. Geographic information systems were used to map and highlight areas that have any combination of high late stage breast cancer incidence and significantly associated risk factors. Results: The differences in mean rates of late stage breast cancer between eight states considered in this analysis are statistically significant. Factors that have statistically negative association with late stage breast cancer incidence across the eight states include: density of mammography facilities, percent population with Bachelor's degree and English literacy while percent black population has statistically significant positive association with late stage breast cancer incidence. Conclusions: This study describes geographic disparities in late stage breast cancer incidence and identifies areas that might benefit from targeted interventions. The results suggest that in the eight US states examined, higher rates of late stage breast cancer are more common in areas with predominantly black population, where English literacy, percentage of population with college degree and screening availability are low. The approach described in this work may be utilized both within and outside US, wherever cancer registry systems and technologies offer the same opportunity to identify places where further investigation and interventions for reducing cancer burden are needed. C1 [Tatalovich, Zaria; Zhu, Li; Rolin, Alicia; Lewis, Denise R.; Harlan, Linda C.; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Tatalovich, Zaria] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. RP Tatalovich, Z (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. EM tatalovichzp@mail.nih.gov NR 34 TC 2 Z9 2 U1 4 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD OCT 24 PY 2015 VL 14 AR 31 DI 10.1186/s12942-015-0025-5 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU1SE UT WOS:000363300800001 PM 26497363 ER PT J AU Fairlie, L Karalius, B Patel, K van Dyke, RB Hazra, R Hernan, MA Siberry, GK Seage, GR Agwu, A Wiznia, A AF Fairlie, Lee Karalius, Brad Patel, Kunjal van Dyke, Russell B. Hazra, Rohan Hernan, Miguel A. Siberry, George K., III Seage, George R. Agwu, Allison Wiznia, Andrew CA Pediat HIV AIDS Cohort Study Int Maternal Pediat Adolescent AID TI CD4(+) and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States SO AIDS LA English DT Article DE CD4(+) and viral load outcomes; HIV-infected children; virological failure ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOLOGICAL OUTCOMES; PROTEASE INHIBITOR; AFRICAN CHILDREN; OPEN-LABEL; ADOLESCENTS; MORTALITY; PREDICTORS; ADHERENCE; INFANTS AB Objective: This study compared 12-month CD4(+) and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies.Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C.Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4(+)% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models.Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4(+)% from baseline, 0.59 percentage points [95% confidence interval (95% CI) -1.01 to 2.19], not different than those who continued failing cART (71%) (-0.64 percentage points, P=0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P=0.64). Children discontinuing all ART (7%) experienced significant CD4(+)% decline -3.18 percentage points (95% CI -5.25 to -1.11) compared with those initiating new cART (P=0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log(10)VL by 12 months, the new cART group having the largest drop (-1.15 log(10)VL).Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. C1 [Fairlie, Lee] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst WRHI, Johannesburg, South Africa. [Karalius, Brad; Patel, Kunjal; Hernan, Miguel A.; Seage, George R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [van Dyke, Russell B.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Hazra, Rohan; Siberry, George K., III] NICHD, NIH, Bethesda, MD USA. [Hernan, Miguel A.] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. [Agwu, Allison] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wiznia, Andrew] Albert Einstein Coll Med, Jacobi Med Ctr, Family Based Serv, Bronx, NY 10467 USA. RP Fairlie, L (reprint author), Wits RHI, Hillbrow Hlth Precinct, 22 Esselen St, ZA-2001 Johannesburg, South Africa. EM lfairlie@wrhi.ac.za FU National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) [UM1AI068632, UM1AI068616, UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH); National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases (NIAID); Office of AIDS Research; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; Harvard University School of Public Health [HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University School of Medicine [HD052104, 3U01 HD052104-06S1]; NIAID [U01 AI068632, UM01 AI069463-08]; NICHD; NIMH [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health under NIAID [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group [1 U01 AI068616]; IMPAACT Group; NICHD [N01-DK-9-001/HHSN267200800001C] FX Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.; PHACS was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases (NIAID), the Office of AIDS Research, the National Institute of Mental Health (NIMH), the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3) (Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104, 3U01 HD052104-06S1) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Kenneth Rich; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). Overall support for IMPAACT was provided by NIAID (U01 AI068632), NICHD and NIMH (AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the NIAID cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). L.F. is funded by NIAID UM01 AI069463-08 (IMPAACT) and Cooperative Agreement AID-674-A-00-08-00005-00 PEPFAR/USAID. NR 36 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD OCT 23 PY 2015 VL 29 IS 16 BP 2109 EP 2119 DI 10.1097/QAD.0000000000000809 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4IF UT WOS:000368476000002 PM 26182197 ER PT J AU Cillo, AR Hilldorfer, BB Lalama, CM McKinnon, JE Coombs, RW Tenorio, AR Fox, L Gandhi, RT Ribaudo, H Currier, JS Gulick, RM Wilkin, TJ Mellors, JW AF Cillo, Anthony R. Hilldorfer, Benedict B. Lalama, Christina M. McKinnon, John E. Coombs, Robert W. Tenorio, Allan R. Fox, Lawrence Gandhi, Rajesh T. Ribaudo, Heather Currier, Judith S. Gulick, Roy M. Wilkin, Timothy J. Mellors, John W. TI Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4(+) T-cell recovery SO AIDS LA English DT Article DE antiretroviral therapy intensification; HIV-1 immunotherapeutics; HIV-1 persistence; maraviroc; suboptimal T-cell recovery ID HIV-INFECTED PATIENTS; IMMUNE ACTIVATION; RALTEGRAVIR INTENSIFICATION; HIV-1-INFECTED PATIENTS; COMBINATION THERAPY; RANDOMIZED-TRIAL; DISEASE; BLOOD; APOPTOSIS; RESPONSES AB Background:Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4(+) T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals with incomplete CD4(+) T-cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks.Design:A5256 was a single-arm trial in which individuals on suppressive ART with incomplete CD4(+) T-cell recovery added maraviroc for 24 weeks.Methods:We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-long terminal repeat (2-LTR) circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4(+) and CD8(+) T-cell immune activation (%CD38(+)HLA-DR+) and apoptosis (%caspase3(+)/Bcl-2(-)).Results:No effect of maraviroc was found on the probability of detectable plasma viremia (1copy/ml; n=31, exact McNemar P=1.0) or detectable 2-LTR circles (n=28, P=0.25) or on total HIV-1 DNA (n=28, 90% confidence interval -0.1, +0.3 log(10)copies/10(6) CD4(+) T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38(+)HLA-DR+ CD4(+) T-cells (Spearman=-0.52, P=0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38(+)HLA-DR+ CD4(+) T-cells during maraviroc intensification (Spearman=0.44, P=0.018).Conclusion:In individuals on suppressive ART with incomplete CD4(+) T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4(+) T-cell immune activation especially in individuals with low preintensification levels of HIV-1 DNA. C1 [Cillo, Anthony R.; Hilldorfer, Benedict B.; McKinnon, John E.; Mellors, John W.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Lalama, Christina M.; Ribaudo, Heather] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [McKinnon, John E.] Henry Ford Hosp, Dept Med, Div Infect Dis, Detroit, MI 48202 USA. [Coombs, Robert W.] Univ Washington, Sch Med, Dept Lab Med & Med, Seattle, WA USA. [Tenorio, Allan R.] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Fox, Lawrence] NIAID, HIV Res Branch, Bethesda, MD 20892 USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Currier, Judith S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gulick, Roy M.; Wilkin, Timothy J.] Cornell Univ, Weill Med Coll, Div Infect Dis, New York, NY 10021 USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Scaife S818,3550 Terrace St, Pittsburgh, PA 15261 USA. EM jwm1@pitt.edu FU National Institute of Allergy and Infectious Diseases [UM1AI068636]; National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); National Center for Research Resources [TR000457]; AIDS Clinical Trials Group to the Pittsburgh Virology Specialty Laboratory [AI068636]; Statistical and Data Management Center [AI068634, AAI38855]; University of Washington Center for AIDS Research (CFAR) [P30AI027757]; Pitt AIDS Research Training Grant [T32 AI065380-08]; [AI069412-08]; [AI069513]; [AI069419]; [AI069471]; [AI069472]; [AI069465]; [AI069532]; [AI069556]; [AI069424]; [AI069432]; [AI069496]; [AI069477]; [AI069494]; [AI069511]; [AI069484-07]; [AI069501]; [AI069471-08]; [AI069423-08]; [AI069439-08]; [AI069447]; [AI069452-08]; [AI69418-02]; [AI069534-08]; [AI069503-08]; [P30AI50410]; [P30AI050409]; [P30AI045008-15] FX The project described was supported by Award Number UM1AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). Participating clinical trials units were supported by the following grants: AI069412-08, AI069494, AI069513, AI069419, AI069471, AI069412-08, AI069472, AI069465, AI069532, AI069556, AI069424, AI069432, AI069496, AI069477, AI069494, AI069511, AI069484-07, AI069494, AI069501, AI069471-08, AI069423-08, AI069439-08, AI069447, AI069452-08, AI69418-02, AI069534-08, and AI069503-08. Centers for AIDS Research received support from the following grants: P30AI50410, P30AI050409 and P30AI045008-15. The National Center for Research Resources grant TR000457 supported the Clinical and Translational Science Center. This work was also supported by grants from the AIDS Clinical Trials Group to the Pittsburgh Virology Specialty Laboratory (AI068636) and the Statistical and Data Management Center (AI068634; AAI38855). R.W.C. received support from the University of Washington Center for AIDS Research (CFAR grant: P30AI027757). A.R.C. and B.B.H. received support from the Pitt AIDS Research Training Grant (T32 AI065380-08). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Allergy and Infectious Diseases or the National Institute of Health. NR 40 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD OCT 23 PY 2015 VL 29 IS 16 BP 2121 EP 2129 DI 10.1097/QAD.0000000000000810 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4IL UT WOS:000368476600001 PM 26544577 ER PT J AU van der Straten, A Montgomery, ET Musara, P Etima, J Naidoo, S Laborde, N Hartmann, M Levy, L Bennie, T Cheng, H Piper, J Grossman, CI Marrazzo, J Mensch, B AF van der Straten, Ariane Montgomery, Elizabeth T. Musara, Petina Etima, Juliane Naidoo, Sarita Laborde, Nicole Hartmann, Miriam Levy, Lisa Bennie, Thola Cheng, Helen Piper, Jeanna Grossman, Cynthia I. Marrazzo, Jeanne Mensch, Barbara CA Microbicide Trials Network-003D St TI Disclosure of pharmacokinetic drug results to understand nonadherence SO AIDS LA English DT Article DE adherence; HIV preexposure prophylaxis; microbicide; pharmacokinetic drug detection; VOICE-D Study; women AB Objectives:In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. Methods:We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N=79), inconsistent (1-74%, N=28) or high (75%; N=20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. Results:We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Conclusion:Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [van der Straten, Ariane; Montgomery, Elizabeth T.; Laborde, Nicole; Hartmann, Miriam; Cheng, Helen] RTI Int, Womens Global Hlth Imperat, San Francisco, CA 94104 USA. [van der Straten, Ariane] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Musara, Petina] Univ Zimbabwe Univ Calif San Francisco Collaborat, Harare, Zimbabwe. [Etima, Juliane] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda. [Naidoo, Sarita] South African Med Res Council, HIV Prevent Res Unit, Durban, South Africa. [Levy, Lisa] FHI360, Durham, NC USA. [Bennie, Thola] Univ Cape Town, Dept Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Piper, Jeanna] NIAID, Div Aids, Bethesda, MD 20892 USA. [Grossman, Cynthia I.] NIMH, Bethesda, MD 20892 USA. [Marrazzo, Jeanne] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Mensch, Barbara] Populat Council, New York, NY 10021 USA. RP van der Straten, A (reprint author), RTI Int, 351 Calif St,Suite 500, San Francisco, CA 94104 USA. EM ariane@rti.org OI Marrazzo, Jeanne/0000-0002-9277-7364 FU U.S. National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases [UM1AI068633, UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Mental Health FX This study was designed and implemented by the MTN. MTN-003D was funded by the U.S. National Institutes of Health (NIH). The MTN is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. NR 0 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD OCT 23 PY 2015 VL 29 IS 16 BP 2161 EP 2171 DI 10.1097/QAD.0000000000000801 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4IR UT WOS:000368477200001 PM 26544581 ER PT J AU Conley, LJ Bush, TJ Rupert, AW Sereti, I Patel, P Brooks, JT Baker, JV AF Conley, Lois J. Bush, Timothy J. Rupert, Adam W. Sereti, Irini Patel, Pragna Brooks, John T. Baker, Jason V. CA SUN Study Understand Nat Hist HIV TI Obesity is associated with greater inflammation and monocyte activation among HIV-infected adults receiving antiretroviral therapy SO AIDS LA English DT Article DE contemporary antiretroviral therapy; HIV; monocyte activation; obesity; systemic inflammation ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; T-CELL-ACTIVATION; VIRUS-INFECTION; AIDS; COAGULATION; MORTALITY; RISK; INDIVIDUALS; PREVALENCE; DISEASE AB Objectives:Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been associated with excess HIV-related cardiovascular disease and mortality. Methods:We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers [soluble CD163 (sCD163), sCD14], and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels. Results:Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4(+) cell count was 475 (308-697)cells/l, and 21% were obese (BMI 30kg/m(2)). In univariable models, obesity, smoking, and lower CD4(+) cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 [odds ratio (OR) 1.96; P = 0.02], highly sensitive C-reactive protein (OR 2.79; P<0.001) and sCD163 (OR 1.94; P=0.02), and elevated frequency of CD14(+)CD16(+) (OR 1.77; P=0.03) and CD14(dim)CD16(+) (OR 1.97; P=0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation. Conclusion:Obesity was prevalent and independently associated with greater monocyte activation and systemic inflammation. Research is needed to determine how adipose tissue excess is functionally related to persistent immunologic abnormalities among HIV-infected persons with viral suppression. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Conley, Lois J.; Bush, Timothy J.; Patel, Pragna; Brooks, John T.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30333 USA. [Rupert, Adam W.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, AIDS Monitoring Lab, Frederick, MD USA. [Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA. [Baker, Jason V.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Baker, Jason V.] Hennepin Cty Med Ctr, Div Infect Dis, Minneapolis, MN 55415 USA. RP Conley, LJ (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM ljc2@cdc.gov FU Intramural Research Program of NIAID/NIH; Leidos Biomedical Research, Inc. [HHSN261200800001E]; US Centers for Disease Control and Prevention [200-2002-00610, 200-2002-00611, 200-2002-00612, 200-2002-00613, 200-2007-23633, 200-2007-23634, 200-2007-23635, 200-2007-23636]; CDC; SUN Study Principal Investigator at Hennepin County Medical Center FX Financial support was provided by the Intramural Research Program of NIAID/NIH, Leidos Biomedical Research, Inc., contract number HHSN261200800001E, and the US Centers for Disease Control and Prevention contract numbers: 200-2002-00610, 200-2002-00611, 200-2002-00612, 200-2002-00613, 200-2007-23633, 200-2007-23634, 200-2007-23635, and 200-2007-23636. As the SUN Study sponsor, the CDC, along with the SUN Study Principal Investigator at Hennepin County Medical Center, and the lead investigator at the National Institute of Allergy and Infectious Disease, were the primary investigators involved with this analysis. They provided the study design, collection, analysis, and interpretation of data, writing of the report, and decision to submit the manuscript for publication at The Lancet HIV. NR 32 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD OCT 23 PY 2015 VL 29 IS 16 BP 2201 EP 2207 DI 10.1097/QAD.0000000000000817 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4IW UT WOS:000368477700003 PM 26544583 ER PT J AU de Martel, C Shiels, MS Franceschi, S Simard, EP Vignat, J Hall, HI Engels, EA Plummer, M AF de Martel, Catherine Shiels, Meredith S. Franceschi, Silvia Simard, Edgar P. Vignat, Jerome Hall, H. Irene Engels, Eric A. Plummer, Martyn TI Cancers attributable to infections among adults with HIV in the United States SO AIDS LA English DT Article DE AIDS; attributable fraction; cancer; HIV; infection; United States ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATOCELLULAR-CARCINOMA; HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; ANAL CANCER; COHORT; POPULATION; WOMEN; METAANALYSIS AB Objective:HIV-infected people are at increased risk of cancers of infectious origin. We estimated the burden of cancer attributable to infections among HIV-infected people in the United States in 2008.Design:Incidence rates for cancer sites associated with infections were estimated from record linkage between HIV/AIDS registries and cancer registries.Methods:Rates were applied to estimates of the population living with diagnosed HIV in the United States in 2008 to obtain the number of incident cancer cases. Site-specific attributable fractions and corresponding 95% confidence intervals (CIs) were estimated from infection prevalence among cancer cases. Infection prevalence data were derived from literature review of case series.Results:Of an estimated 6200 incident cancer cases (95% CI 6000-6500), 2500 (95% CI 2400-2700) were attributable to infection (attributable fraction = 40%, 95% CI 39-42). The most important infections were Kaposi sarcoma herpes virus, Epstein-Barr virus, and human papillomavirus, which together were responsible for 2200 new cancer cases (95% CI 2100-2400), mainly Kaposi sarcoma, lymphomas, and ano-genital cancers. The attributable fraction in HIV-infected people was highest in the age group 20-29 years (69%, 95% CI 65-72). MSM were the HIV transmission group with the highest attributable fraction (48%, 95% CI 46-50), due to the high incidence of both Kaposi sarcoma and anal cancer.Conclusion:The very high fraction of cancer attributable to infection in HIV-infected people points to special opportunities to prevent these cancers, that is, avoidance, detection, and early treatment of cancer-associated infections, and universal early detection and uninterrupted treatment of HIV infection to avoid immunosuppression. C1 [de Martel, Catherine; Franceschi, Silvia; Vignat, Jerome; Plummer, Martyn] Int Agcy Res Canc, F-69372 Lyon 08, France. [Shiels, Meredith S.; Engels, Eric A.] NCI, Rockville, MD USA. [Simard, Edgar P.] Amer Canc Soc, Atlanta, GA 30329 USA. [Hall, H. Irene] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Plummer, M (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM plummerm@iarc.fr FU Fondation de France [00039621]; Intramural Research Program of the National Cancer Institute, NCI; Bill & Melinda Gates Foundation [OPP1053353] FX The present study was supported by a grant from the Fondation de France (Grant number: 00039621) and by the Intramural Research Program of the National Cancer Institute, NCI. C.deM. was partly supported by a grant from the Bill & Melinda Gates Foundation (OPP1053353). NR 34 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD OCT 23 PY 2015 VL 29 IS 16 BP 2173 EP 2181 DI 10.1097/QAD.0000000000000808 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4IU UT WOS:000368477500001 PM 26182198 ER PT J AU Kuszak, AJ Jacobs, D Gurnev, PA Shiota, T Louis, JM Lithgow, T Bezrukov, SM Rostovtseva, TK Buchanan, SK AF Kuszak, Adam J. Jacobs, Daniel Gurnev, Philip A. Shiota, Takuya Louis, John M. Lithgow, Trevor Bezrukov, Sergey M. Rostovtseva, Tatiana K. Buchanan, Susan K. TI Evidence of Distinct Channel Conformations and Substrate Binding Affinities for the Mitochondrial Outer Membrane Protein Translocase Pore Tom40 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; GENERAL IMPORT PORE; PREPROTEIN TRANSLOCASE; SACCHAROMYCES-CEREVISIAE; PRECURSOR PROTEINS; RECEPTOR COMPLEX; CONDUCTING PORE; PRESEQUENCE; BIOGENESIS; MACHINERY AB Nearly all mitochondrial proteins are coded by the nuclear genome and must be transported into mitochondria by the translocase of the outer membrane complex. Tom40 is the central subunit of the translocase complex and forms a pore in the mitochondrial outer membrane. To date, the mechanism it utilizes for protein transport remains unclear. Tom40 is predicted to comprise a membrane-spanning beta-barrel domain with conserved beta-helical domains at both the N and C termini. To investigate Tom40 function, including the role of the N- and C-terminal domains, recombinant forms of the Tom40 protein from the yeast Candida glabrata, and truncated constructs lacking the N- and/or C-terminal domains, were functionally characterized in planar lipid membranes. Our results demonstrate that each of these Tom40 constructs exhibits at least four distinct conductive levels and that full-length and truncated Tom40 constructs specifically interact with a presequence peptide in a concentration- and voltage-dependent manner. Therefore, neither the first 51 amino acids of the N terminus nor the last 13 amino acids of the C terminus are required for Tom40 channel formation or for the interaction with a presequence peptide. Unexpectedly, substrate binding affinity was dependent upon the Tom40 state corresponding to a particular conductive level. A model where two Tom40 pores act in concert as a dimeric protein complex best accounts for the observed biochemical and electrophysiological data. These results provide the first evidence for structurally distinct Tom40 conformations playing a role in substrate recognition and therefore in transport function. C1 [Kuszak, Adam J.; Jacobs, Daniel; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Louis, John M.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Jacobs, Daniel; Gurnev, Philip A.; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Gurnev, Philip A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. [Shiota, Takuya; Lithgow, Trevor] Monash Univ, Dept Microbiol, Melbourne, Vic 3800, Australia. RP Rostovtseva, TK (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bldg 9,Rm 1E-106,9 Mem Dr, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov; skbuchan@helix.nih.gov FU National Institutes of Health grants from Intramural Research Program of NIDDK; Intramural Research Program of Eunice Kennedy Shriver NICHD; National Science Foundation EAGER Award [1249199]; Gluckstern fund of the University of Massachusetts; Australian Research Council Discovery Project Grant; Australian Research Council Linkage International Grant FX This work was supported, in whole or in part, by National Institutes of Health grants from Intramural Research Program of NIDDK (to A. J. K., D. J., and S. K. B.) and Intramural Research Program of Eunice Kennedy Shriver NICHD (to T. K. R. and S. M. B.). The authors declare that they have no conflicts of interest with the contents of this article.; Supported by National Science Foundation EAGER Award 1249199 and the Gluckstern fund of the University of Massachusetts.; Australian Research Council Laureate Fellow and acknowledges support from an Australian Research Council Discovery Project Grant and Australian Research Council Linkage International Grant. NR 60 TC 2 Z9 2 U1 4 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 2015 VL 290 IS 43 BP 26204 EP 26217 DI 10.1074/jbc.M115.642173 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CU4VA UT WOS:000363527300038 PM 26336107 ER PT J AU Sonkin, D AF Sonkin, Dmitriy TI Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors SO ELIFE LA English DT Article AB A number of TP53-MDM2 inhibitors are currently under investigation as therapeutic agents in a variety of clinical trials in patients with TP53 wild type tumors. Not all wild type TP53 tumors are sensitive to such inhibitors. In an attempt to improve selection of patients with TP53 wild type tumors, an mRNA expression signature based on 13 TP53 transcriptional target genes was recently developed (Jeay et al. 2015). Careful reanalysis of TP53 status in the study validation data set of cancer cell lines considered to be TP53 wild type detected TP53 inactivating alterations in 23% of cell lines. The subsequent reanalysis of the remaining TP53 wild type cell lines clearly demonstrated that unfortunately the 13-gene signature cannot predict response to TP53-MDM2 inhibitor in TP53 wild type tumors. C1 [Sonkin, Dmitriy] NCI, Div Canc Treatment & Diag, Rockville, MD USA. RP Sonkin, D (reprint author), NCI, Div Canc Treatment & Diag, Rockville, MD USA. EM dmitriy.sonkin@nih.gov OI Sonkin, Dmitriy/0000-0002-1649-0652 NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD OCT 22 PY 2015 VL 4 AR e10279 DI 10.7554/eLife.10279 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA DJ0MR UT WOS:000373898700001 ER PT J AU Li, ZJ Chen, P Su, R Li, YY Hu, C Wang, YG Arnovitz, S He, M Gurbuxani, S Zuo, ZX Elkahloun, AG Li, SL Weng, HY Huang, H Neilly, MB Wang, SS Olson, EN Larson, RA Le Beau, MM Zhang, JW Jiang, X Wei, MJ Jin, J Liu, PP Chen, JJ AF Li, Zejuan Chen, Ping Su, Rui Li, Yuanyuan Hu, Chao Wang, Yungui Arnovitz, Stephen He, Miao Gurbuxani, Sandeep Zuo, Zhixiang Elkahloun, Abdel G. Li, Shenglai Weng, Hengyou Huang, Hao Neilly, Mary Beth Wang, Shusheng Olson, Eric N. Larson, Richard A. Le Beau, Michelle M. Zhang, Jiwang Jiang, Xi Wei, Minjie Jin, Jie Liu, Paul P. Chen, Jianjun TI Overexpression and knockout of miR-126 both promote leukemogenesis SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GAIN-OF-FUNCTION; MICRORNA EXPRESSION PROFILES; BREAST-CANCER METASTASIS; MLL-REARRANGED LEUKEMIA; EMBRYONIC STEM-CELLS; TUMOR-SUPPRESSOR; C-KIT; VASCULAR INTEGRITY; FUNCTION MUTATIONS AB It is generally assumed that gain-and loss-of-function manipulations of a functionally important gene should lead to the opposite phenotypes. We show in this study that both overexpression and knockout of microRNA (miR)-126 surprisingly result in enhanced leukemogenesis in cooperation with the t(8;21) fusion genes AML1-ETO/RUNX1-RUNX1T1 and AML1-ETO9a (a potent oncogenic isoform of AML1-ETO). In accordance with our observation that increased expression of miR-126 is associated with unfavorable survival in patients with t(8; 21) acute myeloid leukemia (AML), we show that miR-126 overexpression exhibits a stronger effect on long-term survival and progression of AML1-ETO9a-mediated leukemia stemcells/leukemia initiating cells (LSCs/LICs) inmice than does miR-126 knockout. Furthermore, miR-126 knockout substantially enhances responsiveness of leukemia cells to standard chemotherapy. Mechanistically, miR-126 overexpression activates genes that are highly expressed in LSCs/LICs and/or primitive hematopoietic stem/progenitor cells, likely through targeting ERRFI1 and SPRED1, whereas miR-126 knockout activates genes that are highly expressed in committed, more differentiated hematopoietic progenitor cells, presumably through inducing FZD7 expression. Our data demonstrate that miR-126 plays a critical but 2-faceted role in leukemia and thereby uncover a new layer of miRNA regulation in cancer. Moreover, because miR-126 depletion can sensitize AML cells to standard chemotherapy, our data also suggest that miR-126 represents a promising therapeutic target. C1 [Li, Zejuan; Chen, Ping; Li, Yuanyuan; Hu, Chao; Wang, Yungui; Arnovitz, Stephen; He, Miao; Zuo, Zhixiang; Li, Shenglai; Weng, Hengyou; Huang, Hao; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Jiang, Xi; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Su, Rui; Hu, Chao; Wang, Yungui; Zuo, Zhixiang; Weng, Hengyou; Jiang, Xi; Chen, Jianjun] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45219 USA. [Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China. [He, Miao; Wei, Minjie] China Med Univ, Dept Pharmacol, Shenyang, Liaoning, Peoples R China. [Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Elkahloun, Abdel G.; Liu, Paul P.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel G.; Liu, Paul P.] NHGRI, Microarray Core, NIH, Bethesda, MD 20892 USA. [Wang, Shusheng; Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Wang, Shusheng] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. [Zhang, Jiwang] Loyola Univ, Ctr Med, Cardinal Bernardin Canc Ctr, Inst Oncol, Maywood, IL 60153 USA. RP Chen, JJ (reprint author), Univ Cincinnati, Coll Med, 3125 Eden Ave,Room 3316, Cincinnati, OH 45219 USA. EM zjli@uchicago.edu; chen3jj@uc.edu RI Zuo, Zhixiang/M-4441-2016; OI Zuo, Zhixiang/0000-0002-2492-2689; Larson, Richard/0000-0001-9168-3203 FU American Cancer Society; Leukemia & Lymphoma Society; National Institutes of Health National Cancer Institute [R01 CA178454, R01 CA182528, R01 CA127277]; American Cancer Society Illinois Division; Gabrielle's Angel Foundation for Cancer Research; National Human Genome Research Institute, National Institutes of Health FX This work was supported in part by an American Cancer Society Research Scholar grant (J.C.); a Leukemia & Lymphoma Society Special Fellowship (Z.L.); National Institutes of Health National Cancer Institute grants R01 CA178454, R01 CA182528, and R01 CA127277 (J.C.); a Leukemia & Lymphoma Society Translational Research Grant (J.C.); an American Cancer Society Illinois Division Research Scholar grant (Z.L.); Gabrielle's Angel Foundation for Cancer Research (J.C., Z.L., X.J., and H.H.); and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (A.G.E. and P.P.L.). NR 65 TC 9 Z9 10 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 22 PY 2015 VL 126 IS 17 BP 2005 EP 2015 DI 10.1182/blood-2015-04-639062 PG 11 WC Hematology SC Hematology GA CY4PA UT WOS:000366389200011 PM 26361793 ER PT J AU Zetsche, B Gootenberg, JS Abudayyeh, OO Slaymaker, IM Makarova, KS Essletzbichler, P Volz, SE Joung, J van der Oost, J Regev, A Koonin, EV Zhang, F AF Zetsche, Bernd Gootenberg, Jonathan S. Abudayyeh, Omar O. Slaymaker, Ian M. Makarova, Kira S. Essletzbichler, Patrick Volz, Sara E. Joung, Julia van der Oost, John Regev, Aviv Koonin, Eugene V. Zhang, Feng TI Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System SO CELL LA English DT Article ID CRYSTAL-STRUCTURE; STREPTOCOCCUS-THERMOPHILUS; SURVEILLANCE COMPLEX; ADAPTIVE IMMUNITY; ESCHERICHIA-COLI; TARGET DNA; BACTERIA; SPECIFICITY; PROKARYOTES; CLEAVAGE AB The microbial adaptive immune system CRISPR mediates defense against foreign genetic elements through two classes of RNA-guided nuclease effectors. Class 1 effectors utilize multi-protein complexes, whereas class 2 effectors rely on single-component effector proteins such as the well-characterized Cas9. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we identified two candidate enzymes from Acid-aminococcus and Lachnospiraceae, with efficient genome-editing activity in human cells. Identifying this mechanism of interference broadens our understanding of CRISPR-Cas systems and advances their genome editing applications. C1 [Zetsche, Bernd; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Slaymaker, Ian M.; Essletzbichler, Patrick; Volz, Sara E.; Joung, Julia; Regev, Aviv; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Zetsche, Bernd; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Slaymaker, Ian M.; Essletzbichler, Patrick; Volz, Sara E.; Joung, Julia; Zhang, Feng] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Zetsche, Bernd; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Slaymaker, Ian M.; Essletzbichler, Patrick; Volz, Sara E.; Joung, Julia; Zhang, Feng] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Zetsche, Bernd; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Slaymaker, Ian M.; Essletzbichler, Patrick; Volz, Sara E.; Joung, Julia; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Zetsche, Bernd] Bonn Med Sch, Inst Pathol, Dept Dev Pathol, D-53127 Bonn, Germany. [Gootenberg, Jonathan S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [van der Oost, John] Wageningen Univ, Dept Agrotechnol & Food Sci, Microbiol Lab, NL-6703 HB Wageningen, Netherlands. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Zhang, F (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM zhang@broadinstitute.org OI Essletzbichler, Patrick/0000-0003-2237-0005 FU intramural program of the US Department of Health and Human Services; D.O.E. Computational Science Graduate Fellowship; NIMH [5DP1-MH100706]; Poitras Center Foundation; Vallee Foundation; Paul G. Allen Foundation; New York Stem Cell Foundation; Simons Foundation FX We would like to thank R. Macrae for critical reading of the manuscript. We would like to thank Wayne Conlan and David S. Weiss for generously providing F. novicida genomic DNA and cell pellets, respectively, Doug Daniels for kindly providing us with the bacterial expression vector, and Sergei Shmakov and Yuri Wolf for help with sequence analysis. E.V.K. and K.S.M are supported by the intramural program of the US Department of Health and Human Services (to the National Library of Medicine). J.S.G. is supported by a D.O.E. Computational Science Graduate Fellowship. F.Z. is supported by the NIMH (5DP1-MH100706), the Poitras Center, Vallee, Simons, Paul G. Allen, and New York Stem Cell Foundations, David R. Cheng, Tom Harriman, and Bob Metcalfe. A patent application has been filed related to this work, and the authors plan to make the reagents widely available to the academic community through Addgene and to provide software tools via the Zhang lab website (www.genome-engineering.org). F.Z. is a founder of Editas Medicine and a scientific advisor for Editas Medicine and Horizon Discovery. NR 43 TC 263 Z9 284 U1 74 U2 222 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 22 PY 2015 VL 163 IS 3 BP 759 EP 771 DI 10.1016/j.cell.2015.09.038 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CW2NK UT WOS:000364828900027 PM 26422227 ER PT J AU Carta, D Bortolozzi, R Hamel, E Basso, G Moro, S Viola, G Ferlin, MG AF Carta, Davide Bortolozzi, Roberta Hamel, Ernest Basso, Giuseppe Moro, Stefano Viola, Giampietro Ferlin, Maria Grazia TI Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; ANTIMITOTIC AGENTS; DRUG-COMBINATION; STRUCTURAL BASIS; FORCE-FIELD; SHOW POTENT; CELL-DEATH; IN-VITRO; TUBULIN; COLCHICINE AB A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI(50) values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 mu M) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets. C1 [Carta, Davide; Moro, Stefano; Ferlin, Maria Grazia] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy. [Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Dept Womens & Childrens Hlth, Lab Oncohematol, I-35128 Padua, Italy. [Hamel, Ernest] NCI, Screening Technol Branch,Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, NIH, Frederick, MD 21702 USA. RP Ferlin, MG (reprint author), Univ Padua, Dept Pharmaceut & Pharmacol Sci, Via Marzolo 5, I-35131 Padua, Italy. EM mariagrazia.ferlin@unipd.it RI Viola, Giampietro/I-4095-2012; Moro, Stefano/A-2979-2012; Bortolozzi, Roberta/D-4950-2015 OI Viola, Giampietro/0000-0001-9329-165X; Moro, Stefano/0000-0002-7514-3802; Bortolozzi, Roberta/0000-0002-3357-4815 FU University of Padova, Italy; Italian Ministry for University and Research (MIUR), Rome, Italy FX The synthetic work coordinated by M.G.F. was carried out with financial support from the University of Padova, Italy, and the Italian Ministry for University and Research (MIUR), Rome, Italy. The molecular modeling work coordinated by S.M. was carried out with financial support from the University of Padova, Italy, and the Italian Ministry for University and Research (MIUR), Rome, Italy. S.M. is also very grateful to the Chemical Computing Group for its scientific and technical partnership. G.V., R.B. and G.B. thank the Fondazione Cariparo by the "Progetto Ricerca Pediatrica". The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. NR 51 TC 3 Z9 3 U1 4 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD OCT 22 PY 2015 VL 58 IS 20 BP 7991 EP 8010 DI 10.1021/acs.jmedchem.5b00805 PG 20 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CV0CS UT WOS:000363915600009 PM 26418966 ER PT J AU Young, NS Ogawa, S AF Young, Neal S. Ogawa, Seishi TI Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Ogawa, Seishi] Kyoto Univ, Kyoto, Japan. RP Young, NS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM youngns@nhlbi.nih.gov NR 2 TC 2 Z9 2 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 22 PY 2015 VL 373 IS 17 BP 1675 EP 1676 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CU1YH UT WOS:000363317800021 PM 26488702 ER PT J AU Mammen, AL Tiniakou, E AF Mammen, Andrew L. Tiniakou, Eleni TI Intravenous Immune Globulin for Statin-Triggered Autoimmune Myopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Mammen, Andrew L.] NIH, Bethesda, MD 20892 USA. [Tiniakou, Eleni] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Mammen, AL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM andrew.mammen@nih.gov FU Intramural NIH HHS [ZIA AR041203-01]; NIAMS NIH HHS [T32 AR048522, T32-AR-048522] NR 5 TC 13 Z9 13 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 22 PY 2015 VL 373 IS 17 BP 1680 EP 1682 DI 10.1056/NEJMc1506163 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CU1YH UT WOS:000363317800030 PM 26488714 ER PT J AU Zhang, Q Fan, LX Hou, F Dong, AP Wang, YX Tong, YF AF Zhang, Qi Fan, Lixin Hou, Feng Dong, Aiping Wang, Yun-Xing Tong, Yufeng TI New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins SO SCIENTIFIC REPORTS LA English DT Article ID TARGET MESSENGER-RNAS; IN-SITU PROTEOLYSIS; CELL DIFFERENTIATION; CONJUGATING ENZYME; PROTEINS; DISEASE; REPRESSION; ALIGNMENT; FAMILY; DOMAIN AB Roquins are a family of highly conserved RNA-binding proteins that also contain a RING-type E3 ubiquitin ligase domain. They repress constitutive decay elements containing mRNAs and play a critical role in RNA homeostasis and immunological self-tolerance. Here we present the crystal structures of the RNA-binding region of Roquin paralog RC3H2 in both apo- and RNA-bound forms. The RNA-binding region has a bipartite architecture composed of ROQ and HEPN domains, and can bind to stem-loop and double-stranded RNAs simultaneously. The two domains undergo a large orientation change to accommodate RNA duplex binding. We profiled E2 ubiquitin-conjugating enzymes that pair with Roquins and found that RC3H1 and RC3H2 interact with two sets of overlapping but not identical E2 enzymes to drive the assembly of polyubiquitin chains of different linkages. Crystal structures, small-angle X-ray scattering, and E2 profiling revealed that while the two paralogs are highly homologous, RC3H2 and RC3H1 are different in their structures and functions. We also demonstrated that RNA duplex binding to RC3H2 cross-talks with its E3 ubiquitin ligase function using an in vitro auto-ubiquitination assay. C1 [Zhang, Qi; Hou, Feng; Dong, Aiping; Tong, Yufeng] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. [Fan, Lixin] Leidos Biomed Res Inc, Small Angle Xray Scattering Core Facil, Ctr Canc Res, Natl Canc Inst,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. [Tong, Yufeng] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5G 1L7, Canada. RP Tong, YF (reprint author), Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. EM yufeng.tong@utoronto.ca RI Tong, Yufeng/D-2785-2011; OI Tong, Yufeng/0000-0001-7740-1812; Zhang, Qi/0000-0003-1121-8817 FU AbbVie [1097737]; Bayer Pharma AG; Boehringer Ingelheim; Canada Foundation for Innovation; Eshelman Institute for Innovation; Genome Canada; Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD] [115766]; Janssen; Merck Co.; Novartis Pharma AG; Ontario Ministry of Economic Development and Innovation; Pfizer; Sao Paulo Research Foundation-FAPESP; Takeda; Wellcome Trust; DOE Office of Science [DE-AC02-06CH11357] FX We thank Dr. Yi Sheng (York University, Toronto) for her critical comments on the manuscript, Dr. Rachel Harding (University of Toronto) for proof-reading. The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck & Co., Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, Sao Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust. For the SAXS experiments, we gratefully acknowledge the use of the SAXS core facility at the Center for Cancer Research, National Cancer Institute (NCI). The shared scattering beamline 12ID-B resource is allocated under the PUP-24152 agreement between the National Cancer Institute and Argonne National Laboratory (ANL). We thank Dr. Xiaobing Zuo (ANL) for his expert support. Use of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, was operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. NR 51 TC 5 Z9 5 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 22 PY 2015 VL 5 AR 15660 DI 10.1038/srep15660 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9NM UT WOS:000363143900001 PM 26489670 ER PT J AU Guderian, S Dzieciol, AM Gadian, DG Jentschke, S Doeller, CF Burgess, N Mishkin, M Vargha-Khadem, F AF Guderian, Sebastian Dzieciol, Anna M. Gadian, David G. Jentschke, Sebastian Doeller, Christian F. Burgess, Neil Mishkin, Mortimer Vargha-Khadem, Faraneh TI Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amnesia; human; memory; navigation; spatial; virtual reality ID DEVELOPMENTAL AMNESIA; HABIT FORMATION; MONKEYS; PATHOLOGY; LESIONS; DAMAGE; INACTIVATION; ORGANIZATION; BOUNDARIES; LANDMARKS AB The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. C1 [Guderian, Sebastian; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Dzieciol, Anna M.; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, Cognit Neurosci & Neuropsychiat Sect, London WC1N 1EH, England. [Dzieciol, Anna M.; Vargha-Khadem, Faraneh] Great Ormond St Hosp Sick Children, London WC1N 1EH, England. [Gadian, David G.] UCL, Inst Child Hlth, Dev Imaging & Biophys Sect, London WC1N 1EH, England. [Jentschke, Sebastian] Free Univ Berlin, Cluster Languages Emot, D-14195 Berlin, Germany. [Doeller, Christian F.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Burgess, Neil] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Burgess, Neil] UCL, Inst Neurol, London WC1N 3AR, England. RP Guderian, S (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr,Room 1B80, Bethesda, MD 20892 USA. EM guderians@mail.nih.gov; f.vargha-khadem@ucl.ac.uk RI Burgess, Neil/B-2420-2009 OI Burgess, Neil/0000-0003-0646-6584 FU Medical Research Council [G0300117/65439]; Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Project [ZIAMH000478]; UK Central and East London Research Network [5177]; European Research Council (ERC) [StG 261177]; Netherlands Organisation for Scientific Research (NWO) [Vidi 45212009] FX This work was supported by Medical Research Council Grant G0300117/65439, Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services Project ZIAMH000478, UK Central and East London Research Network (5177), the European Research Council (ERC-StG 261177) and the Netherlands Organisation for Scientific Research (NWO-Vidi 45212009). We thank all the participants in this study, in particular, the patients and their families. NR 38 TC 6 Z9 6 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 21 PY 2015 VL 35 IS 42 BP 14123 EP 14131 DI 10.1523/JNEUROSCI.0801-15.2015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CX9VB UT WOS:000366052700004 PM 26490854 ER PT J AU Corey, L Gilbert, PB Tomaras, GD Haynes, BF Pantaleo, G Fauci, AS AF Corey, Lawrence Gilbert, Peter B. Tomaras, Georgia D. Haynes, Barton F. Pantaleo, Giuseppe Fauci, Anthony S. TI Immune correlates of vaccine protection against HIV-1 acquisition SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Review ID NEUTRALIZING ANTIBODY-RESPONSE; EFFICACY TRIAL; RHESUS-MONKEYS; FC-RECEPTOR; SIV CHALLENGES; INFECTION; RV144; GP120; V2; IMMUNOGENICITY AB The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4(+) T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition. C1 [Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, HIV Vaccine Trials Network, Seattle, WA 98109 USA. [Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA. [Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Pantaleo, Giuseppe] Lausanne Univ Hosp, CH-1011 Lausanne, Switzerland. [Pantaleo, Giuseppe] Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland. [Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Corey, L (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, HIV Vaccine Trials Network, 1124 Columbia St, Seattle, WA 98109 USA. EM lcorey@fredhutch.org RI Tomaras, Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016 FU NIAID of the NIH [UM1AI068618, U01AI 068614-05, UM1AI068635]; Duke Center for AIDS Research Immunology Core [AI064518]; Bill and Melinda Gates Foundation [OPP1040758, OPP1032144, OPP1068333] FX Research reported in this publication was supported by the NIAID of the NIH under award nos. UM1AI068618, U01AI 068614-05, and UM1AI068635; Duke Center for AIDS Research Immunology Core (AI064518); and the Bill and Melinda Gates Foundation (OPP1040758, OPP1032144, and OPP1068333). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 59 TC 25 Z9 25 U1 4 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD OCT 21 PY 2015 VL 7 IS 310 AR 310rv7 DI 10.1126/scitranslmed.aac7732 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CY4BA UT WOS:000366352400007 PM 26491081 ER PT J AU Huston, SJ Stopfer, M Cassenaer, S Aldworth, ZN Laurent, G AF Huston, Stephen J. Stopfer, Mark Cassenaer, Stijn Aldworth, Zane N. Laurent, Gilles TI Neural Encoding of Odors during Active Sampling and in Turbulent Plumes SO NEURON LA English DT Article ID OLFACTORY NETWORK DYNAMICS; LOCUST ANTENNAL LOBE; TEMPORAL STRUCTURE; BEHAVING RATS; DISCRIMINATION; INFORMATION; SYSTEM; SNIFF; BULB; REPRESENTATIONS AB Sensory inputs are often fluctuating and intermittent, yet animals reliably utilize them to direct behavior. Here we ask how natural stimulus fluctuations influence the dynamic neural encoding of odors. Using the locust olfactory system, we isolated two main causes of odor intermittency: chaotic odor plumes and active sampling behaviors. Despite their irregularity, chaotic odor plumes still drove dynamic neural response features including the synchronization, temporal patterning, and short-term plasticity of spiking in projection neurons, enabling classifier-based stimulus identification and activating downstream decoders (Kenyon cells). Locusts can also impose odor intermittency through active sampling movements with their unrestrained antennae. Odors triggered immediate, spatially targeted antennal scanning that, paradoxically, weakened individual neural responses. However, these frequent but weaker responses were highly informative about stimulus location. Thus, not only are odor-elicited dynamic neural responses compatible with natural stimulus fluctuations and important for stimulus identification, but locusts actively increase intermittency, possibly to improve stimulus localization. C1 [Huston, Stephen J.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA. [Stopfer, Mark; Aldworth, Zane N.] NICHD, NIH, Bethesda, MD 20892 USA. [Cassenaer, Stijn] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Laurent, Gilles] Max Planck Inst Brain Res, D-60438 Frankfurt, Germany. RP Laurent, G (reprint author), Max Planck Inst Brain Res, Max von Laue Str 4, D-60438 Frankfurt, Germany. EM gilles.laurent@brain.mpg.de FU NIH; Max Planck Society; U.S. Office of Naval Research; NIH-NICHD FX This work was supported by the NIH and the Max Planck Society (G.L.), by grants from the U.S. Office of Naval Research (G.L. and S.C.), and by an intramural NIH-NICHD grant (M.S.). We thank Kristin Branson for advice on the automated antennal tracking and the Laurent Lab and Simon Laughlin for discussion and comments. NR 57 TC 3 Z9 3 U1 7 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD OCT 21 PY 2015 VL 88 IS 2 BP 403 EP 418 DI 10.1016/j.neuron.2015.09.007 PG 16 WC Neurosciences SC Neurosciences & Neurology GA CU8HQ UT WOS:000363783000018 PM 26456047 ER PT J AU Kamal, AK Shaikh, Q Pasha, O Azam, I Islam, M Memon, AA Rehman, H Akram, MA Affan, M Nazir, S Aziz, S Jan, M Andani, A Muqeet, A Ahmed, B Khoja, S AF Kamal, Ayeesha Kamran Shaikh, Quratulain Pasha, Omrana Azam, Iqbal Islam, Muhammad Memon, Adeel Ali Rehman, Hasan Akram, Masood Ahmed Affan, Muhammad Nazir, Sumaira Aziz, Salman Jan, Muhammad Andani, Anita Muqeet, Abdul Ahmed, Bilal Khoja, Shariq TI A randomized controlled behavioral intervention trial to improve medication adherence in adult stroke patients with prescription tailored Short Messaging Service (SMS)-SMS4Stroke study SO BMC NEUROLOGY LA English DT Article DE Stroke; Medication adherence; SMS; Prevention; Non communicable disease; mHealth; IT technology; Lower and middle income countries; Cost effectiveness ID GLOBAL BURDEN; SYSTEMATIC ANALYSIS; PAKISTAN HEALTH; SELF-REPORT; DISEASE; SMS; PROTOCOL; OUTCOMES; MODEL; CARE AB Background: The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan. Methods: This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition to usual care, received reminder SMS for 2 months that contained a) Personalized, prescription tailored daily medication reminder(s) b) Twice weekly health information SMS. The Health Belief Model and Social Cognitive theory were used to design the language and content of messages. Frontline SMS software was used for SMS delivery. Medication adherence was self-reported and measured on the validated Urdu version of Morisky Medication Adherence Questionnaire. Multiple linear regression was used to model the outcome against intervention and other covariates. Analysis was conducted by intention-to-treat principle. Results: Two hundred participants were enrolled. 38 participants were lost to follow-up. After 2 months, the mean medication score was 7.4 (95 % CI: 7.2-7.6) in the intervention group while 6.7 (95 % CI: 6.4-7.02) in the control group. The adjusted mean difference (Delta) was 0.54 (95 % CI: 0.22-0.85). The mean diastolic blood pressure in the intervention group was 2.6 mmHg (95 % CI; -5.5 to 0.15) lower compared to the usual care group. Conclusion: A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in resource poor areas. C1 [Kamal, Ayeesha Kamran; Jan, Muhammad; Andani, Anita] Natl Inst Hlth, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv,Sect Neurol,Dept Med, Karachi 74800, Pakistan. [Kamal, Ayeesha Kamran; Shaikh, Quratulain; Memon, Adeel Ali; Affan, Muhammad; Nazir, Sumaira; Aziz, Salman; Jan, Muhammad; Andani, Anita] Aga Khan Univ, Karachi 74800, Pakistan. [Shaikh, Quratulain] Natl Inst Hlth, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Karachi 74800, Pakistan. [Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Epidemiol & Biostat Program, Karachi 74800, Pakistan. [Azam, Iqbal; Islam, Muhammad] Aga Khan Univ, Dept Community Hlth Sci, Biostat, Karachi 74800, Pakistan. [Memon, Adeel Ali; Affan, Muhammad; Nazir, Sumaira; Aziz, Salman] Natl Inst Hlth, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Study SMS4Stroke, Karachi 74800, Pakistan. [Rehman, Hasan; Akram, Masood Ahmed] Aga Khan Univ, Stroke Serv, Karachi 74800, Pakistan. [Muqeet, Abdul] Aga Khan Dev Network, eHlth Resource Ctr, eHlth Innovat, Global, Karachi, Pakistan. [Ahmed, Bilal] Aga Khan Univ, Dept Med, Epidemiol & Biostat, Karachi 74800, Pakistan. [Khoja, Shariq] Tech4Life Enterprises, Washington, DC USA. [Khoja, Shariq] United Nations Fdn, Evidence Capac & Policy mHlth Alliance, Washington, DC USA. RP Kamal, AK (reprint author), Natl Inst Hlth, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv,Sect Neurol,Dept Med, Stadium Rd, Karachi 74800, Pakistan. EM ayeesha.kamal@aku.edu RI Emchi, Karma/Q-1952-2016 FU Fogarty International Center, National Institutes of Health; Fogarty International Center [D43TW008660]; National Institute of Neurologic Disorders and Stroke; Grand Challenges Canada-Bold ideas with Big Impact, University Research Council Aga Khan University (URC, AKU), Higher Education Commission (HEC), Gov. of Pakistan; Baylor College of Medicine, BCM Center for Globalization FX Dr Ayeesha Kamran Kamal is the co-director and recipient of grant entitled, "The International Cerebrovascular Translational Clinical Research Training Program" (Fogarty International Center, National Institutes of Health). Dr. Quratulain Shaikh is a neurovascular research fellow whose mentored research practicum training is currently funded by Award Number D43TW008660 from the Fogarty International Center and the National Institute of Neurologic Disorders and Stroke. This work has been directly facilitated by the above training and research grant.; Dr Ayeesha Kamran Kamal is also funded by Grand Challenges Canada-Bold ideas with Big Impact, University Research Council Aga Khan University (URC, AKU), Higher Education Commission (HEC), Gov. of Pakistan; She is also collaboratively funded from Baylor College of Medicine, BCM Center for Globalization on work on medical prescription literacy. NR 51 TC 5 Z9 5 U1 10 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD OCT 21 PY 2015 VL 15 AR 212 DI 10.1186/s12883-015-0471-5 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CU1VV UT WOS:000363310900001 PM 26486857 ER PT J AU Krajacich, BJ Lopez, JE Raffel, SJ Schwan, TG AF Krajacich, Benjamin J. Lopez, Job E. Raffel, Sandra J. Schwan, Tom G. TI Vaccination with the variable tick protein of the relapsing fever spirochete Borrelia hermsii protects mice from infection by tick-bite SO PARASITES & VECTORS LA English DT Article DE Ornithodoros hermsi; Tick-borne relapsing fever; Spirochetosis ID OUTER-SURFACE PROTEIN; LYME-DISEASE SPIROCHETE; GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE GLPQ; ANTIGENIC VARIATION; ACTIVE IMMUNIZATION; C OSPC; BURGDORFERI INFECTION; MONOCLONAL-ANTIBODY; RECOMBINANT OSPA; TRANSMISSION AB Background: Tick-borne relapsing fevers of humans are caused by spirochetes that must adapt to both warm-blooded vertebrates and cold-blooded ticks. In western North America, most human cases of relapsing fever are caused by Borrelia hermsii, which cycles in nature between its tick vector Ornithodoros hermsi and small mammals such as tree squirrels and chipmunks. These spirochetes alter their outer surface by switching off one of the bloodstream-associated variable major proteins (Vmps) they produce in mammals, and replacing it with the variable tick protein (Vtp) following their acquisition by ticks. Based on this reversion to Vtp in ticks, we produced experimental vaccines comprised on this protein and tested them in mice challenged by infected ticks. Methods: The vtp gene from two isolates of B. hermsii that encoded antigenically distinct types of proteins were cloned, expressed, and the recombinant Vtp proteins were purified and used to vaccinate mice. Ornithodoros hermsi ticks that were infected with one of the two strains of B. hermsii from which the vtp gene originated were used to challenge mice that received one of the two Vtp vaccines or only adjuvant. Mice were then followed for infection and seroconversion. Results: The Vtp vaccines produced protective immune responses in mice challenged with O. hermsi ticks infected with B. hermsii. However, polymorphism in Vtp resulted in mice being protected only from the spirochete strain that produced the same Vtp used in the vaccine; mice challenged with spirochetes producing the antigenically different Vtp than the vaccine succumbed to infection. Conclusions: We demonstrate that by having knowledge of the phenotypic changes made by B. hermsii as the spirochetes are acquired by ticks from infected mammals, an effective vaccine was developed that protected mice when challenged with infected ticks. However, the Vtp vaccines only protected mice from infection when challenged with that strain producing the identical Vtp. A vaccine containing multiple Vtp types may have promise as an oral vaccine for wild mammals if applied to geographic settings such as small islands where the mammal diversity is low and the Vtp types in the B. hermsii population are defined. C1 [Lopez, Job E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lopez, Job E.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Raffel, Sandra J.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM tschwan@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Ralph Larson and Don Dale for help with the animal work, Anita Mora for help with the figures, and Jay Carroll, Dan Dulebohn and Martha Thayer for reviewing the manuscript. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 104 TC 2 Z9 2 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD OCT 21 PY 2015 VL 8 AR 546 DI 10.1186/s13071-015-1170-1 PG 14 WC Parasitology SC Parasitology GA CU2YN UT WOS:000363389800001 PM 26490040 ER PT J AU Shrestha, S Foxman, B Berus, J van Panhuis, WG Steiner, C Viboud, C Rohani, P AF Shrestha, Sourya Foxman, Betsy Berus, Joshua van Panhuis, Willem G. Steiner, Claudia Viboud, Cecile Rohani, Pejman TI The role of influenza in the epidemiology of pneumonia SO SCIENTIFIC REPORTS LA English DT Article ID HONG-KONG INFLUENZA; PNEUMOCOCCAL PNEUMONIA; BACTERIAL PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; LETHAL SYNERGISM; UNITED-STATES; MOUSE MODEL; VIRUS; INFECTION AB Interactions arising from sequential viral and bacterial infections play important roles in the epidemiological outcome of many respiratory pathogens. Influenza virus has been implicated in the pathogenesis of several respiratory bacterial pathogens commonly associated with pneumonia. Though clinical evidence supporting this interaction is unambiguous, its population-level effects-magnitude, epidemiological impact and variation during pandemic and seasonal outbreaks-remain unclear. To address these unknowns, we used longitudinal influenza and pneumonia incidence data, at different spatial resolutions and across different epidemiological periods, to infer the nature, timing and the intensity of influenza-pneumonia interaction. We used a mechanistic transmission model within a likelihood-based inference framework to carry out formal hypothesis testing. Irrespective of the source of data examined, we found that influenza infection increases the risk of pneumonia by similar to 100-fold. We found no support for enhanced transmission or severity impact of the interaction. For model-validation, we challenged our fitted model to make out-of-sample pneumonia predictions during pandemic and non-pandemic periods. The consistency in our inference tests carried out on several distinct datasets, and the predictive skill of our model increase confidence in our overall conclusion that influenza infection substantially enhances the risk of pneumonia, though only for a short period. C1 [Shrestha, Sourya] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Shrestha, Sourya] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Shrestha, Sourya] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 22105 USA. [Foxman, Betsy] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Berus, Joshua] Univ Michigan, Undergrad Res Opportun Program, Ann Arbor, MI 48109 USA. [van Panhuis, Willem G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Steiner, Claudia] US Dept HHS, Healthcare Cost & Utilizat Project, Ctr Delivery Org & Markets, Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. [Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. [Rohani, Pejman] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Rohani, Pejman] Univ Georgia, Sch Vet Med, Dept Infect Dis, Athens, GA 30602 USA. [Rohani, Pejman] NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Shrestha, S (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM sourya@jhu.edu FU Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center; National Institutes of Health; MIDAS, National Institute of General Medical Sciences [U54-GM111274]; Pfizer Inc. FX We would like to thank the Illinois Department of Public Health for voluntarily participating in the HCUP. We would also like to thank Marc Lipsitch for helpful suggestions. PR received support from the Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, the Fogarty International Center, National Institutes of Health and by MIDAS, National Institute of General Medical Sciences U54-GM111274. PR and BF were also supported by an investigator-initiated grant from Pfizer Inc. NR 57 TC 2 Z9 2 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 21 PY 2015 VL 5 AR 15314 DI 10.1038/srep15314 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU1MI UT WOS:000363285600001 PM 26486591 ER PT J AU Matveeva, OV Guo, ZS Senin, VM Senina, AV Shabalina, SA Chumakov, PM AF Matveeva, Olga V. Guo, Zong S. Senin, Vyacheslav M. Senina, Anna V. Shabalina, Svetlana A. Chumakov, Peter M. TI Oncolysis by paramyxoviruses: preclinical and clinical studies SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Review ID NEWCASTLE-DISEASE-VIRUS; RECOMBINANT SENDAI-VIRUS; SODIUM-IODIDE SYMPORTER; MEASLES-VACCINE VIRUS; FUSOGENIC MEMBRANE-GLYCOPROTEINS; TUMOR-SELECTIVE REPLICATION; ANTITUMOR IMMUNE-RESPONSES; PHASE I/II TRIAL; OVARIAN-CANCER; MATRIX METALLOPROTEINASES AB Preclinical studies demonstrate that a broad spectrum of human malignant cells can be killed by oncolytic paramyxoviruses, which include cells of ecto-, endo-, and mesodermal origin. In clinical trials, significant reduction in size or even complete elimination of primary tumors and established metastases are reported. Different routes of viral administration (intratumoral, intravenous, intradermal, intraperitoneal, or intrapleural), and single-versus multiple-dose administration schemes have been explored. The reported side effects are grade 1 and 2, with the most common among them being mild fever. Some advantages in using paramyxoviruses as oncolytic agents versus representatives of other viral families exist. The cytoplasmic replication results in a lack of host genome integration and recombination, which makes paramyxoviruses safer and more attractive candidates for widely used therapeutic oncolysis in comparison with retroviruses or some DNA viruses. The list of oncolytic paramyxovirus representatives includes attenuated measles virus (MV), mumps virus (MuV), low pathogenic Newcastle disease (NDV), and Sendai (SeV) viruses. Metastatic cancer cells frequently overexpress on their surface some molecules that can serve as receptors for MV, MuV, NDV, and SeV. This promotes specific viral attachment to the malignant cell, which is frequently followed by specific viral replication. The paramyxoviruses are capable of inducing efficient syncytium-mediated lyses of cancer cells and elicit strong immunomodulatory effects that dramatically enforce anticancer immune surveillance. In general, preclinical studies and phase 1-3 clinical trials yield very encouraging results and warrant continued research of oncolytic paramyxoviruses as a particularly valuable addition to the existing panel of cancer-fighting approaches. C1 [Matveeva, Olga V.] Biopolymer Design LLC, Acton, MA 01721 USA. [Matveeva, Olga V.; Chumakov, Peter M.] Engelhardt Inst Mol Biol, Moscow, Russia. [Guo, Zong S.] Univ Pittsburgh, Inst Canc, Div Surg Oncol, Pittsburgh, PA USA. [Senin, Vyacheslav M.] Blokhin Russian Canc Res Ctr, Moscow, Russia. [Senina, Anna V.] Huntsman Canc Inst, Salt Lake City, UT USA. [Shabalina, Svetlana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Matveeva, OV (reprint author), Biopolymer Design LLC, Acton, MA 01721 USA.; Matveeva, OV (reprint author), Engelhardt Inst Mol Biol, Moscow, Russia.; Shabalina, SA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM olga.matveeva@gmail.com; shabalin@ncbi.nlm.nih.gov FU Russian Ministry of Education [RFMEFI57714X0033]; Intramural Research Program of the National Library of Medicine, NIH FX We thank Dmitriy Zamarin and John F. Atkins for critical reading of the manuscript. We are grateful to Brigit Sullivan, ORS, NIH Library Writing Center, for editing - assistance. The work was supported by the Russian Ministry of Education, unique project code - RFMEFI57714X0033. This research was also supported in part by the Intramural Research Program of the National Library of Medicine, NIH. NR 182 TC 3 Z9 3 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2372-7705 J9 Mol Ther-Oncolytics JI Mol. Ther.-Oncolytics PD OCT 21 PY 2015 VL 2 AR UNSP 150017 DI 10.1038/mto.2015.17 PG 14 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA EE2RV UT WOS:000389432800001 ER PT J AU Topol, A English, JA Flaherty, E Rajarajan, P Hartley, BJ Gupta, S Desland, F Zhu, S Goff, T Friedman, L Rapoport, J Felsenfeld, D Cagney, G Mackay-Sim, A Savas, JN Aronow, B Fang, G Zhang, B Cotter, D Brennand, KJ AF Topol, A. English, J. A. Flaherty, E. Rajarajan, P. Hartley, B. J. Gupta, S. Desland, F. Zhu, S. Goff, T. Friedman, L. Rapoport, J. Felsenfeld, D. Cagney, G. Mackay-Sim, A. Savas, J. N. Aronow, B. Fang, G. Zhang, B. Cotter, D. Brennand, K. J. TI Increased abundance of translation machinery in stem cell-derived neural progenitor cells from four schizophrenia patients SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID MESSENGER-RNA TRANSLATION; CHILDHOOD-ONSET SCHIZOPHRENIA; DE-NOVO MUTATIONS; NEURODEVELOPMENTAL MODEL; INTELLECTUAL DISABILITY; PROTEIN-SYNTHESIS; GENE; EXPRESSION; DISORDERS; REVEALS AB The genetic and epigenetic factors contributing to risk for schizophrenia (SZ) remain unresolved. Here we demonstrate, for the first time, perturbed global protein translation in human-induced pluripotent stem cell (hiPSC)-derived forebrain neural progenitor cells (NPCs) from four SZ patients relative to six unaffected controls. We report increased total protein levels and protein synthesis, together with two independent sets of quantitative mass spectrometry evidence indicating markedly increased levels of ribosomal and translation initiation and elongation factor proteins, in SZ hiPSC NPCs. We posit that perturbed levels of global protein synthesis in SZ hiPSC NPCs represent a novel post-transcriptional mechanism that might contribute to disease progression. C1 [Topol, A.; Flaherty, E.; Rajarajan, P.; Hartley, B. J.; Desland, F.; Goff, T.; Brennand, K. J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [English, J. A.; Cotter, D.] Beaumont Hosp, Royal Coll Surg Ireland, Dublin 9, Ireland. [Gupta, S.; Aronow, B.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Biomed Informat, Cincinnati, OH USA. [Zhu, S.; Fang, G.; Zhang, B.] Icahn Sch Med Mt Sinai, Dept Genet & Genom, New York, NY 10029 USA. [Friedman, L.; Rapoport, J.] NIMH, Childhood Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Felsenfeld, D.] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Cagney, G.] UCD Conway Inst Biomol & Biomed Res, Dublin, Ireland. [Mackay-Sim, A.] Griffith Univ, Eskitis Inst Drug Discovery, Brisbane, Qld 4111, Australia. [Savas, J. N.] Scripps Res Inst, Dept Chem Physiol, La Jolla, CA 92037 USA. [Brennand, K. J.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Brennand, K. J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Brennand, KJ (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, Dept Psychiat, 1425 Madison Ave, New York, NY 10029 USA. EM kristen.brennand@mssm.edu RI Brennand, Kristen/J-8704-2012; Mackay-Sim, Alan/C-3431-2008; OI Brennand, Kristen/0000-0003-0993-5956; Mackay-Sim, Alan/0000-0003-4446-5371; Cagney, Gerard/0000-0001-7189-9496 FU Brain and Behavior Young Investigator Grant; National Institute of Health (NIH) [R01 MH101454, R01 MH106056]; New York Stem Cell Foundation; Health Research Board Clinical Scientist Award; NIH [R00DC013805-02]; Aronow laboratory [U19 MH194172] FX Kristen J Brennand is a New York Stem Cell Foundation-Robertson Investigator. The Brennand Laboratory is supported by a Brain and Behavior Young Investigator Grant, National Institute of Health (NIH) grants R01 MH101454 and R01 MH106056 and the New York Stem Cell Foundation. The Cotter Laboratory is supported by Health Research Board Clinical Scientist Award. JN Savas is supported by NIH award R00DC013805-02; the Aronow laboratory by U19 MH194172. We thank the high-throughput screening core at Icahn School of Medicine at Mount Sinai, directed by Dan Felsenfeld, for critical assistance with high-content imaging and analysis. NR 75 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD OCT 20 PY 2015 VL 5 AR e662 DI 10.1038/tp.2015.118 PG 12 WC Psychiatry SC Psychiatry GA DA2ZC UT WOS:000367664700003 PM 26485546 ER PT J AU Lee, S Zipunnikov, V Reich, DS Pham, DL AF Lee, Seonjoo Zipunnikov, Vadim Reich, Daniel S. Pham, Dzung L. TI Statistical image analysis of longitudinal RAVENS images SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE longitudinal functional principal component analysis; regional analysis of volumes examined in normalized space; voxel-based morphometry; multiple sclerosis; brain volume measurement ID VOXEL-BASED MORPHOMETRY; PRINCIPAL COMPONENT ANALYSIS; GRAY-MATTER ATROPHY; MULTIPLE-SCLEROSIS; VENTRICULAR ENLARGEMENT; BRAIN ATROPHY; REGISTRATION; PERFORMANCE; IMPAIRMENT; DISEASE AB Regional analysis of volumes examined in normalized space (RAVENS) are transformation images used in the study of brain morphometry. In this paper, RAVENS images are analyzed using a longitudinal variant of voxel-based morphometry (VBM) and longitudinal functional principal component analysis (LFPCA) for high-dimensional images. We demonstrate that the latter overcomes the limitations of standard longitudinal VBM analyses, which does not separate registration errors from other longitudinal changes and baseline patterns. This is especially important in contexts where longitudinal changes are only a small fraction of the overall observed variability, which is typical in normal aging and many chronic diseases. Our simulation study shows that LFPCA effectively separates registration error from baseline and longitudinal signals of interest by decomposing RAVENS images measured at multiple visits into three components: a subject-specific imaging random intercept that quantifies the cross-sectional variability, a subject-specific imaging slope that quantifies the irreversible changes over multiple visits, and a subject-visit specific imaging deviation. We describe strategies to identify baseline/longitudinal variation and registration errors combined with covariates of interest. Our analysis suggests that specific regional brain atrophy and ventricular enlargement are associated with multiple sclerosis (MS) disease progression. C1 [Lee, Seonjoo] Columbia Univ, Dept Psychiat & Biostat, New York, NY USA. [Lee, Seonjoo] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Zipunnikov, Vadim; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Reich, Daniel S.] NINDS, Div Neuroimmunol & Neurovirol, Bethesda, MD 20892 USA. [Pham, Dzung L.] Henry M Jackson Fdn Adv Mil Med, Cr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. RP Pham, DL (reprint author), Henry M Jackson Fdn Adv Mil Med, Cr Neurosci & Regenerat Med, Bethesda, MD 20817 USA. EM dzung.pham@nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute of Health [R01NS070906, Z01NS003119, K01AG051348, R01HL12407, R01NS060910]; Department of Defense in the Center for Neuroscience and Regenerative Medicine FX Research reported in this work was supported by National Institute of Health under award numbers R01NS070906, Z01NS003119, K01AG051348, R01HL12407 and R01NS060910. Support for this work included funding from the Department of Defense in the Center for Neuroscience and Regenerative Medicine. NR 41 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD OCT 20 PY 2015 VL 9 AR 368 DI 10.3389/fnins.2015.00368 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CY9DN UT WOS:000366707700001 PM 26539071 ER PT J AU Do, K Wilsker, D Ji, JP Zlott, J Freshwater, T Kinders, RJ Collins, J Chen, AP Doroshow, JH Kummar, S AF Do, Khanh Wilsker, Deborah Ji, Jiuping Zlott, Jennifer Freshwater, Tomoko Kinders, Robert J. Collins, Jerry Chen, Alice P. Doroshow, James H. Kummar, Shivaani TI Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DNA-DAMAGING AGENTS; REPLICATION; CELLS; CHK1; ACTIVATION; EFFICACY; THERAPY; BINDING AB Purpose Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent kinase (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor of Wee1 kinase with single-agent antitumor activity in preclinical models. We conducted a phase I study of single-agent AZD1775 in adult patients with refractory solid tumors to determine its maximum-tolerated dose (MTD), pharmacokinetics, and modulation of phosphorylated Tyr15-Cdk (pY15-Cdk) and phosphorylated histone H2AX (H2AX) levels in paired tumor biopsies. Patients and Methods AZD1775 was administered orally twice per day over 2.5 days per week for up to 2 weeks per 21-day cycle (3 + 3 design). At the MTD, paired tumor biopsies were obtained at baseline and after the fifth dose to determine pY15-Cdk and H2AX levels. Six patients with BRCA-mutant solid tumors were also enrolled at the MTD. Results Twenty-five patients were enrolled. The MTD was established as 225 mg twice per day orally over 2.5 days per week for 2 weeks per 21-day cycle. Confirmed partial responses were observed in two patients carrying BRCA mutations: one with head and neck cancer and one with ovarian cancer. Common toxicities were myelosuppression and diarrhea. Dose-limiting toxicities were supraventricular tachyarrhythmia and myelosuppression. Accumulation of drug (t(1/2) approximately 11 hours) was observed. Reduction in pY15-Cdk levels (two of five paired biopsies) and increases in H2AX levels (three of five paired biopsies) were demonstrated. Conclusion This is the first report of AZD1775 single-agent activity in patients carrying BRCA mutations. Proof-of-mechanism was demonstrated by target modulation and DNA damage response in paired tumor biopsies. (C) 2015 by American Society of Clinical Oncology C1 [Do, Khanh; Zlott, Jennifer; Collins, Jerry; Chen, Alice P.; Doroshow, James H.; Kummar, Shivaani] NCI, Bethesda, MD 20892 USA. [Wilsker, Deborah; Ji, Jiuping; Kinders, Robert J.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD USA. [Freshwater, Tomoko] Merck Res Labs Oncol, Boston, MA USA. RP Kummar, S (reprint author), NCI, Div Canc Treatment & Diag, 31 Ctr Dr,Bldg 31,Rm 3A44, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Supported by Contract No. HHSN261200800001E with the National Cancer Institute, National Institutes of Health. NR 21 TC 41 Z9 42 U1 3 U2 11 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 OCT 20 PY 2015 VL 33 IS 30 BP 3409 EP + DI 10.1200/JCO.2014.60.4009 PG 10 WC Oncology SC Oncology GA CX9IQ UT WOS:000366019300011 PM 25964244 ER PT J AU Palmore, TN Henderson, DK AF Palmore, Tara N. Henderson, David K. TI Intensifying the Focus on the Contribution of the Inanimate Environment to Health Care-Associated Infections SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Palmore, Tara N.; Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Ctr Clin, Bldg 10,Room 6-1480,MSC 1504, Bethesda, MD 20892 USA. EM dkh@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 20 PY 2015 VL 163 IS 8 BP 642 EP + DI 10.7326/M15-1798 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CU7QV UT WOS:000363737400025 PM 26259010 ER PT J AU Kadri, S O'Grady, NP AF Kadri, Sameer O'Grady, Naomi P. TI After source control in intraabdominal infections, 4-day and longer-duration antibiotics did not differ at 30 days SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Kadri, Sameer; O'Grady, Naomi P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Kadri, S (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 20 PY 2015 VL 163 IS 8 AR JC6 DI 10.7326/ACPJC-2015-163-8-006 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CU7QV UT WOS:000363737400007 PM 26502143 ER PT J AU Little, MP AF Little, Mark P. TI Ionising radiation in the workplace SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID BOMB SURVIVORS; CANCER-RISKS; CHILDHOOD; MORTALITY; LEUKEMIA; WORKERS C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM mark.little@nih.gov OI Little, Mark/0000-0003-0980-7567 NR 15 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD OCT 20 PY 2015 VL 351 AR h5405 DI 10.1136/bmj.h5405 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CV3FJ UT WOS:000364143900007 PM 26486561 ER PT J AU Lee, NR Anand, P Will, E Adeyemi, EI Clasen, LS Blumenthal, JD Giedd, JN Daunhauer, LA Fidler, DJ Edgin, JO AF Lee, Nancy Raitano Anand, Payal Will, Elizabeth Adeyemi, Elizabeth I. Clasen, Liv S. Blumenthal, Jonathan D. Giedd, Jay N. Daunhauer, Lisa A. Fidler, Deborah J. Edgin, Jamie O. TI Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY) SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE executive function; age; development; Trisomy 21; klinefelter syndrome; trisomy X syndrome; behavior; aneuploidy ID AUTISM SPECTRUM DISORDERS; ALZHEIMERS-DISEASE; KLINEFELTER SYNDROME; BEHAVIOR CHANGES; WORKING-MEMORY; Y-CHROMOSOMES; EXTRA X; CHILDREN; PERSONALITY; POPULATION AB Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. C1 [Lee, Nancy Raitano; Adeyemi, Elizabeth I.; Clasen, Liv S.; Blumenthal, Jonathan D.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Lee, Nancy Raitano] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Anand, Payal; Edgin, Jamie O.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Will, Elizabeth; Daunhauer, Lisa A.; Fidler, Deborah J.] Colorado State Univ, Human Dev & Family Studies, Ft Collins, CO 80523 USA. [Giedd, Jay N.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Lee, NR (reprint author), Drexel Univ, Dept Psychol, 3141 Chestnut St,Stratton 119, Philadelphia, PA 19104 USA. EM nrl39@drexel.edu RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016 OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713 FU Intramural Research Program of National Institutes of Health, National Institute of Mental Health [ZIA MH00279413]; extramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD07434601A1]; Research Down Syndrome; LuMind Research Down Syndrome Foundation; US Department of Education/Institute for Education Sciences [R324A110136]; US Department of Education/National Institute of Disability and Rehabilitation Research [H133G100197] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health (ZIA MH00279413; JG, NL, EA, JB, LC), the extramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development-R01HD07434601A1 (JE, PA), Research Down Syndrome (JE, PA), the LuMind Research Down Syndrome Foundation (JE, PA), US Department of Education/Institute for Education Sciences-R324A110136 (DF, LD, EW), and the US Department of Education/National Institute of Disability and Rehabilitation Research-H133G100197 (DF, LD, EW). we'd like to thank the individuals and families who participated in these research studies. We are grateful for their time and efforts. NR 53 TC 1 Z9 1 U1 4 U2 10 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PD OCT 20 PY 2015 VL 9 AR 264 DI 10.3389/fnbh.2015.00254 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CU8IJ UT WOS:000363785100001 PM 26539087 ER PT J AU Trombetta-Lima, M Winnischofer, SMB Demasi, MAA Astorino, R Carreira, ACO Wei, BY Ribas, TD Konig, MS Bowman-Colin, C Oba-Shinjo, SM Marie, SKN Stetler-Stevenson, W Sogayar, MC AF Trombetta-Lima, Marina Brochado Winnischofer, Sheila Maria Almeida Demasi, Marcos Angelo Astorino Filho, Renato Oliveira Carreira, Ana Claudia Wei, Beiyang Ribas, Thais de Assis Konig, Michelle Silberspitz Bowman-Colin, Christian Oba-Shinjo, Sueli Mieko Nagahashi Marie, Suely Kazue Stetler-Stevenson, William Sogayar, Mari Cleide TI Isolation and characterization of novel RECK tumor suppressor gene splice variants SO ONCOTARGET LA English DT Article DE RECK; GBM; splicing; isoforms; MMP ID CYSTEINE-RICH PROTEIN; MATRIX-METALLOPROTEINASE; KAZAL MOTIFS; DOWN-REGULATION; VEGF-A; CANCER; GLIOMA; INHIBITORS; INVASION; PATHWAY AB Glioblastoma multiforme is the most common and lethal of the central nervous system glial-derived tumors. RECK suppresses tumor invasion by negatively regulating at least three members of the matrix metalloproteinase family: MMP-9, MMP-2, and MT1-MMP. A positive correlation has been observed between the abundance of RECK expression in tumor samples and a more favorable prognosis for patients with several types of tumors. In the present study, novel alternatively spliced variants of the RECK gene: RECK-B and RECK-I were isolated by RT-PCR and sequenced. The expression levels and profiles of these alternative RECK transcripts, as well as canonical RECK were determined in tissue samples of malignant astrocytomas of different grades and in a normal tissue RNA panel by qRT-PCR. Our results show that higher canonical RECK expression, accompanied by a higher canonical to alternative transcript expression ratio, positively correlates with higher overall survival rate after chemotherapeutic treatment of GBM patients. U87MG and T98G cells over-expressing the RECK-B alternative variant display higher anchorage-independent clonal growth and do not display modulation of, respectively, MMP-2 and MMP-9 expression. Our findings suggest that RECK transcript variants might have opposite roles in GBM biology and the ratio of their expression levels may be informative for the prognostic outcome of GBM patients. C1 [Trombetta-Lima, Marina; Almeida Demasi, Marcos Angelo; Astorino Filho, Renato; Oliveira Carreira, Ana Claudia; Sogayar, Mari Cleide] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP, Brazil. [Trombetta-Lima, Marina; Almeida Demasi, Marcos Angelo; Astorino Filho, Renato; Oliveira Carreira, Ana Claudia; Ribas, Thais de Assis; Konig, Michelle Silberspitz; Bowman-Colin, Christian; Oba-Shinjo, Sueli Mieko; Nagahashi Marie, Suely Kazue; Sogayar, Mari Cleide] Univ Sao Paulo, NUCEL NETCEM Fac Med, BR-05360120 Sao Paulo, SP, Brazil. [Brochado Winnischofer, Sheila Maria] Univ Fed Parana, Dept Bioquim & Biol Mol, BR-81531990 Curitiba, Parana, Brazil. [Bowman-Colin, Christian] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Wei, Beiyang; Stetler-Stevenson, William] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Oba-Shinjo, Sueli Mieko; Nagahashi Marie, Suely Kazue] Univ Sao Paulo, Fac Med, Dept Neurol, BR-01246000 Sao Paulo, SP, Brazil. RP Sogayar, MC (reprint author), Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP, Brazil. EM mcsoga@iq.usp.br RI Trombetta Lima, Marina/P-1757-2015; Carreira, Ana Claudia/B-7655-2012; Marie, Suely/D-1870-2012; Oba-Shinjo, Sueli /C-4017-2012 OI Trombetta Lima, Marina/0000-0002-3687-6210; FU FAPESP-Fundacao de Apoio a Pesquisa do Estado de Sao Paulo [01/10707-7, 08/53971-5, 04/12133-6, 2010/51634-1]; CNPq-Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [457601/2013-2, 401828/2012-3, 401430/2013-8]; FINEP-Financiadora de Estudos e Projetos [01.06.0664.00, 01.08.0622.00]; BNDES-Banco Nacional de Desenvolvimento Economico e Social [09.2.1066.1]; CAPES-Coordenacao para o Aperfeicoamento do Ensino Superior [BEX 0518/11-5]; Fulbright Program [BEX 0518/11-5] FX This work was supported by FAPESP-Fundacao de Apoio a Pesquisa do Estado de Sao Paulo [grant numbers 01/10707-7, 08/53971-5, 04/12133-6, 2010/51634-1], CNPq-Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, [grants numbers 457601/2013-2; 401828/2012-3 and 401430/2013-8], FINEP-Financiadora de Estudos e Projetos [01.06.0664.00, 01.08.0622.00] and BNDES-Banco Nacional de Desenvolvimento Economico e Social [09.2.1066.1], joint CAPES-Coordenacao para o Aperfeicoamento do Ensino Superior and The Fulbright Program [BEX 0518/11-5]. NR 57 TC 2 Z9 2 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 20 PY 2015 VL 6 IS 32 BP 33120 EP 33133 DI 10.18632/oncotarget.5305 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DQ UT WOS:000363186600077 PM 26431549 ER PT J AU Rao, CV Janakiram, NB Madka, V Devarkonda, V Brewer, M Biddick, L Lightfoot, S Steele, VE Mohammed, A AF Rao, Chinthalapally V. Janakiram, Naveena B. Madka, Venkateshwar Devarkonda, Vishal Brewer, Misty Biddick, Laura Lightfoot, Stan Steele, Vernon E. Mohammed, Altaf TI Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma SO ONCOTARGET LA English DT Article DE chemoprevention; inflammation; EGFR; pancreatic cancer ID EPIDERMAL-GROWTH-FACTOR; SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; RECEPTOR TYROSINE KINASE; INTRAEPITHELIAL NEOPLASIA; PREVENTS PROGRESSION; CARCINOMA CELLS; STEM-CELLS; CANCER; CELECOXIB; MICE AB Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX), and epidermal growth factor receptor (EGRF) are over-expressed in human pancreatic ductal adenocarcinoma (PDAC). Using next-generation sequencing (NGS) analysis, we show significant increase in COX-2, 5-LOX, and EGFR expression during PDAC progression. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and EGFR simultaneously, we tested effects of licofelone (dual 5-LOX-COX inhibitor), and gefitinib (EGFR inhibitor), individually and in combination, on pancreatic intraepithelial neoplasms (PanINs) and their progression to PDAC using genetically engineered mice. Individually, licofelone (L) and gefitinib (G) significantly inhibited incidence of PDAC in male (72% L, 90% G, p < 0.0001) and female (90% L, 85% G, p < 0.0001) mice. The combination drug treatment produced complete inhibition of PDAC in both genders. Pancreata of mice receiving combination treatment showed significantly fewer Dclk1-positive cancer stem-like cells, inhibition of COX-2, 5-LOX, PCNA, EGFR and beta-catenin expression (p < 0.05-0.0002), increased p21 expression. Significant changes in tumor immune responses and desmoplastic reaction was observed by NGS analysis in combination treatment (p < 0.05). In summary, early simultaneous targeting of 5-LOX-COX- and EGFR pathways may provide additive inhibitory effects leading to complete suppression of PDAC. C1 [Rao, Chinthalapally V.; Janakiram, Naveena B.; Madka, Venkateshwar; Devarkonda, Vishal; Brewer, Misty; Biddick, Laura; Lightfoot, Stan; Mohammed, Altaf] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Ctr Canc Prevent & Drug Dev,Hem Onc Sect,Stephens, Oklahoma City, OK 73106 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, Ctr Canc Prevent & Drug Dev,Hem Onc Sect,Stephens, Oklahoma City, OK 73106 USA. EM cv-rao@ouhsc.edu; altaf-mohammed@ouhsc.edu FU National Institute of General Medical Sciences of the National Institutes of Health [8P20GM103447]; National Cancer Institute [N01-CN-53300]; Kerley-Cade Endowed Chair Fund FX The authors thank the University of Oklahoma Health Sciences Center Rodent Barrier Facility staff. We also want to thank Kathy Kyler for valuable suggestions and editorial help. We also thank the Laboratory for Genomics and Bioinformatics at the OUHSC for providing core services for sequencing of pancreatic tissues. Transcriptome analysis was supported by the National Center for Research Resources and the National Institute of General Medical Sciences of the National Institutes of Health through Grant Number 8P20GM103447.; This work was supported in part by the National Cancer Institute grant N01-CN-53300 and Kerley-Cade Endowed Chair Fund to C.V. Rao. NR 39 TC 2 Z9 2 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 20 PY 2015 VL 6 IS 32 BP 33290 EP 33305 DI 10.18632/oncotarget.5396 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DQ UT WOS:000363186600090 PM 26429877 ER PT J AU Martin, EW Buzza, MS Driesbaugh, KH Liu, SH Fortenberry, YM Leppla, SH Antalis, TM AF Martin, Erik W. Buzza, Marguerite S. Driesbaugh, Kathryn H. Liu, Shihui Fortenberry, Yolanda M. Leppla, Stephen H. Antalis, Toni M. TI Targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden SO ONCOTARGET LA English DT Article DE anthrax toxin; membrane-anchored serine protease; testisin; hepsin; prodrug ID TESTICULAR GERM-CELLS; LETHAL TOXIN; PROSTATE-CANCER; C INHIBITOR; PROTECTIVE ANTIGEN; EPITHELIAL-CELLS; MAMMALIAN-CELLS; OVARIAN-CANCER; IN-VIVO; CLINICOPATHOLOGICAL PARAMETERS AB The membrane-anchored serine proteases are a unique group of trypsin-like serine proteases that are tethered to the cell surface via transmembrane domains or glycosyl-phosphatidylinositol-anchors. Overexpressed in tumors, with pro-tumorigenic properties, they are attractive targets for protease-activated prodrug-like anti-tumor therapies. Here, we sought to engineer anthrax toxin protective antigen (PrAg), which is proteolytically activated on the cell surface by the proprotein convertase furin to instead be activated by tumor cell-expressed membrane-anchored serine proteases to function as a tumoricidal agent. PrAg's native activation sequence was mutated to a sequence derived from protein C inhibitor (PCI) that can be cleaved by membrane-anchored serine proteases, to generate the mutant protein PrAg-PCIS. PrAg-PCIS was resistant to furin cleavage in vitro, yet cytotoxic to multiple human tumor cell lines when combined with FP59, a chimeric anthrax toxin lethal factor-Pseudomonas exotoxin fusion protein. Molecular analyses showed that PrAg-PCIS can be cleaved in vitro by several serine proteases including the membrane-anchored serine protease testisin, and mediates increased killing of testisin-expressing tumor cells. Treatment with PrAg-PCIS also potently attenuated the growth of testisin-expressing xenograft tumors in mice. The data indicates PrAg can be engineered to target tumor cell-expressed membrane-anchored serine proteases to function as a potent tumoricidal agent. C1 [Martin, Erik W.; Buzza, Marguerite S.; Driesbaugh, Kathryn H.; Antalis, Toni M.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Martin, Erik W.; Buzza, Marguerite S.; Driesbaugh, Kathryn H.; Antalis, Toni M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Liu, Shihui; Leppla, Stephen H.] NIAID, NIH, Bethesda, MD 20892 USA. [Fortenberry, Yolanda M.] Johns Hopkins Univ, Div Pediat Hematol, Sch Med, Baltimore, MD 21205 USA. RP Antalis, TM (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. EM tantalis@som.umaryland.edu FU National Institutes of Health [HL084387, HL118390, HL096407]; National Institute of Allergy and Infectious Diseases, NIH; Mary Kay Ash Foundation; NIH T32 Integrative Training Program in Membrane Biology Fellowship [5T32GM008181-25] FX This work was supported by National Institutes of Health grants HL084387 (to T.M.A.), HL118390 (to T.M.A.), HL096407 (to Y.F.), the intramural research program of the National Institute of Allergy and Infectious Diseases, NIH (S.H.L., S.L.), and the Mary Kay Ash Foundation (T.M.A.). E.W.M. was supported by a NIH T32 Integrative Training Program in Membrane Biology Fellowship (5T32GM008181-25). NR 103 TC 2 Z9 2 U1 2 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 20 PY 2015 VL 6 IS 32 BP 33534 EP 33553 DI 10.18632/oncotarget.5214 PG 20 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DQ UT WOS:000363186600108 PM 26392335 ER PT J AU O'Neil, PK Rollauer, SE Noinaj, N Buchanan, SK AF O'Neil, Patrick K. Rollauer, Sarah E. Noinaj, Nicholas Buchanan, Susan K. TI Fitting the Pieces of the beta-Barrel Assembly Machinery Complex SO BIOCHEMISTRY LA English DT Article ID OUTER-MEMBRANE PROTEINS; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI BAMB; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; EVOLUTIONARY CONSERVATION; ESSENTIAL COMPONENT; PERIPLASMIC DOMAIN; LIPOPROTEIN BAMC; YAET COMPLEX AB beta-Barrel membrane proteins are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria; however, exactly how they are folded and inserted remains unknown. Over the past decade, both functional and structural studies have greatly contributed to addressing this elusive mechanism. It is known that a conserved core machinery is required for each organelle, though the overall composition varies significantly. The vast majority of studies that aimed to understand the biogenesis of beta-barrel membrane proteins has been conducted in Gram-negative bacteria. Here, it is the task of a multicomponent complex known as the beta-barrel assembly machinery (BANI) complex to fold and insert new beta-barrel membrane proteins into the outer membrane. In this review, we will discuss recent discoveries with the goal of utilizing all reported structural and functional studies to piece together a current structural model for the fully assembled BAN' complex. C1 [O'Neil, Patrick K.; Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. [Rollauer, Sarah E.; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM nnoinaj@purdue.edu; skbuchan@helix.nih.gov RI Rollauer, Sarah/L-4576-2016 OI Rollauer, Sarah/0000-0002-2116-3170 FU Department of Biological Sciences at Purdue University; National Institute of Allergy and Infectious Diseases [1K22AI113078-01]; Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Sir Henry Wellcome Post-Doctoral Fellowship [103040/Z/13/Z] FX N.N. and P.K.O. are supported by the Department of Biological Sciences at Purdue University and by the National Institute of Allergy and Infectious Diseases (1K22AI113078-01). S.E.R and S.K.B. are supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. S.E.R. is also supported by a Sir Henry Wellcome Post-Doctoral Fellowship (103040/Z/13/Z). NR 69 TC 5 Z9 5 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 2015 VL 54 IS 41 BP 6303 EP 6311 DI 10.1021/acs.biochem.5b00852 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CU2IQ UT WOS:000363347600003 PM 26394220 ER PT J AU Cook, NL Mensah, GA AF Cook, Nakela L. Mensah, George A. TI Eliminating Health Disparities What Can We Learn From the Veterans Health Administration? SO CIRCULATION LA English DT Editorial Material DE Editorials; coronary disease; ethnology; health status disparities; mortality rate; renal insufficiency; chronic; stroke ID ETHNIC-DIFFERENCES; DISEASE; CARE; ATHEROSCLEROSIS; MORTALITY; OUTCOMES; SYSTEM; BLACK; RACE; MEN C1 [Cook, Nakela L.; Mensah, George A.] NHLBI, Bethesda, MD 20892 USA. RP Cook, NL (reprint author), NHLBI, 31 Ctr Dr,MSC 2486,Bldg 31,Room 5A48, Bethesda, MD 20892 USA. EM cookn2@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 17 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 20 PY 2015 VL 132 IS 16 BP 1519 EP 1521 DI 10.1161/CIRCULATIONAHA.115.018953 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CT6VJ UT WOS:000362950200001 PM 26384520 ER PT J AU Fontana, M Pica, S Reant, P Abdel-Gadir, A Treibel, TA Banypersad, SM Maestrini, V Barcella, W Rosmini, S Bulluck, H Sayed, RH Patel, K Mamhood, S Bucciarelli-Ducci, C Whelan, CJ Herrey, AS Lachmann, HJ Wechalekar, AD Manisty, CH Schelbert, EB Kellman, P Gillmore, JD Hawkins, PN Moon, JC AF Fontana, Marianna Pica, Silvia Reant, Patricia Abdel-Gadir, Amna Treibel, Thomas A. Banypersad, Sanjay M. Maestrini, Viviana Barcella, William Rosmini, Stefania Bulluck, Heerajnarain Sayed, Rabya H. Patel, Ketna Mamhood, Shameem Bucciarelli-Ducci, Chiara Whelan, Carol J. Herrey, Anna S. Lachmann, Helen J. Wechalekar, Ashutosh D. Manisty, Charlotte H. Schelbert, Eric B. Kellman, Peter Gillmore, Julian D. Hawkins, Philip N. Moon, James C. TI Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis SO CIRCULATION LA English DT Article DE amyloidosis; cardiac imaging techniques; magnetic resonance imaging; prognosis ID BRAIN NATRIURETIC PEPTIDE; AL AMYLOIDOSIS; SYSTEMIC AMYLOIDOSIS; INVERSION-RECOVERY; CMR; QUANTIFICATION; OUTCOMES; SHMOLLI AB Background The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 2413 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). Conclusions There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. C1 [Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Rosmini, Stefania; Bulluck, Heerajnarain; Herrey, Anna S.; Manisty, Charlotte H.; Moon, James C.] Heart Hosp, London W1G 8PH, England. [Fontana, Marianna; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Bulluck, Heerajnarain; Moon, James C.] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England. [Barcella, William] UCL, Dept Stat Sci, London WC1E 6BT, England. [Fontana, Marianna; Banypersad, Sanjay M.; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Whelan, Carol J.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Gillmore, Julian D.; Hawkins, Philip N.] UCL, Royal Free Hosp, Natl Amyloidosis Ctr, London, England. [Bucciarelli-Ducci, Chiara] Univ Bristol, Bristol Heart Inst, Bristol BS8 1TH, Avon, England. [Schelbert, Eric B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. RP Moon, JC (reprint author), Heart Hosp, Imaging Ctr, 16-18 Westmoreland St, London W1G 8PH, England. EM j.moon@ucl.ac.uk OI moon, james/0000-0001-8071-1491; Bucciarelli-Ducci, Chiara/0000-0002-2515-0852 FU British Heart Foundation [FS/12/56/29723]; Rosetrees Trust; National Institute for Health Research [DRF-2013-06-102]; Higher Education Funding Council for England; Bristol NIHR Biomedical Research Unit; Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme FX Dr Fontana is supported by a Clinical Research Training Fellowships from the British Heart Foundation (FS/12/56/29723). A. Abdel-Gadir is supported by the Rosetrees Trust. T. A. Treibel is supported by the National Institute for Health Research (DRF-2013-06-102). Dr Moon is supported by the Higher Education Funding Council for England. Dr Bucciarelli-Ducci is supported by the Bristol NIHR Biomedical Research Unit. This work was undertaken at the University College London Hospital and University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. NR 27 TC 34 Z9 35 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 20 PY 2015 VL 132 IS 16 BP 1570 EP 1579 DI 10.1161/CIRCULATIONAHA.115.016567 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CT6VJ UT WOS:000362950200008 PM 26362631 ER PT J AU Germain, RN Fowlkes, BJ Samelson, LE Leonard, WJ AF Germain, Ronald N. Fowlkes, B. J. Samelson, Lawrence E. Leonard, Warren J. TI William E. Paul, MD (1936-2015) SO IMMUNITY LA English DT Biographical-Item C1 [Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Fowlkes, B. J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD OCT 20 PY 2015 VL 43 IS 4 BP 617 EP 619 DI 10.1016/j.immuni.2015.10.006 PG 3 WC Immunology SC Immunology GA CU4ED UT WOS:000363478700001 PM 26788561 ER PT J AU Lindman, BR Tong, CW Carlson, DE Balke, CW Jackson, EA Madhur, MS Barac, A Abdalla, M Brittain, EL Desai, N Kates, AM Freeman, AM Mann, DL AF Lindman, Brian R. Tong, Carl W. Carlson, Drew E. Balke, C. William Jackson, Elizabeth A. Madhur, Meena S. Barac, Ana Abdalla, Marwah Brittain, Evan L. Desai, Nihar Kates, Andrew M. Freeman, Andrew M. Mann, Douglas L. TI National Institutes of Health Career Development Awards for Cardiovascular Physician-Scientists Recent Trends and Strategies for Success SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE awards and prizes; biomedical research; early-career investigators; fellowships and scholarships; grants; mentors ID OPPORTUNITIES; K08 AB Nurturing the development of cardiovascular physician-scientist investigators is critical for sustained progress in cardiovascular science and improving human health. The transition from an inexperienced trainee to an independent physician-scientist is a multifaceted process requiring a sustained commitment from the trainee, mentors, and institution. A cornerstone of this training process is a career development (K) award from the National Institutes of Health (NIH). These awards generally require 75% of the awardee's professional effort devoted to research aims and diverse career development activities carried out in a mentored environment over a 5-year period. We report on recent success rates for obtaining NIH K awards, provide strategies for preparing a successful application and navigating the early career period for aspiring cardiovascular investigators, and offer cardiovascular division leadership perspectives regarding K awards in the current era. Our objective is to offer practical advice that will equip trainees considering an investigator path for success. (C) 2015 by the American College of Cardiology Foundation. C1 [Lindman, Brian R.; Balke, C. William; Kates, Andrew M.; Mann, Douglas L.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Tong, Carl W.] Texas A&M Univ, Hlth Sci Ctr, Coll Med, Baylor Scott & White Hlth, Temple, TX USA. [Carlson, Drew E.] NHLBI, Off Res Training & Career Dev, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Balke, C. William] John Cochran VA Med Ctr, St Louis, MO USA. [Jackson, Elizabeth A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Madhur, Meena S.; Brittain, Evan L.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Barac, Ana] MedStar Heart & Vasc Inst, Washington, DC USA. [Abdalla, Marwah] Columbia Univ, Med Ctr, New York, NY USA. [Desai, Nihar] Yale Univ, Sch Med, New Haven, CT USA. [Freeman, Andrew M.] Natl Jewish Hlth, Denver, CO USA. RP Lindman, BR (reprint author), Washington Univ, Sch Med, Div Cardiovasc, Campus Box 8086,660 South Euclid Ave, St Louis, MO 63110 USA. EM blindman@dom.wustl.edu OI Lindman, Brian/0000-0002-6879-5343 FU NIH [K23 HL116660, K08 HL114877, K08HL121671, HL117323-02S2, R01 HL111094, U10 HL110309]; Doris Duke Clinical Scientist Development Award [2014106]; American Heart Association (AHA) Clinical Research Program Award [13CRP17080096]; AHA [14GRNT20490025]; Gilead Cardiovascular Scholars Award; Georgetown-Howard Universities Center for Clinical Translational Science (GHUCCTS) KL2 Award [5KL2TR000102-04]; AHA Fellow-to-Faculty Award [13TF16070002]; Actelion ENTELLIGENCE Young Investigator Award; Agency for Healthcare Research and Quality grant [K12HS023000]; Roche Diagnostics; Gilead Sciences; Genentech; Cell Therapeutics; Yale University from Johnson and Johnson; Yale University from Centers of Medicare & Medicaid Services FX Dr. Lindman is supported by NIH grant K23 HL116660, a Doris Duke Clinical Scientist Development Award (#2014106), and an American Heart Association (AHA) Clinical Research Program Award (#13CRP17080096). Dr. Tong is supported by NIH grant K08 HL114877 and a shared (co-principal investigator) AHA grant-in-aid 14GRNT20490025. Dr. Madhur is supported by NIH grant K08HL121671 and a Gilead Cardiovascular Scholars Award. Dr. Barac is supported by Georgetown-Howard Universities Center for Clinical Translational Science (GHUCCTS) KL2 Award, 5KL2TR000102-04. Dr. Abdalla is supported by NIH grant HL117323-02S2. Dr. Brittain is supported by an AHA Fellow-to-Faculty Award (#13TF16070002) and an Actelion ENTELLIGENCE Young Investigator Award. Dr. Desai is supported by Agency for Healthcare Research and Quality grant K12HS023000. Dr. Mann is supported by NIH grants R01 HL111094 and U10 HL110309. Dr. Lindman has received research support from and served on the scientific advisory board for Roche Diagnostics. Dr. Jackson has consulted for McKesson and the American College of Cardiology; and served as an expert witness for Motley Rice, LLC. Dr. Madhur has received research funding from Gilead Sciences. Dr. Barac has received research support and honoraria for lectures from Genentech; and has received consultancy fees from Cell Therapeutics. Dr. Desai is a recipient of a research grant through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing and from the Centers of Medicare & Medicaid Services to develop and maintain performance measures that are used for public reporting. Dr. Freeman has served as a consultant for Gilead; and has served as a speaker for Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The opinions expressed in this article are the authors' own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, the Agency for Healthcare Research and Quality, or the United States Government. Drs. Lindman and Tong contributed equally to the work. NR 17 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 20 PY 2015 VL 66 IS 16 BP 1816 EP 1827 DI 10.1016/j.jacc.2015.08.858 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU2CI UT WOS:000363329300011 PM 26483107 ER PT J AU Banerjee, A Abdelmegeed, MA Jang, S Song, BJ AF Banerjee, Atrayee Abdelmegeed, Mohamed A. Jang, Sehwan Song, Byoung-Joon TI Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats SO PLOS ONE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NONALCOHOLIC STEATOHEPATITIS; PHARMACOLOGICAL INHIBITION; MITOCHONDRIAL DYSFUNCTION; MICROBIAL TRANSLOCATION; MACROPHAGE INFILTRATION; BARRIER DYSFUNCTION; INFECTED PATIENTS; HEPATIC-FIBROSIS; ENVELOPE PROTEIN AB The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT) or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH) (3.5 g/kg/dose oral gavages at 12-h intervals) or dextrose (Control). Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4), leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1) were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART), are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART. C1 [Banerjee, Atrayee; Abdelmegeed, Mohamed A.; Jang, Sehwan; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. EM bj.song@nih.gov FU Intramural Program fund of the National Institute on Alcohol Abuse and Alcoholism FX All of the research for this work was supported by the Intramural Program fund of the National Institute on Alcohol Abuse and Alcoholism. NR 70 TC 4 Z9 4 U1 3 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 20 PY 2015 VL 10 IS 10 AR e0140498 DI 10.1371/journal.pone.0140498 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7XI UT WOS:000363028100039 PM 26484872 ER PT J AU Busser, BW Lin, YS Yang, YQ Zhu, J Chen, GK Michelson, AM AF Busser, Brian W. Lin, Yongshun Yang, Yanqin Zhu, Jun Chen, Guokai Michelson, Alan M. TI An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis SO PLOS ONE LA English DT Article ID CONGENITAL HEART-DISEASE; HISTONE MODIFICATIONS; TRANSGENIC RNAI; DROSOPHILA; NETWORKS; MODEL; MUTATIONS; CHROMATIN; RESOURCE; CULTURE AB Here we used predictive gene expression signatures within a multi-species framework to identify the genes that underlie cardiac cell fate decisions in differentiating embryonic stem cells. We show that the overlapping orthologous mouse and human genes are the most accurate candidate cardiogenic genes as these genes identified the most conserved developmental pathways that characterize the cardiac lineage. An RNAi-based screen of the candidate genes in Drosophila uncovered numerous novel cardiogenic genes. shRNA knockdown combined with transcriptome profiling of the newly-identified transcription factors zinc finger protein 503 and zinc finger E-box binding homeobox 2 and the well-known cardiac regulatory factor NK2 homeobox 5 revealed that zinc finger E-box binding homeobox 2 activates terminal differentiation genes required for cardiomyocyte structure and function whereas zinc finger protein 503 and NK2 homeobox 5 are required for specification of the cardiac lineage. We further demonstrated that an essential role of NK2 homeobox 5 and zinc finger protein 503 in specification of the cardiac lineage is the repression of gene expression programs characteristic of alternative cell fates. Collectively, these results show that orthologous gene expression signatures can be used to identify conserved cardiogenic pathways. C1 [Busser, Brian W.; Yang, Yanqin; Zhu, Jun; Michelson, Alan M.] NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Lin, Yongshun; Chen, Guokai] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Busser, BW (reprint author), NHLBI, Syst Biol Ctr, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM brian.busser@cellectis.com; michelsonam@nhlbi.nih.gov FU National Heart Lung and Blood Institute Division of Intramural Research FX This work was supported by the National Heart Lung and Blood Institute Division of Intramural Research [to AMM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 0 Z9 0 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 20 PY 2015 VL 10 IS 10 AR e0141066 DI 10.1371/journal.pone.0141066 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7XI UT WOS:000363028100110 PM 26485529 ER PT J AU Harskamp-van Ginkel, MW London, SJ Magnus, MC Gademan, MG Vrijkotte, TG AF Harskamp-van Ginkel, Margreet W. London, Stephanie J. Magnus, Maria C. Gademan, Maaike G. Vrijkotte, Tanja G. TI A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort SO PLOS ONE LA English DT Article ID GESTATIONAL WEIGHT-GAIN; PREPREGNANCY OBESITY; ASTHMA; PREGNANCY; RISK; OVERWEIGHT; ABCD; LIFE; METAANALYSIS; SYMPTOMS AB Background A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort. Methods For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. Results At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Conclusions Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI. C1 [Harskamp-van Ginkel, Margreet W.; Gademan, Maaike G.; Vrijkotte, Tanja G.] Acad Med Ctr, Dept Publ Hlth, NL-1100 DD Amsterdam, Netherlands. [London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Durham, NC USA. [London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Durham, NC USA. [Magnus, Maria C.] Norwegian Inst Publ Hlth, Div Epidemiol, Dept Chron Dis, Oslo, Norway. RP Vrijkotte, TG (reprint author), Acad Med Ctr, Dept Publ Hlth, POB 22660, NL-1100 DD Amsterdam, Netherlands. EM t.vrijkotte@amc.uva.nl OI London, Stephanie/0000-0003-4911-5290 FU Netherlands Organization for Health Research and Development (ZonMW) [40-00812-98-11010]; Academic Medical Center, Amsterdam; Public Health Service Amsterdam, Amsterdam; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [ZO1 ES49019] FX This study was supported by the Netherlands Organization for Health Research and Development (ZonMW, TOPgrant: 40-00812-98-11010), the Academic Medical Center, Amsterdam and the Public Health Service Amsterdam, Amsterdam. Dr. London is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (ZO1 ES49019). NR 39 TC 1 Z9 1 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 20 PY 2015 VL 10 IS 10 AR e0140641 DI 10.1371/journal.pone.0140641 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7XI UT WOS:000363028100055 PM 26485533 ER PT J AU Ricketts, CJ Linehan, WM AF Ricketts, Christopher J. Linehan, W. Marston TI Gender Specific Mutation Incidence and Survival Associations in Clear Cell Renal Cell Carcinoma (CCRCC) SO PLOS ONE LA English DT Article ID ESCAPES X-INACTIVATION; GENE-EXPRESSION; JARID1C AB Renal cell carcinoma (RCC) is diagnosed in >200,000 individuals worldwide each year, accounting for similar to 2% of all cancers, but the spread of this disease amongst genders is distinctly uneven. In the U.S. the male:female incidence ratio is approximately 2:1. A potential hypothesis is mutation spectra may differ between tumors dependent upon the gender of the patient, such as mutations of X chromosome encoded genes being more prevalent in male-derived tumors. Combined analysis of three recent large-scale clear cell renal cell carcinoma (CCRCC) mutation sequencing projects identified a significantly increased mutation frequency of PBRM1 and the X chromosome encoded KDM5C in tumors from male patients and BAP1 in tumors from female patients. Mutation of BAP1 had previously been significantly associated with poorer overall survival; however, when stratified by gender, mutation of BAP1 only significantly affected overall survival in female patients. Mutation of chromatin remodeling genes alters gene regulation, but the overall effect of these alterations may also be modified by the presence of other gender specific factors. Thus, the combination of gender and mutation of a specific gene, such as BAP1, may have implications not only for prognosis but also for understanding the role of chromatin remodeling gene mutations in kidney cancer progression. C1 [Ricketts, Christopher J.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM WML@nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; [ZIA BC011028] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Funding was provided by a grant (ZIA BC011028) awarded to Dr. W. Marston Linehan. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 2 Z9 3 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 20 PY 2015 VL 10 IS 10 AR e0140257 DI 10.1371/journal.pone.0140257 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7XI UT WOS:000363028100025 PM 26484545 ER PT J AU Elagha, A Farrag, A AF Elagha, Abdalla Farrag, Azza TI When a Thrombus Is Life-Saving SO CIRCULATION LA English DT Editorial Material ID MYOCARDIAL-INFARCTION C1 [Elagha, Abdalla; Farrag, Azza] Cairo Univ Hosp, Dept Cardiol, Cairo, Egypt. [Elagha, Abdalla] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. RP Elagha, A (reprint author), Kasr Alaini Hosp, Cardiovasc Dept, 1 Saraya St,Third Floor, Cairo 11211, Egypt. EM abdalla.elagha@kasralainy.edu.eg OI Elagha, Abdalla/0000-0003-3136-2293 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 20 PY 2015 VL 132 IS 16 BP E199 EP E201 DI 10.1161/CIRCULATIONAHA.115.017317 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CT6VG UT WOS:000362949900001 PM 26481567 ER PT J AU Klein, HG Flegel, WA Natanson, C AF Klein, Harvey G. Flegel, Willy A. Natanson, Charles TI Red Blood Cell Transfusion Precision vs Imprecision Medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SURGERY; TRIALS C1 [Klein, Harvey G.; Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. EM hklein@dtm.cc.nih.gov NR 8 TC 7 Z9 7 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 20 PY 2015 VL 314 IS 15 BP 1557 EP 1558 DI 10.1001/jama.2015.10890 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CT7XK UT WOS:000363028500010 PM 26355383 ER PT J AU Bayat, A Burbelo, PD Browne, SK Quinlivan, M Martinez, B Holland, SM Buvanendran, A Kroin, JS Mannes, AJ Breuer, J Cohen, JI Iadarola, MJ AF Bayat, Ahmad Burbelo, Peter D. Browne, Sarah K. Quinlivan, Mark Martinez, Bianca Holland, Steven M. Buvanendran, Asokumar Kroin, Jeffrey S. Mannes, Andrew J. Breuer, Judith Cohen, Jeffrey I. Iadarola, Michael J. TI Anti-cytokine autoantibodies in postherpetic neuralgia SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Anti-cytokine autoantibodies; Herpes zoster (HZ); Opportunistic infection; Pain; PHN; Shingles; Varicella zoster virus (VZV) ID VARICELLA-ZOSTER-VIRUS; REGIONAL PAIN SYNDROME; HERPES-ZOSTER; IMMUNE-RESPONSES; VACCINE; IMMUNODEFICIENCY; AUTOIMMUNITY; INFECTION; ADULTS AB Background: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. Methods: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. Results: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-a, interferon-gamma, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-a, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. Conclusions: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN. C1 [Bayat, Ahmad; Mannes, Andrew J.; Iadarola, Michael J.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA. [Browne, Sarah K.; Martinez, Bianca; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Quinlivan, Mark; Breuer, Judith] UCL, Div Infect & Immun, London WC1E 6BT, England. [Buvanendran, Asokumar; Kroin, Jeffrey S.] Rush Univ, Dept Anesthesiol, Med Ctr, Chicago, IL 60612 USA. [Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov OI Breuer, Judith/0000-0001-8246-0534 FU National Institutes of Health Clinical Center; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; VZV Research Foundation; UK National Institutes for Health Research UCL/UCLH Biomedical Research Centre FX This work was supported by the intramural research programs of the National Institutes of Health Clinical Center, National Institute of Dental and Craniofacial Research, the National Institute of Allergy and Infectious Diseases, and the VZV Research Foundation. JB receives funding from the UK National Institutes for Health Research UCL/UCLH Biomedical Research Centre. The authors declare no financial interests that may represent a competing interest. NR 34 TC 0 Z9 0 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 20 PY 2015 VL 13 AR 333 DI 10.1186/s12967-015-0695-6 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CT7QI UT WOS:000363009200002 PM 26482341 ER PT J AU Janik, JE Morris, JC O'Mahony, D Pittaluga, S Jaffe, ES Redon, CE Bonner, WM Brechbiel, MW Paik, CH Whatley, M Chen, C Lee, JH Fleisher, TA Brown, M White, JD Stewart, DM Fioravanti, S Lee, CC Goldman, CK Bryant, BR Junghans, RP Carrasquillo, JA Worthy, T Corcoran, E Conlon, KC Waldmann, TA AF Janik, John E. Morris, John C. O'Mahony, Deirdre Pittaluga, Stefania Jaffe, Elaine S. Redon, Christophe E. Bonner, William M. Brechbiel, Martin W. Paik, Chang H. Whatley, Millie Chen, Clara Lee, Jae-Ho Fleisher, Thomas A. Brown, Maggie White, Jeffrey D. Stewart, Donn M. Fioravanti, Suzanne Lee, Cathryn C. Goldman, Carolyn K. Bryant, Bonita R. Junghans, Richard P. Carrasquillo, Jorge A. Worthy, Tat'Yana Corcoran, Erin Conlon, Kevin C. Waldmann, Thomas A. TI Y-90-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE radioimmunotherapy; Y-90-daclizumab; Hodgkin's lymphoma; myelodysplastic syndrome ID T-CELL LEUKEMIA; IBRITUMOMAB TIUXETAN RADIOIMMUNOTHERAPY; REED-STERNBERG CELLS; IN-VIVO FORMATION; PHASE-I; DISEASE; THERAPY; TAC; CANCER; INTERLEUKIN-2-RECEPTOR AB Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody Y-90-daclizumab. Y-90 provides strong beta emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with Y-90-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (gamma-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of gamma-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated Y-90-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients. C1 [Janik, John E.; Morris, John C.; O'Mahony, Deirdre; White, Jeffrey D.; Stewart, Donn M.; Fioravanti, Suzanne; Lee, Cathryn C.; Goldman, Carolyn K.; Bryant, Bonita R.; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C.; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Redon, Christophe E.; Bonner, William M.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Ctr Canc, NIH, Bethesda, MD 20892 USA. [Paik, Chang H.; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Carrasquillo, Jorge A.] NIH, Nucl Med Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Fleisher, Thomas A.; Brown, Maggie] NIH, Immunol Serv, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Junghans, Richard P.] Roger Williams Med Ctr, Dept Med, Providence, RI 02908 USA. RP Waldmann, TA (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov OI Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH; National Institute for Allergy and Infectious Diseases Radiation/Nuclear Countermeasures Program FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, and by the National Institute for Allergy and Infectious Diseases Radiation/Nuclear Countermeasures Program. NR 51 TC 5 Z9 5 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 20 PY 2015 VL 112 IS 42 BP 13045 EP 13050 DI 10.1073/pnas.1516107112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9LN UT WOS:000363138600046 PM 26438866 ER PT J AU Gordon, EB Hart, GT Tran, TM Waisberg, M Akkaya, M Kim, AS Hamilton, SE Pena, M Yazew, T Qi, CF Lee, CF Lo, YC Miller, LH Powell, JD Pierce, SK AF Gordon, Emile B. Hart, Geoffrey T. Tran, Tuan M. Waisberg, Michael Akkaya, Munir Kim, Ann S. Hamilton, Sara E. Pena, Mirna Yazew, Takele Qi, Chen-Feng Lee, Chen-Fang Lo, Ying-Chun Miller, Louis H. Powell, Jonathan D. Pierce, Susan K. TI Targeting glutamine metabolism rescues mice from late-stage cerebral malaria SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral malaria; adjunctive therapy; CD8(+) T cells; glutamine metabolism; DON ID T-LYMPHOCYTE ACTIVATION; MALAWIAN CHILDREN; PLASMODIUM-FALCIPARUM; CELL RESPONSES; IN-VIVO; BRAIN; ACCUMULATION; PATHOGENESIS; PARASITE AB The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15-25% in African children despite effective antimalarial chemotherapy. There are no adjunctive treatments for CM, so there is an urgent need to identify new targets for therapy. Here we show that the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) rescues mice from CM when administered late in the infection a time at which mice already are suffering blood-brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by accumulation of parasite-specific CD8(+) effector T cells and infected red blood cells in the brain. Remarkably, within hours of DON treatment mice showed blood-brain barrier integrity, reduced brain swelling, decreased function of activated effector CD8(+) T cells in the brain, and levels of brain metabolites that resembled those in uninfected mice. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children. C1 [Gordon, Emile B.; Hart, Geoffrey T.; Tran, Tuan M.; Waisberg, Michael; Akkaya, Munir; Kim, Ann S.; Pena, Mirna; Yazew, Takele; Qi, Chen-Feng; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Hamilton, Sara E.] Univ Minnesota, Sch Med, Ctr Immunol, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA. [Lee, Chen-Fang; Lo, Ying-Chun; Powell, Jonathan D.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Res Ctr, Dept Oncol, Baltimore, MD 21287 USA. [Lee, Chen-Fang] Chang Gung Mem Hosp, Chang Gung Transplantat Inst, Dept Liver & Transplantat Surg, Taoyuan 333, Taiwan. [Miller, Louis H.] NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. RP Miller, LH (reprint author), NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. EM lmiller@niaid.nih.gov; Jpowell@jhmi.edu; spierce@nih.gov OI AKKAYA, Munir/0000-0002-9949-9424 FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases; NIH [R01AI077610] FX This study was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases and by NIH Grant R01AI077610 (to J.D.P.). NR 37 TC 5 Z9 5 U1 1 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 20 PY 2015 VL 112 IS 42 BP 13075 EP 13080 DI 10.1073/pnas.1516544112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9LN UT WOS:000363138600051 PM 26438846 ER PT J AU Villarino, AV O'Shea, JJ Hunter, CA AF Villarino, Alejandro V. O'Shea, John J. Hunter, Christopher A. TI IL-27 shakes up the establishment of ectopic lymphoid structures SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material C1 [Villarino, Alejandro V.; O'Shea, John J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Hunter, Christopher A.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. RP Villarino, AV (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM alejandro.villarino@nih.gov; John.Oshea@nih.gov; chunter@vet.upenn.edu NR 1 TC 0 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 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 2015 VL 212 IS 11 BP 1757 EP 1757 DI 10.1084/jem.21211insight4 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CZ2HX UT WOS:000366926800004 PM 26482142 ER PT J AU Weber, EW Han, F Tauseef, M Birnbaumer, L Mehta, D Muller, WA AF Weber, Evan W. Han, Fei Tauseef, Mohammad Birnbaumer, Lutz Mehta, Dolly Muller, William A. TI TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-ADHESION MOLECULE; POTENTIAL CANONICAL 6; BORDER RECYCLING COMPARTMENT; LIGHT-CHAIN KINASE; IN-VIVO; VASCULAR-PERMEABILITY; PECAM-1 CD31; SHEAR-STRESS; VE-CADHERIN; CA2+ ENTRY AB Leukocyte transendothelial migration (TEM) is a tightly regulated, multistep process that is critical to the inflammatory response. A transient increase in endothelial cytosolic free calcium ion concentration (up arrow[Ca2+]i) is required for TEM. However, the mechanism by which endothelial up arrow[Ca2+]i regulates TEM and the channels mediating this up arrow[Ca2+]i are unknown. Buffering up arrow[Ca2+]i in endothelial cells does not affect leukocyte adhesion or locomotion but selectively blocks TEM, suggesting a role for up arrow[Ca2+]i specifically for this step. Transient receptor potential canonical 6 (TRPC6), a Ca2+ channel expressed in endothelial cells, colocalizes with platelet/endothelial cell adhesion molecule-1 (PECAM) to surround leukocytes during TEM and clusters when endothelial PECAM is engaged. Expression of dominant-negative TRPC6 or shRNA knockdown in endothelial cells arrests neutrophils apically over the junction, similar to when PECAM is blocked. Selectively activating endothelial TRPC6 rescues TEM during an ongoing PECAM blockade, indicating that TRPC6 functions downstream of PECAM. Furthermore, endothelial TRPC6 is required for trafficking of lateral border recycling compartment membrane, which facilitates TEM. Finally, mice lacking TRPC6 in the nonmyeloid compartment (i.e., endothelium) exhibit a profound defect in neutrophil TEM with no effect on leukocyte trafficking. Our findings identify endothelial TRPC6 as the calcium channel mediating the up arrow[Ca2+]i required for TEM at a step downstream of PECAM homophilic interactions. C1 [Weber, Evan W.; Han, Fei; Muller, William A.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Tauseef, Mohammad; Mehta, Dolly] Univ Illinois, Chicago Coll Med, Ctr Lung & Vasc Biol, Dept Pharmacol, Chicago, IL 60612 USA. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Muller, WA (reprint author), Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. EM wamuller@northwestern.edu FU National Institutes of Health (NIH) [R01HL046849, R37HL064774]; American Heart Association [14PRE18550021, 12PRE9330014]; Intramural Research Division of the NIH [ZO1-ES-101684]; Sidney & Bess Eisenberg Memorial Fund FX This work was supported by the National Institutes of Health (NIH; grants R01HL046849 and R37HL064774 to W.A. Muller) and predoctoral training grants from the American Heart Association (14PRE18550021 and 12PRE9330014 to E.W. Weber) and in part by the Intramural Research Division of the NIH (grant ZO1-ES-101684 to L. Birnbaumer). Publication of this research was supported by the Sidney & Bess Eisenberg Memorial Fund. NR 92 TC 8 Z9 8 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 2015 VL 212 IS 11 BP 1883 EP 1899 DI 10.1084/jem.20150353 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CZ2HX UT WOS:000366926800016 PM 26392222 ER PT J AU Wang, L Jacobson, O Avdic, D Rotstein, BH Weiss, ID Collier, L Chen, XY Vasdev, N Liang, SH AF Wang, Lu Jacobson, Orit Avdic, Din Rotstein, Benjamin H. Weiss, Ido D. Collier, Lee Chen, Xiaoyuan Vasdev, Neil Liang, Steven H. TI Ortho-Stabilized F-18-Azido Click Agents and their Application in PET Imaging with Single-Stranded DNA Aptamers SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE aptamers; bioconjugation; fluorine; PET imaging; radiopharmaceuticals ID POSITRON-EMISSION-TOMOGRAPHY; OLIGONUCLEOTIDE APTAMER; DERIVATIVES; PEPTIDES; PROBES; F-18; PTK7; 1,2,3-TRIAZOLES; CHEMISTRY; BOMBESIN AB Azido F-18-arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition ("click chemistry") for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high-yielding direct radiofluorination for azido F-18-arenes was achieved through the development of an ortho-oxygen-stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido F-18-arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules. C1 [Wang, Lu; Avdic, Din; Rotstein, Benjamin H.; Collier, Lee; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Wang, Lu; Avdic, Din; Rotstein, Benjamin H.; Collier, Lee; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Jacobson, Orit; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Weiss, Ido D.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; vasdev.neil@mgh.harvard.edu; liang.steven@mgh.harvard.edu FU Department of Radiology, MGH/HMS; NIBIB, NIH; NIH FX This work was supported by the Department of Radiology, MGH/HMS, and intramural research program of NIBIB, NIH. We thank Professor Lee Josephson for helpful discussion. S.H.L is a recipient of an NIH career development award. NR 48 TC 10 Z9 10 U1 15 U2 57 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD OCT 19 PY 2015 VL 54 IS 43 BP 12777 EP 12781 DI 10.1002/anie.201505927 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CU3KB UT WOS:000363422700049 PM 26308650 ER PT J AU Berga-Bolanos, R Sharma, A Steinke, FC Pyaram, K Kim, YH Sultana, DA Fang, JX Chang, CH Xue, HH Heller, NM Sen, JM AF Berga-Bolanos, Rosa Sharma, Archna Steinke, Farrah C. Pyaram, Kalyani Kim, Yeung-Hyen Sultana, Dil A. Fang, Jessie X. Chang, Cheong-Hee Xue, Hai-Hui Heller, Nicola M. Sen, Jyoti Misra TI beta-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation SO BMC IMMUNOLOGY LA English DT Article DE Beta-catenin; iNKT cells; iNKT2; iNKT17; IL-17RB ID KILLER T-CELLS; NKT CELLS; AIRWAY HYPERREACTIVITY; IMMUNE-SYSTEM; ASTHMA; IL-25; ACTIVATION; THYMOCYTES; SELECTION; EXPRESSION AB Background: Invariant Natural Killer T (iNKT) cells have been implicated in lung inflammation in humans and also shown to be a key cell type in inducing allergic lung inflammation in mouse models. iNKT cells differentiate and acquire functional characteristics during development in the thymus. However, the correlation between development of iNKT cells in the thymus and role in lung inflammation remains unknown. In addition, transcriptional control of differentiation of iNKT cells into iNKT cell effector subsets in the thymus during development is also unclear. In this report we show that beta-catenin dependent mechanisms direct differentiation of iNKT2 and iNKT17 subsets but not iNKT1 cells. Methods: To study the role for beta-catenin in lung inflammation we utilize mice with conditional deletion and enforced expression of beta-catenin in a well-established mouse model for IL-25-dependen lung inflammation. Results: Specifically, we demonstrate that conditional deletion of beta-catenin permitted development of mature iNKT1 cells while impeding maturation of iNKT2 and 17 cells. A role for beta-catenin expression in promoting iNKT2 and iNKT17 subsets was confirmed when we noted that enforced transgenic expression of beta-catenin in iNKT cell precursors enhanced the frequency and number of iNKT2 and iNKT17 cells at the cost of iNKT1 cells. This effect of expression of beta-catenin in iNKT cell precursors was cell autonomous. Furthermore, iNKT2 cells acquired greater capability to produce type-2 cytokines when beta-catenin expression was enhanced. Discussion: This report shows that beta-catenin deficiency resulted in a profound decrease in iNKT2 and iNKT17 subsets of iNKT cells whereas iNKT1 cells developed normally. By contrast, enforced expression of beta-catenin promoted the development of iNKT2 and iNKT17 cells. It was important to note that the majority of iNKT cells in the thymus of C57BL/6 mice were iNKT1 cells and enforced expression of beta-catenin altered the pattern to iNKT2 and iNKT17 cells suggesting that beta-catenin may be a major factor in the distinct pathways that critically direct differentiation of iNKT effector subsets. Conclusions: Thus, we demonstrate that beta-catenin expression in iNKT cell precursors promotes differentiation toward iNKT2 and iNKT17 effector subsets and supports enhanced capacity to produce type 2 and 17 cytokines which in turn augment lung inflammation in mice. C1 [Berga-Bolanos, Rosa; Sharma, Archna; Sultana, Dil A.; Sen, Jyoti Misra] NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA. [Steinke, Farrah C.; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Interdisciplinary Immunol Grad Program, Iowa City, IA 52242 USA. [Pyaram, Kalyani; Kim, Yeung-Hyen; Chang, Cheong-Hee] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48109 USA. [Fang, Jessie X.; Heller, Nicola M.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Sch Med, Baltimore, MD 21287 USA. [Sen, Jyoti Misra] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA. [Sen, Jyoti Misra] NIA, NIH, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA. EM Jyoti-Sen@nih.gov RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 FU Intramural Research Program of the National Institute on Aging at the National Institutes of Health FX We thank NIA animal facility and genotyping facility for animal husbandry and genotyping, Juliet Meltsner, Kamalvishnu Gottimukkala, Wandi Zhu and Lynette Naler for technical help, Ranjan Sen and Wandi Zhu for insightful comments on the manuscript and the Tetramer Facility of the US National Institutes of Health for providing PE- and APC-conjugated mouse CD1d tetramers loaded with glycolipid PBS-57. This research was supported by the Intramural Research Program of the National Institute on Aging at the National Institutes of Health. Authors declare no conflict of interest. NR 40 TC 1 Z9 1 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD OCT 19 PY 2015 VL 16 AR 62 DI 10.1186/s12865-015-0121-0 PG 10 WC Immunology SC Immunology GA CT7QF UT WOS:000363008900001 PM 26482437 ER PT J AU Miller, MA Moss, ML Powell, G Petrovich, R Edwards, L Meyer, AS Griffith, LG Lauffenburger, DA AF Miller, Miles A. Moss, Marcia L. Powell, Gary Petrovich, Robert Edwards, Lori Meyer, Aaron S. Griffith, Linda G. Lauffenburger, Douglas A. TI Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain SO SCIENTIFIC REPORTS LA English DT Article ID GROWTH-FACTOR RECEPTOR; HEPARIN-BINDING EGF; EPITHELIAL-CELL PROLIFERATION; BREAST-TUMOR PROGRESSION; LIGAND-BINDING; KINASE INHIBITORS; TISSUE INHIBITOR; MELTRIN-ALPHA; CANCER CELLS; IN-VIVO AB Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, "decoy" antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling. C1 [Miller, Miles A.; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Moss, Marcia L.] BioZyme Inc, Apex, NC 27523 USA. [Powell, Gary; Petrovich, Robert; Edwards, Lori] NIEHS, Res Triangle Pk, NC 27709 USA. RP Lauffenburger, DA (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM lauffen@mit.edu FU NIH [R01-CA096504, U54-CA112967] FX This work was partially supported by NIH grants R01-CA096504 and U54-CA112967. The authors thank the Swanson Biotechnology Center for use of microscopy and flow cytometry facilities. NR 65 TC 6 Z9 6 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 19 PY 2015 VL 5 AR 15150 DI 10.1038/srep15150 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7FK UT WOS:000362979400001 PM 26477568 ER PT J AU LaVerda, NL Goldsmith, DF Alavanja, MCR Hunting, KL AF LaVerda, Nancy L. Goldsmith, David F. Alavanja, Michael C. R. Hunting, Katherine L. TI PESTICIDE EXPOSURES AND BODY MASS INDEX (BMI) OF PESTICIDE APPLICATORS FROM THE AGRICULTURAL HEALTH STUDY SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID PERSISTENT ORGANIC POLLUTANTS; NUTRITION EXAMINATION SURVEY; SELF-REPORTED WEIGHT; 3RD NATIONAL-HEALTH; ORGANOCHLORINE PESTICIDES; ENDOCRINE DISRUPTORS; INSULIN-RESISTANCE; OBESITY EPIDEMIC; VALIDITY; VALIDATION AB Endocrine-disrupting chemicals, including pesticides, may be associated with weight gain. This is the first longitudinal study to examine a potential association between weight gain and pesticides using data on 8,365 male pesticide applicators from the Agricultural Health Study (AHS) cohort established in 1993. The relationship between total cumulative days of exposure to pesticide functional/chemical classes and to the four most frequently used individual pesticides was studied in relation to body mass index (BMI) at the time of 5-yr follow-up (beginning in 1998) with the length of the exposure period dating back to age 20 yr. Multiple regression, Spearman correlation, ordinal logistic regression, and logistic regression models all utilized a Bonferroni-adjusted p value, were adjusted for relevant covariates, and were stratified by state of residence (Iowa/North Carolina) and presence/absence of weight-related health conditions. Adjusted multiple regression yielded statistically significant positive parameter estimates for the study sample and Iowa subgroups with consistent findings for triazine herbicides and atrazine: Change in BMI per 100 cumulative pesticide exposure days ranged from 0.07 to 0.11 for triazine herbicides and from 0.10 to 0.19 for atrazine. Ordinal logistic regression compared normal weight with overweight and with obese using the zero exposure category as referent. Statistically significant adjusted odds ratios identified for the study sample and both state subgroups for the highest level of atrazine exposure ranged from 1.4 to 1.7. Further investigation is warranted to evaluate the associations identified here. C1 [LaVerda, Nancy L.; Goldsmith, David F.; Hunting, Katherine L.] George Washington Univ, Milken Inst, Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC USA. [Alavanja, Michael C. R.] NCI, Rockville, MD USA. [Goldsmith, David F.] Georgetown Univ, Dept Human Sci, Washington, DC USA. RP LaVerda, NL (reprint author), 1280 21st St NW, Washington, DC 20036 USA. EM nlaverda@gwu.edu FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP01 0119] FX We thank all of the pesticide applicators and their spouses for their participation in the Agricultural Health Study. This article is based on the doctoral dissertation of Nancy L. LaVerda, who performed the bulk of the work under the supervision of Drs. Goldsmith and Hunting. We thank Drs. Dante Verme and Heather J. Hoffman, both from the Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, for their assistance with the statistical analysis plan and SAS programming. We also thank the four anonymous peer reviewers who provided valuable suggestions on this research. This work was supported in part by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030), and the National Cancer Institute (Z01-CP01 0119). NR 64 TC 3 Z9 3 U1 4 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD OCT 18 PY 2015 VL 78 IS 20 BP 1255 EP 1276 DI 10.1080/15287394.2015.1074844 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CW4NI UT WOS:000364967900001 PM 26479458 ER PT J AU Tuo, JS Wang, YJ Cheng, R Li, YC Chen, M Qiu, FF Qian, HH Shen, DF Penalva, R Xu, HP Ma, JX Chan, CC AF Tuo, Jingsheng Wang, Yujuan Cheng, Rui Li, Yichao Chen, Mei Qiu, Fangfang Qian, Haohua Shen, Defen Penalva, Rosana Xu, Heping Ma, Jian-Xing Chan, Chi-Chao TI Wnt signaling in age-related macular degeneration: human macular tissue and mouse model SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Wnt signaling; Antibody against Wnt receptor LRP6; Mouse model; Retinal lesion; Ccl2(-/-)/Cx3cr1(-/-)/rd8 mouse; Ccl2(-/-)/Cx3cr1(gfp/gfp) mouse; Serum kallistatin ID FOCAL RETINAL DEGENERATION; EYE DISEASE; CCL2/CX3CR1-DEFICIENT MICE; PIGMENT EPITHELIUM; PATHOGENIC ROLE; MURINE MODEL; RISK-FACTORS; PATHWAY; INFLAMMATION; CANCER AB Background: The wingless-type MMTV integration site (Wnt) signaling is a group of signal transduction pathways. In canonical Wnt pathway, Wnt ligands bind to low-density lipoprotein receptor-related protein 5 or 6 (LRP5 or LRP6), resulting in phosphorylation and activation of the receptor. We hypothesize that canonical Wnt pathway plays a role in the retinal lesion of age-related macular degeneration (AMD), a leading cause of irreversible central visual loss in elderly. Methods: We examined LRP6 phosphorylation and Wnt signaling cascade in human retinal sections and plasma kallistatin, an endogenous inhibitor of the Wnt pathway in AMD patients and non-AMD subjects. We also used the Ccl2(-/-)/Cx3cr1(-/-)/rd8 and Ccl2(-/-)/Cx3cr1(gfp/gfp) mouse models with AMD-like retinal degeneration to further explore the involvement of Wnt signaling activation in the retinal lesions in those models and to preclinically evaluate the role of Wnt signaling suppression as a potential therapeutic option for AMD. Results: We found higher levels of LRP6 (a key Wnt signaling receptor) protein phosphorylation and transcripts of the Wnt pathway-targeted genes, as well as higher beta-catenin protein in AMD macula compared to controls. Kallistatin was decreased in the plasma of AMD patients. Retinal non-phosphorylated-beta-catenin and phosphorylated-LRP6 were higher in Ccl2(-/-)/Cx3cr1(-/-)/rd8 mice than that in wild type. Intravitreal administration of an anti-LRP6 antibody slowed the progression of retinal lesions in Ccl2(-/-)/Cx3cr1(-/-)/rd8 and Ccl2(-/-)/Cx3cr1(gfp/gfp) mice. Electroretinography of treated eyes exhibited larger amplitudes compared to controls in both mouse models. A2E, a retinoid byproduct associated with AMD was lower in the treated eyes of Ccl2(-/-)/Cx3cr1(-/-)/rd8 mice. Anti-LRP6 also suppressed the expression of Tnf-alpha and Icam-1 in Ccl2(-/-)/Cx3cr1(-/-)/rd8 retinas. Conclusions: Wnt signaling may be disturbed in AMD patients, which could contribute to the retinal inflammation and increased A2E levels found in AMD. Aberrant activation of canonical Wnt signaling might also contribute to the focal retinal degenerative lesions of mouse models with Ccl2 and Cx3cr1 deficiency, and intravitreal administration of anti-LRP6 antibody could be beneficial by deactivating the canonical Wnt pathway. C1 [Tuo, Jingsheng; Wang, Yujuan; Shen, Defen; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cheng, Rui; Qiu, Fangfang; Ma, Jian-Xing] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA. [Li, Yichao; Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. [Chen, Mei; Penalva, Rosana; Xu, Heping] Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016; OI Xu, Heping/0000-0003-4000-931X FU Intramural Research Program of National Eye Institute, National Institutes of Health; NIH [EY019309, EY018659, EY012231]; Fight for Sight Pioneering eye research, UK; JDRF grant FX This work was supported by the Intramural Research Program of National Eye Institute, National Institutes of Health; NIH research Grants EY019309, EY018659, and EY012231; Fight for Sight Pioneering eye research, UK; and a JDRF grant. We thank Mr. Nicholas Popp (NEI) for language editing. NR 56 TC 3 Z9 3 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 17 PY 2015 VL 13 AR 330 DI 10.1186/s12967-015-0683-x PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CT5TX UT WOS:000362874900001 PM 26476672 ER PT J AU Huestis, MA Concheiro, M Scheidweiler, KB Anizan, S Lehner, KR Bukhari, MO Suzuki, M Rice, KC Baumann, MH AF Huestis, M. A. Concheiro, M. Scheidweiler, K. B. Anizan, S. Lehner, K. R. Bukhari, M. O. Suzuki, M. Rice, K. C. Baumann, M. H. TI In Vivo Toxicokinetics of Novel Psychoactive Substances (NPS) in Rats SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 51st Congress of the European-Societies-of-Toxicology (EUROTOX) CY SEP 13-16, 2015 CL Portuguese Soc Pharmacol, Sect Toxicol, Porto, PORTUGAL SP European Soc Toxicol HO Portuguese Soc Pharmacol, Sect Toxicol C1 [Lehner, K. R.; Bukhari, M. O.; Baumann, M. H.] Designer Drug Res Unit, Baltimore, MD USA. [Suzuki, M.; Rice, K. C.] NIDA, Drug Design & Synth Sect, IRP, Baltimore, MD USA. [Suzuki, M.; Rice, K. C.] NIAAA, NIH, Baltimore, MD USA. [Suzuki, M.] Otsuka Pharmaceut Co Ltd, Qs Res Inst, Med Chem Grp, Tokushima 77101, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 16 PY 2015 VL 238 IS 2 SU S MA S06-3 BP S23 EP S24 DI 10.1016/j.toxlet.2015.08.199 PG 2 WC Toxicology SC Toxicology GA DE5SY UT WOS:000370693800066 ER PT J AU Nogare, DD Chitnis, AB AF Nogare, Damian Dalle Chitnis, Ajay B. TI ORGAN SIZE Connecting physical cues and tissue patterning SO ELIFE LA English DT Editorial Material C1 [Nogare, Damian Dalle; Chitnis, Ajay B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neural Dev Dynam, Bethesda, MD 20892 USA. RP Nogare, DD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neural Dev Dynam, Bethesda, MD 20892 USA. EM dalledam@mail.nih.gov; chitnisa@mail.nih.gov NR 7 TC 0 Z9 0 U1 1 U2 1 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD OCT 16 PY 2015 VL 4 AR e11375 DI 10.7554/eLife.11375 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CU1MS UT WOS:000363286600001 ER PT J AU Guasch, L Peach, ML Nicklaus, MC AF Guasch, Laura Peach, Megan L. Nicklaus, Marc C. TI Tautomerism of Warfarin: Combined Chemoinformatics, Quantum Chemical, and NMR Investigation SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID DATABASES; FORMS; ACID; SITE AB Warfarin, an important anticoagulant drug, can exist in solution in 40 distinct tautomeric forms through both prototropic tautomerism and ring chain tautomerism. We have investigated all warfarin tautomers with computational and NMR approaches. Relative energies calculated at the B3LYP/6-311G++(d,p) level of theory indicate that the 4-hydroxycoumarin cyclic hemiketal tautomer is the most stable tautomer in aqueous solution, followed by the 4-hydroxycoumarin open-chain tautomer. This is in agreement with our NMR. experiments where the spectral assignments indicate that warfarin exists mainly as a mixture of cyclic hemiketal diastereomers, with an open-chain tautomer as a minor component. We present a diagram of the interconversion of warfarin created taking into account the calculated equilibrium constants (pK(T)) for all tautomeric reactions. These findings help with gaining further understanding of proton transfer and ring closure tautomerization processes. We also discuss the results in the context of chemoinformatics rules for handling tautomerism. C1 [Guasch, Laura; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Peach, Megan L.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Biol Chem Lab, Basic Sci Program, Frederick, MD 21702 USA. RP Nicklaus, MC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM mn1@helix.nih.gov OI Nicklaus, Marc/0000-0002-4775-7030 FU U.S. Department of Health and Human Services; National Institutes of Health at the Center for Cancer Research, National Cancer Institute; Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX This study used the high-performance computational capabilities of the Biowulf Linux cluster (http://biowulf.nih.gov) at the National Institutes of Health (Bethesda, MD, USA). The authors thank Joseph J. Barchi for his help with the NMR experiments. All funding for this project came from the U.S. Department of Health and Human Services; specifically, L.G. and M.C.N. acknowledge support of this research by the Intramural Research Program of the National Institutes of Health, at the Center for Cancer Research, National Cancer Institute; and M.L.P. was supported by Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E. NR 27 TC 1 Z9 1 U1 3 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 16 PY 2015 VL 80 IS 20 BP 9900 EP 9909 DI 10.1021/acs.joc.5b01370 PG 10 WC Chemistry, Organic SC Chemistry GA CU0QU UT WOS:000363224600010 PM 26372257 ER PT J AU Hamlington, B Ivey, LE Brenna, E Biesecker, LG Biesecker, BB Sapp, JC AF Hamlington, Barbara Ivey, Lauren E. Brenna, Ethan Biesecker, Leslie G. Biesecker, Barbara B. Sapp, Julie C. TI Characterization of Courtesy Stigma Perceived by Parents of Overweight Children with Bardet-Biedl Syndrome SO PLOS ONE LA English DT Article ID AFFILIATE STIGMA; OBESITY; EXPERIENCES; CHILDHOOD; HEALTH AB Background A child's obesity is generally perceived by the public to be under the control of the child's parents. While the health consequences of childhood obesity are well understood, less is known about psychological and social effects of having an obese child on parents. We set out to characterize stigma and courtesy stigma experiences surrounding obesity among children with Bardet-Biedl syndrome (BBS), a multisystem genetic disorder, and their parents. Methods Twenty-eight parents of children with BBS participated in semi-structured interviews informed by social stigmatization theory, which describes courtesy stigma as parental perception of stigmatization by association with a stigmatized child. Parents were asked to describe such experiences. Results Parents of children with BBS reported the child's obesity as the most frequent target of stigmatization. They perceived health care providers as the predominant source of courtesy stigma, describing interactions that resulted in feeling devalued and judged as incompetent parents. Conclusions Parents of children with BBS feel blamed by others for their child's obesity and described experiences that suggest health care providers may contribute to courtesy stigma and thus impede effective communication about managing obesity. Health care providers may reinforce parental feelings of guilt and responsibility by repeating information parents may have previously heard and ignoring extremely challenging barriers to weight management, such as a genetic predisposition to obesity. Strategies to understand and incorporate parents' perceptions and causal attributions of their children's weight may improve communication about weight control. C1 [Hamlington, Barbara] US Oncol, Rocky Mt Canc Ctr, Denver, CO USA. [Hamlington, Barbara; Brenna, Ethan; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Ivey, Lauren E.; Biesecker, Leslie G.; Sapp, Julie C.] NHGRI, Metab Genet & Mol Genom Branch, Bethesda, MD 20892 USA. RP Sapp, JC (reprint author), NHGRI, Metab Genet & Mol Genom Branch, Bethesda, MD 20892 USA. EM sappj@mail.nih.gov FU Intramural Program of the National Human Genome Research Institute [1 ZIA HG200388] FX This work was funded as part of the Intramural Program of the National Human Genome Research Institute (1 ZIA HG200388). NR 25 TC 1 Z9 1 U1 3 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 16 PY 2015 VL 10 IS 10 AR e0140705 DI 10.1371/journal.pone.0140705 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU0DF UT WOS:000363185500087 PM 26473736 ER PT J AU Mishra, S Harris, TB Hsueh, WC Hue, T Leak, TS Li, RL Mehta, M Vaisse, C Sahyoun, NR AF Mishra, Suruchi Harris, Tamara B. Hsueh, Wen-Chi Hue, Trisha Leak, Tennille S. Li, Rongling Mehta, Mira Vaisse, Christian Sahyoun, Nadine R. TI The Association of Serum Leptin with Mortality in Older Adults SO PLOS ONE LA English DT Article ID PLASMA LEPTIN; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; HEART-FAILURE; NITRIC-OXIDE; WEIGHT-LOSS; FAT-CONTENT; RISK; INSULIN AB Objective Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines. Methods The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years). Results Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines. Conclusions The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines. C1 [Mishra, Suruchi; Mehta, Mira; Sahyoun, Nadine R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. [Hsueh, Wen-Chi] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. [Hue, Trisha] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Leak, Tennille S.] Michigan Publ Hlth Inst, Okemos, MI USA. [Li, Rongling] NHGRI, NIH, Rockville, MD USA. [Vaisse, Christian] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Vaisse, Christian] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Mishra, S (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM sumishra@umd.edu FU National Institute on Aging [N 01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Health, National Institute on Aging FX This research is supported by National Institute on Aging contracts no. N 01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106, and by the Intramural Research Program of the National Institute of Health, National Institute on Aging. NR 48 TC 3 Z9 3 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 16 PY 2015 VL 10 IS 10 AR e0140763 DI 10.1371/journal.pone.0140763 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU0DF UT WOS:000363185500105 PM 26473487 ER PT J AU Zhao, J Mou, YS Bernstock, JD Klimanis, D Wang, SX Spatz, M Maric, D Johnson, K Klinman, DM Li, XH Li, XH Hallenbeck, JM AF Zhao, Jing Mou, Yongshan Bernstock, Joshua D. Klimanis, Dace Wang, Sixian Spatz, Maria Maric, Dragan Johnson, Kory Klinman, Dennis M. Li, Xiaohong Li, Xinhui Hallenbeck, John M. TI Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats SO PLOS ONE LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; REGULATORY T-CELLS; NLRP3 INFLAMMASOME; TISSUE DISTRIBUTION; IMMUNE-SYSTEM; MOUSE LUNG; IN-VIVO; ACTIVATION; MICE; DEATH AB The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1 beta. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1 beta production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1 beta, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies. C1 [Zhao, Jing; Li, Xiaohong] Shandong Univ, Jinan Cent Hosp, Dept Neurol, Jinan 250013, Shandong, Peoples R China. [Zhao, Jing; Mou, Yongshan; Bernstock, Joshua D.; Klimanis, Dace; Spatz, Maria; Li, Xinhui; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Wang, Sixian] Cornell Univ, Coll Arts & Sci, Ithaca, NY USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. [Johnson, Kory] NINDS, Informat Technol & Bioinformat Program, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis M.] NCI, Canc & Inflammat Program, NIH, Bethesda, MD 20892 USA. RP Li, XH (reprint author), Shandong Univ, Jinan Cent Hosp, Dept Neurol, 105 Jiefang Rd, Jinan 250013, Shandong, Peoples R China. EM xiaohong-li@sdu.edu.cn; lixinh@mail.nih.gov; hallenbj@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke/National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke/National Institutes of Health. NR 85 TC 5 Z9 5 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 16 PY 2015 VL 10 IS 10 AR e0140772 DI 10.1371/journal.pone.0140772 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU0DF UT WOS:000363185500107 PM 26473731 ER PT J AU Alfaro, KM Gage, JC Rosenbaum, AJ Ditzian, LR Maza, M Scarinci, IC Miranda, E Villalta, S Felix, JC Castle, PE Cremer, ML AF Alfaro, Karla M. Gage, Julia C. Rosenbaum, Alan J. Ditzian, Lauren R. Maza, Mauricio Scarinci, Isabel C. Miranda, Esmeralda Villalta, Sofia Felix, Juan C. Castle, Philip E. Cremer, Miriam L. TI Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program SO BMC PUBLIC HEALTH LA English DT Article DE HPV; Community health promoters; Cervical cancer; Adherence; Screening; Underserved populations; Education ID PARTICIPATION; PERCEPTIONS; PREVENTION; BARRIERS AB Background: Cervical cancer is the third most commonly occurring cancer among women and the fourth leading cause of cancer-related deaths in women worldwide, with more than 85 % of these cases occurring in developing countries. These global disparities reflect the differences in cervical cancer screening rates between high-income and medium-and low-income countries. At 19 %, El Salvador has the lowest reported screening coverage of all Latin American countries. The purpose of this study is to identify factors affecting public sector HPV DNA-based cervical cancer screening participation in El Salvador. Methods: This study was nested within a public sector screening program where health promoters used door-to-door outreach to recruit women aged 30-49 years to attend educational sessions about HPV screening. A subgroup of these participants was chosen randomly and questioned about demographic factors, healthcare utilization, previous cervical cancer screening, and HPV knowledge. Women then scheduled screening appointments at their public health clinics. Screening participants were adherent if they attended their scheduled appointment or rescheduled and were screened within 6 months. The association between non-adherence and demographic variables, medical history, history of cancer, sexual history, birth control methods, and screening barriers was assessed using Chi-square tests of significance and logistic regression. Results: All women (n = 409) enrolled in the study scheduled HPV screening appointments, and 88 % attended. Non-adherence was associated with a higher number of lifetime partners and being under-screened-defined as not having participated in cervical cancer screening within the previous 3 years (p = 0.03 and p = 0.04, respectively); 22.8 % of participants in this study were under-screened. Conclusions: Adherence to cervical cancer screening after educational sessions was higher than expected, in part due to interactions with the community-based health promoters as well as the educational session itself. More effective recruitment methods targeted toward under-screened women are required. C1 [Alfaro, Karla M.; Ditzian, Lauren R.; Maza, Mauricio] Basic Hlth Int, San Salvador, El Salvador. [Gage, Julia C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Rosenbaum, Alan J.] Univ Pittsburgh, Dept Obstet & Gynecol, Sch Med, Pittsburgh, PA 15213 USA. [Rosenbaum, Alan J.] US Dept State, Fulbright US Student Program, Washington, DC 20005 USA. [Rosenbaum, Alan J.] Ohio State Univ, Wexner Med Ctr, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Scarinci, Isabel C.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA. [Miranda, Esmeralda; Villalta, Sofia] Minist Hlth El Salvador, San Salvador, El Salvador. [Felix, Juan C.] Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. [Castle, Philip E.] Global Canc Initiat, Chestertown, MD 21620 USA. [Cremer, Miriam L.] Cleveland Clin, OB GYN & Womens Hlth Inst, Cleveland, OH 44195 USA. RP Cremer, ML (reprint author), Cleveland Clin, OB GYN & Womens Hlth Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM mcremer@ccf.org FU Einhorn Family Charitable Trust; Fulbright U.S. Student Program; Union for International Cancer Control FX The authors would like to thank the Einhorn Family Charitable Trust, the Fulbright U.S. Student Program, and the Union for International Cancer Control for their support. NR 21 TC 0 Z9 0 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 16 PY 2015 VL 15 AR 1058 DI 10.1186/s12889-015-2360-7 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT9ES UT WOS:000363120000001 PM 26474762 ER PT J AU Kandula, NR Dave, S De Chavez, PJ Bharucha, H Patel, Y Seguil, P Kumar, S Baker, DW Spring, B Siddique, J AF Kandula, Namratha R. Dave, Swapna De Chavez, Peter John Bharucha, Himali Patel, Yasin Seguil, Paola Kumar, Santosh Baker, David W. Spring, Bonnie Siddique, Juned TI Translating a heart disease lifestyle intervention into the community: the South Asian Heart Lifestyle Intervention (SAHELI) study; a randomized control trial SO BMC PUBLIC HEALTH LA English DT Article DE Cardiovascular disease prevention; South Asian; Randomized clinical trial ID DIABETES PREVENTION PROGRAM; CARDIOVASCULAR RISK-FACTORS; CULTURE-CENTERED APPROACH; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; METABOLIC SYNDROME; INDIAN IMMIGRANTS; UNITED-STATES; ETHNIC-GROUPS; HEALTH AB Background: South Asians (Asian Indians and Pakistanis) are the second fastest growing ethnic group in the United States (U.S.) and have an increased risk of atherosclerotic cardiovascular disease (ASCVD). This pilot study evaluated a culturally-salient, community-based healthy lifestyle intervention to reduce ASCVD risk among South Asians. Methods: Through an academic-community partnership, medically underserved South Asian immigrants at risk for ASCVD were randomized into the South Asian Heart Lifestyle Intervention (SAHELI) study. The intervention group attended 6 interactive group classes focused on increasing physical activity, healthful diet, weight, and stress management. They also received follow-up telephone support calls. The control group received translated print education materials about ASCVD and healthy behaviors. Primary outcomes were feasibility and initial efficacy, measured as change in moderate/vigorous physical activity and dietary saturated fat intake at 3- and 6-months. Secondary clinical and psychosocial outcomes were also measured. Results: Participants' (n = 63) average age was 50 (SD = 8) years, 63 % were female, 27 % had less than or equal to a high school education, one-third were limited English proficient, and mean BMI was 30 kg/m2 (SD +/- 5). There were no significant differences in change in physical activity or saturated fat intake between the intervention and control group. Compared to the control group, the intervention group showed significant weight loss (-1.5 kg, p-value = 0.04) and had a greater sex-adjusted decrease in hemoglobin A1C (-0.43 %, p-value <0.01) at 6 months. Study retention was 100 %. Conclusions: This pilot study suggests that a culturally-salient, community-based lifestyle intervention was feasible for engaging medically underserved South Asian immigrants and more effective at addressing ASCVD risk factors than print health education materials. C1 [Kandula, Namratha R.; Dave, Swapna; Seguil, Paola; Baker, David W.] Northwestern Univ, Dept Gen Internal Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Bharucha, Himali; Kumar, Santosh] Metropolitan Asian Family Serv, Chicago, IL 60645 USA. [Kandula, Namratha R.; De Chavez, Peter John; Spring, Bonnie; Siddique, Juned] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Patel, Yasin] NHLBI, NIH, Bethesda, MD 20892 USA. RP Kandula, NR (reprint author), Northwestern Univ, Dept Gen Internal Med, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM nkandula@nm.org FU National Institutes of Health [R21HL113743] FX National Institutes of Health #R21HL113743. NR 56 TC 5 Z9 5 U1 5 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 16 PY 2015 VL 15 AR 1064 DI 10.1186/s12889-015-2401-2 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT5SX UT WOS:000362872300001 PM 26475629 ER PT J AU Caldwell, BM Harenski, CL Harenski, KA Fede, SJ Steele, VR Koenigs, MR Kiehl, KA AF Caldwell, Brendan M. Harenski, Carla L. Harenski, Keith A. Fede, Samantha J. Steele, Vaughn R. Koenigs, Michael R. Kiehl, Kent A. TI Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE Cocaine; Moral Intuition; Social Cognition; fMRI; Psychopathy ID ANTERIOR CINGULATE CORTEX; SUBSTANCE USE DISORDERS; VENTROMEDIAL PREFRONTAL DAMAGE; INFERIOR FRONTAL-CORTEX; DECISION-MAKING; CRIMINAL PSYCHOPATHS; FUNCTIONAL MRI; NEURAL BASIS; ORBITOFRONTAL CORTEX; EMOTION INTERACTIONS AB Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, IOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition. C1 [Caldwell, Brendan M.; Harenski, Carla L.; Harenski, Keith A.; Fede, Samantha J.; Kiehl, Kent A.] Mind Res Network, Albuquerque, NM 87131 USA. [Caldwell, Brendan M.; Harenski, Carla L.; Harenski, Keith A.; Fede, Samantha J.; Kiehl, Kent A.] Lovelace Biomed & Environm Res Inst, Albuquerque, NM USA. [Fede, Samantha J.; Kiehl, Kent A.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Steele, Vaughn R.] NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD USA. [Koenigs, Michael R.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. RP Caldwell, BM (reprint author), Mind Res Network, Albuquerque, NM 87131 USA. EM bcaldwell@mrn.org FU National Institute on Drug Abuse [1R01DA026964-01A1, 1R01DA026505-01A1, 1R01DA020870-01] FX This research was supported by the following grants from the National Institute on Drug Abuse: 1R01DA026964-01A1, 1R01DA026505-01A1, 1R01DA020870-01 (PI: Kiehl). NR 159 TC 2 Z9 2 U1 4 U2 16 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD OCT 16 PY 2015 VL 9 AR 565 DI 10.3389/fnhum.2015.00565 PG 17 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CT8JL UT WOS:000363061600002 PM 26528169 ER PT J AU Kenealey, J Subramanian, P Comitato, A Bullock, J Keehan, L Polato, F Hoover, D Marigo, V Becerra, SP AF Kenealey, Jason Subramanian, Preeti Comitato, Antonella Bullock, Jeanee Keehan, Laura Polato, Federica Hoover, David Marigo, Valeria Becerra, S. Patricia TI Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment Epithelium-derived Factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOPTOSIS-INDUCING FACTOR; PROTEIN-PROTEIN DOCKING; INDUCED CELL-DEATH; RETINAL DEGENERATION; FACTOR PEDF; CHOROIDAL NEOVASCULARIZATION; INTERPHOTORECEPTOR MATRIX; NEUROTROPHIC ACTIVITY; ROYAL-COLLEGE; SURGEONS RATS AB The cytoprotective effects of pigment epithelium-derived factor (PEDF) require interactions between an as of a yet undefined region with a distinct ectodomain on the PEDF receptor (PEDFR). Here we characterized the area in PEDF that interacts with PEDF-R to promote photoreceptor survival. Molecular docking studies suggested that the ligand binding site of PEDF-R interacts with the neurotrophic region of PEDF (44-mer, positions 78-121). Binding assays demonstrated that PEDF-R bound the 44-mer peptide. Moreover, peptide P1 from the PEDF-R ectodomain had affinity for the 44-mer and a shorter fragment within it, 17-mer (positions 98-114). Single residue substitutions to alanine along the 17-mer sequence were designed and tested for binding and biological activity. Altered 17-mer[R99A] did not bind to the P1 peptide, whereas 17-mer[H105A] had higher affinity than the unmodified 17-mer. Peptides 17-mer, 17-mer[H105A], and 44-mer exhibited cytoprotective effects in cultured retina R28 cells. Intravitreal injections of these peptides and PEDF in the rd1 mouse model of retinal degeneration decreased the numbers of dying photoreceptors, 17-mer[H105A] being most effective. The blocking peptide P1 hindered their protective effects both in retina cells and in vivo. Thus, in addition to demonstrating that the region composed of positions 98-114 of PEDF contains critical residues for PEDF-R interaction that mediates survival effects, the findings reveal distinct small PEDF fragments with neurotrophic effects on photoreceptors. C1 [Kenealey, Jason; Subramanian, Preeti; Bullock, Jeanee; Keehan, Laura; Polato, Federica; Becerra, S. Patricia] NEI, NIH, Bethesda, MD 20892 USA. [Hoover, David] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Comitato, Antonella; Marigo, Valeria] Univ Modena & Reggio Emilia, Dept Life Sci, I-41125 Modena, Italy. [Bullock, Jeanee] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. RP Becerra, SP (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov FU National Eye Institute, National Institutes of Health Intramural Research Program; Fondazione Telethon Grant [GGP06096]; E-RARE (RHORCOD); Italian Ministry Grant [20094CZ3M2] FX This work was supported, in whole or in part, by National Eye Institute, National Institutes of Health Intramural Research Program (to S.P.B.). This work was also supported by Fondazione Telethon Grant GGP06096, by E-RARE 2009 (RHORCOD), and by Italian Ministry Grant 20094CZ3M2 (to V.M.). The authors declare that they have no conflicts of interest with the contents of this article. NR 38 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 2015 VL 290 IS 42 BP 25241 EP 25253 DI 10.1074/jbc.M115.645846 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT6ZO UT WOS:000362962800004 PM 26304116 ER PT J AU Desai, SS Kharade, SS Parekh, VI Iyer, S Agarwal, SK AF Desai, Shruti S. Kharade, Sampada S. Parekh, Vaishali I. Iyer, Sucharitha Agarwal, Sunita K. TI Pro-oncogenic Roles of HLXB9 Protein in Insulinoma Cells through Interaction with Nono Protein and Down-regulation of the c-Met Inhibitor Cblb (Casitas B-lineage Lymphoma b) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; PANCREATIC NEUROENDOCRINE TUMORS; MEN1 GENE; MICE DEVELOP; TYPE-1 MEN1; MOUSE MODEL; YANG 1; EXPRESSION; MUTATIONS; P54(NRB) AB Pancreatic islet beta-cells that lack the MEN1-encoded protein menin develop into tumors. Such tumors express the phosphorylated isoform of the beta-cell differentiation transcription factor HLXB9. It is not known how phospho-HLXB9 acts as an oncogenic factor in insulin-secreting beta-cell tumors (insulinomas). In this study we investigated the binding partners and target genes of phospho-HLXB9 in mouse insulinoma MIN6 beta-cells. Co-immunoprecipitation coupled with mass spectrometry showed a significant association of phospho-HLXB9 with the survival factor p54nrb/Nono (54-kDa nuclear RNA-binding protein, non-POU-domain-containing octamer). Endogenous phospho-HLXB9 co-localized with endogenous Nono in the nucleus. Overexpression of HLXB9 decreased the level of overexpressed Nono but not endogenousNono. Anti-phospho-HLXB9 chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) identified the c-Met inhibitor, Cblb, as a direct phospho-HLXB9 target gene. Phospho-HLXB9 occupied the promoter of Cblb and reduced the expression of Cblb mRNA. Cblb overexpression or HLXB9 knockdown decreased c-Met protein and reduced cell migration. Also, increased phospho-HLXB9 coincided with reduced Cblb and increased c-Met in insulinomas of two mouse models of menin loss. These data provide mechanistic insights into the role of phospho-HLXB9 as a pro-oncogenic factor by interacting with a survival factor and by promoting the oncogenic c-Met pathway. These mechanisms have therapeutic implications for reducing beta-cell proliferation in insulinomas by inhibiting phospho-HLXB9 or its interaction with Nono and modulating the expression of its direct (Cblb) or indirect(c-Met) targets. Our data also implicate the use of pro-oncogenic activities of phospho-HLXB9 in beta-cell expansion strategies to alleviate beta-cell loss in diabetes. C1 [Desai, Shruti S.; Kharade, Sampada S.; Parekh, Vaishali I.; Iyer, Sucharitha; Agarwal, Sunita K.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIH, Bldg 10,Rm 8C-101, Bethesda, MD 20814 USA. EM sunitaa@mail.nih.gov RI Regan, Clinton/E-6250-2012; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU National Institutes of Health [1ZIADK075035-03] FX This work was supported, in whole or in part, by National Institutes of Health Grant 1ZIADK075035-03 (NIDDK; Intramural Research Program; to S. K. A.). The authors declare that they have no conflicts of interest with the contents of this article. NR 44 TC 1 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 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 2015 VL 290 IS 42 BP 25595 EP 25608 DI 10.1074/jbc.M115.661413 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT6ZO UT WOS:000362962800033 PM 26342078 ER PT J AU Yao, W Beckwith, SL Zheng, TN Young, T Dinh, VT Ranjan, A Morrison, AJ AF Yao, Wei Beckwith, Sean L. Zheng, Tina Young, Thomas Dinh, Van T. Ranjan, Anand Morrison, Ashby J. TI Assembly of the Arp5 (Actin-related Protein) Subunit Involved in Distinct INO80 Chromatin Remodeling Activities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; COMPLEX PROMOTES; NUCLEOSOME; GENOME; REVEALS; BINDING; YEAST; SWR1; TRANSLOCATION AB ATP-dependent chromatin remodeling, which repositions and restructures nucleosomes, is essential to all DNA-templated processes. The INO80 chromatin remodeling complex is an evolutionarily conserved complex involved in diverse cellular processes, including transcription, DNA repair, and replication. The functional diversity of the INO80 complex can, in part, be attributed to specialized activities of distinct subunits that compose the complex. Furthermore, structural analyses have identified biochemically discrete subunit modules that assemble along the Ino80 ATPase scaffold. Of particular interest is the Saccharomyces cerevisiae Arp5-Ies6 module located proximal to the Ino80 ATPase and the Rvb1-Rvb2 helicase module needed for INO80-mediated in vitro activity. In this study we demonstrate that the previously uncharacterized Ies2 subunit is required for Arp5-Ies6 association with the catalytic components of the INO80 complex. In addition, Arp5-Ies6 module assembly with the INO80 complex is dependent on distinct conserved domains within Arp5, Ies6, and Ino80, including the spacer region within the Ino80 ATPase domain. Arp5-Ies6 interacts with chromatin via assembly with the INO80 complex, as IES2 and INO80 deletion results in loss of Arp5-Ies6 chromatin association. Interestingly, ectopic addition of the wild-type Arp5-Ies6 module stimulates INO80-mediated ATP hydrolysis and nucleosome sliding in vitro. However, the addition of mutant Arp5 lacking unique insertion domains facilitates ATP hydrolysis in the absence of nucleosome sliding. Collectively, these results define the requirements of Arp5-Ies6 assembly, which are needed to couple ATP hydrolysis to productive nucleosome movement. C1 [Yao, Wei; Beckwith, Sean L.; Zheng, Tina; Young, Thomas; Dinh, Van T.; Morrison, Ashby J.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Ranjan, Anand] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Morrison, AJ (reprint author), Stanford Univ, Dept Biol, 371 Serra Mall, Stanford, CA 94305 USA. EM ashbym@stanford.edu RI Regan, Clinton/E-6250-2012; OI Morrison, Ashby/0000-0003-1228-5093 FU National Institutes of Health [R00 GM085212]; Frederick Terman Award; Stanford Graduate Fellowship FX This work was supported, in whole or in part, by National Institutes of Health Grant R00 GM085212 (to A. J. M.). This work was also supported by a Frederick Terman Award (to A. J. M.) and a Stanford Graduate Fellowship (to S. L. B.). The authors declare that they have no conflicts of interest with the contents of this article. NR 46 TC 4 Z9 4 U1 4 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 2015 VL 290 IS 42 BP 25700 EP 25709 DI 10.1074/jbc.M115.674887 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT6ZO UT WOS:000362962800041 PM 26306040 ER PT J AU Lin, YH Doms, AG Cheng, E Kim, B Evans, TR Machner, MP AF Lin, Yi-Han Doms, Alexandra G. Cheng, Eric Kim, Byoungkwan Evans, Timothy R. Machner, Matthias P. TI Host Cell-catalyzed S-Palmitoylation Mediates Golgi Targeting of the Legionella Ubiquitin Ligase GobX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN PALMITOYLATION; PNEUMOPHILA GENOME; EFFECTOR PROTEINS; FATTY-ACYLATION; GTPASE RAB1; LOCALIZATION; SYSTEM; FAMILY; 2-BROMOPALMITATE; TRAFFICKING AB The facultative intracellular pathogen Legionella pneumophila, the causative agent of Legionnaires disease, infects and replicates within human alveolar macrophages. L. pneumophila delivers almost 300 effector proteins into the besieged host cell that alter signaling cascades and create conditions that favor intracellular bacterial survival. In order for the effectors to accomplish their intracellular mission, their activity needs to be specifically directed toward the correct host cell protein or target organelle. Here, we show that the L. pneumophila effector GobX possesses E3 ubiquitin ligase activity that is mediated by a central region homologous to mammalian U-box domains. Furthermore, we demonstrate that GobX exploits host cell S-palmitoylation to specifically localize to Golgi membranes. The hydrophobic palmitate moiety is covalently attached to a cysteine residue at position 175, which is part of an amphipathic alpha-helix within the C-terminal region of GobX. Site-directed mutagenesis of cysteine 175 or residues on the hydrophobic face of the amphipathic helix strongly attenuated palmitoylation and Golgi localization of GobX. Together, our study provides evidence that the L. pneumophila effector GobX exploits two post-translational modification pathways of host cells, ubiquitination and S-palmitoylation. C1 [Lin, Yi-Han; Doms, Alexandra G.; Cheng, Eric; Kim, Byoungkwan; Evans, Timothy R.; Machner, Matthias P.] Eunice Kennedy Shriver NICHD, Microbial Pathogenesis Unit, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Machner, MP (reprint author), Eunice Kennedy Shriver NICHD, Cell Biol & Metab Program, Bldg 18,Rm 101,18 Lib Dr, Bethesda, MD 20892 USA. EM machnerm@mail.nih.gov FU National Institutes of Health from the Intramural Research Program [1ZIAHD008893-04] FX This work was supported, in whole or in part, by National Institutes of Health Grant 1ZIAHD008893-04 from the Intramural Research Program. The authors declare that they have no conflicts of interest with the contents of this article. NR 62 TC 3 Z9 4 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 2015 VL 290 IS 42 BP 25766 EP 25781 DI 10.1074/jbc.M115.637397 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT6ZO UT WOS:000362962800047 PM 26316537 ER PT J AU He, YH Ding, Y Zhan, F Zhang, HM Han, B Hu, GQ Zhao, KJ Yang, N Yu, Y Mao, L Song, JZ AF He, Yanghua Ding, Yi Zhan, Fei Zhang, Huanmin Han, Bo Hu, Gangqing Zhao, Keji Yang, Ning Yu, Ying Mao, Li Song, Jiuzhou TI The conservation and signatures of lincRNAs in Marek's disease of chicken SO SCIENTIFIC REPORTS LA English DT Article ID LONG NONCODING RNAS; GENE-EXPRESSION; HUMAN GENOME; TRANSCRIBED REGIONS; CHROMATIN; REVEALS; SEQ; EVOLUTION; DIFFERENTIATION; ANNOTATION AB Long intergenic non-coding RNAs (lincRNAs) associated with a number of cancers and other diseases have been identified in mammals, but they are still formidable to be comprehensively identified and characterized. Marek's disease (MD) is a T cell lymphoma of chickens induced by Marek's disease virus (MDV). Here, we used a MD chicken model to develop a precise pipeline for identifying lincRNAs and to determine the roles of lincRNAs in T cell tumorigenesis. More than 1,000 lincRNA loci were identified in chicken bursa. Computational analyses demonstrated that lincRNAs are conserved among different species such as human, mouse and chicken. The putative lincRNAs were found to be associated with a wide range of biological functions including immune responses. Interestingly, we observed distinct lincRNA expression signatures in bursa between MD resistant and susceptible lines of chickens. One of the candidate lincRNAs, termed linc-satb1, was found to play a crucial role in MD immune response by regulating a nearby protein-coding gene SATB1. Thus, our results manifested that lincRNAs may exert considerable influence on MDV-induced T cell tumorigenesis and provide a rich resource for hypothesis-driven functional studies to reveal genetic mechanisms underlying susceptibility to tumorigenesis. C1 [He, Yanghua; Ding, Yi; Zhan, Fei; Song, Jiuzhou] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Zhang, Huanmin] ARS, USDA, Avian Dis & Oncol Lab, E Lansing, MI 48823 USA. [Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Han, Bo; Yang, Ning; Yu, Ying] China Agr Univ, Dept Anim Genet & Breeding, Coll Anim Sci & Technol, Natl Engn Lab Anim Breeding, Beijing 100193, Peoples R China. [Mao, Li] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. RP Song, JZ (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM songj88@umd.edu FU National Research Initiative Competitive Grant from USDA National Institute of Food and Agriculture [USDA-NRI/NIFA 2010-65205-20588]; China National Science Foundations International Program Competitive Grant [21023130] FX This project was supported by the National Research Initiative Competitive Grant (No. USDA-NRI/NIFA 2010-65205-20588) from the USDA National Institute of Food and Agriculture and by the China National Science Foundations International Program Competitive Grant (No. 21023130). NR 64 TC 3 Z9 3 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 16 PY 2015 VL 5 AR 15184 DI 10.1038/srep15184 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT5SP UT WOS:000362871500001 PM 26471251 ER PT J AU Melikov, K Hara, A Yamoah, K Zaitseva, E Zaitsev, E Chernomordik, LV AF Melikov, Kamran Hara, Ann Yamoah, Kwabena Zaitseva, Elena Zaitsev, Eugene Chernomordik, Leonid V. TI Efficient entry of cell-penetrating peptide nona-arginine into adherent cells involves a transient increase in intracellular calcium SO BIOCHEMICAL JOURNAL LA English DT Article DE calcium imaging; calcium intracellular release; cell-penetrating peptide (CPP); microscopy; phosphatidylserine; transient receptor potential channels (TRP channels) ID PLASMA-MEMBRANE; FLUFENAMIC ACID; RICH PEPTIDES; DELIVERY; PHOSPHATIDYLSERINE; TRANSLOCATION; TRANSDUCTION; LACTADHERIN; PROTEINS; TAT AB Understanding the mechanism of entry of cationic peptides such as nona-arginine (R-9) into cells remains an important challenge to their use as efficient drug-delivery vehicles. At nanomolar to low micromolar R-9 concentrations and at physiological temperature, peptide entry involves endocytosis. In contrast, at a concentration >= 10 mu M, R-9 induces a very effective non-endocytic entry pathway specific for cationic peptides. We found that a similar entry pathway is induced at 1-2 mu M concentrations of R-9 if peptide application is accompanied by a rapid temperature drop to 15 degrees C. Both at physiological and at sub-physiological temperatures, this entry mechanism was inhibited by depletion of the intracellular ATP pool. Intriguingly, we found that R-9 at 10-20 mu M and 37 degrees C induces repetitive spikes in intracellular Ca2+ concentration. This Ca2+ signalling correlated with the efficiency of the peptide entry. Pre-loading cells with the Ca2+ chelator BAPTA(1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) inhibited both Ca2+ spikes and peptide entry, suggesting that an increase in intracellular Ca2+ precedes and is required for peptide entry. One of the hallmarks of Ca2+ signalling is a transient cell-surface exposure of phosphatidylserine (PS), a lipid normally residing only in the inner leaflet of the plasma membrane. Blocking the accessible PS with the PS-binding domain of lactadherin strongly inhibited non-endocytic R-9 entry, suggesting the importance of PS externalization in this process. To conclude, we uncovered a novel mechanistic link between calcium signalling and entry of cationic peptides. This finding will enhance our understanding of the properties of plasma membrane and guide development of future drug-delivery vehicles. C1 [Melikov, Kamran; Hara, Ann; Yamoah, Kwabena; Zaitseva, Elena; Zaitsev, Eugene; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bldg 10,Room 10D05,10 Ctr Dr, Bethesda, MD 20892 USA. RP Melikov, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bldg 10,Room 10D05,10 Ctr Dr, Bethesda, MD 20892 USA. EM melikovk@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (to L.V.C.). NR 43 TC 3 Z9 3 U1 2 U2 10 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2015 VL 471 BP 221 EP 230 DI 10.1042/BJ20150272 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DC4CZ UT WOS:000369169000007 PM 26272944 ER PT J AU Yoo, KH Oh, S Kang, K Hensel, T Robinson, GW Hennighausen, L AF Yoo, Kyung Hyun Oh, Sumin Kang, Keunsoo Hensel, Tim Robinson, Gertraud W. Hennighausen, Lothar TI Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID REPRESSIVE COMPLEX 2; EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE; EPIGENETIC REPRESSION; SELF-RENEWAL; DIFFERENTIATION; EXPRESSION; METHYLATION; EPITHELIUM; PREGNANCY AB Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy of these loci by STAT5, EZH1 and RNA Pol II. Limited activation of differentiation-specific genes was observed in mammary epithelium lacking both EZH2 and STAT5, suggesting a modulating but not mandatory role for STAT5. Loss of EZH2 did not result in overt changes in genome-wide and gene-specific H3K27me3 profiles, suggesting compensation through enhanced EZH1 recruitment. Differentiated mammary epithelia did not form in the combined absence of EZH1 and EZH2. Transplantation experiments failed to demonstrate a role for EZH2 in the activity of mammary stem and progenitor cells. In summary, while EZH1 and EZH2 serve redundant functions in the establishment of H3K27me3 marks and the formation of mammary alveoli, the presence of EZH2 is required to control progressive differentiation of milk secreting epithelium during pregnancy. C1 [Yoo, Kyung Hyun; Oh, Sumin; Kang, Keunsoo; Hensel, Tim; Robinson, Gertraud W.; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Oh, Sumin] Dankook Univ, Dept Nanobiomed Sci, Cheonan 330714, Chungnam, South Korea. [Oh, Sumin] Dankook Univ, PLUS NBM Global Res Ctr Regenerat Med BK21, Cheonan 330714, Chungnam, South Korea. [Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan 330714, Chungnam, South Korea. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov FU Intramural Research Programs (IRP) of NIDDK; NIH FX Intramural Research Programs (IRP) of NIDDK. Funding for open access charge: NIH. NR 67 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 15 PY 2015 VL 43 IS 18 BP 8774 EP 8789 DI 10.1093/nar/gkv776 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CY4VI UT WOS:000366406500021 PM 26250110 ER PT J AU Conforti, F Wang, YS Rodriguez, JA Alberobello, AT Zhang, YW Giaccone, G AF Conforti, Fabio Wang, Yisong Rodriguez, Jose A. Alberobello, Anna Teresa Zhang, Yu-Wen Giaccone, Giuseppe TI Molecular Pathways: Anticancer Activity by Inhibition of Nucleocytoplasmic Shuttling SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; WILD-TYPE P53; NUCLEAR-EXPORT; SELECTIVE INHIBITORS; OVARIAN-CANCER; BREAST-CANCER; CELL SURVIVAL; DNA-DAMAGE; KAPPA-B; CRM1 AB A dynamic distribution between nucleus and cytoplasm (nucleocytoplasmic shuttling) is one of the control mechanisms adapted by normal cells to regulate the activity of a variety of molecules. Growing evidence suggests that dysregulation of the nucleocytoplasmic shuttling is involved in promoting abnormal cell survival, tumor progression, and drug resistance, and is associated with poor cancer prognosis. Aberrant nucleocytoplasmic shuttling in cancer cells mayresult from a hyperactive status of diverse signal-transduction pathways, such as the PI3K-AKT and MAPK pathways, or from alterations in the general nuclear import/export machinery. Among the large number of molecules involved in the shuttling process, exportin XPO1, also known as chromosome region maintenance 1, appears to play a particularly prominent role in pathogenesis of both hematological malignancies and solid tumors. Given the importance of nucleocytoplasmic shuttling in cancer pathogenesis and the rapidly expanding knowledge in this field, attempts have been made to develop compounds able to revert the aberrant nucleocytoplasmic shuttling. A promising new drug, KPT-330 (Selinexor), which belongs to the class of XPO1 inhibitors called selective inhibitors of nuclear export, is now being tested in phase I/II clinical trials. (C) 2015 AACR. C1 [Conforti, Fabio; Wang, Yisong; Alberobello, Anna Teresa; Zhang, Yu-Wen; Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Wang, Yisong] NCI, Bethesda, MD 20892 USA. [Rodriguez, Jose A.] Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Leioa, Spain. RP Giaccone, G (reprint author), Georgetown Univ, 3970 Reservoir Rd Northwest, Washington, DC 20007 USA. EM gg496@georgetown.edu RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU Karyopharm Therapeutics FX G. Giaccone reports receiving a commercial research grant from Karyopharm Therapeutics. No potential conflicts of interest were disclosed by the other authors. NR 61 TC 5 Z9 5 U1 1 U2 6 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 OCT 15 PY 2015 VL 21 IS 20 BP 4508 EP 4513 DI 10.1158/1078-0432.CCR-15-0408 PG 6 WC Oncology SC Oncology GA CV7WH UT WOS:000364486300004 PM 26324742 ER PT J AU Bates, SE AF Bates, Susan E. TI On Innovating and Inspiring the Clinical Trial Enterprise SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT 15 PY 2015 VL 21 IS 20 BP 4526 EP 4526 DI 10.1158/1078-0432.CCR-15-0038 PG 1 WC Oncology SC Oncology GA CV7WH UT WOS:000364486300006 PM 26473187 ER PT J AU Bates, SE Berry, DA Balasubramaniam, S Bailey, S LoRusso, PM Rubin, EH AF Bates, Susan E. Berry, Donald A. Balasubramaniam, Sanjeeve Bailey, Stuart LoRusso, Patricia M. Rubin, Eric H. TI Advancing Clinical Trials to Streamline Drug Development SO CLINICAL CANCER RESEARCH LA English DT Article ID HER2-POSITIVE BREAST-CANCER; DOSE-ESCALATION; OPEN-LABEL; PHASE-III; DESIGN; APPROVAL; CHEMOTHERAPY; PERTUZUMAB; THERAPY AB The last decade in oncology has been marked by the identification of numerous new potential cancer targets and even more agents designed to inhibit them. The matrix of new targets, new agents, and the companion diagnostics required to identify the right patient for the right drug has created a major challenge for the clinical trial process. This has been compounded by the addition of new immunomodulators targeting the host immune system rather than the tumor. Recognizing the need for new approaches, industry, investigators, and regulators have responded to this challenge. New clinical trial designs are being evaluated to incorporate the genomic sequence data being obtained almost routinely after cancer diagnosis. New dose-finding approaches are being proposed to identify the maximum effective dose rather than the maximum tolerated dose. The FDA is involved in the drug approval process from points early in development and has accepted registration quality data from expansion cohorts in support of drug approval. Despite progress on several fronts, many challenges remain, including the lack of predictability of preclinical data for clinical results and phase II data for phase III results, an infrastructure that can be an obstacle to clinical trial development and implementation, and the increasing use of contracted clinical research organizations that limit a fit-for-purpose approach to clinical trial execution. Perhaps most challenging and important of all are the difficulties with clinical trial accrual that can prevent study completion. Both the innovations and the challenges highlight the important role of process in progress in clinical oncology. (C) 2015 AACR. C1 [Bates, Susan E.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Balasubramaniam, Sanjeeve] FDA, Ctr Drug Evaluat & Res, Off Hematol & Oncol Prod, Silver Spring, MD USA. [Bailey, Stuart] Novartis Inst BioMed Res, Cambridge, MA USA. [LoRusso, Patricia M.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Rubin, Eric H.] Merck Res Labs, N Wales, PA USA. RP Bates, SE (reprint author), Columbia Univ, Med Ctr, Div Hematol Oncol, Herbert Irving Pavill,9th Floor, New York, NY 10032 USA. EM seb2227@cumc.columbia.edu OI Balasubramaniam, Sanjeeve/0000-0002-0643-2117 FU Astex Pharmaceuticals; Genentech; Novartis FX D.A. Berry is an employee of and a consultant/advisory board member for Berry Consultants. P.M. LoRusso reports receiving commercial research support from Astex Pharmaceuticals, Genentech, and Novartis; speakers bureau honoraria from Genentech; and is a consultant/advisory board member for Pfizer. No potential conflicts of interest were disclosed by the other authors. NR 42 TC 6 Z9 6 U1 0 U2 7 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 OCT 15 PY 2015 VL 21 IS 20 BP 4527 EP 4535 DI 10.1158/1078-0432.CCR-15-0039 PG 9 WC Oncology SC Oncology GA CV7WH UT WOS:000364486300007 PM 26473188 ER PT J AU Siu, LL Conley, BA Boerner, S LoRusso, PM AF Siu, Lillian L. Conley, Barbara A. Boerner, Scott LoRusso, Patricia M. TI Next-Generation Sequencing to Guide Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; PHASE-II; BIOMARKERS; GENOME; MUTATIONS; MEDICINE; ONCOLOGY; THERAPY; DESIGN; BREAST AB Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many "driver" molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology and stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages, and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria. (C) 2015 AACR. C1 [Siu, Lillian L.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Conley, Barbara A.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Boerner, Scott; LoRusso, Patricia M.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. RP Siu, LL (reprint author), Univ Hlth Network, 610 Univ Ave,Suite 5-718, Toronto, ON M5G 2M9, Canada. EM lillian.siu@uhn.ca FU NCI NIH HHS [UM1 CA186644] NR 34 TC 10 Z9 10 U1 0 U2 2 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 OCT 15 PY 2015 VL 21 IS 20 BP 4536 EP 4544 DI 10.1158/1078-0432.CCR-14-3215 PG 9 WC Oncology SC Oncology GA CV7WH UT WOS:000364486300008 PM 26473189 ER PT J AU Herman, SEM Mustafa, RZ Jones, J Wong, DH Farooqui, M Wiestner, A AF Herman, Sarah E. M. Mustafa, Rashida Z. Jones, Jade Wong, Deanna H. Farooqui, Mohammed Wiestner, Adrian TI Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID BRUTONS TYROSINE KINASE; TUMOR PROLIFERATION; MICROENVIRONMENTAL INTERACTIONS; RECEPTOR; ACTIVATION; PCI-32765; MIGRATION; CHEMOKINE; CXCR4; CLL AB Purpose: Ibrutinib leads to a transient lymphocytosis in patients with chronic lymphocytic leukemia (CLL) that develops within hours of starting drug and is due to the efflux of cells from lymphoid tissues into the blood. We therefore sought to investigate the in vivo effect of ibrutinib on migration and adhesion of CLL cells. Experimental Design: Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays. Results: Adhesion of CLL cells to fibronectin was rapidly (within hours) and almost completely inhibited (median reduction 98% on day 28, P < 0.001), while the effect on migration to chemokines was more moderate (median reduction 64%, P = 0.008) and less uniform. Although cell surface expression of key adhesion molecules such as CD49d, CD29, and CD44 were modestly reduced, this was only apparent after weeks of treatment. Stimulation of CLL cells from patients on ibrutinib with PMA, which activates PKC independent of BTK, restored the ability of the cells to adhere to fibronectin in a VLA-4-dependent manner. Finally, the addition of ibrutinib to CLL cells adhered to fibronectin in vitro caused the detachment of 17% of the cells, on average; consisten t with in vivo observations of an increasing lymphocytosis within 4 hours of starting ibrutinib. Conclusions: Inhibition of BTK and VLA-4-dependent adhesion of CLL cells to stroma and stromal components provides a mechanistic explanation for the treatment-induced lymphocytosis and may reduce CD49d-dependent prosurvival signals in the tissue microenvironment. (C)2015 AACR. C1 [Herman, Sarah E. M.; Mustafa, Rashida Z.; Jones, Jade; Wong, Deanna H.; Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Jones, Jade] NIH, Med Res Scholars Program, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnea@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung and Blood Institute, the NIH; NIH Medical Research Scholars Program; NIH; Intramural Research Program of the National Heart, Lung and Blood Institute; Leona M. and Harry B. Helmsley Charitable Trust; Howard Hughes Medical Institute FX This work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute, the NIH (to A. Wiestner). J. Jones was supported by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as well as other private donors. This work was also supported by the Intramural Research Program of the National Heart, Lung and Blood Institute. NR 49 TC 17 Z9 17 U1 1 U2 5 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 OCT 15 PY 2015 VL 21 IS 20 BP 4642 EP 4651 DI 10.1158/1078-0432.CCR-15-0781 PG 10 WC Oncology SC Oncology GA CV7WH UT WOS:000364486300019 PM 26089373 ER PT J AU Dutta, S Sriskanda, S Boobalan, E Alur, RP Elkahloun, A Brooks, BP AF Dutta, Sunit Sriskanda, Shahila Boobalan, Elangovan Alur, Ramakrishna P. Elkahloun, Abdel Brooks, Brian P. TI nlz1 is required for cilia formation in zebrafish embryogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Kupffer's vesicle; Motile cilia; Wnt; Nlz1; Foxj1; Left-right asymmetry; Coloboma ID LEFT-RIGHT ASYMMETRY; CONVERGENT EXTENSION MOVEMENTS; IN-SITU HYBRIDIZATION; PLANAR CELL POLARITY; KUPFFERS VESICLE; LATERALITY ORGAN; EPITHELIAL-CELLS; WNT; FOXJ1; VERTEBRATE AB The formation of cilia is a fundamental developmental process affecting diverse functions such as cellular signaling, tissue morphogenesis and body patterning. However, the mechanisms of ciliogenesis during vertebrate development are not fully understood. In this report we describe a novel role of the Nlz1 protein in ciliogenesis. We demonstrate morpholino-mediated knockdown of nlz1 in zebrafish causes abnormal specification of the cells of Kupffer's vesicle (KV); a severe reduction of the number of cilia in IN, the pronephros, and the neural floorplate; and a spectrum of later phenotypes reminiscent of human ciliopathies. In vitro and in vivo data indicate that Nlz1 acts downstream of Foxj1a and Wnt8a/presumed canonical Wnt signaling. Furthermore, Nlz1 contributes to motile cilia formation by positively regulating Wnt11/presumed non-canonical Wnt signaling. Together, our data suggest a novel role of nlz1 in ciliogenesis and the morphogenesis of multiple tissues. Published by Elsevier Inc. C1 [Dutta, Sunit; Sriskanda, Shahila; Boobalan, Elangovan; Alur, Ramakrishna P.; Brooks, Brian P.] NEI, Unit Pediat Dev & Genet Ophthalmol, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, Microarray Core, NIH, Bethesda, MD 20892 USA. RP Brooks, BP (reprint author), NEI, Unit Pediat Dev & Genet Ophthalmol, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA EY000469-04, ZIA EY000469-06, ZIA EY000469-05] NR 54 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD OCT 15 PY 2015 VL 406 IS 2 BP 203 EP 211 DI 10.1016/j.ydbio.2015.08.019 PG 9 WC Developmental Biology SC Developmental Biology GA CW2DN UT WOS:000364801400011 PM 26327644 ER PT J AU Park, BC Yim, YI Zhao, XH Olszewski, MB Eisenberg, E Greene, LE AF Park, Bum-Chan Yim, Yang-In Zhao, Xiaohong Olszewski, Maciej B. Eisenberg, Evan Greene, Lois E. TI The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain SO JOURNAL OF CELL SCIENCE LA English DT Article DE GAK; Auxilin; Chaperone; Clathrin ID G-ASSOCIATED KINASE; MANNOSE 6-PHOSPHATE RECEPTOR; TRANS-GOLGI NETWORK; MEDIATED ENDOCYTOSIS; IN-VIVO; COATED VESICLES; MULTIPLE ROLES; AUXILIN; MICE; RECRUITMENT AB Cyclin-G-associated kinase (GAK), the ubiquitously expressed J-domain protein, is essential for the chaperoning and uncoating of clathrin that is mediated by Hsc70 (also known as HSPA8). Adjacent to the C-terminal J-domain that binds to Hsc70, GAK has a clathrin-binding domain that is linked to an N-terminal kinase domain through a PTEN-like domain. Knocking out GAK in fibroblasts caused inhibition of clathrin-dependent trafficking, which was rescued by expressing a 62-kDa fragment of GAK, comprising just the clathrin-binding and J-domains. Expressing this fragment as a transgene in mice rescued the lethality and the histological defects caused by knocking out GAK in the liver or in the brain. Furthermore, when both GAK and auxilin (also known as DNAJC6), the neuronal-specific homolog of GAK, were knocked out in the brain, mice expressing the 62-kDa GAK fragment were viable, lived a normal life-span and had no major behavior abnormalities. However, these mice were about half the size of wild-type mice. Therefore, the PTEN-like domains of GAK and auxilin are not essential for Hsc70-dependent chaperoning and uncoating of clathrin, but depending on the tissue, these domains appear to increase the efficiency of these co-chaperones. C1 [Park, Bum-Chan; Yim, Yang-In; Zhao, Xiaohong; Olszewski, Maciej B.; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov RI Olszewski, Maciej/C-2021-2015 OI Olszewski, Maciej/0000-0003-0961-0801 FU Intramural Research Program in the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program in the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH). Deposited in PMC for release after 12 months. NR 42 TC 4 Z9 4 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2015 VL 128 IS 20 BP 3811 EP 3821 DI 10.1242/jcs.171058 PG 11 WC Cell Biology SC Cell Biology GA CV8ID UT WOS:000364525500013 PM 26345367 ER PT J AU Curd, A Cleasby, A Makowska, K York, A Shroff, H Peckham, M AF Curd, Alistair Cleasby, Alexa Makowska, Katarzyna York, Andrew Shroff, Hari Peckham, Michelle TI Construction of an instant structured illumination microscope SO METHODS LA English DT Article DE Construction; Fluorescence microscopy; Instant structured illumination microscope; Super-resolution ID FLUORESCENCE MICROSCOPY; RESOLUTION LIMIT; BREAKING; CELLS; LIVE AB A challenge in biological imaging is to capture high-resolution images at fast frame rates in live cells. The "instant structured illumination microscope" (iSIM) is a system designed for this purpose. Similarly to standard structured illumination microscopy (SIM), an iSIM provides a twofold improvement over wide-field microscopy, in x, y and z, but also allows much faster image acquisition, with real-time display of super-resolution images. The assembly of an iSIM is reasonably complex, involving the combination and alignment of many optical components, including three micro-optics arrays (two lenslet arrays and an array of pinholes, all with a pitch of 222 mu m) and a double-sided scanning mirror. In addition, a number of electronic components must be correctly controlled. Construction of the system is therefore not trivial, but is highly desirable, particularly for live-cell imaging. We report, and provide instructions for, the construction of an iSIM, including minor modifications to a previous design in both hardware and software. The final instrument allows us to rapidly acquire fluorescence images at rates faster than 100 fps, with approximately twofold improvement in resolution in both x-y and z; sub-diffractive biological features have an apparent size (full width at half maximum) of 145 nm (lateral) and 320 nm (axial), using a 1.49 NA objective and 488 nm excitation. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Curd, Alistair; Cleasby, Alexa; Makowska, Katarzyna; Peckham, Michelle] Univ Leeds, Sch Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England. [York, Andrew; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. RP Curd, A (reprint author), Univ Leeds, Sch Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England. EM a.curd@leeds.ac.uk RI Shroff, Hari/E-7247-2016; Peckham, Michelle/J-4991-2015 OI Shroff, Hari/0000-0003-3613-8215; Peckham, Michelle/0000-0002-3754-2028 FU MRC [MR/K015613/1]; Intramural Research Program of the NIH National Institute of Biomedical Imaging and Bioengineering FX This work was supported by MRC grant ref MR/K015613/1. Thanks to David Towers for discussion of the system PSF.; The NIH (NIBIB), which employs AGY and HS, has granted licenses to various commercial entities for existing patent rights covering the instant SIM technology that are owned by the United States of America. Generally, commercial entities are welcome to apply for commercialization or internal-use licenses. A royalty-free, non-exclusive, paid up license is hereby granted to academic and other non-profit institutions wishing to build their own instant SIM for the purposes of conducting basic research not related to a commercial activity. This work was supported by the Intramural Research Program of the NIH National Institute of Biomedical Imaging and Bioengineering. NR 17 TC 1 Z9 1 U1 4 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD OCT 15 PY 2015 VL 88 BP 37 EP 47 DI 10.1016/j.ymeth.2015.07.012 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CV9LD UT WOS:000364607800006 PM 26210400 ER PT J AU Nath, A Kury, P do Olival, GS Dolei, A Karlsson, H Groc, L Schneider, M Kriesel, J Touraine, JL Mallet, F Marche, PN Arnaud, F Feschotte, C Perron, H AF Nath, Avindra Kuery, Patrick do Olival, Guilherme Sciascia Dolei, Antonina Karlsson, Hakan Groc, Laurent Schneider, Marion Kriesel, John Touraine, Jean-Louis Mallet, Francois Marche, Patrice N. Arnaud, Frederick Feschotte, Cedric Perron, Herve TI First international workshop on human endogenous retroviruses and diseases, HERVs & disease 2015 SO MOBILE DNA LA English DT Editorial Material AB The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human endogenous retroviruses (HERVs) in complex human diseases. C1 [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Kuery, Patrick] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany. [do Olival, Guilherme Sciascia] Emilio Ribas Infectol Inst Neurosci, Sao Paulo, SP, Brazil. [do Olival, Guilherme Sciascia] CATEM Multiple Sclerosis Ctr Santa Casa Sao Paulo, Sao Paulo, SP, Brazil. [Dolei, Antonina] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Karlsson, Hakan] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Groc, Laurent] Univ Bordeaux 2, Inst Interdisciplinaire Neurosci, CNRS, UMR 5297, F-33076 Bordeaux, France. [Schneider, Marion] Univ Hosp, Dept Anesthesiol, Ulm, Germany. [Kriesel, John] Univ Utah, Sch Med, Div Infect Dis, Salt Lake City, UT USA. [Touraine, Jean-Louis] Ctr Hosp Lyon Sud, Canc Biomarkers Res Grp, Joint Unit Hosp Civils Lyon, BioMerieux, F-69310 Pierre Benite, France. [Mallet, Francois] Univ Lyon 1, Sch Med, F-69365 Lyon, France. [Marche, Patrice N.] Univ Grenoble, INSERM, U823, Grenoble, France. [Arnaud, Frederick] Univ Lyon 1, Inst Natl Rech Agron, UMR754, F-69365 Lyon, France. [Arnaud, Frederick] Ecole Prat Hautes Etud, Lyon, France. [Arnaud, Frederick] SFR BioSci Gerland, Lyon, France. [Feschotte, Cedric] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Perron, Herve] Geneuro, Geneva, Switzerland. [Perron, Herve] Geneuro Innovat, Lyon, France. RP Perron, H (reprint author), Geneuro, Geneva, Switzerland. EM hp@geneuro.com RI Marche, Patrice/K-5060-2013 OI Marche, Patrice/0000-0002-8930-9340 NR 0 TC 0 Z9 0 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PD OCT 15 PY 2015 VL 6 AR 20 DI 10.1186/s13100-015-0051-7 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CT7QG UT WOS:000363009000001 ER PT J AU Nath, A Kury, P do Olival, GS Dolei, A Karlsson, H Groc, L Schneider, M Kriesel, J Touraine, JL Mallet, F Marche, PN Arnaud, F Feschotte, C Perron, H AF Nath, Avindra Kuery, Patrick do Olival, Guilherme Sciascia Dolei, Antonina Karlsson, Hakan Groc, Laurent Schneider, Marion Kriesel, John Touraine, Jean-Louis Mallet, Francois Marche, Patrice N. Arnaud, Frederick Feschotte, Cedric Perron, Herve TI First international workshop on human endogenous retroviruses and diseases, HERVs & disease 2015 SO MOBILE DNA LA English DT Article AB The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human endogenous retroviruses (HERVs) in complex human diseases. C1 [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Kuery, Patrick] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany. [do Olival, Guilherme Sciascia] Emilio Ribas Infectol Inst Neurosci, Sao Paulo, SP, Brazil. [do Olival, Guilherme Sciascia] CATEM Multiple Sclerosis Ctr Santa Casa Sao Paulo, Sao Paulo, SP, Brazil. [Dolei, Antonina] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Karlsson, Hakan] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Groc, Laurent] Univ Bordeaux 2, Inst Interdisciplinaire Neurosci, CNRS UMR 5297, F-33076 Bordeaux, France. [Schneider, Marion] Univ Hosp, Dept Anesthesiol, Ulm, Germany. [Kriesel, John] Univ Utah, Sch Med, Div Infect Dis, Salt Lake City, UT USA. [Touraine, Jean-Louis] Ctr Hosp Lyon Sud, Canc Biomarkers Res Grp, BioMerieux, Joint Unit Hosp Civils Lyon, F-69310 Pierre Benite, France. [Mallet, Francois] Univ Lyon 1, Sch Med, F-69365 Lyon, France. [Marche, Patrice N.] Univ Grenoble, INSERM U823, Grenoble, France. [Arnaud, Frederick] Univ Lyon 1, INRA, UMR754, F-69365 Lyon, France. [Arnaud, Frederick] Ecole Prat Hautes Etud, Lyon, France. [Arnaud, Frederick] SFR BioSci Gerland, Lyon, France. [Feschotte, Cedric] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Perron, Herve] Geneuro, Geneva Switzerland & Geneuro Innovat, Lyon, France. RP Perron, H (reprint author), Geneuro, Geneva Switzerland & Geneuro Innovat, Lyon, France. EM hp@geneuro.com FU ARSEP/AFM France; National Institutes of Health [R01-GM112972] FX PK and PM are supported by a grant from ARSEP/AFM France. C.F. lab is supported by grant R01-GM112972 from the National Institutes of Health. NR 0 TC 0 Z9 0 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PD OCT 15 PY 2015 VL 6 AR 20 DI 10.1186/s13100-015-0051-7 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CT4YX UT WOS:000362814700001 ER PT J AU Cheng, Q Yakel, JL AF Cheng, Qing Yakel, Jerrel L. TI The effect of alpha 7 nicotinic receptor activation on glutamatergic transmission in the hippocampus SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE alpha 17 Nicotinic acetylcholine receptor; Glutamatergic transmission; Hippocampus; Calcium; cAMP ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-A; ACETYLCHOLINE-RECEPTORS; ACH RECEPTORS; RAT HIPPOCAMPAL; SYNAPTIC-TRANSMISSION; IN-VIVO; NEUROTRANSMITTER RELEASE; CHOLINERGIC MECHANISMS AB Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory, however the cellular mechanism of these actions remains elusive. With help from newly developed biosensors and optogenetic tools, recent studies provide new insights on signaling mechanisms involved in the activation of nAChRs. Here we will review alpha 7 nAChR's action in the tri-synaptic pathway in the hippocampus. The effects of a7 nAChR activation via either exogenous compounds or endogenous cholinergic innervation are detailed for spontaneous and evoked glutamatergic synaptic transmission and synaptic plasticity, as well as the underlying signaling mechanisms. In summary, alpha 7 nAChRs trigger intracellular calcium rise and calcium-dependent signaling pathways to enhance glutamate release and induce glutamatergic synaptic plasticity. Published by Elsevier Inc. C1 [Cheng, Qing; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cheng, Q (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS Intramural Research Program/NIH FX We would like to thank Drs. Serena Dudek and Christian Erxleben for the helpful reading and suggestions on our manuscript. This research was funded by the NIEHS Intramural Research Program/NIH. The authors declare no competing financial interests. NR 122 TC 2 Z9 2 U1 6 U2 15 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 OCT 15 PY 2015 VL 97 IS 4 SI SI BP 439 EP 444 DI 10.1016/j.bcp.2015.07.015 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CU3PL UT WOS:000363437200010 PM 26212541 ER PT J AU Mallick, P Shah, P Gandhi, A Ghose, R AF Mallick, Pankajini Shah, Pranav Gandhi, Adarsh Ghose, Romi TI Impact of obesity on accumulation of the toxic irinotecan metabolite, SN-38, in mice SO LIFE SCIENCES LA English DT Article DE Obesity; Ugt1a1; SN-38; Irinotecan; Colorectal cancer; Chemotherapy; Pharmacokinetics ID FATTY LIVER-DISEASE; HEPATIC COLORECTAL METASTASES; HUMAN UDP-GLUCURONOSYLTRANSFERASES; DIET-INDUCED OBESITY; CANCER-PATIENTS; GENE-EXPRESSION; 7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38; BETA-GLUCURONIDASE; ADIPOSE-TISSUE; PHASE-I AB Aim: Our aim is to investigate the impact of high fat diet-induced obesity on plasma concentrations of the toxic irinotecan metabolite, SN-38, in mice. Main methods: Diet-induced obese (DID, 60% kcal fed) and lean mice (10% kcal fed) were treated orally with a single dose of 10 mg/kg irinotecan to determine pharmacokinetic (PR) parameters. Feces and livers were collected for quantification of irinotecan and its metabolites (SN-38 82SN-38G). SN-38G formation by Ugtl al enzyme was analyzed in liver S9 fractions. Expression of the pro-inflammatory cytokine, TNF-alpha was determined in liver and plasma. Hepatic beta-glucuronidase and carboxylesterase enzymes (CES) were also determined. Key findings: AUC(0 - 8) and C-max. of SN-38 increased by 2-fold in DID mice compared to their lean controls. This was accompanied by a similar to 2-fold reduction in AUC(0-8) and C-max of SN-38G in DID mice. There were no differences in the PR parameters of irinotecan in DID or lean mice. Conversion of SN-38 to SN-38G by Ugtlal enzyme was reduced by similar to 2-fold in liver S9 fractions in DID mice. Furthermore, in DID mice, beta-glucuronidase activity increased by 2-fold, whereas there was no change in CES activity. TNF-alpha mRNA expression was 3 fold higher in DID mice. Significance: Our study demonstrates that reduced hepatic Ugtl a activity during obesity likely contributes to reduced glucuronidation, and results in higher levels of the toxic metabolite, SN-38. Thus, irinotecan dosage should be closely monitored for effective and safe chemotherapy in obese cancer patients who are at a higher risk of developing liver toxicity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mallick, Pankajini; Ghose, Romi] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. [Shah, Pranav] Natl Ctr Adv Translat Sci, Div Preclin Innovat, Rockville, MD USA. [Gandhi, Adarsh] Lundbeck Res Inc USA, Dept Bioanal & Physiol, Paramus, NJ USA. RP Ghose, R (reprint author), Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, 1441 Moursund St, Houston, TX 77030 USA. EM rghose@uh.edu NR 66 TC 6 Z9 6 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD OCT 15 PY 2015 VL 139 BP 132 EP 138 DI 10.1016/j.lfs.2015.08.017 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CU7IO UT WOS:000363710100018 PM 26334566 ER PT J AU Prasad, V AF Prasad, Vinay TI Prostate Cancer Screening: The Pendulum Has Swung, and the Burden of Proof Is with Proponents SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Prasad, V (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM vinayak.k.prasad@gmail.com NR 11 TC 2 Z9 2 U1 0 U2 4 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X EI 1532-0650 J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT 15 PY 2015 VL 92 IS 8 BP 678 EP 680 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CT7MN UT WOS:000362998900002 PM 26554407 ER PT J AU Johnson, JT Sleeper, LA Chen, S Ohye, RG Gaies, MG Williams, IA Sachdeva, R Pruetz, JD Tatum, GH Thacker, D Brunetti, MA Frommelt, MA Jacobs, JP Kirsh, JA Lambert, LM Newburger, JW Pemberton, VL Zyblewski, SC Divanovic, AA Pinto, NM AF Johnson, Joyce T. Sleeper, Lynn A. Chen, Shan Ohye, Richard G. Gaies, Michael G. Williams, Ismee A. Sachdeva, Ritu Pruetz, Jay D. Tatum, Gregory H. Thacker, Deepika Brunetti, Marissa A. Frommelt, Michele A. Jacobs, Jeffrey P. Kirsh, Joel A. Lambert, Linda M. Newburger, Jane W. Pemberton, Victoria L. Zyblewski, Sinai C. Divanovic, Allison A. Pinto, Nelangi M. CA Pediat Heart Network Investigators TI Associations Between Day of Admission and Day of Surgery on Outcome and Resource Utilization in Infants With Hypoplastic Left Heart Syndrome Who Underwent Stage I Palliation (from the Single Ventricle Reconstruction Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NORWOOD PROCEDURE; MORTALITY; WEEKENDS; CHILDREN; WEEKDAY; STROKE; DISEASE AB Newborns with hypoplastic left heart syndrome and other single right ventricular variants require substantial health care resources. Weekend acute care has been associated with worse outcomes and increased resource use in other populations but has not been studied in patients with single ventricle. Subjects of the Single Ventricle Reconstruction trial were classified by whether they had a weekend admission and by day of the week of Norwood procedure. The primary outcome was hospital length of stay (LOS); secondary outcomes included transplant-free survival, intensive care unit (ICU) LOS, and days of mechanical ventilation. The Student's t test with log transformation and the Wilcoxon rank-sum test were used to analyze associations. Admission day was categorized for 533 of 549 subjects (13% weekend). The day of the Norwood was Thursday/Friday in 39%. There was no difference in median hospital LOS, transplant-free survival, ICU LOS, or days ventilated for weekend versus non-weekend admissions. Day of the Norwood procedure was not associated with a difference in hospital LOS, transplant-free survival, ICU LOS, or days ventilated. Prenatally diagnosed infants born on the weekend had lower mean birth weight, younger gestational age, and were more likely to be intubated but did not have a difference in measured outcomes. In conclusion, in this cohort of patients with single right ventricle, neither weekend admission nor end-of-the-week Norwood procedure was associated with increased use of hospital resources or poorer outcomes. We speculate that the complex postoperative course following the Norwood procedure outweighs any impact that day of admission or operation may have on these outcomes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Johnson, Joyce T.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Sleeper, Lynn A.; Chen, Shan] New England Res Inst Inc, Watertown, MA USA. [Ohye, Richard G.; Gaies, Michael G.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Williams, Ismee A.] Columbia Univ, Med Ctr, New York, NY USA. [Sachdeva, Ritu] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Pruetz, Jay D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Tatum, Gregory H.] Duke Childrens Hosp & Hlth Ctr, Durham, NC USA. [Thacker, Deepika] Nemours Alfred L DuPont Hosp Children, Wilmington, DE USA. [Brunetti, Marissa A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Frommelt, Michele A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Jacobs, Jeffrey P.] All Childrens Hosp, St Petersburg, FL USA. [Kirsh, Joel A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Lambert, Linda M.; Pinto, Nelangi M.] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA. [Newburger, Jane W.] Boston Childrens Hosp, Boston, MA USA. [Pemberton, Victoria L.] NHLBI, Bethesda, MD 20892 USA. [Zyblewski, Sinai C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Divanovic, Allison A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. RP Johnson, JT (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. EM jtjohnson@luriechildrens.org FU National Heart, Lung, and Blood Institute (NHLBI) [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057, HL109781, HL109737] FX Supported by U01 grants HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057, HL109781, and HL109737 from the National Heart, Lung, and Blood Institute (NHLBI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI or National Institutes of Health. NR 17 TC 1 Z9 1 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2015 VL 116 IS 8 BP 1263 EP 1269 DI 10.1016/j.amjcard.2015.07.044 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT8VO UT WOS:000363095200018 PM 26303634 ER PT J AU White, AJ Nichols, HB Bradshaw, PT Sandler, DP AF White, Alexandra J. Nichols, Hazel B. Bradshaw, Patrick T. Sandler, Dale P. TI Overall and Central Adiposity and Breast Cancer Risk in the Sister Study SO CANCER LA English DT Article DE adiposity; body mass index; breast neoplasms; waist circumference ID HORMONE-RECEPTOR STATUS; BODY-MASS INDEX; WAIST CIRCUMFERENCE; UNITED-STATES; OBESITY; WOMEN; SIZE; PREMENOPAUSAL; ESTROGEN; HEALTH AB BACKGROUND: Greater body mass index (BMI), a measure of overall adiposity, is associated with a higher risk of postmenopausal breast cancer. The role of central adiposity, often measured by waist circumference, is less well understood, especially among premenopausal women. The objective of the current study was to examine multiple measures of adiposity in relation to breast cancer in a prospective cohort study. METHODS: A total of 50,884 Sister Study cohort participants aged 35 to 74 years were enrolled from 2003 through 2009. Inclusion criteria for the cohort included having a sister previously diagnosed with breast cancer. Trained study personnel measured height, weight, and waist and hip circumference during a home visit and study participants completed a detailed questionnaire. Using Cox regression analysis, we estimated multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with adiposity measurements, considering tumor subtype and menopausal status. RESULTS: In total, 2009 breast cancers were diagnosed during follow-up (mean=5.4 years). Weight, BMI, waist circumference, and waist-to-hip ratio were found to be positively associated with overall breast cancer risk and HRs were greater among postmenopausal women, those with hormonally responsive tumors, and women who were not currently using postmenopausal hormones. In models that adjusted for BMI, waist circumference associations persisted among both postmenopausal women (81-88 cm vs <= 80 cm: HR=1.16 [95% CI 1.01-1.35] and > 88 cm vs <= 80 cm: HR=1.30 [95% CI 1.10-1.54]) and premenopausal women (81-88 cm vs <= 80 cm: HR=1.56 [95% CI 1.19-2.04] and > 88 cm vs <= 80 cm: HR=1.30 [95% CI 0.91-1.87]). CONCLUSIONS: Findings from this large, prospective study with examiner-measured body size indicate that waist circumference is independently and positively associated with both premenopausal and postmenopausal breast cancer risk. (c) 2015 American Cancer Society. C1 [White, Alexandra J.; Nichols, Hazel B.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Bradshaw, Patrick T.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. RP Nichols, HB (reprint author), Univ N Carolina, Dept Epidemiol, 2102A McGavran Greenberg Hall,135 Dauer Dr, Chapel Hill, NC 27599 USA. EM hazel.nichols@unc.edu OI Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES044005]; Avon Foundation [02-2012-085]; National Center for Advancing Translational Sciences [KL2-TR001109]; UNC Lineberger Cancer Control Education Program [R25 CA57726] FX Supported in part by the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES044005), the Avon Foundation (02-2012-085), the National Center for Advancing Translational Sciences (KL2-TR001109), and the UNC Lineberger Cancer Control Education Program (R25 CA57726). NR 35 TC 8 Z9 8 U1 1 U2 3 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 OCT 15 PY 2015 VL 121 IS 20 BP 3700 EP 3708 DI 10.1002/cncr.29552 PG 9 WC Oncology SC Oncology GA CU1EN UT WOS:000363262700019 PM 26193782 ER PT J AU Lu, Y Cuellar-Partida, G Painter, JN Nyholt, DR Morris, AP Fasching, PA Hein, A Burghaus, S Beckmann, MW Lambrechts, D Van Nieuwenhuysen, E Vergote, I Vanderstichele, A Doherty, JA Rossing, MA Wicklund, KG Chang-Claude, J Eilber, U Rudolph, A Wang-Gohrke, S Goodman, MT Bogdanova, N Dork, T Durst, M Hillemanns, P Runnebaum, IB Antonenkova, N Butzow, R Leminen, A Nevanlinna, H Pelttari, LM Edwards, RP Kelley, JL Modugno, F Moysich, KB Ness, RB Cannioto, R Hogdall, E Jensen, A Giles, GG Bruinsma, F Kjaer, SK Hildebrandt, MAT Liang, D Lu, KH Wu, XF Bisogna, M Dao, F Levine, DA Cramer, DW Terry, KL Tworoger, SS Missmer, S Bjorge, L Salvesen, HB Kopperud, RK Bischof, K Aben, KKH Kiemeney, LA Massuger, LFAG Brooks-Wilson, A Olson, SH McGuire, V Rothstein, JH Sieh, W Whittemore, AS Cook, LS Le, ND Gilks, CB Gronwald, J Jakubowska, A Lubinski, J Gawelko, J Song, HL Tyrer, JP Wentzensen, N Brinton, L Trabert, B Lissowska, J Mclaughlin, JR Narod, SA Phelan, C Anton-Culver, H Ziogas, A Eccles, D Gayther, SA Gentry-Maharaj, A Menon, U Ramus, SJ Wu, AH Dansonka-Mieszkowska, A Kupryjanczyk, J Timorek, A Szafron, L Cunningham, JM Fridley, BL Winham, SJ Bandera, EV Poole, EM Morgan, TK Risch, HA Goode, EL Schildkraut, JM Webb, PM Pearce, CL Berchuck, A Pharoah, PDP Montgomery, GW Zondervan, KT Chenevix-Trench, G MacGregor, S AF Lu, Yi Cuellar-Partida, Gabriel Painter, Jodie N. Nyholt, Dale R. Morris, Andrew P. Fasching, Peter A. Hein, Alexander Burghaus, Stefanie Beckmann, Matthias W. Lambrechts, Diether Van Nieuwenhuysen, Els Vergote, Ignace Vanderstichele, Adriaan Doherty, Jennifer Anne Rossing, Mary Anne Wicklund, Kristine G. Chang-Claude, Jenny Eilber, Ursula Rudolph, Anja Wang-Gohrke, Shan Goodman, Marc T. Bogdanova, Natalia Doerk, Thilo Duerst, Matthias Hillemanns, Peter Runnebaum, Ingo B. Antonenkova, Natalia Butzow, Ralf Leminen, Arto Nevanlinna, Heli Pelttari, Liisa M. Edwards, Robert P. Kelley, Joseph L. Modugno, Francesmary Moysich, Kirsten B. Ness, Roberta B. Cannioto, Rikki Hogdall, Estrid Jensen, Allan Giles, Graham G. Bruinsma, Fiona Kjaer, Susanne K. Hildebrandt, Michelle A. T. Liang, Dong Lu, Karen H. Wu, Xifeng Bisogna, Maria Dao, Fanny Levine, Douglas A. Cramer, Daniel W. Terry, Kathryn L. Tworoger, Shelley S. Missmer, Stacey Bjorge, Line Salvesen, Helga B. Kopperud, Reidun K. Bischof, Katharina Aben, Katja K. H. Kiemeney, Lambertus A. Massuger, Leon F. A. G. Brooks-Wilson, Angela Olson, Sara H. McGuire, Valerie Rothstein, Joseph H. Sieh, Weiva Whittemore, Alice S. Cook, Linda S. Le, Nhu D. Gilks, C. Blake Gronwald, Jacek Jakubowska, Anna Lubinski, Jan Gawelko, Jan Song, Honglin Tyrer, Jonathan P. Wentzensen, Nicolas Brinton, Louise Trabert, Britton Lissowska, Jolanta Mclaughlin, John R. Narod, Steven A. Phelan, Catherine Anton-Culver, Hoda Ziogas, Argyrios Eccles, Diana Gayther, Simon A. Gentry-Maharaj, Aleksandra Menon, Usha Ramus, Susan J. Wu, Anna H. Dansonka-Mieszkowska, Agnieszka Kupryjanczyk, Jolanta Timorek, Agnieszka Szafron, Lukasz Cunningham, Julie M. Fridley, Brooke L. Winham, Stacey J. Bandera, Elisa V. Poole, Elizabeth M. Morgan, Terry K. Risch, Harvey A. Goode, Ellen L. Schildkraut, Joellen M. Webb, Penelope M. Pearce, Celeste L. Berchuck, Andrew Pharoah, Paul D. P. Montgomery, Grant W. Zondervan, Krina T. Chenevix-Trench, Georgia MacGregor, Stuart CA Australian Ovarian Canc Study IEC TI Shared genetics underlying epidemiological association between endometriosis and ovarian cancer SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; RISK-FACTORS; SUSCEPTIBILITY LOCI; METAANALYSIS; CARCINOMA; VARIANTS; BIOLOGY; MODEL AB Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. C1 [Lu, Yi; Cuellar-Partida, Gabriel; MacGregor, Stuart] QIMR Berghofer Med Res Inst, Stat Genet, Herston, Qld 4006, Australia. [Painter, Jodie N.] QIMR Berghofer Med Res Inst, Mol Canc Epidemiol, Herston, Qld 4006, Australia. [Webb, Penelope M.] QIMR Berghofer Med Res Inst, Populat Hlth Dept, Herston, Qld 4006, Australia. [Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Mol Epidemiol, Herston, Qld 4006, Australia. [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Herston, Qld 4006, Australia. [Nyholt, Dale R.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Australian Ovarian Canc Study] Peter MacCallum Canc Ctr, Div Res, East Melbourne, Australia. [Morris, Andrew P.; Zondervan, Krina T.] Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England. [Zondervan, Krina T.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen Nuremberg, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium. [Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium. [Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. [Doherty, Jennifer Anne] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Epidemiol & Biostat Sect, Hanover, NH 03755 USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany. [Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Community & Populat Hlth Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Bogdanova, Natalia] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany. [Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany. [Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Jena Univ Hosp, Dept Gynecol, Jena, Germany. [Antonenkova, Natalia] NN Alexandrov Natl Canc Ctr Belarus, Minsk, Byelarus. [Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland. [Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Helsinki Univ Hosp, Helsinki, Finland. [Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA. [Edwards, Robert P.; Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA. [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Moysich, Kirsten B.; Cannioto, Rikki] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark. [Hogdall, Estrid] Herlev Hosp, Dept Pathol, Mol Unit, DK-2730 Herlev, Denmark. [Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Gynaecol, DK-2100 Copenhagen, Denmark. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Giles, Graham G.; Bruinsma, Fiona] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Bisogna, Maria; Dao, Fanny; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Terry, Kathryn L.; Tworoger, Shelley S.; Missmer, Stacey; Poole, Elizabeth M.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tworoger, Shelley S.; Missmer, Stacey; Poole, Elizabeth M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Missmer, Stacey] Brigham & Womens Hosp, Dept Obstet & Gynecol Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen, Norway. [Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. H.] Netherlands Comprehens Canc Org, Utrecht, Netherlands. [Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Obstet & Gynaecol, NL-6525 ED Nijmegen, Netherlands. [Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Gilks, C. Blake] Univ British Columbia, Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Gawelko, Jan] Univ Rzeszow, Fac Med, Inst Nursing & Hlth Sci, Rzeszow, Poland. [Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England. [Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Mclaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA. [Eccles, Diana] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc, Dept Prevent Med, Los Angeles, CA 90033 USA. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Womens Canc, London, England. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Szafron, Lukasz] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Szafron, Lukasz] Inst Oncol, Warsaw, Poland. [Timorek, Agnieszka] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland. [Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland. [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN USA. [Winham, Stacey J.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA. [Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA. [Fridley, Brooke L.] Univ Kansas, Dept Biostat, Kansas City, KS USA. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Morgan, Terry K.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Morgan, Terry K.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA. [Pearce, Celeste L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. RP MacGregor, S (reprint author), QIMR Berghofer Med Res Inst, Locked Bag 2000, Herston, Qld 4029, Australia. EM stuart.macgregor@qimrberghofer.edu.au RI salvesen, Helga/C-1187-2017; Cuellar Partida, Gabriel/C-6686-2017; Lee, Sang Hong/A-2569-2011; Gronwald, Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; Hein, Alexander/F-6999-2010; Bandera, Elisa/M-4169-2014; Macgregor, Stuart/C-6442-2009; Brooks-Wilson, Angela/E-9399-2012; Montgomery, Grant/B-7148-2008; Trabert, Britton/F-8051-2015; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016; Dork, Thilo/J-8620-2012 OI salvesen, Helga/0000-0002-4438-8831; Cuellar Partida, Gabriel/0000-0001-7648-4097; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Visscher, Peter/0000-0002-2143-8760; Giles, Graham/0000-0003-4946-9099; Winham, Stacey/0000-0002-8492-9102; Lee, Sang Hong/0000-0001-9701-2718; Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770; Hein, Alexander/0000-0003-2601-3398; Bandera, Elisa/0000-0002-8789-2755; Macgregor, Stuart/0000-0001-6731-8142; Brooks-Wilson, Angela/0000-0003-1009-6408; Montgomery, Grant/0000-0002-4140-8139; Aben, Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; FU QIMR Berghofer-Weekend to End Women's Cancers Research Grant [WEWC140014]; Wellcome Trust [WT084766/Z/08/Z, 076113, 085475]; National Health and Medical Research Council (NHMRC) of Australia [241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498]; Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne); European Commission [223175 HEALTH F2 2009-223175]; Genetic Associations and Mechanisms in Oncology (GAME-ON): A NCI Cancer Post-GWAS Initiative [U19-CA148112]; Ovarian Cancer Research Fund [PPD/RPCI.07]; California Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes of Health Research [MOP-86727]; Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New SouthWales; 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]; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal; Helsinki University Central Hospital Research Fund; Helse Vest; Norwegian Cancer Society; Norwegian Research Council; Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; L & 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-CA80668]; NIH/National Center for Research Resources/General Clinical Research Center [MO1-RR000056]; US Army Medical Research and Material Command [DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802]; US Public Health Service [PSA-042205]; National Health and Medical Research Council of Australia [199600, 400281]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01GB 9401]; State of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P. 685]; German Cancer Research Center; 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 'Womens Health Theme'; Royal Marsden Hospital; WorkSafeBC 14; NHMRC Early Career Fellowship; NHMRC Fellowship [339462, 613674]; Australian Research Council (ARC) Future Fellowship [FT0991022]; Wellcome Trust Senior Research Fellowship in Basic Biomedical Science [WT098017]; NHMRC Fellowships Scheme [339446, 619667]; Wellcome Trust Research Career Development Fellowship [WT085235/Z/08/Z]; National Health and Medical Research Council; ARC Future Fellowship; [R01-CA058860]; [R01-CA061107]; [R01-CA061132]; [R01-CA063678]; [R01-CA063682]; [R01-CA067262]; [R01-CA071766]; [R01-CA074850]; [R01-CA080978]; [R01-CA083918]; [R01-CA087538]; [R01-CA092044]; [K07-CA143047]; [K22-CA138563]; [N01-CN55424]; [N01-PC67001]; [N01-PC067010]; [N01-PC035137]; [P01-CA017054]; [P01-CA087696]; [P30-CA072720]; [P30-CA15083]; [R01-CA095023]; [R01-CA122443]; [R01-CA112523]; [R01-CA114343]; [R01-CA126841]; [R01-CA136924]; [R03-CA113148]; [R03-CA115195]; [U01-CA069417]; [U01-CA071966]; [UM1-CA186107]; [UM1-CA176726]; [P30-CA008748]; [P50-CA159981]; [P50-CA105009]; [P50-CA136393]; [R01-CA149429]; [R01-CA014089]; [R01-CA016056]; [R01-CA017054]; [R01-CA049449]; [R01-CA050385]; [R01-CA054419]; [R01-CA058598] FX This study was supported by the QIMR Berghofer-Weekend to End Women's Cancers Research Grant (WEWC140014). The endometriosis GWAS was supported by a grant from the Wellcome Trust (WT084766/Z/08/Z) and makes use of WTCCC2 control data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of these data is available from http://www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under awards 076113 and 085475. The QIMR study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne) and donations from N. Hawkins and S. Hawkins. The COGS project is funded through a European Commission's Seventh Framework Programme Grant (agreement number 223175 HEALTH F2 2009-223175); the Genetic Associations and Mechanisms in Oncology (GAME-ON): A NCI Cancer Post-GWAS Initiative (U19-CA148112); 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).; Funding of the constituent studies was provided by the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New SouthWales; 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); the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; 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-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, 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-CA067262, R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R03-CA113148, R03-CA115195, U01-CA069417, U01-CA071966, UM1-CA186107, UM1-CA176726 and Intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Center (MO1-RR000056); the US Army Medical Research and Material Command (DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802); the US Public Health Service (PSA-042205); 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 (01GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P. 685); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; Eve Appeal; 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 'Womens Health Theme' and the Royal Marsden Hospital; and WorkSafeBC 14. Investigator-specific funding: Y.L. was supported by the NHMRC Early Career Fellowship. D.R.N. was supported by the NHMRC Fellowship (339462 and 613674) and the Australian Research Council (ARC) Future Fellowship (FT0991022) schemes. A.P.M. was supported by a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science (WT098017). G.W.M. was supported by the NHMRC Fellowships Scheme (339446, 619667). K.T.Z. was supported by a Wellcome Trust Research Career Development Fellowship (WT085235/Z/08/Z). G.C.T. is supported by the National Health and Medical Research Council. S.M. was supported by an ARC Future Fellowship. NR 37 TC 5 Z9 7 U1 10 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2015 VL 24 IS 20 BP 5955 EP 5964 DI 10.1093/hmg/ddv306 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT7VM UT WOS:000363022600024 PM 26231222 ER PT J AU Polizzotto, MN Millo, C Uldrick, TS Aleman, K Whatley, M Wyvill, KM O'Mahony, D Marshall, V Whitby, D Maass-Moreno, R Steinberg, SM Little, RF Yarchoan, R AF Polizzotto, Mark N. Millo, Corina Uldrick, Thomas S. Aleman, Karen Whatley, Millie Wyvill, Kathleen M. O'Mahony, Deirdre Marshall, Vickie Whitby, Denise Maass-Moreno, Roberto Steinberg, Seth M. Little, Richard F. Yarchoan, Robert TI F-18-fluorodeoxyglucose Positron Emission Tomography in Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease: Correlation With Activity, Severity, Inflammatory and Virologic Parameters SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Castleman disease; human herpesvirus 8 (HHV-8)/Kaposi sarcoma herpesvirus (KSHV); HIV; F-18-FDG positron emission tomography ID HIV-INFECTED PATIENTS; FDG-PET; DNA-SEQUENCES; HODGKIN-LYMPHOMA; UNKNOWN ORIGIN; RITUXIMAB; TUMOR; ACTIVATION; THERAPY; PLUS AB Background. Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a lymphoproliferative inflammatory disorder commonly associated with human immunodeficiency virus (HIV). Its presentation may be difficult to distinguish from HIV and its complications, including lymphoma. Novel imaging strategies could address these problems. Methods. We prospectively characterized 18F-fluorodeoxyglucose positron emission tomography (PET) findings in 27 patients with KSHV-MCD. Patients were imaged with disease activity and at remission with scans evaluated blind to clinical status. Symptoms, C-reactive protein level, and HIV and KSHV loads were assessed in relation to imaging findings. Results. KSHV-MCD activity was associated with hypermetabolic symmetric lymphadenopathy (median maximal standardized uptake value [SUVmax], 6.0; range, 2.0-8.0) and splenomegaly (3.4; 1.2-11.0), with increased metabolism also noted in the marrow (2.1; range, 1.0-3.5) and salivary glands (3.0; range, 2.0-6.0). The 18F-fluorodeoxyglucose PET abnormalities improved at remission, with significant SUVmax decreases in the lymph nodes (P=.004), spleen (P=.008), marrow (P=.004), and salivary glands (P =.004). Nodal SUVmax correlated with symptom severity (P=.005), C-reactive protein level (R=0.62; P =.004), and KSHV load (R=0.54; P=.02) but not HIV load (P=.52). Conclusions. KSHV-MCD activity is associated with 18F-FDG PET abnormalities of the lymph nodes, spleen, marrow, and salivary glands. These findings have clinical implications for the diagnosis and monitoring of KSHV-MCD and shed light on its pathobiologic mechanism. C1 [Polizzotto, Mark N.; Uldrick, Thomas S.; Aleman, Karen; Wyvill, Kathleen M.; O'Mahony, Deirdre; Little, Richard F.; Yarchoan, Robert] NIH, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Millo, Corina; Whatley, Millie; Maass-Moreno, Roberto] NIH, Positron Emiss Tomog Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Marshall, Vickie; Whitby, Denise] Frederick Natl Canc Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD USA. RP Yarchoan, R (reprint author), NIH, HIV & AIDS Malignancy Branch, Ctr Canc Res, Rm 6N106,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM robert.yarchoan@nih.gov FU NCI, NIH; NCI [HHSN261200800001E] FX This work was supported by the Intramural Research Program of the NCI, NIH, and with federal funds from the NCI (contract HHSN261200800001E). NR 51 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2015 VL 212 IS 8 BP 1250 EP 1260 DI 10.1093/infdis/jiv204 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CU0GY UT WOS:000363195400012 PM 25828248 ER PT J AU Najarro, K Nguyen, H Chen, GB Xu, M Alcorta, S Yao, X Zukley, L Metter, EJ Truong, T Lin, Y Li, HF Oelke, M Xu, XY Ling, SM Longo, DL Schneck, J Leng, S Ferrucci, L Weng, NP AF Najarro, Kevin Huy Nguyen Chen, Guobing Xu, Mai Alcorta, Sandy Yao, Xu Zukley, Linda Metter, E. Jeffrey Thai Truong Lin, Yun Li, Huifen Oelke, Mathias Xu, Xiyan Ling, Shari M. Longo, Dan L. Schneck, Jonathan Leng, Sean Ferrucci, Luigi Weng, Nan-ping TI Telomere Length as an Indicator of the Robustness of B- and T-Cell Response to Influenza in Older Adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE telomere; influenza vaccine; CD8 T cells; antibody; CMV; CD28(-) T cells ID STEM-CELLS; DYSKERATOSIS-CONGENITA; SHORTENED TELOMERES; ELDERLY INDIVIDUALS; LYMPHOCYTE SUBSETS; INTRINSIC DEFECTS; HUMAN FIBROBLASTS; IN-VIVO; INFECTION; IMMUNOSENESCENCE AB Background. Telomeres provide a key mechanism for protecting the integrity of chromosomes and their attrition after cell division and during aging are evident in lymphocytes. However, the significance of telomere shortening in age-associated decline of immune function is unknown. Methods. We selected 22 HLA-A2-positive healthy older adults who have relatively short or long telomere lengths to compare their antibody response against the influenza vaccine, and their CD8(+) T-cell response against an influenza antigen. Results. B cells from individuals with a robust antibody response to the influenza vaccine had significantly longer telomeres than those with a poor antibody response. Monocyte-derived antigen-presenting cells of both short and long telomere groups induced similar expansions of influenza M1-specific CD8(+) T cells. Vaccination did not increase M1-specific CD8(+) T cells in blood, but M1-specific CD8(+) T cells from the long telomere group exhibited significantly greater expansion in vitro than those from the short telomere group. Finally, M1-specific CD8(+) T cells that underwent more expansions had significantly longer telomeres than cells with fewer divisions. Conclusions. Telomere length is positively associated with a robust lymphocyte response, and telomere attrition may contribute to the age-associated decline of adaptive immunity. C1 [Najarro, Kevin; Huy Nguyen; Chen, Guobing; Xu, Mai; Thai Truong; Lin, Yun; Weng, Nan-ping] Johns Hopkins Univ, Sch Med, Lab Mol Biol & Immunol, Baltimore, MD USA. [Alcorta, Sandy; Zukley, Linda; Metter, E. Jeffrey; Li, Huifen; Ling, Shari M.; Ferrucci, Luigi] Johns Hopkins Univ, Sch Med, Translat Gerontol Branch, Baltimore, MD USA. [Yao, Xu; Li, Huifen; Leng, Sean] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Oelke, Mathias; Schneck, Jonathan] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Xu, Xiyan] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Longo, Dan L.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIH, 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA. EM Wengn@mail.nih.gov RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 FU National Institute on Aging; Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging and the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 45 TC 6 Z9 6 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 OCT 15 PY 2015 VL 212 IS 8 BP 1261 EP 1269 DI 10.1093/infdis/jiv202 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CU0GY UT WOS:000363195400013 PM 25828247 ER PT J AU Halliley, JL Khurana, S Krammer, F Fitzgerald, T Coyle, EM Chung, KY Baker, SF Yang, HM Martinez-Sobrido, L Treanor, JJ Subbarao, K Golding, H Topham, DJ Sangster, MY AF Halliley, Jessica L. Khurana, Surender Krammer, Florian Fitzgerald, Theresa Coyle, Elizabeth M. Chung, Ka Yan Baker, Steven F. Yang, Hongmei Martinez-Sobrido, Luis Treanor, John J. Subbarao, Kanta Golding, Hana Topham, David J. Sangster, Mark Y. TI High-Affinity H7 Head and Stalk Domain-Specific Antibody Responses to an Inactivated Influenza H7N7 Vaccine After Priming With Live Attenuated Influenza Vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Avian influenza; H7 hemagglutinin; live attenuated; vaccine; antibody affinity; anti-stalk antibodies; memory B cells ID MEMORY B-CELLS; VIRUS-VACCINE; AVIAN INFLUENZA; HEALTHY-ADULTS; H5N1 VACCINE; HUMANS; REPERTOIRE; IMMUNOGENICITY; MATURATION; INDUCTION AB Recent studies have shown that live attenuated influenza vaccines (LAIVs) expressing avian influenza virus hemagglutinins (HAs) prime for strong protective antibody responses to an inactivated influenza vaccine (IIV) containing the HA. To better understand this priming effect, we compared H7 HA head and stalk domain-specific B-cell responses in H7N7 LAIV-primed subjects and non-H7-primed controls after a single dose of H7N7 IIV. As previously reported, H7N7 LAIV-primed subjects but not control subjects generated strong hemagglutination-inhibiting and neutralizing antibody responses to the H7N7 IIV. Here, we found that the quantity, epitope diversity, and affinity of H7 head-specific antibodies increased rapidly in only H7N7 LAIV-primed subjects after receipt of the IIV. However, all cohorts generated a vigorous, high-affinity, stalk-specific antibody response. Consistent increases in circulating memory B-cell frequencies after receipt of the IIV reflected the specificity of high-affinity antibody production. Our findings emphasize the value of LAIVs as a vehicle for prepandemic vaccination. C1 [Halliley, Jessica L.; Topham, David J.; Sangster, Mark Y.] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA. [Fitzgerald, Theresa; Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, Div Infect Dis, Rochester, NY 14642 USA. [Baker, Steven F.; Martinez-Sobrido, Luis] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Yang, Hongmei] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Krammer, Florian] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA. [Khurana, Surender; Coyle, Elizabeth M.; Chung, Ka Yan; Golding, Hana] Food & Drug Adm, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sangster, MY (reprint author), Univ Rochester, Med Ctr, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA. EM mark_sangster@urmc.rochester.edu OI Krammer, Florian/0000-0003-4121-776X FU National Institutes of Health (NIH) Respiratory Pathogens Research Center [HHSN272201200005C]; Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), NIH; NIH Centers for Excellence in Influenza Research and Surveillance [HHSN272201400008C, HHSN266200700008C]; DIR, NIAID, NIH [HHSN272200900026C] FX This work was supported by the National Institutes of Health (NIH) Respiratory Pathogens Research Center (contract HHSN272201200005C); the Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), NIH; the NIH Centers for Excellence in Influenza Research and Surveillance (contracts HHSN272201400008C [F. K.] and HHSN266200700008C [L. M.-S.]); and the DIR, NIAID, NIH, (Cooperative Research and Development Agreement between the Laboratory of Infectious Diseases, NIAID, NIH, and MedImmune, and the Department of Health and Human Services Biomedical Advanced Research and Development Authority for the clinical trial of H7 vaccines [clinical trials registration NCT01534468]) (contract HHSN272200900026C). NR 41 TC 11 Z9 11 U1 0 U2 5 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 OCT 15 PY 2015 VL 212 IS 8 BP 1270 EP 1278 DI 10.1093/infdis/jiv210 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CU0GY UT WOS:000363195400014 PM 25838266 ER PT J AU Podany, AT Bao, YJ Swindells, S Chaisson, RE Andersen, JW Mwelase, T Supparatpinyo, K Mohapi, L Gupta, A Benson, CA Kim, P Fletcher, CV AF Podany, Anthony T. Bao, Yajing Swindells, Susan Chaisson, Richard E. Andersen, Janet W. Mwelase, Thando Supparatpinyo, Khuanchai Mohapi, Lerato Gupta, Amita Benson, Constance A. Kim, Peter Fletcher, Courtney V. CA AIDS Clinical Trials Grp A5279 Stu TI Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV/AIDS; tuberculosis; rifapentine; pharmacokinetics; pharmacodynamics ID LATENT TUBERCULOSIS; 600 MG/DAY; RIFAMPIN; THERAPY; ADULTS; RECOMMENDATIONS; METABOLISM; GENOTYPE; EXPOSURE; CYP2A6 AB Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations >= 1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval,.97-1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations >= 1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression. C1 [Podany, Anthony T.; Fletcher, Courtney V.] Univ Nebraska, Med Ctr, Coll Pharm, Omaha, NE 68198 USA. [Bao, Yajing; Andersen, Janet W.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Swindells, Susan; Fletcher, Courtney V.] Univ Nebraska, Med Ctr, Infect Dis Internal Med, Omaha, NE 68198 USA. [Chaisson, Richard E.] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. [Mwelase, Thando] Univ Witwatersrand, Johannesburg, South Africa. [Supparatpinyo, Khuanchai] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai, Chiang Mai Prov, Thailand. [Supparatpinyo, Khuanchai] Chiang Mai Univ, Fac Med, Chiang Mai, Chiang Mai Prov, Thailand. [Mohapi, Lerato] Univ Witwatersrand, Soweto, South Africa. [Mohapi, Lerato] Baragwanath Hosp, Soweto, South Africa. [Gupta, Amita] Johns Hopkins Univ, Sch Med, Ctr Clin Global Hlth Educ, Baltimore, MD USA. [Benson, Constance A.] Univ Calif San Diego, Antiviral Res Ctr, San Diego, CA 92103 USA. [Kim, Peter] NIAID, Div Aids, Bethesda, MD 20892 USA. RP Fletcher, CV (reprint author), Univ Nebraska, Med Ctr, Coll Pharm, 986000 Nebraska Med Ctr, Omaha, NE 68198 USA. EM cfletcher@unmc.edu FU NIAID of NIH [UM1 AI068634, UM1 AI068636, UM1 AI106701]; NIAID [UM1 AI069463, UM1 AI069438, UM1 AI068632, UM1 AI069432, UM1 AI069477, UM1 AI069481, UM AI069423] FX This work was supported by the NIAID of the NIH (UM1 AI068634, UM1 AI068636, and UM1 AI106701). Clinical site support was provided in part by the NIAID (UM1 AI069463, UM1 AI069438, UM1 AI068632, UM1 AI069432, UM1 AI069477, UM1 AI069481 and UM AI069423). NR 31 TC 7 Z9 7 U1 1 U2 3 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 OCT 15 PY 2015 VL 61 IS 8 BP 1322 EP 1327 DI 10.1093/cid/civ464 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WN UT WOS:000362953800017 PM 26082504 ER PT J AU Dominique, JK Ortiz-Osorno, AA Fitzgibbon, J Gnanashanmugam, D Gilpin, C Tucker, T Peel, S Peter, T Kim, P Smith, S AF Dominique, Joyelle K. Ortiz-Osorno, Alberto A. Fitzgibbon, Joseph Gnanashanmugam, Devasena Gilpin, Christopher Tucker, Timothy Peel, Sheila Peter, Trevor Kim, Peter Smith, Steven TI Implementation of HIV and Tuberculosis Diagnostics: The Importance of Context SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE diagnostics; HIV; tuberculosis; diagnostics' implementation; point-of-care ID RESOURCE-LIMITED SETTINGS; XPERT MTB/RIF; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; DEVELOPING-COUNTRIES; HEALTH SYSTEMS; RURAL UGANDA; CARE; AFRICA; TESTS AB Background. Novel diagnostics have been widely applied across human immunodeficiency virus (HIV) and tuberculosis prevention and treatment programs. To achieve the greatest impact, HIV and tuberculosis diagnostic programs must carefully plan and implement within the context of a specific healthcare system and the laboratory capacity. Methods. A workshop was convened in Cape Town in September 2014. Participants included experts from laboratory and clinical practices, officials from ministries of health, and representatives from industry. Results. The article summarizes best practices, challenges, and lessons learned from implementation experiences across sub-Saharan Africa for (1) building laboratory programs within the context of a healthcare system; (2) utilizing experience of clinicians and healthcare partners in planning and implementing the right diagnostic; and (3) evaluating the effects of new diagnostics on the healthcare system and on patient health outcomes. Conclusions. The successful implementation of HIV and tuberculosis diagnostics in resource-limited settings relies on careful consideration of each specific context. C1 [Dominique, Joyelle K.] Off Sci Management & Operat, Office Global Res, Rockville, MD USA. [Ortiz-Osorno, Alberto A.] Henry M Jackson Fdn, Div Aids, Clin Res Implementat Subject Matter Expert, Rockville, MD USA. [Ortiz-Osorno, Alberto A.; Fitzgibbon, Joseph] NIAID, Therapeut Res Program, Div Aids, US Dept Hlth & Human Serv,NIH, Rockville, MD 20892 USA. [Gnanashanmugam, Devasena; Kim, Peter] Div Aids, Prevent Sci Program, Adolescent & Pediat Res Branch, Geneva, Switzerland. [Gilpin, Christopher] WHO, CH-1211 Geneva, Switzerland. [Tucker, Timothy] Advisory & Dev Consulting, Strateg Evaluat, Cape Town, South Africa. [Peel, Sheila] Walter Reed Army Inst Res, US Mil HIV Res Program, Diagnost & Lab Monitoring, Silver Spring, MD USA. [Peter, Trevor] Clinton Hlth Access Initiat, Diagnost, Gaborone, Botswana. [Smith, Steven] US Dept Hlth & Human Serv, Off Global Affairs, Pretoria, South Africa. RP Ortiz-Osorno, AA (reprint author), NIAID, Therapeut Res Program, Henry M Jackson Fdn, Div Aids,HHS,NIH, 5601 Fishers Lane,Off 9B27, Rockville, MD 20892 USA. EM bortiz@niaid.nih.gov FU NIAID, NIH [HHSN272200800014C] FX This work was supported, in part, by the NIAID, NIH (contract number HHSN272200800014C). NR 46 TC 2 Z9 2 U1 1 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 OCT 15 PY 2015 VL 61 SU 3 BP S119 EP S125 DI 10.1093/cid/civ552 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900003 PM 26409272 ER PT J AU Graham, SM Cuevas, LE Jean-Philippe, P Browning, R Casenghi, M Detjen, AK Gnanashanmugam, D Hesseling, AC Kampmann, B Mandalakas, A Marais, BJ Schito, M Spiegel, HML Starke, JR Worrell, C Zar, HJ AF Graham, Stephen M. Cuevas, Luis E. Jean-Philippe, Patrick Browning, Renee Casenghi, Martina Detjen, Anne K. Gnanashanmugam, Devasena Hesseling, Anneke C. Kampmann, Beate Mandalakas, Anna Marais, Ben J. Schito, Marco Spiegel, Hans M. L. Starke, Jeffrey R. Worrell, Carol Zar, Heather J. TI Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE childhood tuberculosis; tuberculosis classification; tuberculosis case definitions; tuberculosis diagnosis ID XPERT MTB/RIF ASSAY; PULMONARY TUBERCULOSIS; CHILDHOOD TUBERCULOSIS; STOOL SAMPLES; DIAGNOSIS; METAANALYSIS; CONSENSUS; ACCURACY; BURDEN; TIME AB Consensus case definitions for childhood tuberculosis have been proposed by an international expert panel, aiming to standardize the reporting of cases in research focusing on the diagnosis of intrathoracic tuberculosis in children. These definitions are intended for tuberculosis diagnostic evaluation studies of symptomatic children with clinical suspicion of intrathoracic tuberculosis, and were not intended to predefine inclusion criteria into such studies. Feedback from researchers suggested that further clarification was required and that these case definitions could be further improved. Particular concerns were the perceived complexity and overlap of some case definitions, as well as the potential exclusion of children with acute onset of symptoms or less severe disease. The updated case definitions proposed here incorporate a number of key changes that aim to reduce complexity and improve research performance, while maintaining the original focus on symptomatic children suspected of having intrathoracic tuberculosis. The changes proposed should enhance harmonized classification for intrathoracic tuberculosis disease in children across studies, resulting in greater comparability and the much-needed ability to pool study results. C1 [Graham, Stephen M.] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Ctr Int Child Hlth, Parkville, Vic 3052, Australia. [Graham, Stephen M.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Graham, Stephen M.; Detjen, Anne K.] Int Union TB & Lung Dis, Paris, France. [Graham, Stephen M.] Burnet Inst, Melbourne, Vic, Australia. [Cuevas, Luis E.] Univ Liverpool Liverpool Sch Trop Med, Dept Clin Sci, Liverpool, Merseyside, England. [Jean-Philippe, Patrick; Schito, Marco; Spiegel, Hans M. L.] Henry M Jackson Fdn, Rockville, MD USA. [Browning, Renee; Gnanashanmugam, Devasena] NIAID, Div AIDS, NIH, Rockville, MD 20852 USA. [Casenghi, Martina] Med Sans Frontieres, Geneva, Switzerland. [Hesseling, Anneke C.] Univ Stellenbosch, Dept Pediat & Child Hlth, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Cape Town, South Africa. [Kampmann, Beate] Univ London Imperial Coll Sci Technol & Med, Dept Paediat, London SW7 2AZ, England. [Kampmann, Beate] MRC Unit, Vaccinol Theme, Serrekunda, Gambia. [Mandalakas, Anna; Starke, Jeffrey R.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Marais, Ben J.] Marie Bashir Inst Infect Dis & Biosecur, Westmead, NSW, Australia. [Marais, Ben J.] Sydney Emerging Infect Dis & Biosecur Inst, Westmead, NSW, Australia. [Marais, Ben J.] Childrens Hosp, Westmead, NSW, Australia. [Marais, Ben J.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. [Zar, Heather J.] Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, MRC Unit Child & Adolescent Hlth, ZA-7700 Rondebosch, South Africa. RP Graham, SM (reprint author), Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Ctr Int Child Hlth, Flemington Rd, Parkville, Vic 3052, Australia. EM steve.graham@rch.org.au OI Cuevas, Luis E./0000-0002-6581-0587; Kampmann, Beate/0000-0002-6546-4709 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN272200800014C] FX This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (contract number HHSN272200800014C). NR 35 TC 7 Z9 7 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 OCT 15 PY 2015 VL 61 SU 3 BP S179 EP S187 DI 10.1093/cid/civ581 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900012 PM 26409281 ER PT J AU Hamilton, CD Swaminathan, S Christopher, DJ Ellner, J Gupta, A Sterling, TR Rolla, V Srinivasan, S Karyana, M Siddiqui, S Stoszek, SK Kim, P AF Hamilton, Carol D. Swaminathan, Soumya Christopher, Devasahayam J. Ellner, Jerrold Gupta, Amita Sterling, Timothy R. Rolla, Valeria Srinivasan, Sudha Karyana, Muhammad Siddiqui, Sophia Stoszek, Sonia K. Kim, Peter TI RePORT International: Advancing Tuberculosis Biomarker Research Through Global Collaboration SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; biological markers; biological specimen banks; prospective studies; specimen handling ID HIV; RIFAPENTINE; CHALLENGES; INFECTION AB Progress in tuberculosis clinical research is hampered by a lack of reliable biomarkers that predict progression from latent to active tuberculosis, and subsequent cure, relapse, or failure. Regional Prospective Observational Research in Tuberculosis (RePORT) International represents a consortium of regional cohorts (RePORT India, RePORT Brazil, and RePORT Indonesia) that are linked through the implementation of a Common Protocol for data and specimen collection, and are poised to address this critical research need. Each RePORT network is designed to support local, in-country tuberculosis-specific data and specimen biorepositories, and associated research. Taken together, the expected results include greater global clinical research capacity in high-burden settings, and increased local access to quality data and specimens for members of each network and their domestic and international collaborators. Additional networks are expected to be added, helping to spur tuberculosis treatment and prevention research around the world. C1 [Hamilton, Carol D.] Global Hlth Populat & Nutr, Sci Affairs, FHI 360, Durham, NC 27701 USA. [Hamilton, Carol D.] Duke Univ, Sch Med, Dept Med, Div Infect Dis, Durham, NC 27706 USA. [Swaminathan, Soumya] Natl Inst Res TB, Dept Clin Res, Madras, Tamil Nadu, India. [Swaminathan, Soumya] Natl Inst Res TB, Dept Clin Res, Pune, Maharashtra, India. [Christopher, Devasahayam J.] Christian Med Coll & Hosp, Pulm Med, Vellore, Tamil Nadu, India. [Ellner, Jerrold] Boston Univ, Sch Med, Boston, MA 02215 USA. [Gupta, Amita] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sterling, Timothy R.] Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37235 USA. [Rolla, Valeria] Fiocruz MS, Natl Inst Infect Dis Evandro Chagas, BR-21045900 Rio De Janeiro, Brazil. [Srinivasan, Sudha; Kim, Peter] NIAID, Div AIDS, NIH, Rockville, MD USA. [Karyana, Muhammad; Siddiqui, Sophia] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Rockville, MD USA. [Stoszek, Sonia K.] Westat Corp, Hlth Studies Sect, Rockville, MD USA. [Karyana, Muhammad] Indonesia Minist Hlth, Natl Inst Res & Dev, Jakarta, Indonesia. RP Hamilton, CD (reprint author), Global Hlth Populat & Nutr, FHI 360, 359 Blackwell St, Durham, NC 27701 USA. EM chamilton@fhi360.org FU US Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services; Indian Department of Biotechnology, the Ministry of Science and Technology; Indian Council of Medical Research; US Office of AIDS Research; US NIAID; Brazil's Ministry of Health and Department of Science and Technology; Indonesia National Institute of Health Research and Development FX For the efforts of Westat and its subcontract with FHI360, this project has been funded in whole or in part with federal funds from the US Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under the contract "NIAID HIV and Other Infectious Diseases Clinical Research Support Services (CRSS)."; The Regional Prospective Observational Research in Tuberculosis (RePORT) India work is supported by the Indian Department of Biotechnology, the Ministry of Science and Technology, and the Indian Council of Medical Research, with cofunding by the US Office of AIDS Research and the US NIAID. The RePORT Brazil work is supported by Brazil's Ministry of Health and Department of Science and Technology, with cofunding by the US Office of AIDS Research and the US NIAID. The RePORT Indonesia work is supported by the Indonesia National Institute of Health Research and Development and the US NIAID. NR 9 TC 4 Z9 4 U1 0 U2 7 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 OCT 15 PY 2015 VL 61 SU 3 BP S155 EP S159 DI 10.1093/cid/civ611 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900008 PM 26409277 ER PT J AU Mahon, RN Hafner, R AF Mahon, Robert N. Hafner, Richard TI Immune Cell Regulatory Pathways Unexplored as Host-Directed Therapeutic Targets for Mycobacterium tuberculosis: An Opportunity to Apply Precision Medicine Innovations to Infectious Diseases SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; host-directed therapy; precision medicine; immunometabolism; signaling pathways ID ENDOPLASMIC-RETICULUM STRESS; ADJUVANT-INDUCED ARTHRITIS; TYPE-2 DIABETES-MELLITUS; ALPHA-INDUCED APOPTOSIS; SALT-INDUCIBLE KINASES; OXIDATIVE STRESS; VITAMIN-D; TNF-ALPHA; KAPPA-B; POLY(ADP-RIBOSE) POLYMERASE AB The lack of novel antimicrobial drugs in development for tuberculosis treatment has provided an impetus for the discovery of adjunctive host-directed therapies (HDTs). Several promising HDT candidates are being evaluated, but major advancement of tuberculosis HDTs will require understanding of the master or "core" cell signaling pathways that control intersecting immunologic and metabolic regulatory mechanisms, collectively described as "immunometabolism." Core regulatory pathways conserved in all eukaryotic cells include poly (ADP-ribose) polymerases (PARPs), sirtuins, AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR) signaling. Critical interactions of these signaling pathways with each other and their roles as master regulators of immunometabolic functions will be addressed, as well as how Mycobacterium tuberculosis is already known to influence various other cell signaling pathways interacting with them. Knowledge of these essential mechanisms of cell function regulation has led to breakthrough targeted treatment advances for many diseases, most prominently in oncology. Leveraging these exciting advances in precision medicine for the development of innovative next-generation HDTs may lead to entirely new paradigms for treatment and prevention of tuberculosis and other infectious diseases. C1 [Mahon, Robert N.] Adv Mil Med Inc, Henry M Jackson Fdn, Div AIDS, Bethesda, MD 20892 USA. [Mahon, Robert N.] NIAID, NIH, Bethesda, MD 20892 USA. [Hafner, Richard] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Mahon, RN (reprint author), NIAID, Div Aids, NIH, 5601 Fishers Lane,Rm 9E30, Bethesda, MD 20892 USA. EM rhafner@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); US Department of Health and Human Services [HHSN272200800014C] FX This project was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), US Department of Health and Human Services (contract number HHSN272200800014C). NR 209 TC 7 Z9 7 U1 6 U2 16 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 OCT 15 PY 2015 VL 61 SU 3 BP S200 EP S216 DI 10.1093/cid/civ621 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900014 PM 26409283 ER PT J AU Nicol, MP Gnanashanmugam, D Browning, R Click, ES Cuevas, LE Detjen, A Graham, SM Levin, M Makhene, M Nahid, P Perez-Velez, CM Reither, K Song, R Spiegel, HML Worrell, C Zar, HJ Walzl, G AF Nicol, Mark Patrick Gnanashanmugam, Devasena Browning, Renee Click, Eleanor S. Cuevas, Luis E. Detjen, Anne Graham, Steve M. Levin, Michael Makhene, Mamodikoe Nahid, Payam Perez-Velez, Carlos M. Reither, Klaus Song, Rinn Spiegel, Hans M. L. Worrell, Carol Zar, Heather J. Walzl, Gerhard TI A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; children; diagnosis; biomarker; blueprint ID XPERT MTB/RIF ASSAY; PULMONARY TUBERCULOSIS; INTRATHORACIC TUBERCULOSIS; CHILDHOOD TUBERCULOSIS; RAPID DIAGNOSIS; STOOL SAMPLES; CHILDREN; AFRICA; URINE; DNA AB Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area. C1 [Nicol, Mark Patrick] Univ Cape Town, Div Med Microbiol, ZA-7700 Rondebosch, South Africa. [Nicol, Mark Patrick] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. [Nicol, Mark Patrick] Natl Hlth Lab Serv, Cape Town, South Africa. [Gnanashanmugam, Devasena; Browning, Renee; Makhene, Mamodikoe; Worrell, Carol] NIAID, Bethesda, MD 20892 USA. [Click, Eleanor S.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Cuevas, Luis E.] Univ Liverpool Liverpool Sch Trop Med, Dept Clin Sci, Liverpool, Merseyside, England. [Detjen, Anne; Graham, Steve M.] Int Union TB & Lung Dis, Paris, France. [Graham, Steve M.] Univ Melbourne, Ctr Int Child Hlth, Melbourne, Vic, Australia. [Graham, Steve M.] Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia. [Graham, Steve M.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Graham, Steve M.] Burnet Inst, Melbourne, Vic, Australia. [Levin, Michael] Univ London Imperial Coll Sci Technol & Med, Dept Pediat, London, England. [Nahid, Payam] Univ Calif San Francisco, Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Perez-Velez, Carlos M.] Univ Arizona, Banner Univ, Coll Med, Div Infect Dis,Med Ctr Phoenix, Tucson, AZ 85721 USA. [Reither, Klaus] Univ Basel, Swiss Trop & Publ Hlth Inst, CH-4003 Basel, Switzerland. [Song, Rinn] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Song, Rinn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Spiegel, Hans M. L.] NIAID, HJF DAIDS, Div Henry M Jackson Fdn, Adv Mil Med Inc,NIH, Bethesda, MD 20892 USA. [Zar, Heather J.] Univ Cape Town, Red Cross Childrens Hosp, Dept Paediat & Child Hlth, ZA-7700 Rondebosch, South Africa. [Zar, Heather J.] Univ Cape Town, Med Res Council, Unit Child & Adolescent Hlth, ZA-7700 Rondebosch, South Africa. [Walzl, Gerhard] Univ Stellenbosch, Dept Sci & Technol, ZA-7600 Stellenbosch, South Africa. [Walzl, Gerhard] Univ Stellenbosch, Ctr Excellence Biomed TB Res, Natl Res Fdn,Div Mol Biol & Human Genet, Med Res Council,Ctr TB Res,Fac Med & Hlth Sci, ZA-7600 Stellenbosch, South Africa. RP Nicol, MP (reprint author), Fac Hlth Sci, Anzio Rd, ZA-7925 Cape Town, South Africa. EM mark.nicol@uct.ac.za OI Nicol, Mark/0000-0002-1366-4805; Walzl, Gerhard/0000-0003-2487-125X; Cuevas, Luis E./0000-0002-6581-0587 FU NIAID/NIH; Eunice Kennedy Shriver NICHD; US Department of Health and Human Services [HHSN272200800014C] FX This work was supported by NIAID/NIH and the Eunice Kennedy Shriver NICHD. This project has also been supported in part with federal funds from the NIAID/NIH, US Department of Health and Human Services (contract no. HHSN272200800014C). NR 30 TC 4 Z9 4 U1 2 U2 3 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 OCT 15 PY 2015 VL 61 SU 3 BP S164 EP S172 DI 10.1093/cid/civ613 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900010 PM 26409279 ER PT J AU Schito, M Maeurer, M Kim, P Hanna, D Zumla, A AF Schito, Marco Maeurer, Markus Kim, Peter Hanna, Debra Zumla, Alimuddin TI Translating the Tuberculosis Research Agenda: Much Accomplished, but Much More to Be Done SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; research; drug resistance; new treatment regimens; resource-limited settings ID DRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; HIV VACCINE; AFRICA; EVOLUTION; MUTATION; AUTOPSY; BURDEN AB Despite the availability of effective diagnostics and curative treatment regimens for tuberculosis, millions of people die each year of this disease. The steady global increase in the number of tuberculosis cases caused by multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis are of major concern, especially in light of the thin tuberculosis drug pipeline. New tuberculosis drugs are undergoing clinical evaluation, and renewed hope comes from fresh approaches to improve treatment outcomes using a range of adjunct host-directed cellular and repurposed drug therapies. Current efforts in developing second-generation and new rapid point-of-care diagnostic assays take advantage of recent genetic and molecular advances. Slow progress in the development of prophylactic and therapeutic vaccines requires increased funding for basic as well as translational research. Although major challenges remain, these can be overcome by cementing our resolve, raising advocacy, bolstering global funder investments, and leveraging more effective collaborations through equitable public-private partnerships. C1 [Schito, Marco; Hanna, Debra] Crit Path Inst, Crit Path TB Drug Regimens CPTR, Tucson, AZ 85718 USA. [Maeurer, Markus] Karolinska Inst, Dept Lab Med, Therapeut Immunol Div, Stockholm, Sweden. [Maeurer, Markus] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Kim, Peter] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Zumla, Alimuddin] UCL, Div Infect & Immun, London, England. [Zumla, Alimuddin] UCL, Ctr Clin Microbiol, London, England. [Zumla, Alimuddin] Univ Coll Hosp NHS Trust, Biomed Res Ctr, London, England. RP Schito, M (reprint author), Crit Path Inst, Crit Path TB Drug Regimens CPTR, 1730 River Rd,Ste 200, Tucson, AZ 85718 USA. EM mschito@c-path.org OI Zumla, Alimuddin/0000-0002-5111-5735 FU Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This article appears as part of the supplement "Advances in Tuberculosis Research: A Blueprint for Opportunities." This article was sponsored by the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 40 TC 6 Z9 6 U1 0 U2 11 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 OCT 15 PY 2015 VL 61 SU 3 BP S95 EP S101 DI 10.1093/cid/civ608 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900001 PM 26409286 ER PT J AU Schito, M Migliori, GB Fletcher, HA McNerney, R Centis, R D'Ambrosio, L Bates, M Kibiki, G Kapata, N Corrah, T Bomanji, J Vilaplana, C Johnson, D Mwaba, P Maeurer, M Zumla, A AF Schito, Marco Migliori, Giovanni Battista Fletcher, Helen A. McNerney, Ruth Centis, Rosella D'Ambrosio, Lia Bates, Matthew Kibiki, Gibson Kapata, Nathan Corrah, Tumena Bomanji, Jamshed Vilaplana, Cris Johnson, Daniel Mwaba, Peter Maeurer, Markus Zumla, Alimuddin TI Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE tuberculosis; diagnostics; drugs; vaccines; management ID MULTIDRUG-RESISTANT TUBERCULOSIS; CROSS-PRIMING AMPLIFICATION; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE PHASE TREATMENT; AFRICAN POUCHED RATS; SUB-SAHARAN AFRICA; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; BACTERICIDAL ACTIVITY; RADIOIODINATED DPA-713 AB Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required. C1 [Schito, Marco] Crit Path Inst, Crit Path TB Drug Regimens, Tucson, AZ 85718 USA. [Migliori, Giovanni Battista; Centis, Rosella; D'Ambrosio, Lia] Fdn S Maugeri, Care & Res Inst, World Hlth Org Collaborating Ctr TB & Lung Dis, Tradate, Italy. [Fletcher, Helen A.] London Sch Hyg & Trop Med, Dept Immunol & Infect, Brighton, E Sussex, England. [McNerney, Ruth] TB Alert, Brighton, E Sussex, England. [Bates, Matthew; Kapata, Nathan; Mwaba, Peter] Univ Zambia, Univ Teaching Hosp, Univ Coll London Med Sch Res & Training Project, Lusaka, Zambia. [Kibiki, Gibson] Kilimanjaro Clin Res Inst, Moshi, Tanzania. [Corrah, Tumena] Northwick Pk Hosp & Clin Res Ctr, Dept Infect Dis & Trop Med, London, England. [Bomanji, Jamshed] Univ Coll London Hosp NHS Fdn Trust, Dept Nucl Imaging, London, England. [Vilaplana, Cris] Fdn Inst Invest Ciencies Salut German Trias i Puj, Unitat TB Expt, Barcelona, Spain. [Johnson, Daniel] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Maeurer, Markus] Karolinska Inst, Dept Lab Med & Microbiol, Therapeut Immunol, Stockholm, Sweden. [Maeurer, Markus] Karolinska Inst, Dept Tumour & Cell Biol, Stockholm, Sweden. [Zumla, Alimuddin] UCL, Div Infect & Immun, London WC1E 6BT, England. [Zumla, Alimuddin] UCL Hosp NHS Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England. RP Schito, M (reprint author), Crit Path Inst, Crit Path TB Drug Regimens, 1730 E River Rd,Ste 200, Tucson, AZ 85718 USA. EM mschito@c-path.org OI Zumla, Alimuddin/0000-0002-5111-5735; Migliori, Giovanni Battista/0000-0002-2597-574X; Vilaplana, Cristina/0000-0002-2808-7270; Fletcher, Helen/0000-0002-0435-1006 FU Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This article appears as part of the supplement "Advances in Tuberculosis Research: A Blueprint for Opportunities." This article was sponsored by the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 100 TC 9 Z9 9 U1 2 U2 24 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 OCT 15 PY 2015 VL 61 SU 3 BP S102 EP S118 DI 10.1093/cid/civ609 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900002 PM 26409271 ER PT J AU Starks, AM Aviles, E Cirillo, DM Denkinger, CM Dolinger, DL Emerson, C Gallarda, J Hanna, D Kim, PS Liwski, R Miotto, P Schito, M Zignol, M AF Starks, Angela M. Aviles, Enrique Cirillo, Daniela M. Denkinger, Claudia M. Dolinger, David L. Emerson, Claudia Gallarda, Jim Hanna, Debra Kim, Peter S. Liwski, Richard Miotto, Paolo Schito, Marco Zignol, Matteo TI Collaborative Effort for a Centralized Worldwide Tuberculosis Relational Sequencing Data Platform SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Mycobacterium tuberculosis; drug resistance; database ID DRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS AB Continued progress in addressing challenges associated with detection and management of tuberculosis requires new diagnostic tools. These tools must be able to provide rapid and accurate information for detecting resistance to guide selection of the treatment regimen for each patient. To achieve this goal, globally representative genotypic, phenotypic, and clinical data are needed in a standardized and curated data platform. A global partnership of academic institutions, public health agencies, and nongovernmental organizations has been established to develop a tuberculosis relational sequencing data platform (ReSeqTB) that seeks to increase understanding of the genetic basis of resistance by correlating molecular data with results from drug susceptibility testing and, optimally, associated patient outcomes. These data will inform development of new diagnostics, facilitate clinical decision making, and improve surveillance for drug resistance. ReSeqTB offers an opportunity for collaboration to achieve improved patient outcomes and to advance efforts to prevent and control this devastating disease. C1 [Starks, Angela M.] Ctr Dis Control & Prevent, Div TB Eliminat, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30329 USA. [Aviles, Enrique; Hanna, Debra; Liwski, Richard; Schito, Marco] Crit Path Inst, Tucson, AZ USA. [Cirillo, Daniela M.; Miotto, Paolo] Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, I-20132 Milan, Italy. [Denkinger, Claudia M.; Dolinger, David L.] Fdn Innovat New Diagnost, Geneva, Switzerland. [Emerson, Claudia] St Michaels Hosp, Li Ka Shing Knowledge Inst, Ctr Eth Social & Cultural Risk, Toronto, ON M5B 1W8, Canada. [Gallarda, Jim] Bill & Melinda Gates Fdn, Seattle, WA USA. [Kim, Peter S.] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Zignol, Matteo] WHO, TB Monitoring & Evaluat, Global TB Programme, CH-1211 Geneva, Switzerland. RP Starks, AM (reprint author), Ctr Dis Control & Prevent, Div TB Eliminat, 1600 Clifton Rd NE,Bldg 17,Rm 4040,MS F08, Atlanta, GA 30329 USA. EM astarks@cdc.gov RI Miotto, Paolo/E-3940-2017 OI Miotto, Paolo/0000-0003-4610-2427 FU Bill & Melinda Gates Foundation [OPP1115209]; Critical Path Institute [OPP1115887] FX This work was supported by the Bill & Melinda Gates Foundation to Foundation for Innovative New Diagnostics (FIND) (grant number OPP1115209) and the Critical Path Institute (grant number OPP1115887). NR 27 TC 9 Z9 9 U1 0 U2 0 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 OCT 15 PY 2015 VL 61 SU 3 BP S141 EP S146 DI 10.1093/cid/civ610 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6WG UT WOS:000362952900006 PM 26409275 ER PT J AU Booth, BJ Ward, MH Turyk, ME Stayner, LT AF Booth, Benjamin J. Ward, Mary H. Turyk, Mary E. Stayner, Leslie T. TI Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study SO ENVIRONMENTAL HEALTH LA English DT Article DE Childhood cancer; Environmental epidemiology; Crop density; Pesticides ID BRAIN-TUMORS; PESTICIDE EXPOSURE; LEUKEMIA; COMMUNITY; CHILDREN; CALIFORNIA; HERBICIDES; PROXIMITY; FARM AB Background: There is limited evidence for an association between agricultural pesticide exposure and certain types of childhood cancers. Numerous studies have evaluated exposure to pesticides and childhood cancer and found positive associations. However, few studies have examined the density of agricultural land use as a surrogate for residential exposure to agricultural pesticides and results are mixed. We examined the association of county level agricultural land use and the incidence of specific childhood cancers. Methods: We linked county-level agricultural census data (2002 and 2007) and cancer incidence data for children ages 0-4 diagnosed between 2004 and 2008 from cancer registries in six Midwestern states. Crop density (percent of county area that was harvested) was estimated for total agricultural land, barley, dry beans, corn, hay, oats, sorghum, soybeans, sugar beets, and wheat. Rate ratios and 95 % confidence intervals were estimated using generalized estimating equation Poisson regression models and were adjusted for race, sex, year of diagnosis, median household income, education, and population density. Results: We found statistically significant exposure-response relationships for dry beans and total leukemias (RR per 1 % increase in crop density = 1.09, 95 % CI = 1.03-1.14) and acute lymphoid leukemias (ALL) (RR = 1.10, 95 % CI = 1.04-1.16); oats and acute myeloid leukemias (AML) (RR = 2.03, 95 % CI = 1.25, 3.28); and sugar beets and total leukemias (RR = 1.11, 95 % CI = 1.04, 1.19) and ALL (RR = 1.11, 95 % CI = 1.02, 1.21). State-level analyses revealed some additional positive associations for total leukemia and CNS tumors and differences among states for several crop density-cancer associations. However, some of these analyses were limited by low crop prevalence and low cancer incidence. Conclusions: Publicly available data sources not originally intended to be used for health research can be useful for generating hypotheses about environmental exposures and health outcomes. The associations observed in this study need to be confirmed by analytic epidemiologic studies using individual level exposure data and accounting for potential confounders that could not be taken into account in this ecologic study. C1 [Booth, Benjamin J.; Turyk, Mary E.; Stayner, Leslie T.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60607 USA. [Booth, Benjamin J.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Booth, BJ (reprint author), Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60607 USA. EM benjamin.booth@nih.gov FU US CDC Environmental Public Health Tracking Program [200-2010-37442]; intramural research program of the National Cancer Institute FX This work was financially supported by the US CDC Environmental Public Health Tracking Program Contract #200-2010-37442. This research was partially supported by the intramural research program of the National Cancer Institute. NR 40 TC 3 Z9 3 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD OCT 15 PY 2015 VL 14 AR 82 DI 10.1186/s12940-015-0070-3 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA CT5QO UT WOS:000362865500001 PM 26467084 ER PT J AU Kumaran, R Cookson, MR AF Kumaran, Ravindran Cookson, Mark R. TI Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease SO HUMAN MOLECULAR GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; REPEAT KINASE 2; AUTOSOMAL-DOMINANT PARKINSONISM; EXTRACELLULAR ALPHA-SYNUCLEIN; 1 MUTATION CARRIERS; P-TYPE ATPASE; MICROGLIAL ACTIVATION; TAU PHOSPHORYLATION; RISK-FACTORS; MOUSE MODEL AB In the past few years, there have been a large number of genes identified that contribute to the lifetime risk of Parkinson's disease (PD). Some genes follow a Mendelian inheritance pattern, but others are risk factors for apparently sporadic PD. Here, we will focus on those genes nominated by genome-wide association studies (GWAS) in sporadic PD, with a particular emphasis on genes that overlap between familial and sporadic disease such as those encoding a-synuclein (SNCA), tau (MAPT), and leucine-rich repeat kinase 2 (LRRK2). We will advance the view that there are likely relationships between these genes that map not only to neuronal processes, but also to neuroinflammation. We will particularly discuss evidence for a role of PD proteins in microglial activation and regulation of the autophagy-lysosome system that is dependent on microtubule transport in neurons. Thus, there are at least two non-mutually exclusive pathways that include both non-cell-autonomous and cell-autonomous mechanisms in the PD brain. Collectively, these data have highlighted the amount of progress made in understanding PD and suggest ways forward to further dissect this disorder. C1 [Kumaran, Ravindran; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural Research Program of the NIH, National Institute of Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute of Aging. NR 132 TC 13 Z9 13 U1 3 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2015 VL 24 SI 1 BP R32 EP R44 DI 10.1093/hmg/ddv236 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CT7VC UT WOS:000363021600005 PM 26101198 ER PT J AU Claudio, E Tassi, I Wang, HS Tang, WH Ha, HL Siebenlist, U AF Claudio, Estefania Tassi, Ilaria Wang, Hongshan Tang, Wanhu Ha, Hye-lin Siebenlist, Ulrich TI Cutting Edge: IL-25 Targets Dendritic Cells To Attract IL-9-Producing T Cells in Acute Allergic Lung Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE LYMPHOID-CELLS; IMMUNITY; ASTHMA; EXPRESSION; CYTOKINES; PATHOLOGY AB Asthma is a common inflammatory disease of airways that is often associated with type 2 responses triggered by allergens, such as house dust mites (HDMs). IL-25 is a key mucosal cytokine that may be produced by stressed epithelial cells; it rapidly activates type 2 innate lymphoid cells to produce IL-13 and IL-5. When administered directly into lungs, IL-25 induces acute inflammation. However, the mechanisms underlying IL-25-initiated inflammation and the roles of this cytokine in the context of HDM-induced allergic inflammation are not fully understood. We show in this article that lung-resident conventional dendritic cells were direct targets of IL-25. IL-25-stimulated dendritic cells rapidly induced mediators, such as the chemokine CCL17, which, in turn, attracted IL-9-producing T cells. Importantly, these mechanisms also operated during HDM-induced allergic lung inflammation. C1 [Claudio, Estefania; Tassi, Ilaria; Wang, Hongshan; Tang, Wanhu; Ha, Hye-lin; Siebenlist, Ulrich] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIH, Bldg 10,Room 11B115A, Bethesda, MD 20892 USA. EM us3n@nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 23 TC 2 Z9 3 U1 1 U2 6 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 OCT 15 PY 2015 VL 195 IS 8 BP 3525 EP 3529 DI 10.4049/jimmunol.1500436 PG 5 WC Immunology SC Immunology GA CT7BM UT WOS:000362968100007 PM 26371249 ER PT J AU Romano, A Doria, NA Mendez, J Sacks, DL Peters, NC AF Romano, Audrey Doria, Nicole A. Mendez, Jonatan Sacks, David L. Peters, Nathan C. TI Cutaneous Infection with Leishmania major Mediates Heterologous Protection against Visceral Infection with Leishmania infantum SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; CROSS-IMMUNITY; DONOVANI INFECTION; EASTERN SUDAN; MEMORY CD4(+); C57BL/6 MICE; SAND FLIES; SRI-LANKA; MEXICANA; PARASITES AB Visceral leishmaniasis (VL) is a fatal disease of the internal organs caused by the eukaryotic parasite Leishmania. Control of VL would best be achieved through vaccination. However, this has proven to be difficult partly because the correlates of protective immunity are not fully understood. In contrast, protective immunity against nonfatal cutaneous leishmaniasis (CL) is well defined and mediated by rapidly recruited, IFN-gamma-producing Ly6C(+)CD4(+) T cells at the dermal challenge site. Protection against CL is best achieved by prior infection or live vaccination with Leishmania major, termed leishmanization. A long-standing question is whether prior CL or leishmanization can protect against VL. Employing an intradermal challenge model in mice, we report that cutaneous infection with Leishmania major provides heterologous protection against visceral infection with Leishmania infantum. Protection was associated with a robust CD4(+) T cell response at the dermal challenge site and in the viscera. In vivo labeling of circulating cells revealed that increased frequencies of IFN-gamma(+)CD4(+) T cells at sites of infection are due to recruitment or retention of cells in the tissue, rather than increased numbers of cells trapped in the vasculature. Shortly after challenge, IFN-gamma-producing cells were highly enriched for Ly6C(+)T-bet(+) cells in the viscera. Surprisingly, this heterologous immunity was superior to homologous immunity mediated by prior infection with L. infantum. Our observations demonstrate a common mechanism of protection against different clinical forms of leishmaniasis. The efficacy of leishmanization against VL may warrant the introduction of the practice in VL endemic areas or during outbreaks of disease. C1 [Romano, Audrey; Doria, Nicole A.; Mendez, Jonatan; Sacks, David L.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Peters, Nathan C.] Univ Calgary, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Snyder Inst Chron Dis, Calgary, AB T2N 4Z6, Canada. RP Peters, NC (reprint author), Univ Calgary, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Snyder Inst Chron Dis, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada. EM ncpeters@ucalgary.ca FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; University of Calgary start-up funds FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and by University of Calgary start-up funds (to N.C.P.). NR 73 TC 3 Z9 3 U1 2 U2 7 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 OCT 15 PY 2015 VL 195 IS 8 BP 3816 EP 3827 DI 10.4049/jimmunol.1500752 PG 12 WC Immunology SC Immunology GA CT7BM UT WOS:000362968100035 PM 26371247 ER PT J AU Shalaeva, DN Galperin, MY Mulkidjanian, AY AF Shalaeva, Daria N. Galperin, Michael Y. Mulkidjanian, Armen Y. TI Eukaryotic G protein-coupled receptors as descendants of prokaryotic sodium-translocating rhodopsins SO BIOLOGY DIRECT LA English DT Article DE Vision; Bacteriorhodopsin; Halorhodopsin; Sensory rhodopsin; Proteorhodopsin; Opioid receptor; GPCR; Evolution; Signal transduction; Chemoreceptor ID RESOLUTION CRYSTAL-STRUCTURE; DRIVEN NA+ PUMP; RETINAL PROTEINS; HELIX-F; BACTERIORHODOPSIN PHOTOCYCLE; RETINYLIDENE PROTEINS; COMPARATIVE GENOMICS; STRUCTURAL INSIGHTS; ANGSTROM RESOLUTION; MICROBIAL RHODOPSIN AB Microbial rhodopsins and G-protein coupled receptors (GPCRs, which include animal rhodopsins) are two distinct (super) families of heptahelical (7TM) membrane proteins that share obvious structural similarities but no significant sequence similarity. Comparison of the recently solved high-resolution structures of the sodium-translocating bacterial rhodopsin and various Na+-binding GPCRs revealed striking similarity of their sodium-binding sites. This similarity allowed us to construct a structure-guided sequence alignment for the two (super)families, which highlighted their evolutionary relatedness. Our analysis supports a common underlying molecular mechanism for both families that involves a highly conserved aromatic residue playing a pivotal role in rotation of the 6th transmembrane helix. C1 [Shalaeva, Daria N.; Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Shalaeva, Daria N.; Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow 119992, Russia. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia. [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de RI Mulkidjanian, Armen/J-8086-2013 OI Mulkidjanian, Armen/0000-0001-5844-3064 FU Federal Ministry of Education and Research of Germany; German Academic Exchange Service; Russian Science Foundation [14-14-00592, 14-50-00029]; NIH Intramural Research Program at the National Library of Medicine; Osnabrueck University FX We gratefully acknowledge helpful discussions with Professors A.V. Bogachev, L.S. Brown, V.P. Skulachev, H.-J. Steinhoff and G.Vriend and their interest in this work. This work was supported by the Osnabrueck University, Federal Ministry of Education and Research of Germany (AYM), a fellowship from the German Academic Exchange Service (DNS), grants from the Russian Science Foundation (14-14-00592, structural analysis of GPCRs, 14-50-00029 sequence and evolutionary analyses of the 7TM-receptors) and the NIH Intramural Research Program at the National Library of Medicine (MYG). NR 100 TC 2 Z9 3 U1 3 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD OCT 15 PY 2015 VL 10 AR 63 DI 10.1186/s13062-015-0091-4 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CT4UN UT WOS:000362802900001 PM 26472483 ER PT J AU Germain, RN AF Germain, Ronald N. TI William E. Paul (1936-2015) OBITUARY SO NATURE LA English DT Biographical-Item C1 [Germain, Ronald N.] US Natl Inst Allergy & Infect Dis, Lab Syst Biol, NIH, Bethesda, MD 20850 USA. [Germain, Ronald N.] Immunol Lab, New York, NY USA. RP Germain, RN (reprint author), US Natl Inst Allergy & Infect Dis, Lab Syst Biol, NIH, Bethesda, MD 20850 USA. EM rgermain@niaid.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 15 PY 2015 VL 526 IS 7573 BP 324 EP 324 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT3TQ UT WOS:000362730200027 PM 26469035 ER PT J AU Hung, CC Yen, CC Ciuchta, JL Papoti, D Bock, NA Leopold, DA Silva, AC AF Hung, Chia-Chun Yen, Cecil C. Ciuchta, Jennifer L. Papoti, Daniel Bock, Nicholas A. Leopold, David A. Silva, Afonso C. TI Functional MRI of visual responses in the awake, behaving marmoset SO NEUROIMAGE LA English DT Article DE Marmoset; fMRI; Vision; Visual system; Primate ID LATERAL GENICULATE-NUCLEUS; MACAQUE CEREBRAL-CORTEX; CALLITHRIX-JACCHUS; COMMON MARMOSET; NEUROSCIENCE RESEARCH; SUPERIOR COLLICULUS; OCCIPITAL COMPLEX; RECEPTIVE-FIELDS; STRIATE CORTEX; MODEL SYSTEM AB The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species' cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500 mu m in-plane resolution in a 30 cm horizontal bore at 7 T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution. Published by Elsevier C1 [Hung, Chia-Chun; Yen, Cecil C.; Ciuchta, Jennifer L.; Papoti, Daniel; Silva, Afonso C.] NINDS, NIH, Lab Funct & Mol Imaging, Cerebral Microcirculat Sect, Bethesda, MD 20892 USA. [Hung, Chia-Chun; Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20892 USA. [Bock, Nicholas A.] McMaster Univ, Med Phys & Appl Radiat Sci, Hamilton, ON L8S 4K1, Canada. [Leopold, David A.] NEI, NINDS, NIMH, Neurophysiol Imaging Facil, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), NINDS, NIH, Lab Funct & Mol Imaging, Cerebral Microcirculat Sect, 49 Convent Dr MSC 1065,Bldg 49 Room 3A72, Bethesda, MD 20892 USA. EM SilvaA@ninds.nih.gov RI Yen, Cecil/C-2212-2009; OI Yen, Cecil/0000-0002-1519-9791; Leopold, David/0000-0002-1345-6360 FU Intramural Research Programs of the National Institute of Neurological Disorders and Stroke; National Institute of Mental Health FX This research was supported by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health. The authors want to thank Julian Day-Cooney and Xianfeng (Lisa) Zhang for technical assistance. NR 69 TC 4 Z9 4 U1 4 U2 23 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 OCT 15 PY 2015 VL 120 BP 1 EP 11 DI 10.1016/j.neuroimage.2015.06.090 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CS4DK UT WOS:000362025000001 PM 26149609 ER PT J AU Conforto, A Anjos, S Sterr, A de Andrade, K Cohen, L AF Conforto, A. Anjos, S. Sterr, A. de Andrade, K. Cohen, L. TI Translational neurorehabilitation in the third world SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Conforto, A.; Anjos, S.; de Andrade, K.] Univ Sao Paulo, Hosp Clin, Neurol, Sao Paulo, Brazil. [Conforto, A.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. [Sterr, A.] Univ Surrey, Sch Psychol, Guildford, Surrey, England. [Cohen, L.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1576 BP E458 EP E458 DI 10.1016/j.jns.2015.09.150 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802403 ER PT J AU Dhawan, PS Goodman, BP Toro, C Dyck, PJB Giannini, C Bosch, EP AF Dhawan, P. S. Goodman, B. P. Toro, C. Dyck, P. J. B. Giannini, C. Bosch, E. P. TI Fosmn Syndrome: a Tdp-43 proteinopathy? SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Dhawan, P. S.; Goodman, B. P.; Bosch, E. P.] Mayo Clin Arizona, Neurol, Scottsdale, AZ USA. [Toro, C.] NIH, Neurol, Bldg 10, Bethesda, MD 20892 USA. [Dyck, P. J. B.; Giannini, C.] Mayo Clin Rochester, Neurol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1124 BP E332 EP E332 DI 10.1016/j.jns.2015.08.1184 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802034 ER PT J AU Hallett, M AF Hallett, M. TI Peripheral nerve injuries SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Hallett, M.] NINDS, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1735 BP E502 EP E502 DI 10.1016/j.jns.2015.09.309 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802561 ER PT J AU Hallett, M AF Hallett, M. TI The Physiology of Will SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Hallett, M.] NINDS, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1682 BP E487 EP E487 DI 10.1016/j.jns.2015.09.256 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802508 ER PT J AU Silberberg, D Ewart-Pierce, E Sturke, R AF Silberberg, D. Ewart-Pierce, E. Sturke, R. TI A learning collaborative for implementation science in neuroscience SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Silberberg, D.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Ewart-Pierce, E.; Sturke, R.] NIH, Div Int Sci Policy Planning & Evaluat, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1729 BP E500 EP E501 DI 10.1016/j.jns.2015.09.303 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802555 ER PT J AU Theodore, W AF Theodore, W. TI Focal epilepsies refractory to AEDs: Algorithms to identify treatable causes SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 22nd World Congress of Neurology (WCN) CY OCT 31-NOV 05, 2015 CL Santiago, CHILE C1 [Theodore, W.] NINDS, Clin Epilepsy, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2015 VL 357 SU 1 MA 1582 BP E460 EP E460 DI 10.1016/j.jns.2015.09.156 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX8JV UT WOS:000384634802409 ER PT J AU Murphy, G Freedman, ND Michel, A Fan, JH Taylor, PR Pawlita, M Qiao, YL Zhang, H Yu, K Abnet, CC Dawsey, SM AF Murphy, Gwen Freedman, Neal D. Michel, Angelika Fan, Jin-Hu Taylor, Philip R. Pawlita, Michael Qiao, You-Lin Zhang, Han Yu, Kai Abnet, Christian C. Dawsey, Sanford M. TI Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Helicobacter pylori; multiplex serology; gastric cancer; esophageal cancer ID MULTIPLEX SEROLOGY; GENERAL-POPULATION; ATROPHIC GASTRITIS; PROTEINS; LINXIAN; CHINA; SEROPOSITIVITY; ASSOCIATION; ESOPHAGEAL; INFECTION AB Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to 4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta-analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA. What's new? How H. pylori infection cause cancer in one person but remain harmless in another? And more importantly, can they be distinguished ahead of time, and the cancer halted before it begins? These authors showed that people who tested positive for a multiplex of 15 H. pylori antigens were more likely to develop gastric cancer. They then identified 6 individual antigens which increase the risk of gastric cancer. The multiplex assay, then, may be a useful risk-stratification tool in high risk areas. C1 [Murphy, Gwen; Freedman, Neal D.; Taylor, Philip R.; Zhang, Han; Yu, Kai; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Michel, Angelika; Pawlita, Michael] German Canc Res Ctr, Div Genome Modificat & Carcinogenesis, Infect & Canc Program, Heidelberg, Germany. [Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China. RP Murphy, G (reprint author), NCI, Nutr Epidemiol Branch, DCEG, 9609 Med Ctr Dr,Rm 6E314, Bethesda, MD 20892 USA. EM murphygw@mail.nih.gov; qiaoy@cicams.ac.cn RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Zhang, Han/K-2118-2016; Qiao, You-Lin/B-4139-2012; Waterboer, Tim/G-1252-2010; OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843; Zhang, Han/0000-0001-7977-9616; Qiao, You-Lin/0000-0001-6380-0871; Pawlita, Michael/0000-0002-4720-8306 FU Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services FX Grant sponsor: Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services NR 29 TC 2 Z9 2 U1 2 U2 45 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD OCT 15 PY 2015 VL 137 IS 8 BP 1938 EP 1946 DI 10.1002/ijc.29543 PG 9 WC Oncology SC Oncology GA CO7OV UT WOS:000359350600021 PM 25845708 ER PT J AU Lin, SC Brown, RE Shuler, MGH Petersen, CCH Kepecs, A AF Lin, Shih-Chieh Brown, Ritchie E. Shuler, Marshall G. Hussain Petersen, Carl C. H. Kepecs, Adam TI Optogenetic Dissection of the Basal Forebrain Neuromodulatory Control of Cortical Activation, Plasticity, and Cognition SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nucleus basalis; GABAergic; reinforcement; reward timing; cortical state; motivational salience ID PRIMARY VISUAL-CORTEX; DEEP BRAIN-STIMULATION; HIPPOCAMPAL SYNAPTIC PLASTICITY; RECEPTIVE-FIELD PLASTICITY; NUCLEUS BASALIS; CHOLINERGIC NEURONS; GABAERGIC NEURONS; CEREBRAL-CORTEX; BARREL CORTEX; PARVALBUMIN NEURONS AB The basal forebrain (BF) houses major ascending projections to the entire neocortex that have long been implicated in arousal, learning, and attention. The disruption of the BF has been linked with major neurological disorders, such as coma and Alzheimer's disease, as well as in normal cognitive aging. Although it is best known for its cholinergic neurons, the BF is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific BF cell types have led to a renaissance in the study of the BF and are beginning to yield new insights about cell-type-specific circuit mechanisms during behavior. These approaches enable us to determine the behavioral conditions under which cholinergic and noncholinergic BF neurons are activated and how they control cortical processing to influence behavior. Here we discuss recent advances that have expanded our knowledge about this poorly understood brain region and laid the foundation for future cell-type-specific manipulations to modulate arousal, attention, and cortical plasticity in neurological disorders. C1 [Lin, Shih-Chieh] NIA, NIH, Baltimore, MD 21224 USA. [Brown, Ritchie E.] Vet Adm Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Brown, Ritchie E.] Harvard Univ, Sch Med, Brockton, MA 02301 USA. [Shuler, Marshall G. Hussain] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. [Petersen, Carl C. H.] Fed Inst Technol Lausanne, Brain Mind Inst, Lab Sensory Proc, CH-1015 Lausanne, Switzerland. [Kepecs, Adam] Cold Spring Harbor Lab, Neurosci, Cold Spring Harbor, NY 11724 USA. RP Lin, SC (reprint author), NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, 251 Bayview Blvd,Suite 100,9C220, Baltimore, MD 21224 USA. EM shih-chieh.lin@nih.gov OI Lin, Shih-Chieh/0000-0003-3693-5476; Brown, Ritchie/0000-0002-7164-4132 FU Veterans Administration; National Institute on Aging Intramural Research Program; National Institute of Neurological Disorders and Stroke [R01 NS075531, NS088661, R21 NS093000]; National Institute of Mental Health [R01MH039683, MH093665]; National Heart, Lung, and Blood Institute [R01 HL095491]; John Merck Foundation; McKnight Foundation; European Research Council; Swiss National Science Foundation; National Alliance for Research on Schizophrenia and Depression Young Investigator Award FX This research was funded in part by the Veterans Administration, the National Institute on Aging Intramural Research Program, National Institute of Neurological Disorders and Stroke Grants R01 NS075531, NS088661, and R21 NS093000, National Institute of Mental Health Grants R01MH039683 and MH093665, National Heart, Lung, and Blood Institute Grant R01 HL095491, the John Merck and McKnight Foundations, the European Research Council, the Swiss National Science Foundation, and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award. NR 113 TC 9 Z9 9 U1 7 U2 24 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 14 PY 2015 VL 35 IS 41 BP 13896 EP 13903 DI 10.1523/JNEUROSCI.2590-15.2015 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CX9US UT WOS:000366051800010 PM 26468190 ER PT J AU Schu, DJ Zhang, AX Gottesman, S Storz, G AF Schu, Daniel J. Zhang, Aixia Gottesman, Susan Storz, Gisela TI Alternative Hfq-sRNA interaction modes dictate alternative mRNA recognition SO EMBO JOURNAL LA English DT Article DE ChiX; Hfq; MgrR; RyhB ID ESCHERICHIA-COLI HFQ; SMALL REGULATORY RNAS; BINDING SMALL RNAS; SM-LIKE PROTEIN; INTERACTION SURFACES; TARGET RECOGNITION; OUTER-MEMBRANE; RPOS; TRANSLATION; COMPETITION AB Many bacteria use small RNAs (sRNAs) and the RNA chaperone Hfq to regulate mRNA stability and translation. Hfq, a ring-shaped homohexamer, has multiple faces that can bind both sRNAs and their mRNA targets. We find that Hfq has at least two distinct ways in which it interacts with sRNAs; these different binding properties have strong effects on the stability of the sRNA in vivo and the sequence requirements of regulated mRNAs. Class I sRNAs depend on proximal and rim Hfq sites for stability and turn over rapidly. Class II sRNAs are more stable and depend on the proximal and distal Hfq sites for stabilization. Using deletions and chimeras, we find that while Class I sRNAs regulate mRNA targets with previously defined ARN repeats, Class II sRNAs regulate mRNAs carrying UA-rich rim-binding sites. We discuss how these different binding modes may correlate with different roles in the cell, with Class I sRNAs acting as emergency responders and Class II sRNAs acting as silencers. C1 [Schu, Daniel J.; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. [Zhang, Aixia; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. EM gottesms@helix.nih.gov; storzg@mail.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Intramural Research Program of the National Institutes of Health; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; Center for Cancer Research FX We thank N. Majdalani as well as S. Woodson and members of her laboratory for helpful discussions. We thank N. De Lay, T. Updegrove, J. Chen, and other members of our laboratories for their comments on the manuscript. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research and in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 58 TC 22 Z9 22 U1 6 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD OCT 14 PY 2015 VL 34 IS 20 BP 2557 EP 2573 DI 10.15252/embj.201591569 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CW5PN UT WOS:000365048600008 PM 26373314 ER PT J AU Kotal, J Langhansova, H Lieskovska, J Andersen, JF Francischetti, IMB Chavakis, T Kopecky, J Pedra, JHF Kotsyfakis, M Chmelar, J AF Kotal, Jan Langhansova, Helena Lieskovska, Jaroslava Andersen, John F. Francischetti, Ivo M. B. Chavakis, Triantafyllos Kopecky, Jan Pedra, Joao H. F. Kotsyfakis, Michail Chmelar, Jindrich TI Modulation of host immunity by tick saliva SO JOURNAL OF PROTEOMICS LA English DT Review DE Adaptive immunity; Innate immunity; Saliva; Salivary glands; Tick ID IXODES-RICINUS TICKS; CD4(+) T-CELLS; RHIPICEPHALUS BOOPHILUS MICROPLUS; HAEMAPHYSALIS-LONGICORNIS TICKS; CHRONIC ALLERGIC INFLAMMATION; TISSUE-RESIDENT MACROPHAGES; AMBLYOMMA-CAJENNENSE NYMPHS; HISTAMINE-BINDING PROTEINS; ANATOLICUM FEEDING SITES; ANTIGEN-PRESENTING CELLS AB Next generation sequencing and proteomics have helped to comprehensively characterize gene expression in tick salivary glands at both the transcriptome and the proteome level. Functional data are, however, lacking. Given that tick salivary secretions are critical to the success of the tick transmission lifecycle and, as a consequence, for host colonization by the pathogens they spread, we thoroughly review here the literature on the known interactions between tick saliva (or tick salivary gland extracts) and the innate and adaptive vertebrate immune system. The information is intended to serve as a reference for functional characterization of the numerous genes and proteins expressed in tick salivary glands with an ultimate goal to develop novel vector and pathogen control strategies. Significance: We overview all the known interactions of tick saliva with the vertebrate immune system. The provided information is important, given the recent developments in high-throughput transcriptomic and proteomic analysis of gene expression in tick salivary glands, since it may serve as a guideline for the functional characterization of the numerous newly-discovered genes expressed in tick salivary glands. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kotal, Jan; Langhansova, Helena; Lieskovska, Jaroslava; Kopecky, Jan; Chmelar, Jindrich] Univ South Bohemia Ceske Budejovice, Fac Sci, Budweis, Czech Republic. [Kotal, Jan; Kotsyfakis, Michail] Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Lab Genom & Prote Dis Vectors, CZ-37005 Budweis, Czech Republic. [Andersen, John F.; Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Chavakis, Triantafyllos; Chmelar, Jindrich] Tech Univ Dresden, Dept Clin Pathobiochem, D-01062 Dresden, Germany. [Pedra, Joao H. F.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Kotsyfakis, M (reprint author), Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Lab Genom & Prote Dis Vectors, Branisovska 31, CZ-37005 Budweis, Czech Republic. EM mich_kotsyfakis@yahoo.com RI Kotsyfakis, Michail/G-9525-2014; Langhansova, Helena /G-9292-2014; Lieskovska, Jaroslava/G-9309-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Pedra, Joao/0000-0001-8740-2667 FU Grant Agency of the Czech Republic (GACR) [P502/12/2409]; Academy of Sciences of the Czech Republic [RVO60077344]; European Union (EU) [PIRG07-GA-2010-268177]; National Institutes of Health [R01 AI093653]; University of Maryland, Baltimore School of Medicine; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH; USA); Academy of Sciences of the Czech Republic FX We thank Nextgenediting (www.nextgenediting.com) for providing editorial assistance and the anonymous reviewers for their constructive comments. This work was supported by the Grant Agency of the Czech Republic (GACR grant P502/12/2409 to MK), the Academy of Sciences of the Czech Republic (grant no. RVO60077344 to the Biology Center-Institute of Parasitology), and the 7th Framework Program of the European Union (EU FP7; Marie Curie Reintegration grant PIRG07-GA-2010-268177 to MK). This publication reflects only the authors' views and the European Union is not liable for any use that may be made of the information contained herein. MK and JHFP were supported by the National Institutes of Health (R01 AI093653) and JHFP was supported by start-up funds provided by the University of Maryland, Baltimore School of Medicine. JFA and IMBF were supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH; USA). MK received support from the Academy of Sciences of the Czech Republic (Jan Evangelista Purkyne Fellowship). NR 175 TC 13 Z9 13 U1 7 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 EI 1876-7737 J9 J PROTEOMICS JI J. Proteomics PD OCT 14 PY 2015 VL 128 BP 58 EP 68 DI 10.1016/j.jprot.2015.07.005 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CW3HI UT WOS:000364882200006 PM 26189360 ER PT J AU Ngwuta, JO Chen, M Modjarrad, K Joyce, MG Kanekiyo, M Kumar, A Yassine, HM Moin, SM Killikelly, AM Chuang, GY Druz, A Georgiev, IS Rundlet, EJ Sastry, M Stewart-Jones, GBE Yang, YP Zhang, BS Nason, MC Capella, C Peeples, ME Ledgerwood, JE McLellan, JS Kwong, PD Graham, BS AF Ngwuta, Joan O. Chen, Man Modjarrad, Kayvon Joyce, M. Gordon Kanekiyo, Masaru Kumar, Azad Yassine, Hadi M. Moin, Syed M. Killikelly, April M. Chuang, Gwo-Yu Druz, Aliaksandr Georgiev, Ivelin S. Rundlet, Emily J. Sastry, Mallika Stewart-Jones, Guillaume B. E. Yang, Yongping Zhang, Baoshan Nason, Martha C. Capella, Cristina Peeples, Mark E. Ledgerwood, Julie E. McLellan, Jason S. Kwong, Peter D. Graham, Barney S. TI Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; FUSION GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; CILIATED CELLS; INFECTION; PROTEIN; MOTAVIZUMAB; EPITOPES; VACCINE; DESIGN AB Respiratory syncytial virus (RSV) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. Viral entry is mediated by a type I fusion glycoprotein (F) that transitions from a metastable prefusion (pre-F) to a stable postfusion (post-F) trimer. A highly neutralization-sensitive epitope, antigenic site empty set, is found only on pre-F. We determined what fraction of neutralizing (NT) activity in human sera is dependent on antibodies specific for antigenic site empty set or other antigenic sites on F in healthy subjects from ages 7 to 93 years. Adsorption of individual sera with stabilized pre-F protein removed >90% of NT activity and depleted binding antibodies to both F conformations. In contrast, adsorption with post-F removed similar to 30% of NT activity, and binding antibodies to pre-F were retained. These findings were consistent across all age groups. Protein competition neutralization assays with pre-F mutants in which sites empty set or II were altered to knock out binding of antibodies to the corresponding sites showed that these sites accounted for similar to 35 and <10% of NT activity, respectively. Binding competition assays with monoclonal antibodies (mAbs) indicated that the amount of site empty set-specific antibodies correlated with NT activity, whereas the magnitude of binding competed by site II mAbs did not correlate with neutralization. Our results indicate that RSV NT activity in human sera is primarily derived from pre-F-specific antibodies, and therefore, inducing or boosting NT activity by vaccination will be facilitated by using pre-F antigens that preserve site empty set. C1 [Ngwuta, Joan O.; Chen, Man; Modjarrad, Kayvon; Joyce, M. Gordon; Kanekiyo, Masaru; Kumar, Azad; Yassine, Hadi M.; Moin, Syed M.; Killikelly, April M.; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S.; Rundlet, Emily J.; Sastry, Mallika; Stewart-Jones, Guillaume B. E.; Yang, Yongping; Zhang, Baoshan; Nason, Martha C.; Ledgerwood, Julie E.; McLellan, Jason S.; Kwong, Peter D.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Modjarrad, Kayvon] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Capella, Cristina; Peeples, Mark E.] Ohio State Univ, Coll Med, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43205 USA. [Capella, Cristina; Peeples, Mark E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA. [McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU American Recovery and Reinvestment Act by the NIH [HHSN2722010000491] FX Funding: Funding for the VRC 700 trial was provided by the American Recovery and Reinvestment Act of 2009 (Recovery Act) through contract #HHSN2722010000491 awarded to the EMMES Corporation by the NIH. NR 27 TC 30 Z9 30 U1 13 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD OCT 14 PY 2015 VL 7 IS 309 AR 309ra162 DI 10.1126/scitranslmed.aac4241 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CW8FO UT WOS:000365235100004 PM 26468324 ER PT J AU Little, MP Kwon, D Zablotska, LB Brenner, AV Cahoon, EK Rozhko, AV Polyanskaya, ON Minenko, VF Golovanov, I Bouville, A Drozdovitch, V AF Little, Mark P. Kwon, Deukwoo Zablotska, Lydia B. Brenner, Alina V. Cahoon, Elizabeth K. Rozhko, Alexander V. Polyanskaya, Olga N. Minenko, Victor F. Golovanov, Ivan Bouville, Andre Drozdovitch, Vladimir TI Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident SO PLOS ONE LA English DT Article ID ATOMIC-BOMB SURVIVORS; INCIDENCE DOSE-RESPONSE; MEASUREMENT ERROR; REGRESSION CALIBRATION; CHILDHOOD-CANCER; POOLED ANALYSIS; MONTE-CARLO; RADIATION; COHORT; RECONSTRUCTION AB Background The excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of I-131 released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error. Methods We examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996-2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied. Results There was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy(-) (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy(-) (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy(-) (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy(-) (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053-0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2). Conclusions In summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters. C1 [Little, Mark P.; Brenner, Alina V.; Cahoon, Elizabeth K.; Bouville, Andre; Drozdovitch, Vladimir] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Bethesda, MD 20892 USA. [Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Zablotska, Lydia B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Rozhko, Alexander V.; Polyanskaya, Olga N.] Republican Res Ctr Radiat Med & Human Ecol, Gomel 246040, Byelarus. [Minenko, Victor F.] Res Inst Nucl Problems, Minsk, Byelarus. [Golovanov, Ivan] Burnasyan Fed Med Biophys Ctr, Moscow, Russia. RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Bethesda, MD 20892 USA. EM mark.little@nih.gov OI Little, Mark/0000-0003-0980-7567 FU Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics; NCI [NO1-CP-21178, 5K07CA132918] FX This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. Dr Zablotska's work is supported by NCI contract NO1-CP-21178 and NCI grant 5K07CA132918. NR 43 TC 1 Z9 3 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 14 PY 2015 VL 10 IS 10 AR e0139826 DI 10.1371/journal.pone.0139826 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU0CK UT WOS:000363183100060 PM 26465339 ER PT J AU Lu, XX Liu, F Durham, SE Tarasov, SG Walters, KJ AF Lu, Xiuxiu Liu, Fen Durham, Sarah E. Tarasov, Sergey G. Walters, Kylie J. TI A High Affinity hRpn2-Derived Peptide That Displaces Human Rpn13 from Proteasome in 293T Cells SO PLOS ONE LA English DT Article ID DEUBIQUITINATING ENZYME; UBIQUITIN RECEPTOR; 26S PROTEASOMES; SUBUNIT; UCH37; ACTIVATION; CANCER; DOMAIN; ADRM1; S5A AB Rpn13 is a proteasome ubiquitin receptor that has emerged as a therapeutic target for human cancers. Its ubiquitin-binding activity is confined to an N-terminal Pru (pleckstrin-like receptor for ubiquitin) domain that also docks it into the proteasome, while its C-terminal DEUBAD (DEUBiquitinase ADaptor) domain recruits deubiquitinating enzyme Uch37 to the proteasome. Bis-benzylidine piperidone derivatives that were found to bind covalently to Rpn13 C88 caused the accumulation of polyubiquitinated proteins as well as ER stress-related apoptosis in various cancer cell lines, including bortezomib-resistant multiple myeloma lines. We find that a 38-amino acid peptide derived from the C-terminus of proteasome PC repeat protein hRpn2/PSMD1 binds to hRpn13 Pru domain with 12 nM affinity. By using NMR, we identify the hRpn13-interacting amino acids in this hRpn2 fragment, some of which are conserved among eukaryotes. Importantly, we find the hRpn2-derived peptide to immunoprecipitate endogenous Rpn13 from 293T cells, and to displace it from the proteasome. These findings indicate that this region of hRpn2 is the primary binding site for hRpn13 in the proteasome. Moreover, the hRpn2-derived peptide was no longer able to interact with endogenous hRpn13 when a strictly conserved phenylalanine (F948 in humans) was replaced with arginine or a stop codon, or when Y950 and I951 were substituted with aspartic acid. Finally, over-expression of the hRpn2-derived peptide leads to an increased presence of ubiquitinated proteins in 293T cells. We propose that this hRpn2-derived peptide could be used to develop peptide-based strategies that specifically target hRpn13 function in the proteasome. C1 [Lu, Xiuxiu; Liu, Fen; Durham, Sarah E.; Walters, Kylie J.] NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Durham, Sarah E.] Middletown High Sch, Middletown, MD USA. [Tarasov, Sergey G.] NCI, Biophys Resource, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Walters, KJ (reprint author), NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21701 USA. EM kylie.walters@nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research [1ZIABC011490]; Werner H. Kirsten student internship program FX This research was funded by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, awarded to KJW (project number 1ZIABC011490). Sarah Durham was funded by the Werner H. Kirsten student internship program. The funders had no role in the study design, data collection and analyses, decision to publish, or preparation of the manuscript. NR 26 TC 2 Z9 2 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 14 PY 2015 VL 10 IS 10 AR e0140518 DI 10.1371/journal.pone.0140518 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU0CK UT WOS:000363183100136 PM 26466095 ER PT J AU Defaye, FB Desalegn, D Danis, M Hurst, S Berhane, Y Norheim, OF Miljeteig, I AF Defaye, Frehiwot Berhane Desalegn, Dawit Danis, Marion Hurst, Samia Berhane, Yemane Norheim, Ole Frithjof Miljeteig, Ingrid TI A survey of Ethiopian physicians' experiences of bedside rationing: extensive resource scarcity, tough decisions and adverse consequences SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Ethics; Clinical; Allocation of health care resources; Health provider perspective; Bedside rationing; Ethiopia ID INDIAN NEONATAL UNIT; OF-LIFE DECISIONS; HEALTH-CARE; DEVELOPING-COUNTRIES; INTERVENTIONS; DOCTORS AB Background: Resource scarcity in health care is a universal challenge. In high-income settings, bedside rationing is commonly discussed and debated as a means to addressing scarcity. However, little is known about physicians' experiences in resource-limited contexts in low-income countries. Here we describe physicians' experiences regarding scarcity of resources, bedside rationing, use of various strategies to save resources, and perceptions of the consequences of rationing in Ethiopia. Methods: A national survey was conducted amongst physicians from 49 public hospitals using stratified, multi-stage sampling in six regions. All physicians in the selected hospitals were invited to respond to a self-administered questionnaire. Data were weighted and analyzed using descriptive statistics. Results: In total, 587 physicians responded (91 % response rate). The majority had experienced system-wide shortages of various types of medical services. The services most frequently reported to be in short supply, either daily or weekly, were access to surgery, specialist and intensive care units, drug prescriptions and admission to hospital (52, 49, 46, 47 and 46 % respectively). The most common rationing strategies used daily or weekly were limiting laboratory tests, hospital drugs, radiological investigations and providing second best treatment (47, 47, 47 and 39 % respectively). Availability of institutional or national guidelines for whom to see and treat first was lacking. Almost all respondents had witnessed different adverse consequences of resource scarcity; 54 % reported seeing patients who, in their estimation, had died due to resource scarcity. Almost 9 out of 10 physicians were so troubled by limited resources that they often regretted their choice of profession. Conclusion: This study provides the first glimpses of the untold story of resource shortage and bedside rationing in Ethiopia. Physicians encounter numerous dilemmas due to resource scarcity, and they report they lack adequate guidance for how to handle them. The consequences for patients and the professionals are substantial. C1 [Defaye, Frehiwot Berhane; Norheim, Ole Frithjof; Miljeteig, Ingrid] Univ Bergen, Dept Global Publ Hlth & Primary Care, Res Grp Global Hlth Priorities, N-5018 Bergen, Norway. [Desalegn, Dawit] Univ Addis Ababa, Coll Hlth Sci, Addis Ababa, Ethiopia. [Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Hurst, Samia] Univ Geneva, Sch Med, Inst Eth Hist & Humanities, CH-1211 Geneva, Switzerland. [Berhane, Yemane] Addis Continental Inst Publ Hlth, Addis Ababa, Ethiopia. [Miljeteig, Ingrid] Helse Bergen Hlth Trust, Dept Res & Dev, Bergen, Norway. RP Miljeteig, I (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Res Grp Global Hlth Priorities, Kalfarveien 21, N-5018 Bergen, Norway. EM Ingrid.miljeteig@uib.no RI Hurst, Samia/A-9661-2008; OI Hurst, Samia/0000-0002-1980-5226; Berhane, Yemane/0000-0002-2527-1339; Norheim, Ole F./0000-0002-5748-5956 FU NORAD/ the Norwegian Research Council; Department of Bioethics at the National Institutes of Health in the US FX The project was funded by NORAD/ the Norwegian Research Council through the project "Priorities 2020". MD received support from the Department of Bioethics in the intramural program at the National Institutes of Health in the US. NR 29 TC 1 Z9 1 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD OCT 14 PY 2015 VL 15 AR 467 DI 10.1186/s12913-015-1131-6 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CT5RI UT WOS:000362868000001 PM 26467298 ER PT J AU Zhou, W Gao, X Liu, DB Chen, XY AF Zhou, Wen Gao, Xia Liu, Dingbin Chen, Xiaoyuan TI Gold Nanoparticles for In Vitro Diagnostics SO CHEMICAL REVIEWS LA English DT Review ID SURFACE-ENHANCED RAMAN; PLASMON RESONANCE BIOSENSOR; FREE COLORIMETRIC DETECTION; BIO-BARCODE ASSAY; AMPLIFIED VOLTAMMETRIC DETECTION; STABILIZED AU NANOCLUSTERS; SEMICONDUCTOR QUANTUM DOTS; HIGHLY SENSITIVE DETECTION; CANCER BIOMARKER PROTEINS; PROSTATE-SPECIFIC ANTIGEN C1 [Zhou, Wen; Gao, Xia; Liu, Dingbin] Nankai Univ, State Key Lab Med Chem Biol, Tianjin Key Lab Mol Recognit & Biosensing, Coll Chem,Res Ctr Analyt Sci, Tianjin 300071, Peoples R China. [Zhou, Wen; Gao, Xia; Liu, Dingbin] Nankai Univ, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China. [Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Liu, DB (reprint author), Nankai Univ, State Key Lab Med Chem Biol, Tianjin Key Lab Mol Recognit & Biosensing, Coll Chem,Res Ctr Analyt Sci, 94 Weijin Rd, Tianjin 300071, Peoples R China. EM liudb@nankai.edu.cn; shawn.chen@nih.gov FU National Natural Science Foundation of China [21475066, 81401463]; Fundamental Research Funds for Central Universities (China); Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We acknowledge the support from the National Natural Science Foundation of China (Grants 21475066 and 81401463), the Fundamental Research Funds for Central Universities (China), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 504 TC 80 Z9 80 U1 87 U2 318 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 EI 1520-6890 J9 CHEM REV JI Chem. Rev. PD OCT 14 PY 2015 VL 115 IS 19 SI SI BP 10575 EP 10636 DI 10.1021/acs.chemrev.5b00100 PG 62 WC Chemistry, Multidisciplinary SC Chemistry GA CT7NR UT WOS:000363002300005 PM 26114396 ER PT J AU Salahuddin, T Natarajan, B Playford, MP Joshi, AA Teague, H Masmoudi, Y Selwaness, M Chen, MY Bluemke, DA Mehta, NN AF Salahuddin, Taufiq Natarajan, Balaji Playford, Martin P. Joshi, Aditya A. Teague, Heather Masmoudi, Youssef Selwaness, Mariana Chen, Marcus Y. Bluemke, David A. Mehta, Nehal N. TI Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis SO EUROPEAN HEART JOURNAL LA English DT Article DE Cholesterol efflux capacity (CEC); HDL efflux; Non-calcified plaque burden; Coronary plaque burden; Quantitative coronary computed tomography angiography (CCTA); Psoriasis; Inflammatory atherogenesis; Lipids ID COMPUTED-TOMOGRAPHY; CT ANGIOGRAPHY; RISK; EVENTS AB Aims Cholesterol efflux capacity (CEC) was recently shown to predict future cardiovascular (CV) events. Psoriasis both increases CV risk and impairs CEC. However, whether having poor CEC is associated with coronary plaque burden is currently unknown. We aimed to assess the cross-sectional relationship between coronary plaque burden assessed by quantitative coronary computed tomography angiography (CCTA) with CEC in a well-phenotyped psoriasis cohort. Methods and results Total burden and non-calcified burden (NCB) plaque indices were assessed in 101 consecutive psoriasis patients using quantitative software. Cholesterol efflux capacity was quantified using a cell-based ex vivo assay measuring the ability of apoB-depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Cholesterol efflux capacity was inversely correlated with NCB (unadjusted beta-coefficient -0.33; P < 0.001), and this relationship persisted after adjustment for CV risk factors (beta -0.24; P < 0.001), HDL-C levels (beta -0.22; P < 0.001), and apoA1 levels (beta -0.19; P < 0.001). Finally, we observed a significant gender interaction (P < 0.001) whereby women with low CEC had higher NCB compared to men with low CEC. Conclusions We show that CEC is inversely associated with prevalent coronary plaque burden measured by quantitative CCTA. Low CEC may therefore be an important biomarker for subclinical coronary atherosclerosis in psoriasis. C1 [Salahuddin, Taufiq; Natarajan, Balaji; Playford, Martin P.; Joshi, Aditya A.; Teague, Heather; Masmoudi, Youssef; Chen, Marcus Y.; Mehta, Nehal N.] NHLBI, Cardiovasc & Pulm Branch, NIH, CRC, Bethesda, MD 20892 USA. [Selwaness, Mariana; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Mehta, NN (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, CRC, 10 Ctr Dr,Room 5-5140, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health (NIH) Intramural grant by the National Heart, Lung, and Blood Institute (NHLBI DIR grant) [HL006193-01]; NIH Clinical Center; NIH; Pfizer Inc.; Doris Duke Charitable Foundation; Newport Foundation; American Association for Dental Research; Howard Hughes Medical Institute; Colgate-Palmolive Company FX This work was supported by National Institutes of Health (NIH) Intramural grant by the National Heart, Lung, and Blood Institute (NHLBI DIR grant HL006193-01) and the NIH Clinical Center. This research was made possible in part through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. NR 15 TC 8 Z9 8 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD OCT 14 PY 2015 VL 36 IS 39 BP 2662 EP 2665 DI 10.1093/eurheartj/ehv339 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT5CJ UT WOS:000362824800016 PM 26188212 ER PT J AU Gunti, S Messer, RJ Xu, CF Yan, M Coleman, WG Peterson, KE Hasenkrug, KJ Notkins, AL AF Gunti, Sreenivasulu Messer, Ronald J. Xu, Chengfu Yan, Ming Coleman, William G., Jr. Peterson, Karin E. Hasenkrug, Kim J. Notkins, Abner L. TI Stimulation of Toll-Like Receptors profoundly influences the titer of polyreactive antibodies in the circulation SO SCIENTIFIC REPORTS LA English DT Article ID B-CELL REPERTOIRE; DEHYDROGENASE-ELEVATING VIRUS; MONOCLONAL AUTOANTIBODIES; LYMPHOCYTE; APOPTOSIS; RESPONSES; ANTIGENS; SITE; IGM AB Polyreactive antibodies are a major component of the natural antibody repertoire and bind to a variety of structurally unrelated molecules. These antibodies are thought to provide a first line of defense against bacterial infections and play a major role in the clearance of apoptotic cells. What triggers the secretion of these antibodies has remained an enigma. Using a surrogate assay for measuring polyreactive antibodies, we found that about 50% of serum IgM is polyreactive and that stimulation of TLR4(+/+), but not TLR4(-/-), mice resulted in a 40 fold increase in polyreactive antibodies. Stimulation of TLRs 3, 7, 9 also increased the secretion of polyreactive antibodies. Infection with a virus or tissue damage induced by a toxin similarly led to an increase in polyreactive antibodies in MyD88(+/+), but not MyD88(-/-) mice. We conclude that stimulation of TLRs is a key link in the mechanism of polyreactive antibody secretion into the circulation. C1 [Gunti, Sreenivasulu; Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Messer, Ronald J.; Peterson, Karin E.; Hasenkrug, Kim J.] NIAID, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. [Xu, Chengfu; Yan, Ming; Coleman, William G., Jr.] NIDDK, Pharmacol Sect, Lab Bacterial Genet, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU US National Institutes of Health FX This research was supported by the Intramural Research Program of the US National Institutes of Health. The views expressed in this manuscript represent the opinion of the authors, and do not necessarily represent the official views of the NIH. NR 28 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 14 PY 2015 VL 5 AR 15066 DI 10.1038/srep15066 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT3OD UT WOS:000362715200002 PM 26463758 ER PT J AU Hoinka, J Dao, P Przytycka, TM AF Hoinka, Jan Phuong Dao Przytycka, Teresa M. TI AptaGUI-A Graphical User Interface for the Efficient Analysis of HT-SELEX Data SO MOLECULAR THERAPY-NUCLEIC ACIDS LA English DT Letter ID RNA SECONDARY STRUCTURE C1 [Hoinka, Jan; Phuong Dao; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. RP Hoinka, J; Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM Teresa.Przytycka@nih.gov NR 6 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2162-2531 J9 MOL THER-NUCL ACIDS JI Mol. Ther.-Nucl. Acids PD OCT 13 PY 2015 VL 4 AR e257 DI 10.1038/mtna.2015.26 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DC0MV UT WOS:000368912500001 PM 26461977 ER PT J AU Han, B Compton, WM Jones, CM Cai, R AF Han, Beth Compton, Wilson M. Jones, Christopher M. Cai, Rong TI Nonmedical Prescription Opioid Use and Use Disorders Among Adults Aged 18 Through 64 Years in the United States, 2003-2013 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; PAIN RELIEVERS; ANALGESIC ABUSE; OVERDOSE DEATHS; TRENDS; FREQUENCY; EPIDEMIC AB IMPORTANCE Since 1999, the United States has experienced increases in morbidity and mortality associated with nonmedical use of prescription opioids. OBJECTIVE To assess national trends in and characteristics of nonmedical prescription opioid use and use disorders and the national trend in related mortality. DESIGN, SETTING, AND PARTICIPANTS Prevalence of nonmedical use and use disorders and related risk factors were based on data from 472 200 persons aged 18 through 64 years who participated in the 2003-2013 National Surveys on Drug Use and Health. Mortality was based on the 2003-2013 National Vital Statistics System's Multiple Cause of Death Files. EXPOSURES Prevalence of nonmedical use of prescription opioids. MAIN OUTCOMES AND MEASURES Nonmedical prescription opioid use and use disorders. RESULTS Among adults aged 18 through 64 years, the prevalence of nonmedical use of prescription opioids decreased from 5.4% (95% CI, 5.08%-5.70%) in 2003 to 4.9% (95% CI, 4.58%-5.22%) in 2013 (absolute difference, -0.5%; 95% CI, -0.11% to -0.89%), but the prevalence of prescription opioid use disorders increased from 0.6% (95% CI, 0.54%-0.76%) in 2003 to 0.9% (95% CI, 0.75%-1.01%) in 2013 (absolute difference, 0.3%; 95% CI, 0.03%-0.43%). The 12-month prevalence of high-frequency use (>= 200 days) also increased from 0.3% (95% CI, 0.19%-0.35%) in 2003 to 0.4% (95% CI, 0.31%-0.48%) in 2013 (absolute difference, 0.1%; 95% CI, 0.01%-0.29%). Mortality assessed by drug overdose death rates involving prescription opioids increased from 4.5 per 100 000 (95% CI, 4.42-4.61) in 2003 to 7.8 per 100 000 (95% CI, 7.64-7.89) in 2013 (absolute difference, 3.3; 95% CI, 3.09-3.41) among adults aged 18 through 64 years. The mean number of days of nonmedical use of prescription opioids increased from 2.1 (95% CI, 1.83-2.37) in 2003 to 2.6 (95% CI, 2.27-2.85) in 2013 (absolute difference, 0.5, 95% CI, 0.05-0.86). The model-adjusted prevalence of having prescription opioid use disorders among nonmedical users increased to 15.7% (95% CI, 13.87%-17.67%) in 2010,16.1% (95% CI, 14.36%-17.99%) in 2011, 17.0% (95% CI, 15.07%-19.12%) in 2012, and 16.9% (95% CI, 14.95%-19.03%) in 2013 from 12.7% (95% CI, 11.04%-14.53%) in 2003. CONCLUSIONS AND RELEVANCE During the 2003-2013 years, among adults aged 18 through 64 years, the percentage of nonmedical use of prescription opioids decreased. In contrast, the prevalence of prescription opioid use disorders, frequency of use, and related mortality increased. C1 [Han, Beth; Cai, Rong] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD 20857 USA. [Compton, Wilson M.] NIDA, NIH, Bethesda, MD USA. [Jones, Christopher M.] US FDA, Silver Spring, MD USA. RP Han, B (reprint author), Subst Abuse & Mental Hlth Serv Adm, One Choke Cherry Rd,Room 2-1079, Rockville, MD 20857 USA. EM beth.han@samhsa.hhs.gov FU Substance Abuse and Mental Health Services Administration; National Institute on Drug Abuse; US Food and Drug Administration FX This study was jointly sponsored by the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, and the US Food and Drug Administration. The National Surveys on Drug Use and Health were supported by contracts from the Substance Abuse and Mental Health Services Administration. NR 37 TC 37 Z9 37 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2015 VL 314 IS 14 BP 1468 EP 1478 DI 10.1001/jama.2015.11859 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CT2QI UT WOS:000362647800014 PM 26461997 ER PT J AU Rogers, T Ratnayaka, K Schenke, WH Sonmez, M Kocaturk, O Mazal, JR Chen, MY Faranesh, AZ Lederman, RJ AF Rogers, Toby Ratnayaka, Kanishka Schenke, William H. Sonmez, Merdim Kocaturk, Ozgur Mazal, Jonathan R. Chen, Marcus Y. Faranesh, Anthony Z. Lederman, Robert J. TI Fully Percutaneous Transthoracic Left Atrial Entry and Closure to Deliver Large Caliber Transcatheter Mitral Valve Implants SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 27th Annual Symposium on Transcatheter Cardiovascular Therapeutics (TCT) CY OCT 11-15, 2015 CL San Francisco, CA DE Magnetic resonance imaging; cardiovascular; Mitral valve; Transcatheter intervention C1 [Rogers, Toby; Ratnayaka, Kanishka; Schenke, William H.; Sonmez, Merdim; Kocaturk, Ozgur; Mazal, Jonathan R.; Chen, Marcus Y.; Faranesh, Anthony Z.; Lederman, Robert J.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 13 PY 2015 VL 66 IS 15 SU S MA TCT-158 BP B56 EP B57 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU2CF UT WOS:000363329000122 ER PT J AU Zdobnova, T Sokolova, E Stremovskiy, O Karpenko, D Telford, W Turchin, I Balalaeva, I Deyev, S AF Zdobnova, Tatiana Sokolova, Evgeniya Stremovskiy, Oleg Karpenko, Dmitry Telford, William Turchin, Ilya Balalaeva, Irina Deyev, Sergey TI A novel far-red fluorescent xenograft model of ovarian carcinoma for preclinical evaluation of HER2-targeted immunotoxins SO ONCOTARGET LA English DT Article DE xenograft tumor model; far-red fluorescent protein; ovarian carcinoma; HER2; immunotoxin ID CANCER-CELLS; TUMOR-CELLS; PSEUDOMONAS EXOTOXIN; BREAST-CANCER; IN-VIVO; RECOMBINANT IMMUNOTOXIN; PANCREATIC-CANCER; FUSION PROTEIN; MOUSE MODEL; ANTIBODY AB We have created a novel fluorescent model of a human ovarian carcinoma xenograft overexpressing receptor HER2, a promising molecular target of solid tumors. The model is based on a newly generated SKOV-kat cell line stably expressing far-red fluorescent protein Katushka. Katushka is most suitable for the in vivo imaging due to an optimal combination of high brightness and emission in the "window of tissue transparency". The relevance of the fluorescent model for the in vivo monitoring of tumor growth and response to treatment was demonstrated using a newly created HER2-targeted recombinant immunotoxin based on the 4D5scFv antibody and a fragment of the Pseudomonas exotoxin A. C1 [Zdobnova, Tatiana; Sokolova, Evgeniya; Balalaeva, Irina; Deyev, Sergey] Lobachevsky State Univ Nizhny Novgorod, Nizhnii Novgorod 603950, Russia. [Stremovskiy, Oleg; Karpenko, Dmitry; Deyev, Sergey] Russian Acad Sci, Inst Bioorgan Chem, Moscow 117997, Russia. [Telford, William] NCI, NIH, Bethesda, MD 20892 USA. [Turchin, Ilya] Russian Acad Sci, Inst Appl Phys, Nizhnii Novgorod 603950, Russia. RP Deyev, S (reprint author), Lobachevsky State Univ Nizhny Novgorod, Nizhnii Novgorod 603950, Russia. EM deyev@ibch.ru RI Turchin, Ilya/E-3863-2014 OI Turchin, Ilya/0000-0002-8471-7361 FU RSF [14-24-00106]; Ministry of Education and Science of the Russian Federation [14.Z50.31.0022] FX This research was supported by RSF grant (no. 14-24-00106) in the part of construction of the immunotoxin and cell studies, and project no. 14.Z50.31.0022 of the Ministry of Education and Science of the Russian Federation in the part of work related with generation of a fluorescent xenograft tumor model and in vivo imaging experiments. NR 36 TC 7 Z9 7 U1 1 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 13 PY 2015 VL 6 IS 31 BP 30919 EP 30928 DI 10.18632/oncotarget.5130 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DD UT WOS:000363185200050 PM 26436696 ER PT J AU Jiang, L Xu, YL Zeng, XL Fang, JC Morse, HC Zhou, JX AF Jiang, Lei Xu, Yulian Zeng, Xinli Fang, Jianchen Morse, Herbert C., III Zhou, Jeff X. TI Suppression of CD300A inhibits the growth of diffuse large B-cell lymphoma SO ONCOTARGET LA English DT Article DE diffuse large B-cell lymphoma; CD300A; PI3K/AKT; lymphomagenesis ID RECEPTOR IRP60 CD300A; NK CELLS; EXPRESSION; PATHOGENESIS; SURVIVAL; PATHWAY; SYK; SUPERFAMILY; REGULATORS; MOLECULES AB CD300A is a type I transmembrane receptor protein which has shown inhibitory effects on B-cell receptor-mediated signals. In an analysis of public dataset, we found that CD300A mRNA levels were inversely correlated with the overall survival time of patients with diffuse large B-cell lymphoma (DLBCL). To decipher the role of CD300A in DLBCL, we knocked down the expression levels of CD300A in DLBCL cells and found that decreasing levels of CD300A significantly inhibited cell proliferation of OCI-Ly01, Farage, and SUDHL-4 cells, but not of VAL, OCI-Ly10, or SUDHL-8 cells. Mechanistically, reduced expression of CD300A resulted in a marked attenuation of AKT phosphorylation, a key molecular event in tumorigenesis, in OCI-Ly01, Farage, and SUDHL-4 cells. Pharmacologic inhibition of PI3K displayed a similar inhibitory effect on cell proliferation. Furthermore, using a xenograft animal model, we found that decreasing levels of CD300A in OCI-Ly01 and Farage cells significantly inhibited tumor formation in vivo. Collectively, our results suggested an oncogenic role of CD300A in DLBCL which could serve as a potential biomarker and therapeutic target for this malignant disease. C1 [Jiang, Lei; Xu, Yulian; Zhou, Jeff X.] Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Dept Pathol, Ningbo 315211, Zhejiang, Peoples R China. [Zeng, Xinli] Ningbo Second Peoples Hosp, Dept ENT, Ningbo, Zhejiang, Peoples R China. [Fang, Jianchen] Ningbo Pathol Serv Ctr, Ningbo, Zhejiang, Peoples R China. [Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. RP Zhou, JX (reprint author), Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Dept Pathol, Ningbo 315211, Zhejiang, Peoples R China. EM jeffxzhou@gmail.com FU National Natural Science Foundation of China (NSFC) [81172251, 81400098]; K.C. Wong Magna Fund at Ningbo University; Disciplinary Project of Ningbo University [xkl141057]; Zhejiang Provincial Key Laboratory of Pathophysiology [ZJKLP201402]; Intramural Research Program of the NIAID, NIH FX We are grateful to Dr. John E. Coligan and his lab at the National Institutes of Health for insightful discussion about this study. The work was supported by the National Natural Science Foundation of China (NSFC) (grant # 81172251 and # 81400098), the K.C. Wong Magna Fund at Ningbo University, Disciplinary Project of Ningbo University (xkl141057), Zhejiang Provincial Key Laboratory of Pathophysiology (ZJKLP201402), and in part by the Intramural Research Program of the NIAID, NIH. NR 34 TC 1 Z9 1 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 13 PY 2015 VL 6 IS 31 BP 31191 EP 31202 DI 10.18632/oncotarget.5152 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DD UT WOS:000363185200070 PM 26435477 ER PT J AU Gabitzsch, ES Tsang, KY Palena, C David, JM Fantini, M Kwilas, A Rice, AE Latchman, Y Hodge, JW Gulley, JL Madan, RA Heery, CR Balint, JP Jones, FR Schlom, J AF Gabitzsch, Elizabeth S. Tsang, Kwong Yok Palena, Claudia David, Justin M. Fantini, Massimo Kwilas, Anna Rice, Adrian E. Latchman, Yvette Hodge, James W. Gulley, James L. Madan, Ravi A. Heery, Christopher R. Balint, Joseph P., Jr. Jones, Frank R. Schlom, Jeffrey TI The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic SO ONCOTARGET LA English DT Article DE cancer vaccines; adenovirus vaccines; tumor antigens; immunotherapy; brachyury ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR BRACHYURY; HUMAN CARCINOEMBRYONIC ANTIGEN; CARCINOMA CELL-POPULATIONS; MONOCLONAL-ANTIBODY DF3; HUMAN DENDRITIC CELLS; T-LYMPHOCYTE EPITOPE; COLORECTAL-CANCER; PROSTATE-CANCER; LUNG-CANCER AB Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4(+) and CD8(+) T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies. C1 [Gabitzsch, Elizabeth S.; Rice, Adrian E.; Latchman, Yvette; Balint, Joseph P., Jr.; Jones, Frank R.] Etubics Corp, Seattle, WA USA. [Tsang, Kwong Yok; Palena, Claudia; David, Justin M.; Fantini, Massimo; Kwilas, Anna; Hodge, James W.; Heery, Christopher R.; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gulley, James L.; Madan, Ravi A.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016; Hodge, James/D-5518-2015; OI Gulley, James/0000-0002-6569-2912; Hodge, James/0000-0001-5282-3154; Fantini, Massimo/0000-0002-8164-2587 FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health; National Cancer Institute Small Business Innovative Research (SBIR) Grants [2R44CA134063-02, 1R43CA186357-01A1, HHSN261201100097C] FX Laboratory of Tumor Immunology and Biology, NCI:; Studies conducted in the Laboratory of Tumor Immunology and Biology were funded by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health.; Etubics Corporation:; This study was funded in part by the National Cancer Institute Small Business Innovative Research (SBIR) Grants 2R44CA134063-02, 1R43CA186357-01A1; HHSN261201100097C. NR 82 TC 4 Z9 4 U1 1 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 13 PY 2015 VL 6 IS 31 BP 31344 EP 31359 DI 10.18632/oncotarget.5181 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DD UT WOS:000363185200083 PM 26374823 ER PT J AU Lee, M Beggs, SM Gildea, D Bupp, S Lichtenberg, J Trivedi, NS Hu, Y Bodine, DM Crawford, NPS AF Lee, Minnkyong Beggs, Sarah M. Gildea, Derek Bupp, Sujata Lichtenberg, Jens Trivedi, Niraj S. Hu, Ying Bodine, David M. Crawford, Nigel P. S. CA NISC Comparative Sequencing Progra TI Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc SO ONCOTARGET LA English DT Article DE necdin; c-Myc; germline polymorphisms; metastasis suppressors; breast cancer ID PRADER-WILLI-SYNDROME; TUMOR PROGRESSION; GENE; EXPRESSION; DISRUPTION; PREDICTOR; SIGNATURE; INTERACTS; PROTEINS; MODIFIER AB Metastasis is the primary cause of death in breast cancer. Earlier studies using a mammary tumorigenesis mouse model identified Necdin (Ndn) as a germline modifier of metastasis. Differential expression of Ndn induces a gene-expression signature that predicts prognosis in human breast cancer. Additionally, a non-synonymous germline single nucleotide polymorphism (T50C; V17A) in Ndn distinguishes mouse strains with differing metastatic capacities. To better understand how hereditary factors influence metastasis in breast cancer, we characterized NDN-mediated transcription. Haplotype analysis in a well-characterized breast cancer cohort revealed that NDN germline variation is associated with both NDN expression levels and patient outcome. To examine the role of NDN in mammary tumor metastasis and transcriptional regulation, mouse mammary tumor cell lines stably over-expressing either the wildtype 50T or variant 50C Ndn allele were generated. Cells over-expressing Ndn 50T, but not Ndn 50C, exhibited significant decrease in cell invasiveness and pulmonary metastases compared to control cells. Transcriptome analyses identified a 71-gene expression signature that distinguishes cells over-expressing the two Ndn allelic variants. Furthermore, ChIP assays revealed c-Myc, a target gene of NDN, to be differentially regulated by the allelic variants. These data demonstrate that NDN and the T50C allele regulate gene expression and metastasis efficiency. C1 [Lee, Minnkyong; Beggs, Sarah M.; Bupp, Sujata; Lichtenberg, Jens; Bodine, David M.; Crawford, Nigel P. S.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Gildea, Derek; Trivedi, Niraj S.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [NISC Comparative Sequencing Progra] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Hu, Ying] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA. RP Crawford, NPS (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM crawforn@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, USA FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, USA. NR 38 TC 2 Z9 2 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 13 PY 2015 VL 6 IS 31 BP 31557 EP 31568 DI 10.18632/oncotarget.5230 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DD UT WOS:000363185200097 PM 26384308 ER PT J AU Muthana, SM Gulley, JL Hodge, JW Schlom, J Gildersleeve, JC AF Muthana, Saddam M. Gulley, James L. Hodge, James W. Schlom, Jeffrey Gildersleeve, Jeffrey C. TI ABO blood type correlates with survival on prostate cancer vaccine therapy SO ONCOTARGET LA English DT Article DE cancer vaccine; immunotherapy; PROSTVAC-FV; Glycan microarray; blood type ID SERUM ANTIBODIES; GROUP ANTIGENS; VI ANTIGENS; PROSTVAC-VF; MICROARRAY; GLYCOME; SYSTEM; FUTURE AB Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging. Previously, we found that pre-treatment serum IgM to blood group A (BG-A) correlated with survival for patients treated with PROSTVAC-VF, a therapeutic cancer vaccine in phase III clinical trials for the treatment of prostate cancer. These results suggested that ABO blood type might influence efficacy. Unfortunately, blood types were not available in the clinical records for all but 8 patients and insufficient amounts of sera were left for standard blood typing methods. To test the hypothesis, therefore, we developed a new glycan microarray-based method for determining ABO blood type. The method requires only 4 mu L of serum, provides 97% accuracy, and allows simultaneous profiling of many other serum anti-glycan antibodies. After validation with 220 healthy subjects of known blood type, the method was then applied to 74 PROSTVAC-VF patients and 37 control patients from a phase II trial. In this retrospective study, we found that type B and O PROSTVAC-VF patients demonstrated markedly improved clinical outcomes relative to A and AB patients, including longer median survival, longer median survival relative to Halabi predicted survival, and improved overall survival via Kaplan-Meier survival analysis (p = 0.006). Consequently, blood type may provide an inexpensive screen to pre-select patients likely to benefit from PROSTVAC-VF therapy. C1 [Muthana, Saddam M.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Muthana, Saddam M.] Alfaisal Univ, Coll Sci & Gen Studies, Dept Chem, Riyadh, Saudi Arabia. [Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hodge, James W.; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM gildersj@mail.nih.gov RI Gulley, James/K-4139-2016; Hodge, James/D-5518-2015 OI Gulley, James/0000-0002-6569-2912; Hodge, James/0000-0001-5282-3154 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute), Professor Tom Tolbert (University of Kansas), Professor Lai-Xi Wang (University of Maryland), Professor Xuefei Huang (Michigan State University), Professor Todd Lowary (University of Alberta) and Dr. Joseph Barchi (National Cancer Institute) for contributing glycans for the array. We thank Dr. Stephanie Wang for generous financial support of this work. In addition, this work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 35 TC 2 Z9 2 U1 1 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 13 PY 2015 VL 6 IS 31 BP 32244 EP 32256 DI 10.18632/oncotarget.4993 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0DD UT WOS:000363185200147 PM 26338967 ER PT J AU Obeng-Adjei, N Portugal, S Tran, TM Yazew, TB Skinner, J Li, SP Jain, A Feigner, PL Doumbo, OK Kayentao, K Ongoiba, A Traore, B Crompton, PD AF Obeng-Adjei, Nyamekye Portugal, Silvia Tran, Tuan M. Yazew, Takele B. Skinner, Jeff Li, Shanping Jain, Aarti Feigner, Philip L. Doumbo, Ogobara K. Kayentao, Kassoum Ongoiba, Aissata Traore, Boubacar Crompton, Peter D. TI Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children SO CELL REPORTS LA English DT Article ID T-FOLLICULAR-HELPER; CXC CHEMOKINE RECEPTOR-5; PLASMODIUM-FALCIPARUM; ANTIBODY-RESPONSES; VACCINE DEVELOPMENT; HUMORAL IMMUNITY; GERMINAL-CENTERS; DIFFERENTIATION; INFECTION; EXPRESSION AB Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency are poorly understood. Recently, T follicular helper (Tfh) cells have been shown to play a critical role in generating long-lived antibody responses. We show that Malian children have resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal center Tfh cells phenotypically and functionally. Within this population, PD-1(+)CXCR5(+)CXCR3(-) Tfh cells are superior to Th1-polarized PD-1(+)CXCR5(+)CXCR3(+) Tfh cells in helping B cells. Longitudinally, we observed that malaria drives Th1 cytokine responses, and accordingly, the less-functional Th1-polarized Tfh subset was preferentially activated and its activation did not correlate with antibody responses. These data provide insights into the Tfh cell biology underlying suboptimal antibody responses to malaria in children and suggest that vaccine strategies that promote CXCR3(-) Tfh cell responses may improve malaria vaccine efficacy. C1 [Obeng-Adjei, Nyamekye; Portugal, Silvia; Tran, Tuan M.; Yazew, Takele B.; Skinner, Jeff; Li, Shanping; Crompton, Peter D.] NIAID, Malaria Infect Biol & Immun Unit, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Jain, Aarti; Feigner, Philip L.] Univ Calif Irvine, Sch Med, Div Infect Dis, Irvine, CA 92697 USA. [Doumbo, Ogobara K.; Kayentao, Kassoum; Ongoiba, Aissata; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Int Ctr Excellence Res, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. RP Crompton, PD (reprint author), NIAID, Malaria Infect Biol & Immun Unit, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM pcrompton@niaid.nih.gov RI Crompton, Peter/N-1130-2016; OI Skinner, Jeff/0000-0001-5697-0442 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH FX We thank the residents of Kalifabougou, Mali for participating in this study. The study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. For assistance with images, we thank Ethan Tyler (Medical Arts Design Section, NIH). NR 47 TC 18 Z9 18 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD OCT 13 PY 2015 VL 13 IS 2 BP 425 EP 439 DI 10.1016/j.celrep.2015.09.004 PG 15 WC Cell Biology SC Cell Biology GA CT6VU UT WOS:000362951500019 PM 26440897 ER PT J AU Hammond, GRV Takasuga, S Sasaki, T Balla, T AF Hammond, Gerald R. V. Takasuga, Shunsuke Sasaki, Takehiko Balla, Tamas TI The ML1Nx2 Phosphatidylinositol 3,5-Bisphosphate Probe Shows Poor Selectivity in Cells SO PLOS ONE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; LYSOSOMAL MEMBRANE; MAMMALIAN ORTHOLOG; ENDOCYTIC PATHWAY; 5-KINASE ACTIVITY; LIPID KINASE; IN-VIVO; PIKFYVE; 3-PHOSPHATE; FAB1P AB Phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P-2) is a quantitatively minor phospholipid in eukaryotic cells that plays a fundamental role in regulating endocytic membrane traffic. Despite its clear importance for cellular function and organism physiology, mechanistic details of its biology have so far not been fully elucidated. In part, this is due to a lack of experimental tools that specifically probe for PtdIns(3,5)P-2 in cells to unambiguously identify its dynamics and site(s) of action. In this study, we have evaluated a recently reported PtdIns(3,5)P-2 biosensor, GFP-ML1Nx2, for its veracity as such a probe. We report that, in live cells, the localization of this biosensor to sub-cellular compartments is largely independent of PtdIns(3,5)P-2, as assessed after pharmacological, chemical genetic or genomic interventions that block the lipid's synthesis. We therefore conclude that it is unwise to interpret the localization of ML1Nx2 as a true and unbiased biosensor for PtdIns(3,5)P-2. C1 [Hammond, Gerald R. V.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA. [Hammond, Gerald R. V.; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Takasuga, Shunsuke; Sasaki, Takehiko] Akita Univ, Grad Sch Med, Dept Med Biol, Akita 0108543, Japan. [Sasaki, Takehiko] Akita Univ, Biosignal Res Ctr, Akita 0108543, Japan. RP Hammond, GRV (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA. EM ghammond@pitt.edu RI Hammond, Gerald/A-5759-2016; OI Hammond, Gerald/0000-0002-6660-3272; Balla, Tamas/0000-0002-9077-3335 FU Department of Cell Biology University of Pittsburgh; intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health; Core Research for Evolutional Science and Technology (CREST, JST); Funding Program for Next Generation World-Leading Researchers (NEXT, MEXT); JSPS KAKENHI [20790054, 22790055] FX GH was funded by funds from the Department of Cell Biology University of Pittsburgh. GH and TB were supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. ST and TS were funded in part by research grants from Core Research for Evolutional Science and Technology (CREST, JST), and Funding Program for Next Generation World-Leading Researchers (NEXT, MEXT), and also by research grants from JSPS KAKENHI Grant Number 20790054, 22790055. NR 44 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 13 PY 2015 VL 10 IS 10 AR e0139957 DI 10.1371/journal.pone.0139957 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT6ZJ UT WOS:000362962300040 PM 26460749 ER PT J AU Poleg-Polsky, A AF Poleg-Polsky, Alon TI Effects of Neural Morphology and Input Distribution on Synaptic Processing by Global and Focal NMDA-Spikes SO PLOS ONE LA English DT Article ID NEOCORTICAL PYRAMIDAL NEURONS; IN-VIVO; BASAL DENDRITES; SENSORY INPUT; APICAL DENDRITES; CORTICAL LAYERS; TUFT DENDRITES; VISUAL-CORTEX; CELLS; INTEGRATION AB Cortical neurons can respond to glutamatergic stimulation with regenerative N-Methyl-D-aspartic acid (NMDA)-spikes. NMDA-spikes were initially thought to depend on clustered synaptic activation. Recent work had shown however a new variety of a global NMDA-spike, which can be generated by randomly distributed inputs. Very little is known about the factors that influence the generation of these global NMDA-spikes, as well the potentially distinct rules of synaptic integration and the computational significance conferred by the two types of NMDA-spikes. Here I show that the input resistance (R-IN) plays a major role in influencing spike initiation; while the classical, focal NMDA-spike depended upon the local (dendritic) RIN, the threshold of global NMDA-spike generation was set by the somatic RIN. As cellular morphology can exert a large influence on RIN, morphologically distinct neuron types can have dissimilar rules for NMDA-spikes generation. For example, cortical neurons in superficial layers were found to be generally prone to global NMDA-spike generation. In contrast, electric properties of cortical layer 5b cells clearly favor focal NMDA-spikes. These differences can translate into diverse synaptic integration rules for the different classes of cortical cells; simulated superficial layers neurons were found to exhibit strong synaptic interactions between different dendritic branches, giving rise to a single integrative compartment mediated by the global NMDA-spike. In these cells, efficiency of postsynaptic activation was relatively little dependent on synaptic distribution. By contrast, layer 5b neurons were capable of true multi-unit computation involving independent integrative compartments formed by clustered synaptic input which could trigger focal NMDA-spikes. In a sharp contrast to superficial layers neurons, randomly distributed synaptic inputs were not very effective in driving firing the layer 5b cells, indicating a possibility for different computation performed by these important cortical neurons. C1 Natl Inst Neurol Disorder & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20824 USA. RP Poleg-Polsky, A (reprint author), Natl Inst Neurol Disorder & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20824 USA. EM polegpolskya@mail.nih.gov FU NINDS Intramural Research Program [NS003145] FX This work was supported by the NINDS Intramural Research Program (NS003145). NR 62 TC 0 Z9 1 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 13 PY 2015 VL 10 IS 10 AR e0140254 DI 10.1371/journal.pone.0140254 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT6ZJ UT WOS:000362962300074 PM 26460829 ER PT J AU Woodworth, D Mayer, E Leu, K Ashe-McNalley, C Naliboff, BD Labus, JS Tillisch, K Kutch, JJ Farmer, MA Apkarian, AV Johnson, KA Mackey, SC Ness, TJ Landis, JR Deutsch, G Harris, RE Clauw, DJ Mullins, C Ellingson, BM AF Woodworth, Davis Mayer, Emeran Leu, Kevin Ashe-McNalley, Cody Naliboff, Bruce D. Labus, Jennifer S. Tillisch, Kirsten Kutch, Jason J. Farmer, Melissa A. Apkarian, A. Vania Johnson, Kevin A. Mackey, Sean C. Ness, Timothy J. Landis, J. Richard Deutsch, Georg Harris, Richard E. Clauw, Daniel J. Mullins, Chris Ellingson, Benjamin M. CA MAPP Res Network TI Unique Microstructural Changes in the Brain Associated with Urological Chronic Pelvic Pain Syndrome (UCPPS) Revealed by Diffusion Tensor MRI, Super-Resolution Track Density Imaging, and Statistical Parameter Mapping: A MAPP Network Neuroimaging Study SO PLOS ONE LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; CHRONIC BACK-PAIN; CYSTITIS/PAINFUL BLADDER SYNDROME; WHITE-MATTER ABNORMALITIES; MULTIPLE-SCLEROSIS; BASAL GANGLIA; GRAY-MATTER; WEIGHTED MRI; COEFFICIENTS; CORTEX AB Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively. We hypothesized patients with UCPPS may have microstructural differences in the brain compared with healthy control subjects (HCs), as well as patients with irritable bowel syndrome (IBS), a common gastrointestinal pain disorder. In the current study we performed population-based voxel-wise DTI and super-resolution track density imaging (TDI) in a large, two-center sample of phenotyped patients from the multicenter cohort with UCPPS (N = 45), IBS (N = 39), and HCs (N = 56) as part of the MAPP Research Network. Compared with HCs, UCPPS patients had lower fractional anisotropy (FA), lower generalized anisotropy (GA), lower track density, and higher mean diffusivity (MD) in brain regions commonly associated with perception and integration of pain information. Results also showed significant differences in specific anatomical regions in UCPPS patients when compared with IBS patients, consistent with microstructural alterations specific to UCPPS. While IBS patients showed clear sex related differences in FA, MD, GA, and track density consistent with previous reports, few such differences were observed in UCPPS patients. Heat maps illustrating the correlation between specific regions of interest and various pain and urinary symptom scores showed clustering of significant associations along the cortico-basal ganglia-thalamic-cortical loop associated with pain integration, modulation, and perception. Together, results suggest patients with UCPPS have extensive microstructural differences within the brain, many specific to syndrome UCPPS versus IBS, that appear to be localized to regions associated with perception and integration of sensory information and pain modulation, and seem to be a consequence of longstanding pain. C1 [Woodworth, Davis; Leu, Kevin; Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Woodworth, Davis; Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomed Phys, Los Angeles, CA 90095 USA. [Woodworth, Davis; Mayer, Emeran; Ashe-McNalley, Cody; Labus, Jennifer S.; Tillisch, Kirsten; Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Ctr Neurobiol Stress & PAIN, Los Angeles, CA 90095 USA. [Mayer, Emeran; Ashe-McNalley, Cody; Labus, Jennifer S.; Tillisch, Kirsten] Univ Calif Los Angeles, David Geffen Sch Med, Dept Digest Dis & Gastroenterol, Los Angeles, CA 90095 USA. [Mayer, Emeran; Naliboff, Bruce D.; Labus, Jennifer S.; Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Leu, Kevin; Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Bioengn, Los Angeles, CA 90095 USA. [Farmer, Melissa A.; Apkarian, A. Vania] Northwestern Univ, Dept Physiol, Chicago, IL 60611 USA. [Johnson, Kevin A.; Mackey, Sean C.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Ness, Timothy J.] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL USA. [Landis, J. Richard] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Deutsch, Georg] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Harris, Richard E.; Clauw, Daniel J.] Univ Michigan, Dept Anestesiol, Ann Arbor, MI 48109 USA. [Mullins, Chris] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Kutch, Jason J.] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA USA. RP Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. EM bellingson@mednet.ucla.edu OI Apkarian, A. Vania/0000-0002-9788-7458; Ness, Timothy/0000-0002-7908-4459 FU National Institute of Diabetes and Digestive and Kidney Dis-eases (NIDDK), National Institutes of Health (NIH) [DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, DK82316]; NIH/NIDDK [DK 058351 (EAM), DK 064539 (EAM)] FX Funding for the MAPP Research Network was obtained under coopera-tive agreements from the National Institute of Diabetes and Digestive and Kidney Dis-eases (NIDDK), National Institutes of Health (NIH) grants DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316. In addition, this work was supported in part by NIH/NIDDK grants DK 058351 (EAM) and DK 064539 (EAM). NR 54 TC 4 Z9 4 U1 3 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 13 PY 2015 VL 10 IS 10 AR e0140250 DI 10.1371/journal.pone.0140250 PG 30 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT6ZJ UT WOS:000362962300073 PM 26460744 ER PT J AU Sun, XY Driscoll, MK Guven, C Das, S Parent, CA Fourkas, JT Losert, W AF Sun, Xiaoyu Driscoll, Meghan K. Guven, Can Das, Satarupa Parent, Carole A. Fourkas, John T. Losert, Wolfgang TI Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell migration; actin waves; contact guidance; Dictyostelium discoideum; neutrophils ID DICTYOSTELIUM-DISCOIDEUM CELLS; CONTACT GUIDANCE; SOLID SUBSTRATE; ACTIN WAVES; MIGRATION; CHEMOTAXIS; ACTIVATION; DIRECTION; MOVEMENT; BEHAVIOR AB Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay. Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales. These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas. The direction and strength of the guidance is sensitive to the details of the nano/microtopography, suggesting that this phenomenon plays a context-dependent role in vivo. We demonstrate that appropriate asymmetric nano/microtopography can unidirectionally bias internal actin polymerization waves and that cells move with the same preferred direction as these waves. This phenomenon is observed both for the pseudopod-dominated migration of the amoeboid Dictyostelium discoideum and for the lamellipod-driven migration of human neutrophils. The conservation of this mechanism across cell types and the asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance is important in biology and physiology. C1 [Sun, Xiaoyu; Fourkas, John T.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Driscoll, Meghan K.; Guven, Can; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Driscoll, Meghan K.; Guven, Can; Das, Satarupa; Losert, Wolfgang] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. [Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fourkas, John T.; Losert, Wolfgang] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. RP Fourkas, JT (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM fourkas@umd.edu; wlosert@umd.edu RI Fourkas, John/B-3500-2009; OI Fourkas, John/0000-0002-4522-9584; Das, Satarupa/0000-0002-4217-9972 FU National Institutes of Health (NIH) [R01GM085574]; Graduate Dean's Dissertation Fellowship; Maryland NanoCenter and its NispLab; National Science Foundation as an Materials Research Science and Engineering Center Shared Experimental Facility; Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH FX We acknowledge Dr. Nikos Liaros for helping us with Greek. Support from National Institutes of Health (NIH) Grant R01GM085574 is gratefully acknowledged. X.S. was partially supported by the Graduate Dean's Dissertation Fellowship. We appreciate the support of the Maryland NanoCenter and its NispLab. The NispLab is supported in part by the National Science Foundation as an Materials Research Science and Engineering Center Shared Experimental Facility. Part of this research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 36 TC 8 Z9 8 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 2015 VL 112 IS 41 BP 12557 EP 12562 DI 10.1073/pnas.1502970112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9IQ UT WOS:000363130900020 PM 26417076 ER PT J AU Patai, EZ Gadian, DG Cooper, JM Dzieciol, AM Mishkin, M Vargha-Khadem, F AF Patai, Eva Zita Gadian, David G. Cooper, Janine M. Dzieciol, Anna M. Mishkin, Mortimer Vargha-Khadem, Faraneh TI Extent of hippocampal atrophy predicts degree of deficit in recall SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampus; developmental amnesia; recall; recognition ID MEDIAL TEMPORAL-LOBE; IMPAIRED RECOGNITION MEMORY; DEVELOPMENTAL AMNESIA; ORGANIC AMNESIA; DAMAGE; RECOLLECTION; FAMILIARITY; PERCEPTION; PATHOLOGY; PATIENT AB Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition. C1 [Patai, Eva Zita; Gadian, David G.; Cooper, Janine M.; Dzieciol, Anna M.; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, London WC1N 1EH, England. [Mishkin, Mortimer] NIH, Bethesda, MD 20892 USA. [Vargha-Khadem, Faraneh] Great Ormond St Hosp Sick Children, Natl Hlth Serv Fdn Trust, London WC1N 3JH, England. RP Mishkin, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM mishkinm@mail.nih.gov; f.vargha-khadem@ucl.ac.uk FU Medical Research Council [G03000117/65439]; Central and East London Research Network [5177]; Intramural Research Program of the National Institute of Mental Health, National Institutes of Health FX Our grateful thanks to the participants and their families for their continued support of our research, Anna Adlam for collecting behavioral data on four of the participants, and Sharon Geva for helpful comments. This work was supported by the Medical Research Council (Programme Grant G03000117/65439); the Central and East London Research Network (5177); and the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 27 TC 3 Z9 3 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 2015 VL 112 IS 41 BP 12830 EP 12833 DI 10.1073/pnas.1511904112 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9IQ UT WOS:000363130900066 PM 26417089 ER PT J AU Londono-Renteria, B Drame, PM Weitzel, T Rosas, R Gripping, C Cardenas, JC Alvares, M Wesson, DM Poinsignon, A Remoue, F Colpitts, TM AF Londono-Renteria, Berlin Drame, Papa M. Weitzel, Thomas Rosas, Reinaldo Gripping, Crystal Cardenas, Jenny C. Alvares, Marcela Wesson, Dawn M. Poinsignon, Anne Remoue, Franck Colpitts, Tonya M. TI An. gambiae gSG6-P1 evaluation as a proxy for human-vector contact in the Americas: a pilot study SO PARASITES & VECTORS LA English DT Article ID SALIVARY PROTEIN GSG6; ANOPHELES-GAMBIAE; ANTIBODY-RESPONSE; HUMAN EXPOSURE; AEDES-AEGYPTI; MALARIA TRANSMISSION; TROPICAL AFRICA; MOSQUITO; PEPTIDE; BITES AB Background: During blood meal, the female mosquito injects saliva able to elicit an immune response in the vertebrate. This immune response has been proven to reflect the intensity of exposure to mosquito bites and risk of infection for vector transmitted pathogens such as malaria. The peptide gSG6-P1 of An. gambiae saliva has been demonstrated to be antigenic and highly specific to Anopheles as a genus. However, the applicability of gSG6-P1 to measure exposure to different Anopheles species endemic in the Americas has yet to be evaluated. The purpose of this pilot study was to test whether human participants living in American countries present antibodies able to recognize the gSG6-P1, and whether these antibodies are useful as a proxy for mosquito bite exposure and malaria risk. Methods: We tested human serum samples from Colombia, Chile, and the United States for the presence of IgG antibodies against gSG6-P1 by ELISA. Antibody concentrations were expressed as delta optical density (Delta OD) of each sera tested in duplicates. The difference in the antibody concentrations between groups was tested using the nonparametric Mann Whitney test (independent groups) and the nonparametric Wilcoxon matched-pairs signed rank test (dependent groups). All differences were considered significant with a P < 0.05. Results: We found that the concentration of gSG6-P1 antibodies was significantly correlated with malaria infection status and mosquito bite exposure history. People with clinical malaria presented significantly higher concentrations of IgG anti-gSG6-P1 antibodies than healthy controls. Additionally, a significant raise in antibody concentrations was observed in subjects returning from malaria endemic areas. Conclusion: Our data shows that gSG6-P1 is a suitable candidate for the evaluation of exposure to Anopheles mosquito bites, risk of malaria transmission, and effectiveness of protection measures against mosquito bites in the Americas. C1 [Londono-Renteria, Berlin; Colpitts, Tonya M.] Univ S Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Drame, Papa M.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Weitzel, Thomas] Univ Desarrollo, Clin Alemana, Programa Med Viajero, Lab Clin, Santiago, Chile. [Rosas, Reinaldo] Hosp Mil, Santiago, Chile. [Gripping, Crystal; Wesson, Dawn M.] Tulane Univ, Dept Trop Med, New Orleans, LA 70118 USA. [Cardenas, Jenny C.] Hosp Los Patios, Los Patios, Norte De Santan, Colombia. [Alvares, Marcela] Hosp Emiro Quintero, Ocana, Norte De Santan, Colombia. [Poinsignon, Anne; Remoue, Franck] Inst Rech Dev IRD, Bouake, Cote Ivoire. [Londono-Renteria, Berlin] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29209 USA. RP Londono-Renteria, B (reprint author), Univ S Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. EM blondono@uscmed.sc.edu OI Colpitts, Tonya/0000-0003-3915-1554; Weitzel, Thomas/0000-0002-9804-2123; Londono-Renteria, Berlin/0000-0001-5956-5274 FU University of Pamplona; Colciencias (Colombia) FX The authors thank the University of Pamplona and Colciencias (Colombia) as well as Dr. Christopher Mores at Louisiana State University (USA) for their support in this study. We also thank Charles Apperson, Meagan Vaughn, Sheana Funkhouser and Steve Meshnick for providing samples. NR 45 TC 3 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD OCT 13 PY 2015 VL 8 AR 533 DI 10.1186/s13071-015-1160-3 PG 8 WC Parasitology SC Parasitology GA CT3OQ UT WOS:000362716600001 PM 26464073 ER PT J AU Jia, JL Han, YH Kim, HC Ahn, M Kwon, JW Luo, Y Gunasekaran, P Lee, SJ Lee, KS Bang, JK Kim, NH Namgoong, S AF Jia, Jia-Lin Han, Young-Hyun Kim, Hak-Cheol Ahn, Mija Kwon, Jeong-Woo Luo, Yibo Gunasekaran, Pethaiah Lee, Soo-Jae Lee, Kyung S. Bang, Jeong Kyu Kim, Nam-Hyung Namgoong, Suk TI Structural basis for recognition of Emi2 by Polo-like kinase 1 and development of peptidomimetics blocking oocyte maturation and fertilization SO SCIENTIFIC REPORTS LA English DT Article ID EARLY EMBRYONIC MITOSIS; CYCLIN B1 DEGRADATION; MEIOTIC MATURATION; MOUSE OOCYTES; METAPHASE ARREST; BOX DOMAIN; CYTOSTATIC FACTOR; CA2+ OSCILLATIONS; XENOPUS EGGS; MEIOSIS-II AB In a mammalian oocyte, completion of meiosis is suspended until fertilization by a sperm, and the cell cycle is arrested by a biochemical activity called cytostatic factor (CSF). Emi2 is one of the CSFs, and it maintains the protein level of maturation promoting factor (MPF) by inhibiting ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). Degradation of Emi2 via ubiquitin-mediated proteolysis after fertilization requires phosphorylation by Polo-like kinase 1 (Plk1). Therefore, recognition and phosphorylation of Emi2 by Plk1 are crucial steps for cell cycle resumption, but the binding mode of Emi2 and Plk1 is poorly understood. Using biochemical assays and X-ray crystallography, we found that two phosphorylated threonines (Thr(152) and Thr(176)) in Emi2 are each responsible for the recruitment of one Plk1 molecule by binding to its C-terminal polo box domain (PBD). We also found that meiotic maturation and meiosis resumption via parthenogenetic activation were impaired when Emi2 interaction with Plk1-PBD was blocked by a peptidomimetic called 103-8. Because of the inherent promiscuity of kinase inhibitors, our results suggest that targeting PBD of Plk1 may be an effective strategy for the development of novel and specific contraceptive agents that block oocyte maturation and/or fertilization. C1 [Jia, Jia-Lin; Han, Young-Hyun; Kim, Hak-Cheol; Kwon, Jeong-Woo; Luo, Yibo; Gunasekaran, Pethaiah; Kim, Nam-Hyung; Namgoong, Suk] Chungbuk Natl Univ, Dept Anim Sci, Cheongju, Chungcheongbuk, South Korea. [Lee, Soo-Jae] Chungbuk Natl Univ, Coll Pharm, Cheongju, Chungcheongbuk, South Korea. [Ahn, Mija; Bang, Jeong Kyu] Korea Basic Sci Inst, Div Magnet Resonance, Ochang, South Korea. [Lee, Kyung S.] NCI, NIH, Rockville, MD USA. RP Bang, JK (reprint author), Korea Basic Sci Inst, Div Magnet Resonance, Ochang, South Korea. EM bangjk@kbsi.re.kr; nhkim@chungbuk.ac.kr; suknamgoong@chungbuk.ac.kr FU Next Generation Biogreen 21 Program, Rural Developmental Agency, Republic of Korea [PJ011206, PJ011126]; Korea Basic Science Institute's Research Program [T35418]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2014R1A1A2008159] FX This study was supported by grants from the Next Generation Biogreen 21 Program to S.N. (PJ011206) and to N.H.K. (PJ011126), Rural Developmental Agency, Republic of Korea and also supported by the Korea Basic Science Institute's Research Program grant to J.K.B. (T35418) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education to Y.H.H. (NRF-2014R1A1A2008159). NR 53 TC 1 Z9 1 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 13 PY 2015 VL 5 AR 14626 DI 10.1038/srep14626 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT2MA UT WOS:000362634800001 PM 26459104 ER PT J AU Ramnarine, S Zhang, J Chen, LS Culverhouse, R Duan, WM Hancock, DB Hartz, SM Johnson, EO Olfson, E Schwantes-An, TH Saccone, NL AF Ramnarine, Shelina Zhang, Juan Chen, Li-Shiun Culverhouse, Robert Duan, Weimin Hancock, Dana B. Hartz, Sarah M. Johnson, Eric O. Olfson, Emily Schwantes-An, Tae-Hwi Saccone, Nancy L. TI When Does Choice of Accuracy Measure Alter Imputation Accuracy Assessments? SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; NICOTINE DEPENDENCE; AFRICAN-AMERICANS; ADMIXED POPULATIONS; SMOKING-BEHAVIOR; QUALITY-CONTROL; METAANALYSES; HAPLOTYPES; VARIANTS AB Imputation, the process of inferring genotypes for untyped variants, is used to identify and refine genetic association findings. Inaccuracies in imputed data can distort the observed association between variants and a disease. Many statistics are used to assess accuracy; some compare imputed to genotyped data and others are calculated without reference to true genotypes. Prior work has shown that the Imputation Quality Score (IQS), which is based on Cohen's kappa statistic and compares imputed genotype probabilities to true genotypes, appropriately adjusts for chance agreement; however, it is not commonly used. To identify differences in accuracy assessment, we compared IQS with concordance rate, squared correlation, and accuracy measures built into imputation programs. Genotypes from the 1000 Genomes reference populations (AFR N = 246 and EUR N = 379) were masked to match the typed single nucleotide polymorphism (SNP) coverage of several SNP arrays and were imputed with BEAGLE 3.3.2 and IMPUTE2 in regions associated with smoking behaviors. Additional masking and imputation was conducted for sequenced subjects from the Collaborative Genetic Study of Nicotine Dependence and the Genetic Study of Nicotine Dependence in African Americans (N = 1,481 African Americans and N = 1,480 European Americans). Our results offer further evidence that concordance rate inflates accuracy estimates, particularly for rare and low frequency variants. For common variants, squared correlation, BEAGLE R-2, IMPUTE2 INFO, and IQS produce similar assessments of imputation accuracy. However, for rare and low frequency variants, compared to IQS, the other statistics tend to be more liberal in their assessment of accuracy. IQS is important to consider when evaluating imputation accuracy, particularly for rare and low frequency variants. C1 [Ramnarine, Shelina; Duan, Weimin; Saccone, Nancy L.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. [Zhang, Juan] Univ Sci & Technol China, Chinese Acad Sci, Sch Life Sci, Key Lab Brain Funct & Dis, Hefei 230026, Anhui, Peoples R China. [Chen, Li-Shiun; Hartz, Sarah M.; Olfson, Emily] Washington Univ, Dept Psychiat, St Louis, MO USA. [Culverhouse, Robert] Washington Univ, Dept Med, St Louis, MO USA. [Hancock, Dana B.] RTI Int, Behav Hlth & Criminal Justice Div, Behav & Urban Hlth Program, Res Triangle Pk, NC USA. [Johnson, Eric O.] RTI Int, Fellow Program, Res Triangle Pk, NC USA. [Johnson, Eric O.] RTI Int, Behav Hlth & Criminal Justice Div, Res Triangle Pk, NC USA. [Schwantes-An, Tae-Hwi] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA. RP Saccone, NL (reprint author), Washington Univ, Dept Genet, St Louis, MO 63110 USA. EM nlims@genetics.wustl.edu OI Hancock, Dana/0000-0003-2240-3604 FU National Institute on Drug Abuse (NIDA) [R01DA026911]; NIDA [R21DA033827, P01DA035825, R01DA035825, R01DA025888, K08DA032680]; National Institutes of Health [T32GM07200, UL1TR000448, F30AA023685, TL1TR000449]; NCI [P01CA089392]; NIH [HHSN268201100011I, K08DA030398]; Division of Intramural Research at National Human Genome Research Institute, National Institutes of Health FX NLS, WD, JZ, SR, and RC were supported by R01DA026911 from the National Institute on Drug Abuse (NIDA). RC was also supported by R21DA033827 from NIDA. NLS, WD, and RC were also supported by P01DA035825 from NIDA. DBH and EOJ were supported by R01DA035825 from NIDA. EOJ was also supported by R01DA025888 from NIDA. EO was supported by T32GM07200, UL1TR000448, F30AA023685, and TL1TR000449 from the National Institutes of Health. This work was also supported by P01CA089392 from NCI and HHSN268201100011I from NIH. LC was supported by K08DA030398 from NIH. SMH was supported by K08DA032680 from NIDA. TSA was supported by the Division of Intramural Research at National Human Genome Research Institute, 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 35 TC 2 Z9 2 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 12 PY 2015 VL 10 IS 10 AR e0137601 DI 10.1371/journal.pone.0137601 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT6YZ UT WOS:000362961100001 PM 26458263 ER PT J AU Diaz, G Zamboni, F Tice, A Farci, P AF Diaz, Giacomo Zamboni, Fausto Tice, Ashley Farci, Patrizia TI Integrated ordination of miRNA and mRNA expression profiles SO BMC GENOMICS LA English DT Article DE MicroRNAs; mRNA; Multidimensional scaling; Gene expression; Kendall correlation; Partial correlations; Normal liver; Acute liver failure (ALF); Hepatitis B virus ID MICRORNAS; DUPLEXES; CANCER; CORTEX; SET AB Background: Several studies have investigated miRNA and mRNA co-expression to identify regulatory networks at the transcriptional level. A typical finding of these studies is the presence of both negative and positive miRNA-mRNA correlations. Negative correlations are consistent with the expected, faster degradation of target mRNAs, whereas positive correlations denote the existence of feed-forward regulations mediated by transcription factors. Both mechanisms have been characterized at the molecular level, although comprehensive methods to represent miRNA-mRNA correlations are lacking. At present, genome-wide studies are able to assess the expression of more than 1000 mature miRNAs and more than 35,000 well-characterized human genes. Even if studies are generally restricted to a small subset of genes differentially expressed in specific diseases or experimental conditions, the number of potential correlations remains very high, and needs robust multivariate methods to be conveniently summarized by a small set of data. Results: Nonparametric Kendall correlations were calculated between miRNAs and mRNAs differentially expressed in livers of patients with acute liver failure (ALF) using normal livers as controls. Spurious correlations due to the histopathological composition of samples were removed by partial correlations. Correlations were then transformed into distances and processed by multidimensional scaling (MDS) to map the miRNA and mRNA relationships. These showed: (a) a prominent displacement of miRNA and mRNA clusters in ALF livers, as compared to control livers, indicative of gene expression dysregulation; (b) a clustering of mRNAs consistent with their functional annotations [CYP450, transcription factors, complement, proliferation, HLA class II, monocytes/macrophages, T cells, T-NK cells and B cells], as well as a clustering of miRNAs with the same seed sequence; and (c) a tendency of miRNAs and mRNAs to populate distinct regions of the MDS plot. MDS also allowed to visualize the network of miRNA-mRNA target pairs. Conclusions: Different features of miRNA and mRNA relationships can be represented as thematic maps within the framework of MDS obtained from pairwise correlations. The symmetric distribution of positive and negative correlations between miRNA and mRNA expression suggests that miRNAs are involved in a complex bidirectional molecular network, including, but not limited to, the inhibitory regulation of miRNA targets. C1 [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Tice, Ashley; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Diaz, G (reprint author), Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. EM gdiaz@unica.it; pfarci@niaid.nih.gov FU Intramural Research Program of National Institutes of Health, National Institute of Allergy and Infectious Diseases; Regione Autonoma della Sardegna [CRP-60086] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases; and Regione Autonoma della Sardegna [grant number CRP-60086] to GD. NR 34 TC 0 Z9 0 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 12 PY 2015 VL 16 AR 767 DI 10.1186/s12864-015-1971-9 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CT1TZ UT WOS:000362585900002 PM 26459852 ER PT J AU Raver, SM Lin, SC AF Raver, Sylvina M. Lin, Shih-Chieh TI Basal forebrain motivational salience signal enhances cortical processing and decision speed SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Review DE nucleus basalis; behavioral flexibility; attention; decision making; rat; gain modulation ID DEEP BRAIN-STIMULATION; NUCLEUS BASALIS; EXCITOTOXIC LESIONS; CHOLINERGIC NEURONS; PARVALBUMIN NEURONS; ALZHEIMERS-DISEASE; INCENTIVE SALIENCE; PALLIDAL NEURONS; CEREBRAL-CORTEX; RAT AB The basal forebrain (BF) contains major projections to the cerebral cortex, and plays a well documented role in arousal, attention, decision making, and in modulating cortical activity. BF neuronal degeneration is an early event in Alzheimer's disease (AD) and dementias, and occurs in normal cognitive aging. While the BF is best known for its population of cortically projecting cholinergic neurons, the region is anatomically and neurochemically diverse, and also contains prominent populations of non-cholinergic projection neurons. In recent years, increasing attention has been dedicated to these non-cholinergic BF neurons in order to better understand how non-cholinergic BF circuits control cortical processing and behavioral performance. In this review, we focus on a unique population of putative non-cholinergic BF neurons that encodes the motivational salience of stimuli with a robust ensemble bursting response. We review recent studies that describe the specific physiological and functional characteristics of these BF salience encoding neurons in behaving animals. These studies support the unifying hypothesis whereby BF salience-encoding neurons act as a gain modulation mechanism of the decision-making process to enhance cortical processing of behaviorally relevant stimuli, and thereby facilitate faster and more precise behavioral responses. This function of BF salience encoding neurons represents a critical component in determining which incoming stimuli warrant an animal's attention, and is therefore a fundamental and early requirement of behavioral flexibility. C1 [Raver, Sylvina M.; Lin, Shih-Chieh] NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. RP Lin, SC (reprint author), NIA, Neural Circuits & Cognit Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. EM shih-chieh.lin@nih.gov OI Lin, Shih-Chieh/0000-0003-3693-5476 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 57 TC 2 Z9 2 U1 1 U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PD OCT 12 PY 2015 VL 9 AR 277 DI 10.3389/fnbeh.2015.00277 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CT0YA UT WOS:000362522800001 PM 26528157 ER PT J AU Godlewski, G Jourdan, T Szanda, G Tam, J Cinar, R Harvey-White, J Liu, J Mukhopadhyay, B Pacher, P Mo, FM Osei-Hyiaman, D Kunos, G AF Godlewski, Grzegorz Jourdan, Tony Szanda, Gergoe Tam, Joseph Cinar, Resat Harvey-White, Judith Liu, Jie Mukhopadhyay, Bani Pacher, Pal Mo, Fong Ming Osei-Hyiaman, Douglas Kunos, George TI Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue SO SCIENTIFIC REPORTS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MAINTAINS MEIOTIC ARREST; MOUSE OOCYTES; INSULIN-RESISTANCE; MOLECULAR-CLONING; LEPTIN RESISTANCE; OVARIAN FAILURE; DEFICIENT MICE; LAEVIS OOCYTES; GENES AB We report an unexpected link between aging, thermogenesis and weight gain via the orphan G protein-coupled receptor GPR3. Mice lacking GPR3 and maintained on normal chow had similar body weights during their first 5 months of life, but gained considerably more weight thereafter and displayed reduced total energy expenditure and lower core body temperature. By the age of 5 months GPR3 KO mice already had lower thermogenic gene expression and uncoupling protein 1 protein level and showed impaired glucose uptake into interscapular brown adipose tissue (iBAT) relative to WT littermates. These molecular deviations in iBAT of GPR3 KO mice preceded measurable differences in body weight and core body temperature at ambient conditions, but were coupled to a failure to maintain thermal homeostasis during acute cold challenge. At the same time, the same cold challenge caused a 17-fold increase in Gpr3 expression in iBAT of WT mice. Thus, GPR3 appears to have a key role in the thermogenic response of iBAT and may represent a new therapeutic target in age-related obesity. C1 [Godlewski, Grzegorz; Jourdan, Tony; Szanda, Gergoe; Tam, Joseph; Cinar, Resat; Harvey-White, Judith; Liu, Jie; Mukhopadhyay, Bani; Mo, Fong Ming; Osei-Hyiaman, Douglas; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Pacher, Pal] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD 20892 USA. RP Godlewski, G (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,RM 2S-18,MSC-9413, Bethesda, MD 20892 USA. EM godlewskig@mail.nih.gov; George.Kunos@nih.gov OI CINAR, RESAT/0000-0002-8597-7253 FU intramural research program of National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health FX This study was supported by funds from the intramural research program of National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health. NR 53 TC 2 Z9 2 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 12 PY 2015 VL 5 AR 14953 DI 10.1038/srep14953 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT1LO UT WOS:000362560000001 PM 26455425 ER PT J AU Safronetz, D Rosenke, K Westover, JB Martellaro, C Okumura, A Furuta, Y Geisbert, J Saturday, G Komeno, T Geisbert, TW Feldmann, H Gowen, BB AF Safronetz, David Rosenke, Kyle Westover, Jonna B. Martellaro, Cynthia Okumura, Atsushi Furuta, Yousuke Geisbert, Joan Saturday, Greg Komeno, Takashi Geisbert, Thomas W. Feldmann, Heinz Gowen, Brian B. TI The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset SO SCIENTIFIC REPORTS LA English DT Article ID VIRAL HEMORRHAGIC-FEVER; IN-VIVO ACTIVITIES; T-705 FAVIPIRAVIR; MOUSE MODEL; CYNOMOLGUS MACAQUES; CLINICAL-DISEASE; HAMSTER MODEL; WEST-AFRICA; EFFICACY; RIBAVIRIN AB With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs. C1 [Safronetz, David; Rosenke, Kyle; Martellaro, Cynthia; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT USA. [Westover, Jonna B.; Gowen, Brian B.] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA. [Okumura, Atsushi] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Furuta, Yousuke; Komeno, Takashi] Toyama Chem Co Ltd, Res Labs, Toyama, Japan. [Saturday, Greg] NIAID, Rocky Mt Vet Branch, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT USA. [Geisbert, Joan; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Geisbert, Joan; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP Safronetz, D (reprint author), Publ Hlth Agcy Canada, Zoonot Dis & Special Pathogens, Winnipeg, MB, Canada. EM david.safronetz@phac-aspc.gc.ca; brian.gowen@usu.edu RI Okumura, Atsushi/E-8012-2015 OI Okumura, Atsushi/0000-0002-7779-3059 FU Division of Intramural Research (DIR) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Rocky Mountain RCE [U54 AI-065357] FX This work was supported in part by the Division of Intramural Research (DIR) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and the Rocky Mountain RCE (subaward to BBG as part of NIH grant U54 AI-065357; J. Belisle, PI). We thank Sandy Skorupa, Jayne Faris, Amanda Weidow, Kathy Cordova and Richard Cole for assistance with animal procedures and husbandry and Tina Thomas, Rebecca Rosenke and Dan Long for preparing the slides for IHC (Rocky Mountain Veterinary Branch, NIAID, NIH). NR 39 TC 6 Z9 6 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 12 PY 2015 VL 5 AR 14775 DI 10.1038/srep14775 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT1KY UT WOS:000362558400001 PM 26456301 ER PT J AU Shi, M DeRoo, LA Sandler, DP Weinberg, CR AF Shi, Min DeRoo, Lisa A. Sandler, Dale P. Weinberg, Clarice R. TI Migraine and possible etiologic heterogeneity for hormone-receptor-negative breast cancer SO SCIENTIFIC REPORTS LA English DT Article ID POSTMENOPAUSAL WOMEN; RISK; HISTORY; HEALTH; PREMENOPAUSAL; PREVENTION; ESTROGEN; COHORT AB Migraine headache is often timed with the menstrual cycle. Some studies have reported reduced risk of breast cancer in migraineurs but most of those did not distinguish menstrually-related from non-menstrually-related migraine. To examine the possible associations between breast cancer and migraine overall and between cancer subcategories and the two migraine subtypes, we used a cohort study of 50,884 women whose sister had breast cancer and a sister-matched case-control study including 1,418 young-onset (<50 years) breast cancer cases. We analyzed the two studies individually and also in tandem via a hybrid Cox model, examining subcategories of breast cancer in relation to menstrually-related and non-menstrually-related migraine. History of migraine was not associated with breast cancer overall. Migraine showed an inverse association with ductal carcinoma in situ (HR = 0.77; 95%CI (0.62,0.96)). Also, women with non-menstrually-related migraine had increased risk (HR = 1.30, 95% CI (0.93,1.81)) while women with menstrually-related migraine had decreased risk (HR = 0.63, 95% CI (0.42,0.96)) of hormone-receptor-negative (ER-/PR-) cancer, with a significant contrast in estimated effects (P = 0.005). While replication of these subset-based findings will be needed, effect specificity could suggest that while migraine has little overall association with breast cancer, menstrual migraine may be associated with reduced risk of ER-/PR-breast cancer. C1 [Shi, Min; Weinberg, Clarice R.] NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [DeRoo, Lisa A.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [DeRoo, Lisa A.; Sandler, Dale P.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. RP Weinberg, CR (reprint author), NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES040007; Z01-ES45002]; Susan G. Komen for the Cure [FAS 0703856] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES040007; Z01-ES45002). The Two Sister Study was partially supported by Susan G. Komen for the Cure (FAS 0703856). We thank Drs. Katie O'Brien and Hazel Nichols for their careful review and valuable comments. NR 28 TC 1 Z9 1 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 12 PY 2015 VL 5 AR 14943 DI 10.1038/srep14943 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT1MW UT WOS:000362563600001 PM 26456840 ER PT J AU Eggly, S Hamel, LM Chou, WYS Thai, CL Debono, DJ Chapman, R Albrecht, TL Penner, L AF Eggly, Susan Hamel, Lauren M. Chou, Wen-Ying Sylvia Thai, Chan L. Debono, David Joseph Chapman, Robert Albrecht, Terrance Lynn Penner, Louis TI Oncologists' discussions of treatment goals and prognosis during clinic visits with African Americans with advanced cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Palliative Care in Oncology Symposium CY OCT 09-10, 2015 CL Boston, MA C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NIH, NCI, Rockville, MD USA. Karmanos Canc Ctr, Bloomfield Hills, MI USA. Henry Ford Hosp, Detroit, MI 48202 USA. Wayne State Univ, Detroit, MI USA. NR 0 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 OCT 10 PY 2015 VL 33 IS 29 SU S MA 34 PG 1 WC Oncology SC Oncology GA DO9LD UT WOS:000378107000033 ER PT J AU Halpern, MT Urato, M Schwartz, M Kent, EE AF Halpern, Michael T. Urato, Matthew Schwartz, Margot Kent, Erin E. TI Health plan, physician, and medical care ratings among end-of-life (EOL) cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Palliative Care in Oncology Symposium CY OCT 09-10, 2015 CL Boston, MA C1 Univ Arizona, Coll Publ Hlth, Tucson, AZ USA. RTI Int, Res Triangle Pk, NC USA. RTI Int, Waltham, MA USA. NCI, NIH, Rockville, MD USA. NR 0 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 OCT 10 PY 2015 VL 33 IS 29 SU S MA 80 PG 1 WC Oncology SC Oncology GA DO9LD UT WOS:000378107000079 ER PT J AU Kent, EE Litzelman, K Rowland, JH AF Kent, Erin E. Litzelman, Kristin Rowland, Julia Howe TI Health behaviors and coping among informal caregivers of lung and colorectal cancer survivors: Distribution and interrelationships. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Palliative Care in Oncology Symposium CY OCT 09-10, 2015 CL Boston, MA C1 NCI, NIH, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 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 OCT 10 PY 2015 VL 33 IS 29 SU S MA 229 PG 1 WC Oncology SC Oncology GA DO9LD UT WOS:000378107000221 ER PT J AU Kent, EE Litzelman, K Rowland, JH AF Kent, Erin E. Litzelman, Kristin Rowland, Julia Howe TI Correlates of and interrelationships among social stressors, relationship quality, and family functioning among informal cancer caregivers. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Palliative Care in Oncology Symposium CY OCT 09-10, 2015 CL Boston, MA C1 NCI, NIH, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2015 VL 33 IS 29 SU S MA 230 PG 1 WC Oncology SC Oncology GA DO9LD UT WOS:000378107000222 ER PT J AU Hayes, DN Van Waes, C Seiwert, TY AF Hayes, D. Neil Van Waes, Carter Seiwert, Tanguy Y. TI Genetic Landscape of Human Papillomavirus-Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; COMPREHENSIVE GENOMIC CHARACTERIZATION; MULTIPLE HUMAN CANCERS; OROPHARYNGEAL CANCER; NASOPHARYNGEAL CARCINOMA; PLUS CETUXIMAB; HPV INFECTION; RECURRENT; ACTIVATION; MUTATIONS AB Head and neck cancer is the fifth most common cancer worldwide. It is often amenable to curative intent therapy when localized to the head and neck region, but it carries a poor prognosis when it is recurrent or metastatic. Therefore, initial treatment decisions are critical to improve patient survival. However, multimodality therapy used with curative intent is toxic. The balance between offering intensive versus tolerable and function-preserving therapy has been thrown into sharp relief with the recently described epidemic of human papillomavirus-associated head and neck squamous cell carcinomas characterized by improved clinical outcomes compared with smoking-associated head and neck tumors. Model systems and clinical trials have been slow to address the clinical questions that face the field to date. With this as a background, a host of translational studies have recently reported the somatic alterations in head and neck cancer and have highlighted the distinct genetic and biologic differences between viral and tobacco-associated tumors. This review seeks to summarize the main findings of studies, including The Cancer Genome Atlas, for the clinician scientist, with a goal of leveraging this new knowledge toward the betterment of patients with head and neck cancer. (C) 2015 by American Society of Clinical Oncology C1 [Hayes, D. Neil] Univ N Carolina, Chapel Hill, NC 27599 USA. [Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Seiwert, Tanguy Y.] Univ Chicago, Chicago, IL 60637 USA. RP Hayes, DN (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA. EM hayes@med.unc.edu FU GeneCentric FX GeneCentric NR 63 TC 18 Z9 18 U1 5 U2 9 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 OCT 10 PY 2015 VL 33 IS 29 BP 3227 EP + DI 10.1200/JCO.2015.62.1086 PG 10 WC Oncology SC Oncology GA CY5UW UT WOS:000366474000002 PM 26351353 ER PT J AU Gillison, ML Chaturvedi, AK Anderson, WF Fakhry, C AF Gillison, Maura L. Chaturvedi, Anil K. Anderson, William F. Fakhry, Carole TI Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ORAL HUMAN-PAPILLOMAVIRUS; UNITED-STATES; HPV INFECTION; RISK-FACTORS; OROPHARYNGEAL CANCER; INCIDENCE TRENDS; CERVICAL-CANCER; INCIDENCE RATES; TONGUE CANCER; YOUNG MEN AB Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention. (C) 2015 by American Society of Clinical Oncology C1 [Gillison, Maura L.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Chaturvedi, Anil K.; Anderson, William F.] NCI, NIH, Rockville, MD USA. [Fakhry, Carole] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Gillison, ML (reprint author), Ohio State Univ, 420 West 12th Ave,Room 620, Columbus, OH 43210 USA. EM Maura.Gillison@osumc.edu RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 NR 72 TC 55 Z9 55 U1 3 U2 11 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 OCT 10 PY 2015 VL 33 IS 29 BP 3235 EP + DI 10.1200/JCO.2015.61.6995 PG 9 WC Oncology SC Oncology GA CY5UW UT WOS:000366474000003 PM 26351338 ER PT J AU Roter, DL Erby, LH Rimal, RN Smith, KC Larson, S Bennett, IM Cole, KW Guan, Y Molloy, M Bienstock, J AF Roter, Debra L. Erby, Lori H. Rimal, Rajiv N. Smith, Katherine C. Larson, Susan Bennett, Ian M. Cole, Katie Washington Guan, Yue Molloy, Matthew Bienstock, Jessica TI Empowering Women's Prenatal Communication: Does Literacy Matter? SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID MEDICAL VISIT COMMUNICATION; GENETIC-COUNSELING DIALOGUE; RANDOMIZED-CONTROLLED-TRIAL; HEALTH LITERACY; CARE; QUALITY; PARTICIPATION; HYPERTENSION; DEMAND; RIAS AB This study was designed to evaluate the impact of an interactive computer program developed to empower prenatal communication among women with restricted literacy skills. A total of 83 women seeing 17 clinicians were randomized to a computer-based communication activation intervention (Healthy Babies Healthy Moms [HBHM]) or prenatal education (Baby Basics [BB]) prior to their prenatal visit. Visit communication was coded with the Roter Interaction Analysis System, and postvisit satisfaction was reported. Participants were on average 24 years of age and 25 weeks pregnant; 80% were African American. Two thirds scored <= 8th grade on a literacy screener. Women with literacy deficits were more verbally active, disclosed more medical and psychosocial/lifestyle information, and were rated as more dominant by coders in the HBHM group relative to their counterparts in the BB group (all ps<.05). Clinicians were less verbally dominant and more patient centered with literate HBHM relative to BB group women (p<.05); there was a similar, nonsignificant trend (p<.1) for lower literate women. Clinicians communicated less medical information and made fewer reassurance statements to lower literate women in the HBHM relative to the BB group (p<.05). There was a trend toward lower visit satisfaction for women with restricted literacy in the HBHM relative to the BB group (p<.1); no difference in satisfaction was evident for more literate women. The HBHM intervention empowered communication of all women and facilitated verbal engagement and relevant disclosure of medical and psychosocial information of women with literacy deficits. Satisfaction, however, tended to be lower for these women. C1 [Roter, Debra L.; Smith, Katherine C.; Larson, Susan; Cole, Katie Washington; Guan, Yue] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Erby, Lori H.] NHGRI, Social & Behav Res Branch, NIH, Rockville, MD USA. [Rimal, Rajiv N.] George Washington Univ, Dept Prevent & Community Hlth, Washington, DC USA. [Bennett, Ian M.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Molloy, Matthew] Johns Hopkins Sch Med, Johns Hopkins Childrens Ctr, Baltimore, MD USA. [Bienstock, Jessica] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD USA. RP Roter, DL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, 624 North Broadway, Baltimore, MD 21205 USA. EM droterl@tjhu.edu FU National Institute of Child Health and Human Development [RO1 HD050437] FX This study was funded by Grant No. RO1 HD050437 from the National Institute of Child Health and Human Development, "Amelioration of Literacy Deficits in Prenatal Care." NR 27 TC 4 Z9 4 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD OCT 9 PY 2015 VL 20 SU 2 SI SI BP 60 EP 68 DI 10.1080/10810730.2015.1080330 PG 9 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA CU7BL UT WOS:000363690000008 PM 26513032 ER PT J AU Tacheau, A Le Floc'h, S Finet, G Doyley, MM Pettigrew, RI Cloutier, G Ohayon, J AF Tacheau, A. Le Floc'h, S. Finet, G. Doyley, M. M. Pettigrew, R. I. Cloutier, G. Ohayon, J. TI An intravascular coronary plaque elasticity reconstruction method using limited depth penetration ultrasound signals SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Meeting Abstract DE Modulography; linear elasticity; inverse problem; vulnerable plaques; coronary disease ID THICKNESS C1 [Tacheau, A.; Ohayon, J.] UJF, CNRS, Lab TIMC IMAG DyCTiM2, UMR 5525, Grenoble, France. [Le Floc'h, S.] Univ Montpellier 2, CNRS UMR 5508, Lab LMGC, Montpellier, France. [Finet, G.] Hosp Civils Lyon, Lyon, France. [Finet, G.] Univ Lyon 1, F-69365 Lyon, France. [Finet, G.] INSERM, U886, F-69008 Lyon, France. [Doyley, M. M.] Univ Rochester, Dept Elect & Comp Engn, Rochester, NY USA. [Pettigrew, R. I.] NIDDK, NIH, Bethesda, MD USA. [Cloutier, G.] CRCHUM, Lab Biorheol & Med Ultrason, Montreal, PQ, Canada. [Ohayon, J.] Univ Savoie Mont Blanc, Polytech Annecy Chambery, Le Bourget Du Lac, France. RP Ohayon, J (reprint author), UJF, CNRS, Lab TIMC IMAG DyCTiM2, UMR 5525, Grenoble, France. EM jacques.ohayon@imag.fr FU University Grenoble-Alpes, France (AGIR); la Region Rhone-Alpes FX Antoine Tacheau held a doctoral fellowship from University Grenoble-Alpes, France (AGIR 2013). Funding of this project was provided by a grant from la Region Rhone-Alpes 2014-2015. NR 6 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-5842 EI 1476-8259 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PD OCT 9 PY 2015 VL 18 SU 1 SI SI BP 2066 EP 2067 DI 10.1080/10255842.2015.1069604 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA CT5EQ UT WOS:000362831400008 PM 26260190 ER PT J AU Miller, TW Soto-Pantoja, DR Schwartz, AL Sipes, JM DeGraff, WG Ridnour, LA Wink, DA Roberts, DD AF Miller, Thomas W. Soto-Pantoja, David R. Schwartz, Anthony L. Sipes, John M. DeGraff, William G. Ridnour, Lisa A. Wink, David A. Roberts, David D. TI CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-IRRADIATED RATS; C-MYC; MASS-SPECTROMETRY; TUMOR-CELLS; IN-VIVO; MITOCHONDRIAL BIOGENESIS; URINARY-EXCRETION; GENE-EXPRESSION; MICE; IDENTIFICATION AB Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury. C1 [Miller, Thomas W.; Soto-Pantoja, David R.; Schwartz, Anthony L.; Sipes, John M.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Miller, Thomas W.] Paradigm Shift Therapeut, Rockville, MD 20852 USA. [Soto-Pantoja, David R.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Soto-Pantoja, David R.] Wake Forest Sch Med, Dept Hypertens, Winston Salem, NC 27157 USA. [Soto-Pantoja, David R.] Wake Forest Sch Med, Vasc Res Ctr, Winston Salem, NC 27157 USA. RP Soto-Pantoja, DR (reprint author), Wake Forest Sch Med, Dept Canc Biol & Hypertens, Winston Salem, NC 27157 USA. EM dsotopan@wakehealth.edu; droberts@helix.nih.gov RI Regan, Clinton/E-6250-2012; Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU National Institutes of Health [ZIASC009172, ZIA BC 010898, ZIASC009174]; NCI Directors Career Development Innovation Award; NCI Office of Biotechnology Partnerships; Avon Foundation FX This work was supported, in whole or in part, by National Institutes of Health Projects ZIASC009172, ZIA BC 010898, and ZIASC009174 (Intramural Research Program of the NCI; to D. D. R. and D. A. W), an NCI Directors Career Development Innovation Award (to T. W. M.), and by the NCI Office of Biotechnology Partnerships (to D. S.-P.). This work was also supported by the Avon Foundation (to T. W. M.). The authors declare that they have no conflicts of interest with the contents of this article. NR 60 TC 6 Z9 6 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 2015 VL 290 IS 41 BP 24858 EP 24874 DI 10.1074/jbc.M115.665752 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT1YF UT WOS:000362598300020 PM 26311851 ER PT J AU Henderson, MJ Baldwin, HA Werley, CA Boccardo, S Whitaker, LR Yan, XK Holt, GT Schreiter, ER Looger, LL Cohen, AE Kim, DS Harvey, BK AF Henderson, Mark J. Baldwin, Heather A. Werley, Christopher A. Boccardo, Stefano Whitaker, Leslie R. Yan, Xiaokang Holt, Graham T. Schreiter, Eric R. Looger, Loren L. Cohen, Adam E. Kim, Douglas S. Harvey, Brandon K. TI A Low Affinity GCaMP3 Variant (GCaMPer) for Imaging the Endoplasmic Reticulum Calcium Store SO PLOS ONE LA English DT Article ID ENCODED CA2+ INDICATORS; FLUORESCENT PROTEINS; MOUSE MODEL; DISEASE; RELEASE; NEURONS; PUMPS; HOMEOSTASIS; EXPRESSION; ORGANELLES AB Endoplasmic reticulum calcium homeostasis is critical for cellular functions and is disrupted in diverse pathologies including neurodegeneration and cardiovascular disease. Owing to the high concentration of calcium within the ER, studying this subcellular compartment requires tools that are optimized for these conditions. To develop a single-fluorophore genetically encoded calcium indicator for this organelle, we targeted a low affinity variant of GCaMP3 to the ER lumen (GCaMPer (10.19)). A set of viral vectors was constructed to express GCaMPer in human neuroblastoma cells, rat primary cortical neurons, and human induced pluripotent stem cell-derived cardiomyocytes. We observed dynamic changes in GCaMPer (10.19) fluorescence in response to pharmacologic manipulations of the ER calcium store. Additionally, periodic calcium efflux from the ER was observed during spontaneous beating of cardiomyocytes. GCaMPer (10.19) has utility in imaging ER calcium in living cells and providing insight into luminal calcium dynamics under physiologic and pathologic states. C1 [Henderson, Mark J.; Baldwin, Heather A.; Whitaker, Leslie R.; Yan, Xiaokang; Harvey, Brandon K.] NIDA, NIH, Baltimore, MD 21224 USA. [Werley, Christopher A.; Boccardo, Stefano; Cohen, Adam E.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Cohen, Adam E.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Cohen, Adam E.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cohen, Adam E.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Holt, Graham T.; Schreiter, Eric R.; Looger, Loren L.; Kim, Douglas S.] Howard Hughes Med Inst, Ashburn, VA 20147 USA. RP Henderson, MJ (reprint author), NIDA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM hendersonmj@mail.nih.gov; BHarvey@intra.nida.nih.gov FU Intramural Research Program, National Institute on Drug Abuse; Howard Hughes Medical Institute; US National Institutes of Health [1-R01-EB012498-01, 1-DP2-OD007428]; Office of Naval Research PECASE award [N00014-11-1-0549]; Roche Postdoctoral Fellowship FX This work was funded by the Intramural Research Program, National Institute on Drug Abuse (MJH HAB LWR BKH); Howard Hughes Medical Institute (ERS LLL DSK); US National Institutes of Health grants 1-R01-EB012498-01 and New Innovator grant 1-DP2-OD007428, and Office of Naval Research PECASE award N00014-11-1-0549 (CAW, SB, AEC). AEC is supported by the Howard Hughes Medical Institute. SB was supported by a Roche Postdoctoral Fellowship. NR 47 TC 7 Z9 7 U1 3 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 9 PY 2015 VL 10 IS 10 AR e0139273 DI 10.1371/journal.pone.0139273 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TY UT WOS:000362511200009 PM 26451944 ER PT J AU Risso, D Taglioli, L De Iasio, S Gueresi, P Alfani, G Nelli, S Rossi, P Paoli, G Tofanelli, S AF Risso, Davide Taglioli, Luca De Iasio, Sergio Gueresi, Paola Alfani, Guido Nelli, Sergio Rossi, Paolo Paoli, Giorgio Tofanelli, Sergio TI Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach SO PLOS ONE LA English DT Article ID POPULATION STRUCTURES; MIGRATION MATRICES; SURNAMES; ANCESTRY; SARDINIA AB This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. C1 [Risso, Davide] NIDCD, NIH, Bethesda, MD 20854 USA. [Risso, Davide] Univ Bologna, Lab Mol Anthropol, I-40126 Bologna, Italy. [Risso, Davide] Univ Bologna, Ctr Genome Biol, Dept BiGeA, I-40126 Bologna, Italy. [Taglioli, Luca; Paoli, Giorgio; Tofanelli, Sergio] Univ Pisa, Dipartimento Biol, I-56126 Pisa, Italy. [De Iasio, Sergio] Univ Parma, Dipartimento Genet Biol Microrganismi Antropol, I-43124 Parma, Italy. [Gueresi, Paola] Univ Bologna, Dipartimento Sci Stat, I-40126 Bologna, Italy. [Alfani, Guido] Bocconi Univ, Dondena Ctr, Milan, Italy. [Alfani, Guido] IGIER, Milan, Italy. [Nelli, Sergio] Archivio Stato, Lucca, Italy. [Rossi, Paolo] Univ Pisa, Dipartimento Fis, I-56127 Pisa, Italy. RP Tofanelli, S (reprint author), Univ Pisa, Dipartimento Biol, Via Ghini 13, I-56126 Pisa, Italy. EM sergio.tofanelli@unipi.it OI Risso, Davide/0000-0001-9848-8996 NR 25 TC 0 Z9 0 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 9 PY 2015 VL 10 IS 10 AR e0140146 DI 10.1371/journal.pone.0140146 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TY UT WOS:000362511200042 PM 26452043 ER PT J AU Turanov, AA Everley, RA Hybsier, S Renko, K Schomburg, L Gygi, SP Hatfield, DL Gladyshev, VN AF Turanov, Anton A. Everley, Robert A. Hybsier, Sandra Renko, Kostja Schomburg, Lutz Gygi, Steven P. Hatfield, Dolph L. Gladyshev, Vadim N. TI Regulation of Selenocysteine Content of Human Selenoprotein P by Dietary Selenium and Insertion of Cysteine in Place of Selenocysteine SO PLOS ONE LA English DT Article ID CANCER; MOUSE; EXPRESSION; HEALTH; GENE AB Selenoproteins are a unique group of proteins that contain selenium in the form of selenocysteine (Sec) co-translationally inserted in response to a UGA codon with the help of cis- and trans-acting factors. Mammalian selenoproteins contain single Sec residues, with the exception of selenoprotein P (SelP) that has 7-15 Sec residues depending on species. Assessing an individual's selenium status is important under various pathological conditions, which requires a reliable selenium biomarker. Due to a key role in organismal selenium homeostasis, high Sec content, regulation by dietary selenium, and availability of robust assays in human plasma, SelP has emerged as a major biomarker of selenium status. Here, we found that Cys is present in various Sec positions in human SelP. Treatment of cells expressing SelP with thiophosphate, an analog of the selenium donor for Sec synthesis, led to a nearly complete replacement of Sec with Cys, whereas supplementation of cells with selenium supported Sec insertion. SelP isolated directly from human plasma had up to 8% Cys inserted in place of Sec, depending on the Sec position. These findings suggest that a change in selenium status may be reflected in both SelP concentration and its Sec content, and that availability of the SelP-derived selenium for selenoprotein synthesis may be overestimated under conditions of low selenium status due to replacement of Sec with Cys. C1 [Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Everley, Robert A.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Hybsier, Sandra; Renko, Kostja; Schomburg, Lutz] Charite, Dept Urol, Inst Expt Endocrinol, D-13353 Berlin, Germany. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu OI Bermano, Giovanna/0000-0001-6027-6437 FU National Institutes of Health [GM061603] FX This work was supported by National Institutes of Health GM061603 (to VNG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 5 Z9 5 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 9 PY 2015 VL 10 IS 10 AR e0140353 DI 10.1371/journal.pone.0140353 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TY UT WOS:000362511200066 PM 26452064 ER PT J AU Guo, YB Singh, PK Levin, HL AF Guo, Yabin Singh, Parmit Kumar Levin, Henry L. TI A long terminal repeat retrotransposon of Schizosaccharomyces japonicus integrates upstream of RNA pol III transcribed genes SO MOBILE DNA LA English DT Article DE Tj1; Long terminal repeat retrotransposon; Schizosaccharomyces japonicus; Schizosaccharomyces pombe; Integration ID FUNCTIONAL DROSOPHILA CENTROMERE; REVERSE TRANSCRIPTION; POLYMERASE-III; FISSION YEAST; LTR RETROTRANSPOSONS; GERM-CELLS; TY3; RETROVIRUSES; ELEMENTS; HETEROCHROMATIN AB Background: Transposable elements (TEs) are common constituents of centromeres. However, it is not known what causes this relationship. Schizosaccharomyces japonicus contains 10 families of Long Terminal Repeat (LTR)-retrotransposons and these elements cluster in centromeres and telomeres. In the related yeast, Schizosaccharomyces pombe LTR-retrotransposons Tf1 and Tf2 are distributed in the promoter regions of RNA pol II transcribed genes. Sequence analysis of TEs indicates that Tj1 of S. japonicus is related to Tf1 and Tf2, and uses the same mechanism of self-primed reverse transcription. Thus, we wondered why these related retrotransposons localized in different regions of the genome. Results: To characterize the integration behavior of Tj1 we expressed it in S. pombe. We found Tj1 was active and capable of generating de novo integration in the chromosomes of S. pombe. The expression of Tj1 is similar to Type C retroviruses in that a stop codon at the end of Gag must be present for efficient integration. 17 inserts were sequenced, 13 occurred within 12 bp upstream of tRNA genes and 3 occurred at other RNA pol III transcribed genes. The link between Tj1 integration and RNA pol III transcription is reminiscent of Ty3, an LTR-retrotransposon of Saccharomyces cerevisiae that interacts with TFIIIB and integrates upstream of tRNA genes. Conclusion: The integration of Tj1 upstream of tRNA genes and the centromeric clustering of tRNA genes in S. japonicus demonstrate that the clustering of this TE in centromere sequences is due to a unique pattern of integration. C1 [Singh, Parmit Kumar; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bldg 18 T,Room 106, Bethesda, MD 20892 USA. EM levinh@mail.nih.gov OI , Guo/0000-0001-8316-8527 FU Intramural Research Programs of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Programs of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. We thank Dr. Nicholas Rhind for his help in accessing sequences of S. japonicus. NR 51 TC 1 Z9 1 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PD OCT 9 PY 2015 VL 6 AR 19 DI 10.1186/s13100-015-0048-2 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CT1CF UT WOS:000362534200001 PM 26457121 ER PT J AU Toh, S Holbrook-Smith, D Stogios, PJ Onopriyenko, O Lumba, S Tsuchiya, Y Savchenko, A McCourt, P AF Toh, Shigeo Holbrook-Smith, Duncan Stogios, Peter J. Onopriyenko, Olena Lumba, Shelley Tsuchiya, Yuichiro Savchenko, Alexei McCourt, Peter TI Structure-function analysis identifies highly sensitive strigolactone receptors in Striga SO SCIENCE LA English DT Article ID PARASITIC PLANTS; ARABIDOPSIS; GERMINATION; PERCEPTION; RICE; HERMONTHICA AB Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels. C1 [Toh, Shigeo; Holbrook-Smith, Duncan; Lumba, Shelley; McCourt, Peter] Univ Toronto, Cell & Syst Biol, Toronto, ON M5S 3B2, Canada. [Stogios, Peter J.; Onopriyenko, Olena; Savchenko, Alexei] Univ Toronto, Banting & Best Dept Med Res, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada. [Stogios, Peter J.] NIAID, Ctr Struct Genom Infect Dis, NIH, Bethesda, MD 20892 USA. [Tsuchiya, Yuichiro] Nagoya Univ, Inst Transformat Biomol, Chikusa Ku, Nagoya, Aichi 4648602, Japan. RP McCourt, P (reprint author), Univ Toronto, Cell & Syst Biol, 25 Willcocks St, Toronto, ON M5S 3B2, Canada. EM peter.mccourt@utoronto.ca OI Stogios, Peter/0000-0001-8663-1425; Holbrook-Smith, Duncan/0000-0003-0787-3165 FU National Science and Engineering Research Council of Canada FX We thank A. Babikier for providing the Striga seeds and T. Nakagawa for the pGWB611 binary vector. Rice lines were provided by the National Genetic Resources Program at the U.S. Department of Agriculture. This work was supported by a grant from the National Science and Engineering Research Council of Canada to P.M. We thank R. Di Leo for technical assistance. Nucleotide and amino acid sequences corresponding to ShD14 and ShHTLs have been deposited with GenBank under accession KR013120 to KR013131. S.T., D.H.-S., P.M., and the University of Toronto have filed a U.S. provisional patent application (US62/151,701) that relates to the specific topic "Strigolactone biosensors." We declare no financial conflicts of interest in relation to the work. The supplementary materials contain additional data. NR 17 TC 27 Z9 27 U1 13 U2 71 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 9 PY 2015 VL 350 IS 6257 BP 203 EP 207 DI 10.1126/science.aac9476 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS9JB UT WOS:000362405600038 PM 26450211 ER PT J AU Wang, C McKeithan, TW Gong, Q Zhang, WW Bouska, A Rosenwald, A Gascoyne, RD Wu, XW Wang, JH Muhammad, Z Jiang, B Rohr, J Cannon, A Steidl, C Fu, K Li, YP Hung, S Weisenburger, DD Greiner, TC Smith, L Ott, G Rogan, EG Staudt, LM Vose, J Iqbal, J Chan, WC AF Wang, Chao McKeithan, Timothy W. Gong, Qiang Zhang, Weiwei Bouska, Alyssa Rosenwald, Andreas Gascoyne, Randy D. Wu, Xiwei Wang, Jinhui Muhammad, Zahid Jiang, Bei Rohr, Joseph Cannon, Andrew Steidl, Christian Fu, Kai Li, Yuping Hung, Stacy Weisenburger, Dennis D. Greiner, Timothy C. Smith, Lynette Ott, German Rogan, Eleanor G. Staudt, Louis M. Vose, Julie Iqbal, Javeed Chan, Wing C. TI IDH2(R172) mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FOLLICULAR HELPER-CELLS; IDH2 MUTATIONS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; TET2; CANCER; MANAGEMENT; RHOA; DIFFERENTIATION; MALIGNANCIES AB Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma (PTCL) with a poor prognosis. We performed targeted resequencing on 92 cases of PTCL and identified frequent mutations affecting RHOA, TET2, DNMT3A, and isocitrate dehydrogenase 2 (IDH2). Although IDH2 mutations are largely confined to AITL, mutations of the other 3 can be found in other types of PTCL, although at lower frequencies. These findings indicate a key role of epigenetic regulation in the pathogenesis of AITL. However, the epigenetic alterations induced by these mutations and their role in AITL pathogenesis are still largely unknown. We correlated mutational status with gene expression and global DNA methylation changes in AITL. Strikingly, AITL cases with IDH2(R172) mutations demonstrated a distinct gene expression signature characterized by down-regulation of genes associated with T-H1 differentiation (eg, STAT1 and IFNG) and a striking enrichment of an interleukin 12-induced gene signature. Ectopic expression of IDH2(R172K) in the Jurkat cell line andCD4(+) T cells led to markedly increased levels of 2-hydroxyglutarate, histone-3 lysinemethylation, and 5-methylcytosine and a decrease of 5-hydroxymethylcytosine. Correspondingly, clinical samples with IDH2 mutations displayed a prominent increase in H3K27me3 and DNA hypermethylation of gene promoters. Integrative analysis of gene expression and promoter methylation revealed recurrently hypermethylated genes involved in T-cell receptor signaling and T-cell differentiation that likely contribute to lymphomagenesis in AITL. C1 [Wang, Chao] Shandong Univ, Sch Med, Jinan 250100, Peoples R China. [Wang, Chao; Zhang, Weiwei; Bouska, Alyssa; Jiang, Bei; Rohr, Joseph; Cannon, Andrew; Fu, Kai; Greiner, Timothy C.; Iqbal, Javeed] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Wang, Chao; McKeithan, Timothy W.; Gong, Qiang; Jiang, Bei; Rohr, Joseph; Li, Yuping; Weisenburger, Dennis D.; Chan, Wing C.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, Wurzburg, Germany. [Rosenwald, Andreas] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97070 Wurzburg, Germany. [Gascoyne, Randy D.; Steidl, Christian; Hung, Stacy] British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. [Gascoyne, Randy D.; Steidl, Christian; Hung, Stacy] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Wu, Xiwei; Wang, Jinhui] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA USA. [Muhammad, Zahid; Rogan, Eleanor G.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Environm Agr & Occupat Hlth, Omaha, NE USA. [Smith, Lynette] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Vose, Julie] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA. RP Iqbal, J (reprint author), Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. EM jiqbal@unmc.edu; jochan@coh.org OI Gong, Qiang/0000-0001-8502-6813 FU Lymphoma Research Foundation [F-263549]; Leukemia and Lymphoma Society [6129-14]; University of Nebraska Medical Center Clinical-Translational Research Scholars Program; National Institutes of Health; National Cancer Institute Eppley Cancer Center [P30CA036727]; City of Hope Cancer Center [P30 CA033572]; Specialized Programs of Research Excellence [1 P50 CA136411-01 01A1 PP-4]; Chinese Scholarship Council FX This work was supported in part by the Lymphoma Research Foundation (F-263549, to J.I.), the translational research program of the Leukemia and Lymphoma Society (6129-14, to J.I.), the University of Nebraska Medical Center Clinical-Translational Research Scholars Program, the National Institutes of Health, National Cancer Institute Eppley Cancer Center support grant P30CA036727, City of Hope Cancer Center support grant P30 CA033572, and Specialized Programs of Research Excellence (1 P50 CA136411-01 01A1 PP-4, to W.C.C.). C.W. and B.J. were recipients of Chinese Scholarship Council funding. NR 52 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 8 PY 2015 VL 126 IS 15 BP 1741 EP 1752 DI 10.1182/blood-2015-05-644591 PG 12 WC Hematology SC Hematology GA CX1JC UT WOS:000365451500007 PM 26268241 ER PT J AU Prasad, V Mailankody, S AF Prasad, Vinay Mailankody, Sham TI How should we assess the value of innovative drugs in oncology? Lessons from cost-effectiveness analyses SO BLOOD LA English DT Letter ID RITUXIMAB; LYMPHOMA; INTERGROUP C1 [Prasad, Vinay; Mailankody, Sham] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA. [Prasad, Vinay] Oregon Hlth & Sci Univ, Hematol Oncol Serv, Knight Canc Ctr, Portland, OR 97201 USA. [Mailankody, Sham] Mem Sloan Kettering Canc Ctr, Myeloma Serv, Div Hematol Malignancies, New York, NY 10065 USA. RP Mailankody, S (reprint author), Mem Sloan Kettering Canc Ctr, Myeloma Serv, Div Hematol Malignancies, SR 505N3,Scholars Bldg,5th Floor,1233 York Ave, New York, NY 10065 USA. EM mailanks@mskcc.org NR 8 TC 1 Z9 2 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 8 PY 2015 VL 126 IS 15 BP 1860 EP 1861 DI 10.1182/blood-2015-07-657478 PG 2 WC Hematology SC Hematology GA CX1JC UT WOS:000365451500023 PM 26320099 ER PT J AU Bhatt, S Weiss, DJ Cameron, E Bisanzio, D Mappin, B Dalrymple, U Battle, KE Moyes, CL Henry, A Eckhoff, PA Wenger, EA Briet, O Penny, MA Smith, TA Bennett, A Yukich, J Eisele, TP Griffin, JT Fergus, CA Lynch, M Lindgren, F Cohen, JM Murray, CLJ Smith, DL Hay, SI Cibulskis, RE Gething, PW AF Bhatt, S. Weiss, D. J. Cameron, E. Bisanzio, D. Mappin, B. Dalrymple, U. Battle, K. E. Moyes, C. L. Henry, A. Eckhoff, P. A. Wenger, E. A. Briet, O. Penny, M. A. Smith, T. A. Bennett, A. Yukich, J. Eisele, T. P. Griffin, J. T. Fergus, C. A. Lynch, M. Lindgren, F. Cohen, J. M. Murray, C. L. J. Smith, D. L. Hay, S. I. Cibulskis, R. E. Gething, P. W. TI The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015 SO NATURE LA English DT Article ID SUB-SAHARAN AFRICA; TEMPORAL ANALYSIS; PARASITE RATE; DISEASE; BURDEN; IMPACT; ENDEMICITY; INFECTION; RISK AB Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies. C1 [Bhatt, S.; Weiss, D. J.; Cameron, E.; Bisanzio, D.; Mappin, B.; Dalrymple, U.; Battle, K. E.; Moyes, C. L.; Henry, A.; Smith, D. L.; Gething, P. W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Eckhoff, P. A.; Wenger, E. A.] Intellectual Ventures, Inst Dis Modeling, Bellevue, WA 98005 USA. [Briet, O.; Penny, M. A.; Smith, T. A.] Swiss Trop & Publ Hlth Inst, Epidemiol & Publ Hlth, CH-4002 Basel, Switzerland. [Briet, O.; Penny, M. A.; Smith, T. A.] Univ Basel, CH-4001 Basel, Switzerland. [Bennett, A.] Univ Calif San Francisco, Malaria Eliminat Initiat, San Francisco, CA 94143 USA. [Yukich, J.; Eisele, T. P.] Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Appl Malaria Res & Evaluat, New Orleans, LA 70112 USA. [Cohen, J. M.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England. [Fergus, C. A.; Lynch, M.; Cibulskis, R. E.] WHO, Global Malaria Programme, CH-1211 Geneva 27, Switzerland. [Lindgren, F.] Univ Bath, Dept Math Sci, Bath BA2 7AY, Avon, England. [Cohen, J. M.] Clinton Hlth Access Initiat, Boston, MA 02127 USA. [Murray, C. L. J.; Smith, D. L.; Hay, S. I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. [Smith, D. L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD 20850 USA. [Smith, D. L.; Hay, S. I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Hay, S. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England. EM peter.gething@zoo.ox.ac.uk RI Smith, Thomas/B-5569-2015; Hay, Simon/F-8967-2015; Penny, Melissa/N-6838-2015; OI Smith, Thomas/0000-0002-3650-9381; Hay, Simon/0000-0002-0611-7272; Penny, Melissa/0000-0002-4972-593X; Mappin, Bonnie/0000-0002-1205-719X; Cohen, Justin/0000-0003-4481-6784; Gething, Peter/0000-0001-6759-5449 FU UK Medical Research Council (MRC) [K00669X]; UK Department for International Development (DFID) MRC/DFID [K00669X]; Bill and Melinda Gates Foundation (BMGF) [OPP1068048, OPP1106023]; BMGF [OPP1106023, OPP1032350, OPP1110495, OPP1119467, OPP1093011]; Wellcome Trust [095066]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; MRC Fellowship [G1002284]; Global Good Fund FX The authors acknowledge assistance from M. Renshaw in providing information from the Roll Back Malaria Harmonization Working Group Programmatic Gap Analysis and other guidance in the interpretation of our results. We thank members of the Roll Back Malaria Monitoring and Evaluation Reference Group and the World Health Organization Surveillance Monitoring and Evaluation Technical expert Group for their feedback and suggestions. We thank C. Burgert of the DHS (Demographic and Health Surveys) Program for her assistance with DHS Survey access and interpretation. P.W.G. is a Career Development Fellow(no. K00669X) jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and receives support from the Bill and Melinda Gates Foundation (BMGF; nos OPP1068048, OPP1106023). These grants also support E.C., S.B., B.M., U.D., D.J.W., D.B. and A.H. The Swiss TPH component was supported through the project no. OPP1032350 funded by the BMGF. D.L.S. is funded by the BMGF (OPP1110495). S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (no. 095066), which also supports K.E.B., and grants from the BMGF (nos. OPP1119467, OPP1106023 and OPP1093011). S.I.H. and D.L.S. also acknowledge funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. J.T.G. is funded by an MRC Fellowship (no. G1002284). E.A.W. and P.A.E. are funded by the Global Good Fund. NR 26 TC 178 Z9 183 U1 27 U2 78 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 8 PY 2015 VL 526 IS 7572 BP 207 EP + DI 10.1038/nature15535 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS9GV UT WOS:000362399000037 PM 26375008 ER PT J AU da Fonseca, DM Hand, TW Han, SJ Gerner, MY Zaretsky, AG Byrd, AL Harrison, OJ Ortiz, AM Quinones, M Trinchieri, G Brenchley, JM Brodsky, IE Germain, RN Randolph, GJ Belkaid, Y AF da Fonseca, Denise Morais Hand, Timothy W. Han, Seong-Ji Gerner, Michael Y. Zaretsky, Arielle Glatman Byrd, Allyson L. Harrison, Oliver J. Ortiz, Alexandra M. Quinones, Mariam Trinchieri, Giorgio Brenchley, Jason M. Brodsky, Igor E. Germain, Ronald N. Randolph, Gwendalyn J. Belkaid, Yasmine TI Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity SO CELL LA English DT Article ID MESENTERIC LYMPH-NODES; DENDRITIC CELLS; YERSINIA-PSEUDOTUBERCULOSIS; CROHNS-DISEASE; DEVELOPING-COUNTRIES; BACTERIAL PATHOGENS; ORAL TOLERANCE; INFLAMMATION; RESPONSES; ANTIGEN AB Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node. As a consequence, canonical mucosal immune functions, including tolerance and protective immunity, are persistently compromised. Post-resolution of infection, signals derived from the microbiota maintain inflammatory mesentery remodeling and consequently, transient ablation of the microbiota restores mucosal immunity. Our results indicate that persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long-term. C1 [da Fonseca, Denise Morais; Hand, Timothy W.; Han, Seong-Ji; Zaretsky, Arielle Glatman; Byrd, Allyson L.; Harrison, Oliver J.; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [da Fonseca, Denise Morais; Hand, Timothy W.; Han, Seong-Ji; Zaretsky, Arielle Glatman; Byrd, Allyson L.; Harrison, Oliver J.; Belkaid, Yasmine] NIAID, Immun Barrier Sites Initiat, NIH, Bethesda, MD 20892 USA. [da Fonseca, Denise Morais] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, Brazil. [Gerner, Michael Y.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Byrd, Allyson L.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. [Byrd, Allyson L.] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. [Ortiz, Alexandra M.; Brenchley, Jason M.] NIAID, Program Tissue Immun & Repair, NIH, Bethesda, MD 20892 USA. [Ortiz, Alexandra M.; Brenchley, Jason M.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. [Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Brodsky, Igor E.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Randolph, Gwendalyn J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID), NIH; FAPESP [2012/14669-7]; CNPq/CAPES [10986-13-8]; FDA/ODS Scholarship FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID), NIH. D.M.F. was supported by FAPESP (2012/14669-7) and CNPq/CAPES (10986-13-8). T.W.H. was supported by a FDA/ODS Scholarship. We thank J.D. Clements (University of Tulane School of Medicine) for providing the E. coli dmLT. We thank D. Trageser-Cesler and C. Acevedo (NIAID Gnotobiotic Animal Facility); NIAID animal facility staff; K. Holmes, C. Eigsti, T. Moyer, and E. Stregevsky (NIAID Flow Cytometry facility); O. Schwartz, J. Kabat, L. Koo, and M. Smelkinson (NIAID Biological Imaging facility) and N. Bubunenko, D. Sun, R. Winkler-Pickett, K. Beacht, J. Davis, M. Solano-Dias and J. Legrand for technical assistance. We thank N. Bouladoux, S. Henri, A. Poholek, M. Constantinides, V. Ridaura and all the members of the Y.B. laboratory for critical reading of the manuscript and helpful discussions. NR 70 TC 4 Z9 4 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD OCT 8 PY 2015 VL 163 IS 2 BP 354 EP 366 DI 10.1016/j.cell.2015.08.030 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT6WE UT WOS:000362952700013 ER PT J AU Lubega, M Nakyaanjo, N Nansubuga, S Hiire, E Kigozi, G Nakigozi, G Lutalo, T Nalugoda, F Serwadda, D Gray, R Wawer, M Kennedy, C Reynolds, SJ AF Lubega, Muhamadi Nakyaanjo, Neema Nansubuga, Sumaya Hiire, Edgar Kigozi, Godfrey Nakigozi, Gertrude Lutalo, Tom Nalugoda, Fred Serwadda, David Gray, Ronald Wawer, Maria Kennedy, Caitlin Reynolds, Steven James TI Understanding the socio-structural context of high HIV transmission in kasensero fishing community, South Western Uganda SO BMC PUBLIC HEALTH LA English DT Article ID SEXUAL MIXING PATTERNS; POSTTRIAL FOLLOW-UP; ANTIRETROVIRAL THERAPY; MALE CIRCUMCISION; RISK BEHAVIORS; PROSPECTIVE COHORT; TRANSACTIONAL SEX; NYANZA PROVINCE; LAKE VICTORIA; HIV/AIDS AB Background: In Kasensero fishing community, home of the first recorded case of HIV in Uganda, HIV transmission remains high with an incidence of 4.3 and 3.1 per 100 person-years in women and men, respectively, and an HIV prevalence of 44 %, reaching up to 74 % among female sex workers. We explored the social contextual factors for the high HIV transmission at Kasensero to inform future policy and preventive interventions. Methods: We conducted 20 in-depth interviews, including both HIV positive and HIV negative respondents, and 12 focus-group discussions involving a total of 92 respondents from the Kasensero fishing community from April-September 2014. Content analysis was performed to identify recurrent themes. Results: Our findings suggest that the high HIV transmission in Kasensero is a complex function of eight themes including; positive/negative attitudes about HIV and combination HIV prevention such as the demand for services versus ART/circumcision disinhibition; HIV depository; Multiple partners; Frequent unprotected sex; Clothing; Parental behaviors; Pressure within the sex industry; and Cross generational sex. Conclusions: The current combination HIV prevention services by the RHSP need to be enhanced with more government involvement including ensuring sustainable supply of ART and circumcision services since they are reportedly highly demanded. Community involvement through the engagement of popular peers could also help in the campaign to change the HIV predisposing culture, misconceptions and risky social norms of the population. Social Context HIV Transmission Fishing Community. C1 [Lubega, Muhamadi; Nakyaanjo, Neema; Hiire, Edgar; Kigozi, Godfrey; Nakigozi, Gertrude; Lutalo, Tom; Nalugoda, Fred; Serwadda, David; Gray, Ronald; Wawer, Maria; Reynolds, Steven James] Rakai Hlth Sci Program, Kalisizo, Uganda. [Lubega, Muhamadi] Karolinsika Inst, Dept Publ Hlth Sci, IHCAR, Div Global Hlth, Stockholm, Sweden. [Lubega, Muhamadi; Nansubuga, Sumaya] Busoga Univ, Sch Grad Studies & Res, Iganga, Uganda. [Lubega, Muhamadi; Reynolds, Steven James] NIAID, Integrated Res Div, NIH, Bethesda, MD 20892 USA. [Gray, Ronald; Wawer, Maria; Kennedy, Caitlin; Reynolds, Steven James] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Lubega, M (reprint author), Rakai Hlth Sci Program, Old Bukoba Rd,POB 279, Kalisizo, Uganda. EM dlmuhamadi@yahoo.co.uk FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rakai Health Sciences Program; Busoga University School of Graduate Studies FX We also wish to acknowledge funding for this study in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (SJR), Rakai Health Sciences Program and Busoga University School of Graduate Studies. NR 62 TC 2 Z9 2 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 8 PY 2015 VL 15 AR 1033 DI 10.1186/s12889-015-2371-4 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT3LY UT WOS:000362709400001 PM 26449622 ER PT J AU Yokoyama, T Yoshizaki, A Simon, KL Kirby, MR Anderson, SM Candotti, F AF Yokoyama, Tadafumi Yoshizaki, Ayumi Simon, Karen L. Kirby, Martha R. Anderson, Stacie M. Candotti, Fabio TI Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice SO PLOS ONE LA English DT Article ID SYNDROME PROTEIN-DEFICIENCY; T-CELLS; AUTOIMMUNITY; WASP; ABNORMALITIES; HOMEOSTASIS; IGA AB The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19(+)CD1d(high)CD5(+) B cells (CD1d(high)CD5(+) Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1d(high)CD5(+) Breg cells as compared to age-matched WT control mice. CD1d(high)CD5(+) Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4(+) T cells. Interestingly, CD1d(high)CD5(+) Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS. C1 [Yokoyama, Tadafumi; Simon, Karen L.; Kirby, Martha R.; Anderson, Stacie M.; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Yokoyama, Tadafumi; Simon, Karen L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Yoshizaki, Ayumi] Univ Tokyo, Fac Med, Dept Dermatol, Tokyo 113, Japan. [Candotti, Fabio] Univ Lausanne Hosp, Div Immunol & Allergy, Lausanne, Switzerland. RP Candotti, F (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM Fabio.Candotti@chuv.ch FU National Human Genome Research Institute, NIH [Z01-HG000121]; Swiss National Science Foundation [310030_156795] FX This work was supported by the Intramural Funds of the National Human Genome Research Institute, NIH (Project Z01-HG000121), and the Swiss National Science Foundation (Grant no. 310030_156795). NR 20 TC 2 Z9 2 U1 3 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 8 PY 2015 VL 10 IS 10 AR e0139729 DI 10.1371/journal.pone.0139729 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TW UT WOS:000362511000049 PM 26448644 ER PT J AU Burbelo, PD Keller, J Wagner, J Klimavicz, JS Bayat, A Rhodes, CS Diarra, B Chetchotisakd, P Suputtamongkol, Y Kiertiburanakul, S Holland, SM Browne, SK Siddiqui, S Kovacs, JA AF Burbelo, Peter D. Keller, Jason Wagner, Jason Klimavicz, James S. Bayat, Ahmad Rhodes, Craig S. Diarra, Bassirou Chetchotisakd, Ploenchan Suputtamongkol, Yupin Kiertiburanakul, Sasisopin Holland, Steven M. Browne, Sarah K. Siddiqui, Sophia Kovacs, Joseph A. TI Serological diagnosis of pulmonary Mycobacterium tuberculosis infection by LIPS using a multiple antigen mixture SO BMC MICROBIOLOGY LA English DT Article DE Antibodies; Latent tuberculosis infection (LTBI); Luciferase immunoprecipitation systems (LIPS); Mycobacterium tuberculosis; Pulmonary TB; Serology ID LATENT TUBERCULOSIS; ANTIBODY-RESPONSES; 4-ANTIGEN MIXTURE; IDENTIFICATION; TECHNOLOGIES; BIOMARKERS; PROTEINS; ASSAYS; TOOLS AB Background: There is an urgent need for a simple and accurate test for the diagnosis of human Mycobacterium tuberculosis, the infectious agent causing tuberculosis (TB). Here we describe a serological test based on light emitting recombinant proteins for the diagnosis of pulmonary Mycobacterium tuberculosis infection. Methods: Luciferase Immunoprecipitation Systems (LIPS), a fluid-phase immunoassay, was used to examine antibody responses against a panel of 24 different M. tuberculosis proteins. Three different strategies were used for generating the constructs expressing the recombinant fusion M. tuberculosis proteins with luciferase: synthetic gene synthesis, Gateway recombination cloning, and custom PCR synthesis. A pilot cohort of African pulmonary TB patients was used for initial antibody screening and confirmatory studies with selected antigens were performed with a cohort from Thailand and healthy US blood donors. In addition to testing M. tuberculosis antigens separately, a mixture that tested seven antigens simultaneously was evaluated for diagnostic performance. Results: LIPS testing of a pilot set of serum samples from African pulmonary TB patients identified a potential subset of diagnostically useful M. tuberculosis antigens. Evaluation of a second independent cohort from Thailand validated highly significant antibody responses against seven antigens (PstS1, Rv0831c, FbpA, EspB, bfrB, HspX and ssb), which often showed robust antibody levels up to 50-to 1000-fold higher than local community controls. Marked heterogeneity of antibody responses was observed in the patients and the combined results demonstrated 73.5 % sensitivity and 100 % specificity for detection of pulmonary TB. A LIPS test simultaneously employing the seven M. tuberculosis antigen as a mixture matched the combined diagnostic performance of the separate tests, but showed an even higher diagnostic sensitivity (90 %) when a cut-off based on healthy US blood donors was used. Conclusion: A LIPS immunoassay employing multiple M. tuberculosis antigens shows promise for the rapid and quantitative serological detection of pulmonary TB. C1 [Burbelo, Peter D.; Klimavicz, James S.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA. [Keller, Jason; Wagner, Jason; Bayat, Ahmad] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Rhodes, Craig S.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Diarra, Bassirou] USTTB, Project SEREFO, Bamako, Mali. [Chetchotisakd, Ploenchan] Khon Kaen Univ, Khon Kaen, Thailand. [Suputtamongkol, Yupin] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Kiertiburanakul, Sasisopin] Mahidol Univ, Ramathibodi Hosp, Fac Med, Bangkok 10400, Thailand. [Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Siddiqui, Sophia] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Kovacs, Joseph A.] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. [Burbelo, Peter D.] NIDCR, Dent Clin Res Core, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases, the Clinical Center; Project Serefo; NIH Clinical Research Center; Office of AIDS Research FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, the National Institute of Allergy and Infectious Diseases, the Clinical Center, in part with funds from Project Serefo and by a Bench to Bedside award from the NIH Clinical Research Center, which was funded by the Office of AIDS Research. NR 23 TC 1 Z9 2 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD OCT 8 PY 2015 VL 15 AR 205 DI 10.1186/s12866-015-0545-y PG 9 WC Microbiology SC Microbiology GA CT0KT UT WOS:000362484900001 PM 26449888 ER PT J AU Laucis, NC Hays, RD Bhattacharyya, T AF Laucis, Nicholas C. Hays, Ron D. Bhattacharyya, Timothy TI Scoring the SF-36 in Orthopaedics: A Brief Guide SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID QUALITY-OF-LIFE; PREFERENCE-BASED MEASURE; 36-ITEM SHORT-FORM; HEALTH SURVEY; MEDICAL OUTCOMES; FRACTURES; SURGERY; SCORES; SF-12; SCALES AB The Short Form-36 (SF-36) is the most widely used health-related quality-of-life measure in research to date. There are currently two sources for the SF-36 and scoring instructions: licensing them from Optum, Inc., or obtaining them from publicly available documentation from the RAND Corporation. The SF-36 yields eight scale scores and two summary scores. The physical component summary (PCS) and mental component summary (MCS) scores were derived using an orthogonal-factor analytic model that forced the PCS and MCS to be uncorrelated, and it has been shown to contribute to an inflation of the MCS in patients with substantial physical disability. Oblique scoring can reduce this inflation of the MCS in orthopaedic studies. Spreadsheets to score the SF-36, along with a copy of the questionnaire, are provided. C1 [Laucis, Nicholas C.; Bhattacharyya, Timothy] NIAMSD, Clin & Investigat Orthoped Surg Unit, NIH, Bethesda, MD 20892 USA. [Hays, Ron D.] UCLA, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RP Laucis, NC (reprint author), NIAMSD, Clin & Investigat Orthoped Surg Unit, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 4-2339,MSC1498, Bethesda, MD 20892 USA. EM bhattacharyyat@mail.nih.gov FU NIA NIH HHS [P30-AG021684]; NIMHD NIH HHS [2 P20-MD000182] NR 38 TC 6 Z9 8 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT 7 PY 2015 VL 97A IS 19 BP 1628 EP 1634 DI 10.2106/JBJS.O.00030 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CY4SP UT WOS:000366398900012 PM 26446970 ER PT J AU Haque, RU Wittig, JH Damera, SR Inati, SK Zaghloul, KA AF Haque, Rafi U. Wittig, John H., Jr. Damera, Srikanth R. Inati, Sara K. Zaghloul, Kareem A. TI Cortical Low-Frequency Power and Progressive Phase Synchrony Precede Successful Memory Encoding SO JOURNAL OF NEUROSCIENCE LA English DT Article DE attention; episodic memory; phase synchrony ID PREDICTS LATER RECOLLECTION; TOP-DOWN; EPISODIC MEMORY; HUMAN BRAIN; BOTTOM-UP; SELECTIVE ATTENTION; PREFRONTAL CORTEX; SPATIAL ATTENTION; OSCILLATIONS; THETA AB Neural activity preceding an event can influence subsequent memory formation, yet the precise cortical dynamics underlying this activity and the associated cognitive states remain unknown. We investigate these questions here by examining intracranial EEG recordings as 28 participants with electrodes placed for seizure monitoring participated in a verbal paired-associates memory task. We found that, preceding successfully remembered word pairs, an orientation cue triggered a low-frequency 2-4 Hz phase reset in the right temporoparietal junction with concurrent increases in low-frequency power across cortical regions that included the prefrontal cortex and left temporal lobe. Regions that exhibited a significant increase in 2-4 Hz power were functionally bound together through progressive low-frequency 2-4 Hz phase synchrony. Our data suggest that the interaction between power and phase synchrony reflects the engagement of attentional networks that in large part determine the extent to which memories are successfully encoded. C1 [Haque, Rafi U.; Wittig, John H., Jr.; Damera, Srikanth R.; Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Inati, Sara K.] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Zaghloul, KA (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20,10 Ctr Dr, Bethesda, MD 20892 USA. EM kareem.zaghloul@nih.gov FU Intramural Research Program of the National Institute for Neurological Disorders and Stroke; National Institutes of Health [MH055687, MH061975, NS067316, MH017168] FX This work was supported by the Intramural Research Program of the National Institute for Neurological Disorders and Stroke. Data collection at the University of Pennsylvania and at Thomas Jefferson University was supported by National Institutes of Health Grants MH055687, MH061975, NS067316, and MH017168. We thank the clinical teams at the University of Pennsylvania Hospital and Thomas Jefferson Hospital for assistance in data collection. We are indebted to all patients who have selflessly volunteered their time to participate in this study. We thank John F. Burke for helpful and insightful comments on this manuscript. NR 41 TC 1 Z9 1 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 7 PY 2015 VL 35 IS 40 BP 13577 EP 13586 DI 10.1523/JNEUROSCI.0687-15.2015 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CX9UJ UT WOS:000366050900005 PM 26446212 ER PT J AU Mizuguchi, T Barrowman, J Grewal, SIS AF Mizuguchi, Takeshi Barrowman, Jemima Grewal, Shiv I. S. TI Chromosome domain architecture and dynamic organization of the fission yeast genome SO FEBS LETTERS LA English DT Review DE Heterochromatin; Cohesin; Rabl; Genome organization; Hi-C; Fission yeast ID RNA-POLYMERASE-III; SPINDLE-POLE BODY; MICROTUBULE-ORGANIZING CENTER; LONG-RANGE INTERACTIONS; CCCTC-BINDING FACTOR; MATING-TYPE REGION; GENE-EXPRESSION; SCHIZOSACCHAROMYCES-POMBE; NUCLEAR-ORGANIZATION; MEIOTIC PROPHASE AB Advanced techniques including the chromosome conformation capture (3C) methodology and its derivatives are complementing microscopy approaches to study genome organization, and are revealing new details of three-dimensional (3D) genome architecture at increasing resolution. The fission yeast Schizosaccharomyces pombe (S. pombe) comprises a small genome featuring organizational elements of more complex eukaryotic systems, including conserved heterochromatin assembly machinery. Here we review key insights into genome organization revealed in this model system through a variety of techniques. We discuss the predominant role of Rabl-like configuration for interphase chromosome organization and the dynamic changes that occur during mitosis and meiosis. High resolution Hi-C studies have also revealed the presence of locally crumpled chromatin regions called "globules" along chromosome arms, and implicated a critical role for pericentromeric heterochromatin in imposing fundamental constraints on the genome to maintain chromosome territoriality and stability. These findings have shed new light on the connections between genome organization and function. It is likely that insights gained from the S. pombe system will also broadly apply to higher eukaryotes. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Mizuguchi, Takeshi; Barrowman, Jemima; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuguchi, T (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM mizuguchit@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX We regret that we were unable to cite all work due to space constraints. We thank Drs. Julia Promisel Cooper, Tomoyasu Sugiyama and Hernan Diego Folco for comments. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 178 TC 4 Z9 5 U1 1 U2 9 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 OCT 7 PY 2015 VL 589 IS 20 SI SI BP 2975 EP 2986 DI 10.1016/j.febslet.2015.06.008 PN A PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CV9JP UT WOS:000364603800013 PM 26096785 ER PT J AU Vogtmann, E Corley, DA Almers, LM Cardwell, CR Murray, LJ Abnet, CC AF Vogtmann, Emily Corley, Douglas A. Almers, Lucy M. Cardwell, Chris R. Murray, Liam J. Abnet, Christian C. TI Oral Bisphosphonate Exposure and the Risk of Upper Gastrointestinal Cancers SO PLOS ONE LA English DT Article ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; LOW BONE-DENSITY; ESOPHAGEAL CANCER; NATIONWIDE POPULATION; PREVENT FRACTURES; COLORECTAL-CANCER; ALENDRONATE; OSTEOPOROSIS; VALIDATION; MORTALITY AB The association between oral bisphosphonate use and upper gastrointestinal cancer has been controversial. Therefore, we examined the association with esophageal and gastric cancer within the Kaiser Permanente, Northern California population. A total of 1,011 cases of esophageal (squamous cell carcinoma and adenocarcinoma) and 1,923 cases of gastric adenocarcinoma (cardia, non-cardia and other) diagnosed between 1997 and 2011 from the Kaiser Permanente, Northern California cancer registry were matched to 49,886 and 93,747 controls, respectively. Oral bisphosphonate prescription fills at least one year prior to the index date were extracted. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between prospectively evaluated oral bisphosphonate use with incident esophageal and gastric cancer diagnoses with adjustment for potential confounders. After adjustment for potential confounders, no significant associations were found for esophageal squamous cell carcinoma (OR 0.88; 95% CI: 0.51, 1.52), esophageal adenocarcinoma (OR 0.68; 95% CI: 0.37, 1.24), or gastric non-cardia adenocarcinoma (OR 0.83, 95% CI: 0.59, 1.18), but we observed an adverse association with gastric cardia adenocarcinoma (OR 1.64; 95% CI: 1.07, 2.50). In conclusion, we observed no association between oral bisphosphonate use and esophageal cancer risk within a large community-based population. A significant association was detected with gastric cardia and other adenocarcinoma risk, although this needs to be replicated. C1 [Vogtmann, Emily; Abnet, Christian C.] 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. [Corley, Douglas A.; Almers, Lucy M.] Kaiser Permanente, Div Res, Oakland, CA USA. [Cardwell, Chris R.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. RP Vogtmann, E (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM emily.vogtmann@nih.gov RI Abnet, Christian/C-4111-2015; OI Abnet, Christian/0000-0002-3008-7843; Cardwell, Chris/0000-0002-2689-4335 FU Intramural Research Program; Cancer Prevention Fellowship Program of the National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program and the Cancer Prevention Fellowship Program of the National Institutes of Health and the National Cancer Institute. NR 26 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 7 PY 2015 VL 10 IS 10 AR e0140180 DI 10.1371/journal.pone.0140180 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TS UT WOS:000362510600149 PM 26445463 ER PT J AU Hancock, DB Reginsson, GW Gaddis, NC Chen, X Saccone, NL Lutz, SM Qaiser, B Sherva, R Steinberg, S Zink, F Stacey, SN Glasheen, C Chen, J Gu, F Frederiksen, BN Loukola, A Gudbjartsson, DF Bruske, I Landi, MT Bickeboller, H Madden, P Farrer, L Kaprio, J Kranzler, HR Gelernter, J Baker, TB Kraft, P Amos, CI Caporaso, NE Hokanson, JE Bierut, LJ Thorgeirsson, TE Johnson, EO Stefansson, K AF Hancock, D. B. Reginsson, G. W. Gaddis, N. C. Chen, X. Saccone, N. L. Lutz, S. M. Qaiser, B. Sherva, R. Steinberg, S. Zink, F. Stacey, S. N. Glasheen, C. Chen, J. Gu, F. Frederiksen, B. N. Loukola, A. Gudbjartsson, D. F. Brueske, I. Landi, M. T. Bickeboeller, H. Madden, P. Farrer, L. Kaprio, J. Kranzler, H. R. Gelernter, J. Baker, T. B. Kraft, P. Amos, C. I. Caporaso, N. E. Hokanson, J. E. Bierut, L. J. Thorgeirsson, T. E. Johnson, E. O. Stefansson, K. TI Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID LUNG-CANCER RISK; ACETYLCHOLINE-RECEPTORS; GENOTYPE IMPUTATION; SMOKING-BEHAVIOR; SUSCEPTIBILITY LOCUS; EUROPEAN-AMERICANS; CONTROLLED-TRIAL; CANDIDATE GENES; FAGERSTROM TEST; QUALITY-CONTROL AB We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P = 8.0 x 10(-9) across all the samples for rs2273500-C (frequency = 0.15; odds ratio = 1.12 and 95% confidence interval = 1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P = 7.3 x 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N = 28 998, odds ratio = 1.06 and 95% confidence interval = 1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences. C1 [Hancock, D. B.; Glasheen, C.] Res Triangle Inst Int, Behav Hlth & Criminal Justice Res Div, Behav & Urban Hlth Program, Res Triangle Pk, NC 27709 USA. [Reginsson, G. W.; Steinberg, S.; Zink, F.; Stacey, S. N.; Gudbjartsson, D. F.; Thorgeirsson, T. E.; Stefansson, K.] deCODE Genet Amgen, Reykjavik, Iceland. [Gaddis, N. C.] Res Triangle Inst Int, Res Comp Div, Res Triangle Pk, NC USA. [Chen, X.; Chen, J.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA. [Chen, X.] Univ Nevada, Nevada Inst Personalized Med, Las Vegas, NV 89154 USA. [Chen, X.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Saccone, N. L.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. [Lutz, S. M.] Univ Colorado, Dept Biostat & Informat, Aurora, CO USA. [Qaiser, B.; Loukola, A.; Kaprio, J.] Univ Helsinki, Dept Publ Hlth, Fac Med, Helsinki, Finland. [Sherva, R.; Farrer, L.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Gu, F.; Landi, M. T.; Caporaso, N. E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,United States Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Frederiksen, B. N.] Iowa Dept Publ Hlth, Des Moines, IA 50319 USA. [Brueske, I.] German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany. [Bickeboeller, H.] Univ Gottingen, Dept Genet Epidemiol, D-37073 Gottingen, Germany. [Madden, P.; Bierut, L. J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Farrer, L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Farrer, L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kaprio, J.] Natl Inst Hlth & Welf, Helsinki, Finland. [Kaprio, J.] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Kranzler, H. R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, Educ & Clin Ctr, VISN Mental Illness Res 4, Philadelphia, PA USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Gelernter, J.] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA. [Baker, T. B.] Univ Wisconsin, Ctr Tobacco Res & Intervent, Madison, WI USA. [Kraft, P.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, P.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Amos, C. I.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Hanover, NH USA. [Amos, C. I.] Geisel Sch Med Dartmouth, Dept Genet, Hanover, NH USA. [Amos, C. I.] Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Hanoven, NH USA. [Hokanson, J. E.] Univ Colorado, Dept Epidemiol, Aurora, CO USA. [Johnson, E. O.] Res Triangle Inst Int, Fellow Program, Res Triangle Pk, NC 27709 USA. [Johnson, E. O.] Res Triangle Inst Int, Behav Hlth & Criminal Justice Res Div, Res Triangle Pk, NC 27709 USA. [Stefansson, K.] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Hancock, DB (reprint author), Res Triangle Inst Int, Behav Hlth & Criminal Justice Res Div, Behav & Urban Hlth Program, East Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM dhancock@rti.org OI Gaddis, Nathan/0000-0001-5205-7138; Farrer, Lindsay/0000-0001-5533-4225; Hancock, Dana/0000-0003-2240-3604; Loukola, Anu-Maria/0000-0003-0542-5967; Kaprio, Jaakko/0000-0002-3716-2455; Thorgeirsson, Thorgeir/0000-0002-5149-7040 FU National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) [R01 DA035825] FX This work was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) grant number R01 DA035825. Acknowledgments for the study samples used to conduct the GWAS meta-analysis, independent replication testing for nicotine dependence and follow-up association testing with lung cancer are included in the Supplementary Information. NR 92 TC 13 Z9 13 U1 4 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD OCT 6 PY 2015 VL 5 AR e651 DI 10.1038/tp.2015.149 PG 11 WC Psychiatry SC Psychiatry GA DA2YR UT WOS:000367663600002 PM 26440539 ER PT J AU Denis, RGP Joly-Amado, A Webber, E Langlet, F Schaeffer, M Padilla, SL Cansell, C Dehouck, B Castel, J Delbes, AS Martinez, S Lacombe, A Rouch, C Kassis, N Fehrentz, JA Martinez, J Verdie, P Hnasko, TS Palmiter, RD Krashes, MJ Guler, AD Magnan, C Luquet, S AF Denis, Raphael G. P. Joly-Amado, Aurelie Webber, Emily Langlet, Fanny Schaeffer, Marie Padilla, Stephanie L. Cansell, Celine Dehouck, Benedicte Castel, Julien Delbes, Anne-Sophie Martinez, Sarah Lacombe, Amelie Rouch, Claude Kassis, Nadim Fehrentz, Jean-Alain Martinez, Jean Verdie, Pascal Hnasko, Thomas S. Palmiter, Richard D. Krashes, Michael J. Gueler, Ali D. Magnan, Christophe Luquet, Serge TI Palatability Can Drive Feeding Independent of AgRP Neurons SO CELL METABOLISM LA English DT Article ID CAUSES GHRELIN RESISTANCE; FOOD-INTAKE; NPY/AGRP NEURONS; BODY-WEIGHT; MELANOCORTIN NEURONS; METABOLIC SYNDROME; NUCLEUS-ACCUMBENS; ENERGY-BALANCE; DOPAMINE; MICE AB Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake-a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling. C1 [Denis, Raphael G. P.; Joly-Amado, Aurelie; Cansell, Celine; Castel, Julien; Delbes, Anne-Sophie; Martinez, Sarah; Lacombe, Amelie; Rouch, Claude; Kassis, Nadim; Magnan, Christophe; Luquet, Serge] Univ Paris Diderot, CNRS, Unite Mixte Rech 8251, Unite Biol Fonct & Adaptat,Sorbonne Paris Cite, F-75205 Paris, France. [Schaeffer, Marie] Inst Genom Fonct, CNRS, Unite Mixte Rech 5203, F-34000 Montpellier, France. [Schaeffer, Marie] INSERM, U661, F-34000 Montpellier, France. [Schaeffer, Marie] Univ Montpellier, Unite Mixte Rech 5203, F-34000 Montpellier, France. [Langlet, Fanny; Dehouck, Benedicte] Jean Pierre Aubert Res Ctr, INSERM, F-59000 Lille, France. [Langlet, Fanny; Dehouck, Benedicte] Univ Droit & Sante Lille, Fac Med, F-59000 Lille, France. [Fehrentz, Jean-Alain; Martinez, Jean; Verdie, Pascal] Univ Montpellier, Ecole Natl Super Chim Montpellier, CNRS, Inst Biomol Max Mousseron,Unite Mixte Rech 5247, F-34093 Montpellier 5, France. [Hnasko, Thomas S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA. [Padilla, Stephanie L.; Palmiter, Richard D.; Gueler, Ali D.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Padilla, Stephanie L.; Palmiter, Richard D.; Gueler, Ali D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Webber, Emily; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Webber, Emily; Krashes, Michael J.] NIDA, Baltimore, MD 21224 USA. RP Luquet, S (reprint author), Univ Paris Diderot, CNRS, Unite Mixte Rech 8251, Unite Biol Fonct & Adaptat,Sorbonne Paris Cite, F-75205 Paris, France. EM serge.luquet@univ-paris-diderot.fr OI luquet, serge/0000-0001-8668-6645; Martinez, Jean/0000-0002-9267-4621 FU Young Investigator ATIP grant from the Centre National la Recherche Scientifique (CNRS); Region Ile-de-France; University Paris Diderot-Paris 7; "Agence Nationale de la Recherche" [ANR-09-BLAN-0267-02, ANR 11 BSV1 021 01]; French Department of National Education and Research; Societe Francophone du Diabete; SFNEP-ANTADIR; Societe Francophone de Nutrition; CNRS; Societe Francophone du Diabete-Roche FX This work was supported by a Young Investigator ATIP grant from the Centre National la Recherche Scientifique (CNRS), a research and equipment grant from the Region Ile-de-France, by the University Paris Diderot-Paris 7, and "Agence Nationale de la Recherche" grants ANR-09-BLAN-0267-02 and ANR 11 BSV1 021 01. R.G.P. received a post-doctoral grant from the Region Ile-de-France. A.J.A. received a national merit scholarship from the French Department of National Education and Research, a research grant from the Societe Francophone du Diabete, and a research grant from SFNEP-ANTADIR. R.D. received a fellowship from the Region Ile de France and a merit grant from the Societe Francophone de Nutrition. C.C. received a Ph.D. fellowship from the CNRS and a research grant from the Societe Francophone du Diabete-Roche. We acknowledge the technical platform metabolism of the Unit "Biologie Fonctionnelle et Adaptative" (University Paris Diderot, Sorbonne Paris Cite, BFA, UMR 8251 CNRS, 75205 Paris, France) for metabolic and molecular analysis and the animal core facility "Buffon" of the University Paris Diderot Paris 7/Institut Jacques Monod, Paris for animal husbandry and breeding. We thank Olja Kacanski for administrative support and Gaelle Charlon, Le Parco Isabelle, Sandrine Olivre, and Ludovic Maingault for care of animals. We also thank Colin T. Phillips and Hicham Lamrini for essential help with collecting stress-induced responses and feeding data in AgRP-ablated animals. We acknowledge Bryan Roth for kindly providing the KOR viruses. Finally, we would like to thank Michael Cowley and Scott Sternson for valuable scientific input and Diane Durnam for manuscript editing. NR 51 TC 13 Z9 13 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD OCT 6 PY 2015 VL 22 IS 4 BP 646 EP 657 DI 10.1016/j.cmet.2015.07.011 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CW7PW UT WOS:000365192600014 PM 26278050 ER PT J AU Ma, XR Xu, LY Alberobello, AT Gavrilova, O Bagattin, A Skarulis, M Liu, J Finkel, T Mueller, E AF Ma, Xinran Xu, Lingyan Alberobello, Anna Teresa Gavrilova, Oksana Bagattin, Alessia Skarulis, Monica Liu, Jie Finkel, Toren Mueller, Elisabetta TI Celastrol Protects against Obesity and Metabolic Dysfunction through Activation of a HSF1-PGC1 alpha Transcriptional Axis SO CELL METABOLISM LA English DT Article ID BROWN ADIPOSE-TISSUE; TRANSGENIC MOUSE MODEL; DIET-INDUCED OBESITY; HEAT-SHOCK RESPONSE; MOLECULAR CHAPERONES; ENERGY-EXPENDITURE; BEIGE ADIPOCYTES; SKELETAL-MUSCLE; STRESS-RESPONSE; GOD VINE AB Altering the balance between energy intake and expenditure is a potential strategy for treating obesity and metabolic syndrome. Nonetheless, despite years of progress in identifying diverse molecular targets, biological-based therapies are limited. Here we demonstrate that heat shock factor 1 (HSF1) regulates energy expenditure through activation of a PGC1 alpha-dependent metabolic program in adipose tissues and muscle. Genetic modulation of HSF1 levels altered white fat remodeling and thermogenesis, and pharmacological activation of HSF1 via celastrol was associated with enhanced energy expenditure, increased mitochondrial function in fat and muscle and protection against obesity, insulin resistance, and hepatic steatosis during high-fat diet regimens. The beneficial metabolic changes elicited by celastrol were abrogated in HSF1 knockout mice. Overall, our findings identify the temperature sensor HSF1 as a regulator of energy metabolism and demonstrate that augmenting HSF1 via celastrol represents a possible therapeutic strategy to treat obesity and its myriad metabolic consequences. C1 [Ma, Xinran; Xu, Lingyan; Alberobello, Anna Teresa; Bagattin, Alessia; Mueller, Elisabetta] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20892 USA. [Skarulis, Monica] NIDDK, Clin Endocrine Sect, NIH, Bethesda, MD 20892 USA. [Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Mueller, E (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM elisabettam@niddk.nih.gov FU NIDDK Intramural Research Program of the NIH FX We are thankful to Richard Proia and Marc Reitman for reading the manuscript; to Pasha Sarraf for discussions throughout the project; and to Tatyana Chanturiya, Rachel Perron, and Ulrich Baxa for technical assistance. We also thank Jeffrey Kopp, Hidefumi Wakashin, and Shashi Shivrastav for kindly sharing their Seahorse Instrument; and Danielle Springer, Michele Allen, and Audrey Noguchi from the NHLBI murine core facility for technical support in metabolic phenotyping. This research was supported by funds of the NIDDK Intramural Research Program of the NIH. NR 52 TC 25 Z9 26 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD OCT 6 PY 2015 VL 22 IS 4 BP 695 EP 708 DI 10.1016/j.cmet.2015.08.005 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CW7PW UT WOS:000365192600018 PM 26344102 ER PT J AU Kraemer, MUG Perkins, TA Cummings, DAT Zakar, R Hay, SI Smith, DL Reiner, RC AF Kraemer, M. U. G. Perkins, T. A. Cummings, D. A. T. Zakar, R. Hay, S. I. Smith, D. L. Reiner, R. C., Jr. TI Big city, small world: density, contact rates, and transmission of dengue across Pakistan SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE dengue; epidemiology; heterogeneity; mixing; spatial dynamics; spatial accessibility ID TIME-SERIES; VIRUS TRANSMISSION; HUMAN MOVEMENT; AEDES-AEGYPTI; EPIDEMIOLOGIC MODELS; MEASLES EPIDEMICS; SPATIAL DYNAMICS; COMMUNITY SIZE; POPULATION; NETWORK AB Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e. each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of 'mixing parameters' when disaggregating data across an urban-rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions. We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof. C1 [Kraemer, M. U. G.; Smith, D. L.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Perkins, T. A.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Perkins, T. A.] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA. [Perkins, T. A.; Hay, S. I.; Smith, D. L.; Reiner, R. C., Jr.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Cummings, D. A. T.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Zakar, R.] Univ Punjab, Dept Publ Hlth, Lahore 54590, Pakistan. [Hay, S. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Hay, S. I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. [Smith, D. L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD 20850 USA. [Reiner, R. C., Jr.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. RP Kraemer, MUG (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England. EM moritz.kraemer@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015 OI Hay, Simon/0000-0002-0611-7272 FU German Academic Exchange Service (DAAD); RAPIDD programme of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center, National Institutes of Health; Wellcome Trust [095066]; Bill & Melinda Gates Foundation [OPP1093011] FX M.U.G.K. acknowledges funding from the German Academic Exchange Service (DAAD). T.A.P., S.I.H. and R.C.R. acknowledge the support from the RAPIDD programme of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. S.I.H. is funded by a Senior Research Fellowship from the Wellcome Trust (no. 095066) and a grant from the Bill & Melinda Gates Foundation (no. OPP1093011). Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 7 Z9 7 U1 1 U2 12 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD OCT 6 PY 2015 VL 12 IS 111 AR 20150468 DI 10.1098/rsif.2015.0468 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU4HE UT WOS:000363487600004 PM 26468065 ER PT J AU Reiner, RC Guerra, C Donnelly, MJ Bousema, T Drakeley, C Smith, DL AF Reiner, Robert C., Jr. Guerra, Carlos Donnelly, Martin J. Bousema, Teun Drakeley, Chris Smith, David L. TI Estimating malaria transmission from humans to mosquitoes in a noisy landscape SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE disease ecology; infectious disease dynamics; mosquito-borne pathogen; non-Markovian dynamics ID PLASMODIUM-FALCIPARUM TRANSMISSION; ENVIRONMENTAL NOISE; POPULATION-DYNAMICS; ELIMINATION; RATES; COLOR; STRATEGIES; VACCINES; AFRICA; MODEL AB A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. C1 [Reiner, Robert C., Jr.; Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Reiner, Robert C., Jr.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Reiner, Robert C., Jr.] Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA. [Guerra, Carlos] Ctr Dis Dynam Econ & Policy, Washington, DC USA. [Donnelly, Martin J.] Univ Liverpool, Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England. [Donnelly, Martin J.] Wellcome Trust Sanger Inst, Malaria Programme, Cambridge, England. [Bousema, Teun; Drakeley, Chris] London Sch Hyg & Trop Med, Dept Immunol & Infect, London WC1, England. [Bousema, Teun] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands. [Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA. [Smith, David L.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. RP Reiner, RC (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM rcreiner@indiana.edu RI Bousema, Teun/N-3574-2014 FU Malaria Vaccine Initiative; Research and Policy for Infectious Disease Dynamics (RAPIDD) programme of the Science and Technology Directorate; Department of Homeland Security; Fogarty International Center, National Institutes of Health; Bill & Melinda Gates Foundation [OPP1110495, OPP1034789]; National Institutes of Health/National Institute of Allergy and Infectious Diseases [U19AI089674]; European Research Council [ERC-2014-StG 639776] FX R.C.R. and D.L.S. acknowledge funding from the Malaria Vaccine Initiative and from the Research and Policy for Infectious Disease Dynamics (RAPIDD) programme of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health as well as funding from the Bill & Melinda Gates Foundation (grant no. OPP1110495). D.L.S., M.J.D. and C.D. acknowledge funding from National Institutes of Health/National Institute of Allergy and Infectious Diseases (U19AI089674). T.B. acknowledges funding from the Bill & Melinda Gates Foundation (OPP1034789) and the European Research Council (ERC-2014-StG 639776). NR 52 TC 0 Z9 0 U1 0 U2 4 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD OCT 6 PY 2015 VL 12 IS 111 AR 20150478 DI 10.1098/rsif.2015.0478 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CU4HE UT WOS:000363487600005 PM 26400195 ER PT J AU Ren, L Mendoza, A Zhu, J Briggs, JW Halsey, C Hong, ES Burkett, SS Morrow, J Lizardo, MM Osborne, T Li, SQ Luu, HH Meltzer, P Khanna, C AF Ren, Ling Mendoza, Arnulfo Zhu, Jack Briggs, Joseph W. Halsey, Charles Hong, Ellen S. Burkett, Sandra S. Morrow, James Lizardo, Michael M. Osborne, Tanasa Li, Samuel Q. Luu, Hue H. Meltzer, Paul Khanna, Chand TI Characterization of the metastatic phenotype of a panel of established osteosarcoma cells SO ONCOTARGET LA English DT Article DE osteosarcoma; PHLDA1/TDAG51; tumor metastasis ID SOFT-TISSUE TUMORS; MURINE OSTEOSARCOMA; PULMONARY METASTASIS; PROGNOSTIC-FACTORS; ORTHOTOPIC MODEL; GENE-EXPRESSION; LUNG METASTASIS; OSTEO-SARCOMA; MOUSE MODEL; REAL-TIME AB Osteosarcoma (OS) is the most common bone tumor in pediatric patients. Metastasis is a major cause of mortality and morbidity. The rarity of this disease coupled with the challenges of drug development for metastatic cancers have slowed the delivery of improvements in long-term outcomes for these patients. In this study, we collected 18 OS cell lines, confirmed their expression of bone markers and complex karyotypes, and characterized their in vivo tumorgenicity and metastatic potential. Since prior reports included conflicting descriptions of the metastatic and in vivo phenotypes of these models, there was a need for a comparative assessment of metastatic phenotypes using identical procedures in the hands of a single investigative group. We expect that this single characterization will accelerate the study of this metastatic cancer. Using these models we evaluated the expression of six previously reported metastasis-related OS genes. Ezrin was the only gene consistently differentially expressed in all the pairs of high/low metatstatic OS cells. We then used a subtractive gene expression approach of the high and low human metastatic cells to identify novel genes that may be involved in OS metastasis. PHLDA1 (pleckstrin homology-like domain, family A) was identified as one of the genes more highly expressed in the high metastatic compared to low metastatic cells. Knocking down PHLDA1 with siRNA or shRNA resulted in down regulation of the activities of MAPKs (ERK1/2), c-Jun N-terminal kinases (JNK), and p38 mitogen-activated protein kinases (MAPKs). Reducing the expression of PHLDA1 also delayed OS metastasis progression in mouse xenograft models. C1 [Ren, Ling; Mendoza, Arnulfo; Briggs, Joseph W.; Hong, Ellen S.; Lizardo, Michael M.; Khanna, Chand] NCI, Mol Oncol Sect, Metastasis Biol Grp, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Zhu, Jack; Meltzer, Paul] NCI, Genet Branch, Bethesda, MD 20892 USA. [Halsey, Charles] NCI, Mol Pathol Unit, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Burkett, Sandra S.] NCI, Comparat Mol Cytogenet Core Facil, Ctr Canc Res, Bethesda, MD 20892 USA. [Morrow, James; Li, Samuel Q.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Osborne, Tanasa] Natl Inst Environm Hlth, Res Triangle Pk, NC USA. [Luu, Hue H.] Univ Chicago, Med & Biol Sci, Dept Orthoped Surg & Rehabil Med, Chicago, IL 60637 USA. RP Khanna, C (reprint author), NCI, Mol Oncol Sect, Metastasis Biol Grp, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM ckhanna@animalci.com FU NIH Intramural Research Program FX This research is supported by the NIH Intramural Research Program. NR 61 TC 8 Z9 8 U1 4 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 6 PY 2015 VL 6 IS 30 BP 29469 EP 29481 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0CL UT WOS:000363183200078 PM 26320182 ER PT J AU Sourbier, C Scroggins, BT Mannes, PZ Liao, PJ Siems, K Wolf, D Beutler, JA Linehan, WM Neckers, L AF Sourbier, Carole Scroggins, Bradley T. Mannes, Philip Z. Liao, Pei-Jyun Siems, Karsten Wolf, Dietmar Beutler, John A. Linehan, W. Marston Neckers, Leonard TI Tonantzitlolone cytotoxicity toward renal cancer cells is PKC theta- and HSF1-dependent SO ONCOTARGET LA English DT Article DE englerin A; bryostatin; renal tumors; RCC; PKC theta ID HEAT-SHOCK FACTOR-1; DITERPENE TONANTZITLOLONE; TUMOR-CELLS; CARCINOMA; HSF1; HYPOXIA; PROTEIN; ACTIVATION; ENGLERIN; INSULIN AB Elucidating the targets and mechanism of action of natural products is strategically important prior to drug development and assessment of potential clinical applications. In this report, we elucidated the main targets and mechanism of action of the natural product tonantzitlolone (TZL) in clear cell renal cell carcinoma (CCRCC). We identified TZL as a dual PKC alpha and PKC theta activator in vitro, although in CCRCC cells its activity was mostly PKC theta-dependent. Through activation of PKC theta, TZL induced an insulin resistant phenotype by inhibiting IRS1 and the PI3K/Akt pathway. Simultaneously, TZL activated the heat shock factor 1 (HSF1) transcription factor driving glucose dependency. Thus, similar to the selective PKC theta activator englerin A, TZL induces a metabolic catastrophe in CCRCC, starving cells of glucose while simultaneously increasing their glycolytic dependency. C1 [Sourbier, Carole; Mannes, Philip Z.; Liao, Pei-Jyun; Linehan, W. Marston; Neckers, Leonard] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Scroggins, Bradley T.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Siems, Karsten; Wolf, Dietmar] AnalytiCon Discovery GmbH, D-14473 Potsdam, Germany. [Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM neckersl@mail.nih.gov FU National Cancer Institute [Z01 BC010683-03, 1ZIABC011038-07] FX The authors would like to thank Dr. Dale Nagle, University of Mississippi for permission to share his data on NSC#741581 (sodwanone W). This research was supported with funds from the Intramural Research Program, National Cancer Institute (project # Z01 BC010683-03 [LN], project # 1ZIABC011038-07 [WML]). The authors declare no conflicts of interest. NR 26 TC 3 Z9 3 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD OCT 6 PY 2015 VL 6 IS 30 BP 29963 EP 29974 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CU0CL UT WOS:000363183200113 PM 26298773 ER PT J AU Valantine, HA Collins, FS AF Valantine, Hannah A. Collins, Francis S. TI National Institutes of Health addresses the science of diversity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diversity; scientific workforce; underrepresentation in science; culture; biomedical research ID ACADEMIC MEDICINE; CONTROLLED-TRIAL; GENDER; INTERVENTION; WORKFORCE; STUDENTS; FACULTY; MATTERS; THREAT; BIASES AB The US biomedical research workforce does not currently mirror the nation's population demographically, despite numerous attempts to increase diversity. This imbalance is limiting the promise of our biomedical enterprise for building knowledge and improving the nation's health. Beyond ensuring fairness in scientific workforce representation, recruiting and retaining a diverse set of minds and approaches is vital to harnessing the complete intellectual capital of the nation. The complexity inherent in diversifying the research workforce underscores the need for a rigorous scientific approach, consistent with the ways we address the challenges of science discovery and translation to human health. Herein, we identify four cross-cutting diversity challenges ripe for scientific exploration and opportunity: research evidence for diversity's impact on the quality and outputs of science; evidence-based approaches to recruitment and training; individual and institutional barriers to workforce diversity; and a national strategy for eliminating barriers to career transition, with scientifically based approaches for scaling and dissemination. Evidence-based data for each of these challenges should provide an integrated, stepwise approach to programs that enhance diversity rapidly within the biomedical research workforce. C1 [Valantine, Hannah A.] US Natl Inst Hlth, Sci Workforce Divers, Bethesda, MD 20814 USA. [Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD 20814 USA. RP Valantine, HA (reprint author), US Natl Inst Hlth, Sci Workforce Divers, Bethesda, MD 20814 USA. EM hannah.valantine@nih.gov NR 23 TC 17 Z9 17 U1 5 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 6 PY 2015 VL 112 IS 40 BP 12240 EP 12242 DI 10.1073/pnas.1515612112 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9GQ UT WOS:000363125400024 PM 26392553 ER PT J AU Won, MH Ro, H Dawid, IB AF Won, Minho Ro, Hyunju Dawid, Igor B. TI Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pancreas; Numb; Notch; morpholino; TALEN ID NUMB FAMILY PROTEINS; MAMMALIAN NUMB; NOTCH; ENDOCRINE; DOMAIN; EXPRESSION; UBIQUITYLATION; MORPHOGENESIS; DEGRADATION; MODULATION AB The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use. C1 [Won, Minho; Dawid, Igor B.] NICHHD, Sect Dev Biol, Bethesda, MD 20892 USA. [Ro, Hyunju] Chungnam Natl Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Daejeon 305764, South Korea. RP Dawid, IB (reprint author), NICHHD, Sect Dev Biol, Bethesda, MD 20892 USA. EM idawid@nih.gov FU Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health; Basic Science Research Program of the National Research Foundation of Korea, Ministry of Education [NRF-2015R1D1A4A01016532] FX We thank Greg Palardy and Damian Dalle Nogare for advice on microscopy; John Gonzales and Allisan Aquilina-Beck for help with fish husbandry; T.-Y. Choi and Jin-Gu Lee for helpful discussion; and T.-Y. Choi, N. Ninov, D. Y. Stainier, C.V. Wright, and L. Godinho for reagents and zebrafish lines. This work has been supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health, and by the Basic Science Research Program of the National Research Foundation of Korea, Ministry of Education (NRF-2015R1D1A4A01016532). NR 45 TC 1 Z9 1 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 6 PY 2015 VL 112 IS 40 BP 12426 EP 12431 DI 10.1073/pnas.1517033112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9GQ UT WOS:000363125400057 PM 26392552 ER PT J AU Zhang, ML Griner, LAM Ju, W Duveau, DY Guha, R Petrus, MN Wen, B Maeda, M Shinn, P Ferrer, M Conlon, KD Bamford, RN O'Shea, JJ Thomas, CJ Waldmann, TA AF Zhang, Meili Griner, Lesley A. Mathews Ju, Wei Duveau, Damien Y. Guha, Rajarshi Petrus, Michael N. Wen, Bernard Maeda, Michiyuki Shinn, Paul Ferrer, Marc Conlon, Kevin D. Bamford, Richard N. O'Shea, John J. Thomas, Craig J. Waldmann, Thomas A. TI Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adult T-cell leukemia; Janus kinase; ruxolitinib; navitoclax ID JAK2 INHIBITOR; INTERFERON-ALPHA; ORAL JAK1; LYMPHOMA; RUXOLITINIB; THERAPY; INTERLEUKIN-2; PROLIFERATION; MYELOFIBROSIS; MALIGNANCIES AB Adult T-cell leukemia (ATL) develops in individuals infected with human T-cell lymphotropic virus-1 (HTLV-1). Presently there is no curative therapy for ATL. HTLV-1-encoded protein Tax (transactivator from the X-gene region) up-regulates Bcl-xL (B-cell lymphoma-extra large) expression and activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems, resulting in amplified JAK/STAT signaling. Inhibition of JAK signaling reduces cytokine-dependent ex vivo proliferation of peripheral blood mononuclear cells (PBMCs) from ATL patients in smoldering/chronic stages. Currently, two JAK inhibitors are approved for human use. In this study, we examined activity of multiple JAK inhibitors in ATL cell lines. The selective JAK inhibitor ruxolitinib was examined in a high-throughput matrix screen combined with >450 potential therapeutic agents, and Bcl-2/Bcl-xL inhibitor navitoclax was identified as a strong candidate for multicomponent therapy. The combination was noted to strongly activate BAX (Bcl-2-associated X protein), effect mitochondrial depolarization, and increase caspase 3/7 activities that lead to cleavage of PARP (poly ADP ribose polymerase) and Mcl-1 (myeloid cell leukemia 1). Ruxolitinib and navitoclax independently demonstrated modest antitumor efficacy, whereas the combination dramatically lowered tumor burden and prolonged survival in an ATL murine model. This combination strongly blocked ex vivo proliferation of five ATL patients' PBMCs. These studies provide support for a therapeutic trial in patients with smoldering/chronic ATL using a drug combination that inhibits JAK signaling and antiapoptotic protein Bcl-xL. C1 [Zhang, Meili; Ju, Wei; Petrus, Michael N.; Wen, Bernard; Conlon, Kevin D.; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhang, Meili] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick, MD 21702 USA. [Griner, Lesley A. Mathews; Duveau, Damien Y.; Guha, Rajarshi; Shinn, Paul; Ferrer, Marc; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Maeda, Michiyuki] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. [Bamford, Richard N.] Transponics, Jacobus, PA 17347 USA. [O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Thomas, CJ (reprint author), NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. EM craigt@mail.nih.gov; tawald@helix.nih.gov FU Division of Preclinical Innovation, National Center for Advancing Translational Sciences; Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; National Center for Advancing Translational Sciences, National Human Genome Research Institute; National Cancer Institute (NCI), Center for Cancer Research; NCI, NIH [N01-CO-12400] FX This research was supported by the Division of Preclinical Innovation, National Center for Advancing Translational Sciences; the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; the Intramural Research Programs of the National Center for Advancing Translational Sciences, National Human Genome Research Institute and National Cancer Institute (NCI), Center for Cancer Research. This project has been funded in part with federal funds from the NCI, NIH, under Contract N01-CO-12400. NR 36 TC 7 Z9 9 U1 4 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 6 PY 2015 VL 112 IS 40 BP 12480 EP 12485 DI 10.1073/pnas.1516208112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9GQ UT WOS:000363125400066 PM 26396258 ER PT J AU Yu, JY Li, MH Wilkins, J Ding, SL Swartz, TH Esposito, AM Zheng, YM Freed, EO Liang, C Chen, BK Liu, SL AF Yu, Jingyou Li, Minghua Wilkins, Jordan Ding, Shilei Swartz, Talia H. Esposito, Anthony M. Zheng, Yi-Min Freed, Eric O. Liang, Chen Chen, Benjamin K. Liu, Shan-Lu TI IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein SO CELL REPORTS LA English DT Article ID WEST NILE VIRUS; CELL-TO-CELL; DENGUE VIRUS; VIRAL ENTRY; ANTIVIRAL RESPONSE; CYTOPLASMIC TAIL; FAMILY PROTEINS; RELEASE; FUSION; VIRIONS AB The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection. C1 [Yu, Jingyou; Li, Minghua; Wilkins, Jordan; Zheng, Yi-Min; Liu, Shan-Lu] Univ Missouri, Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA. [Swartz, Talia H.; Esposito, Anthony M.; Chen, Benjamin K.] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, Inst Immunol, New York, NY 10029 USA. [Ding, Shilei; Liang, Chen] McGill AIDS Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Ding, Shilei; Liang, Chen] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. [Freed, Eric O.] Natl Canc Inst Frederick, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Frederick, MD 21702 USA. RP Liu, SL (reprint author), Univ Missouri, Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA. EM liushan@missouri.edu RI Liu, Shan-Lu/L-5923-2016; Li, Minghua/M-8776-2016; OI Liu, Shan-Lu/0000-0003-1620-3817; Swartz, Talia/0000-0003-1572-045X; Chen, Benjamin K/0000-0002-5404-1997 FU NIH [AI112381, AI109464, AI105584, AI107095, GM113885, DA028866]; Canadian Institutes of Health Research (CIHR); Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH; Intramural AIDS Targeted Antiviral Program FX We thank Walther Mothes for provision of the Jurkat/inGLuc cells that made this work possible. We also thank the NIH AIDS reagent program for supplying important reagents. We thank Boris Hartmann for help with Amnis flow cytometric experiments. This work was supported by NIH grants to S.-L.L. (AI112381, AI109464, AI105584, and AI107095) and B.K.C. (GM113885 and DA028866) as well as by Canadian Institutes of Health Research (CIHR) (C.L.). Research in the Freed lab is supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, and by the Intramural AIDS Targeted Antiviral Program. NR 47 TC 12 Z9 12 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD OCT 6 PY 2015 VL 13 IS 1 BP 145 EP 156 DI 10.1016/j.celrep.2015.08.055 PG 12 WC Cell Biology SC Cell Biology GA CT0VY UT WOS:000362517000015 PM 26387945 ER PT J AU Makowska-Grzyska, M Kim, YC Gorla, SK Wei, Y Mandapati, K Zhang, MJ Maltseva, N Modi, G Boshoff, HI Gu, MY Aldrich, C Cuny, GD Hedstrom, L Joachimiak, A AF Makowska-Grzyska, Magdalena Kim, Youngchang Gorla, Suresh Kumar Wei, Yang Mandapati, Kavitha Zhang, Minjia Maltseva, Natalia Modi, Gyan Boshoff, Helena I. Gu, Minyi Aldrich, Courtney Cuny, Gregory D. Hedstrom, Lizbeth Joachimiak, Andrzej TI Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds SO PLOS ONE LA English DT Article ID INOSINE MONOPHOSPHATE DEHYDROGENASE; MYCOPHENOLIC ADENINE-DINUCLEOTIDE; 5'-MONOPHOSPHATE DEHYDROGENASE; CRYPTOSPORIDIUM-PARVUM; INHIBITOR SELECTIVITY; CRYSTAL-STRUCTURE; MOLECULAR-INTERACTIONS; KINETIC MECHANISM; STRUCTURAL BASIS; BINDING AB Tuberculosis (TB) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug-and extensively-drug resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of NAD(+) to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics. C1 [Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Gu, Minyi; Joachimiak, Andrzej] Univ Chicago, Ctr Struct Genom Infect Dis, Chicago, IL 60637 USA. [Kim, Youngchang; Joachimiak, Andrzej] Argonne Natl Lab, Struct Biol Ctr, Biosci, Argonne, IL 60439 USA. [Gorla, Suresh Kumar; Wei, Yang; Mandapati, Kavitha; Zhang, Minjia; Modi, Gyan; Hedstrom, Lizbeth] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. [Boshoff, Helena I.] NIAID, TB Res Sect, Bethesda, MD 20892 USA. [Aldrich, Courtney] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN USA. [Cuny, Gregory D.] Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. [Cuny, Gregory D.; Hedstrom, Lizbeth] Brandeis Univ, Dept Chem, Waltham, MA 02254 USA. RP Hedstrom, L (reprint author), Brandeis Univ, Dept Biol, 415 South St, Waltham, MA 02254 USA. EM hedstrom@brandeis.edu; andrzejj@anl.gov FU National Institute of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700058C, HHSN272201200026C]; Intramural Research Program of NIAID; U.S. Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; [AI093459] FX This work was supported by the National Institute of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) [contracts HHSN272200700058C and HHSN272201200026C to the Center of Structural Genomics of Infectious Diseases], grant AI093459 (to LH) and the Intramural Research Program of NIAID (HB). The use of Structural Biology Center beamlines was supported by the U.S. Department of Energy, Office of Biological and Environmental Research [contract DE-AC02-06CH11357]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 3 Z9 4 U1 5 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 6 PY 2015 VL 10 IS 10 AR e0138976 DI 10.1371/journal.pone.0138976 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT0TP UT WOS:000362510300011 PM 26440283 ER PT J AU Pepper, DJ Schomaker, M Wilkinson, RJ de Azevedo, V Maartens, G AF Pepper, Dominique J. Schomaker, Michael Wilkinson, Robert J. de Azevedo, Virginia Maartens, Gary TI Independent predictors of tuberculosis mortality in a high HIV prevalence setting: a retrospective cohort study SO AIDS RESEARCH AND THERAPY LA English DT Article DE Tuberculosis; HIV; Mortality; Predictors; Multivariate analysis ID HUMAN-IMMUNODEFICIENCY-VIRUS; RURAL SOUTH-AFRICA; PULMONARY TUBERCULOSIS; RISK-FACTORS; FOLLOW-UP; CLINICAL DETERIORATION; TREATMENT OUTCOMES; REDUCES MORTALITY; DRUG-RESISTANCE; EARLY DEATH AB Background: Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment. Methods: We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike's Information Criterion to obtain the most relevant predictors of death. Results: Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective. Conclusion: We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment. C1 [Pepper, Dominique J.; Wilkinson, Robert J.; Maartens, Gary] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Schomaker, Michael] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Schomaker, Michael] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa. [Wilkinson, Robert J.] Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, ZA-7925 Cape Town, South Africa. [Wilkinson, Robert J.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W2 1PG, England. [de Azevedo, Virginia] City Hlth, Cape Town, South Africa. Groote Schuur Hosp, Div Pharmacol, ZA-7925 Cape Town, South Africa. RP Maartens, G (reprint author), Univ Cape Town, Dept Med, Anzio Rd, ZA-7925 Cape Town, South Africa. EM Gary.Maartens@uct.ac.za RI Maartens, Gary/F-3836-2014; OI Maartens, Gary/0000-0003-3080-6606; Wilkinson, Robert/0000-0002-2753-1800 FU Wellcome Trust [104803] NR 42 TC 4 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-6405 J9 AIDS RES THER JI Aids Res. Ther. PD OCT 6 PY 2015 VL 12 AR 35 DI 10.1186/s12981-015-0076-5 PG 9 WC Infectious Diseases SC Infectious Diseases GA CS7DV UT WOS:000362245200001 PM 26448780 ER PT J AU Silverberg, MJ Lau, B Achenbach, CJ Jing, YZ Althoff, KN D'Souza, G Engels, EA Hessol, NA Brooks, JT Burchell, AN Gill, MJ Goedert, JJ Hogg, R Horberg, MA Kirk, GD Kitahata, MM Korthuis, PT Mathews, WC Mayor, A Modur, SP Napravnik, S Novak, RM Patel, P Rachlis, AR Sterling, TR Willig, JH Justice, AC Moore, RD Dubrow, R AF Silverberg, Michael J. Lau, Bryan Achenbach, Chad J. Jing, Yuezhou Althoff, Keri N. D'Souza, Gypsyamber Engels, Eric A. Hessol, Nancy A. Brooks, John T. Burchell, Ann N. Gill, M. John Goedert, James J. Hogg, Robert Horberg, Michael A. Kirk, Gregory D. Kitahata, Mari M. Korthuis, Philip T. Mathews, William C. Mayor, Angel Modur, Sharada P. Napravnik, Sonia Novak, Richard M. Patel, Pragna Rachlis, Anita R. Sterling, Timothy R. Willig, James H. Justice, Amy C. Moore, Richard D. Dubrow, Robert CA Int Epidemiologic Databases TI Cumulative Incidence of Cancer Among Persons With HIV in North America A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; AIDS-DEFINING MALIGNANCIES; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; FORCE RECOMMENDATION STATEMENT; HUMAN-PAPILLOMAVIRUS VACCINE; UNITED-STATES; INFECTED INDIVIDUALS; HIV-1-INFECTED PATIENTS; LUNG-CANCER; ANAL CANCER AB Background: Cancer is increasingly common among persons with HIV. Objective: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. Design: Cohort study. Setting: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. Participants: 86 620 persons with HIV and 196 987 uninfected adults. Measurements: Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. Results: Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. Limitation: Secular trends in screening, smoking, and viral co-infections were not evaluated. Conclusion: Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non- Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation. C1 Kaiser Permanente No Calif, Oakland, CA USA. Johns Hopkins Sch Med, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Northwestern Univ, Feinberg Sch Med, Ctr Global Hlth, Lurie Canc Ctr, Chicago, IL 60611 USA. Univ Illinois, Coll Med, Chicago, IL USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Toronto, Ontario HIV Treatment Network, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. Univ Calgary, Calgary, AB, Canada. British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. Kaiser Permanente, Midatlantic Permanente Res Inst, Rockville, MD USA. Univ Washington, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Cent Caribe, Sch Med, Retrovirus Res Ctr, Bayamon, PR USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Alabama Birmingham, Birmingham, AL USA. Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Silverberg, MJ (reprint author), Kaiser Permanente, Div Res, 2000 Broadway,2nd Floor, Oakland, CA 94612 USA. EM Michael.J.Silverberg@kp.org RI Gill, John/G-7083-2016; OI Gill, John/0000-0002-8546-8790; Mayor, Angel M./0000-0002-7705-837X; Hogg, Robert/0000-0003-3463-5488; Justice, Amy/0000-0003-0139-5502 FU National Institutes of Health FX National Institutes of Health. NR 74 TC 29 Z9 30 U1 2 U2 13 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 6 PY 2015 VL 163 IS 7 BP 507 EP + DI 10.7326/M14-2768 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA CT0OQ UT WOS:000362496400004 PM 26436616 ER PT J AU Grant, EK Faranesh, AZ Cross, RR Olivieri, LJ Hamann, KS O'Brien, KJ Hansen, MS Donofrio, MT Lederman, RJ Ratnayaka, K Slack, MC AF Grant, Elena K. Faranesh, Anthony Z. Cross, Russell R. Olivieri, Laura J. Hamann, Karin S. O'Brien, Kendall J. Hansen, Michael S. Donofrio, Mary T. Lederman, Robert J. Ratnayaka, Kanishka Slack, Michael C. TI Image Fusion Guided Device Closure of Left Ventricle to Right Atrium Shunt SO CIRCULATION LA English DT Editorial Material C1 [Grant, Elena K.; Faranesh, Anthony Z.; Cross, Russell R.; Olivieri, Laura J.; Hamann, Karin S.; O'Brien, Kendall J.; Hansen, Michael S.; Donofrio, Mary T.; Lederman, Robert J.; Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. [Grant, Elena K.; Faranesh, Anthony Z.; Hansen, Michael S.; Lederman, Robert J.; Ratnayaka, Kanishka] NHLBI, Div Intramural Res, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20982 USA. [Slack, Michael C.] Univ Maryland, Childrens Heart Program, Baltimore, MD 21201 USA. RP Grant, EK (reprint author), NHLBI, NIH, Bldg 10,Room 2c713,MSC 1538, Bethesda, MD 20982 USA. EM elena.grant@nih.gov RI Hansen, Michael/J-5391-2015 OI Hansen, Michael/0000-0002-8087-8731 FU Intramural NIH HHS [Z01 HL005062-06]; NHLBI NIH HHS [HHSN268201500001C, HHSN268201500001I, Z01-HL006039]; PHS HHS [268201500001C] NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 6 PY 2015 VL 132 IS 14 BP 1366 EP 1367 DI 10.1161/CIRCULATIONAHA.115.013724 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CS6UA UT WOS:000362217000011 PM 26438770 ER PT J AU Delling, FN Rong, J Larson, MG Lehman, B Osypiuk, E Stantchev, P Slaugenhaupt, SA Benjamin, EJ Levine, RA Vasan, RS AF Delling, Francesca N. Rong, Jian Larson, Martin G. Lehman, Birgitta Osypiuk, Ewa Stantchev, Plamen Slaugenhaupt, Susan A. Benjamin, Emelia J. Levine, Robert A. Vasan, Ramachandran S. TI Response to Letter Regarding Article, "Familial Clustering of Mitral Valve Prolapse in the Community" SO CIRCULATION LA English DT Letter C1 [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA. [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Delling, Francesca N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. [Rong, Jian] Boston Univ, Sch Med, Dept Med, Neurol Sect, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Sect Math, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Sect Stat, Boston, MA 02215 USA. [Slaugenhaupt, Susan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Med, Boston, MA USA. RP Delling, FN (reprint author), Boston Univ, Boston, MA 02215 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23 HL116652, 1R01HL126136, 1R01HL128914, 2R01HL092577, K23HL116652, N01-HC-25195, R01HL107385]; PHS HHS [268201500001I] NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 6 PY 2015 VL 132 IS 14 BP E187 EP E188 DI 10.1161/CIRCULATIONAHA.115.016788 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CS6UD UT WOS:000362217300009 PM 26438779 ER PT J AU Traynor, BJ Angelini, C AF Traynor, Bryan J. Angelini, Corrado TI [An] enumeration shall be made ... SO NEUROLOGY LA English DT Editorial Material AB The last decade has revolutionized our understanding of the genetic defects that give rise to neurologic diseases. This genomic knowledge has provided us with remarkable insights into the cellular mechanisms underlying neuronal dysfunction; furthermore, the genetic dissection of heterogeneous neurologic disorders, such as ataxias and hereditary spastic paraparesis, has influenced clinical services and trials. Even in late-onset diseases, and in individuals without an obvious family history, the importance of genetics is increasingly recognized. There is a pressing need to collect neuroepidemiologic data for rare genetic disorders and to develop new techniques that facilitate this collection. C1 [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Angelini, Corrado] Fdn Osped San Camillo IRCCS, Venice, Italy. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov OI Angelini, Corrado/0000-0002-9554-8794 FU Intramural NIH HHS NR 4 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 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD OCT 6 PY 2015 VL 85 IS 14 BP 1191 EP 1192 DI 10.1212/WNL.0000000000001998 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CS6OQ UT WOS:000362200300002 PM 26341871 ER PT J AU Yang, L Xie, SH Feng, XS Chen, YH Zheng, TZ Dai, M Zhou, CK Hu, ZB Li, N Hang, D AF Yang, Lin Xie, Shuanghua Feng, Xiaoshuang Chen, Yuheng Zheng, Tongzhang Dai, Min Zhou, Cindy Ke Hu, Zhibin Li, Ni Hang, Dong TI Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis SO SCIENTIFIC REPORTS LA English DT Article ID POLYMERASE-CHAIN-REACTION; 72 ARG72PRO POLYMORPHISM; HPV DNA; SEROLOGIC EVIDENCE; VIRAL-INFECTIONS; ASSOCIATION; TISSUE; CARCINOMA; BENIGN; VIRUS AB Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84-20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52-18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29-2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. C1 [Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Dai, Min; Li, Ni] Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst & Hosp, Natl Off Canc Prevent & Control, Beijing 100730, Peoples R China. [Yang, Lin] Peking Univ, Coll Med 4, Beijing Jishuitan Hosp, Dept Hosp Infect Control, Beijing 100871, Peoples R China. [Zheng, Tongzhang] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Zhou, Cindy Ke] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hu, Zhibin; Hang, Dong] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Peoples R China. RP Li, N (reprint author), Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst & Hosp, Natl Off Canc Prevent & Control, Beijing 100730, Peoples R China. EM lini1240@hotmail.com; hangdong@njmu.edu.cn RI Zhou, Cindy /H-2165-2015 OI Zhou, Cindy /0000-0003-4814-4305 FU China Scholarship Council (CSC); Scientific Research Foundation for Returned Scholars, Ministry of Education of China; National Natural Science Foundation of China [81172757, 81373079]; Beijing Nova Program [xx2012067]; Natural Science Foundation of Beijing Municipality [7123225]; US National Institutes of Health, National Cancer Institute FX This work is supported in part by the scholarship from China Scholarship Council (CSC) and Scientific Research Foundation for Returned Scholars, Ministry of Education of China for the conduct of the research and preparation of the article. This work was supported in part by the National Natural Science Fund from the National Natural Science Foundation of China (grant no. 81172757 and 81373079), Beijing Nova Program (grant no.xx2012067) and Natural Science Foundation of Beijing Municipality (grant no.7123225). Cindy Ke Zhou was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute. NR 72 TC 0 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 6 PY 2015 VL 5 AR 14667 DI 10.1038/srep14667 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS7IJ UT WOS:000362257000001 PM 26441160 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI Archaeal ancestors of eukaryotes: not so elusive any more SO BMC BIOLOGY LA English DT Article ID NUCLEAR-PORE-COMPLEX; MICROBIAL DIVERSITY; DOMAIN ARCHAEA; DARK-MATTER; ORIGIN; EVOLUTION; LIFE; TREE; INSIGHTS; GENOMES AB The origin of eukaryotes is one of the hardest problems in evolutionary biology and sometimes raises the ominous specter of irreducible complexity. Reconstruction of the gene repertoire of the last eukaryotic common ancestor (LECA) has revealed a highly complex organism with a variety of advanced features but no detectable evolutionary intermediates to explain their origin. Recently, however, genome analysis of diverse archaea led to the discovery of apparent ancestral versions of several signature eukaryotic systems, such as the actin cytoskeleton and the ubiquitin network, that are scattered among archaea. These findings inspired the hypothesis that the archaeal ancestor of eukaryotes was an unusually complex form with an elaborate intracellular organization. The latest striking discovery made by deep metagenomic sequencing vindicates this hypothesis by showing that in phylogenetic trees eukaryotes fall within a newly identified archaeal group, the Lokiarchaeota, which combine several eukaryotic signatures previously identified in different archaea. The discovery of complex archaea that are the closest living relatives of eukaryotes is most compatible with the symbiogenetic scenario for eukaryogenesis. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU US Department of Health and Human Services FX The author's research is supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine, NIH). NR 73 TC 14 Z9 14 U1 9 U2 61 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD OCT 5 PY 2015 VL 13 AR 84 DI 10.1186/s12915-015-0194-5 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CS7QV UT WOS:000362280900001 PM 26437773 ER PT J AU Rollauer, SE Sooreshjani, MA Noinaj, N Buchanan, SK AF Rollauer, Sarah E. Sooreshjani, Moloud A. Noinaj, Nicholas Buchanan, Susan K. TI Outer membrane protein biogenesis in Gram-negative bacteria SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE beta-barrel membrane protein; outer membrane; protein folding; beta-barrel assembly machinery complex; insertase; lateral gate ID BARREL ASSEMBLY MACHINERY; PERIPLASMIC CHAPERONE SKP; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; MOLECULAR CHAPERONE; DIFFERENTIAL PROTEOMICS; ESSENTIAL COMPONENT; SHIGELLA-FLEXNERI; HIGH-TEMPERATURE; STRUCTURAL BASIS AB Gram-negative bacteria contain a double membrane which serves for both protection and for providing nutrients for viability. The outermost of these membranes is called the outer membrane (OM), and it contains a host of fully integrated membrane proteins which serve essential functions for the cell, including nutrient uptake, cell adhesion, cell signalling and waste export. For pathogenic strains, many of these outer membrane proteins (OMPs) also serve as virulence factors for nutrient scavenging and evasion of host defence mechanisms. OMPs are unique membrane proteins in that they have a beta-barrel fold and can range in size from 8 to 26 strands, yet can Still serve many different functions for the cell. Despite their essential roles in cell survival and virulence, the exact mechanism for the biogenesis of these OMPs into the OM has remained largely unknown. However, the past decade has witnessed significant progress towards unravelling the pathways and mechanisms necessary for moulding a nascent polypeptide into a functional OMP within the OM. Here, we will review some of these recent discoveries that have advanced our understanding of the biogenesis' of OMPs in Gram-negative bacteria, starting with synthesis in the cytoplasm to folding and insertion into the OM. C1 [Rollauer, Sarah E.; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA. [Sooreshjani, Moloud A.; Noinaj, Nicholas] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. RP Noinaj, N (reprint author), Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA. EM nnoinaj@purdue.edu; skbuchan@helix.nih.gov RI Rollauer, Sarah/L-4576-2016 OI Rollauer, Sarah/0000-0002-2116-3170 FU Department of Biological Sciences at Purdue University; National Institute of Allergy and Infectious Diseases [1K22AI113078-01]; Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Sir Henry Wellcome Post-Doctoral Fellowship [103040/Z/13/Z] FX M.A.S. and N.N. are supported by the Department of Biological Sciences at Purdue University and by the National Institute of Allergy and Infectious Diseases (1K22AI113078-01). S.E.R. and S.K.B. are supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. S.E.R. is also supported by a Sir Henry Wellcome Post-Doctoral Fellowship (103040/Z/13/Z). NR 90 TC 9 Z9 9 U1 3 U2 23 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 EI 1471-2970 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD OCT 5 PY 2015 VL 370 IS 1679 AR 20150023 DI 10.1098/rstb.2015.0023 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CT3IS UT WOS:000362701000008 ER PT J AU Wikramaratna, PS Rambaut, A AF Wikramaratna, Paul S. Rambaut, Andrew TI Relationship between haemagglutination inhibition titre and immunity to influenza in ferrets SO VACCINE LA English DT Article DE Haemagglutination inhibition assay; Influenza; Ferrets; Antigenic evolution ID VIRUS VACCINES; INACTIVATED INFLUENZA; ANTIBODY-TITERS; B VIRUSES; INFECTION; PROTECTION; IMMUNIZATION; H1N1; ASSAYS; MODEL AB Our understanding of the antigenic evolution of the human influenza virus is chiefly derived from experiments in which serum from influenza infected ferrets is tested against panels of virus isolates in the haemagglutination inhibition (HI) assay. The interpretation of these results has been much aided by the development of antigenic mapping techniques, which suppose that the antigenic distance between two different influenza viruses is directly proportional to their fold-difference in titre in this assay. Yet, antigenic distance is not necessarily the same as cross-protection, and high levels of protection have been observed in humans against strains to which they have low HI titres. However, no study has previously addressed the relationship between HI titre and cross-protection in ferrets: the standard animal model. This study fills this gap by analysing published data where pre-challenge HI titres are available for individual ferrets, and post-challenge outcomes have been recorded. Ultimately, this work confirms that it is the absolute, rather than relative, HI titre that determines the extent of immunity and that there is a threshold HI titre beyond which ferrets are completely protected from infection. Nevertheless, this titre is much higher in ferrets than has been suggested for humans. Further, we are consequently able to show that using distance between strains within an antigenic map to predict cross-protection between influenza viruses can be misleading. (C) 2015 The Authors. Published by Elsevier Ltd. C1 [Wikramaratna, Paul S.; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH8 9YL, Midlothian, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland. RP Wikramaratna, PS (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH8 9YL, Midlothian, Scotland. EM pwikramaratna@gmail.com FU European Research Council under European Community's Seventh Framework Programme [278433-PREDEMICS]; ERC [260864] FX The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 278433-PREDEMICS and ERC Grant Agreement No. 260864. NR 33 TC 2 Z9 2 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD OCT 5 PY 2015 VL 33 IS 41 BP 5380 EP 5385 DI 10.1016/j.vaccine.2015.08.065 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CS7ZT UT WOS:000362306200007 PM 26342848 ER PT J AU Lin, YJ Chang, JS Liu, X Tsang, HY Chien, WK Chen, JH Hsieh, HY Hsueh, KC Shiao, YT Li, JP Lin, CW Lai, CH Wu, JY Chen, CH Lin, JG Lin, TH Liao, CC Huang, SM Lan, YC Ho, TJ Liang, WM Yeh, YC Lin, JC Tsai, FJ AF Lin, Ying-Ju Chang, Jeng-Sheng Liu, Xiang Tsang, Hsinyi Chien, Wen-Kuei Chen, Jin-Hua Hsieh, Hsin-Yang Hsueh, Kai-Chung Shiao, Yi-Tzone Li, Ju-Pi Lin, Cheng-Wen Lai, Chih-Ho Wu, Jer-Yuarn Chen, Chien-Hsiun Lin, Jaung-Geng Lin, Ting-Hsu Liao, Chiu-Chu Huang, Shao-Mei Lan, Yu-Ching Ho, Tsung-Jung Liang, Wen-Miin Yeh, Yi-Chun Lin, Jung-Chun Tsai, Fuu-Jen TI Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan SO SCIENTIFIC REPORTS LA English DT Article ID GENOME-WIDE ASSOCIATION; TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; HUMAN SYNOVIAL FIBROBLASTS; ENDOTHELIAL-CELLS; ALLERGIC DISEASES; REACTIVE PROTEIN; PHOSPHOLIPASE-C; POLYMORPHISM; CHILDREN AB Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD. C1 [Lin, Ying-Ju; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Tsai, Fuu-Jen] China Med Univ Hosp, Genet Ctr, Dept Med Res, Taichung, Taiwan. [Lin, Ying-Ju; Li, Ju-Pi; Wu, Jer-Yuarn; Chen, Chien-Hsiun; Lin, Jaung-Geng; Ho, Tsung-Jung; Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung, Taiwan. [Chang, Jeng-Sheng; Hsieh, Hsin-Yang] China Med Univ, Childrens Hosp, Taichung, Taiwan. [Chang, Jeng-Sheng] China Med Univ, Sch Med, Taichung, Taiwan. [Liu, Xiang; Tsang, Hsinyi] NIAID, NIH, Bethesda, MD 20892 USA. [Chien, Wen-Kuei; Chen, Jin-Hua] Taipei Med Univ, Coll Management, Ctr Biostat, Taipei, Taiwan. [Chen, Jin-Hua] Taipei Med Univ, Coll Management, Sch Hlth Care Adm, Taipei, Taiwan. [Hsieh, Hsin-Yang] China Med Univ, Childrens Hosp, Pediat Emergency Div, Taichung, Taiwan. [Hsueh, Kai-Chung] Kai Chung Hsueh Clin, Taichung, Taiwan. [Shiao, Yi-Tzone] China Med Univ Hosp, Ctr Heart, Taichung, Taiwan. [Li, Ju-Pi] China Med Univ Hosp, Rheumatism Res Ctr, Taichung, Taiwan. [Lin, Cheng-Wen] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan. [Lai, Chih-Ho] Chang Gung Univ, Grad Inst Biomed Sci, Dept Microbiol & Immunol, Taoyuan, Taiwan. [Wu, Jer-Yuarn; Chen, Chien-Hsiun] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. [Yeh, Yi-Chun] China Med Univ, Dept Hlth Risk Management, Taichung, Taiwan. [Liang, Wen-Miin; Yeh, Yi-Chun] China Med Univ, Sch Publ Hlth, Grad Inst Biostat, Taichung, Taiwan. [Lin, Jung-Chun] Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan. [Tsai, Fuu-Jen] Asia Univ, Dept Biotechnol & Bioinformat, Taichung, Taiwan. RP Tsai, FJ (reprint author), China Med Univ Hosp, Genet Ctr, Dept Med Res, Taichung, Taiwan. EM d0704@mail.cmuh.org.tw RI Lai, Chih-Ho/M-2433-2013; Lan, Yu-Ching/F-2449-2017 OI Lai, Chih-Ho/0000-0001-9229-818X; Lan, Yu-Ching/0000-0003-4781-6405 FU China Medical University [CMU102-PH-01, CMU100-S-01]; China Medical University Hospital [DMR-102-083, DMR-104-029, DMR-104-089]; National Science Council; Ministry of Science and Technology, Taiwan [NSC101-2314-B-039-008-MY3, NSC 102-2314-B-039 -011 -MY3, MOST 103-2320-B-039 -006 -MY3]; China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan FX This study was supported by grants from the China Medical University (CMU102-PH-01 and CMU100-S-01), the China Medical University Hospital (DMR-102-083, DMR-104-029, and DMR-104-089), the National Science Council, the Ministry of Science and Technology, Taiwan (NSC101-2314-B-039-008-MY3, NSC 102-2314-B-039 -011 -MY3, and MOST 103-2320-B-039 -006 -MY3), and China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan. We thank the National Center for Genome Medicine of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, for technical and bioinformatics support. We also thank Drs. Ya-Hui Chi, Kuan-Teh Jeang, and Willy W.L. Hong for technical help and suggestions. NR 56 TC 2 Z9 2 U1 4 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD OCT 5 PY 2015 VL 5 AR 14762 DI 10.1038/srep14762 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS6GE UT WOS:000362175600002 PM 26434682 ER PT J AU van der Weyden, C Dickinson, M Bates, SE Prince, HM AF van der Weyden, Carrie Dickinson, Michael Bates, Susan E. Prince, Henry Miles TI Use of romidepsin for the treatment of mycosis fungoides and Sezary syndrome - role of romidepsin in the current therapeutic landscape and implications for future practice SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Article DE cutaneous T-cell lymphoma; depsipeptide; histone deacetylase inhibitors; mycosis fungoides; romidepsin; Sezary syndrome ID T-CELL LYMPHOMA; HISTONE DEACETYLASE INHIBITOR; PHASE-II TRIAL; CHROMOBACTERIUM-VIOLACEUM NO-968; DEPSIPEPTIDE FR901228; SYSTEMIC THERAPY; UNITED-STATES; FK228; PHARMACOKINETICS; PATTERNS AB Introduction: Cutaneous T-cell lymphoma (CTCL) encompasses a rare group of hematologic malignancies, in which complete and durable responses to treatment are often elusive, with patients requiring multiple successive lines of therapy. Traditional chemotherapeutic agents do not seem to deliver lasting responses and are not without cumulative toxicity. In this context, focus has shifted to biologic and immunomodulatory agents, of which the histone deacetylase inhibitor (HDACi) romidepsin has attracted interest for its tolerability and proven efficacy in around one-third of patients in two pivotal clinical trials.Areas covered: In this review, we survey existing preclinical and clinical data for romidepsin from its discovery to use in prospective clinical trials. Pharmacology, toxicity and current market overview including potential comparators are also examined.Expert opinion: There is a clear and demonstrable role for romidepsin in the treatment of CTCL given convincing long-term Phase II efficacy data. Nonetheless, prospective data are lacking to guide selection between different biologic agents and to better identify those patients most likely to benefit from this therapy. We suggest that comparative trials between biologic agents, and ongoing research into CTCL pathogenesis and biomarkers of disease response are required to guide this decision-making process in future. C1 [van der Weyden, Carrie; Dickinson, Michael; Prince, Henry Miles] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [van der Weyden, Carrie; Dickinson, Michael; Prince, Henry Miles] Univ Melbourne, Dept Haematol, Melbourne, Vic 3010, Australia. [Bates, Susan E.] NCI, NIH, Dev Therapeut Branch, Bethesda, MD 20892 USA. RP Prince, HM (reprint author), Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. EM Miles.Prince@petermac.org FU Celgene Pharmaceuticals; NCI FX M Prince is an advisory board member, and recipient of research funding and honorarium from Celgene Pharmaceuticals. M Dickinson also receives research funding and honorarium from Celgene Pharmaceuticals. S Bates receives research funding via a collaborative research and development agreements between the NCI and Celgene Pharmaceuticals. 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 42 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD OCT 3 PY 2015 VL 3 IS 10 BP 1231 EP 1239 DI 10.1517/21678707.2015.1089169 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DC7LD UT WOS:000369400500001 ER PT J AU How, J Minden, MD Brian, L Chen, EX Brandwein, J Schuh, AC Schimmer, AD Gupta, V Webster, S Degelder, T Haines, P Stayner, LA McGill, S Wang, LS Piekarz, R Wong, T Siu, LL Espinoza-Delgado, I Holleran, JL Egorin, MJ Yee, KWL AF How, Jonathan Minden, Mark D. Brian, Leber Chen, Eric X. Brandwein, Joseph Schuh, Andre C. Schimmer, Aaron D. Gupta, Vikas Webster, Sheila Degelder, Tammy Haines, Patricia Stayner, Lee-Anne McGill, Shauna Wang, Lisa Piekarz, Richard Wong, Tracy Siu, Lillian L. Espinoza-Delgado, Igor Holleran, Julianne L. Egorin, Merrill J. Yee, Karen W. L. TI A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Decitabine; vorinostat; hypomethylating agent; histone deacetylase inhibitor; acute myeloid leukemia ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; MYELODYSPLASTIC SYNDROMES; DNA METHYLTRANSFERASE; OLDER PATIENTS; VALPROIC ACID; ANTINEOPLASTIC ACTION; MYELOGENOUS LEUKEMIA; 1ST-LINE TREATMENT AB This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules. C1 [How, Jonathan; Minden, Mark D.; Brian, Leber; Chen, Eric X.; Brandwein, Joseph; Schuh, Andre C.; Schimmer, Aaron D.; Gupta, Vikas; Webster, Sheila; Degelder, Tammy; Haines, Patricia; Stayner, Lee-Anne; McGill, Shauna; Wang, Lisa; Wong, Tracy; Siu, Lillian L.; Yee, Karen W. L.] Princess Margaret Phase I Consortium, Toronto, ON, Canada. [Piekarz, Richard; Espinoza-Delgado, Igor] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Yee, KWL (reprint author), Princess Margaret Canc Ctr, Div Med Oncol & Hematol, 610 Univ Ave,5-218, Toronto, ON M5G 2M9, Canada. EM karen.yee@uhn.ca FU NCI [N01-CM-62203, U01-CA-132123] FX This work was supported by the NCI Contract Number: N01-CM-62203 and U01-CA-132123. NR 55 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT 3 PY 2015 VL 56 IS 10 BP 2793 EP 2802 DI 10.3109/10428194.2015.1018248 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CW8IC UT WOS:000365241700008 PM 25682963 ER PT J AU Lionakis, MS AF Lionakis, Michail S. TI Virulence profile: Michail Lionakis SO VIRULENCE LA English DT Editorial Material C1 NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lionakism@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2150-5594 EI 2150-5608 J9 VIRULENCE JI Virulence PD OCT 3 PY 2015 VL 6 IS 7 BP 722 EP 725 DI 10.1080/21505594.2015.1090244 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CV4LZ UT WOS:000364239900010 PM 26367813 ER PT J AU Osera, C Martindale, JL Amadio, M Kim, J Yang, XL Moad, CA Indig, FE Govoni, S Abdelmohsen, K Gorospe, M Pascale, A AF Osera, Cecilia Martindale, Jennifer L. Amadio, Marialaura Kim, Jiyoung Yang, Xiaoling Moad, Christopher A. Indig, Fred E. Govoni, Stefano Abdelmohsen, Kotb Gorospe, Myriam Pascale, Alessia TI Induction of VEGFA mRNA translation by CoCl2 mediated by HuR SO RNA BIOLOGY LA English DT Article DE biotin pulldown; mass spectrometry; post-transcriptional gene regulation; polysome profiling; ribonucleoprotein complex; RNA-binding proteins ID ENDOTHELIAL GROWTH-FACTOR; BINDING PROTEIN HUR; PIGMENT EPITHELIAL-CELLS; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; HNRNP L; STABILITY; HYPOXIA; STABILIZATION; ANGIOGENESIS AB Vascular endothelial growth factor (VEGF) A is a master regulator of neovascularization and angiogenesis. VEGFA is potently induced by hypoxia and by pathological conditions including diabetic retinopathy and tumorigenesis. Fine-tuning of VEGFA expression by different stimuli is important for maintaining tissue vascularization and organ homeostasis. Here, we tested the effect of the hypoxia mimetic cobalt chloride (CoCl2) on VEGFA expression in human cervical carcinoma HeLa cells. We found that CoCl2 increased the levels of VEGFA mRNA and VEGFA protein without affecting VEGFA mRNA stability. Biotin pulldown analysis to capture the RNA-binding proteins (RBPs) bound to VEGFA mRNA followed by mass spectrometry analysis revealed that the RBP HuR [human antigen R, a member of the embryonic lethal abnormal vision (ELAV) family of proteins], interacts with VEGFA mRNA. VEGFA mRNA-tagging experiments showed that exposure to CoCl2 increases the interaction of HuR with VEGFA mRNA and promoted the colocalization of HuR and the distal part of the VEGFA 3-untranslated region (UTR) in the cytoplasm. We propose that under hypoxia-like conditions, HuR enhances VEGFA mRNA translation. C1 [Osera, Cecilia; Martindale, Jennifer L.; Kim, Jiyoung; Yang, Xiaoling; Moad, Christopher A.; Indig, Fred E.; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Osera, Cecilia; Amadio, Marialaura; Govoni, Stefano; Pascale, Alessia] Univ Pavia, Pharmacol Sect, Dept Drug Sci, Lab Cellular & Mol Neuropharmacol, I-27100 Pavia, Italy. RP Osera, C (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM cecilia.osera@unipv.it RI Osera, Cecilia/K-3677-2016 OI Osera, Cecilia/0000-0002-7406-7166 FU NIA-IRP, NIH; EMBO short-term fellowship; Fondazione Banca del Monte di Lombardia fellowship FX JLM, JK, XY, CAM, FEI, KA, and MG were supported by the NIA-IRP, NIH. CO was supported by an EMBO short-term fellowship and by the Fondazione Banca del Monte di Lombardia fellowship. NR 50 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD OCT 3 PY 2015 VL 12 IS 10 BP 1121 EP 1130 DI 10.1080/15476286.2015.1085276 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CU1ZY UT WOS:000363322200008 PM 26325091 ER PT J AU Kreitchmann, R Megazzini, K Melo, VH Coelho, DF Watts, DH Krauss, M Gouvea, MI Duarte, G Losso, MH Siberry, GK AF Kreitchmann, Regis Megazzini, Karen Melo, Victor Hugo Coelho, Debora Fernandes Watts, D. Heather Krauss, Margot Gouvea, Maria Isabel Duarte, Geraldo Losso, Marcelo H. Siberry, George K. TI Repeat pregnancy in women with HIV infection in Latin America and the Caribbean SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; predictors of repeat pregnancy; pregnancy; Latin America ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED WOMEN; PREDICTORS; ADHERENCE; DESIRE; RATES; POSTPARTUM; OUTCOMES; BRAZIL AB Intended and unintended pregnancies occur frequently among human immunodeficiency virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and characteristics associated with this outcome among HIV-infected women in Latin America and the Caribbean who were participating in the National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI, 124 (9.2%) had one or more repeat pregnancies on study. Median time between the index delivery and date of conception of the subsequent pregnancy was 1.4 years (range 0.1-5.7). Younger age (odds ratio [OR]=1.07, 95% confidence interval [CI]: 1.04-1.11 per one year decrease in age), hospitalization during the index pregnancy or up to six months post-partum [OR=2.0, 95% CI: 1.2-3.4], and poor index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR=3.4, 95% CI: 1.4-8.4) were associated with increased occurrence of repeat pregnancy in multivariable analysis. Among women with repeat pregnancies, the proportion receiving antiretroviral treatment (vs. prophylaxis) increased from 39.4% at the time of the index pregnancy to 81.8% at the time of the repeat pregnancy (p<0.001). These results can help identify women most likely to benefit from reproductive counseling in order to assist with healthy pregnancy planning and prevention of unintended pregnancies. C1 [Kreitchmann, Regis; Coelho, Debora Fernandes] Irmandade Santa Casa Misericordia Porto Alegre, BR-90020090 Porto Alegre, RS, Brazil. [Megazzini, Karen; Krauss, Margot] WESTAT Corp, Rockville, MD 20850 USA. [Melo, Victor Hugo] Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil. [Watts, D. Heather] US Dept State, Washington, DC 20520 USA. [Gouvea, Maria Isabel] Hosp Fed Servidores Estado, BR-20221903 Rio De Janeiro, RJ, Brazil. [Duarte, Geraldo] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil. [Losso, Marcelo H.] Hosp Gen Agudos Jose Maria Ramos Mejia, HIV Unit, Buenos Aires, DF, Argentina. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Pediat Infect Dis MPID Branch, NIH, Bethesda, MD 20892 USA. RP Kreitchmann, R (reprint author), Irmandade Santa Casa Misericordia Porto Alegre, Prof Annes Dias 285, BR-90020090 Porto Alegre, RS, Brazil. EM regis.kr@terra.com.br FU NICHD [N01-HD-3-3345, HHSN267200800001C, HHSN275201300003C] FX Supported by NICHD Contracts N01-HD-3-3345 (2002-2007), HHSN267200800001C (2007-2012), and HHSN275201300003C (2012-2017). NR 25 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT 3 PY 2015 VL 27 IS 10 BP 1289 EP 1297 DI 10.1080/09540121.2015.1050987 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA CT5VP UT WOS:000362879500012 PM 26288031 ER PT J AU Holl, HM Gao, S Fei, ZJ Andrews, C Brooks, SA AF Holl, Heather M. Gao, Shan Fei, Zhangjun Andrews, Caroline Brooks, Samantha A. TI Generation of a de novo transcriptome from equine lamellar tissue SO BMC GENOMICS LA English DT Article DE Equine; transcriptome; laminitis; RNA-seq; assembly ID INFLAMMATORY GENE-EXPRESSION; LONG NONCODING RNAS; DNA-SEQUENCING DATA; CARBOHYDRATE OVERLOAD; LAMINITIS; GENOME; SEQ; HORSES; FRAMEWORK; ALIGNMENT AB Background: Laminitis, the structural failure of interdigitated tissue that suspends the distal skeleton within the hoof capsule, is a devastating disease that is the second leading cause of both lameness and euthanasia in the horse. Current transcriptomic research focuses on the expression of known genes. However, as this tissue is quite unique and equine gene annotation is largely derived from computational predictions, there are likely yet uncharacterized transcripts that may be involved in the etiology of laminitis. In order to create a novel annotation resource, we performed whole transcriptome sequencing of sagittal lamellar sections from one control and two laminitis affected horses. Results: Whole transcriptome sequencing of the three samples resulted in 113 million reads. Overall, 88 % of the reads mapped to the equCab2 reference genome, allowing for the identification of 119,430 SNPs. The de novo assembly generated around 75,000 transcripts, of which 36,000 corresponded to known annotations. Annotated transcript models are hosted in a public data repository and thus can be easily accessed or loaded into genome browsers. RT-PCR of 12 selected assemblies confirmed structure and expression in lamellar tissue. Conclusions: Transcriptome sequencing represents a powerful tool to expand on equine annotation and identify novel targets for further laminitis research. C1 [Holl, Heather M.; Brooks, Samantha A.] Univ Florida, Dept Anim Sci, Gainesville, FL 32611 USA. [Gao, Shan; Fei, Zhangjun] Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. [Andrews, Caroline] NCI, Lab Mol Immunoregulat, Bethesda, MD 20892 USA. RP Brooks, SA (reprint author), Univ Florida, Dept Anim Sci, Gainesville, FL 32611 USA. EM samantha.brooks@ufl.edu NR 52 TC 5 Z9 5 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 3 PY 2015 VL 16 AR 739 DI 10.1186/s12864-015-1948-8 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CS7GU UT WOS:000362252900001 PM 26432030 ER PT J AU Coleman, R Powles, T Paterson, A Gnant, M Anderson, S Diel, I Gralow, J von Minckwitz, G Moebus, V Bergh, J Pritchard, KI Bliss, J Cameron, D Evans, V Pan, H Peto, R Bradley, R Gray, R Bartsch, R Dubsky, P Fesl, C Fohler, H Gnant, M Greil, R Jakesz, R Lang, A Luschin-Ebengreuth, G Marth, C Mlineritsch, B Samonigg, H Singer, CF Steger, GG Stoger, H Olivotto, I Ragaz, J Christiansen, P Ejlertsen, B Ewertz, M Jensen, MB Moller, S Mouridsen, HT Eiermann, W Hilfrich, J Jonat, W Kaufmann, M Kreienberg, R Schumacher, M Blohmer, JU Costa, SD Eidtmann, H Gerber, B Jackisch, C Loibl, S von Minckwitz, G Dafni, U Markopoulos, C Blomqvist, C Saarto, T Ahn, JH Jung, KH Perrone, F Anderson, S Bass, G Brown, A Bryant, J Costantino, J Dignam, J Fisher, B Geyer, C Mamounas, EP Paik, S Redmond, C Swain, S Wickerham, L Wolmark, N Perez, E Ingle, JN Suman, VJ Hadji, P A'Hern, R Dowsett, M Makris, A Parton, M Pennert, K Powles, TJ Smith, IE Yarnold, JR Clack, G Van Poznak, C Safra, T Bell, R Cameron, D Coleman, RE Dodwell, D Hinsley, S Marshall, HC Solomayer, E Fehm, T Coleman, RE Lester, J Winter, MC Horsman, JM Aft, R Brufsky, AM Coleman, R Llombart, HA AF Coleman, R. Powles, T. Paterson, A. Gnant, M. Anderson, S. Diel, I. Gralow, J. von Minckwitz, G. Moebus, V. Bergh, J. Pritchard, K. I. Bliss, J. Cameron, D. Evans, V. Pan, H. Peto, R. Bradley, R. Gray, R. Bartsch, R. Dubsky, P. Fesl, C. Fohler, H. Gnant, M. Greil, R. Jakesz, R. Lang, A. Luschin-Ebengreuth, G. Marth, C. Mlineritsch, B. Samonigg, H. Singer, C. F. Steger, G. G. Stoeger, H. Olivotto, I. Ragaz, J. Christiansen, P. Ejlertsen, B. Ewertz, M. Jensen, M-B Moller, S. Mouridsen, H. T. Eiermann, W. Hilfrich, J. Jonat, W. Kaufmann, M. Kreienberg, R. Schumacher, M. Blohmer, J. U. Costa, S. D. Eidtmann, H. Gerber, B. Jackisch, C. Loibl, S. von Minckwitz, G. Dafni, U. Markopoulos, C. Blomqvist, C. Saarto, T. Ahn, J-H Jung, K. H. Perrone, F. Anderson, S. Bass, G. Brown, A. Bryant, J. Costantino, J. Dignam, J. Fisher, B. Geyer, C. Mamounas, E. P. Paik, S. Redmond, C. Swain, S. Wickerham, L. Wolmark, N. Perez, E. Ingle, J. N. Suman, V. J. Hadji, P. A'Hern, R. Dowsett, M. Makris, A. Parton, M. Pennert, K. Powles, T. J. Smith, I. E. Yarnold, J. R. Clack, G. Van Poznak, C. Safra, T. Bell, R. Cameron, D. Coleman, R. E. Dodwell, D. Hinsley, S. Marshall, H. C. Solomayer, E. Fehm, T. Coleman, R. E. Lester, J. Winter, M. C. Horsman, J. M. Aft, R. Brufsky, A. M. Coleman, R. Llombart, H. A. CA Early Breast Canc Trialists' Novartis Pharmaceuticals TI Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials SO LANCET LA English DT Article ID ZOLEDRONIC ACID; ORAL CLODRONATE; POSTMENOPAUSAL WOMEN; BONE; METASTASIS; SURVIVAL; THERAPY; CELLS; RISK; PAMIDRONATE AB Background Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs). Findings We received data on 18 766 women (18 206 [97%] in trials of 2-5 years of bisphosphonate) with median follow-up 5.6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0.94, 95% CI 0.87-1.01; 2p=0.08), distant recurrence (0.92, 0.85-0.99; 2p=0.03), and breast cancer mortality (0.91, 0.83-0.99; 2p=0.04) were of only borderline significance, but the reduction in bone recurrence was more definite (0.83, 0.73-0.94; 2p=0.004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0.86, 95% CI 0.78-0.94; 2p=0.002), distant recurrence (0.82, 0.74-0.92; 2p=0.0003), bone recurrence (0.72, 0.60-0.86; 2p=0.0002), and breast cancer mortality (0.82, 0.73-0.93; 2p=0.002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0.06 for trend with menopausal status) or age (2p=0.03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0.85, 95% CI 0.75-0.97; 2p=0.02). Interpretation Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began. Copyright (C) Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Open Access article distributed under the terms of CC BY. C1 [Coleman, R.] Univ Sheffield, Weston Pk Hosp, Sheffield Canc Res Ctr, Sheffield S10 2TN, S Yorkshire, England. [Powles, T.] Royal Marsden Hosp, Sutton, Surrey, England. [Paterson, A.] Tom Baker Canc Clin, Calgary, AB, Canada. [Paterson, A.] Univ Calgary, Calgary, AB, Canada. [Gnant, M.] Med Univ Vienna, Dept Surg, Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria. [Gnant, M.] Med Univ Vienna, Ctr Comprehens Canc, Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria. [Anderson, S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Diel, I.] Ctr Gynecol Oncol, Mannheim, Germany. [Gralow, J.] Univ Washington, Sch Med, Seattle, WA USA. [von Minckwitz, G.] German Breast Grp, Neu Isenburg, Germany. [Moebus, V.] Klinikum Frankfurt Hochst, Frankfurt, Germany. [Bergh, J.] Karolinska Inst, Stockholm, Sweden. [Bergh, J.] St Gorans Univ Hosp, S-11281 Stockholm, Sweden. [Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, K. I.] Univ Toronto, Toronto, ON, Canada. [Bliss, J.] Inst Canc Res, Div Clin Studies, ICR CTSU, London SW3 6JB, England. [Cameron, D.] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Evans, V.; Pan, H.; Peto, R.; Bradley, R.; Gray, R.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England. [Bartsch, R.; Dubsky, P.; Fesl, C.; Fohler, H.; Gnant, M.; Greil, R.; Jakesz, R.; Lang, A.; Luschin-Ebengreuth, G.; Marth, C.; Mlineritsch, B.; Samonigg, H.; Singer, C. F.; Steger, G. G.; Stoeger, H.] Austrian Breast Canc Study Grp, Vienna, Austria. [Olivotto, I.; Ragaz, J.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Christiansen, P.; Ejlertsen, B.; Ewertz, M.; Jensen, M-B; Moller, S.; Mouridsen, H. T.] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. [Eiermann, W.; Hilfrich, J.; Jonat, W.; Kaufmann, M.; Kreienberg, R.; Schumacher, M.] German Adjuvant Breast Grp, Frankfurt, Germany. [Blohmer, J. U.; Costa, S. D.; Eidtmann, H.; Gerber, B.; Jackisch, C.; Loibl, S.; von Minckwitz, G.] German Breast Grp, Neu Isenburg, Germany. [Dafni, U.; Markopoulos, C.] Hellen Breast Surg Soc, Athens, Greece. [Blomqvist, C.; Saarto, T.] Univ Helsinki, FIN-00014 Helsinki, Finland. [Ahn, J-H; Jung, K. H.] Korean Canc Study Grp, Seoul, South Korea. [Perrone, F.] Ist Nazl Tumori IRCCS Fdn Pascale, Naples, Italy. [Anderson, S.; Bass, G.; Brown, A.; Bryant, J.; Costantino, J.; Dignam, J.; Fisher, B.; Geyer, C.; Mamounas, E. P.; Paik, S.; Redmond, C.; Swain, S.; Wickerham, L.; Wolmark, N.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Perez, E.; Ingle, J. N.; Suman, V. J.] Mayo Clin, North Cent Canc Treatment Grp, Rochester, MN USA. [Hadji, P.] ProBONE Study Grp, Marburg, Germany. [A'Hern, R.; Dowsett, M.; Makris, A.; Parton, M.; Pennert, K.; Powles, T. J.; Smith, I. E.; Yarnold, J. R.] Royal Marsden Hosp, London SW3 6JJ, England. [A'Hern, R.; Dowsett, M.; Makris, A.; Parton, M.; Pennert, K.; Powles, T. J.; Smith, I. E.; Yarnold, J. R.] Royal Marsden Hosp, Sutton, Surrey, England. [Safra, T.] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. [Bell, R.; Cameron, D.; Coleman, R. E.; Dodwell, D.; Hinsley, S.; Marshall, H. C.] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Solomayer, E.; Fehm, T.] Univ Saarland, D-66123 Saarbrucken, Germany. [Coleman, R. E.; Lester, J.; Winter, M. C.; Horsman, J. M.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. [Aft, R.] Washington Univ, St Louis, MO USA. RP Coleman, R (reprint author), Univ Sheffield, Weston Pk Hosp, Sheffield Canc Res Ctr, Sheffield S10 2TN, S Yorkshire, England. RI Greil, Richard/C-7673-2017; OI Greil, Richard/0000-0002-4462-3694; malmstrom, per-uno/0000-0001-8572-9957; Bowden, Sarah/0000-0001-7506-1340; Anderson, Stewart/0000-0001-8948-0650; Warnberg, Fredrik/0000-0002-0130-7296; Cardoso, Fatima/0000-0002-6692-2249; Yarnold, John/0000-0002-9010-1854 FU Cancer Research UK; Medical Research Council; UK Medical Research Council FX Cancer Research UK, Medical Research Council.; We thank the tens of thousands of women who took part in the trials, the many staff in trial centres and participating clinics who helped conduct the trials, and the trialists who shared their data. Funding for individual trials was chiefly from manufacturers (see trial publications) but no commercial funding was sought or used by the secretariat. Funding for the EBCTCG secretariat is through the direct support from Cancer Research UK and the UK Medical Research Council, to the Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK. NR 30 TC 62 Z9 63 U1 5 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD OCT 3 PY 2015 VL 386 IS 10001 BP 1353 EP 1361 DI 10.1016/S0140-6736(15)60908-4 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CS8DP UT WOS:000362316200028 ER PT J AU McNeel, DG Chen, YH Gulley, JL Dwyer, AJ Madan, RA Carducci, MA DiPaola, RS AF McNeel, Douglas G. Chen, Yu-Hui Gulley, James L. Dwyer, Alexander J. Madan, Ravi A. Carducci, Michael A. DiPaola, Robert S. TI Randomized phase II trial of docetaxel with or without PSA-TRICOM vaccine in patients with castrate-resistant metastatic prostate cancer: A trial of the ECOG-ACRIN cancer research group (E1809) SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article ID CELLULAR IMMUNOTHERAPY; INCREASED SURVIVAL; SIPULEUCEL-T; VIRUS; MITOXANTRONE; PREDNISONE; CHEMOTHERAPY; PROSTVAC; ANTIGEN; VECTOR C1 [McNeel, Douglas G.; Dwyer, Alexander J.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gulley, James L.; Madan, Ravi A.] NCI, Bethesda, MD 20892 USA. [Carducci, Michael A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [DiPaola, Robert S.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. RP McNeel, DG (reprint author), Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. EM dm3@medicine.wisc.edu RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Public Health Service [CA180820, CA180794, CA180799, CA180802]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was supported in part by Public Health Service Grants CA180820, CA180794, CA180799, CA180802, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 30 TC 8 Z9 8 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD OCT 3 PY 2015 VL 11 IS 10 BP 2469 EP 2474 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA CR5KZ UT WOS:000361382100030 PM 26111351 ER PT J AU Wen, XB Cao, DJ Jones, RW Hoshino, Y Yuan, LJ AF Wen, Xiaobo Cao, Dianjun Jones, Ronald W. Hoshino, Yasutaka Yuan, Lijuan TI Tandem truncated rotavirus VP8*subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE P type; rotavirus; subunit vaccine; universal T cell epitope; VP8*protein ID SEVERE COMBINED IMMUNODEFICIENCY; REASSORTANT ROTAVIRUS; GASTROENTERITIS; CHILDREN; INTUSSUSCEPTION; INFANTS; RISK; MICE; PROTECTION; ANTIBODIES AB The two currently available live oral rotavirus vaccines, Rotarix((R)) and RotaTeq((R)), are highly efficacious in the developed countries. However, the efficacy of such vaccines in resource deprived countries in Africa and Southeast Asia is low. We reported previously that a bacterially-expressed rotavirus P2-P[8] VP8* subunit vaccine candidate administered intramuscularly elicited high-titers of neutralizing antibodies in guinea pigs and mice and significantly shortened the duration of diarrhea in neonatal gnotobiotic pigs upon oral challenge with virulent human rotavirus Wa strain. To further improve its vaccine potential and provide wider coverage against rotavirus strains of global and regional epidemiologic importance, we constructed 2 tandem recombinant VP8* proteins, P2-P[8] VP8*-P[8] VP8* and P2-P[8] VP8*-P[6] VP8* based on Escherichia coli expression system. The two resulting recombinant tandem proteins were highly soluble and P2-P[8] VP8*-P[8] VP8* was generated with high yield. Moreover, guinea pigs immunized intramuscularly by 3 doses of the P2-P[8] VP8*-P[8] VP8* or P2-P[8] VP8*-P[6] VP8* vaccine with aluminum phosphate adjuvant developed high titers of homotypic and heterotypic neutralizing antibodies against human rotaviruses bearing G1-G4, G8, G9 and G12 with P[8], P[4] or P[6] combination. The results suggest that these 2 subunit vaccines in monovalent or bivalent formulation can provide antigenic coverage to almost all the rotavirus G (VP7) types and major P (VP4) types of global as well as regional epidemiologic importance. C1 [Wen, Xiaobo] Heilongjiang Bayi Agr Univ, Coll Anim Sci & Vet Med, Daqing, Heilongjiang Pr, Peoples R China. [Cao, Dianjun; Yuan, Lijuan] Virginia Polytech Inst & State Univ, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. [Jones, Ronald W.; Hoshino, Yasutaka] NIAID, Rotavirus Vaccine Dev Sect, Lab Infect Dis, NIH, Bethesda, MD 20892 USA. RP Yuan, LJ (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. EM lyuan@vt.edu FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA; National Natural Science Foundation of China [31201909]; Doctoral Initiating Project of Heilongjiang Province [LBH-Q13134] FX This work was partially supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA and National Natural Science Foundation of China (Grant No. 31201909) and Doctoral Initiating Project of Heilongjiang Province (No. LBH-Q13134). NR 50 TC 2 Z9 2 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD OCT 3 PY 2015 VL 11 IS 10 BP 2483 EP 2489 PG 7 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA CR5KZ UT WOS:000361382100032 PM 26091081 ER PT J AU Danis, M Wendler, D Kim, S AF Danis, Marion Wendler, David Kim, Scott TI Acceptable Approaches to Enrolling Adults Who Cannot Consent in More Than Minimal Risk Research SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID SURROGATE CONSENT; DEMENTIA-RESEARCH; ALZHEIMERS-DISEASE; CAPACITY; APPOINT; PROXY C1 [Danis, Marion; Wendler, David; Kim, Scott] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Dept Bioeth, Ctr Clin, Builiding 10,Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov FU Department of Bioethics in the Clinical Center part of National Institutes of Health FX This work was funded by the Department of Bioethics in the Clinical Center, which is part of the intramural program of the National Institutes of Health. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD OCT 3 PY 2015 VL 15 IS 10 BP 70 EP 71 DI 10.1080/15265161.2015.1075806 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CT8EQ UT WOS:000363048200026 ER PT J AU Arigo, D Smyth, JM Suls, JM AF Arigo, Danielle Smyth, Joshua M. Suls, Jerry M. TI Perceptions of similarity and response to selected comparison targets in type 2 diabetes SO PSYCHOLOGY & HEALTH LA English DT Article DE illness self-care; perceived similarity; diabetes; motivation; social comparison ID SOCIAL-COMPARISON INFORMATION; QUALITY-OF-LIFE; CANCER-PATIENTS; SELF-EFFICACY; IMPACT; MOTIVATION; FOCUS; CONSEQUENCES; BEHAVIORS; BARRIERS AB Objective: Social comparisons (i.e. self-evaluations relative to others) may affect motivation for diabetes self-care behaviours. Comparisons can have either positive or negative effects, but it is not clear what differentiates these responses. This study tested the effect of a patient's perceived similarity to a comparison target on motivation for self-care. Design: Individuals with type 2 diabetes (n=180, M-A1c=7.59%) selected to read one of four brief descriptions of a patient with diabetes. Main outcome measures: Participants rated their motivation for self-care behaviours prior and subsequent to reading and reported the extent to which they focused on similarities between the self and the selected patient while reading. Results: Perceived similarity moderated the effect of selection on motivation for self-care (p=.01, eta(2 )= .06). Increased motivation was observed if participants focused on similarities with patients 'doing better' (i.e. high coping effectiveness/low symptom severity) and decreased motivation if they focused on similarities with patients 'doing worse' (low coping effectiveness/high symptom severity). Conclusions: Providing social comparison information in diabetes management (and perhaps other chronic diseases) may improve motivation for self-care among some patients. A subset of patients, however, may benefit from guidance to focus on similarities with certain targets. C1 [Arigo, Danielle] Univ Scranton, Dept Psychol, Scranton, PA 18510 USA. [Smyth, Joshua M.] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. [Smyth, Joshua M.] Penn State Univ, Dept Med, University Pk, PA 16802 USA. [Suls, Jerry M.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Arigo, D (reprint author), Univ Scranton, Dept Psychol, Scranton, PA 18510 USA. EM danielle.arigo@scranton.edu OI Smyth, Joshua/0000-0002-0904-5390 NR 38 TC 0 Z9 0 U1 1 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0887-0446 EI 1476-8321 J9 PSYCHOL HEALTH JI Psychol. Health PD OCT 3 PY 2015 VL 30 IS 10 BP 1206 EP 1220 DI 10.1080/08870446.2015.1040018 PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA CO9IX UT WOS:000359489700005 PM 25871344 ER PT J AU Wells, ML Hicks, SN Perera, L Blackshear, PJ AF Wells, Melissa L. Hicks, Stephanie N. Perera, Lalith Blackshear, Perry J. TI Functional Equivalence of an Evolutionarily Conserved RNA Binding Module SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ZINC-FINGER PROTEINS; AU-RICH ELEMENT; MESSENGER-RNA; SCHIZOSACCHAROMYCES-POMBE; POSTTRANSCRIPTIONAL REGULATION; TRISTETRAPROLIN FAMILY; DEGRADATION; DOMAIN; DESTABILIZATION; DEADENYLATION AB Members of the tristetraprolin (TIP) family of proteins participate in the regulation of mRNA turnover after initially binding to AU-rich elements in target mRNAs. Related proteins from most groups of eukaryotes contain a conserved tandem zinc finger (TZF) domain consisting of two closely spaced, similar CCCH zinc fingers that form the primary RNA binding domain. There is considerable sequence variation within the 'ern, domains from different family members within a single organism and from different organisms, raising questions about sequence-specific effects on RNA binding and decay promotion. We hypothesized that TZF domains from evolutionarily distant species are functionally interchangeable. The single family member expressed in the fission yeast Schizosaccharomyces pombe, Zfsl, promotes the turnover of several dozen transcripts, some of which are involved in cell-cell interactions. Using knockin techniques, we replaced the 'ern, domain of S. pornbe Zfsl with the equivalent domains from human TTP and the single family member proteins expressed in the silkworm Bombyx mori, the pathogenic yeast Candida mondii, and the plant Chromolaena odorata. We found that the TZF domains from these widely disparate species could completely substitute for the native S. pornbe TZF domain, as determined by measurement of target transcript levels and the flocculation phenotype characteristic of Zfs1 deletion. Recombinant TZF domain peptides from several of these species bound to an AU-rich RNA oligonucleotide with comparably high affinity. We conclude that the TZF domains from TTP family members in these evolutionarily widely divergent species are functionally interchangeable in mRNA binding and decay. C1 [Wells, Melissa L.; Hicks, Stephanie N.; Blackshear, Perry J.] NIEHS, Signal Transduct Lab, NIH, Res Triangle Pk, NC 27709 USA. [Perera, Lalith] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, F1-13,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU NIEHS/National Institutes of Health FX This research was supported, in whole or in part, by the intramural research program of the NIEHS/National Institutes of Health. The authors declare that they have no conflicts of interest with the contents of this article. NR 27 TC 3 Z9 3 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 2015 VL 290 IS 40 BP 24413 EP 24423 DI 10.1074/jbc.M115.673012 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CS6UR UT WOS:000362218900029 PM 26292216 ER PT J AU Wolf, G Greenberg, D Macfarlan, TS AF Wolf, Gernot Greenberg, David Macfarlan, Todd S. TI Spotting the enemy within: Targeted silencing of foreign DNA in mammalian genomes by the Kruppel-associated box zinc finger protein family SO MOBILE DNA LA English DT Review DE KRAB zinc finger proteins; Transcription factors; Endogenous retroviruses; Transposable elements; Epigenetic silencing; Adaptive evolution ID EMBRYONIC STEM-CELLS; LONG TERMINAL REPEAT; SCALE RECOMBINATION PATTERNS; PRIMER-BINDING SITE; KRAB-ZNF GENES; ENDOGENOUS RETROVIRUSES; TRANSCRIPTION FACTORS; TRANSPOSABLE ELEMENTS; HISTONE METHYLTRANSFERASE; MEIOTIC RECOMBINATION AB Tandem C2H2-type zinc finger proteins (ZEPs) constitute the largest transcription factor family in animals. Tandem-54's bind DNA in a sequence-specific manner through arrays of multiple zinc finger domains that allow high flexibility and specificity in target recognition. In tetrapods, a large proportion of tandem-ZFPs contain Kruppel-associated-box (KRAB) repression domains, which are able to induce epigenetic silencing through the KAP1 corepressor. The KRAB-ZFP family continuously amplified in tetrapods through segmental gene duplications, often accompanied by deletions, duplications, and mutations of the zinc finger domains. As a result, tetrapod genomes contain unique sets of KRAB-ZFP genes, consisting of ancient and recently evolved family members. Although several hundred human and mouse KRAB-ZEPs have been identified or predicted, the biological functions of most KRAB-ZFP family members have gone unexplored. Furthermore, the evolutionary forces driving the extraordinary KRAB-ZFP expansion and diversification have remained mysterious for decades. In this review, we highlight recent studies that associate KRAB-ZITs with the repression of parasitic DNA elements in the mammalian germ line and discuss the hypothesis that the KRAB-ZFP family primarily evolved as an adaptive genomic surveillance system against foreign DNA. Finally, we comment on the computational, genetic, and biochemical challenges of studying KRAB-ZITs and attempt to predict how these challenges may be soon overcome. C1 [Wolf, Gernot; Macfarlan, Todd S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Greenberg, David] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. RP Macfarlan, TS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM todd.macfarlan@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development DIR [HD008933] FX We thank Sofie Salama for valuable comments on the manuscript, Giovanni Maki for help with the Illustrations and Gary Howard, Crystal Herron and Stephen Ordway for editorial assistance. T.S.M. is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development DIR grant HD008933. NR 200 TC 13 Z9 14 U1 3 U2 24 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PD OCT 2 PY 2015 VL 6 AR 17 DI 10.1186/s13100-015-0050-8 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA CS6DC UT WOS:000362166400001 PM 26435754 ER PT J AU Haab, BB Huang, Y Balasenthil, S Partyka, K Tang, HY Anderson, M Allen, P Sasson, A Zeh, H Kaul, K Kletter, D Ge, SK Bern, M Kwon, R Blasutig, I Srivastava, S Frazier, ML Sen, S Hollingsworth, MA Rinaudo, JA Killary, AM Brand, RE AF Haab, Brian B. Huang, Ying Balasenthil, Seetharaman Partyka, Katie Tang, Huiyuan Anderson, Michelle Allen, Peter Sasson, Aaron Zeh, Herbert Kaul, Karen Kletter, Doron Ge, Shaokui Bern, Marshall Kwon, Richard Blasutig, Ivan Srivastava, Sudhir Frazier, Marsha L. Sen, Subrata Hollingsworth, Michael A. Rinaudo, Jo Ann Killary, Ann M. Brand, Randall E. TI Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens SO PLOS ONE LA English DT Article ID MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN; DIAGNOSIS; CA19-9; BIOMARKERS; ADENOCARCINOMA; IDENTIFICATION; CARCINOMA; DISEASES; MARKERS AB The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9. C1 [Haab, Brian B.; Partyka, Katie; Tang, Huiyuan] Van Andel Res Inst, Grand Rapids, MI USA. [Huang, Ying; Ge, Shaokui] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Balasenthil, Seetharaman; Frazier, Marsha L.; Sen, Subrata; Killary, Ann M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Anderson, Michelle; Kwon, Richard] Univ Michigan, Ann Arbor, MI 48109 USA. [Allen, Peter] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sasson, Aaron; Hollingsworth, Michael A.] Univ Nebraska Med Ctr, Omaha, NE USA. [Zeh, Herbert; Brand, Randall E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Kaul, Karen] Northshore Univ Healthsyst, Evanston, IL USA. [Kletter, Doron; Bern, Marshall] Xerox Corp, Palo Alto Res Ctr, Palo Alto, CA 94304 USA. [Blasutig, Ivan] Univ Hlth Network, Toronto, ON, Canada. [Srivastava, Sudhir; Killary, Ann M.] NCI, Rockville, MD USA. RP Brand, RE (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. EM brandre@upmc.edu OI Blasutig, Ivan/0000-0001-7310-2647 FU Early Detection Research Network of the National Cancer Institute [U01CA152653, U01CA111302] FX This work was funded by the Early Detection Research Network of the National Cancer Institute (U01CA152653 to B. B. Haab, R. E. Brand, and P. Allen; and U01CA111302 to A. M. Killary, M. L. Frazier, and S. Sen). The authors would also like to thank the Early Detection Research Network for providing the pancreatic samples used for this study. NR 39 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 2 PY 2015 VL 10 IS 10 AR e0139049 DI 10.1371/journal.pone.0139049 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS6HH UT WOS:000362178700030 PM 26431551 ER PT J AU Kuhs, KAL Kuniholm, MH Pfeiffer, RM Chen, S Desai, S Edlin, BR Peters, MG Plankey, M Sharp, GB Strickler, HD Villacres, MC Quinn, TC Gange, SJ Prokunina-Olsson, L Greenblatt, RM O'Brien, TR AF Kuhs, Krystle A. Lang Kuniholm, Mark H. Pfeiffer, Ruth M. Chen, Sabrina Desai, Seema Edlin, Brian R. Peters, Marion G. Plankey, Michael Sharp, Gerald B. Strickler, Howard D. Villacres, Maria C. Quinn, Thomas C. Gange, Stephen J. Prokunina-Olsson, Ludmila Greenblatt, Ruth M. O'Brien, Thomas R. TI Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital Herpes SO PLOS ONE LA English DT Article ID WOMENS INTERAGENCY HIV; HEPATITIS-C VIRUS; GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; SPONTANEOUS CLEARANCE; IL28B; THERAPY; WIHS AB IFNL4-Delta G/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-lambda 4 protein is generated only in individuals who carry the IFNL4-Delta G allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-Delta G, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-Delta G/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)-infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV-1 and HSV-2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV-2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-Delta G/TT genotyping was determined by Taq-Man. We compared women with IFNL4-Delta G/Delta G or IFNL4-TT/Delta G genotypes (i.e., IFNL4-Delta G carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8% were positive for HSV-1 and 79.0% were positive for HSV-2. We observed no association between IFNL4-Delta G/TT genotype and any outcome: HSV-1 or HSV-2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV-2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV-2 DNA level (p = 0.68). In this large prospective study, IFNL4-Delta G/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes. C1 [Kuhs, Krystle A. Lang; O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kuniholm, Mark H.; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chen, Sabrina] Informat Management Serv Inc, Calverton, MD USA. [Desai, Seema] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Edlin, Brian R.] Natl Dev & Res Inst Inc, Inst Infect Dis Res, New York, NY USA. [Peters, Marion G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Plankey, Michael] Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA. [Sharp, Gerald B.] NIAID, Epidemiol Branch, Div Aids, Bethesda, MD 20892 USA. [Villacres, Maria C.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Kuhs, KAL (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM Krystle.Kuhs@nih.gov FU National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Cancer Institute (NCI); National Institute on Drug Abuse (NIDA); National Institute on Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Deafness and other Communication Disorders (NIDCD); NIH Office of Research on Women's Health; Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics) FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen), U01-AI-034993; Metropolitan Washington WIHS (Mary Young), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I - WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). This specific study was supported by the Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics). The funders of WIHS had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Co-author Sabrina Chen, an employee of Information Management Services (IMS), performed data analysis for this manuscript under a contract between IMS and the Division of Cancer Epidemiology and Genetics. IMS had no other role in the study design, data collection, decision to publish, or preparation of the manuscript. The specific role of author Sabrina Chen is articulated in the 'author contributions' section." This specific study was supported by the Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 1 Z9 1 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 2 PY 2015 VL 10 IS 10 AR e0138827 DI 10.1371/journal.pone.0138827 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS6HH UT WOS:000362178700020 ER PT J AU Oshida, K Vasani, N Thomas, RS Applegate, D Gonzalez, FJ Aleksunes, LM Klaassen, CD Corton, JC AF Oshida, Keiyu Vasani, Naresh Thomas, Russell S. Applegate, Dawn Gonzalez, Frank J. Aleksunes, Lauren M. Klaassen, Curtis D. Corton, J. Christopher TI Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR) SO TOXICOLOGY LA English DT Article DE Aryl hydrocarbon receptor; Peroxisome proliferator-activated receptor; Transcript profiling; Liver cancer; Constitutive activated receptor; Keap1; Nrf2; Pregnane X receptor ID PPAR-ALPHA; CYCLOOXYGENASE-2 EXPRESSION; NONGENOTOXIC CARCINOGENS; RISK-ASSESSMENT; FATTY LIVER; MICE; ACTIVATION; HEPATOCYTES; GLUCOSE; DIOXIN AB The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dioxin-like compounds (DLC) as well as some drugs and endogenous tryptophan metabolites. Short-term activation of AhR can lead to hepatocellular steatosis, and chronic activation can lead to liver cancer in mice and rats. Analytical approaches were developed to identify biosets in a genomic database in which AhR activity was altered. A set of 63 genes was identified (the AhR gene expression biomarker) that was dependent on AhR for regulation after exposure to TCDD or benzo[a]pyrene and includes the known AhR targets Cyp1a1 and Cyp1b1. A fold-change rank-based test (Running Fisher's test; p-value <= 10(-4)) was used to evaluate the similarity between the AhR biomarker and a test set of 37 and 41 biosets positive or negative, respectively for AhR activation. The test resulted in a balanced accuracy of 95%. The rank-based test was used to identify factors that activate or suppress AhR in an annotated mouse liver/mouse primary hepatocyte gene expression database of similar to 1850 comparisons. In addition to the expected activation of AhR by TCDD and DLC, AhR was activated by AP20189 and phenformin. AhR was suppressed by phenobarbital and 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) in a constitutive activated receptor (CAR)-dependent manner and pregnenolone-16 alpha-carbonitrile in a pregnane X receptor (PXR)-dependent manner. Inactivation of individual genes in nullizygous models led to AhR activation (Pxr, Ghrhr, Taf10) or suppression (Ahr, Ilst6st, Hnf1a). This study describes a novel screening strategy for identifying factors in mouse liver that perturb AhR in a gene expression compendium. Published by Elsevier Ireland Ltd. C1 [Oshida, Keiyu; Vasani, Naresh; Corton, J. Christopher] US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. [Thomas, Russell S.] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA. [Applegate, Dawn] RegeneMed, San Diego, CA 92121 USA. [Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. [Aleksunes, Lauren M.] Rutgers State Univ, Piscataway, NJ 08854 USA. [Klaassen, Curtis D.] Univ Kansas, Med Ctr, Kansas City, KS 66160 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. Environmental Protection Agency FX This study was carried out as part of the EPA Chemicals Safety for Sustainability cancer and steatosis AOP projects. We thank Drs. Julian Preston and Charlene McQueen for support, Dr. Jennifer Fostel for archiving the results in CEBS, Dr. William Ward for guidance in analyzing microarray data, Drs. Lyle Burgoon, Susan Hester, Charles Wood and Sheau-Fung Thai for review of the manuscript and Drs. Oliver Hankinson, and Ivan Rusyn for livers from studies carried out in their labs. The information in this document has been funded in part by the U.S. Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 69 TC 3 Z9 3 U1 6 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 2 PY 2015 VL 336 BP 99 EP 112 DI 10.1016/j.tox.2015.07.005 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CS4PY UT WOS:000362059600013 PM 26215100 ER PT J AU Li, YJ Gaillard, JR McLaughlin, T Sorensen, TIA Periwal, V AF Li, Yanjun Gaillard, Jonathan R. McLaughlin, Tracey Sorensen, Thorkild I. A. Periwal, Vipul TI Macro fat and micro fat: insulin sensitivity and gender dependent response of adipose tissue to isocaloric diet change SO ADIPOCYTE LA English DT Article DE adipose cell distribution; diet; fat mass ID BODY-FAT; OBESITY; SIZE; RESISTANCE; HUMANS; CELLS; RISK AB The adipose cell-size distribution is a quantitative characterization of adipose tissue morphology. At a population level, the adipose cell-size distribution is insulin-sensitivity dependent, and the observed correlation between obesity and insulin resistance is believed to play a key role in the metabolic syndrome. Changes in fat mass can be induced by altered energy intake or even diet composition. These macroscopic changes must manifest themselves as dynamic adipose cell-size distribution alterations at the microscopic level. The dynamic relationship between these 2 independent measurements of body fat is unknown. In this study, we investigate adipose tissue dynamics in response to various isocaloric diet compositions, comparing gender- and insulin sensitivity-dependent differences. A body composition model is used to predict fat mass changes in response to changes in diet composition for 28 individuals, separated into 4 subgroups according to gender and insulin sensitivity/resistance. Adipose cell-size distribution changes in each individual are simulated with a dynamic model and parameters corresponding to lipid turnover and cell growth rates are determined for each subgroup to match the relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive to changes in energy intake and diet composition than insulin sensitive subjects. The different cell-size distribution changes of adipose cells of various sizes in different subject groups further suggest distinct modulations of adipose cell dynamics. C1 [Li, Yanjun; Gaillard, Jonathan R.; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [McLaughlin, Tracey] Stanford Univ, Div Endocrinol & Metab, Sch Med, Palo Alto, CA 94304 USA. [Sorensen, Thorkild I. A.] Univ Copenhagen, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, DK-1168 Copenhagen, Denmark. [Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Capital Region, Denmark. RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM vipulp@mail.nih.gov NR 24 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-3945 EI 2162-397X J9 ADIPOCYTE JI Adipocyte PD OCT 2 PY 2015 VL 4 IS 4 BP 256 EP 263 DI 10.1080/21623945.2015.1017153 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP2UE UT WOS:000359731900005 PM 26451281 ER PT J AU Ma, XR Xu, LY Mueller, E AF Ma, Xinran Xu, Lingyan Mueller, Elisabetta TI Calorie hoarding and thrifting: Foxa3 finds a way SO ADIPOCYTE LA English DT Editorial Material DE aging; Foxa3; obesity; PGC1; PPAR; thrifty ID REGULATES ADIPOCYTE DIFFERENTIATION; NUCLEAR FACTOR 3-GAMMA; WHITE ADIPOSE-TISSUE; TRANSCRIPTION FACTORS; BEIGE ADIPOCYTES; BROWN; FAT; METABOLISM; GENES; EXPANSION AB Obesity and diabetes are major health concerns worldwide. Western diets, often calorically rich, paired with sedentary habits are driving the current worldwide epidemic of pediatric and adult obesity. In addition, age related energy imbalances lead to increased adiposity and metabolic disorders later in life, making the middle aged population particularly susceptible. Here we discuss how Forkhead box A3 (Foxa3), a family member of the forkhead box binding proteins, can potentially contribute to pathology by playing a double role in metabolism. Recent data revealed that Foxa3 favors the selective expansion of visceral depots under high caloric conditions (e.g., high fat diet) and suppresses subcutaneous fat tissue energy expenditure during aging. This evidence suggests that Foxa3 acts to both preserve and conserve calories, by accumulating fat and by reducing metabolic burn. In other words, Foxa3 appears to function to enable energy hoarding, which may be critical for survival of organisms with intermittent exposure to external caloric sources, but pathologic in circumstances where calories are abundant. Understanding how this calorie hoarder gene functions may suggest approaches to combat obesity and associated metabolic disorders. C1 [Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Mueller, E (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM elisabettam@mail.nih.gov NR 40 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-3945 EI 2162-397X J9 ADIPOCYTE JI Adipocyte PD OCT 2 PY 2015 VL 4 IS 4 BP 325 EP 328 DI 10.1080/21623945.2015.1028700 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CP2UE UT WOS:000359731900015 PM 26451291 ER PT J AU Merritt, MA Strickler, HD Einstein, M Yang, H Sherman, ME Wentzensen, N Brouwer-Visser, J Cossio, MJ Whitney, K Yu, H Sgueglia, R Gunter, MJ Huang, GS AF Merritt, M. A. Strickler, H. D. Einstein, M. Yang, H. Sherman, M. E. Wentzensen, N. Brouwer-Visser, J. Cossio, M. J. Whitney, K. Yu, H. Sgueglia, R. Gunter, M. J. Huang, G. S. TI CHARACTERIZATION OF THE INSULIN-IGF AND SEX HORMONE AXES IN HUMAN ENDOMETRIUM AND ASSOCIATIONS WITH ENDOMETRIAL CANCER RISK FACTORS SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Merritt, M. A.; Gunter, M. J.] Univ London Imperial Coll Sci Technol & Med, Epidemiol & Biostat, London, England. [Strickler, H. D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Einstein, M.; Brouwer-Visser, J.; Cossio, M. J.; Huang, G. S.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Yang, H.] NCI, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. [Sherman, M. E.; Wentzensen, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Whitney, K.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Yu, H.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA. [Sgueglia, R.] Albert Einstein Coll Med, Biomarker Analyt Res Core, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD OCT PY 2015 VL 25 IS 9 SU 1 MA ESGO-0326 BP 1563 EP 1563 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DN5XT UT WOS:000377145704173 ER PT J AU Whitworth, PW Beitsch, PD Rotkis, MC Pellicane, JV Murray, M Baron, P Dul, CL Mislowsky, AM Nash, CH Richards, PD Lee, LA Stork, L De Snoo, F Untch, S Gittleman, M Akbari, S Beatty, J AF Whitworth, Pat W. Beitsch, Peter D. Rotkis, Michael C. Pellicane, James V. Murray, Mary Baron, Paul Dul, Carrie L. Mislowsky, Angela Marie Nash, Charles H. Richards, Paul D. Lee, Laura A. Stork, Lisette De Snoo, Femke Untch, Sarah Gittleman, Mark Akbari, Stephanie Beatty, Jennifer TI Functional subtyping with BluePrint 80-gene profile to identify distinct triple-positive subtypes with and without trastuzumab/chemosensitivity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY SEP 25-27, 2015 CL San Francisco, CA SP Amer Soc Clin Oncol C1 NSABP, NRG Oncol, ALLIANCE ACOSOG, Nashville, TN USA. Nashville Breast Ctr, Nashville, TN USA. Dallas Surg Grp, Dallas, TX USA. Northern Indiana Canc Res Consortium, South Bend, IN USA. Virginia Breast Ctr, Bon Secours Canc Inst, Richmond, VA USA. Akron Gen Med Ctr, Akron, OH USA. Canc Specialists Charleston, Charleston, SC USA. Great Lakes Management Spclsts, Grosse Pointe Pk, MI USA. Coastal Carolina Breast Ctr, Murrells Inlet, SC USA. Longst Clin PC, Gainesville, GA USA. Oncol & Hematol Assoc Southwest Virginia, Salem, VA USA. Ctr Comprehens Canc, Palm Springs, CA USA. Agendia, Amsterdam, Netherlands. Agendia, Irvine, CA USA. Breast Care Specialists, Allentown, PA USA. Virginia Hosp, Ctr Reinsch Pierce Family, Ctr Breast Hlth, Arlington, VA USA. Breast Pl, Charleston, SC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2015 VL 33 IS 28 SU S MA 114 PG 1 WC Oncology SC Oncology GA DO9HV UT WOS:000378097000113 ER PT J AU Muller, BG Kaushal, A Sankineni, S Lita, E Hoang, AN George, AK Rais-Bahrami, S Kruecker, J Yan, P Xu, S de la Rosette, JJ Merino, MJ Wood, BJ Pinto, PA Choyke, PL Turkbey, B AF Muller, Berrend G. Kaushal, Aradhana Sankineni, Sandeep Lita, Elena Hoang, Anthony N. George, Arvin K. Rais-Bahrami, Soroush Kruecker, Jochen Yan, Pingkun Xu, Sheng de la Rosette, Jean J. Merino, Maria J. Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. Turkbey, Baris TI Multiparametric magnetic resonance imaging-transrectal ultrasound fusion-assisted biopsy for the diagnosis of local recurrence after radical prostatectomy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Biochemical recurrence; MRI; MRI-ultrasound fusion-guided biopsy ID CONTRAST-ENHANCED-MRI; SALVAGE RADIOTHERAPY; CANCER-DETECTION; RADIATION-THERAPY; PROSTATIC FOSSA; 3 T; ANTIGEN; METAANALYSIS; RISK; MEN AB Objective: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP. Materials and methods: In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined. Results: A total of 10 patients (mean age = 67 y, mean PSA level = 3.44 ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12 cm (range: 0.40-2.20 cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients. Conclusion: MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes. Published by Elsevier Inc. C1 [Muller, Berrend G.; Sankineni, Sandeep; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Muller, Berrend G.; de la Rosette, Jean J.] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands. [Kaushal, Aradhana; Lita, Elena] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Hoang, Anthony N.; George, Arvin K.; Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Dept Urol, Birmingham, AL USA. [Rais-Bahrami, Soroush] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Kruecker, Jochen; Yan, Pingkun] Philips Res North Amer, Briarcliff Manor, NY USA. [Xu, Sheng; Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov OI Rais-Bahrami, Soroush/0000-0001-9466-9925 NR 32 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD OCT PY 2015 VL 33 IS 10 AR 425.e1 DI 10.1016/j.urolonc.2015.05.021 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DN5PD UT WOS:000377121600004 PM 26259666 ER PT J AU Wang, Y Rogan, WJ Chen, HY Chen, PC Su, PH Chen, HY Wang, SL AF Wang, Yan Rogan, Walter J. Chen, Hsin-Yi Chen, Pau-Chung Su, Pen-Hua Chen, Hsiao-Yen Wang, Shu-Li TI Prenatal exposure to perfluroalkyl substances and children's IQ: The Taiwan maternal and infant cohort study SO INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH LA English DT Article DE Perfluoroalkyl substances; Prenatal exposure; IQ; Children ID PERFLUOROALKYL ACIDS; PERFLUORINATED CHEMICALS; THYROID-FUNCTION; SERUM; PERFLUOROCARBOXYLATES; PERFLUOROOCTANOATE; ASSOCIATIONS; BLOOD; AGE AB Background: Perfluoroalkyl substances (PFASs) are a group of fluorinated organic substances that are widely used in consumer products and are often detectable in human tissues. Human studies on prenatal exposure to PFASs and neurodevelopment in children are few and inconsistent. Methods: In the Taiwan Maternal and Infant Cohort Study, we collected serum samples from pregnant women during the third trimester and measured concentrations of 9 PFASs using a high performance liquid chromatography system. A subsample of their children was assessed with full scale intelligence quotient (FSIQ), verbal IQ(VIQ) and performance IQ(PIQ) at both age 5 (n = 120) and 8 years (n = 120). We used multivariate linear regression models to examine prenatal PFAS exposure in relation to IQ scores at each age period. Results: Prenatal perfluoroundecanoic acid (PFUnDA) concentrations were inversely associated with children's PIQ scores at age 5 years, with an adjusted coefficient (beta) of -1.6 (95% confidence interval [CI]: (-3.0, -0.2). When children reached 8 years, most of the prenatal PFASs showed inverse association with children's FSIQ VIQ and PIQ scores. Among them, prenatal perfluorononanoic acid (PFNA) reached significance. Children with higher prenatal PFNA levels had lower VIQ with an adjusted beta of -2.1 (95% Cl: -3.9, -0.2). Conclusions: We found two prenatal PFAS exposure, both long-chain PFASs, in association with decreased IQ test scores in children. Our findings suggest more studies on long-chain PFASs and children's neurodevelopment. (C) 2015 Elsevier GmbH. All rights reserved. C1 [Wang, Yan; Rogan, Walter J.; Wang, Shu-Li] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Wang, Yan] Carter Consulting Inc, Atlanta, GA 30345 USA. [Chen, Hsin-Yi] Natl Taiwan Normal Univ, Dept Special Educ, Taipei, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei 10764, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei 10764, Taiwan. [Su, Pen-Hua; Chen, Hsiao-Yen] Chung Shan Med Univ Hosp, Dept Pediat, Taichung 40201, Taiwan. [Chen, Hsiao-Yen] Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, Miaoli, Taiwan. [Wang, Shu-Li] Natl Def Med Ctr, Dept Publ Hlth, Taipei, Taiwan. RP Wang, SL (reprint author), Natl Def Med Ctr, Dept Publ Hlth, 35 Keyan Rd, Zhunan 350, Miaoli County, Taiwan. EM slwang@nhri.org.tw RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Chen, Pau-Chung/0000-0002-6242-5974 FU National Health Research Institutes, Taiwan [EH-102-SP-01, EH-103-SP-02, EO-103-PP-05]; Ministry of Science and Technology, Taiwan [NSC101-2325-B-400-008, MOST103-2314-B-400-006] FX The study was funded by National Health Research Institutes, Taiwan (EH-102-SP-01, EH-103-SP-02, EO-103-PP-05), Ministry of Science and Technology, Taiwan (NSC101-2325-B-400-008, MOST103-2314-B-400-006). NR 32 TC 2 Z9 2 U1 4 U2 7 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4639 EI 1618-131X J9 INT J HYG ENVIR HEAL JI Int. J. Hyg. Environ. Health. PD OCT PY 2015 VL 218 IS 7 BP 639 EP 644 DI 10.1016/j.ijheh.2015.07.002 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DL6EB UT WOS:000375731300006 PM 26205657 ER PT J AU Narayanan, D Liu, JM Kim, L Chang, KW Lu, L Yao, JH Turkbey, EB Summers, RM AF Narayanan, Divya Liu, Jiamin Kim, Lauren Chang, Kevin W. Lu, Le Yao, Jianhua Turkbey, Evrim B. Summers, Ronald M. TI Automated segmentation of the thyroid gland on thoracic CT scans by multiatlas label fusion and random forest classification SO JOURNAL OF MEDICAL IMAGING LA English DT Article DE thyroid segmentation; multiatlas label fusion; random forest ID ATLAS SEGMENTATION; IMAGES; STRATEGIES; SELECTION AB The thyroid is an endocrine gland that regulates metabolism. Thyroid image analysis plays an important role in both diagnostic radiology and radiation oncology treatment planning. Low tissue contrast of the thyroid relative to surrounding anatomic structures makes manual segmentation of this organ challenging. This work proposes a fully automated system for thyroid segmentation on CT imaging. Following initial thyroid segmentation with multiatlas joint label fusion, a random forest (RF) algorithm was applied. Multiatlas label fusion transfers labels from labeled atlases and warps them to target images using deformable registration. A consensus atlas solution was formed based on optimal weighting of atlases and similarity to a given target image. Following the initial segmentation, a trained RF classifier employed voxel scanning to assign class-conditional probabilities to the voxels in the target image. Thyroid voxels were categorized with positive labels and nonthyroid voxels were categorized with negative labels. Our method was evaluated on CT scans from 66 patients, 6 of which served as atlases for multiatlas label fusion. The system with independent multiatlas label fusion method and RF classifier achieved average dice similarity coefficients of 0.72 +/- 0.13 and 0.57 +/- 0.14, respectively. The system with sequential multiatlas label fusion followed by RF correction increased the dice similarity coefficient to 0.76 +/- 0.11 and improved the segmentation accuracy. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Narayanan, Divya; Liu, Jiamin; Kim, Lauren; Chang, Kevin W.; Lu, Le; Yao, Jianhua; Turkbey, Evrim B.; Summers, Ronald M.] NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 18 TC 1 Z9 1 U1 1 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-4302 EI 2329-4310 J9 J MED IMAGING JI J. Med. Imaging PD OCT-DEC PY 2015 VL 2 IS 4 AR 044006 DI 10.1117/1.JMI.2.4.044006 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5GP UT WOS:000374235100021 PM 26730397 ER PT J AU Rahman, MM Antani, SK Demner-Fushman, D Thoma, GR AF Rahman, Md. Mahmudur Antani, Sameer K. Demner-Fushman, Dina Thoma, George R. TI Biomedical image representation approach using visualness and spatial information in a concept feature space for interactive region-of-interest-based retrieval SO JOURNAL OF MEDICAL IMAGING LA English DT Article DE medical image representation; content-based image retrieval; interactive retrieval; region-based search; image concepts; biomedical literature ID MEDICAL APPLICATIONS; CLASSIFICATION; SYSTEMS; SEARCH; ENGINE AB This article presents an approach to biomedical image retrieval by mapping image regions to local concepts where images are represented in a weighted entropy-based concept feature space. The term "concept" refers to perceptually distinguishable visual patches that are identified locally in image regions and can be mapped to a glossary of imaging terms. Further, the visual significance (e.g., visualness) of concepts is measured as the Shannon entropy of pixel values in image patches and is used to refine the feature vector. Moreover, the system can assist the user in interactively selecting a region-of-interest (ROI) and searching for similar image ROIs. Further, a spatial verification step is used as a postprocessing step to improve retrieval results based on location information. The hypothesis that such approaches would improve biomedical image retrieval is validated through experiments on two different data sets, which are collected from open access biomedical literature. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Rahman, Md. Mahmudur; Thoma, George R.] Morgan State Univ, Dept Comp Sci, Calloway 308,1700 E Cold Spring Lane, Baltimore, MD 21251 USA. [Antani, Sameer K.; Demner-Fushman, Dina] NIH, US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. RP Rahman, MM (reprint author), Morgan State Univ, Dept Comp Sci, Calloway 308,1700 E Cold Spring Lane, Baltimore, MD 21251 USA. EM md.rahman@morgan.edu NR 37 TC 0 Z9 0 U1 1 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-4302 EI 2329-4310 J9 J MED IMAGING JI J. Med. Imaging PD OCT-DEC PY 2015 VL 2 IS 4 AR 046502 DI 10.1117/1.JMI.2.4.046502 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ5GP UT WOS:000374235100029 PM 26730398 ER PT J AU Assassi, S Mayes, MD Pedroza, C Chang, JT Furst, DE Crofford, LJ Nash, R McSweeney, P Csuka, ME Goldmuntz, E Keyes-Elstein, L Wallace, P Sullivan, K AF Assassi, Shervin Mayes, Maureen D. Pedroza, Claudia Chang, Jeffrey T. Furst, Daniel E. Crofford, Leslie J. Nash, Richard McSweeney, Peter Csuka, Mary Ellen Goldmuntz, Ellen Keyes-Elstein, Lynette Wallace, Paul Sullivan, Keith TI Immunoablation Followed By Autologous Stem Cell Transplantation in Systemic Sclerosis Patients Decreases Significantly the Interferon Signatrue SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Assassi, Shervin; Mayes, Maureen D.] Univ Texas Med Sch Houston, Rheumatol, Houston, TX USA. [Pedroza, Claudia; Chang, Jeffrey T.] Univ Texas Med Sch Houston, Houston, TX USA. [Furst, Daniel E.] Univ Calif Los Angeles, David Geffen Sch Med, Med, Los Angeles, CA 90095 USA. [Crofford, Leslie J.] Vanderbilt Univ, Med, Nashville, TN 37235 USA. [Nash, Richard; McSweeney, Peter] Colorado Blood Canc Inst, Denver, CO USA. [Csuka, Mary Ellen] Med Coll Wisconsin, Rheum, Milwaukee, WI 53226 USA. [Goldmuntz, Ellen] NIAID, NIH, Bethesda, MD 20892 USA. [Keyes-Elstein, Lynette] Rho Fed Syst Inc, Chapel Hill, NC USA. [Wallace, Paul] Roswell Pk, Buffalo, NY USA. [Sullivan, Keith] Duke Univ, 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 3259 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204807 ER PT J AU Barnard, J Meednu, N Callahan, K Coca, A Marston, BA Thiele, RG Tabechian, D Bolster, M Curtis, JR Mackay, MC Graf, JD Keating, R Smith, E Boyle, K Keyes-Elstein, L Welch, B Goldmuntz, E Anolik, JH AF Barnard, Jennifer Meednu, Nida Callahan, Kelly Coca, Andreea Marston, Bethany A. Thiele, Ralf G. Tabechian, Darren Bolster, Marcy Curtis, Jeffrey R. Mackay, Meggan C. Graf, Jonathan D. Keating, Richard Smith, Edwin Boyle, Karen Keyes-Elstein, Lynette Welch, Beverly Goldmuntz, Ellen Anolik, Jennifer H. TI Activated Memory B Cells in Rheumatoid Arthritis and Relationship to Anti-TNF Treatment SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Barnard, Jennifer; Callahan, Kelly; Coca, Andreea; Marston, Bethany A.; Thiele, Ralf G.; Tabechian, Darren; Anolik, Jennifer H.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Meednu, Nida] Univ Rochester, Med Ctr, Med Allergy Immunol & Rheumatol, Rochester, NY 14642 USA. [Bolster, Marcy] MUSC, Charleston, SC USA. [Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL USA. [Mackay, Meggan C.] Feinstein Inst Med Res, Autoimmune & Musculoskeletal Disorders, Manhasset, NY USA. [Graf, Jonathan D.] Univ Calif San Francisco, Rosalind Russell Ephraim P Engleman Rheumatol Res, San Francisco, CA 94143 USA. [Keating, Richard] Univ Chicago, Chicago, IL 60637 USA. [Smith, Edwin] MUSC, Dept Med, Div Rheum, Charleston, SC USA. [Boyle, Karen; Keyes-Elstein, Lynette] Rho Fed Syst Inc, Chapel Hill, NC USA. [Welch, Beverly] NIAID, NIH, Bethesda, MD 20892 USA. [Goldmuntz, Ellen] NIAID, DAIT, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2772 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204323 ER PT J AU Barnard, J Meednu, N Callahan, K Boyle, K Keyes-Elstein, L Welch, B Goldmuntz, E Anolik, JH AF Barnard, Jennifer Meednu, Nida Callahan, Kelly Boyle, Karen Keyes-Elstein, Lynette Welch, Beverly Goldmuntz, Ellen Anolik, Jennifer H. TI Decreased Vaccine Responses in Rheumatoid Arthritis Patients Receiving Anti-TNF Treatment and Relationship to B Cell Subsets SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Barnard, Jennifer; Callahan, Kelly; Anolik, Jennifer H.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Meednu, Nida] Univ Rochester, Med Ctr, Med Allergy Immunol & Rheumatol, Rochester, NY 14642 USA. [Boyle, Karen; Keyes-Elstein, Lynette] Rho Fed Syst Inc, Chapel Hill, NC USA. [Welch, Beverly] NIAID, NIH, Bethesda, MD 20892 USA. [Goldmuntz, Ellen] NIAID, DAIT, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 502 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201497 ER PT J AU Barron, K Ombrello, A Stone, D Hoffmann, P Aksentijevich, I Zhou, Q Jones, A Kastner, DL AF Barron, Karyl Ombrello, Amanda Stone, Deborah Hoffmann, Patrycja Aksentijevich, Ivona Zhou, Qing Jones, Anne Kastner, Daniel L. TI Deficiency of Adenosine Deaminase Type II - Expanding the Clinical Spectrum SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Barron, Karyl] NIAID, NIH, Bethesda, MD 20892 USA. [Ombrello, Amanda; Stone, Deborah; Hoffmann, Patrycja; Aksentijevich, Ivona; Zhou, Qing; Jones, Anne] NHGRI, NIH, Bethesda, MD 20892 USA. [Aksentijevich, Ivona] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 3092 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204641 ER PT J AU Biehl, A Ghaderi-Yeganeh, M Manna, Z Dasgupta, A Kaplan, MJ Hasni, S AF Biehl, Ann Ghaderi-Yeganeh, Maryam Manna, Zerai Dasgupta, Abhijit Kaplan, Mariana J. Hasni, Sarfaraz TI Hydroxychloroquine Level Variants and Predictors in a Connective Tissue Disease Population SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Biehl, Ann] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [Ghaderi-Yeganeh, Maryam; Manna, Zerai; Dasgupta, Abhijit; Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA. [Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1802 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203208 ER PT J AU Blanco, LP Lood, C Purmalek, M DeRavin, SS Smith, CK Carmona-Rivera, C Malech, H Ledbetter, J Elkon, KB Kaplan, MJ AF Blanco, Luz P. Lood, Christian Purmalek, Monica DeRavin, Suk See Smith, Carolyne K. Carmona-Rivera, Carmelo Malech, Harry Ledbetter, Jeffrey Elkon, Keith B. Kaplan, Mariana J. TI Mitochondrial Reactive Oxygen Species Modulate Autoimmunity in Systemic Lupus Erythematosus SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Blanco, Luz P.; Purmalek, Monica; Smith, Carolyne K.; Carmona-Rivera, Carmelo; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Lood, Christian] Univ Washington, Internal Med, Seattle, WA 98195 USA. [DeRavin, Suk See; Malech, Harry] NIAID, NIH, Bethesda, MD 20892 USA. [Ledbetter, Jeffrey] Univ Washington, Seattle, WA 98195 USA. [Elkon, Keith B.] Univ Washington, Dept Med & Immunol, Seattle, WA 98195 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2072 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203478 ER PT J AU Canna, S de Jesus, AA Huang, Y Gouni, S Shi, GP Gery, I Goldbach-Mansky, R AF Canna, Scott de Jesus, Adriana Almeida Huang, Yan Gouni, Sushanth Shi, Guangpu Gery, Igal Goldbach-Mansky, Raphaela TI Association of Chronic, Extreme Elevation of Serum IL-18 with the Development of Macrophage Activation Syndrome in a Cohort of Autoinflammatory Disease Patients: A Potential Diagnostic Biomarker? SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Canna, Scott; Gouni, Sushanth] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD USA. [de Jesus, Adriana Almeida; Huang, Yan; Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Shi, Guangpu; Gery, Igal] NEI, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1458 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202719 ER PT J AU Cardenas-Turanzas, M Gonzalez, E Shethia, M Lopez-Olivo, MA Nayak, P Suarez-Almazor, ME AF Cardenas-Turanzas, Marylou Gonzalez, Elsa Shethia, Maithili Lopez-Olivo, Maria A. Nayak, Pratibha Suarez-Almazor, Maria E. TI Assessing Information Needs for Chronic Disease Management in Rheumatoid Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Cardenas-Turanzas, Marylou; Shethia, Maithili] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA. [Gonzalez, Elsa] Texas A&M Univ, Higher Educ Adm, Corpus Christi, TX USA. [Lopez-Olivo, Maria A.; Suarez-Almazor, Maria E.] Univ Texas MD Anderson Canc Ctr, Gen Internal Med, Houston, TX 77030 USA. [Nayak, Pratibha] NIH, Atlanta, GA 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2661 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204212 ER PT J AU Choudhury, SD Biehl, A Ghaderi-yeganeh, M Manna, Z Hasni, S AF Choudhury, Shubhasree Dutta Biehl, Ann Ghaderi-yeganeh, Maryam Manna, Zerai Hasni, Sarfaraz TI Cyclophosphamide and Cumulative Steroid Dose Associated with Higher Risk of Infections in Patients with Lupus Nephritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Choudhury, Shubhasree Dutta] Natl Inst Arthrit Musculoskeletal & Skin Diseases, NIH, Bethesda, MD USA. [Biehl, Ann] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [Ghaderi-yeganeh, Maryam] NIH, Ctr Clin, Dept Pharm, Bethesa, MD USA. [Manna, Zerai; Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 OCT PY 2015 VL 67 SU 10 MA 1818 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203224 ER PT J AU Cudrici, C Agyemang, A Pelletier, M Steinberg, G Siegel, RM AF Cudrici, Cornelia Agyemang, Amma Pelletier, Martin Steinberg, Gregory Siegel, Richard M. TI AMP-Activated Protein Kinase As an Anti-Inflammatory Target for Methotrexate SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Cudrici, Cornelia; Agyemang, Amma; Pelletier, Martin; Siegel, Richard M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, Bethesda, MD USA. [Steinberg, Gregory] McMaster Univ, Dept Med, Div Endocrinol, Hamilton, ON, Canada. 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1378 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202639 ER PT J AU Delgado, M Wilson, L Katz, JD Biehl, A AF Delgado, Martha Wilson, Lorena Katz, James D. Biehl, Ann TI Identifying the Investment Needed to Generate a Durable Prednisone Dose Decrement SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Delgado, Martha; Wilson, Lorena] NIAMSD, NIH, Bethesda, MD 20892 USA. [Katz, James D.] George Washington Univ, Dept Med, Div Rheumatol, Washington, DC USA. [Biehl, Ann] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 118 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201116 ER PT J AU Edwan, JH Goldbach-Mansky, R Colbert, RA AF Edwan, Jehad H. Goldbach-Mansky, Raphaela Colbert, Robert A. TI Events Upstream of Caspase-1 Activation in NLRP3-Mediated Cell Death in NOMID SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Edwan, Jehad H.; Goldbach-Mansky, Raphaela; Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 194 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201192 ER PT J AU Feldon, M Donnelly, C Brunner, HI Johnson, AL Itert, L Rider, LG Giannini, EH AF Feldon, Michal Donnelly, Catherine Brunner, Hermine I. Johnson, Anne Louis Itert, Lukasz Rider, Lisa G. Giannini, Edward H. TI Health Related Quality of Life Is Reduced in Pediatric Patients with Juvenile Idiopathic Arthritis and Juvenile-Onset Fibromyalgia SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Feldon, Michal; Johnson, Anne Louis] Cincinnati Childrens Hosp Med Ctr, Pediat Rheumatol, Cincinnati, OH 45229 USA. [Donnelly, Catherine] Univ Cincinnati, Internal Med, Cincinnati, OH USA. [Brunner, Hermine I.; Giannini, Edward H.] Cincinnati Childrens Hosp Med Ctr, Rheumatol, Cincinnati, OH 45229 USA. [Itert, Lukasz] Cincinnati Childrens Hosp Med Ctr, Div Pediat Rheumatol, Cincinnati, OH 45229 USA. [Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1467 PG 4 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202728 ER PT J AU Feldon, M Farhadi, PN Brunner, HI Itert, L Goldberg, B Faiq, A Wilkerson, J Rose, K Miller, FW Rider, LG Giannini, EH AF Feldon, Michal Farhadi, Payam Noroozi Brunner, Hermine I. Itert, Lukasz Goldberg, Bob Faiq, Abdullah Wilkerson, Jesse Rose, Kathryn Miller, Frederick W. Rider, Lisa G. Giannini, Edward H. TI Health Related Quality of Life Is Reduced in Adult Patients with Idiopathic Inflammatory Myopathies SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Feldon, Michal; Brunner, Hermine I.] Cincinnati Childrens Hosp Med Ctr, Pediat Rheumatol, Cincinnati, OH 45229 USA. [Farhadi, Payam Noroozi; Faiq, Abdullah; Miller, Frederick W.; Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD USA. [Itert, Lukasz] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Goldberg, Bob] Myositis Assoc, Alexandria, VA USA. [Wilkerson, Jesse; Rose, Kathryn] Social & Sci Syst Inc, Durham, NC USA. [Giannini, Edward H.] Cincinnati Childrens Hosp Med Ctr, Rheumatol, Cincinnati, OH 45229 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 281 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201277 ER PT J AU Fujii, T Miljkovic, I Boudreau, RM Guermazi, A Piva, SR Strotmeyer, ES Carbone, L Harris, TB Marques, EA Shea, MK Nevitt, MC Newman, AB Kwoh, CK AF Fujii, Tomoko Miljkovic, Iva Boudreau, Robert M. Guermazi, Ali Piva, Sara R. Strotmeyer, Elsa S. Carbone, Laura Harris, Tamara B. Marques, Elisa A. Shea, M. Kyla Nevitt, Michael C. Newman, Anne B. Kwoh, C. Kent TI Are General and Central Adiposity Associated with MRI-Assessed Structural Changes in the Knees of Older Adults? SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Fujii, Tomoko; Miljkovic, Iva] Univ Pittsburgh, Pittsburgh, PA USA. [Boudreau, Robert M.; Strotmeyer, Elsa S.; Newman, Anne B.] Univ Pittsburgh, Epidemiol, Pittsburgh, PA USA. [Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA. [Piva, Sara R.] Univ Pittsburgh, Phys Therapy, Pittsburgh, PA USA. [Carbone, Laura] Georgia Regents Univ, Rheumatol, Augusta, GA USA. [Harris, Tamara B.; Marques, Elisa A.] NIA, Bethesda, MD 20892 USA. [Shea, M. Kyla] Tuffs Univ, Boston, MA USA. [Nevitt, Michael C.] UCSF, Epidemiol & Biostat, San Francisco, CA USA. [Kwoh, C. Kent] Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2015 VL 67 SU 10 MA 2093 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203499 ER PT J AU Giannelou, A Zhou, Q Sun, HW Yang, D Moir, S Edwan, JH Tsai, WXL Serti, E Stoffels, M Stone, DL Ombrello, AK Barron, K Su, HC Al Sonbul, A Joshi, S Risma, K Sramkova, L Quezado, MM Calvo, K Mones, AA Gutierrez-Cruz, G Gadina, MG Hafner, M Aksentijevich, I Kastner, D AF Giannelou, Angeliki Zhou, Qing Sun, Hong-Wei Yang, Dan Moir, Susan Edwan, Jehad H. Tsai, Wanxia L. Serti, Elisavet Stoffels, Monique Stone, Deborah L. Ombrello, Amanda K. Barron, Karyl Su, Helen C. Al Sonbul, Abdullah Joshi, Sarita Risma, Kimberly Sramkova, Lucie Quezado, Martha M. Calvo, Katherine Mones, Abu-Asab Gutierrez-Cruz, Gustavo Gadina, Massimo G. Hafner, Markus Aksentijevich, Ivona Kastner, Daniel TI Immune Dysregulation in Patients with TRNT1 Deficiency SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Giannelou, Angeliki] NHGRI, NIAMSD, NIH, Bethesda, MD 20892 USA. [Zhou, Qing; Stoffels, Monique; Aksentijevich, Ivona; Kastner, Daniel] NHGRI, NIH, Metab Cardiovasc & Inflammatory Dis Genom Branch, Bethesda, MD 20892 USA. [Sun, Hong-Wei; Edwan, Jehad H.; Tsai, Wanxia L.; Gutierrez-Cruz, Gustavo; Gadina, Massimo G.; Hafner, Markus] NIAMSD, NIH, Bethesda, MD 20892 USA. [Yang, Dan] NHLBI, NIH, Bethesda, MD 20892 USA. [Moir, Susan; Barron, Karyl; Su, Helen C.] NIAID, NIH, Bethesda, MD 20892 USA. [Serti, Elisavet] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Stone, Deborah L.; Ombrello, Amanda K.] NHGRI, NIH, Bethesda, MD 20892 USA. [Al Sonbul, Abdullah] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Joshi, Sarita] Nationwide Childrens Hosp, Columbus, OH USA. [Risma, Kimberly] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Sramkova, Lucie] Charles Univ Prague, Fac Med 2, Prague, Czech Republic. [Sramkova, Lucie] UH Motol, Prague, Czech Republic. [Quezado, Martha M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Calvo, Katherine] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Mones, Abu-Asab] NEI, NIH, Bethesda, MD 20892 USA. [Aksentijevich, Ivona] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 OCT PY 2015 VL 67 SU 10 MA 2096 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203502 ER PT J AU Gibson, M Lee, M Ward, MM Gensler, LS Brown, MA Assassi, S Pence, C Diekman, LA Rahbar, MH Weisman, MH Reveille, JD AF Gibson, Mary Lee, MinJae Ward, Michael M. Gensler, Lianne S. Brown, Matthew A. Assassi, Shervin Pence, Colton Diekman, Laura A. Rahbar, Mohammad H. Weisman, Michael H. Reveille, John D. TI Factors Associated with Anti-TNF Treatment in a Longitudinally Followed Ankylosing Spondylitis (AS) Cohort SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Gibson, Mary; Pence, Colton; Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Rheumatol, Houston, TX 77030 USA. [Lee, MinJae] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, BERD Core, Houston, TX 77030 USA. [Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. [Gensler, Lianne S.] Univ Calif San Francisco, Med Rheumatol, San Francisco, CA 94143 USA. [Brown, Matthew A.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [Assassi, Shervin] Univ Texas Houston, Med Sch Houston, Rheumatol, Houston, TX USA. [Diekman, Laura A.] Univ Texas Houston, Sch Med, Rheumatol, Houston, TX USA. [Rahbar, Mohammad H.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 712 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201706 ER PT J AU Gill, T Asquith, M Brooks, S Rosenbaum, JT Colbert, RA AF Gill, Tejpal Asquith, Mark Brooks, Stephen Rosenbaum, James T. Colbert, Robert A. TI Analysis of HLA-B27 Transgenic Rats Reveals Specific Gut Transcriptome and Microbiome Signatures Associated with Inflammation SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Gill, Tejpal; Brooks, Stephen] NIAMS, NIH, Bethesda, MD USA. [Asquith, Mark] OHSU, Portland, OR USA. [Rosenbaum, James T.] Legacy Hosp Syst, Devers Eye Inst, Portland, OR USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2827 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204378 ER PT J AU Grayson, PC Carmona-Rivera, C Waldman, M Phillips, K Subramaniam, V Thompson, P Graf, JD Kaplan, MJ AF Grayson, Peter C. Carmona-Rivera, Carmelo Waldman, Meryl Phillips, Karran Subramaniam, Venkataraman Thompson, Paul Graf, Jonathan D. Kaplan, Mariana J. TI Levamisole Triggers Neutrophil Extracellular Trap Formation through Muscarinic Receptors in Patients with Drug-Induced Vasculitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Grayson, Peter C.; Kaplan, Mariana J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Carmona-Rivera, Carmelo] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD USA. [Waldman, Meryl] NIDDK, NIH, Bethesda, MD 20892 USA. [Phillips, Karran] NIDA, NIH, Baltimore, MD USA. [Subramaniam, Venkataraman; Thompson, Paul] Univ Massachusetts, Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Graf, Jonathan D.] Univ Calif San Francisco, Rosalind Russell Ephraim P Engleman Rheumatol Res, San Francisco, CA 94143 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1085 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202349 ER PT J AU Gupta, S Tatouli, IP Rosen, LB Hasni, S Alevizos, I Manna, ZG Rivera, J Jiang, C Siegel, RM Holland, SM Moutsopoulos, HM Browne, SK AF Gupta, Sarthak Tatouli, Ioanna P. Rosen, Lindsey B. Hasni, Sarfaraz Alevizos, Illias Manna, Zerai G. Rivera, Juan Jiang, Chao Siegel, Richard M. Holland, Steven M. Moutsopoulos, Haralampos M. Browne, Sarah K. TI Anti-Interferon Autoantibodies in Systemic Lupus Erythematosus Are Biologically Active and Have Distinct Functions SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Gupta, Sarthak; Rosen, Lindsey B.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Gupta, Sarthak; Hasni, Sarfaraz; Manna, Zerai G.; Rivera, Juan; Jiang, Chao] NIAMSD, NIH, Bethesda, MD 20892 USA. [Tatouli, Ioanna P.; Moutsopoulos, Haralampos M.] Natl Univ Athens, Sch Med, Dept Pathophysiol, Athens, Greece. [Alevizos, Illias] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Jiang, Chao] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Siegel, Richard M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, Bethesda, MD USA. [Browne, Sarah K.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2015 VL 67 SU 10 MA 1859 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203265 ER PT J AU Gupta, S Patel, SK Blake, M Gadina, MG Tsai, WXL Carette, S Cuthbertson, D Hoffman, GS Khalidi, NA Koening, CL Langford, CA McAlear, CA Moreland, LW Monach, PA Pagnoux, C Seo, P Specks, U Sreih, AG Ytterberg, SR Browne, SK Holland, SM Kaplan, MJ Merkel, PA Grayson, PC AF Gupta, Sarthak Patel, Seema K. Blake, Mary Gadina, Massimo G. Tsai, Wanxia L. Carette, Simon Cuthbertson, David Hoffman, Gary S. Khalidi, Nader A. Koening, Curry L. Langford, Carol A. McAlear, Carol A. Moreland, Larry W. Monach, Paul A. Pagnoux, Christian Seo, Philip Specks, Ulrich Sreih, Antoine G. Ytterberg, Steven R. Browne, Sarah K. Holland, Steven M. Kaplan, Mariana J. Merkel, Peter A. Grayson, Peter C. CA Vasculitis Clinical Res Consortium TI Anticytokine Autoantibody Profiling in Five Types of Systemic Vasculitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Gupta, Sarthak; Browne, Sarah K.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Gupta, Sarthak; Patel, Seema K.; Blake, Mary; Gadina, Massimo G.; Tsai, Wanxia L.; Kaplan, Mariana J.; Grayson, Peter C.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Carette, Simon; Pagnoux, Christian] Univ Toronto, Mt Sinai Hosp, Div Rheumatol, Toronto, ON M5G 1X5, Canada. [Cuthbertson, David] Univ S Florida, Dept Pediat, Biostat & Informat, Tampa, FL 33620 USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Rheumatol, Cleveland, OH 44106 USA. [Khalidi, Nader A.] McMaster Univ, Div Rheumatol, St Josephs Hlth Care, Hamilton, ON, Canada. [Koening, Curry L.] Univ Utah, Div Rheumatol, Salt Lake City, UT USA. [McAlear, Carol A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Moreland, Larry W.] Univ Pittsburgh, Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Monach, Paul A.] Boston Univ, Sch Med, Rheumatol, Boston, MA 02118 USA. [Seo, Philip] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA. [Specks, Ulrich] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA. [Sreih, Antoine G.] Univ Penn, Dept Rheumatol, Philadelphia, PA 19104 USA. [Ytterberg, Steven R.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Browne, Sarah K.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Merkel, Peter A.] Univ Penn, Div Rheumatol, Penn Vasculitis Ctr, Philadelphia, PA 19104 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 864 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202130 ER PT J AU Hallen, B Kullenberg, T Leinonen, M Wiken, M Goldbach-Mansky, R Olivecrona, H AF Hallen, Bengt Kullenberg, Torbjorn Leinonen, Mika Wiken, Margareta Goldbach-Mansky, Raphaela Olivecrona, Hans TI Dose Adjustment of Anakinra (Kineret (R)) Based on Clinical Response in Patients with Severe Cryopyrin-Associated Periodic Syndromes SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Hallen, Bengt; Kullenberg, Torbjorn; Wiken, Margareta; Olivecrona, Hans] Swedish Orphan Biovitrum, Stockholm, Sweden. [Leinonen, Mika] 4Pharma AB, Stockholm, Sweden. [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 3094 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204643 ER PT J AU Harris, VM Cavett, J Kurien, B Liu, K Koelsch, KA Radfar, L Lewis, DM Stone, DU Li, SB Segal, B Wallace, DJ Weisman, MH Kelly, JA Alarcon-Riquelme, M Pons-Estel, B Jonsson, R Lu, XL Gottenberg, J Anaya, JM Cunninghame-Graham, DS Keystone, EC Huang, AJW Brennan, MT Hughes, P Illei, G Miceli, C Bykerk, VP Hirschfield, G Xie, G Ng, WF Nordmark, G Eriksson, P Omdal, R Rhodus, NL Rischmueller, M Rohrer, MD Wahren-Herlenius, M Witte, T Mariette, X Lessard, C Harley, JB Sivils, KL Scofield, RH AF Harris, Valerie M. Cavett, Joshua Kurien, Biji Liu, Ke Koelsch, Kristi A. Radfar, Lida Lewis, David M. Stone, Donald U. Li, Shibo Segal, Barbara Wallace, Daniel J. Weisman, Michael H. Kelly, Jennifer A. Alarcon-Riquelme, Marta Pons-Estel, Bernado Jonsson, Roland Lu, Xianglan Gottenberg, Jacques Anaya, Juan-Manuel Cunninghame-Graham, Deborah S. Keystone, Edward C. Huang, Andrew J. W. Brennan, Michael T. Hughes, Pamela Illei, G. Miceli, Corinne Bykerk, V. P. Hirschfield, Gideon Xie, Gang Ng, Wan-Fai Nordmark, Gunnel Eriksson, Per Omdal, Roald Rhodus, Nelson L. Rischmueller, Maureen Rohrer, Michael D. Wahren-Herlenius, Marie Witte, Torsten Mariette, Xavier Lessard, Christopher Harley, John B. Sivils, Kathy L. Scofield, Robert Hal TI Klinefelter's Syndrome (47,XXY) Among Men with Sjogren's Syndrome SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Harris, Valerie M.] Univ Oklahoma, Hlth Sci Ctr, Pathol, Oklahoma City, OK USA. [Cavett, Joshua] Univ Oklahoma, Hlth Sci Ctr, Med, Oklahoma City, OK USA. [Kurien, Biji] Oklahoma Med Res Fdn, Arthrit & Immunol, Oklahoma City, OK 73104 USA. [Liu, Ke] Univ Cincinnati & Cincinnati Childre, Cincinnati, OH USA. [Koelsch, Kristi A.] Oklahoma Med Res Fdn, Arthrit& Clin Immunol, Okalahoma City, OK USA. [Radfar, Lida] Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Oral Diag & Radiol Dept, Oklahoma City, OK USA. [Lewis, David M.] Univ Oklahoma, Hlth Sci Ctr, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA. [Stone, Donald U.] King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia. [Li, Shibo; Lu, Xianglan] Univ Oklahoma, Hlth Sci Ctr, Pediat, Oklahoma City, OK USA. [Segal, Barbara] Univ Minnesota, Rheumatol, Minneapolis, MN USA. [Wallace, Daniel J.] Cedars Sinai Med Ctr, West Hollywood, CA USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 USA. [Kelly, Jennifer A.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Alarcon-Riquelme, Marta] Oklahoma Med Res Fdn, Arthrit & Clin Immunol, Oklahoma City, OK USA. [Pons-Estel, Bernado] Hosp Prov Rosario, Rosario, Santa Fe, Argentina. [Jonsson, Roland] Broegelmann Res Lab, Bergen, Norway. [Gottenberg, Jacques] Hautepierre, Strasbourg, France. [Anaya, Juan-Manuel] CIB Rosario Univ, Cell Biol & Immunogenet, Medellin, Colombia. [Cunninghame-Graham, Deborah S.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Keystone, Edward C.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Huang, Andrew J. W.] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. [Brennan, Michael T.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA. [Hughes, Pamela] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA. [Illei, G.] NIDCR, Sjogrens Clin, NIH, Bethesda, MD USA. [Bykerk, V. P.] Univ Toronto, Toronto, ON, Canada. [Hirschfield, Gideon] Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Ctr Liver Res,Sch Immun & Infect, Birmingham, W Midlands, England. [Xie, Gang] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Nordmark, Gunnel] Uppsala Univ, Med Sci, Uppsala, Sweden. [Eriksson, Per] Linkoping Univ Hosp, Rheumatol Clin, S-58185 Linkoping, Sweden. [Omdal, Roald] Clin Immunol Unit, Dept Internal Med, Stavanger, Norway. [Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA. [Rischmueller, Maureen] Queen Elizabeth Hosp, Rheumatol, Adelaide, SA, Australia. [Rohrer, Michael D.] Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA. [Wahren-Herlenius, Marie] Expt Rheumatol Unit, Dept Med, Solna, Sweden. [Witte, Torsten] Hannover Med Sch, Dept Immunol & Rheumatol, Hannover, Germany. [Mariette, Xavier] Univ Paris Sud, Hop Univ Paris Sud, AP HP, Paris, France. [Lessard, Christopher; Sivils, Kathy L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA. [Scofield, Robert Hal] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Scofield, Robert Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, Robert Hal] US Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 3 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 OCT PY 2015 VL 67 SU 10 MA 648 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201642 ER PT J AU Hoffmann, P Ombrello, AK Stone, D Jones, A Barron, K Kastner, D AF Hoffmann, Patrycja Ombrello, Amanda K. Stone, Deborah Jones, Anne Barron, Karyl Kastner, Daniel TI New Clinical Features of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Hoffmann, Patrycja] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Ombrello, Amanda K.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Stone, Deborah; Jones, Anne] NHGRI, NIH, Bethesda, MD 20892 USA. [Barron, Karyl] NIAID, NIH, Bethesda, MD 20892 USA. [Kastner, Daniel] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1407 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202668 ER PT J AU Hwang, M Lee, M Ward, MM Gensler, LS Brown, MA Assassi, S Diekman, LA Rahbar, MH Weisman, MH Reveille, JD AF Hwang, Mark Lee, MinJae Ward, Michael M. Gensler, Lianne S. Brown, Matthew A. Assassi, Shervin Diekman, Laura A. Rahbar, Mohammad H. Weisman, Michael H. Reveille, John D. TI Predictors of Depression Severity in Ankylosing Spondylitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Hwang, Mark] Univ Texas Hlth Sci Ctr Houston, Internal Med, Houston, TX 77030 USA. [Lee, MinJae] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design BERD Core, Houston, TX 77030 USA. [Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. [Gensler, Lianne S.] Univ Calif San Francisco, Med Rheumatol, San Francisco, CA 94143 USA. [Brown, Matthew A.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [Assassi, Shervin; Diekman, Laura A.] Univ Texas Med Sch Houston, Rheumatol, Houston, TX USA. [Rahbar, Mohammad H.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Rheumatol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1708 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203115 ER PT J AU Irizarry-Caro, J Carmona-Rivera, C Novakovich, E Subramaniam, V Thompson, P Kaplan, MJ Grayson, PC AF Irizarry-Caro, Jorge Carmona-Rivera, Carmelo Novakovich, Elaine Subramaniam, Venkataraman Thompson, Paul Kaplan, Mariana J. Grayson, Peter C. TI Neutrophil-Mediated Mechanisms of Drug-Induced Autoimmunity SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Irizarry-Caro, Jorge; Carmona-Rivera, Carmelo; Novakovich, Elaine; Grayson, Peter C.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Subramaniam, Venkataraman] Univ Massachusetts, Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Thompson, Paul] Univ Massachusetts, Worcester, MA 01605 USA. [Kaplan, Mariana J.] NIAMSD, System Autoimmun Branch, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 208 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201205 ER PT J AU Kim, H Liu, Y de Jesus, AA Wesley, R Huang, Y Sanchez, GAM Chapelle, DC Tsai, WXL Gadina, MG Miller, FW Hasni, S Vanderver, A Rider, LG Goldbach-Mansky, R AF Kim, Hanna Liu, Yin de Jesus, Adriana Almeida Wesley, Robert Huang, Yan Sanchez, Gina A. Montealegre Chapelle, Dawn C. Tsai, Wanxia L. Gadina, Massimo G. Miller, Frederick W. Hasni, Sarfaraz Vanderver, Adeline Rider, Lisa G. Goldbach-Mansky, Raphaela TI Cytokine Profile Comparison of Monogenic and Complex Conditions with Interferon-Regulated Gene Signatures in Chronic Atypical Neutrophilic Dermatosis with Lipodsytrophy and Elevated Temperature (CANDLE), SAVI, Aicardi-Goutieres Syndrome, JDM, and SLE SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Kim, Hanna; de Jesus, Adriana Almeida; Huang, Yan; Sanchez, Gina A. Montealegre; Chapelle, Dawn C.; Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Liu, Yin] NIAMS, Sci Review Branch, NIH, Bethesda, MD USA. [Wesley, Robert] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Tsai, Wanxia L.; Gadina, Massimo G.] NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA. [Miller, Frederick W.; Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD USA. [Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA. [Vanderver, Adeline] Childrens Natl Med Ctr, Pediat Neurol, Washington, DC 20010 USA. NR 6 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 OCT PY 2015 VL 67 SU 10 MA 2465 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204016 ER PT J AU Kim, S Coligan, JE Park, JE Stuart, JM Kang, A Myers, L AF Kim, Seunghyun Coligan, John E. Park, Jeoung-Eun Stuart, John M. Kang, Andrew Myers, Linda TI The Role of Leukocyte Associated Immunoglobulin-like Receptor-1 (LAIR-1) in Collagen-Induced Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Kim, Seunghyun] Univ Tennessee, Ctr Hlth Sci, Rheumatol, Memphis, TN 38163 USA. [Coligan, John E.] NIH, Bethesda, MD 20892 USA. [Park, Jeoung-Eun] Univ Tennessee, Memphis, TN USA. [Stuart, John M.] Univ Tennessee, Vet Affairs, Memphis, TN USA. [Kang, Andrew; Myers, Linda] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2558 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204109 ER PT J AU Kuemmerle-Deschner, JB Ozen, S Tyrrell, PN Kone-Paut, I Goldbach-Mansky, R Lachmann, H Blank, N Hoffman, HM Weissbarth-Riedel, E Huegle, B Kallinich, T Gattorno, M Gul, A ter Haar, NM Oswald, M Dedeoglu, F Benseler, SM AF Kuemmerle-Deschner, Jasmin B. Ozen, Seza Tyrrell, Pascal N. Kone-Paut, Isabelle Goldbach-Mansky, Raphaela Lachmann, Helen Blank, Norbert Hoffman, Hal M. Weissbarth-Riedel, Elisabeth Huegle, Boris Kallinich, Tilmann Gattorno, Marco Gul, Ahmet ter Haar, Nienke M. Oswald, Marlen Dedeoglu, Fatma Benseler, Susanne M. TI Development and Validation of Diagnostic Criteria for Cryopyrin Associated Periodic Syndromes SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Kuemmerle-Deschner, Jasmin B.] Univ Klinikum Tubingen, Klin Kinder & Jugendmed, Tubingen, Germany. [Ozen, Seza] Hacettepe Univ, Pediat Nephrol & Rheumatol, Ankara, Turkey. [Tyrrell, Pascal N.] Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. [Kone-Paut, Isabelle] CHU Bicetre, Pediat Rheumatol, Le Kremlin Bicetre, France. [Goldbach-Mansky, Raphaela] NIAMS, NIH, Bethesda, MD USA. [Lachmann, Helen] UCL, Sch Med, UK Natl Amyloidosis Ctr, London W1N 8AA, England. [Blank, Norbert] Heidelberg Univ, Med Rheumatol 5, Heidelberg, Germany. [Hoffman, Hal M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Weissbarth-Riedel, Elisabeth] Univ Kinderklin Hamburg, Pediat, Rheumatol, Hamburg, Germany. [Huegle, Boris] German Ctr Pediat & Adolescent Rheumatol, Pediat Rheumatol, Garmisch Partenkirchen, Germany. [Kallinich, Tilmann] Univ Med Berlin, Charite, Berlin, Germany. [Gattorno, Marco] G Gaslini Inst Children, Pediat, Genoa, Italy. [Gul, Ahmet] Istanbul Univ, Div Rheumatol, Dept Internal Med, Istanbul Fac Med, Istanbul, Turkey. [ter Haar, Nienke M.] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands. [Oswald, Marlen] Univ Hosp Tuebingen, Tubingen, Germany. [Dedeoglu, Fatma] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Benseler, Susanne M.] Univ Calgary, Alberta Childrens Hosp, Rheumatol, Calgary, AB, Canada. 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 3093 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204642 ER PT J AU Lahoutiharahdashti, A Paik, JJ Albayda, J Mammen, A Christopher-Stine, L AF Lahoutiharahdashti, Arash Paik, Julie J. Albayda, Jemima Mammen, Andrew Christopher-Stine, Lisa TI The "Sleeve Sign" in Dermatomyositis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Lahoutiharahdashti, Arash; Albayda, Jemima] Johns Hopkins Univ, Sch Med, Rheumatol, Baltimore, MD USA. [Paik, Julie J.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Mammen, Andrew; Christopher-Stine, Lisa] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Mammen, Andrew] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 305 PG 5 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201300 ER PT J AU Layh-Schmitt, G Lu, SJ Lazowick, E Brooks, S Gadina, M Colbert, RA AF layh-Schmitt, Gerlinde Lu, Shajia Lazowick, Emily Brooks, Stephen Gadina, Massimo Colbert, Robert A. TI Characterization of Mesenchymal Stem Cells Generated from Axial Spondyloarthritis Patient-Derived Induced Pluripotent Stem Cells SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [layh-Schmitt, Gerlinde; Lu, Shajia; Lazowick, Emily; Brooks, Stephen; Gadina, Massimo] NIAMS, NIH, Bethesda, MD USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2825 PG 1 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204376 ER PT J AU Lessard, CJ Li, H Ice, J Adrianto, I Rasmussen, A Grundahl, K Kelly, JA Miceli, C Bowman, S Lester, S Brun, JG Goransson, LG Harboe, E Guthridge, JM Kaufman, KM Eriksson, P Eloranta, ML Kvarnstrom, M Cunninghame-Graham, DS Farris, AD Brennan, MT Chodosh, J Gopalakrishnan, R Huang, AJW Hughes, P Lewis, DM Radfar, L Rohrer, MD Stone, DU Vyse, TJ Gaffney, PM James, JA Harley, JB Omdal, R Wahren-Herlenius, M Illei, GG Witte, T Jonsson, R Rischmueller, M Ronnblom, L Mariette, X Anaya, JM Ng, WF Nordmark, G Montgomery, CG Rhodus, NL Segal, BM Scofield, RH Sivils, KL AF Lessard, Christopher J. Li, He Ice, John Adrianto, Indra Rasmussen, Astrid Grundahl, Kiely Kelly, Jennifer A. Miceli, Corinne Bowman, Simon Lester, Susan Brun, Johan G. Goransson, Lasse G. Harboe, Erna Guthridge, Joel M. Kaufman, Kenneth M. Eriksson, Per Eloranta, Maija-Leena Kvarnstrom, Marika Cunninghame-Graham, Deborah S. Farris, A. Darise Brennan, Michael T. Chodosh, James Gopalakrishnan, Raj Huang, Andrew J. W. Hughes, Pamela Lewis, David M. Radfar, Lida Rohrer, Michael D. Stone, Donald U. Vyse, Timothy J. Gaffney, Patrick M. James, Judith A. Harley, John B. Omdal, Roald Wahren-Herlenius, Marie Illei, Gabor G. Witte, Torsten Jonsson, Roland Rischmueller, Maureen Ronnblom, Lars Mariette, Xavier Anaya, Juan-Manuel Ng, Wan-Fai Nordmark, Gunnel Montgomery, Courtney G. Rhodus, Nelson L. Segal, Barbara M. Scofield, R. Hal Sivils, Kathy L. TI Identification of Novel Sjogren's Syndrome Risk Loci in the Regions of TNFAIP3 and PRDM1 SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Lessard, Christopher J.; Li, He; James, Judith A.; Sivils, Kathy L.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Lessard, Christopher J.; Li, He; Ice, John; Rasmussen, Astrid; Grundahl, Kiely; Kelly, Jennifer A.; Guthridge, Joel M.; Farris, A. Darise; Gaffney, Patrick M.; James, Judith A.; Montgomery, Courtney G.; Scofield, R. Hal; Sivils, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Adrianto, Indra] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Bowman, Simon] Univ Hosp Birmingham, Dept Rheumatol, Birmingham, W Midlands, England. [Lester, Susan] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Brun, Johan G.] Univ Bergen, Inst Internal Med, Bergen, Norway. [Brun, Johan G.; Jonsson, Roland] Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway. [Goransson, Lasse G.; Harboe, Erna; Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Eriksson, Per] Linkoping Univ, Rheumatol AIR, Dept Clin & Expt Med, Linkoping, Sweden. [Eloranta, Maija-Leena] Uppsala Univ, SciLife Lab, Dept Med Sci, Rheumatol, Uppsala, Sweden. [Kvarnstrom, Marika; Wahren-Herlenius, Marie] Karolinska Inst, Dept Med, Stockholm, Sweden. [Cunninghame-Graham, Deborah S.; Vyse, Timothy J.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Brennan, Michael T.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol, Boston, MA USA. [Gopalakrishnan, Raj] Univ Minnesota, Div Oral Pathol, Diagnost & Biol Sci, Minneapolis, MN USA. [Huang, Andrew J. W.] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. [Hughes, Pamela] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA. [Lewis, David M.] Univ Oklahoma, Hlth Sci Ctr, Dept Oral & Maxillofacial Pathol, Coll Dent, Oklahoma City, OK USA. [Radfar, Lida] Univ Oklahoma, Hlth Sci Ctr, Oral Diag & Radiol Dept, Coll Dent, Oklahoma City, OK USA. [Rohrer, Michael D.] Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA. [Stone, Donald U.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA. [Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Witte, Torsten] Hannover Med Sch, Hannover, Germany. [Jonsson, Roland] Univ Bergen, Gade Inst, Broegelmann Res Lab, Bergen, Norway. [Rischmueller, Maureen] Univ Adelaide, Adelaide, SA, Australia. [Rischmueller, Maureen] Queen Elizabeth Hosp, Dept Rheumatol, Adelaide, SA, Australia. [Ronnblom, Lars; Nordmark, Gunnel] Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden. [Ronnblom, Lars; Nordmark, Gunnel] Uppsala Univ, Sci Life Lab, Uppsala, Sweden. [Mariette, Xavier] Univ Paris 11, Hop Univ Paris Sud, AP HP, Paris, France. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Ng, Wan-Fai] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA. [Segal, Barbara M.] Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA. [Scofield, R. Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1052 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202316 ER PT J AU Liao, K Cui, J Rhodes, C Lahey, LJ Playford, M Kuo, IH Frits, M Iannaccone, C Coblyn, JS Weinblatt, M Shadick, N Mehta, NN Sokolove, J AF Liao, Katherine Cui, Jing Rhodes, Christopher Lahey, Lauren J. Playford, Martin Kuo, I-Hsin Frits, Michelle Iannaccone, Christine Coblyn, Jonathan S. Weinblatt, Michael Shadick, Nancy Mehta, Nehal N. Sokolove, Jeremy TI The Association Between HDL Cholesterol Efflux Capacity, Citrullinated ApoA1 and Anti-Citrullinated ApoA1 Antibodies in Rheumatoid Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Liao, Katherine; Cui, Jing; Kuo, I-Hsin; Frits, Michelle; Iannaccone, Christine; Weinblatt, Michael; Shadick, Nancy] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Rhodes, Christopher; Lahey, Lauren J.; Sokolove, Jeremy] VA Palo Alto HealthCare Syst, Med, Palo Alto, CA USA. [Rhodes, Christopher; Lahey, Lauren J.; Sokolove, Jeremy] Stanford Univ, Palo Alto, CA 94304 USA. [Playford, Martin; Mehta, Nehal N.] NHLBI, NIH, Bethesda, MD 20892 USA. [Coblyn, Jonathan S.] Brigham & Womens Hosp, Boston, MA 02115 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1510 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202771 ER PT J AU Lood, C Blanco, LP Purmalek, M Smith, CK Carmona-Rivera, C Ledbetter, J Kaplan, MJ Elkon, KB AF Lood, Christian Blanco, Luz P. Purmalek, Monica Smith, Carolyne K. Carmona-Rivera, Carmelo Ledbetter, Jeffrey Kaplan, Mariana J. Elkon, Keith B. TI Mitochondrial ROS Is a Novel Regulator of Sting-Mediated Type I IFN Production By Governing Extrusion of Oxidized Mitochondrial DNA upon Neutrophil Extracellular Trap Formation. SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Lood, Christian] Univ Washington, Dept Med, Div Rheumatol, Seattle, WA 98195 USA. [Blanco, Luz P.; Purmalek, Monica; Smith, Carolyne K.; Carmona-Rivera, Carmelo; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Ledbetter, Jeffrey] Univ Washington, Seattle, WA 98195 USA. [Elkon, Keith B.] Univ Washington, Div Rheumatol, Seattle, WA 98195 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2073 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203479 ER PT J AU Malle, L Marrero, B Liu, Y Sanchez, GAM Chapelle, DC Kim, H O'Brien, M Ramsey, S Dueckers, G Ozen, S Wittkowski, H Foll, D Tenbrock, K Jones, OY Holland, SM Fontana, J Huang, Y Gonzalez, B Brogan, P Brunner, J Ramanan, AV Hilliard, T Santiago, L Brescia, A Paller, A Brooks, S Deng, ZM de Jesus, AA Goldbach-Mansky, R AF Malle, Louise Marrero, Bernadette Liu, Yin Sanchez, Gina A. Montealegre Chapelle, Dawn C. Kim, Hanna O'Brien, Michelle Ramsey, Suzanne Dueckers, Gregor Ozen, Seza Wittkowski, Helmut Foell, Dirk Tenbrock, Klaus Jones, Olcay Y. Holland, Steven M. Fontana, Joseph Huang, Yan Gonzalez, Benito Brogan, Paul Brunner, Juergen Ramanan, Athimalaipet V. Hilliard, Tom Santiago, Laisa Brescia, AnneMarie Paller, Amy Brooks, Stephen Deng, Zuoming de Jesus, Adriana Almeida Goldbach-Mansky, Raphaela TI Interstitial Lung Disease in Sting-Associated Vasculopathy with Onset in Infancy (SAVI): Genotype-Phenotype Correlation SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Malle, Louise; Marrero, Bernadette; Sanchez, Gina A. Montealegre; Chapelle, Dawn C.; Kim, Hanna; O'Brien, Michelle; Huang, Yan; de Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Liu, Yin] NIAMS, Sci Review Branch, NIH, Bethesda, MD USA. [Kim, Hanna] Alfred I duPont Hosp Children, Pediat Rheumatol, Wilmington, DE USA. [Ramsey, Suzanne] IWK Hlth Ctr, Pediat Rheumatol, Halifax, NS, Canada. [Dueckers, Gregor] HELIOS Klinikum Krefeld, Helios Kliniken Kinderklinik, Krefeld, Germany. [Ozen, Seza] Ist Giannina Gaslini, Paediat Rheumatol Int Trials Org PRINTO, I-16148 Genoa, Italy. [Ozen, Seza] Hacettepe Univ, Pediat Nephrol & Rheumatol, Ankara, Turkey. [Wittkowski, Helmut] Univ Munster, Pediat, D-48149 Munster, Germany. [Foell, Dirk] Univ Munster, D-48149 Munster, Germany. [Tenbrock, Klaus] Univ Aachen, Aachen, Germany. [Jones, Olcay Y.] George Washington Univ, Rheumatol, Washington, DC USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Fontana, Joseph] NHLBI, NIH, Bethesda, MD 20892 USA. [Gonzalez, Benito] Hosp Ninos Luis Calvo Mackenna, Santiago, Chile. [Brogan, Paul] UCL Inst Child Hlth, London, England. [Brogan, Paul] Great Ormond St Hosp NHS Fdn Trust, London, England. [Brunner, Juergen] Univ Klin Kinder Jugendheilkunde, Innsbruck, Austria. [Ramanan, Athimalaipet V.; Hilliard, Tom] Bristol Royal Hosp Children, Bristol, Avon, England. [Santiago, Laisa] All Childrens Hosp Rheumatol, St Petersburg, FL USA. [Brescia, AnneMarie] Alfred I DuPont Hosp Children, Jefferson Med Coll, Willmington, DE USA. [Paller, Amy] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Paller, Amy] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. [Brooks, Stephen] NIAMS, NIH, Bethesda, MD USA. [Deng, Zuoming] NIAMS, Biodata Min & Discovery, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2015 VL 67 SU 10 MA 1025 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202289 ER PT J AU Mandal, J Ward, MM Weisman, M Simard, J Brown, MA Lee, M Rahbar, MH Reveille, JD Gensler, LS AF Mandal, Jennifer Ward, Michael M. Weisman, Michael Simard, Jillian Brown, Matthew A. Lee, MinJae Rahbar, Mohammad H. Reveille, John D. Gensler, Lianne S. TI Gender Differences in Ankylosing Spondylitis: Men Derive Greater Benefit from Tumor Necrosis Factor Alpha Inhibitors SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Mandal, Jennifer] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. [Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. [Weisman, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Simard, Jillian] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, Matthew A.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [Lee, MinJae] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Biostat Epidemiol Res Design BERD Core, Houston, TX 77030 USA. [Rahbar, Mohammad H.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Rheumatol, Houston, TX 77030 USA. [Gensler, Lianne S.] Univ Calif San Francisco, Med Rheumatol, San Francisco, CA 94143 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1743 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203150 ER PT J AU Marder, W Knight, JS Kaplan, MJ Somers, EC Zhang, X O'Dell, AA Padmanabhan, V Lieberman, RW AF Marder, Wendy Knight, Jason S. Kaplan, Mariana J. Somers, Emily C. Zhang, Xu O'Dell, Alexander A. Padmanabhan, Vasantha Lieberman, Richard W. TI Placentas of Lupus Pregnancies Are Characterized By Marked Inflammatory Changes Despite Good Disease Control SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Marder, Wendy; Knight, Jason S.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Kaplan, Mariana J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Somers, Emily C.; Zhang, Xu; Padmanabhan, Vasantha; Lieberman, Richard W.] Univ Michigan, Ann Arbor, MI 48109 USA. [O'Dell, Alexander A.] Univ Michigan, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2121 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203527 ER PT J AU Meisgen, S Hedlund, M Ambrosi, A Folkersen, L Dzikaite-Ottosson, V Ding, B Strandberg, L Biavati, L Ramskold, D Forsberg, D Bergin, L Ruhrmann, S Hamilton, RM Franco-Cereceda, A Hamsten, A Olsson, T Greene, L Eriksson, P Gemzell-Danielsson, K Salomonsson, S Kuchroo, VK Herlenius, E Kockum, I Sonesson, SE Wahren-Herlenius, M AF Meisgen, Sabrina Hedlund, Malin Ambrosi, Aurelie Folkersen, Lasse Dzikaite-Ottosson, Vijole Ding, Bo Strandberg, Linn Biavati, Luca Ramskold, Daniel Forsberg, David Bergin, Lisa Ruhrmann, Sabrina Hamilton, Robert M. Franco-Cereceda, Anders Hamsten, Anders Olsson, Tomas Greene, Lois Eriksson, Per Gemzell-Danielsson, Kristina Salomonsson, Stina Kuchroo, Vijay K. Herlenius, Eric Kockum, Ingrid Sonesson, Sven-Erik Wahren-Herlenius, Marie CA Swedish Congenital Heart Block TI Auxilin Is a Novel Susceptibility Gene for Congenital Heart Block Modulating Cardiac Function SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Meisgen, Sabrina; Hedlund, Malin; Ambrosi, Aurelie; Ding, Bo; Forsberg, David; Bergin, Lisa; Ruhrmann, Sabrina; Franco-Cereceda, Anders; Hamsten, Anders; Eriksson, Per; Gemzell-Danielsson, Kristina; Salomonsson, Stina; Herlenius, Eric; Sonesson, Sven-Erik; Swedish Congenital Heart Block] Karolinska Inst, Stockholm, Sweden. [Folkersen, Lasse] Tech Univ Denmark, Copenhagen, Denmark. [Dzikaite-Ottosson, Vijole] Karolinska Inst, CMM, Rheumatol Unit, Dept Med, Stockholm, Sweden. [Strandberg, Linn; Biavati, Luca] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Ramskold, Daniel] Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden. [Hamilton, Robert M.] Univ Toronto, Hosp Sick Children, Cardiol, Toronto, ON M5G 1X8, Canada. [Olsson, Tomas; Kockum, Ingrid] Karolinska Inst, Dept Clin Neurosci, Neuroimmunol, Stockholm, Sweden. [Greene, Lois] NHLBI, Bethesda, MD 20892 USA. [Kuchroo, Vijay K.] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02114 USA. [Wahren-Herlenius, Marie] Karolinska Inst, Rheumatol Unit, Dept Med, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 1 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 OCT PY 2015 VL 67 SU 10 MA 86 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201084 ER PT J AU Moore, E Lewis, H Smith, CK Subramaniam, V Hoffmann, V Thompson, P Kaplan, MJ AF Moore, Erica Lewis, Huw Smith, Carolyne K. Subramaniam, Venkataraman Hoffmann, Victoria Thompson, Paul Kaplan, Mariana J. TI Role of Topical Administration of Peptidylarginine Deiminase Inhibitors in Murine Lupus SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Moore, Erica; Smith, Carolyne K.; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Lewis, Huw] GSK, Immuno Inflammat, Stevenage, Herts, England. [Subramaniam, Venkataraman] Univ Massachusetts, Boston, MA 02125 USA. [Hoffmann, Victoria] NIH, Bethesda, MD 20892 USA. [Thompson, Paul] Univ Massachusetts, Worcester, MA 01605 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1769 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203175 ER PT J AU Mor-Vaknin, N Saha, AK Legendre, M Carmona-Rivera, C Amin, MA Rabquer, BJ Gonzalez-Hernandez, MJ Jorns, JM Yalavarthi, S Mohan, S Pai, D Angevine, K Adams, B Knight, JS Koch, AE Fox, D Engelke, D Kaplan, MJ Markovitz, D AF Mor-Vaknin, Nirit Saha, Anjan K. Legendre, Maureen Carmona-Rivera, Carmelo Amin, M. Asif Rabquer, Bradley J. Gonzalez-Hernandez, Marta J. Jorns, Julie M. Yalavarthi, Srilakshmi Mohan, Smriti Pai, Dave Angevine, Kristine Adams, Barbara Knight, Jason S. Koch, Alisa E. Fox, David Engelke, Dave Kaplan, Mariana J. Markovitz, David TI DEK-Targeting DNA Aptamers As Novel Therapeutics for Inflammatory Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Mor-Vaknin, Nirit; Legendre, Maureen] Univ Michigan, Infect Dis, Ann Arbor, MI 48109 USA. [Saha, Anjan K.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Carmona-Rivera, Carmelo] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Amin, M. Asif; Markovitz, David] Univ Michigan, Internal Med, Ann Arbor, MI 48109 USA. [Rabquer, Bradley J.] Albion Coll, Ann Arbor, MI USA. [Gonzalez-Hernandez, Marta J.] Univ Michigan, Grad Program Immunol, Ann Arbor, MI 48109 USA. [Jorns, Julie M.] Univ Michigan, Pathol, Ann Arbor, MI 48109 USA. [Yalavarthi, Srilakshmi; Knight, Jason S.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Mohan, Smriti] Univ Michigan, Pediat Rheumatol, Ann Arbor, MI 48109 USA. [Pai, Dave] Scripps Res Inst, San Diego, CA USA. [Angevine, Kristine] Appistry Inc, St Louis, MO USA. [Adams, Barbara] Univ Michigan Hlth Syst, Pediat Rheum PTD, Ann Arbor, MI USA. [Koch, Alisa E.] VA Med Serv, Ann Arbor, MI USA. [Koch, Alisa E.; Fox, David] Univ Michigan, Med Ctr, Div Rheumatol, Internal Med, Ann Arbor, MI USA. [Koch, Alisa E.] Vet Affairs, Internal Med, Ann Arbor, MI USA. [Koch, Alisa E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Engelke, Dave] Univ Michigan, Biochem, Ann Arbor, MI 48109 USA. [Kaplan, Mariana J.] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 933 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202197 ER PT J AU Navid, F Layh-Schmitt, G Colbert, RA AF Navid, Fatemeh layh-Schmitt, GerlinDe Colbert, Robert A. TI Stimulation of Autophagy Reduces Misfolded HLA-B27 in a Rat Model of Spondyloarthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Navid, Fatemeh; layh-Schmitt, GerlinDe] NIAMS, NIH, Bethesda, MD USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2826 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204377 ER PT J AU Newman, K Sawhney, M Katz, JD Siegel, R Brofferio, A Boehm, M AF Newman, Kam Sawhney, Megha Katz, James D. Siegel, Richard Brofferio, Alessandra Boehm, Manfred TI Rheumatic Manifestations May be the First Clinical Presentation of Arterial Calcification Due to CD73 Deficiency SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Newman, Kam] NIAMSD, NIH, Bethesda, MD 20892 USA. [Sawhney, Megha; Brofferio, Alessandra] NIH, Bethesda, MD 20892 USA. [Katz, James D.] George Washington Univ, Dept Med, Div Rheumatol, Washington, DC USA. [Siegel, Richard] NIAMSD, Bethesda, MD 20892 USA. [Boehm, Manfred] NHLBI, Lab Cardiovasc Regenerat Med, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2037 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203443 ER PT J AU Olivecrona, H Goldbach-Mansky, R Kullenberg, T Leinonen, M AF Olivecrona, Hans Goldbach-Mansky, Raphaela Kullenberg, Torbjorn Leinonen, Mika TI The Effect of IL-1 Receptor Antagonist Anakinra (Kineret (R)) on Measures of Central Nervous System Inflammation and Headaches in Pediatric Patients with Severe Cryopyrin-Associated Periodic Syndromes SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Olivecrona, Hans; Kullenberg, Torbjorn] Swedish Orphan Biovitrum, Stockholm, Sweden. [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Leinonen, Mika] 4Pharma AB, Stockholm, Sweden. 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1449 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202710 ER PT J AU Otero, CM Assassi, S Weisman, MH Ward, MM Gensler, LS Brown, MA Wu, MH Hagan, J Reveille, JD Salazar, G AF Otero, Carolina Mejia Assassi, Shervin Weisman, Michael H. Ward, Michael M. Gensler, Lianne S. Brown, Matthew A. Wu, Minghua Hagan, John Reveille, John D. Salazar, Gloria TI The Global miRNA Whole Blood Profile of Ankylosing Spondylitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Otero, Carolina Mejia; Assassi, Shervin; Wu, Minghua; Salazar, Gloria] Univ Texas Med Sch Houston, Rheumatol, Houston, TX USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Rheumatol, Los Angeles, CA 90048 USA. [Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. [Gensler, Lianne S.] Univ Calif San Francisco, Med Rheumatol, San Francisco, CA 94143 USA. [Brown, Matthew A.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia. [Hagan, John] Univ Texas Houston, Neurosurg, Houston, TX USA. [Reveille, John D.] Univ Texas Med Sch Houston, Internal Med Rheumatol, Houston, TX 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2804 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204355 ER PT J AU Park, YH Wood, G Kastner, D Chae, JJ AF Park, Yong Hwan Wood, Geryl Kastner, Daniel Chae, Jae Jin TI Activation of the Pyrin Inflammasome through the RhoA Signaling Pathway in Familial Mediterranean Fever (FMF) and Hyperimmunoglobulinemia D Syndrome (HIDS) SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Park, Yong Hwan; Wood, Geryl; Kastner, Daniel; Chae, Jae Jin] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 195 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201193 ER PT J AU Parks, CG Hoppin, J Costenbader, KH Sandler, D AF Parks, Christine G. Hoppin, Jane Costenbader, Karen H. Sandler, Dale TI Rheumatoid Arthritis in Female Spouses in the Agricultural Health Study: Associations with Pesticides and Other Farm Exposures SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Parks, Christine G.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Hoppin, Jane] N Carolina State Univ, Biol Sci, Raleigh, NC 27695 USA. [Costenbader, Karen H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Sandler, Dale] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2015 VL 67 SU 10 MA 1214 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202478 ER PT J AU Purmalek, M Sakhardande, S Temesgen-Oyelakin, Y Fike, A Salahuddin, T Natarajan, B Manna, Z Joyal, E Hasni, S Mehta, NN Kaplan, MJ AF Purmalek, Monica Sakhardande, Simantini Temesgen-Oyelakin, Yenealem Fike, Alice Salahuddin, Taufiq Natarajan, Balaji Manna, Zerai Joyal, Elizabeth Hasni, Sarfaraz Mehta, Nehal N. Kaplan, Mariana J. TI Innate Immunity, Arterial Inflammation and Vascular Stiffness in Patients with Systemic Lupus Erythematosus SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Purmalek, Monica; Sakhardande, Simantini; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Temesgen-Oyelakin, Yenealem; Manna, Zerai; Joyal, Elizabeth; Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA. [Fike, Alice] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Salahuddin, Taufiq; Natarajan, Balaji; Mehta, Nehal N.] NHLBI, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1787 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203193 ER PT J AU Sakhardande, S Purmalek, M Sampson, M Temesgen-Oyelakim, Y Fike, A Salahuddin, T Natarajan, B Manna, Z Joyal, E Chen, M Hasni, S Mehta, NN Remaley, A Kaplan, MJ AF Sakhardande, Simantini Purmalek, Monica Sampson, Maureen Temesgen-Oyelakim, Yenealem Fike, Alice Salahuddin, Taufiq Natarajan, Balaji Manna, Zerai Joyal, Elizabeth Chen, Marcus Hasni, Sarfaraz Mehta, Nehal N. Remaley, Alan Kaplan, Mariana J. TI Lipoprotein Subfractions and Cardiovascular Disease in Systemic Lupus Erythematosus SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Sakhardande, Simantini; Purmalek, Monica; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Sampson, Maureen] CC NIH, Bethesda, MD USA. [Temesgen-Oyelakim, Yenealem; Fike, Alice] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Salahuddin, Taufiq; Natarajan, Balaji; Chen, Marcus; Mehta, Nehal N.; Remaley, Alan] NHLBI, NIH, Bethesda, MD 20892 USA. [Manna, Zerai; Joyal, Elizabeth; Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA. [Mehta, Nehal N.] NHLBI, Cardiovasc & Pulm Div, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1788 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203194 ER PT J AU Schiffenbauer, A Smith, N Rider, LG Miller, FW AF Schiffenbauer, Adam Smith, Natalie Rider, Lisa G. Miller, Frederick W. TI Tobacco Smoking in Different Racial Groups Is Differentially Associated with the Development of Myositis Autoantibodies and Interstitial Lung Disease in the Idiopathic Inflammatory Myopathies SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Schiffenbauer, Adam; Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD USA. [Smith, Natalie] Purdue Univ, Stat, Allison Pk, PA USA. [Miller, Frederick W.] NIH, Clin Res Branch, Environm Autoimmun Grp, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 285 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201281 ER PT J AU Shwin, KW Carmona-Rivera, C Tsai, W Lee, CCR Novakovich, E Stone, DL Ombrello, AK Goldbach-Mansky, R Gadina, M Kastner, D Aksentijevich, I Kaplan, MJ Grayson, PC AF Shwin, Kyawt W. Carmona-Rivera, Carmelo Tsai, Wanxia Lee, Chya-chia Richard Novakovich, Elaine Stone, Deborah L. Ombrello, Amanda K. Goldbach-Mansky, Raphaela Gadina, Massimo Kastner, Daniel Aksentijevich, Ivona Kaplan, Mariana J. Grayson, Peter C. TI Role of Adenosine and Neutrophils in Inflammation Associated with Mutations in CECR1 Gene SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Shwin, Kyawt W.] NIAMS, NIH, Bethesda, MD USA. [Shwin, Kyawt W.] NIH, Translat Autoinflammatory Dis Sect, Bethesda, MD 20892 USA. [Carmona-Rivera, Carmelo] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD USA. [Tsai, Wanxia] NIH, Translat Immunol, Off Sci & Technol, Bethesda, MD 20892 USA. [Lee, Chya-chia Richard] NCI, NIH, Bethesda, MD 20892 USA. [Lee, Chya-chia Richard] NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. [Novakovich, Elaine; Kaplan, Mariana J.] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD USA. [Stone, Deborah L.; Ombrello, Amanda K.] NHGRI, NIH, Bethesda, MD 20892 USA. [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Gadina, Massimo] NIAMS, Translat Immunol, Off Sci & Technol, NIH, Bethesda, MD USA. [Kastner, Daniel] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Aksentijevich, Ivona] NHGRI, NIH, Metab Cardiovasc & Inflammatory Dis Genom Branch, Bethesda, MD 20892 USA. [Aksentijevich, Ivona] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Grayson, Peter C.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Grayson, Peter C.] NIAMS, Syst Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 3032 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204581 ER PT J AU Singh, N Johnstone, D Martin, K Tempera, I Kaplan, MJ Denny, M AF Singh, Namrata Johnstone, Duncan Martin, Kayla Tempera, Italo Kaplan, Mariana J. Denny, Michael TI Alterations in Nuclear Structure Promote Lupus Autoimmunity in a Mouse Model SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Singh, Namrata] Univ Iowa, Internal Med, Iowa City, IA USA. [Johnstone, Duncan] Temple Univ, Sch Med, Internal Med, Nephrol, Philadelphia, PA 19122 USA. [Martin, Kayla] Temple Univ, Microbiol & Immunol, Philadelphia, PA 19122 USA. [Tempera, Italo] Fels Inst Canc Res, Micorbiol Immunol, Philadelphia, PA USA. [Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Denny, Michael] Temple Univ, Sch Med, Internal Med, Philadelphia, PA 19122 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1758 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203165 ER PT J AU St Clair, EW Baer, AN Noaiseh, G Parke, A Coca, A Utset, T Genovese, MC Wallace, DJ McNamara, J Boyle, K Keyes-Elstein, L Franchimont, N James, JA AF St Clair, E. William Baer, Alan N. Noaiseh, Ghaith Parke, Anne Coca, Andreea Utset, Tammy Genovese, Mark C. Wallace, Daniel J. McNamara, James Boyle, Karen Keyes-Elstein, Lynette Franchimont, Nathalie James, Judith A. CA Autoimmunity Ctr Excellence TI The Clinical Efficacy and Safety of Baminercept, a Lymphotoxin-Beta Receptor Fusion Protein, in Primary Sjogren's Syndrome: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [St Clair, E. William] Duke Univ, Med, Durham, NC USA. [Baer, Alan N.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Noaiseh, Ghaith] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Parke, Anne] Univ Connecticut, Farmington, CT USA. [Coca, Andreea] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Utset, Tammy] Univ Chicago, Chicago, IL 60637 USA. [Genovese, Mark C.] Stanford Univ, Med Ctr, Div Rheumatol, Palo Alto, CA 94304 USA. [Wallace, Daniel J.] Cedars Sinai Med Ctr, West Hollywood, CA USA. [McNamara, James] NIAID, NIH, Bethesda, MD 20892 USA. [Boyle, Karen; Keyes-Elstein, Lynette] Rho Fed Syst Inc, Chapel Hill, NC USA. [Franchimont, Nathalie] Biogen Inc, Cambridge, MA 02142 USA. [James, Judith A.] OU, OMRF, Oklahoma City, OK USA. NR 0 TC 1 Z9 1 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 OCT PY 2015 VL 67 SU 10 MA 3203 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860204752 ER PT J AU Tiniakou, E Pinal-Fernandez, I Christopher-Stine, L Werner, J Lloyd, TE Paik, JJ Albayda, J Danoff, SK Mammen, A AF Tiniakou, Eleni Pinal-Fernandez, Iago Christopher-Stine, Lisa Werner, Jessie Lloyd, Thomas E. Paik, Julie J. Albayda, Jemima Danoff, Sonye K. Mammen, Andrew TI Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase Positive Myopathy Patients without Statin Exposure May Have a Progressive Disease That Worsens Despite Aggressive Immunosuppressive Therapy SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Tiniakou, Eleni] Johns Hopkins Univ, Rheumatol, Baltimore, MD USA. [Pinal-Fernandez, Iago] Univ Autonoma Barcelona, Vall DHebron Univ Hosp, Autoimmune Syst Dis Unit, E-08193 Barcelona, Spain. [Christopher-Stine, Lisa] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Werner, Jessie] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lloyd, Thomas E.] Johns Hopkins, Neurol, Baltimore, MD USA. [Paik, Julie J.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Albayda, Jemima] Johns Hopkins Univ, Sch Med, Rheumatol, Baltimore, MD USA. [Danoff, Sonye K.] Johns Hopkins Sch Med, Med Pulm, Baltimore, MD USA. [Mammen, Andrew] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 2364 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203765 ER PT J AU Tran, TM Hong, S Gill, T Bennett, J Sikora, K Colbert, RA AF Tran, Tri M. Hong, Sohee Gill, Tejpal Bennett, Joshua Sikora, Keith Colbert, Robert A. TI ERAP1 Deficiency Protects HLA-B27 Transgenic Rats from Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Tran, Tri M.; Hong, Sohee; Gill, Tejpal; Bennett, Joshua; Sikora, Keith] NIAMS, NIH, Bethesda, MD USA. [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 983 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202247 ER PT J AU van den Bosch, MH Blom, A Maeda, A Kilts, T van den Berg, W Lafeber, F van Lent, P Young, M van der Kraan, P AF van den Bosch, Martijn H. Blom, Arjen Maeda, Azusa Kilts, Tina van den Berg, Wim Lafeber, Floris van Lent, Peter Young, Marian van der Kraan, Peter TI WISP1 Aggravates Osteoarthritis By Modulation of TGF-beta Signaling and Positive Regulation of Canonical Wnt Signaling SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [van den Bosch, Martijn H.; Blom, Arjen; van den Berg, Wim; van Lent, Peter; van der Kraan, Peter] Radboud Univ Nijmegen, Med Ctr, Expt Rheumatol, NL-6525 ED Nijmegen, Netherlands. [Maeda, Azusa; Kilts, Tina; Young, Marian] NIDCR, NIH, Bethesda, MD USA. [Lafeber, Floris] Univ Med Ctr Utrecht, Rheumatol & Clin Immunol, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2015 VL 67 SU 10 MA 2008 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860203414 ER PT J AU Wang, RS Gabriel, S Ward, MM AF Wang, Runsheng Gabriel, Sherine Ward, Michael M. TI Progression of Patients with Non-Radiographic Axial Spondyloarthritis to Ankylosing Spondylitis: A Population-Based Cohort Study SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Wang, Runsheng; Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. [Gabriel, Sherine] Mayo Clin, Div Rheumatolo, Rochester, MN USA. [Gabriel, Sherine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 709 PG 3 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860201703 ER PT J AU Weller, M Gardner, M Bogus, Z Smith, M Astorri, E Michael, D Zheng, CY Burbelo, P Wilson, PA Lai, ZN Swaim, B Handelman, B Afione, S Bombardieri, M Chiorini, JA AF Weller, Melodie Gardner, Matthew Bogus, Zoe Smith, Michael Astorri, Elisa Michael, Drew Zheng, Changyu Burbelo, Peter Wilson, Paul A. Lai, Zhennan Swaim, Bill Handelman, Beverly Afione, Sandra Bombardieri, Michele Chiorini, John A. TI Detection of a Unique Viral Infection in Salivary Glands of Sjogren's Syndrome Patients and Viral-Mediated Recapitulation of Disease in Vivo SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Weller, Melodie; Gardner, Matthew; Bogus, Zoe; Smith, Michael; Michael, Drew; Zheng, Changyu; Lai, Zhennan; Swaim, Bill; Handelman, Beverly; Afione, Sandra; Chiorini, John A.] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Astorri, Elisa; Bombardieri, Michele] Queen Mary Univ London, William Harvey Res Inst, Ctr Expt Med & Rheumatol, London, England. [Burbelo, Peter] NIDCR, Clin Dent Res Core, NIH, Bethesda, MD USA. [Wilson, Paul A.] NIH, Natl Intramural Database, Div Enterprise & Custom Applicat, Ctr Informat Technol, Bethesda, MD 20892 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1358 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202619 ER PT J AU Wolfe, F Fitzcharles, MA Goldenberg, D Hauser, W Katz, RS Mease, PJ Russell, A Russell, J Walitt, B AF Wolfe, Frederick Fitzcharles, Mary-Ann Goldenberg, Don Haeuser, Winfried Katz, Robert S. Mease, Philip J. Russell, Anthony Russell, Jon Walitt, Brian TI A Comparison of Physician Based and Patient Based Criteria for the Diagnosis of Fibromyalgia SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Wolfe, Frederick] Natl Data Bank, Wichita, KS USA. [Fitzcharles, Mary-Ann] MGH, Montreal, PQ, Canada. [Goldenberg, Don] Newton Wellesley Hosp, Newton, MA USA. [Haeuser, Winfried] Tech Univ Munich, Dept Psychosomat Med & Psychotherapy, D-80290 Munich, Germany. [Katz, Robert S.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Mease, Philip J.] Swedish Med Ctr, Dept Rheumatol, Seattle, WA USA. [Mease, Philip J.] Univ Washington, Seattle, WA 98195 USA. [Russell, Anthony] Univ Alberta, Med, Edmonton, AB, Canada. [Russell, Jon] Fibromyalgia Res & Consulting, San Antonio, TX USA. [Walitt, Brian] NINR, NIH, Bethesda, DC 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 913 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202177 ER PT J AU Yin, HE Lai, ZN Cabrera-Perez, J Glenton, P Patel, A Swaim, W Zheng, CY Guimaro, M Afione, S Nguyen, C Nyberg, F Chiorini, JA AF Yin, Hongen Lai, Zhennan Cabrera-Perez, Javier Glenton, Patricia Patel, Ankur Swaim, William Zheng, Changyu Guimaro, Maria Afione, Sandra Cuong Nguyen Nyberg, Fred Chiorini, John A. TI Aquaporin Gene Therapy Corrects Bone Morphogenetic Protein 6 Associated Exocrine Gland Dysfunction in Mouse Model of Sjogren's Syndrome SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Yin, Hongen] NIDCR, NIH, Bethesda, MD USA. [Lai, Zhennan; Cabrera-Perez, Javier; Patel, Ankur; Swaim, William; Zheng, Changyu; Guimaro, Maria; Cuong Nguyen; Chiorini, John A.] NIDCR, Mptb, NIH, Bethesda, MD USA. [Glenton, Patricia] Univ Florida, Dept Pathol & Infect Dis, Gaineville, FL USA. [Afione, Sandra] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Nyberg, Fred] Uppsala Univ, Div Biol Res Drug Dependence, Dept Pharmaceut Biosci, Uppsala, MD, Sweden. 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1056 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202320 ER PT J AU Zhang, W Lin, W Chen, Y Yang, YJ Chen, H Wu, QJ Fei, YY Hu, CJ Li, YZ Zhang, X Zhao, Y Zhang, FC Zeng, XF Lipsky, PE AF Zhang, Wen Lin, Wei Chen, Yu Yang, Yunjiao Chen, Hua Wu, QingJun Fei, Yunyun Hu, Chaojun Li, Yongzhe Zhang, Xuan Zhao, Yan Zhang, Fengchun Zeng, Xiaofeng Lipsky, Peter E. TI CD19+CD24-CD38hi B-Cell Subset: A Potential Biomarker for IgG4-Related Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Zhang, Wen; Chen, Yu; Yang, Yunjiao; Chen, Hua; Wu, QingJun; Fei, Yunyun; Hu, Chaojun; Zhao, Yan; Zeng, Xiaofeng] Beijing Union Med Coll Hosp, Rheuamtol, Beijing, Peoples R China. [Zhang, Wen] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China. [Zhang, Wen] Peking Union Med Coll, Beijing 100021, Peoples R China. [Lin, Wei; Li, Yongzhe; Zhang, Xuan; Zhang, Fengchun] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Lipsky, Peter E.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 1102 PG 1 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202366 ER PT J AU Zhou, Q Wang, HY Schwartz, DM Stoffels, M Park, YH Zhang, Y Demirkaya, E Takeuchi, M Lyons, JJ Yu, XM Ouyang, C Ombrello, AK Stone, DL Hoffmann, P Jones, A Leavis, HL van Royen-Kerkhof, A Gul, A Ozen, S Siegel, R Gadina, M Chae, J Laxer, R Kastner, DL Aksentijevich, I AF Zhou, Qing Wang, Hongying Schwartz, Daniella M. Stoffels, Monique Park, Yong Hwan Zhang, Yuan Demirkaya, Erkan Takeuchi, Masaki Lyons, Jonathan J. Yu, Xiaomin Ouyang, Claudia Ombrello, Amanda K. Stone, Deborah L. Hoffmann, Patrycja Jones, Anne Leavis, Helen L. van Royen-Kerkhof, Annet Gul, Ahmet Ozen, Seza Siegel, Richard Gadina, Massimo Chae, JaeJin Laxer, Ronald Kastner, Daniel L. Aksentijevich, Ivona TI HA20: A Novel Autoinflammatory Disease Caused By Haploinsufficiency of A20, Encoded By TNFAIP3 SO ARTHRITIS & RHEUMATOLOGY LA English DT Meeting Abstract C1 [Zhou, Qing] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA. [Wang, Hongying; Park, Yong Hwan; Takeuchi, Masaki; Ombrello, Amanda K.; Stone, Deborah L.; Hoffmann, Patrycja; Jones, Anne; Chae, JaeJin; Kastner, Daniel L.; Aksentijevich, Ivona] NHGRI, Bethesda, MD 20892 USA. [Schwartz, Daniella M.] NIAMSD, Rheumatol Fellowship & Training Branch, Bethesda, MD 20892 USA. [Stoffels, Monique] NHGRI, NIH, Bethesda, MD 20892 USA. [Zhang, Yuan; Lyons, Jonathan J.; Yu, Xiaomin] NIAID, Bethesda, MD 20892 USA. [Demirkaya, Erkan] Gulhane Mil Med Acad, Pediat Rheumatol, FMF Arthrit Vasculitis & Orphan Dis Res Ctr FAVOR, Ankara, Turkey. [Ouyang, Claudia] NIAMSD, Bethesda, MD 20892 USA. [Leavis, Helen L.; van Royen-Kerkhof, Annet] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Gul, Ahmet] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey. [Ozen, Seza] Hacettepe Univ, Pediat Nephrol & Rheumatol, Ankara, Turkey. [Siegel, Richard] NIAMSD, NIH, Bethesda, MD 20892 USA. [Gadina, Massimo] NIAMS NIH, Bethesda, MD USA. [Laxer, Ronald] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. 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 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD OCT PY 2015 VL 67 SU 10 MA 899 PG 2 WC Rheumatology SC Rheumatology GA DE8BG UT WOS:000370860202164 ER PT J AU Edlund, MJ Pettiford, AG Hampton, J Forman-Hoffman, VL Ault, KL Colpe, LJ Hedden, SL AF Edlund, Mark J. Pettiford, Adrianne G. Hampton, Joel Forman-Hoffman, Valerie L. Ault, Kimberly L. Colpe, Lisa J. Hedden, Sarra L. TI Adolescents' Assessments of the Helpfulness of Treatment for Major Depression: Results From a National Survey SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PRACTICAL CLINICAL-TRIALS; PRIMARY-CARE; SATISFACTION; DISORDERS; THERAPY; YOUTH; PSYCHOTHERAPY; METAANALYSIS; PERFORMANCE AB Objective: The study investigated perceived helpfulness of counseling or medication in a national sample of adolescents with a major depressive episode. Methods: Secondary data analysis of the National Survey on Drug Use and Health was conducted. The sample comprised adolescents (ages 12-17) with a past-year major depressive episode who reported receiving either counseling and no medication (N = 2,000) or medication and counseling (N = 1,300) for depression in the past year. Adolescents who received counseling only evaluated the helpfulness of counseling, and adolescents who received medication and counseling evaluated the helpfulness of medication. Responses were analyzed by using descriptive statistics and ordered logistic regression models. Results: Among adolescents who received counseling only, 10% reported that counseling was extremely helpful, 22% that it helped a lot, 25% that it helped some, 24% that it helped a little, and 20% that it was not at all helpful. Among adolescents who received medication and counseling, 17% reported that medication was extremely helpful, 30% that it helped a lot, 22% that it helped somewhat, 16% that it helped a little, and 15% that it was not at all helpful. In adjusted models, adolescents with greater parental support and fewer than two delinquent behaviors in the past year were more likely to endorse treatment as helpful. Conclusions: About 32% to 47% of adolescents in the general population reported that depression treatment was extremely helpful or helped a lot. This is substantially lower than response rates in clinical trials. The reasons for these divergent findings merit further investigation. C1 [Edlund, Mark J.; Forman-Hoffman, Valerie L.] RTI Int, Behav & Urban Hlth Program, Res Triangle Pk, NC USA. [Pettiford, Adrianne G.] RTI Int, Children & Families Program, Res Triangle Pk, NC USA. [Hampton, Joel; Ault, Kimberly L.] RTI Int, Div Stat & Data Sci, Res Triangle Pk, NC USA. [Colpe, Lisa J.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Hedden, Sarra L.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. RP Edlund, MJ (reprint author), RTI Int, Behav & Urban Hlth Program, Res Triangle Pk, NC USA. EM medlund@rti.org FU National Institute of Mental Health; Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; [283-2010-0003C]; [0212800] FX This study was funded under contract 283-2010-0003C, project no. 0212800, which was supported by funding from the National Institute of Mental Health. The National Survey on Drug Use and Health is funded by the Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. NR 40 TC 0 Z9 0 U1 5 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2015 VL 66 IS 10 BP 1064 EP 1073 DI 10.1176/appi.ps.201400018 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE6ES UT WOS:000370727100015 PM 26073408 ER PT J AU Cutler, RG AF Cutler, Roy G. TI Coordinated cycling of calorie restriction, exercise, and pharmaceuticals to enhance molecular turnover and removal of age-related neurotoxins SO APPROACHES TO AGING CONTROL LA English DT Article DE AMPK; aging; antioxidant; autophagy; caffeine; fructose; urate oxidase; uric acid ID ACTIVATED PROTEIN-KINASE; URIC-ACID; OXIDATIVE STRESS; EVOLUTIONARY IMPLICATIONS; GLUCOSE-PRODUCTION; PHYSICAL-EXERCISE; MUSCLE-CELLS; FAT STORAGE; AUTOPHAGY; INHIBITION AB Molecular turnover is the balance between synthesis and degradation. The rate of molecular turnover has been shown to decrease with old age and concomitant accumulation of damaged molecules. The onset and progression of the major age-related neurodegenerative diseases has been linked to the accumulation of protein aggregates (e.g. Alzheimer's: beta-amyloid; Parkinson's: alpha-synuclein; Huntington's: Huntingtin; Amyotrophic lateral sclerosis (ALS): mutated SOD1). Researchers have been exploring the use of increasing the rate of molecular turnover to prevent and "clean up" the accumulation of aberrant disease causing molecules by activating catabolic pathways via intermittent fasting, exercise, and drugs aimed at activating autophagy (e.g. rapamycin). However, the often ignored but equally important requirement for increasing molecular renewal is the activation of anabolic pathways to synthesize new proteins, lipids, and carbohydrates. By exploring the connections between the oxidative/reduction control of AMP activated protein kinases (AMPK), autophagy and gluconeogenesis, we propose a protocol using a properly timed cycle approach of diet, exercise, and drugs to enhance the catabolic/anabolic phases of molecular turnover. C1 [Cutler, Roy G.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Cutler, RG (reprint author), Neurosci Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rcutler@nih.gov NR 56 TC 0 Z9 0 U1 5 U2 5 PU SPANISH SOC OF ANTI-AGING MED AND LONGEVITY-SEMAL PI SEVILLA PA COLEGIO OFICIAL DE MEDICOS DE SEVILLA AVDA. DE LA BORBOLLA, SEVILLA, 41013, SPAIN SN 2341-5401 EI 2341-538X J9 APPROACH AGING CONTR JI Approach. Aging Contr. PD OCT PY 2015 IS 19 BP 63 EP 72 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DE5HP UT WOS:000370662300008 ER PT J AU Cong, XM Henderson, WA Graf, J McGrath, JM AF Cong, Xiaomei Henderson, Wendy A. Graf, Joerg McGrath, Jacqueline M. TI Early Life Experience and Gut Microbiome The Brain-Gut-Microbiota Signaling System SO ADVANCES IN NEONATAL CARE LA English DT Article DE brain-gut-microbiota; early life experience; microbiome; neonates; stress ID INTESTINAL MICROBIOTA; PRETERM INFANTS; NECROTIZING ENTEROCOLITIS; MATERNAL SEPARATION; PREMATURE-INFANTS; AXIS DYSFUNCTION; STRESS-RESPONSE; BOWEL-SYNDROME; BEHAVIOR; HEALTH AB Background: Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short-and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. Purpose: The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. Conclusions: The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions. C1 [Cong, Xiaomei] Univ Connecticut, Sch Nursing, 231 Glenbrook Rd U4026, Storrs, CT 06269 USA. [Henderson, Wendy A.] NINR, Digest Disorder Unit, Biobehav Branch, NIH, Bethesda, MD 20892 USA. [Graf, Joerg] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT USA. [McGrath, Jacqueline M.] Univ Connecticut, Connecticut Childrens Med Ctr, Sch Nursing, Storrs, CT USA. RP Cong, XM (reprint author), Univ Connecticut, Sch Nursing, 231 Glenbrook Rd U4026, Storrs, CT 06269 USA. EM xiaomei.cong@uconn.edu OI Graf, Joerg/0000-0001-5320-2712; Henderson, Wendy/0000-0003-3924-7118 FU National Institute of Nursing Research of the National Institutes of Health [1K23NR014674-01] FX This publication was supported by the National Institute of Nursing Research of the National Institutes of Health under Award Number 1K23NR014674-01. NR 81 TC 5 Z9 5 U1 8 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1536-0903 EI 1536-0911 J9 ADV NEONAT CARE JI Adv. Neonatal Care PD OCT PY 2015 VL 15 IS 5 BP 314 EP 323 DI 10.1097/ANC.0000000000000191 PG 10 WC Nursing SC Nursing GA DD1YZ UT WOS:000369720700010 PM 26240939 ER PT J AU Ohta, Y Okabe, T Larmour, C Di Rocco, A Maijenburg, MW Phillips, A Speck, NA Wakitani, S Nakamura, T Yamada, Y Enomoto-Iwamoto, M Pacifici, M Iwamoto, M AF Ohta, Yoichi Okabe, Takahiro Larmour, Colleen Di Rocco, Agnese Maijenburg, Marijke W. Phillips, Amanda Speck, Nancy A. Wakitani, Shigeyuki Nakamura, Takashi Yamada, Yoshihiko Enomoto-Iwamoto, Motomi Pacifici, Maurizio Iwamoto, Masahiro TI Articular Cartilage Endurance and Resistance to Osteoarthritic Changes Require Transcription Factor Erg SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID HORMONE-RELATED PROTEIN; ENDOCHONDRAL BONE-FORMATION; GROWTH-PLATE CHONDROCYTE; HEMATOPOIETIC STEM-CELLS; PARATHYROID-HORMONE; MESSENGER-RNA; MOUSE LIMB; ETS-FAMILY; EXPRESSION; DIFFERENTIATION AB Objective. To determine whether and how the transcription factor Erg participates in the genesis, establishment, and maintenance of articular cartilage. Methods. Floxed Erg mice were mated with Gdf5-Cre mice to generate conditional mutants lacking Erg in their joints. Joints of mutant and control mice were subjected to morphologic and molecular characterization and also to experimental surgically induced osteoarthritis (OA). Gene expression, promoter reporter assays, and gain-and loss-of-function in vitro tests were used to characterize molecular mechanisms of Erg action. Results. Conditional Erg ablation did not elicit obvious changes in limb joint development and overall phenotype in juvenile mice. However, as mice aged, joints of mutant mice degenerated spontaneously and exhibited clear OA-like phenotypic defects. Joints in juvenile mutant mice were more sensitive to surgically induced OA and became defective sooner than operated joints in control mice. Global gene expression data and other studies identified parathyroid hormone-related protein (PTHrP) and lubricin as possible downstream effectors and mediators of Erg action in articular chondrocytes. Reporter assays using control and mutated promoter-enhancer constructs indicated that Erg acted on Ets DNA binding sites to stimulate PTHrP expression. Erg was up-regulated in severely affected areas in human OA articular cartilage but remained barely appreciable in areas of less affected cartilage. Conclusion. The study shows for the first time that Erg is a critical molecular regulator of the endurance of articular cartilage during postnatal life and that Erg can mitigate spontaneous and experimental OA. Erg appears to do this through regulating expression of PTHrP and lubricin, factors known for their protective roles in joints. C1 [Ohta, Yoichi] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ohta, Yoichi] Osaka City Univ, Grad Sch Med, Osaka 558, Japan. [Okabe, Takahiro] Itabashi Chuo Gen Hosp, Tokyo, Japan. [Larmour, Colleen; Di Rocco, Agnese; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio; Iwamoto, Masahiro] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Maijenburg, Marijke W.; Phillips, Amanda; Speck, Nancy A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wakitani, Shigeyuki] Hiroshima Univ, Grad Sch Biomed Sci, Hiroshima, Japan. [Nakamura, Takashi] Tohoku Univ, Grad Sch Dent, Sendai, Miyagi 980, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Iwamoto, M (reprint author), Childrens Hosp Philadelphia, Div Orthopaed Surg, 3615 Civ Ctr Blvd,ARC Suite 902, Philadelphia, PA 19104 USA. EM iwamotom@email.chop.edu RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 FU Japan Orthopaedics and Traumatology Foundation [213]; NIH [R01-AR-062908, R01-AR-046000] FX Supported by the Japan Orthopaedics and Traumatology Foundation (grant 213 to Dr. Okabe) and the NIH (grant R01-AR-062908 to Drs. Enomoto-Iwamoto and Pacifici and grant R01-AR-046000 to Drs. Pacifici and Iwamoto). NR 48 TC 9 Z9 9 U1 3 U2 8 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 OCT PY 2015 VL 67 IS 10 BP 2679 EP 2690 DI 10.1002/art.39243 PG 12 WC Rheumatology SC Rheumatology GA DD3LJ UT WOS:000369823400012 PM 26097038 ER PT J AU Rai, SK Mukherjee, AK AF Rai, Sudhir K. Mukherjee, Ashis Kumar TI Optimization for production of liquid nitrogen fertilizer from the degradation of chicken feather by iron-oxide (Fe3O4) magnetic nanoparticles coupled beta-keratinase SO BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY LA English DT Article DE beta-keratinase; Enzyme immobilization; Iron-oxide magnetic nanoparticle; Poultry waste management; Organic fertilizer ID ALKALINE PROTEASE PRODUCTION; BACILLUS-LICHENIFORMIS; KERATINOLYTIC METALLOPROTEASE; SERINE-PROTEASE; NORTHEAST INDIA; SP NOV.; PURIFICATION; SUBTILIS; IMMOBILIZATION; ENZYME AB There is an escalating demand for balancing crop yields with a reduction in the environmental impacts caused by synthetic fertilizers, and focusing on sustainable agricultural practice using organic fertilizers high in nitrogen and increased soil water retention capability. The current study demonstrates a significantly improved chicken-feather hydrolyzate prepared by Bacillus licheniformis AS-S24-I beta-keratinase coupled iron-oxide magnetic nanoparticles. Biochemical and proteomic characterization suggests alkarnase as a serine protease in nature with broad pH stability as well as incubation temperature. The Scanning Electron Microscope (SEM) study reveals that iron-oxide (Fe3O4) magnetic nanoparticles coupled beta-keratinase can degrade 80-93% of chicken-feather keratin post 48 h of incubation. Chicken feather hydrolyzate demonstrated the release of six volatile compounds post treated with iron-oxide (Fe3O4) magnetic nanoparticles coupled beta-keratinase via Gas Chromatography-Mass Spectrophotometry (GC-MS) and matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) analyzes, respectively. The release of low volatile compounds post degradation recommended that it could be a sustainable method of eco-friendly organic fertilization. The results of the physiochemical analysis suggested improved nitrogen and amino acid levels indicating that chicken-feather hydrolyzate was a good organic fertilizer source. Filtered sterilized chicken-feather hydrolyzate revealed a significant increase in the length and growth of Bengal gram seed germination, as well a rise in the soil microbial population. Thus, the present study offers significant biotechnological applications of chicken-feather hydrolyzate, which could serve as a cheap source of liquid organic fertilizer. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Rai, Sudhir K.; Mukherjee, Ashis Kumar] Tezpur Univ, Sch Sci & Technol, Dept Mol Biol & Biotechnol, Microbial Biotechnol & Prot Res Lab, Tezpur 784028, Assam, India. [Rai, Sudhir K.] NICHD, Sect Eukaryot Transposable Elements, NIH, Bethesda, MD 20892 USA. [Mukherjee, Ashis Kumar] Univ No Colorado, Sch Biol Sci, Greeley, CO 80639 USA. RP Rai, SK (reprint author), NICHD, Sect Eukaryot Transposable Elements, NIH, Bethesda, MD 20892 USA. EM raisk@mail.nih.gov NR 61 TC 2 Z9 2 U1 4 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1878-8181 J9 BIOCATAL AGRIC BIOTE JI Biocatal. Agric. Biotechnol. PD OCT PY 2015 VL 4 IS 4 BP 632 EP 644 DI 10.1016/j.bcab.2015.07.002 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DC4GS UT WOS:000369179400030 ER PT J AU Chang, K Merideth, MA Stratton, P AF Chang, Katherine Merideth, Melissa A. Stratton, Pamela TI Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID MEDROXYPROGESTERONE ACETATE; FERTILITY PRESERVATION; ORAL-CONTRACEPTIVES; SEVERE MENORRHAGIA; BREAST-CANCER; THROMBOCYTOPENIA; CHEMOTHERAPY; PREVENTION; WOMEN; PROTECTION AB There is a growing population of women who have or will undergo hematopoietic stem cell transplant for a variety of malignant and benign conditions. Gynecologists play an important role in addressing the gynecologic and reproductive health concerns for these women throughout the transplant process. As women undergo cell transplantation, they should avoid becoming pregnant and are at risk of uterine bleeding. Thus, counseling about and implementing hormonal treatments such as gonadotropin-releasing hormone agonists, combined hormonal contraceptives, and progestin-only methods help to achieve therapeutic amenorrhea and can serve as contraception during the peritransplant period. In this commentary, we summarize the timing, risks, and benefits of the hormonal options just before, during, and for the year after hematopoietic stem cell transplantation. C1 NW Mem Hosp, Dept Obstet & Gynecol, Chicago, IL 60611 USA. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bethesda, MD USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD USA. EM ps79c@nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 21 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2015 VL 126 IS 4 BP 778 EP 783 DI 10.1097/AOG.0000000000001031 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD0VD UT WOS:000369637500015 PM 26348182 ER PT J AU Fairhurst, RM AF Fairhurst, Rick M. TI Understanding artemisinin-resistant malaria: what a difference a year makes SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE artemisinin; parasite kelch protein; malaria; Plasmodium falciparum; resistance ID PLASMODIUM-FALCIPARUM MALARIA; CHINA-MYANMAR BORDER; SUB-SAHARAN AFRICA; PARASITE CLEARANCE; DIHYDROARTEMISININ-PIPERAQUINE; WESTERN CAMBODIA; K13 PROPELLER; IN-VITRO; K13-PROPELLER POLYMORPHISMS; MULTIDRUG-RESISTANCE AB Purpose of review The emergence of artemisinin resistance in Southeast Asia (SEA), where artemisinin combination therapies (ACTs) are beginning to fail, threatens global endeavors to control and eliminate Plasmodium falciparum malaria. Future efforts to prevent the spread of this calamity to Africa will benefit from last year's tremendous progress in understanding artemisinin resistance. Recent findings Multiple international collaborations have established that artemisinin resistance is associated with slow parasite clearance in patients, increased survival of early-ring-stage parasites in vitro, single-nucleotide polymorphisms (SNPs) in the parasite's kelch protein gene (K13), parasite 'founder' populations sharing a genetic background of four additional SNPs, parasite transcriptional profiles reflecting an 'unfolded protein response' and decelerated parasite development, and elevated parasite phosphatidylinositol-3-kinase activity. In Western Cambodia, where the K13 C580Y mutation is approaching fixation, the frontline ACT is failing to cure nearly half of patients, likely due to partner drug resistance. In Africa, where dozens of K13 mutations have been detected at low frequency, there is no evidence yet of artemisinin resistance. Summary In SEA, clinical and epidemiological investigations are urgently needed to stop the further spread of artemisinin resistance, monitor the efficacy of ACTs where K13 mutations are prevalent, identify currently-available drug regimens that cure ACT failures, and rapidly advance new antimalarial compounds through preclinical studies and clinical trials. C1 [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20854 USA. RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10A, Rockville, MD 20854 USA. EM rfairhurst@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX I am funded by the Intramural Research Program of the NIAID, NIH. NR 50 TC 24 Z9 25 U1 3 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0951-7375 EI 1473-6527 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 2015 VL 28 IS 5 BP 417 EP 425 DI 10.1097/QCO.0000000000000199 PG 9 WC Infectious Diseases SC Infectious Diseases GA DC7UF UT WOS:000369425200003 PM 26237549 ER PT J AU Burns, KM Pemberton, VL Pearson, GD AF Burns, Kristin M. Pemberton, Victoria L. Pearson, Gail D. TI The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE congenital heart disease; pediatric cardiology; research ID CONVERTING ENZYME-INHIBITION; RANDOMIZED CLINICAL-TRIAL; SINGLE-VENTRICLE; NORWOOD PROCEDURE; DESIGN; RATIONALE; CHILDREN; INFANTS; EXPERIENCE; LOSARTAN AB Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. C1 [Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Pearson, GD (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8132, Bethesda, MD 20892 USA. EM pearsong@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 19 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD OCT PY 2015 VL 27 IS 5 BP 548 EP 554 DI 10.1097/MOP.0000000000000260 PG 7 WC Pediatrics SC Pediatrics GA DC7YD UT WOS:000369436000002 PM 26196261 ER PT J AU Farhat, T AF Farhat, Tilda TI Stigma, obesity and adolescent risk behaviors: current research and future directions SO CURRENT OPINION IN PSYCHOLOGY LA English DT Article ID BODY-MASS INDEX; WEIGHT STATUS; SUBSTANCE USE; CHILDHOOD OBESITY; DECISION-MAKING; SEXUAL-BEHAVIOR; HEALTH; DISCRIMINATION; PREVALENCE; OVERWEIGHT AB Adolescents are particularly vulnerable to risk behaviors as, in this life stage, they are experiencing intense physical, psychological and social changes. Adolescents who are overweight/obese, but particularly those who perceive themselves as such, are more likely to engage in risk behaviors than those who are, or perceive, themselves of normal-weight. Weight stigma and discrimination may contribute to this association as they reinforce poor body image and create intense stress. Stress is associated with poor emotion regulation, more impulsive, contextually-determined, and less rational decision-making, leading to greater engagement in risk behaviors. However, pathways from weight stigma/discrimination to risk behavior may be moderated by adolescents' social networks. This review provides a conceptual model and empirical evidence to illustrate the proposed pathways from weight stigma and discrimination to risk behaviors. Public health implications and future research directions are also discussed. C1 [Farhat, Tilda] Natl Inst Minor Hlth & Hlth Dispar, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. RP Farhat, T (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM tilda.farhat@nih.gov FU Intramural NIH HHS [Z99 MD999999] NR 49 TC 2 Z9 2 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-250X J9 CURR OPIN PSYCHOL JI Curr. Opin. Psychol. PD OCT PY 2015 VL 5 BP 56 EP 66 DI 10.1016/j.copsyc.2015.03.021 PG 11 WC Psychology, Multidisciplinary SC Psychology GA DC9XL UT WOS:000369574800011 PM 26086032 ER PT J AU Riley, WT Serrano, KJ Nilsen, W Atienza, AA AF Riley, William T. Serrano, Katrina J. Nilsen, Wendy Atienza, Audie A. TI Mobile and wireless technologies in health behavior and the potential for intensively adaptive interventions SO CURRENT OPINION IN PSYCHOLOGY LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; TELETREATMENT SERVICE; PHYSICAL-ACTIVITY; SYSTEMS; WEIGHT AB Recent advances in mobile and wireless technologies have made real-time assessments of health behaviors and their influences possible with minimal respondent burden. These tech-enabled real-time assessments provide the basis for intensively adaptive interventions (IAIs). Evidence of such studies that adjust interventions based on real-time inputs is beginning to emerge. Although IAIs are promising, the development of intensively adaptive algorithms generate new research questions, and the intensive longitudinal data produced by IAIs require new methodologies and analytic approaches. Research considerations and future directions for IAIs in health behavior research are provided. C1 [Riley, William T.; Serrano, Katrina J.; Atienza, Audie A.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Sci Res & Technol Branch, Bethesda, MD 20892 USA. [Nilsen, Wendy] NIH, Off Director, Off Behav & Social Sci Res, Bethesda, MD USA. RP Riley, WT (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Sci Res & Technol Branch, Bethesda, MD 20892 USA. EM wiriley@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 36 TC 11 Z9 11 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-250X J9 CURR OPIN PSYCHOL JI Curr. Opin. Psychol. PD OCT PY 2015 VL 5 BP 67 EP 71 DI 10.1016/j.copsyc.2015.03.024 PG 5 WC Psychology, Multidisciplinary SC Psychology GA DC9XL UT WOS:000369574800012 PM 26086033 ER PT J AU Ferrer, RA Klein, WMP AF Ferrer, Rebecca A. Klein, William M. P. TI Risk perceptions and health behavior SO CURRENT OPINION IN PSYCHOLOGY LA English DT Article ID PROTECTION MOTIVATION THEORY; UNREALISTIC OPTIMISM; DECISION-MAKING; CANCER WORRY; JUDGMENT; METAANALYSIS; VACCINATION; MODEL; PROBABILITY; ASSOCIATION AB Risk perceptions - or an individual's perceived susceptibility to a threat - are a key component of many health behavior change theories. Risk perceptions are often targeted in health behavior change interventions, and recent meta-analytic evidence suggests that interventions that successfully engage and change risk perceptions produce subsequent increases in health behaviors. Here, we review recent literature on risk perceptions and health behavior, including research on the formation of risk perceptions, types of risk perceptions (including deliberative, affective, and experiential), accuracy of risk perceptions, and associations and interactions among types of risk perceptions. Taken together, existing research suggests that disease risk perceptions are a critical determinant of health behavior, although the nature of the association among risk perceptions and health behavior may depend on the profile of different types of risk perceptions and the accuracy of such perceptions. C1 [Ferrer, Rebecca A.; Klein, William M. P.] NCI, 9609 Med Ctr Dr, Rockville, MD 20852 USA. RP Ferrer, RA (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20852 USA. EM ferrerra@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 55 TC 4 Z9 4 U1 6 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-250X J9 CURR OPIN PSYCHOL JI Curr. Opin. Psychol. PD OCT PY 2015 VL 5 BP 85 EP 89 DI 10.1016/j.copsyc.2015.03.012 PG 5 WC Psychology, Multidisciplinary SC Psychology GA DC9XL UT WOS:000369574800015 PM 26258160 ER PT J AU Stout, NL Harrington, SE Pfalzer, LA Fisher, MI AF Stout, Nicole L. Harrington, Shana E. Pfalzer, Lucinda A. Fisher, Mary Insana TI Breast Cancer Rehabilitation Clinical Examination and Outcomes Assessment SO TOPICS IN GERIATRIC REHABILITATION LA English DT Article DE breast cancer; clinical measurement; functional outcomes; rehabilitation ID PROSPECTIVE SURVEILLANCE MODEL; INDUCED PERIPHERAL NEUROPATHY; LYMPH-NODE DISSECTION; FOLLOW-UP; AROMATASE INHIBITORS; RADICAL-MASTECTOMY; CONTROLLED-TRIAL; RISK-FACTORS; BONE LOSS; SURVIVORS AB Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of the clinical measurement tools best suited for examination and assessment of breast cancer-related impairments and disability. This article aims to provide a comprehensive overview of the evidence supporting the use of various clinical measurement tools for the breast cancer population and highlights the implementation of rehabilitation examination and assessment along the continuum of disease treatment. C1 [Stout, Nicole L.] NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Off Strateg Res, Bldg 10, Bethesda, MD 20892 USA. [Harrington, Shana E.] Creighton Univ, Dept Phys Therapy, Omaha, NE 68178 USA. [Pfalzer, Lucinda A.] Univ Michigan Flint, Doctor Phys Therapy Program, Dayton, OH USA. [Fisher, Mary Insana] Univ Dayton, Dept Phys Therapy, Dayton, OH 45469 USA. RP Stout, NL (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Off Strateg Res, Bldg 10, Bethesda, MD 20892 USA. EM nicole@lexicamed.com NR 66 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0882-7524 EI 1550-2414 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD OCT-DEC PY 2015 VL 31 IS 4 BP 258 EP 272 DI 10.1097/TGR.0000000000000082 PG 15 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA DD0JY UT WOS:000369607400006 ER PT J AU Yoneda, M Molinolo, AA Ward, JM Kimura, S Goodlad, RA AF Yoneda, Mitsuhiro Molinolo, Alfredo A. Ward, Jerrold M. Kimura, Shioko Goodlad, Robert A. TI A Simple Device to Rapidly Prepare Whole Mounts of the Mouse Intestine SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 104; Mouse; murine; intestine; gastrointestinal; colon; whole mount; en face; aberrant; crypts; neoplasia; cancer; colitis; polyp ID CELL-PROLIFERATION; CRYPT FISSION; GROWTH-FACTOR; RATS; MICE; DIMETHYLHYDRAZINE; CANCER; COLON; MODEL; FOCI AB Preparing whole mounts of the mouse small intestine and colon for subsequent analysis or quantification can be time consuming and difficult. We describe the use of a simple device to cut and 'roll' mouse intestines to rapidly prepare whole mount preparations of superior and uniform quality to that which can be achieved by hand. The device comprises a base that holds 4 stainless steel rods and a top, which acts a cutting guide. The rods are inserted into the lumen of the small intestine [divided into thirds] and the colon. The rods and samples are then placed over a piece of filter paper or card into the holding slots in the base of the device. The top of the device is then positioned and serves as a cutting guide. The two angled sections in the center of the top piece are used to guide a knife or scalpel and cut the intestines longitudinally on the top of the rods. Once the intestinal sections have been cut, the top is removed and the card, tissue and rods gently removed from the device and placed on the bench. The rods are then gently rolled sideways to flatten and stick the intestinal segments onto the underlying piece of filter paper or card. The final preparation can then be examined or fixed and stored for later analysis. The preparations are invaluable for the study of intestinal changes in normal or genetically modified mouse models. The preparations have been used for the study and quantification of the effects of inflammation (colitis), damage, pre-cancerous lesions (aberrant crypt foci (ACFs) and mucin depleted foci (MDFs)) and polyps or tumors. C1 [Yoneda, Mitsuhiro; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Molinolo, Alfredo A.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Washington, DC USA. [Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA. [Goodlad, Robert A.] Imperial Coll, Hammersmith Hosp, Ctr Pathol, London, England. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov; r.goodlad@imperial.ac.uk NR 12 TC 0 Z9 0 U1 2 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD OCT PY 2015 IS 104 AR e53042 DI 10.3791/53042 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SB UT WOS:000368572800023 PM 26556642 ER PT J AU Fowler, SL Platz, EA Diener-West, M Hokenmaier, S Truss, M Lewis, C Kanarek, NF AF Fowler, Stephanie L. Platz, Elizabeth A. Diener-West, Marie Hokenmaier, Sarah Truss, Meredith Lewis, Courtney Kanarek, Norma F. TI Comparing the Maryland Comprehensive Cancer Control Plan With Federal Cancer Prevention and Control Recommendations SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction Since the introduction of the Affordable Care Act (ACA) in 2012, 11 million more Americans now have access to preventive services via health care coverage. Several prevention-related recommendations issued by the US Preventive Services Task Force (USPSTF), Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP) are covered under the ACA. State cancer plans often provide prevention strategies, but whether these strategies correspond to federal evidence-based recommendations is unclear. The objective of this article is to assess whether federal evidence-based recommendations, including those covered under the ACA, are included in the Maryland Comprehensive Cancer Control Plan (MCCCP). Methods A total of 19 federal recommendations pertaining to cancer prevention and control were identified. Inclusion of federal cancer-related recommendations by USPSTF, CDC, and ACIP in the MCCCP's goals, objectives, and strategies was examined. Results Nine of the federal recommendations were issued after the MCCCP's publication. MCCCP recommendations corresponded completely with 4 federal recommendations and corresponded only partially with 3. Reasons for partial correspondence included specification of less restrictive at-risk populations or different intervention implementers. Three federal recommendations were not mentioned in the MCCCP's goals, objectives, and strategies. Conclusion Many cancer-related federal recommendations were released after the MCCCP's publication and therefore do not appear in the most current version. We recommend that the results of this analysis be considered in the update of the MCCCP. Our findings underscore the need for a periodic scan for changes to federal recommendations and for adjusting state policies and programs to correspond with federal recommendations, as appropriate for Marylanders. C1 [Fowler, Stephanie L.] NCI, NIH, 9609 Med Ctr Dr,RM 3E-542, Bethesda, MD 20892 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Platz, Elizabeth A.; Kanarek, Norma F.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Diener-West, Marie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Hokenmaier, Sarah; Truss, Meredith; Lewis, Courtney] Maryland Dept Hlth & Mental Hyg, Ctr Canc Prevent & Control, Baltimore, MD USA. [Kanarek, Norma F.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. RP Fowler, SL (reprint author), NCI, NIH, 9609 Med Ctr Dr,RM 3E-542, Bethesda, MD 20892 USA. EM stephanie.fowler@nih.gov FU Maryland Cigarette Restitution Fund at Johns Hopkins; National Cancer Institute (NCI) [P30 CA006973]; NCI Cancer Prevention Fellowship Program FX This work was supported by the Maryland Cigarette Restitution Fund at Johns Hopkins, a Cancer Center Support Grant from the National Cancer Institute (NCI) P30 CA006973, and the NCI Cancer Prevention Fellowship Program. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the Maryland DHMH or the NCI. We also thank Dr Irene Prabhu-Das, NCI, for her invaluable feedback on the revision of the manuscript. NR 14 TC 0 Z9 0 U1 1 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD OCT PY 2015 VL 12 AR E163 DI 10.5888/pcd12.150008 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB6ZY UT WOS:000368665400001 PM 26425867 ER PT J AU Jacobs, P Ang, A Hillhouse, MP Saxon, AJ Nielsen, S Wakim, PG Mai, BE Mooney, LJ Potter, JS Blaine, JD AF Jacobs, Petra Ang, Alfonso Hillhouse, Maureen P. Saxon, Andrew J. Nielsen, Suzanne Wakim, Paul G. Mai, Barbara E. Mooney, Larissa J. Potter, Jennifer S. Blaine, Jack D. TI Treatment Outcomes in Opioid Dependent Patients With Different Buprenorphine/Naloxone Induction Dosing Patterns and Trajectories SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MAINTENANCE TREATMENT; METHADONE; RETENTION; TRIAL; EXPERIENCE; PREDICTORS; HEALTH AB Background and Objectives: Induction is a crucial period of opioid addiction treatment. This study aimed to identify buprenorphine/naloxone (BUP) induction patterns and examine their association with outcomes (opioid use, retention, and related adverse events [AEs]). Methods: The secondary analysis of a study of opioid-dependent adults seeking treatment in eight treatment settings included 740 participants inducted on BUP with flexible dosing. Results: Latent class analysis models detected six distinctive induction trajectories: bup1-started and remained on low; bup2started low, shifted slowly to moderate; bup3-started low, shifted quickly to moderate; bup4-started high, shifted to low; bup5-started and remained on moderate; bup6-started moderate, shifted to high dose (Fig. 1). Baseline characteristics, including Clinical Opioid Withdrawal Scale (COWS), were important predictors of retention. When controlled for the baseline characteristics, bup6 participants were three times less likely to drop out the first 7 days than bup1 participants (adjusted hazard ratio (aHR) = .28, p = .03). Opioid use and AEs were similar across trajectories. Participants on >= 16 mg BUP compared to those on < 16 mg at Day 28 were less likely to drop out (aHR = .013, p = .001) and less likely to have AEs during the first 28 days (aOR = .57, p = .03). Discussion and Conclusions: BUP induction dosing was guided by an objective measure of opioid withdrawal. Participants with higher baseline COWS whose BUP doses were raised more quickly were less likely to drop out in the first 7 days than those whose doses were raised slower. Scientific Significance: This study supports the use of an objective measure of opioid withdrawal (COWS) during BUP induction to improve retention early in treatment. C1 [Jacobs, Petra; Blaine, Jack D.] EMMES Corp, Rockville, MD USA. [Ang, Alfonso; Hillhouse, Maureen P.; Mooney, Larissa J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care, Seattle, WA USA. [Nielsen, Suzanne] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia. [Wakim, Paul G.] NIDA, Ctr Clin Trials Network, Rockville, MD USA. [Mai, Barbara E.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Potter, Jennifer S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Jacobs, P (reprint author), EMMES Corp, Rockville, MD USA. EM petraejacobs@gmail.com OI Nielsen, Suzanne/0000-0001-5341-1055 FU National Institute on Drug Abuse; Clinical Trials Network: Pacific Northwest Node, NIH/NIDA [5 U10 DA013714-08]; NHMRC [1013803] FX The original START study was funded by the National Institute on Drug Abuse, where the buprenorphine/naloxone for START was provided by Reckitt Benckiser Pharmaceuticals. The authors of this secondary analysis collaborated on the implementation of START and received the dataset. Dr. Saxon has grant support from the Clinical Trials Network: Pacific Northwest Node. 5 U10 DA013714-08, NIH/NIDA, served on the Pharmaceutical, Scientific Advisory Board, Alkermes, Inc. and has been a presenter for Reckitt-Benckiser, Inc. He has no publishing constraints. Dr. Nielsen is supported by a NHMRC Research Fellowship (#1013803), has been an investigator on united educational grants from Reckitt-Benckiser, completely unrelated to this work, no publishing constraints. Dr. Blaine has been a treatment advocate for Reckitt Benckiser Pharmaceuticals, Inc., with no publishing constraints. The authors alone are responsible for the content and writing of this paper. NR 23 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD OCT PY 2015 VL 24 IS 7 BP 667 EP 675 DI 10.1111/ajad.12288 PG 9 WC Substance Abuse SC Substance Abuse GA DB4SD UT WOS:000368502500014 PM 26400835 ER PT J AU Porat-Shliom, N Vitale-Cross, L Jarnik, M Van Itallie, C Anderson, J Gutkind, JS Weigert, R Arias, IM AF Porat-Shliom, Natalie Vitale-Cross, Lynn Jarnik, Michal Van Itallie, Christina Anderson, James Gutkind, J. Silvio Weigert, Roberto Arias, Irwin M. TI LKB1 regulates hepatocellular tight junction distribution and function in vivo SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Porat-Shliom, Natalie; Vitale-Cross, Lynn; Jarnik, Michal; Van Itallie, Christina; Anderson, James; Gutkind, J. Silvio; Weigert, Roberto; Arias, Irwin M.] NIH, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 20 BP 217A EP 217A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400021 ER PT J AU Wilson, E Kattakuzhy, S Sims, Z McLaughlin, M Price, A Mo, HM Osinusi, A Masur, H Kohli, A Kottilil, S AF Wilson, Eleanor Kattakuzhy, Sarah Sims, Zayani McLaughlin, Mary Price, Angie Mo, Hongmei Osinusi, Anu Masur, Henry Kohli, Anita Kottilil, Shyam TI Highly Successful Retreatment with Ledipasvir (LDV) and Sofosbuvir (SOF) in HCV GT-1 Patients Who Failed Initial Short Course Therapy with Combination DAA Regimens (NIH SYNERGY Trial) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wilson, Eleanor; Kattakuzhy, Sarah; Price, Angie; Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Infect Dis, Rockville, MD USA. [Wilson, Eleanor; Sims, Zayani; Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [McLaughlin, Mary] NIAID, NIH, Bethesda, MD 20892 USA. [Mo, Hongmei; Osinusi, Anu] Gilead Sci Inc, Foster City, CA 94404 USA. [Kohli, Anita] St Josephs Hosp, Hepatol, Phoenix, AZ USA. [Kohli, Anita] Maricopa Cty Gen Hosp, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 92 BP 255A EP 255A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400093 ER PT J AU Xu, MJ Cai, Y Wang, H Altamirano, JT Odena, G Gonzalez, FJ Bataller, R Gao, B AF Xu, Ming-Jiang Cai, Yan Wang, Hua Altamirano, Jose T. Odena, Gemma Gonzalez, Frank J. Bataller, Ramon Gao, Bin TI Fat-specific Protein 27/CIDEC Promotes Alcoholic Steatohepatitis in Mice and Humans SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Xu, Ming-Jiang; Cai, Yan; Wang, Hua; Gao, Bin] NIAAA, NIH, Rockville, MD 20852 USA. [Altamirano, Jose T.] Vall dHebron Inst Recerca, Barcelona, Spain. [Odena, Gemma; Bataller, Ramon] Univ N Carolina, Chapel Hill, NC USA. [Gonzalez, Frank J.] NIH, Bethesda, MD 20892 USA. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 110 BP 265A EP 266A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400111 ER PT J AU Park, O Oh, Y Swierczewska, M Park, JS Hanes, J Pomper, M Gao, B Lee, S AF Park, Ogyi Oh, Yumin Swierczewska, Magdalena Park, Jong Sung Hanes, Justin Pomper, Martin Gao, Bin Lee, Seulki TI PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by targeting activated hepatic stellate cells SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Park, Ogyi; Oh, Yumin; Swierczewska, Magdalena; Park, Jong Sung; Pomper, Martin; Lee, Seulki] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Park, Ogyi; Oh, Yumin; Swierczewska, Magdalena; Park, Jong Sung; Hanes, Justin; Lee, Seulki] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21205 USA. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 115 BP 268A EP 268A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401001 ER PT J AU Park, O Oh, Y Swierczewska, M Park, JS Hanes, J Pomper, M Gao, B Lee, S AF Park, Ogyi Oh, Yumin Swierczewska, Magdalena Park, Jong Sung Hanes, Justin Pomper, Martin Gao, Bin Lee, Seulki TI PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by targeting activated hepatic stellate cells SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Park, Ogyi; Oh, Yumin; Swierczewska, Magdalena; Park, Jong Sung; Pomper, Martin; Lee, Seulki] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Park, Ogyi; Oh, Yumin; Swierczewska, Magdalena; Park, Jong Sung; Hanes, Justin; Lee, Seulki] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21205 USA. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 115 BP 268A EP 268A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375400116 ER PT J AU Di Bisceglie, AM Lombardero, M Teckman, J Roberts, LR Janssen, HL Belle, SH Hoofnagle, JH AF Di Bisceglie, Adrian M. Lombardero, Manuel Teckman, Jeffrey Roberts, Lewis R. Janssen, Harry L. Belle, Steven H. Hoofnagle, Jay H. TI Objective Determination of Hepatitis B Phenotype using Biochemical and Serological Markers: Immune Tolerant, Immune Active, Inactive Carrier and Indeterminant Status SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Di Bisceglie, Adrian M.; Teckman, Jeffrey] St Louis Univ, St Louis, MO 63103 USA. [Lombardero, Manuel; Belle, Steven H.] Univ Pittsburgh, Pittsburgh, PA USA. [Roberts, Lewis R.] Mayo Clin, Rochester, MN USA. [Janssen, Harry L.] Univ Toronto, Toronto, ON, Canada. [Hoofnagle, Jay H.] NIH, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 121 BP 271A EP 271A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401007 ER PT J AU Ng, VL Sorensen, LG Alonso, EM Fredericks, EM Ye, W Karpen, SJ Shneider, B Bezerra, JA Molleston, JP Murray, KF Rosenthal, P Wang, KS Loomes, KM Hertel, PM Kerkar, N Schwarz, KB Turmelle, YP Haber, BA Sherker, AH Magee, JC Sokol, RJ AF Ng, Vicky L. Sorensen, Lisa G. Alonso, Estella M. Fredericks, Emily M. Ye, Wen Karpen, Saul J. Shneider, Benjamin Bezerra, Jorge A. Molleston, Jean P. Murray, Karen F. Rosenthal, Philip Wang, Kasper S. Loomes, Kathleen M. Hertel, Paula M. Kerkar, Nanda Schwarz, Kathleen B. Turmelle, Yumirle P. Haber, Barbara A. Sherker, Averell H. Magee, John C. Sokol, Ronald J. TI Neurodevelopmental Outcomes in Patients with Biliary Atresia and Native Liver at Ages 1 and 2 Years: Results from ChiLDReN SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ng, Vicky L.] Univ Toronto, Hosp Sick Children, Div Pediat Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada. [Alonso, Estella M.] Ann & Robert H Lurie Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Chicago, IL USA. [Fredericks, Emily M.] Univ Michigan, Div Child Behav Hlth, Ann Arbor, MI 48109 USA. [Fredericks, Emily M.] CS Mott Childrens Hosp, Ann Arbor, MI USA. [Bezerra, Jorge A.] Cincinnat Childrens Hosp Med, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH USA. [Molleston, Jean P.] Indiana Univ Sch Med, Riley Hosp Children, Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA. [Murray, Karen F.] Univ Washington, Med Ctr, Seattle Childrens, Div Gastroenterol & Hepatol, Seattle, WA 98195 USA. [Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, Div Gastroenterol Hepatol & Nutr, San Francisco, CA USA. [Loomes, Kathleen M.] Childrens Hosp Philadelphia, Pediat Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Hertel, Paula M.] Baylor Coll Med, Houston, TX 77030 USA. [Schwarz, Kathleen B.] Johns Hopkins Sch Med, Baltimore, MD USA. [Turmelle, Yumirle P.] Washington Univ, Sch Med, Pediat Gastroenterol Hepatol & Nutr, St Louis, MO USA. [Haber, Barbara A.] Merck, Infect Dis, Clin Res, N Wales, PA USA. [Magee, John C.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Sokol, Ronald J.] Univ Colorado, Sch Med, Dept Pediat, Sect Pediat Gastroenterol Hepatol & Nutr, Denver, CO USA. [Sherker, Averell H.] NIDDKD, Liver Dis Res Branch, NIH, Bethesda, MD USA. [Sorensen, Lisa G.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Karpen, Saul J.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA USA. [Shneider, Benjamin] Baylor Coll Med, Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Wang, Kasper S.] Childrens Hosp Los Angeles, Div Pediat Surg, Los Angeles, CA 90027 USA. [Kerkar, Nanda] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Ye, Wen] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Kerkar, Nanda] Mt Sinai, New York, NY 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 133 BP 277A EP 277A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401018 ER PT J AU Kleiner, DE Brunt, EM Belt, PH Behling, CA Gill, RM Guy, CD Neuschwan-der-Tetri, BA Sanyal, AJ Van Natta, ML AF Kleiner, David E. Brunt, Elizabeth M. Belt, Patricia H. Behling, Cynthia A. Gill, Ryan M. Guy, Cynthia D. Neuschwan-der-Tetri, Brent A. Sanyal, Arun J. Van Natta, Mark L. TI Extending the Ballooning Score Beyond 2: A Proposal for a New Balloon Score SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Belt, Patricia H.; Van Natta, Mark L.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA. [Behling, Cynthia A.] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. [Gill, Ryan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Guy, Cynthia D.] Duke Univ, Med Ctr, Durham, NC USA. [Neuschwan-der-Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 157 BP 288A EP 289A PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401042 ER PT J AU Farci, P Tice, AB Engle, RE Zamboni, F Melis, M Long, ZF Rodriguez-Canales, J Hanson, J Emmert-Buck, MR Kleiner, DE Diaz, G AF Farci, Patrizia Tice, Ashley B. Engle, Ronald E. Zamboni, Fausto Melis, Marta Long, Zhifeng Rodriguez-Canales, Jaime Hanson, Jeffrey Emmert-Buck, Michael R. Kleiner, David E. Diaz, Giacomo TI Viral Expression and Molecular Profiling of Liver Tissue and Microdissected Hepatocytes in Hepatitis D Virus (HDV) - Associated Hepatocellular Carcinoma (HCC) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Farci, Patrizia; Tice, Ashley B.; Engle, Ronald E.; Melis, Marta] NIH, Infect Dis Lab, Bethesda, MD 20892 USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Long, Zhifeng] Personal Diagnostix, Gaithersburg, MD USA. [Rodriguez-Canales, Jaime; Hanson, Jeffrey; Emmert-Buck, Michael R.; Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 166 BP 293A EP 293A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401051 ER PT J AU Gao, YH He, Y Feng, DC Zhou, Z Gao, B AF Gao, Yanhang He, Yong Feng, Dechun Zhou, Zhou Gao, Bin TI Chronic ethanol feeding suppresses Con A induced T cell response and hepatitis in ALDH2-deficient mice SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gao, Yanhang; He, Yong; Feng, Dechun; Zhou, Zhou; Gao, Bin] NIAAA, NIH, Rockville, MD 20852 USA. [Gao, Yanhang] Jilin Univ, Hosp 1, Hepatol, Changchun 130023, Peoples R China. RI Zhou, Zhou/R-7788-2016 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 182 BP 301A EP 301A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401067 ER PT J AU Lee, WM Stravitz, RT Fontana, RJ Hanje, AJ Tillman, H Clasen, KM Durkalski, VL Sherker, AH Doo, E Davis, BC AF Lee, William M. Stravitz, R. Todd Fontana, Robert J. Hanje, A. James Tillman, Holly Clasen, Kristen M. Durkalski, Valerie L. Sherker, Averell H. Doo, Edward Davis, Brian C. TI Safety and Tolerability of Ornithine Phenylacetate to Lower Ammonia in Acute Liver Failure: Preliminary report of the STOP-ALF Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Stravitz, R. Todd] Virginia Commonwealth Univ, Gastroenterol, Richmond, VA USA. [Fontana, Robert J.] Univ Michigan, Gastroenterol, Ann Arbor, MI 48109 USA. [Hanje, A. James] Ohio State Univ, Wexner Sch Med, Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA. [Tillman, Holly; Clasen, Kristen M.; Durkalski, Valerie L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Sherker, Averell H.; Doo, Edward] NIDDK, NIH, Bethesda, MD 20892 USA. [Davis, Brian C.] UT Southwestern Med Ctr, Internal Med, Dallas, TX 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 213 BP 319A EP 319A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401098 ER PT J AU Alao, H Kim, YJ Wright, EC Cam, M Rivera, EM Fryzek, N Kleiner, DE Zhang, F Doo, E Rotman, Y Koh, C Heller, T Hoofnagle, JH Liang, TJ Ghany, MG AF Alao, Hawwa Kim, Yun Ju Wright, Elizabeth C. Cam, Margaret Rivera, Elenita M. Fryzek, Nancy Kleiner, David E. Zhang, Fang Doo, Edward Rotman, Yaron Koh, Christopher Heller, Theo Hoofnagle, Jay H. Liang, T. Jake Ghany, Marc G. TI Rapid Decline In Interferon Stimulated Genes In Prior HCV Non-Responders Re-Treated With Direct Acting Antivirals SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Alao, Hawwa; Kim, Yun Ju; Rivera, Elenita M.; Fryzek, Nancy; Zhang, Fang; Doo, Edward; Rotman, Yaron; Koh, Christopher; Heller, Theo; Hoofnagle, Jay H.; Liang, T. Jake; Ghany, Marc G.] NIH, Liver Dis Branch, Bethesda, MD 20892 USA. [Cam, Margaret] NCI, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, LP, NIH, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 218 BP 321A EP 322A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401103 ER PT J AU Kattakuzhy, S Wilson, E Sidharthan, S McLaughlin, M Silk, R Mo, HM Osinusi, A Kohli, A Masur, H Kottilil, S AF Kattakuzhy, Sarah Wilson, Eleanor Sidharthan, Sreetha McLaughlin, Mary Silk, Rachel Mo, Hongmei Osinusi, Anu Kohli, Anita Masur, Henry Kottilil, Shyam TI Evolution Of Resistance Associated Variants During Initial Treatment, Viral Failure, And Re-Treatment With Directly Acting Antiviral Therapy (NIH SYNERGY Trial) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kohli, Anita] NIH, Immunoregulat Lab, Leidos Biomed Res Inc, Bethesda, MD 20892 USA. [Kattakuzhy, Sarah; Wilson, Eleanor; Silk, Rachel; Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Infect Dis, Baltimore, MD 21201 USA. [Kattakuzhy, Sarah; Wilson, Eleanor; Sidharthan, Sreetha; Masur, Henry; Kottilil, Shyam] NIH, Crit Care Med, Bethesda, MD 20892 USA. [McLaughlin, Mary] NIAID, Bethesda, MD 20892 USA. [Mo, Hongmei; Osinusi, Anu] Gilead Sci Inc, Foster City, CA 94404 USA. [Kohli, Anita] Creighton Univ, Hepatol, Phoenix, AZ 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 220 BP 322A EP 323A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401105 ER PT J AU Aithal, GP Nicoletti, P Bjornsson, E Lucena, MI Andrade, RJ Grove, J Stephens, C Hallberg, P Maitland-van der Zee, AH Martin, JH Cascorbi, I Dillon, JF Laitinen, T Larrey, DG Molokhia, M Kullak-Ublick, GA Ibanez, L Pirmohamed, M Qin, SY Sawle, A Bessone, F Hernandez, N Stolz, A Chalasani, NP Serrano, J Barnhart, HX Fontana, RJ Watkins, P Urban, TJ Daly, AK AF Aithal, Guruprasad P. Nicoletti, Paola Bjornsson, Einar Lucena, M. I. Andrade, Raul J. Grove, Jane Stephens, C. Hallberg, Par Maitland-van der Zee, Anke H. Martin, Jennifer H. Cascorbi, Ingolf Dillon, John F. Laitinen, Tarja Larrey, Dominique G. Molokhia, Mariam Kullak-Ublick, Gerd A. Ibanez, Luisa Pirmohamed, Munir Qin, Shengying Sawle, Ashley Bessone, Fernando Hernandez, Nelia Stolz, Andrew Chalasani, Naga P. Serrano, Jose Barnhart, Huiman X. Fontana, Robert J. Watkins, Paul Urban, Thomas J. Daly, Ann K. TI HLA-A*33:01 is strongly associated with drug-induced liver injury (DILI) due to terbinafine and several other unrelated compounds SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Aithal, Guruprasad P.; Grove, Jane] Nottingham Univ Hosp NHS Trust, NIHR Nottingham Digest Dis Biomed Res Unit, Nottingham, England. [Nicoletti, Paola; Sawle, Ashley] Columbia Univ, New York, NY USA. [Bjornsson, Einar] Landspitali Univ Hosp, Reykjavik, Iceland. [Lucena, M. I.; Andrade, Raul J.] CIBERehd, Madrid, Spain. [Hallberg, Par] Uppsala Univ, Uppsala, Sweden. [Martin, Jennifer H.] Univ Queensland, Brisbane, Qld, Australia. [Martin, Jennifer H.] Princess Alexandra Hosp, Brisbane, Qld, Australia. [Cascorbi, Ingolf] Univ Hosp Schleswig Holstein, Kiel, Germany. [Dillon, John F.] Ninewells Hosp & Med Sch, Dundee, Scotland. [Laitinen, Tarja] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Larrey, Dominique G.] Hop St Eloi, Montpellier, France. [Molokhia, Mariam] Univ London, Kings Coll London, London SW3 6LX, England. [Kullak-Ublick, Gerd A.] Univ Zurich, Zurich, Switzerland. [Ibanez, Luisa] Hosp Univ Vall Hebron, Barcelona, Spain. [Pirmohamed, Munir] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Qin, Shengying] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Watkins, Paul] Hamner UNC Inst Drug Safety Sci, Durham, NC USA. [Urban, Thomas J.] UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Daly, Ann K.] Newcastle Univ, Newcastle, NSW, Australia. [Bessone, Fernando] Univ Nacl Rosario, Fac Ciencias Med, RA-2000 Rosario, Argentina. [Hernandez, Nelia] Univ Republ, Mentevideo, Uruguay. [Lucena, M. I.; Andrade, Raul J.; Stephens, C.] Univ Malaga, E-29071 Malaga, Spain. [Stolz, Andrew] Univ So Calif, Los Angeles, CA USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Serrano, Jose] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Barnhart, Huiman X.] Duke Clin Res Inst, Durham, NC USA. [Maitland-van der Zee, Anke H.] Univ Utrecht, Utrecht, Netherlands. RI Ibanez, Lourdes/F-8316-2014 OI Ibanez, Lourdes/0000-0002-5058-1603 NR 0 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 225 BP 325A EP 326A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401110 ER PT J AU Hameed, B Terrault, N Gill, RM Loomba, R Chalasani, NP Hoofnagle, JH Van Natta, ML AF Hameed, Bilal Terrault, Norah Gill, Ryan M. Loomba, Rohit Chalasani, Naga P. Hoofnagle, Jay H. Van Natta, Mark L. TI Clinical and Metabolic Effects Associated With Weight Loss and Obeticholic Acid In Nonalcoholic Steatohepatitis (NASH) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hameed, Bilal; Terrault, Norah; Gill, Ryan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Loomba, Rohit] Univ Calif San Diego, San Diego, CA 92103 USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Hoofnagle, Jay H.] NIDDK, Bethesda, MD 20892 USA. [Van Natta, Mark L.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 236 BP 331A EP 331A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401121 ER PT J AU Wires, E Henderson, M Trychta, K Harvey, BK AF Wires, Emily Henderson, Mark Trychta, Kathleen Harvey, Brandon K. TI Longitudinal monitoring of hepatic endoplasmic reticulum calcium changes in rats SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wires, Emily; Henderson, Mark; Trychta, Kathleen; Harvey, Brandon K.] NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 323 BP 375A EP 375A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401208 ER PT J AU Allawy, A Davuluri, G Kumar, A Gao, B Xu, MJ McMullen, MR McCullough, RL Dasarathy, S AF Allawy, Allawy Davuluri, Gangarao Kumar, Avinash Gao, Bin Xu, Ming-Jiang McMullen, Megan R. McCullough, Rebecca L. Dasarathy, Srinivasan TI Acute alcohol binge causes skeletal muscle mitochondrial intermediate metabolite deficiency SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Dasarathy, Srinivasan] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Allawy, Allawy; Davuluri, Gangarao; Kumar, Avinash; McMullen, Megan R.; McCullough, Rebecca L.; Dasarathy, Srinivasan] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA. [Allawy, Allawy] Cleveland Clin, Dept Internal Med, Cleveland, OH 44106 USA. [Gao, Bin; Xu, Ming-Jiang] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 334 BP 380A EP 380A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401219 ER PT J AU Mehta, A Wang, MJ Devarajan, K Singal, AG Marrero, JA Feng, ZD Rinaudo, JA Srivastava, S Evans, A Hann, HW Yang, HS Javaid, A Poongkuran, M Lau, D Block, T AF Mehta, Anand Wang, Mengjun Devarajan, Karthik Singal, Amit G. Marrero, Jorge A. Feng, Ziding Rinaudo, Jo Ann Srivastava, Sudhir Evans, Alison Hann, Hie-Won Yang, Hushan Javaid, Asad Poongkuran, Mugilan Lau, Daryl Block, Timothy TI The Doylestown algorithm - a test to improve the performance of AFP in the detection of early stage hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Mehta, Anand; Wang, Mengjun] Drexel Univ, Coll Med, Microbiol & Immunol, Doylestown, PA USA. [Devarajan, Karthik] Fox Chase Canc Ctr, Biostat, Philadelphia, PA 19111 USA. [Singal, Amit G.; Marrero, Jorge A.] Univ Texas Southwestern, Digest & Liver Dis, Dallas, TX USA. [Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Biostat, Houston, TX 77030 USA. [Rinaudo, Jo Ann; Srivastava, Sudhir] NCI, Canc Biomarker Res Grp, Bethesda, MD 20892 USA. [Evans, Alison] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Hann, Hie-Won] Thomas Jefferson Univ Hosp, Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Yang, Hushan] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Javaid, Asad; Poongkuran, Mugilan; Lau, Daryl] Harvard Univ, Sch Med, Boston, MA USA. [Block, Timothy] Baruch Blumberg Inst, Doylestown, PA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 371 BP 398A EP 398A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401255 ER PT J AU Masur, J Kottilil, S Wilson, E Shah, SR AF Masur, Jack Kottilil, Shyam Wilson, Eleanor Shah, Samir R. TI Upper Limit Normal of Alanine Aminotransferase for the Indian Population SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Masur, Jack; Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Wilson, Eleanor] NIH, Crit Care Med Dept, Bethesda, MD 20892 USA. [Shah, Samir R.] Global Hosp, Mumbai, Maharashtra, India. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 578 BP 496A EP 497A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401461 ER PT J AU Bonkovsky, HL Kleiner, DE Gu, JZ Odin, JA Russo, MW Navarro, VJ Vega, M Hoofnagle, JH AF Bonkovsky, Herbert L. Kleiner, David E. Gu, Jiezhun Odin, Joseph A. Russo, Mark W. Navarro, Victor J. Vega, Maricruz Hoofnagle, Jay H. TI The Clinical-Pathological Spectrum and Outcomes of Liver Injury due to Drugs and Botanicals Associated with Loss of Bile Ducts SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Russo, Mark W.] Carolinas Hlth Care Syst, Ctr Liver, Charlotte, NC USA. [Bonkovsky, Herbert L.] Wake Forest NC Baptist Med Ctr, Internal Med Gastroenterol & Hepatol, Winston Salem, NC USA. [Kleiner, David E.] NCI, Lab Pathol, Bethesda, MD 20892 USA. [Odin, Joseph A.] Icahn Sch Med Mt Sinai, Internal Med Gastroenterol & Hepatol, New York, NY 10029 USA. [Gu, Jiezhun] Duke Univ, Clin Res Inst, Durham, NC USA. [Navarro, Victor J.; Vega, Maricruz] Einstein Hlth Care, Internal Med Hepatol, Philadelphia, PA USA. [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 597 BP 505A EP 505A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375401480 ER PT J AU Kaji, K Factor, VM Andersen, JB Durkin, ME Marquardt, JU Conner, EA Hoang, T Yoshiji, H Thorgeirsson, SS AF Kaji, Kosuke Factor, Valentina M. Andersen, Jesper B. Durkin, Marian E. Marquardt, Jens U. Conner, Elizabeth A. Hoang, Tanya Yoshiji, Hitoshi Thorgeirsson, Snorri S. TI DNMT1 is essential for effective postnatal and regenerative growth of adult liver SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaji, Kosuke; Factor, Valentina M.; Andersen, Jesper B.; Durkin, Marian E.; Marquardt, Jens U.; Conner, Elizabeth A.; Hoang, Tanya; Thorgeirsson, Snorri S.] NCI, Labolatory Expt Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Kaji, Kosuke; Yoshiji, Hitoshi] Nara Med Univ, Dept Internal Med 3, Kashihara, Nara 634, Japan. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 677 BP 544A EP 544A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402002 ER PT J AU Gasmi, I Guillot, A Hamdaoui, N Brouillet, A Calderaro, J Rousseau, B Pawlotsky, JM Lafdil, F AF Gasmi, Imsne Guillot, Adrien Hamdaoui, Nabila Brouillet, Arthur Calderaro, Julien Rousseau, Benoit Pawlotsky, Jean-Michel Lafdil, Fouad TI Interleukin-17 mediates liver progenitor cell transformation into cancer stem cells in hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gasmi, Imsne; Hamdaoui, Nabila; Brouillet, Arthur; Calderaro, Julien; Rousseau, Benoit; Pawlotsky, Jean-Michel; Lafdil, Fouad] Univ Paris Est, INSERM, Hop Henri Mondor, U955, Creteil, France. [Gasmi, Imsne; Guillot, Adrien; Hamdaoui, Nabila; Brouillet, Arthur; Calderaro, Julien; Rousseau, Benoit; Pawlotsky, Jean-Michel; Lafdil, Fouad] Univ Paris Est, INSERM, Creteil, France. [Guillot, Adrien] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 693 BP 551A EP 552A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402018 ER PT J AU Takyar, VK Kleiner, DE Wilkins, KJ Surana, P Etzion, O Hoofnagle, JH Liang, TJ Heller, T Koh, C AF Takyar, Varun K. Kleiner, David E. Wilkins, Kenneth J. Surana, Pallavi Etzion, Ohad Hoofnagle, Jay H. Liang, T. Jake Heller, Theo Koh, Christopher TI Diagnostic disparity of FIB4, APRI and AAR in predicting liver fibrosis in HDV/HBV co-infected patients SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Takyar, Varun K.; Surana, Pallavi; Etzion, Ohad; Hoofnagle, Jay H.; Liang, T. Jake; Heller, Theo; Koh, Christopher] NIH, Liver Dis Branch, Bethesda, MD 20892 USA. [Kleiner, David E.] NIH, Pathol Lab, Bethesda, MD 20892 USA. [Wilkins, Kenneth J.] NIDDK, Off Director, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 779 BP 597A EP 598A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402103 ER PT J AU Zhou, Z Xu, MJ Chang, BX Cai, Y Gao, B AF Zhou, Zhou Xu, Ming-Jiang Chang, Binxia Cai, Yan Gao, Bin TI CXCL1 promotes steatohepatitis and fibrosis in a mouse model of high-fat diet-plus-binge ethanol feeding SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Zhou, Zhou; Xu, Ming-Jiang; Chang, Binxia; Cai, Yan; Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD 20852 USA. [Chang, Binxia] Beijing 302 Hosp, Inst Alcohol Liver Dis, Diag & Treatment Ctr Noninfect Liver Dis, Beijing, Peoples R China. RI Zhou, Zhou/R-7788-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 903 BP 655A EP 655A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402227 ER PT J AU Shrivastava, S Meissner, EG Sturdevant, D Poonia, B Kottilil, S AF Shrivastava, Shikha Meissner, Eric G. Sturdevant, Dan Poonia, Bhawna Kottilil, Shyam TI Transcriptomic analysis of CD4+CD25+CD127dim/-T regulatory in HCV-mono-infection and HCV/HIV-Co-infection SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shrivastava, Shikha; Poonia, Bhawna; Kottilil, Shyam] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Meissner, Eric G.] MUSC, Charleston, SC USA. [Sturdevant, Dan] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1029 BP 711A EP 712A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375402352 ER PT J AU Liangpunsakul, S Chalasani, NP Jiang, GL Liu, YL Shah, V Sanyal, AJ Radaeva, S Crabb, DW AF Liangpunsakul, Suthat Chalasani, Naga P. Jiang, Guanglong Liu, Yunlong Shah, Vijay Sanyal, Arun J. Radaeva, Svetlana Crabb, David W. TI Differential microRNA expression profiles in patients with alcoholic hepatitis (AH): Preliminary findings from the Translational Research and Evolving Alcoholic Hepatitis Treatment (TREAT) consortium SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liangpunsakul, Suthat; Chalasani, Naga P.; Crabb, David W.] Indiana Univ Sch Med, Div Gastroenterol Hepatol, Indianapolis, IN 46202 USA. [Jiang, Guanglong; Liu, Yunlong] Indiana Univ, Dept Med & Mol Genet, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46204 USA. [Shah, Vijay] Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Coll Med, Rochester, MN USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Med, Div Gastroenterol & Hepatol, Richmond, VA 23298 USA. [Radaeva, Svetlana] NIAAA, NIH, Rockville, MD 20852 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1332 BP 865A EP 865A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403126 ER PT J AU Cinar, R Iyer, M Liu, ZY Jourdan, T Cao, ZX Erdelyi, K Godlewski, G Szanda, G Liu, J Pacher, P Rice, K Kunos, G AF Cinar, Resat Iyer, Malliga Liu, Ziyi Jourdan, Tony Cao, Zongxian Erdelyi, Katalin Godlewski, Grzegorz Szanda, Gergo Liu, Jie Pacher, Pal Rice, Kenner Kunos, George TI Novel treatment strategy for liver fibrosis by hybrid inhibitors targeting peripheral cannabinoid-1 receptors (CB1R) and inducible NO synthase (iNOS) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Cinar, Resat; Iyer, Malliga; Liu, Ziyi; Jourdan, Tony; Cao, Zongxian; Erdelyi, Katalin; Godlewski, Grzegorz; Szanda, Gergo; Liu, Jie; Pacher, Pal; Rice, Kenner; Kunos, George] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1374 BP 883A EP 884A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403167 ER PT J AU Chascsa, DM Etzion, O Alao, H Fitzhugh, C Tisdale, JF Minniti, C Hsieh, M Kleiner, DE Gharib, AM Takyar, VK Eccleston, JL Heller, T Koh, C AF Chascsa, David M. Etzion, Ohad Alao, Hawwa Fitzhugh, Courtney Tisdale, John F. Minniti, Caterina Hsieh, Matthew Kleiner, David E. Gharib, Ahmed M. Takyar, Varun K. Eccleston, Jason L. Heller, Theo Koh, Christopher TI Transjugular Liver Biopsy Is Safe In Sickle Cell Disease and Provides Insight into Hepatopathy SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Chascsa, David M.; Gharib, Ahmed M.] NIDDK, DDB, NIH, Bethesda, MD 20892 USA. [Etzion, Ohad; Alao, Hawwa; Takyar, Varun K.; Eccleston, Jason L.; Heller, Theo; Koh, Christopher] NIDDK, LDB, Bethesda, MD 20892 USA. [Fitzhugh, Courtney; Tisdale, John F.; Minniti, Caterina; Hsieh, Matthew] NHLBI, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. RI Gharib, Ahmed/O-2629-2016 OI Gharib, Ahmed/0000-0002-2476-481X 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1498 BP 941A EP 942A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403290 ER PT J AU McMillin, M Frampton, GA Grant, S Quinn, MA DeMorrow, S AF McMillin, Matthew Frampton, Gabriel A. Grant, Stephanie Quinn, Matthew A. DeMorrow, Sharon TI Conjugated bile acids suppress the HPA axis via activation of hypothalamic glucocorticoid receptors in a rodent model of chronic biliary obstruction SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [McMillin, Matthew; Frampton, Gabriel A.; Grant, Stephanie; DeMorrow, Sharon] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [McMillin, Matthew; DeMorrow, Sharon] Cent Texas Vet Healthcare Syst, Temple, TX USA. [Quinn, Matthew A.] NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1507 BP 945A EP 946A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403299 ER PT J AU Sun, J Xu, HQ He, XT Wang, JY Wang, XM Gao, B Niu, JQ Gao, YH AF Sun, Jing Xu, Hongqin He, Xiuting Wang, Jingyun Wang, Xiaomei Gao, Bin Niu, Junqi Gao, Yanhang TI Aldehyde dehydrogenases-2 rs671 polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with hepatitis B virus SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Sun, Jing; Xu, Hongqin; He, Xiuting; Wang, Jingyun; Wang, Xiaomei; Niu, Junqi] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. [Gao, Bin; Gao, Yanhang] NIAAA, NIH, Rockville, MD 20852 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1580 BP 981A EP 981A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403372 ER PT J AU Terrault, N Ghany, MG Kang, C Cooper, S Di Bisceglie, AM Fried, MW Belle, SH Hoofnagle, JH AF Terrault, Norah Ghany, Marc G. Kang, Chaeryon Cooper, Stewart Di Bisceglie, Adrian M. Fried, Michael W. Belle, Steven H. Hoofnagle, Jay H. TI Seroprevalence and Clinical Features of Hepatitis D Virus (HDV) Infection in a North American Cohort SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Terrault, Norah] UCSF, San Francisco, CA USA. [Ghany, Marc G.; Hoofnagle, Jay H.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kang, Chaeryon; Belle, Steven H.] Univ Pittsburgh, Pittsburgh, PA USA. [Cooper, Stewart] Calif Pacific Med Ctr, San Francisco, CA USA. [Di Bisceglie, Adrian M.] St Louis Univ, St Louis, MO 63103 USA. [Fried, Michael W.] Univ N Carolina, Chapel Hill, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1598 BP 989A EP 990A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403390 ER PT J AU Wang, JY Sun, J Wang, XM Wu, RH Xu, HQ He, XT Su, LS Niu, JQ Gao, YH AF Wang, Jingyun Sun, Jing Wang, Xiaomei Wu, Ruihong Xu, Hongqin He, Xiuting Su, Lishan Niu, Junqi Gao, Yanhang TI Hepcidin: A new clinical factor in the patients with HBV-related chronic liver diseases SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wang, Jingyun; Sun, Jing; Wang, Xiaomei; Wu, Ruihong; Xu, Hongqin; He, Xiuting; Niu, Junqi] Jilin Univ, Hosp 1, Changchun 130023, Peoples R China. [Su, Lishan] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, CA USA. [Gao, Yanhang] NIAAA, NIH, Rockville, MD 20852 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1620 BP 999A EP 999A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403412 ER PT J AU Chen, ZC Zhao, HY Schuck, P Engle, RE Zamboni, F Diaz, G Kleiner, DE Purcell, RH Farci, P AF Chen, Zhaochun Zhao, Huaying Schuck, Peter Engle, Ronald E. Zamboni, Fausto Diaz, Giacomo Kleiner, David E. Purcell, Robert H. Farci, Patrizia TI Massive Intrahepatic Production of Germ-line Antibodies with High Affinity Against HBcAg Is Specifically Associated with Fulminant But Not with Classic Acute Hepatitis B: New Insights Into Pathogenesis SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Chen, Zhaochun; Engle, Ronald E.; Purcell, Robert H.; Farci, Patrizia] NIH, Infect Dis Lab, Bethesda, MD 20892 USA. [Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Kleiner, David E.] NIH, Pathol Lab, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1646 BP 1011A EP 1012A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403438 ER PT J AU Shin, EC Hernandez-Santos, N Koh, C DeMino, M Heller, T Rehermann, B AF Shin, Eui-Cheol Hernandez-Santos, Nydiaris Koh, Christopher DeMino, Mary Heller, Theo Rehermann, Barbara TI Hepatitis delta virus-induced T-cell recruiting chemokines contribute to inflammatory liver injury in chronic hepatitis delta SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shin, Eui-Cheol; Hernandez-Santos, Nydiaris; Koh, Christopher; DeMino, Mary; Heller, Theo; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Daejeon, South Korea. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1650 BP 1013A EP 1013A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403442 ER PT J AU Hayashi, S Murakami, S Omagari, K Matsui, T Iio, E Isogawa, M Watanabe, T Karino, Y Takamatsu, Y Kohgo, S Maeda, K Mitsuya, H Tanaka, Y AF Hayashi, Sanae Murakami, Shuko Omagari, Katsumi Matsui, Takeshi Iio, Etsuko Isogawa, Masanori Watanabe, Tsunamasa Karino, Yoshiyasu Takamatsu, Yuki Kohgo, Satoru Maeda, Kenji Mitsuya, Hiroaki Tanaka, Yasuhito TI A Novel Entecavir Resistance Mutation RtA186T Causes Viral Breakthrough in Chronic Hepatitis B Patients SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hayashi, Sanae; Murakami, Shuko; Omagari, Katsumi; Iio, Etsuko; Isogawa, Masanori; Watanabe, Tsunamasa; Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi, Japan. [Matsui, Takeshi] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido, Japan. [Karino, Yoshiyasu] Sapporo Kosei Gen Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Takamatsu, Yuki; Tanaka, Yasuhito] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NCI, Bethesda, MD 20892 USA. [Kohgo, Satoru; Maeda, Kenji; Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Tokyo, Japan. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1655 BP 1016A EP 1016A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403447 ER PT J AU Loomes, KM Spino, C Goodrich, NP Hangartner, TN Marker, AE Heubi, JE Kamath, BM Shneider, B Rosenthal, P Hertel, PM Karpen, SJ Kerkar, N Molleston, JP Murray, KF Schwarz, KB Teckman, J Turmelle, YP Whitington, PF Sherker, AH Magee, JC Sokol, RJ AF Loomes, Kathleen M. Spino, Cathie Goodrich, Nathan P. Hangartner, Thomas N. Marker, Amanda E. Heubi, James E. Kamath, Binita M. Shneider, Benjamin Rosenthal, Philip Hertel, Paula M. Karpen, Saul J. Kerkar, Nanda Molleston, Jean P. Murray, Karen F. Schwarz, Kathleen B. Teckman, Jeffrey Turmelle, Yumirle P. Whitington, Peter F. Sherker, Averell H. Magee, John C. Sokol, Ronald J. TI DXA Bone Density in Alagille Syndrome Correlates with Fracture History and Degree of Cholestasis SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Goodrich, Nathan P.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. [Loomes, Kathleen M.] Childrens Hosp Philadelphia, Pediat Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Rosenthal, Philip] UCSF Univ Calif, Div GI Hepatol & Nutr, San Francisco, CA USA. [Karpen, Saul J.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA USA. [Kerkar, Nanda] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Molleston, Jean P.] Indiana Univ, Sch Med, Riley Hosp Children, Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN USA. [Murray, Karen F.] Univ Washington, Med Ctr, Seattle Childrens, Div Gastroenterol & Hepatol, Seattle, WA 98195 USA. [Schwarz, Kathleen B.] Johns Hopkins Sch Med, Baltimore, MD USA. [Turmelle, Yumirle P.] Washington Univ, Sch Med, St Louis, MO USA. [Sherker, Averell H.] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Magee, John C.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Sokol, Ronald J.] Univ Colorado, Dept Pediat, Sect Pediat Gastroentrol Hepatol & Nutr, Aurora, CO USA. [Kamath, Binita M.] Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada. [Kamath, Binita M.] Univ Toronto, Toronto, ON, Canada. [Spino, Cathie] Univ Michigan, Ann Arbor, MI 48109 USA. [Hangartner, Thomas N.; Marker, Amanda E.] Wright State Univ, Dept Biomed Ind & Human Factors Engn, Dayton, OH 45435 USA. [Heubi, James E.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA. [Shneider, Benjamin; Hertel, Paula M.] Baylor Coll Med, Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Teckman, Jeffrey] St Louis Univ, Cardinal Glennon Childrens Med Ctr, St Louis, MO USA. [Whitington, Peter F.] Northwestern Univ, Dept Pediat, Feinberg Med Sch, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1694 BP 1034A EP 1035A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403486 ER PT J AU Lingala, S Garabedian, E Candotti, F Kleiner, DE Wilkins, KJ Heller, T Koh, C AF Lingala, Shilpa Garabedian, Elizabeth Candotti, Fabio Kleiner, David E. Wilkins, Kenneth J. Heller, Theo Koh, Christopher TI Hepatic Manifestations in Adenosine Deaminase-Deficient Severe Combined Immune Deficiency SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lingala, Shilpa; Heller, Theo; Koh, Christopher] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Garabedian, Elizabeth; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. [Wilkins, Kenneth J.] NIDDK, Off Director, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1717 BP 1045A EP 1045A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403509 ER PT J AU Etzion, O Heller, T Han, MAT Patel, R Koh, C Kleiner, DE Mousa, O Loomba, R Bakalov, V Bondy, C AF Etzion, Ohad Heller, Theo Han, Ma Ai Thanda Patel, Ruchi Koh, Christopher Kleiner, David E. Mousa, Omar Loomba, Rohit Bakalov, Vladimir Bondy, Carolyn TI Liver Involvement in Turner's Syndrome, Is Associated with Extra Hepatic Disease Manifestations SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Etzion, Ohad; Heller, Theo; Han, Ma Ai Thanda; Patel, Ruchi; Koh, Christopher; Kleiner, David E.; Mousa, Omar; Loomba, Rohit] NIH, Liver Dis Branch, Rockville, MD USA. [Kleiner, David E.; Bakalov, Vladimir; Bondy, Carolyn] NICHID, Heritable Disorders Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1720 BP 1047A EP 1047A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403512 ER PT J AU Lingala, S Kleiner, DE Lam, C Wolfe, LA Ferreira, CR Krasnewich, D Gahl, WA Ghany, MG AF Lingala, Shilpa Kleiner, David E. Lam, Christina Wolfe, Lynne A. Ferreira, Carlos R. Krasnewich, Donna Gahl, William A. Ghany, Marc G. TI Liver Disease in Subjects with N-Glycanse-1 Deficiency SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lingala, Shilpa; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Lam, Christina; Ferreira, Carlos R.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. [Wolfe, Lynne A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Krasnewich, Donna] NIGMS, Div Genet & Dev Biol, NIH, Bethesda, MD USA. [Wolfe, Lynne A.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1722 BP 1048A EP 1048A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375403514 ER PT J AU Fu, D Haydar, G Kang, SWS Farrell, GC Lippincott-Schwartz, J Arias, IM AF Fu, Dong Haydar, Ghada Kang, Sun Woo Sophie Farrell, Geoffrey C. Lippincott-Schwartz, Jennifer Arias, Irwin M. TI AMPK activation prevents and reverses drug-induced mitochondrial damage in hepatocytes by regulating mitochondrial quality control SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Fu, Dong; Haydar, Ghada; Kang, Sun Woo Sophie] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia. [Farrell, Geoffrey C.] Natl Univ Australia Med Sch, Liver Res Grp, Canberra, ACT, Australia. [Lippincott-Schwartz, Jennifer; Arias, Irwin M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1909 BP 1139A EP 1139A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404154 ER PT J AU Hayashi, PH Rockey, DC Fontana, RJ Tillmann, HL Kaplowitz, N Barnhart, HX Gu, JZ Sherker, AH Chalasani, NP Navarro, VJ Ahmad, J Hoofnagle, JH AF Hayashi, Paul H. Rockey, Don C. Fontana, Robert J. Tillmann, Hans L. Kaplowitz, Neil Barnhart, Huiman X. Gu, Jiezhun Sherker, Averell H. Chalasani, Naga P. Navarro, Victor J. Ahmad, Jawad Hoofnagle, Jay H. TI Death and Liver Transplantations Occurring Within Two Years of Drug-Induced Liver Injury SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hayashi, Paul H.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Rockey, Don C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Tillmann, Hans L.] E Carolina Univ, Greenville, NC USA. [Kaplowitz, Neil] Univ So Calif, Los Angeles, CA USA. [Barnhart, Huiman X.; Gu, Jiezhun] Duke Univ, Durham, NC USA. [Sherker, Averell H.; Hoofnagle, Jay H.] NIH, Bethesda, MD 20892 USA. [Navarro, Victor J.] Einstein Med Ctr, Philadelphia, PA USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Ahmad, Jawad] Mt Sinai Med Ctr, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1922 BP 1145A EP 1146A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404167 ER PT J AU Stolz, A Navarro, VJ Hayashi, PH Chalasani, NP Fontana, RJ Bonkovsky, HL Hwang, S Hoofnagle, JH Kleiner, DE Barnhart, HX AF Stolz, Andrew Navarro, Victor J. Hayashi, Paul H. Chalasani, Naga P. Fontana, Robert J. Bonkovsky, Herbert L. Hwang, Sunil Hoofnagle, Jay H. Kleiner, David E. Barnhart, Huiman X. TI Severe and prolonged jaundice associated with body building supplements (BBS): review of 44 cases from the Drug-Induced Liver Injury Network (DILIN) SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Stolz, Andrew] Univ So Calif, Med, Los Angeles, CA USA. [Navarro, Victor J.] Einstein Med Ctr, Med, Philadelphia, PA USA. [Hayashi, Paul H.] Univ N Carolina, Med, Chapel Hill, NC USA. [Chalasani, Naga P.] Indiana Univ Sch Med, Med, Indianapolis, IN 46202 USA. [Fontana, Robert J.] Univ Michigan, Med, Ann Arbor, MI 48109 USA. [Bonkovsky, Herbert L.; Hwang, Sunil] Carolinas Med Ctr, Med & Res, Charlotte, NC 28203 USA. [Hoofnagle, Jay H.] NIDDK, Div Digest Dis & Nutr, Liver Dis Res Branch, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Lab Pathol, Bethesda, MD 20892 USA. [Barnhart, Huiman X.] Duke Univ, Duke Clin Res Inst, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1923 BP 1146A EP 1146A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404168 ER PT J AU Einar, BS Gu, JZ Kleiner, DE Chalasani, NP Hayashi, PH Hoofnagle, JH AF Einar, Bjornsson S. Gu, Jiezhun Kleiner, David E. Chalasani, Naga P. Hayashi, Paul H. Hoofnagle, Jay H. TI Azathioprine And 6-Mercaptopurine Induced Liver Injury SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Einar, Bjornsson S.] Natl Univ Hosp Iceland, Reykjavik, Iceland. [Einar, Bjornsson S.; Kleiner, David E.] NIH, Bethesda, MD 20892 USA. [Gu, Jiezhun] 3Duke Clin Res Inst, Durham, NC USA. [Chalasani, Naga P.] Indiana Univ Sch Med, Indinapolis, PA USA. [Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA. [Hoofnagle, Jay H.] NIDDK, NIH, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1926 BP 1147A EP 1147A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404171 ER PT J AU Rockey, DC Hayashi, PH Tillmann, HL Gu, JZ Ghabril, M Ahmad, J Stolz, A Fontana, RJ Hoofnagle, JH AF Rockey, Don C. Hayashi, Paul H. Tillmann, Hans L. Gu, Jiezhun Ghabril, Marwan Ahmad, Jawad Stolz, Andrew Fontana, Robert J. Hoofnagle, Jay H. TI Liver Disorders that can Masquerade as Drug-Induced Liver Injury SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rockey, Don C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA. [Tillmann, Hans L.; Gu, Jiezhun] Duke Univ, Durham, NC USA. [Ghabril, Marwan] Indiana Univ, Indianapolis, IN 46204 USA. [Ahmad, Jawad] Mt Sinai, New York, NY USA. [Hoofnagle, Jay H.] NIH, Bethesda, MD 20892 USA. [Stolz, Andrew] Univ So Calif, Los Angeles, CA USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 1931 BP 1149A EP 1150A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404176 ER PT J AU Urban, TJ Nicoletti, P Chalasani, NP Serrano, J Stolz, A Daly, AK Aithal, GP Dillon, JF Barnhart, HX Watkins, PB Fontana, RJ AF Urban, Thomas J. Nicoletti, Paola Chalasani, Naga P. Serrano, Jose Stolz, Andrew Daly, Ann K. Aithal, Guruprasad P. Dillon, John F. Barnhart, Huiman X. Watkins, Paul B. Fontana, Robert J. TI Minocycline hepatotoxicity: Clinical characterization and identification of HLA- B*35:02 as a risk factor SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Urban, Thomas J.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 46202 USA. [Urban, Thomas J.; Watkins, Paul B.] Hamner Inst Drug Safety Sci, Durham, NC 20892 USA. [Nicoletti, Paola] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA. [Chalasani, Naga P.] Indiana Univ Sch Med, Indianapolis, IN USA. [Serrano, Jose] NIDDK, Bethesda, MD USA. [Stolz, Andrew] Univ So Calif, Los Angeles, CA USA. [Daly, Ann K.] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England. [Aithal, Guruprasad P.] Univ Nottingham, Nottingham, England. [Dillon, John F.] Univ Dundee, Dundee, Scotland. [Barnhart, Huiman X.] Duke Univ, Durham, NC USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI BP 1149A EP 1149A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404175 ER PT J AU Shin, JH Chen, J Munoz, NM Katz, L Cortes, AC Shukla, V Kim, S Herlong, HF Machida, K Tsukamoto, H Shetty, K Rashid, A Jogunoori, WS He, AR Johnson, LB Lee, JS White, J Mishra, L AF Shin, Ji-Hyun Chen, Jian Munoz, Nina M. Katz, Lior Cortes, Andrea C. Shukla, Vivek Kim, Sangbae Herlong, H. Franklin Machida, Keigo Tsukamoto, Hidekazu Shetty, Kirti Rashid, Asif Jogunoori, Wilma S. He, Aiwu R. Johnson, Lynt B. Lee, Ju-Seog White, Jon Mishra, Lopa TI Vitamin D deficiency promotes hepatocellular cancer through activation of WNT/TLR signaling with disruption of TGF-beta/Smad3 SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shin, Ji-Hyun; Chen, Jian; Munoz, Nina M.; Cortes, Andrea C.; Kim, Sangbae; Herlong, H. Franklin; Rashid, Asif; Lee, Ju-Seog; Mishra, Lopa] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Katz, Lior] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Shukla, Vivek] NCI, Bethesda, MD 20892 USA. [Machida, Keigo; Tsukamoto, Hidekazu] Univ So Calif, Sch Med, Los Angeles, CA USA. [Shetty, Kirti] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Jogunoori, Wilma S.; White, Jon] Vet Affairs Med Ctr, Washington, DC 20422 USA. [He, Aiwu R.; Johnson, Lynt B.] Georgetown Univ, Washington, DC 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2118 BP 1239A EP 1240A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404360 ER PT J AU Han, MAT Samala, N Rizvi, BS Wilkins, KJ Etzion, O Jones, EC Koh, C Kleiner, DE Pavletic, S Heller, T AF Han, Ma Ai Thanda Samala, Niharika Rizvi, Bisharah S. Wilkins, Kenneth J. Etzion, Ohad Jones, Elizabeth C. Koh, Christopher Kleiner, David E. Pavletic, Steven Heller, Theo TI Liver Enzymes Elevation In The Setting Of Chronic Graft-Versus-Host Disease Is A Non Specific Marker Of Inflammation That Does Not Accurately Predict Disease Related Hepatic Injury SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Rizvi, Bisharah S.] Canton Med Educ Fdn, Internal Med, Canton, OH USA. [Han, Ma Ai Thanda; Samala, Niharika; Wilkins, Kenneth J.; Etzion, Ohad; Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Jones, Elizabeth C.] NIH, Radiol, Ctr Clin, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2144 BP 1251A EP 1252A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404386 ER PT J AU Middleton, MS Heba, E Hooker, CA Neuschwander-Tetri, BA Bashir, MR Fowler, K Sandrasegaran, KE Brunt, EM Kleiner, DE Doo, E Van Natta, ML Tonascia, J Loomba, R Sirlin, CB AF Middleton, Michael S. Heba, Elhamy Hooker, Catherine A. Neuschwander-Tetri, Brent A. Bashir, Mustafa R. Fowler, Kathryn Sandrasegaran, Kumar E. Brunt, Elizabeth M. Kleiner, David E. Doo, Edward Van Natta, Mark L. Tonascia, James Loomba, Rohit Sirlin, Claude B. TI Cross-sectional and longitudinal agreement of magnetic resonance imaging proton density fat fraction with pathologist grading of hepatic steatosis in adults with nonalcoholic steatohepatitis in a multi-center trial SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Middleton, Michael S.; Heba, Elhamy; Hooker, Catherine A.; Sirlin, Claude B.] Univ Calif San Diego, Radiol, San Diego, CA USA. [Neuschwander-Tetri, Brent A.] St Louis Univ, Med, St Louis, MO 63103 USA. [Bashir, Mustafa R.] Duke Univ, Radiol, Durham, NC USA. [Fowler, Kathryn] Washington Univ, Radiol, St Louis, MO USA. [Brunt, Elizabeth M.] Washington Univ, Pathol & Immunol, St Louis, MO USA. [Kleiner, David E.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Doo, Edward] NIH, Liver Dis Res Branch, Bethesda, MD 20892 USA. [Van Natta, Mark L.] Johns Hopkins Univ, Epidemiol, Baltimore, MD USA. [Tonascia, James] Johns Hopkins Univ, Biostat & Epidemiol, Baltimore, MD USA. [Loomba, Rohit] Univ Calif San Diego, Med, San Diego, CA USA. [Sandrasegaran, Kumar E.] Indiana Univ, Radiol, Indianapolis, IN 46204 USA. RI Bashir, Mustafa/P-3428-2015 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2150 BP 1255A EP 1255A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404392 ER PT J AU Ouyang, XS Zhang, JY Feng, DC Cai, SY Garcia-Martinez, I Han, SN Hoque, R Chen, YL Wang, FS Gao, B Torok, NJ Mehal, WZ AF Ouyang, Xinshou Zhang, Ji-Yuan Feng, Dechun Cai, Shi-Ying Garcia-Martinez, Irma Han, Sheng-Na Hoque, Rafaz Chen, Yonglin Wang, Fu-Sheng Gao, Bin Torok, Natalie J. Mehal, Wajahat Z. TI Digoxin provides hepatoprotection through inhibition of HIF-1a-NOX4-ROS active pathway SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ouyang, Xinshou; Cai, Shi-Ying; Garcia-Martinez, Irma; Han, Sheng-Na; Hoque, Rafaz; Chen, Yonglin; Mehal, Wajahat Z.] Yale Univ, New Haven, CT USA. [Zhang, Ji-Yuan; Wang, Fu-Sheng] PLA 302 Hosp, Beijing Hosp 302, Liver Failure Therapy & Res Ctr, Beijing, Peoples R China. [Feng, Dechun; Gao, Bin] NIAAA, NIH, Bethesda, MD USA. [Torok, Natalie J.] Univ Calif Davis, Gastroenterol & Hepatol, Sacramento, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2179 BP 1270A EP 1270A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404420 ER PT J AU Long, MT Pedley, A Massaro, JM Hoffmann, U Fox, CS AF Long, Michelle T. Pedley, Alison Massaro, Joseph M. Hoffmann, Udo Fox, Caroline S. TI Non-invasive hepatic fibrosis markers and cardiometabolic risk among adults in the Framingham Heart Study SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Long, Michelle T.] Boston Med Ctr, Gastroenterol, Boston, MA USA. [Long, Michelle T.; Pedley, Alison; Massaro, Joseph M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Biostat, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Endocrinol, Boston, MA 02115 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2191 BP 1276A EP 1276A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404432 ER PT J AU Vuppalanchi, R Siddiqui, MS Hallinan, EK Abdelmalek, MF Neuschwander-Tetri, BA Loomba, R Kowdley, KV Terrault, N McCullough, AJ Tonascia, J Brunt, EM Kleiner, DE Doo, E Chalasani, NP Sanyal, AJ AF Vuppalanchi, Raj Siddiqui, Mohammad S. Hallinan, Erin K. Abdelmalek, Manal F. Neuschwander-Tetri, Brent A. Loomba, Rohit Kowdley, Kris V. Terrault, Norah McCullough, Arthur J. Tonascia, James Brunt, Elizabeth M. Kleiner, David E. Doo, Edward Chalasani, Naga P. Sanyal, Arun J. TI Transient Elastography is Feasible with High Success Rate for Evaluation of Non-Alcoholic Fatty Liver Disease (NAFLD) in a Multicenter Setting SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Vuppalanchi, Raj; Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Siddiqui, Mohammad S.; Sanyal, Arun J.] Virginia Commonwealth, Richmond, VA USA. [Hallinan, Erin K.; Tonascia, James] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Abdelmalek, Manal F.] Duke, Durham, NC USA. [Neuschwander-Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA. [Loomba, Rohit] Univ Calif San Diego, San Diego, CA 92103 USA. [Kowdley, Kris V.] Swedish Med Ctr, Seattle, WA USA. [Terrault, Norah] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCullough, Arthur J.] Cleveland Clin, Cleveland, OH 44106 USA. [Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Doo, Edward] NIH, Bethesda, MD 20892 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2220 BP 1290A EP 1290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404461 ER PT J AU Yardeni, D Etzion, O Toledano, R Novack, V Shalev, A Wolak, A Rotman, Y AF Yardeni, David Etzion, Ohad Toledano, Ronen Novack, Victor Shalev, Aryeh Wolak, Arik Rotman, Yaron TI The association of ALT levels with myocardial perfusion imaging and cardiovascular morbidity SO HEPATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 13-17, 2015 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Etzion, Ohad; Rotman, Yaron] NIH, Liver Dis Branch, Rockville, MD USA. [Yardeni, David] Soroka Univ Med Ctr, Internal Med Div, Beer Sheva, Israel. [Etzion, Ohad] Soroka Univ Med Ctr, Gastroenterol & Liver Dis, Beer Sheva, Israel. [Toledano, Ronen; Novack, Victor] Soroka Univ Med Ctr, Clin Res Ctr, Beer Sheva, Israel. [Shalev, Aryeh; Wolak, Arik] Soroka Univ Med Ctr, Dept Cardiol, Beer Sheva, Israel. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2015 VL 62 SU 1 SI SI MA 2224 BP 1292A EP 1292A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB2YA UT WOS:000368375404465 ER PT J AU Marangoni, D Vijayasarathy, C Bush, RA Wei, LL Wen, R Sieving, PA AF Marangoni, Dario Vijayasarathy, Camasamudram Bush, Ronald A. Wei, Lisa L. Wen, Rong Sieving, Paul A. TI Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3(-/-) Mouse Model of Achromatopsia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE achromatopsia; CNGB3; CNTF; intravitreal injection; cone photoreceptors ID CELL INTRAOCULAR IMPLANTS; DARK-ADAPTED ELECTRORETINOGRAM; SCOTOPIC THRESHOLD RESPONSE; RETINITIS-PIGMENTOSA; RETINAL DEGENERATION; ACTIVATION STEPS; SCHEMATIC EYE; MICE LACKING; CNTF; RAT AB PURPOSE. Ciliary neurotrophic factor (CNTF) was recently shown to augment cone function in CNGB3 mutant achromat dogs. However, testing CNTF-releasing implant in human CNGB3 achromats failed to show benefit. We evaluated the effects of CNTF protein on the retinal function in an additional achromatopsia model, the CNGB3(-/-) mouse. METHODS. Fifty-nine CNGB3(-/-) mice (postnatal day [PD] +/- SD = 30 +/- 7) received a unilateral intravitreal injection of 1 or 2 mu g CNTF protein, and 15 wild-type (WT) mice (PD = 34 +/- 3) received 1 mu g CNTF. Retinal function was evaluated by flash ERG and photopic flicker ERG (fERG) at 7 and 14 days after treatment. RESULTS. Seven days post CNTF, the photopic b-wave V-max was significantly increased in CNGB3(-/-) mice (P < 0.01), whereas it was reduced in WT mice (P < 0.05). Ciliary neurotrophic factor significantly increased the amplitude of photopic fERG and the photopic oscillatory potentials (OPs) in CNGB3(-/-) mice. Ciliary neurotrophic factor did not alter the scotopic a-wave in either CNGB3(-/-) or WT mice, but it increased the scotopic b-wave k (P < 0.01) in CNGB3(-/-) mice, indicating diminished scotopic sensitivity, and reduced the scotopic b-wave V-max in WT mice (P < 0.05). No difference was found in ERG parameters between 1 or 2 mu g CNTF. Fourteen days after CNTF injection the ERG changes in CNGB3(-/-) mice were lost. CONCLUSIONS. Intravitreal bolus CNTF protein caused a small and transient improvement of cone-mediated function in CNGB3(-/-) mice, whereas it reduced rod-mediated function. The increase in photopic OPs and the lack of changes in scotopic a-wave suggest a CNTF effect on the inner retina. C1 [Marangoni, Dario; Vijayasarathy, Camasamudram; Bush, Ronald A.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Wei, Lisa L.; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Marangoni, Dario] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy. [Wen, Rong] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Room 6A03, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS NR 45 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2015 VL 56 IS 11 BP 6810 EP 6822 DI 10.1167/iovs.15-16866 PG 13 WC Ophthalmology SC Ophthalmology GA DB0YQ UT WOS:000368235100082 PM 26567794 ER PT J AU Olfson, M King, M Schoenbaum, M AF Olfson, Mark King, Marissa Schoenbaum, Michael TI Antipsychotic Treatment of Adults in the United States SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Antipsychotics; Delivery of Care ID COMORBIDITY-SURVEY-REPLICATION; BIPOLAR DISORDER; OLDER-ADULTS; ATYPICAL ANTIPSYCHOTICS; HOME RESIDENTS; DEMENTIA; POPULATION; RISK; CARE; DEPRESSION AB Objective: Despite safety risks associated with antipsychotic medications, little is known about their use in older adults. This article describes patterns of antipsychotic treatment of older and younger adults in the United States. Method: The IMS LifeLink LRx Longitudinal Prescription database was analyzed retrospectively, focusing on adults who filled antipsychotic prescriptions. The database was searched for the years 2006 and 2008-2010. Denominators were adjusted to generalize annual antipsychotic use percentages by sex and single year of age to the US population. Among adults with any antipsychotic use, percentages with short-term (<= 30 days) and long-term (>= 120 days) use, prescriptions from psychiatrists, use of other psychotropic medication classes, and ICD-9 clinical diagnoses were also evaluated. Results: The percentages of US adults by age group who used antipsychotics in 2010 were 0.93% (20-34 years), 1.46% (35-59 years), 1.54% (60-64 years), 1.36% (65-69 years), 1.36% (70-74 years), 1.58% (75-79 years), and 2.09% (80-84 years). Women were consistently more likely than men to use antipsychotics. The percentages of antipsychotic-treated older adults with long-term use were 53.7% (70-74 years), 49.2% (75-79 years), and 46.2% (80-84 years). Among adults with any antipsychotic use, percentages with prescriptions from psychiatrists decreased with age from 66.2% (20-34 years) to 20.6% (80-84 years). Dementia was commonly diagnosed among antipsychotic-treated adults aged 75-79 years (37.2%) and 80-84 years (47.8%) who had any mental disorder or dementia diagnoses. Conclusions: Despite concerns over the safety of antipsychotic treatment of older adults, long-term use is common. Key challenges for clinical research and practice include development and implementation of management strategies for older adults that are safer than antipsychotic medications. C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [King, Marissa] Yale Univ, Sch Management, New Haven, CT USA. [Schoenbaum, Michael] NIMH, Off Sci Policy Planning & Evaluat, NIH, Bethesda, MD 20892 USA. RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@cumc.columbia.edu FU National Institutes of Health; New York State Psychiatric Institute FX This research was funded by contracts from the National Institutes of Health to Yale University (Dr King) and Columbia University (Dr Olfson). Dr Olfson is also supported by the New York State Psychiatric Institute. NR 44 TC 3 Z9 3 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2015 VL 76 IS 10 BP 1346 EP + DI 10.4088/JCP.15m09863 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2OC UT WOS:000368347900021 PM 26528641 ER PT J AU Rodriguez, K Kwan, AC Lai, SH Lima, JAC Vigneault, D Sandfort, V Pattanayak, P Ahlman, MA Mallek, M Sibley, CT Bluemke, DA AF Rodriguez, Karen Kwan, Alan C. Lai, Shenghan Lima, Joao A. C. Vigneault, Davis Sandfort, Veit Pattanayak, Puskar Ahlman, Mark A. Mallek, Marissa Sibley, Christopher T. Bluemke, David A. TI Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ARTERY-DISEASE; QUANTIFICATION; ATHEROSCLEROSIS; PROGRESSION; TRIAL; RISK; ASSOCIATION; MULTICENTER; HISTOLOGY AB Purpose: To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods: This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis. Eligible subjects were asymptomatic individuals older than 55 years who were eligible for statin therapy. Coronary CT angiography was performed by using a 320-detector row scanner. Coronary wall thickness and plaque were evaluated in all epicardial coronary arteries greater than 2 mm in diameter. Images were analyzed by using dedicated software involving an adaptive lumen attenuation algorithm. Total plaque index (calcified plus noncalcified plaque) was defined as plaque volume divided by vessel length. Multivariable regression analysis was performed to determine the relationship between risk factors and plaque indexes. Results: The mean age of the subjects was 65.5 years +/- 6.9 (standard deviation) (36% women), and the median coronary artery calcium (CAC) score was 73 (interquartile range, 1-434). The total coronary plaque index was higher in men than in women (42.06 mm(2) +/- 9.22 vs 34.33 mm(2) +/- 8.35; P < .001). In multivariable analysis controlling for all risk factors, total plaque index remained higher in men than in women (by 5.01 mm(2); P = .03) and in those with higher simvastatin doses (by 0.44 mm(2)/10 mg simvastatin dose equivalent; P = .02). Noncalcified plaque index was positively correlated with systolic blood pressure (b = 0.80 mm(2)/10 mm Hg; P = .03), diabetes (b = 4.47 mm(2); P =.03), and low-density lipoprotein (LDL) cholesterol level (b = 0.04 mm(2)/mg/dL; P = .02); the association with LDL cholesterol level remained significant (P = .02) after additional adjustment for the CAC score. Conclusion: LDL cholesterol level, systolic blood pressure, and diabetes were associated with noncalcified plaque burden at coronary CT angiography in asymptomatic individuals with low-to-moderate risk. (C) RSNA, 2015 C1 [Rodriguez, Karen; Kwan, Alan C.; Vigneault, Davis; Sandfort, Veit; Pattanayak, Puskar; Ahlman, Mark A.; Mallek, Marissa; Sibley, Christopher T.; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Lai, Shenghan] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10-1C355, Bethesda, MD 20892 USA. EM david.bluemke@nih.gov FU National Institutes of Health [EB000072, CL090019] FX This research was supported by the National Institutes of Health (grants EB000072 and CL090019). NR 29 TC 7 Z9 7 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2015 VL 277 IS 1 BP 73 EP 80 DI 10.1148/radiol.2015142551 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3TG UT WOS:000368434000009 PM 26035436 ER PT J AU Tee, MW Won, S Raman, FS Yi, C Vigneault, DM Davies-Venn, C Liu, ST Lardo, AC Lima, JAC Noble, JA Emter, CA Bluemke, DA AF Tee, Michael W. Won, Samuel Raman, Fabio S. Yi, Colin Vigneault, Davis M. Davies-Venn, Cynthia Liu, Songtao Lardo, Albert C. Lima, Joao A. C. Noble, J. Alison Emter, Craig A. Bluemke, David A. TI Regional Strain Analysis with Multidetector CT in a Swine Cardiomyopathy Model: Relationship to Cardiac MR Tagging and Myocardial Fibrosis SO RADIOLOGY LA English DT Article ID MULTISLICE COMPUTED-TOMOGRAPHY; CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; HEART-FAILURE; DIAGNOSIS; ACCURACY; TRACKING; ECHOCARDIOGRAPHY; ANGIOGRAPHY; MOTION AB Purpose: To investigate the use of cine multidetector computed tomography (CT) to detect changes in myocardial function in a swine cardiomyopathy model. Materials and Methods: All animal protocols were in accordance with the Principles for the Utilization and Care of Vertebrate Animals Used in Testing Research and Training and approved by the University of Missouri Animal Care and Use Committee. Strain analysis of cine multidetector CT images of the left ventricle was optimized and analyzed with feature-tracking software. The standard of reference for strain was harmonic phase analysis of tagged cardiac magnetic resonance (MR) images at 3.0 T. An animal model of cardiomyopathy was imaged with both cardiac MR and 320-section multidetector CT at a temporal resolution of less than 50 msec. Three groups were evaluated: control group (n = 5), aortic-banded myocardial hypertrophy group (n = 5), and aortic-banded and cyclosporine Atreated cardiomyopathy group (n = 5). Histologic samples of the myocardium were obtained for comparison with strain results. Dunnett test was used for comparisons of the concentric remodeling group and eccentric remodeling group against the control group. Results: Collagen volume fraction ranged from 10.9% to 14.2%; lower collagen fraction values were seen in the control group than in the cardiomyopathy groups (P < .05). Ejection fraction and conventional metrics showed no significant differences between control and cardiomyopathy groups. Radial strain for both cardiac MR and multidetector CT was abnormal in both concentric (cardiac MR 25.1% +/- 4.2; multidetector CT 28.4% +/- 2.8) and eccentric (cardiac MR 23.2% +/- 2.0; multidetector CT 24.4% +/- 2.1) remodeling groups relative to control group (cardiac MR 18.9% +/- 1.9, multidetector CT 22.0% +/- 1.7, p < .05, all comparisons). Strain values for multidetector CT versus cardiac MR showed better agreement in the radial direction than in the circumferential direction (r = 0.55, P = .03 vs r = 0.40, P = .13, respectively). Conclusion: Multidetector CT strain analysis has potential to identify regional wall-motion abnormalities in cardiomyopathy that is not otherwise detected using conventional metrics of myocardial function. (C) RSNA, 2015 C1 [Tee, Michael W.; Won, Samuel; Raman, Fabio S.; Yi, Colin; Vigneault, Davis M.; Davies-Venn, Cynthia; Liu, Songtao; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Tee, Michael W.; Vigneault, Davis M.; Noble, J. Alison] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX1 3PJ, England. [Lardo, Albert C.; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. [Tee, Michael W.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Vigneault, Davis M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Emter, Craig A.] Univ Missouri, Dept Biomed Sci, Columbia, MO USA. RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Raman, Fabio/0000-0003-2393-9937 FU National Institutes of Health Intramural Research Program [CL090019-04, EB000072-04] FX This research was supported by the National Institutes of Health Intramural Research Program CL090019-04 and EB000072-04. NR 25 TC 1 Z9 1 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2015 VL 277 IS 1 BP 88 EP 94 DI 10.1148/radiol.2015142339 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3TG UT WOS:000368434000011 PM 25853636 ER PT J AU Moley, JF Skinner, M Gillanders, WE Lairmore, TC Rowland, KJ Traugott, AL Jin, LDX Wells, SA AF Moley, Jeffrey F. Skinner, Michael Gillanders, William E. Lairmore, Terry C. Rowland, Kathryn J. Traugott, Amber L. Jin, Linda X. Wells, Samuel A., Jr. TI Management of the Parathyroid Glands During Preventive Thyroidectomy in Patients With Multiple Endocrine Neoplasia Type 2 SO ANNALS OF SURGERY LA English DT Article DE calcitonin; central neck dissection; hyperparathyroidism; hypoparathyroidism; medullary thyroid carcinoma; multiple endocrine neoplasia type 2; recurrent laryngeal nerve; RET proto-oncogene; thyroidectomy ID CENTRAL NECK DISSECTION; PROPHYLACTIC THYROIDECTOMY; RET PROTOONCOGENE; MEN 2A; CARCINOMA; MUTATIONS; FAMILIES; CANCER; RISK; FMTC AB Objectives:Patients with multiple endocrine neoplasia type 2 (MEN2) have mutations in the RET protooncogene and virtually all of them will develop medullary thyroid carcinoma. Family members identified by genetic testing are candidates for preventive thyroidectomy. Management of the parathyroids during thyroidectomy is controversial. Some experts advocate total parathyroidectomy with autotransplantation, whereas others recommend preserving the parathyroids in situ.Methods:Between 1993 and 2000, we performed preventive thyroidectomies on 50 patients with MEN2A (group A). All patients had a central neck dissection (CND) combined with total parathyroidectomy and autotransplantation of parathyroid slivers to the nondominant forearm or to the neck. Between 2003 and the present, we performed 102 preventive thyroidectomies attempting to preserve the parathyroid glands in situ with an intact vascular pedicle (group B). Individual parathyroids were autotransplanted only if they appeared nonviable or could not be preserved intact. Central neck dissection was done only if the serum calcitonin was greater than 40pg/mL.Results:Permanent hypoparathyroidism occurred in 3 (6%) of 50 patients in group A, compared with 1 (1%) of 102 patients in group B (P=0.1). After total thyroidectomy, no patient in either group developed permanent recurrent laryngeal nerve injury or hyperparathyroidism. Immediate postoperative serum calcitonin levels were in the normal range (<5pg/mL) in 100 of 102 patients in group B. No patients in either group have died. Oncologic follow-up of patients in group B is in progress.Conclusions:In patients with MEN2A treated by preventive total thyroidectomy routine total parathyroidectomy with autotransplantation and CND gives excellent long-term results. However, preservation of the parathyroids in situ during preventive thyroidectomy combined with selective CND based on preoperative basal serum calcitonin levels is an effective and safe alternative that results in a very low incidence of hypoparathyroidism. C1 [Moley, Jeffrey F.; Gillanders, William E.; Rowland, Kathryn J.; Traugott, Amber L.; Jin, Linda X.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Skinner, Michael] UT Southwestern, Dept Surg, Dallas, TX USA. [Lairmore, Terry C.] Scott & White Med Ctr, Dept Surg, Temple, TX USA. [Wells, Samuel A., Jr.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Moley, JF (reprint author), Washington Univ, Sch Med, St Louis, MO 63108 USA. EM moleyj@wustl.edu RI Traugott, Amber/J-7490-2016 FU NCI NIH HHS [P30 CA091842] NR 12 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD OCT PY 2015 VL 262 IS 4 BP 641 EP 646 DI 10.1097/SLA.0000000000001464 PG 6 WC Surgery SC Surgery GA DA7QT UT WOS:000367999800010 PM 26366543 ER PT J AU Banydeen, R Rose, AMC Martin, D Aiken, W Alexis, C Andall-Brereton, G Ashing, K Avery, JG Avery, P Deloumeaux, J Ekomaye, N Gabriel, O Hassell, T Hughes, L Hutton, M Jyoti, SK Layne, P Luce, D Patrick, A Prussia, P Smith-Ravin, J Veronique-Baudin, J Blackman, E Roach, V Ragin, C AF Banydeen, Rishika Rose, Angela M. C. Martin, Damali Aiken, William Alexis, Cheryl Andall-Brereton, Glennis Ashing, Kimin Avery, J. Gordon Avery, Penny Deloumeaux, Jacqueline Ekomaye, Natasha Gabriel, Owen Hassell, Trevor Hughes, Lowell Hutton, Maisha Jyoti, Shravana Kumar Layne, Penelope Luce, Daniele Patrick, Alan Prussia, Patsy Smith-Ravin, Juliette Veronique-Baudin, Jacqueline Blackman, Elizabeth Roach, Veronica Ragin, Camille TI Advancing Cancer Control Through Research and Cancer Registry Collaborations in the Caribbean SO CANCER CONTROL LA English DT Article ID PROSTATE-CANCER; MORTALITY-RATES; POPULATION; MARTINIQUE; TRINIDAD; AFRICAN; TOBAGO AB Background: Few national registries exist in the Caribbean, resulting in limited cancer statistics being available for the region. Therefore, estimates are frequently based on the extrapolation of mortality data submitted to the World Health Organization. Thus, regional cancer surveillance and research need promoting, and their synergy must be strengthened. However, differences between countries outweigh similarities, hampering registration and availability of data. Methods: The African-Caribbean Cancer Consortium (AC3) is a broad-based resource for education, training, and research on all aspects of cancer in populations of African descent. The AC3 focuses on capacity building in cancer registration in the Caribbean through special topics, training sessions, and biannual meetings. We review the results from selected AC3 workshops, including an inventory of established cancer registries in the Caribbean region, current cancer surveillance statistics, and a review of data quality. We then describe the potential for cancer research surveillance activities and the role of policymakers. Results: Twelve of 30 Caribbean nations have cancer registries. Four of these nations provide high-quality incidence data, thus covering 14.4% of the population; therefore, regional estimates are challenging. Existing research and registry collaborations must pave the way and are facilitated by organizations like the AC3. Conclusions: Improved coverage for cancer registrations could help advance health policy through targeted research. Capacity building, resource optimization, collaboration, and communication between cancer surveillance and research teams are key to obtaining robust and complete data in the Caribbean. C1 [Banydeen, Rishika] Univ Hosp Martinique, Clin Res & Innovat Unit, Fort De France, Martinique. [Smith-Ravin, Juliette; Veronique-Baudin, Jacqueline] Univ Hosp Martinique, Martinique Canc Registry, Fort De France, Martinique. [Rose, Angela M. C.; Ekomaye, Natasha; Prussia, Patsy] Univ W Indies, Chron Dis Res Ctr, St Michael, Barbados. [Alexis, Cheryl] Univ W Indies, Fac Med Sci, St Michael, Barbados. [Martin, Damali] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Aiken, William] Univ W Indies, Dept Surg, Kingston 7, Jamaica. [Aiken, William] Univ W Indies, Dept Radiol, Kingston 7, Jamaica. [Aiken, William] Univ W Indies, Dept Anaesthesia, Kingston 7, Jamaica. [Aiken, William] Univ W Indies, Dept Intens Care, Kingston 7, Jamaica. [Andall-Brereton, Glennis] Caribbean Publ Hlth Agcy, Surveillance Dis Prevent & Control Div, Port Of Spain, Trinid & Tobago. [Ashing, Kimin] City Hope Natl Med Ctr, Ctr Community Alliance Res & Educ, Dept Populat Sci, Duarte, CA 91010 USA. [Avery, J. Gordon] Univ Med & Hlth Sci, Trinity Palmetto Point, St Kitts & Nevi. [Avery, J. Gordon; Avery, Penny] Nevis Maternal Hlth Fund, Pink Lily Canc Care, Trinity Palmetto Point, St Kitts & Nevi. [Deloumeaux, Jacqueline] Univ Hosp Pointe A Pitre, Guadeloupe Canc Registry, Pointe a Pitre, Guadeloupe. [Gabriel, Owen] Victoria Hosp, Dept Oncol, Castries, St Lucia. [Hassell, Trevor; Hutton, Maisha] Hlth Caribbean Coalit, Bridgetown, Barbados. [Hughes, Lowell] Hughes Med Ctr, Anguilla, British West In, W Ind Assoc St. [Jyoti, Shravana Kumar] Hlth Serv Author Hosp, Georgetown, Cayman Islands, Guyana. [Layne, Penelope] Minist Hlth, Guyana Canc Registry, Queenstown, Guyana. [Luce, Daniele] French Natl Inst Hlth & Med Res, Pointe a Pitre, Guadeloupe. [Patrick, Alan] Tobago Hlth Studies Off, Scarborough, Trinid & Tobago. [Blackman, Elizabeth; Ragin, Camille] Temple Hlth, Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA USA. [Roach, Veronica] Dr Elizabeth Quamina Natl Canc Registry Trinidad, Mt Hope, Trinid & Tobago. RP Ragin, C (reprint author), Fox Chase Canc Ctr, Canc Prevent & Control Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM camille.ragin@fccc.edu RI LUCE, Daniele/J-9125-2015 FU National Cancer Institute [P30 CA006927, R13 CA192672-03] FX Mrs Banydeen, Rose, Layne, and Roach and Drs Aiken, Ashing, Avery, Deloumeaux, Jyoti, Luce, Patrick, Smith-Ravin, Veronique-Baudin, and Ragin are members of the African-Caribbean Cancer Consortium. This work is supported in part by the National Cancer Institute (P30 CA006927) and (R13 CA192672-03 to C.R). No significant relationships exist between the other authors and the companies/organizations whose products or services may be referenced in this article. NR 49 TC 1 Z9 1 U1 0 U2 0 PU H LEE MOFFITT CANCER CENTER & RESEARCH INST PI TAMPA PA 12902 MAGNOLIA DR, TAMPA, FL 33612 USA SN 1073-2748 J9 CANCER CONTROL JI Cancer Control PD OCT PY 2015 VL 22 IS 4 BP 520 EP 530 PG 11 WC Oncology SC Oncology GA DA8JS UT WOS:000368051500019 PM 26678981 ER PT J AU Zhang, MC Xue, AM Shen, YW Oliveira, JB Li, L Zhao, ZQ Burke, A AF Zhang, Mingchang Xue, Aimin Shen, Yiwen Oliveira, Joao Bosco Li, Ling Zhao, Ziqin Burke, Allen TI Mutations of desmoglein-2 in sudden death from arrhythmogenic right ventricular cardiomyopathy and sudden unexplained death SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article; Proceedings Paper CT 20th Meeting of International-Association-of-Forensic-Sciences (IAFS) CY OCT 13-18, 2014 CL Seoul, SOUTH KOREA SP Int Assoc Forensic Sci DE Desmoglein-2; Desmosomal mutation; Sudden cardiac death; Arrhythmogenic right ventricular cardiomyopathy; Sudden unexplained death ID PROTEIN GENE-MUTATIONS; DILATED CARDIOMYOPATHY; HEART-DISEASE; DYSPLASIA/CARDIOMYOPATHY; DYSPLASIA; AUTOPSY; DESMOSOMES; ADHESION; YOUNG; INVOLVEMENT AB Desmoglein-2 (DSG2), a member of the desmosomal cadherin superfamily, has been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which may cause life-threatening ventricular arrhythmias and sudden death. Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy. We sequenced all 15 exons of DSG2 in DNA extracted from post-mortem heart tissues of 25 patients dying with ARVC and 25 from sudden unexplained death (SUD). The primers were designed using the Primer Express 3.0 software. Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130 xl Genetic Analyzer. Mutation damage prediction was made using Mutation Taster, Polyphen and SIFT software. 2 DSG2 mutations (p. S1026Q fsX12, p. G678R) in two ARVC samples and 2 DSG2 mutations(p. E 896K, p. A858 V) in two SUD samples were identified, all the mutations were novel. We concluded that DSG2 mutations may not specific for ARVC and may be related to the fatal arrhythmic events even in patients with a morphological normal heart. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Zhang, Mingchang; Xue, Aimin; Shen, Yiwen; Li, Ling; Zhao, Ziqin; Burke, Allen] Fudan Univ, Shanghai Med Coll, Dept Forens Med, Shanghai 200433, Peoples R China. [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Li, Ling] China Univ Polit Sci & Law, Key Lab Evidence Sci, Div Forens Med, Beijing, Peoples R China. [Li, Ling; Burke, Allen] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. RP Zhang, MC (reprint author), Yixueyuan Rd 138, Shanghai 200032, Peoples R China. EM zmc830921@gmail.com NR 44 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 EI 1872-6283 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD OCT PY 2015 VL 255 BP 85 EP 88 DI 10.1016/j.forsciint.2015.07.052 PG 4 WC Medicine, Legal SC Legal Medicine GA DA7UJ UT WOS:000368009500013 PM 26296472 ER PT J AU Karan, S Scheuerell, C Kiesel, BF Ji, JP Puhalla, S Beumer, JH Gopalakrishnan, M Gobburu, J AF Karan, Sharon Scheuerell, Christie Kiesel, Brian F. Ji, Jiuping Puhalla, Shannon Beumer, Jan H. Gopalakrishnan, Mathangi Gobburu, Joga TI Population PK/PD from a Phase I Study of the Single-Agent PARP Inhibitor, Veliparib, in Patients with PARP Sensitive Tumor Types or BRCA 1/2 -Mutated Cancer SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Meeting Abstract C1 [Karan, Sharon; Scheuerell, Christie; Gopalakrishnan, Mathangi; Gobburu, Joga] Univ Maryland, Sch Pharm, Pharmacometr, Bethesda, MD USA. [Kiesel, Brian F.; Puhalla, Shannon; Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Ji, Jiuping] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD OCT PY 2015 VL 42 SU 1 MA T-60 BP S69 EP S69 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DA5KM UT WOS:000367842000129 ER PT J AU Ralya, A Brundage, RC McGovern, RM Goetz, MP Kummar, S Chen, AP Reid, JM AF Ralya, Andrew Brundage, Richard C. McGovern, Renee M. Goetz, Matthew P. Kummar, Shivaani Chen, Alice P. Reid, Joel M. TI Population Pharmacokinetic Model for Oral Endoxifen in Patients with Breast or Gynecologic Cancers SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Meeting Abstract C1 [Ralya, Andrew; McGovern, Renee M.; Goetz, Matthew P.; Reid, Joel M.] Mayo Clin, Rochester, MN USA. [Brundage, Richard C.] Univ Minnesota, Minneapolis, MN USA. [Kummar, Shivaani] Stanford Univ, Stanford, CA 94305 USA. [Chen, Alice P.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD OCT PY 2015 VL 42 SU 1 MA T-15 BP S49 EP S50 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DA5KM UT WOS:000367842000085 ER PT J AU Yu, XY Xie, Y Pan, XQ Mayfield-Johnson, S Whipple, J Azadbakht, E AF Yu, Xinyu Xie, Yue Pan, Xuequn Mayfield-Johnson, Susan Whipple, Jessica Azadbakht, Elena TI Developing an evidence-based public health informatics course SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article DE Public Health Informatics; Needs Assessment; Education; Public Health Professional; Community-Institutional Relations ID COMPETENCES AB Objectives: This study assessed the need to develop a public health informatics (PHI) introductory course and determine contents of such a course. Methods: Community assessments employing focus group interviews and an online survey were utilized to determine course need and content. Results: Results revealed a need to provide PHI training to graduate public health students and suggested broad course content requirements. Results indicated lack of awareness of libraries and librarians as sources of public health information. Conclusions: A graduate PHI course was developed and delivered. Additionally, implementation of a subject guide increased the library's profile. C1 [Yu, Xinyu] Univ So Mississippi, Sch Lib & Informat Sci, Hattiesburg, MS 39406 USA. [Xie, Yue] Sam Houston State Univ, Dept Hlth Serv & Promot, Huntsville, TX 77340 USA. [Pan, Xuequn] Natl Inst Hlth Clin Ctr, Lab Informat Dev, Bethesda, MD USA. [Mayfield-Johnson, Susan] Univ So Mississippi, Dept Publ Hlth, Hattiesburg, MS 39406 USA. [Azadbakht, Elena] Univ So Mississippi, Univ Lib, Hattiesburg, MS 39406 USA. RP Yu, XY (reprint author), Univ So Mississippi, Sch Lib & Informat Sci, Hattiesburg, MS 39406 USA. EM xinyu.yu@usm.edu; yue.xie@shsu.edu; xuequn.pan@nih.gov; susan.johnson@usm.edu; jessi.gibbons@gmail.com; elena.azadbakht@usm.edu FU Department of Health and Human Services, National Institutes of Health, National Library of Medicine [HHS-N-276-2011-00004-C]; University of Maryland Baltimore; School of Library and Information Science; Department of Public Health at the University of Southern Mississippi FX This project has been funded in whole or in part with federal funds from the Department of Health and Human Services, National Institutes of Health, National Library of Medicine, under contract no. HHS-N-276-2011-00004-C with the University of Maryland Baltimore.; The authors thank the School of Library and Information Science and the Department of Public Health at the University of Southern Mississippi for their support of the project. The authors are indebted to Charles Daughdrill and Ryan Kelly for their assistance in the survey of the Mississippi Public Health Association and the Mississippi Rural Health Association members. NR 12 TC 0 Z9 0 U1 4 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2015 VL 103 IS 4 BP 194 EP 197 DI 10.3163/1536-5050.103.4.007 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA DA3HB UT WOS:000367686700007 PM 26512219 ER PT J AU Belter, CW AF Belter, Christopher W. TI Bibliometric indicators: opportunities and limits SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material DE Bibliometrics; Program Evaluation; Research Personnel/Statistics and Numerical Data; Research/Organization and Administration; Peer Review; Research ID IMPACT FACTOR; CITATION C1 [Belter, Christopher W.] NIH, NIH Lib, Bethesda, MD 20892 USA. RP Belter, CW (reprint author), NIH, NIH Lib, Bldg 10, Bethesda, MD 20892 USA. EM christopher.belter@nih.gov RI Belter, Christopher/L-6487-2013 OI Belter, Christopher/0000-0001-5221-6880 NR 17 TC 6 Z9 6 U1 0 U2 18 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2015 VL 103 IS 4 BP 219 EP 221 DI 10.3163/1536-5050.103.4.014 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA DA3HB UT WOS:000367686700015 PM 26512227 ER PT J AU Montgomery, BEE Rompalo, A Hughes, J Wang, J Haley, D Soto-Torres, L Chege, W Justman, J Kuo, I Golin, C Frew, P Mannheimer, S Hodder, S AF Montgomery, Brooke E. E. Rompalo, Anne Hughes, James Wang, Jing Haley, Danielle Soto-Torres, Lydia Chege, Wairimu Justman, Jessica Kuo, Irene Golin, Carol Frew, Paula Mannheimer, Sharon Hodder, Sally CA HIV Prevention Trials Network 064 Women's HIV SeroIncidence Study T TI Violence Against Women in Selected Areas of the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INTIMATE-PARTNER VIOLENCE; CHILDHOOD SEXUAL-ABUSE; HIV-POSITIVE WOMEN; RURAL SOUTH-AFRICA; LOS-ANGELES-COUNTY; DOMESTIC VIOLENCE; RISK BEHAVIORS; MENTAL-HEALTH; EMOTIONAL ABUSE; SUBSTANCE-ABUSE AB Objectives. We determined the prevalence of recent emotional, physical, and sexual violence against women and their associations with HIV-related risk factors in women living in the United States. Methods. We performed an assessment of women ages 18 to 44 years with a history of unprotected sex and 1 or more personal or partner HIV risk factors in the past 6 months from 2009 to 2010. We used multivariable logistic regression to examine the association of experiencing violence. Results. Among 2099 women, the prevalence of emotional abuse, physical violence, and sexual violence in the previous 6 months was 31%, 19%, and 7%, respectively. Nonmarried status, food insecurity, childhood abuse, depression symptomology, and posttraumatic stress disorder were significantly associated with multiple types of violence. All types of violence were associated with at least 3 different partner or personal HIV risk behaviors, including unprotected anal sex, previous sexually transmitted infection diagnosis, sex work, or partner substance abuse. Conclusions. Our data suggested that personal and partner HIV risk behaviors, mental illness, and specific forms of violence frequently co-occurred in the lives of impoverished women. We shed light on factors purported to contribute to a syndemic in this population. HIV prevention programs in similar populations should address these co-occurring issues in a comprehensive manner. C1 [Montgomery, Brooke E. E.] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. [Rompalo, Anne] Johns Hopkins Sch Med, Baltimore, MD USA. [Hughes, James; Wang, Jing] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Haley, Danielle] FHI 360, Durham, NC USA. [Soto-Torres, Lydia; Chege, Wairimu] NIAID, NIH, Bethesda, MD 20892 USA. [Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Kuo, Irene] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Golin, Carol] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA. [Frew, Paula] Emory Univ, Sch Med, Atlanta, GA USA. [Mannheimer, Sharon] Columbia Univ, Mailman Sch Publ Hlth, Coll Phys & Surg, New York, NY 10027 USA. [Hodder, Sally] Rutgers State Univ, New Jersey Med Sch, New York, NY USA. RP Montgomery, BEE (reprint author), Univ Arkansas Med Sci, Coll Publ Hlth, 4301 W Markham St 820, Little Rock, AR 72205 USA. EM bemontgomery@uams.edu FU HIV Prevention Trials Network (HPTN) Scholars Program - National Institute of Allergy and Infectious Disease; Translational Research Institute (TRI) through the NIH National Center for Research Resources [UL1TR000039, KL2TR000063]; National Center for Advancing Translational Sciences; National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; National Institute of Mental Health [UM1 AI068619, UM 1AI068617, UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5U1Al069466]; University of North Carolina Clinical Trials Unit [AI069423]; University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award [RR 025747]; University of North Carolina Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008]; Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award [UL1 RR 25005] FX The primary author's work on this article was supported through the HIV Prevention Trials Network (HPTN) Scholars Program funded by the National Institute of Allergy and Infectious Disease and by the Translational Research Institute (TRI), grants UL1TR000039 and KL2TR000063 through the NIH National Center for Research Resources and the National Center for Advancing Translational Sciences. Additional funding was received through the National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and National Institute of Mental Health (cooperative agreement no. UM1 AI068619, UM 1AI068617, and UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University (5U1Al069466); University of North Carolina Clinical Trials Unit (AI069423); University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award (RR 025747); University of North Carolina Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and Clinical and Translational Science Award (UL1 RR025008); The Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit(5 UM1 AI069503-07); and The Johns Hopkins Adult AIDS Clinical Trial Unit (AI069465) and The Johns Hopkins Clinical and Translational Science Award (D). NR 82 TC 2 Z9 2 U1 8 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2015 VL 105 IS 10 BP 2156 EP 2166 DI 10.2105/AJPH.2014.302430 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CZ9UC UT WOS:000367441500048 PM 25790408 ER PT J AU Weigand, LA Kwong, K Myers, AC AF Weigand, Letitia A. Kwong, Kevin Myers, Allen C. TI The Effects of Nerve Growth Factor on Nicotinic Synaptic Transmission in Mouse Airway Parasympathetic Neurons SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE nerves; parasympathetic; cholinergic; bronchoconstriction; asthma ID ALLERGIC-ASTHMA; SYMPATHETIC NEURONS; GANGLIONIC NEURONS; AUTONOMIC GANGLIA; SMOOTH-MUSCLE; IN-VITRO; RECEPTORS; MICE; NGF; NEUROTROPHINS AB In autonomic ganglia, acetylcholine (ACh) is released from preganglionic nerve terminals and binds to nicotinic ACh receptors (nAChRs) on postganglionic neurons, resulting in a brief, short-lived synaptic potential (fast excitatory postsynaptic potential [fEPSP]). Although nerve growth factor (NGF) is known to affect sensory and sympathetic nerves, especially during development, little is known regarding its effect on parasympathetic nerves, especially on adult neurons. Elevated levels of NGF and NGF-mediated neural plasticity may have a role in airway diseases, such as asthma and chronic obstructive pulmonary disease. In this study, we characterize the composition and response of nAChRs in parasympathetic neurons located in lower airways of mice, and note the effects of NGF on fEPSPs and on nicotinic currents. Based on immunohistochemical staining, nAChRs are made up of alpha-3 and beta-4 subunits; in addition, tropomyosin-related kinase A, the receptor for NGF, is also expressed by the neurons. Vagus nerve evoked fEPSPs and inward currents evoked by a nicotinic receptor agonist (1,1-dimethyl-4-phenylpiperazinium) were increased by NGF. NGF also affected the action potential after hyperpolarization. These studies were done in mice, which are routinely used to study airway diseases, such as asthma, where the allergen-induced contraction of airway smooth muscle has a well-defined parasympathetic cholinergic component. C1 [Weigand, Letitia A.] NIH, Bethesda, MD 20892 USA. [Kwong, Kevin] GlaxoSmithKline, King Of Prussia, PA USA. [Myers, Allen C.] Johns Hopkins Univ, Dept Med Allergy & Clin Immunol, Baltimore, MD USA. RP Myers, AC (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol, 5501 Hopkins Bayview Circle,1A62, Baltimore, MD 21224 USA. EM amyers@jhmi.edu FU National Institutes of Health [HL088608] FX This work was supported by National Institutes of Health grant HL088608 (A.C.M.). NR 31 TC 1 Z9 1 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 OCT PY 2015 VL 53 IS 4 BP 443 EP 449 DI 10.1165/rcmb.2014-0280OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA CZ9UL UT WOS:000367442400002 PM 25647301 ER PT J AU Bronova, I Smith, B Aydogan, B Weichselbaum, RR Vemuri, K Erdelyi, K Makriyannis, A Pacher, P Berdyshev, EV AF Bronova, Irina Smith, Brett Aydogan, Bulent Weichselbaum, Ralph R. Vemuri, Kiran Erdelyi, Katalin Makriyannis, Alex Pacher, Pal Berdyshev, Evgeny V. TI Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1 SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE radiation-induced pulmonary fibrosis; cannabinoid receptor 1; thoracic irradiation; peripherally restricted CB1 antagonist; AM6545 ID TOTAL-BODY IRRADIATION; INDUCED LUNG INJURY; OXIDATIVE STRESS; MOUSE MODEL; FOOD-INTAKE; CB1; ANTAGONIST; EXPRESSION; CELLS; CARDIOMYOPATHY AB Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis. Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg intraperitoneally three times per week. Animal survival and parameters of pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy) was associated with marked pulmonary inflammation and fibrosis in mice and high mortality within 15 to 18 weeks after exposure. Genetic deletion or pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and increased animal survival. Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation. C1 [Bronova, Irina; Berdyshev, Evgeny V.] Univ Chicago, Dept Med, Div Pulm Crit Care Sleep & Allergy, Chicago, IL 60637 USA. [Smith, Brett; Aydogan, Bulent] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Weichselbaum, Ralph R.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Erdelyi, Katalin] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. [Vemuri, Kiran; Pacher, Pal] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Makriyannis, Alex] Northeastern Univ, Dept Pharmaceut Sci, Ctr Drug Discovery, Boston, MA 02115 USA. [Makriyannis, Alex] Northeastern Univ, Ctr Drug Discovery, Dept Chem & Chem Biol, Boston, MA 02115 USA. RP Berdyshev, EV (reprint author), Natl Jewish Hlth, 1400 Jackson St,K924b, Denver, CO 80206 USA. EM berdysheve@njhealth.org FU National Institutes of Health [5P01 HL098050-04, R01DA007215, R37DA023142, R37DA003801, P01DA009158]; National Institute of Alcohol Abuse and Alcoholism Intramural Research Program FX This work was supported by National Institutes of Health grants 5P01 HL098050-04 (E.V.B.) and R01DA007215, R37DA023142, R37DA003801, and P01DA009158 (A.M.) and by the National Institute of Alcohol Abuse and Alcoholism Intramural Research Program (P.P.). NR 45 TC 1 Z9 1 U1 1 U2 5 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 OCT PY 2015 VL 53 IS 4 BP 555 EP 562 DI 10.1165/rcmb.2014-0331OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA CZ9UL UT WOS:000367442400013 PM 26426981 ER PT J AU Burenbatu Borjigin, M Eerdunduleng Huo, WY Gong, CQ Hasengaowa Zhang, GP Longmei Li, M Zhang, XM Sun, XH Yang, J Wang, SL Narisu, N Liu, YJ Bai, HH AF Burenbatu Borjigin, Mandula Eerdunduleng Huo, Wenyan Gong, Cuiqin Hasengaowa Zhang, Guiping Longmei Li, Ming Zhang, Xuemei Sun, Xiaohui Yang, Jie Wang, Shuanglian Narisu, Narisu Liu, Yangjian Bai, Haihua TI Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE microRNA expression; Immune thrombocytopenia; Mongolian medicine; Qishunbaolier treatment ID REGULATORY T-CELLS; MEDIATED CYTOTOXICITY; PERIPHERAL-BLOOD; PURPURA; MICRORNAS; PLATELETS; DIAGNOSIS; PLASMA; AUTOANTIBODIES; CHILDREN AB Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Burenbatu; Eerdunduleng; Huo, Wenyan; Gong, Cuiqin; Hasengaowa; Longmei; Li, Ming; Zhang, Xuemei; Wang, Shuanglian; Bai, Haihua] Affiliated Hosp Inner Mongolia Univ Nationalities, Tongliao 028000, Inner Mongolia, Peoples R China. [Borjigin, Mandula] Delaware State Univ, Dept Chem, Dover, DE 19709 USA. [Zhang, Guiping; Sun, Xiaohui; Yang, Jie] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China. [Narisu, Narisu] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Liu, Yangjian] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. [Bai, Haihua] Inner Mongolia Univ Nationalities, Sch Life Sci, Tongliao 028000, Inner Mongolia, Peoples R China. RP Liu, YJ (reprint author), Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. EM yangjianliu@gmail.com; hh_bai@163.com FU grants for the Key Project in the Chinese National Science & Technology Pillar Program during the Twelfth Five-year Plan Period [2012BAI27B02]; NHGRI, NIH FX We would like to thank the ITP patients and healthy subjects for providing blood samples to make this study possible. We also thank Dr. Zixing Wang for his help on figure preparation. This work was supported by the grants for the Key Project in the Chinese National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2012BAI27B02). NN was supported by the intramural program of NHGRI, NIH. NR 49 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 EI 1950-6007 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD OCT PY 2015 VL 75 BP 196 EP 204 DI 10.1016/j.biopha.2015.07.022 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DA0TB UT WOS:000367509300031 PM 26297543 ER PT J AU Dekker, J Misteli, T AF Dekker, Job Misteli, Tom TI Long-Range Chromatin Interactions SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; CHROMOSOME CONFORMATION CAPTURE; DISTANT REGULATORY ELEMENTS; NUCLEAR LAMINA INTERACTIONS; TRANSFER-RNA GENES; SPATIAL-ORGANIZATION; X-INACTIVATION; HUMAN GENOME; SEQUENCING REVEALS; ACTIVE CHROMATIN AB To accommodate genomes in the limited space of the cell nucleus and ensure the correct execution of gene expression programs, genomes are packaged in complex fashion in the three-dimensional cell nucleus. As a consequence of the extensive higher-order organization of chromosomes, distantly located genomic regions on the same or distinct chromosomes undergo long-range interactions. This article discusses the nature of long interactions, mechanisms of their formation, and their emerging functional roles in gene regulation and genome maintenance. C1 [Dekker, Job] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 141 TC 15 Z9 16 U1 5 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD OCT PY 2015 VL 7 IS 10 AR a019356 DI 10.1101/cshperspect.a019356 PG 22 WC Cell Biology SC Cell Biology GA CZ9VU UT WOS:000367446000006 PM 26430217 ER PT J AU Maynard, S Fang, EF Scheibye-Knudsen, M Croteau, DL Bohr, VA AF Maynard, Scott Fang, Evandro Fei Scheibye-Knudsen, Morten Croteau, Deborah L. Bohr, Vilhelm A. TI DNA Damage, DNA Repair, Aging, and Neurodegeneration SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID BASE EXCISION-REPAIR; EMBRYONIC STEM-CELLS; STRAND BREAK REPAIR; GROUP-B PROTEIN; SUBSTANTIA-NIGRA NEURONS; FREE-RADICAL THEORY; MITOCHONDRIAL-DNA; OXIDATIVE STRESS; COCKAYNE-SYNDROME; ALZHEIMERS-DISEASE AB Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. C1 [Maynard, Scott; Bohr, Vilhelm A.] Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark. [Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark. EM vbohr@nih.gov OI Scheibye-Knudsen, Morten/0000-0002-6637-1280 NR 172 TC 6 Z9 6 U1 3 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD OCT PY 2015 VL 5 IS 10 AR a025130 DI 10.1101/cshperspect.a025130 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CZ9WM UT WOS:000367448000012 ER PT J AU Dogan, BA Tasci, T Arduc, A Tuna, MM Berker, D Guler, S AF Dogan, Bercem Aycicek Tasci, Tugba Arduc, Ayse Tuna, Mazhar Muslum Berker, Dilek Guler, Serdar TI Are there any causes for increased thyroid volume in women with prolactinoma? SO ANNALES D ENDOCRINOLOGIE LA English DT Article DE Anabolic hormones; Prolactinoma; Thyroid volume ID IODINE-DEFICIENT AREA; INSULIN-RESISTANCE; NODULE PREVALENCE; CANCER CELLS; GROWTH; DISORDERS; PROLIFERATION; ESTRADIOL; ESTROGEN; PROTEIN AB Purpose. - The aim of this study was to evaluate thyroid volume in women with prolactinoma and investigate the relationship between anabolic hormones [insulin, insulin like growth factor (IGF-1), estrogen] and thyroid volume in the patients. Material-method. - Sixty-three euthyroid women with prolactinoma and 60 healthy euthyroid women were included. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), thyroxine (free T4), free tri-iodothyronine (free T3), insulin resistance (IR) which was estimated by the homeostasis model assessment, thyroidal microsome (anti-TPO), antithyroglobulin antibodies (TgAb), estradiol (E2), and insulin like growth factor (IGF-1) were evaluated, and thyroid volume was calculated by B-mode doppler USG. Results. - The mean thyroid volume was significantly higher in women with prolactinoma (82.5 +/- 15.1 mL) than in healthy women (76 +/- 15.1 mL)(P = 0.014), but no correlation was found between thyroid volume and serum PRL levels (P = 0.967). There were also no differences between thyroid volume, anabolic hormones (E2, IGF-1), and insulin resistance in women with prolactinoma (P = 0.776, P = 0.786, P = 0.647, respectively). Conclusions. - Our study did not show an association between anabolic hormones and increased thyroid volume in women with prolactinoma. (C) 2015 Elsevier Masson SAS. All rights reserved. C1 [Dogan, Bercem Aycicek] Darica Farabi State Hosp, Dept Endocrinol & Metab Dis, Darica, Kocaeli, Turkey. [Tasci, Tugba] Ankara Numune Training & Res Hosp, Internal Med, Ankara, Turkey. [Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA. [Tuna, Mazhar Muslum] Dicle Univ, Endocrinol & Metab Dis, Diyarbakir, Turkey. [Berker, Dilek; Guler, Serdar] Ankara Numune Training & Res Hosp, Endocrinol & Metab Dis, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Endocrinol & Metab Dis, Corum, Turkey. RP Dogan, BA (reprint author), Darica Farabi State Hosp, Dept Endocrinol & Metab Dis, Darica, Kocaeli, Turkey. EM bercemay@gmail.com NR 39 TC 0 Z9 0 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 EI 2213-3941 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD OCT PY 2015 VL 76 IS 5 BP 595 EP 600 DI 10.1016/j.ando.2014.12.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ5DL UT WOS:000367122600002 PM 26067294 ER PT J AU Khan, AR AF Khan, Anisur R. TI Consequences of Domestic Violence against Women: Some Reflections from Rural Bangladesh SO ASIAN SOCIAL WORK AND POLICY REVIEW LA English DT Article DE Bangladesh; children; consequences; domestic violence against women; family members; victims ID INTIMATE PARTNER VIOLENCE; BATTERED WOMEN; HEALTH; SAMPLE AB The aim of this study was to explore the consequences of domestic violence against rural Bangladeshi women. Drawing on in-depth qualitative phenomenological interviews with 39 female victims of domestic violence from 8 rural settings of the Netrokona and Mymensingh districts, it was found that domestic violence not only causes serious consequences to the overall health and wellbeing of victims, it also causes negative impacts to their children and family members. For victims, consequences were physical, sexual, reproductive, psychological, and economic. For the children of the victims, consequences were mostly behavioral and psychological, while for family members of the victims, consequences were mainly economic and psychological. This study has significant academic implications because it could trace the consequences of domestic violence in a three dimensional manner. Based on empirical findings, this study proposes policy recommendations, such as campaigning against domestic violence and the proper implementation of laws related to domestic violence. C1 [Khan, Anisur R.] BPATC, Dhaka, Bangladesh. [Khan, Anisur R.] NIDA, GSPA, Bangkok 10240, Thailand. RP Khan, AR (reprint author), NIDA, GSPA, Dev Adm, Seri Thai Rd, Bangkok 10240, Thailand. EM khanpatc@gmail.com NR 66 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1753-1411 J9 ASIAN SOC WORK POLIC JI Asian Soc. Work Policy Rev. PD OCT PY 2015 VL 9 IS 3 BP 210 EP 223 DI 10.1111/aswp.12059 PG 14 WC Social Work SC Social Work GA CZ3CB UT WOS:000366980600002 ER PT J AU Keller, S Fink, S Halperin, H Zviman, M AF Keller, Steven Fink, Sarah Halperin, Henry Zviman, Muz TI Reversal of PEA Arrest Utilizing ECMO in a Porcine Model SO CHEST LA English DT Meeting Abstract C1 [Keller, Steven; Fink, Sarah; Halperin, Henry; Zviman, Muz] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 57A DI 10.1378/chest.2278740 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CY0ZB UT WOS:000366134400055 ER PT J AU Keller, S Fink, S Halperin, H Zviman, M AF Keller, Steven Fink, Sarah Halperin, Henry Zviman, Muz TI Coronary Perfusion Pressure as a Function of ECMO Flow in a Porcine Model of Cardiac Arrest SO CHEST LA English DT Meeting Abstract C1 [Keller, Steven; Fink, Sarah; Halperin, Henry; Zviman, Muz] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 55A DI 10.1378/chest.2278932 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CY0ZB UT WOS:000366134400053 ER PT J AU Keller, S Fink, S Halperin, H Zviman, M AF Keller, Steven Fink, Sarah Halperin, Henry Zviman, Muz TI Cardiac Determinants of Flow Limitation in ECMO in a Porcine Model SO CHEST LA English DT Meeting Abstract C1 [Keller, Steven; Fink, Sarah; Halperin, Henry; Zviman, Muz] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 SU S MA 46A DI 10.1378/chest.2278853 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CY0ZB UT WOS:000366134400044 ER PT J AU Chan, SH Van Hee, VC Bergen, S Szpiro, AA DeRoo, LA London, SJ Marshall, JD Kaufman, JD Sandler, DP AF Chan, Stephanie H. Van Hee, Victor C. Bergen, Silas Szpiro, Adam A. DeRoo, Lisa A. London, Stephanie J. Marshall, Julian D. Kaufman, Joel D. Sandler, Dale P. TI Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FINE PARTICULATE MATTER; SELF-REPORTED HYPERTENSION; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; UNITED-STATES; ASSOCIATION; NOISE; POPULATION; REGRESSION; COHORT AB Background: Exposure to air pollution has been consistently associated with cardiovascular morbidity and mortality, but mechanisms remain uncertain. Associations with blood pressure (BP) may help to explain the cardiovascular effects of air pollution. Objective: We examined the cross-sectional relationship between long-term (annual average) residential air pollution exposure and BP in the National Institute of Environmental Health Sciences' Sister Study, a large U.S. cohort study investigating risk factors for breast cancer and other outcomes. Methods: This analysis included 43,629 women 35-76 years of age, enrolled 2003-2009, who had a sister with breast cancer. Geographic information systems contributed to satellite-based nitrogen dioxide (NO2) and fine particulate matter (<= 2.5 mu m; PM2.5) predictions at participant residences at study entry. Generalized additive models were used to examine the relationship between pollutants and measured BP at study entry, adjusting for cardiovascular disease risk factors and including thin plate splines for potential spatial confounding. Results: A 10-mu g/m(3) increase in PM2.5 was associated with 1.4-mmHg higher systolic BP (95% CI: 0.6, 2.3; p < 0.001), 1.0-mmHg higher pulse pressure (95% CI: 0.4, 1.7; p = 0.001), 0.8-mmHg higher mean arterial pressure (95% CI: 0.2, 1.4; p = 0.01), and no significant association with diastolic BP. A 10-ppb increase in NO2 was associated with a 0.4-mmHg (95% yCI: 0.2, 0.6; p < 0.001) higher pulse pressure. Conclusions: Long-term PM2.5 and NO2 exposures were associated with higher blood pressure. On a population scale, such air pollution-related increases in blood pressure could, in part, account for the increases in cardiovascular disease morbidity and mortality seen in prior studies. C1 [Chan, Stephanie H.; Van Hee, Victor C.; Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98105 USA. [Van Hee, Victor C.; Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA 98105 USA. [Bergen, Silas] Winona State Univ, Dept Math & Stat, Winona, MN 55987 USA. [Szpiro, Adam A.] Univ Washington, Dept Biostat, Seattle, WA 98105 USA. [DeRoo, Lisa A.; Sandler, Dale P.] NIEHS, Chron Dis Epidemiol Grp, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [London, Stephanie J.] NIEHS, Genet Environm & Resp Dis Grp, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Marshall, Julian D.] Univ Minnesota, Dept Civil Engn, Minneapolis, MN USA. [Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. RP Kaufman, JD (reprint author), Univ Washington, 4225 Roosevelt Ave NE,Campus Box 354695, Seattle, WA 98105 USA. EM joelk@uw.edu RI Kaufman, Joel/B-5761-2008; OI Kaufman, Joel/0000-0003-4174-9037; Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health [Z01 ES044005]; NIEHS [K24ES013195, P50ES015915, P30ES07033, K23ES019575, T32ES015459]; U.S. Environmental Protection Agency (EPA) [R831697, R834796] FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health grant Z01 ES044005; by NIEHS grants K24ES013195, P50ES015915, P30ES07033, K23ES019575, and T32ES015459; and by the U.S. Environmental Protection Agency (EPA) grants R831697 and R834796. NR 40 TC 12 Z9 13 U1 4 U2 18 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 OCT PY 2015 VL 123 IS 10 BP 951 EP 958 DI 10.1289/ehp.1408125 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CY8ZW UT WOS:000366698200014 PM 25748169 ER PT J AU Czarnota, J Gennings, C Colt, JS De Roos, AJ Cerhan, JR Severson, RK Hartge, P Ward, MH Wheeler, DC AF Czarnota, Jenna Gennings, Chris Colt, Joanne S. De Roos, Anneclaire J. Cerhan, James R. Severson, Richard K. Hartge, Patricia Ward, Mary H. Wheeler, David C. TI Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID POLYCHLORINATED-BIPHENYLS; RESIDENTIAL PROXIMITY; CARPET DUST; WASTE; BLOOD; ASSOCIATION; SITES AB BACKGROUND: There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals (i.e., one-by-one). OBJECTIVES: We determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk. METHODS: We conducted a population-based case-control study of NHL in four National Cancer Institute-Surveillance, Epidemiology, and End Results centers-Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington-from 1998 to 2000. We used weighted quantile sum (WQS) regression to model the association of a mixture of chemicals and risk of NHL. The WQS index was a sum of weighted quartiles for 5 polychlorinated biphenyls (PCBs), 7 polycyclic aromatic hydrocarbons (PAHs), and 15 pesticides. We estimated chemical mixture weights and effects for study sites combined and for each site individually, and also for histologic subtypes of NHL. RESULTS: The WQS index was statistically significantly associated with NHL overall [odds ratio (OR) = 1.30; 95% CI: 1.08, 1.56; p = 0.006; for one quartile increase] and in the study sites of Detroit (OR = 1.71; 95% CI: 1.02, 2.92; p = 0.045), Los Angeles (OR = 1.44; 95% CI: 1.00, 2.08; p = 0.049), and Iowa (OR = 1.76; 95% CI: 1.23, 2.53; p = 0.002). The index was marginally statistically significant in Seattle (OR = 1.39; 95% CI: 0.97, 1.99; p = 0.071). The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. CONCLUSIONS: An index of chemical mixtures was significantly associated with NHL. Our results show the importance of evaluating chemical mixtures when studying cancer risk C1 [Czarnota, Jenna; Gennings, Chris; Wheeler, David C.] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA 23298 USA. [Colt, Joanne S.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. [De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [Cerhan, James R.] Mayo Clin, Div Epidemiol, Rochester, MN USA. [Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Hartge, Patricia] NCI, Epidemiol & Biostat Program, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. RP Wheeler, DC (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biostat, One Capitol Sq,830 East Main St, Richmond, VA 23298 USA. EM dcwheeler@vcu.edu FU National Institute of Environmental Health Sciences, National Institutes of Health [T32 ES0007334]; Intramural Research Program of the National Cancer Institute, National Institutes of Health, and Public Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] FX J.C. received support from the National Institute of Environmental Health Sciences, National Institutes of Health (grant #T32 ES0007334). This research was partially supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, and Public Health Service (contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, and N02-PC-71105). NR 29 TC 2 Z9 2 U1 0 U2 3 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 OCT PY 2015 VL 123 IS 10 BP 965 EP 970 DI 10.1289/ehp.1408630 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CY8ZW UT WOS:000366698200016 PM 25748701 ER PT J AU Bassig, BA Friesen, MC Vermeulen, R Shu, XO Purdue, MP Stewart, PA Xiang, YB Chow, WH Zheng, TZ Ji, BT Yang, G Linet, MS Hu, W Zhang, HP Zheng, W Gao, YT Rothman, N Lan, Q AF Bassig, Bryan A. Friesen, Melissa C. Vermeulen, Roel Shu, Xiao-Ou Purdue, Mark P. Stewart, Patricia A. Xiang, Yong-Bing Chow, Wong-Ho Zheng, Tongzhang Ji, Bu-Tian Yang, Gong Linet, Martha S. Hu, Wei Zhang, Heping Zheng, Wei Gao, Yu-Tang Rothman, Nathaniel Lan, Qing TI Occupational Exposure to Benzene and Non-Hodgkin Lymphoma in a Population-Based Cohort: The Shanghai Women's Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID DNA COPY NUMBER; CHINESE WORKERS; RISK-FACTORS; NEOPLASMS; SOLVENTS; LEUKEMIA; SUBTYPES; HEMATOTOXICITY; CLASSIFICATION; ABERRATIONS AB BACKGROUND: The association between benzene exposure and non-Hodgkin lymphoma (NHL) has been the subject of debate as a result of inconsistent epidemiologic evidence. An International Agency for Research on Cancer (IARC) working group evaluated benzene in 2009 and noted evidence for a positive association between benzene exposure and NHL risk. OBJECTIVE: We evaluated the association between occupational benzene exposure and NHL among 73,087 women enrolled in the prospective population-based Shanghai Women's Health Study. METHODS: Benzene exposure estimates were derived using a previously developed exposure assessment framework that combined ordinal job-exposure matrix intensity ratings with quantitative benzene exposure measurements from an inspection database of Shanghai factories collected between 1954 and 2000. Associations between benzene exposure metrics and NHL (n = 102 cases) were assessed using Cox proportional hazard models, with study follow-up occurring from December 1996 through December 2009. RESULTS: Women ever exposed to benzene had a significantly higher risk of NHL [hazard ratio (HR) = 1.87, 95% CI: 1.19, 2.96]. Compared with unexposed women, significant trends in NHL risk were observed for increasing years of benzene exposure (p(trend) = 0.006) and increasing cumulative exposure levels (p(trend) = 0.005), with the highest duration and cumulative exposure tertiles having a significantly higher association with NHL (HR = 2.07, 95% CI: 1.07, 4.01 and HR = 2.16, 95% CI: 1.17, 3.98, respectively). CONCLUSIONS: Our findings, using a population-based prospective cohort of women with diverse occupational histories, provide additional evidence that occupational exposure to benzene is associated with NHL risk. C1 [Bassig, Bryan A.; Friesen, Melissa C.; Purdue, Mark P.; Ji, Bu-Tian; Hu, Wei; Rothman, Nathaniel; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20850 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37235 USA. [Stewart, Patricia A.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA. [Linet, Martha S.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Gao, Yu-Tang] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Dept Epidemiol, Shanghai 200030, Peoples R China. RP Bassig, BA (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E618, Rockville, MD 20850 USA. EM bassigb@mail.nih.gov RI Purdue, Mark/C-9228-2016; Friesen, Melissa/A-5362-2009 OI Purdue, Mark/0000-0003-1177-3108; FU National Institutes of Health (NIH) [R37 CA70867]; Intramural Research Program of the National Cancer Institute, NIH FX The Shanghai Women's Health Study was supported in part by National Institutes of Health (NIH) research grant R37 CA70867 and the Intramural Research Program of the National Cancer Institute, NIH. NR 36 TC 2 Z9 2 U1 2 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 OCT PY 2015 VL 123 IS 10 BP 971 EP 977 DI 10.1289/ehp.1408307 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CY8ZW UT WOS:000366698200017 PM 25748391 ER PT J AU Westreich, D Edwards, JK Cole, SR Platt, RW Mumford, SL Schisterman, EF AF Westreich, Daniel Edwards, Jessie K. Cole, Stephen R. Platt, Robert W. Mumford, Sunni L. Schisterman, Enrique F. TI Imputation approaches for potential outcomes in causal inference SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Causal inference; g-formula; multiple imputation; potential outcomes ID MARGINAL STRUCTURAL MODELS; PARAMETRIC G-FORMULA; MISSING DATA; ANTIRETROVIRAL THERAPY; LOGISTIC-REGRESSION; MULTIPLE IMPUTATION; COMPOUND TREATMENTS; ASSUMPTION; DEFINITION; TRANSPORTABILITY AB Background: The fundamental problem of causal inference is one of missing data, and specifically of missing potential outcomes: if potential outcomes were fully observed, then causal inference could be made trivially. Though often not discussed explicitly in the epidemiological literature, the connections between causal inference and missing data can provide additional intuition. Methods: We demonstrate how we can approach causal inference in ways similar to how we address all problems of missing data, using multiple imputation and the parametric g-formula. Results: We explain and demonstrate the use of these methods in example data, and discuss implications for more traditional approaches to causal inference. Conclusions: Though there are advantages and disadvantages to both multiple imputation and g-formula approaches, epidemiologists can benefit from thinking about their causal inference problems as problems of missing data, as such perspectives may lend new and clarifying insights to their analyses. C1 [Westreich, Daniel; Edwards, Jessie K.; Cole, Stephen R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Platt, Robert W.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 2T5, Canada. [Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. RP Westreich, D (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM djw@unc.edu OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 43 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2015 VL 44 IS 5 BP 1731 EP 1737 DI 10.1093/ije/dyv135 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CZ5YJ UT WOS:000367178000040 PM 26210611 ER PT J AU Williams-Hooker, R Draper, CM Lai, C Mitchell, CO Cashion, AK AF Williams-Hooker, Ruth Draper, Catherine M. Lai, Chen Mitchell, Carol O. Cashion, Ann K. TI The Relationship Between Fruit and Vegetable Consumption and Weight Gain in Kidney Transplant Recipients Within 1 Year Posttransplant SO TOPICS IN CLINICAL NUTRITION LA English DT Article DE fruit intake; kidney transplant; vegetable intake; weight gain after transplant ID NUTRITIONAL MANAGEMENT; SOCIOECONOMIC-STATUS; HYPERTENSION AB Kidney transplant recipients must avoid obesity-related complications. To investigate the relationship between fruit/vegetable intake and weight change after transplant, 35 transplant recipients with dietary intake and physical activity records, at baseline, 3, 6, and 12 months after transplant, were included. At all time points, fruit/vegetable intakes were below recommended levels. Baseline body mass index was inversely associated with baseline and overall vegetable intakes. No significant association was found between fruit intake and body mass index/weight change. A significant positive correlation was found between fruit/vegetable intake among weight losers and women. Findings suggest that transplant recipients should be encouraged to consume fruit/vegetables to reduce obesity-related comorbidities. C1 [Williams-Hooker, Ruth; Mitchell, Carol O.] Univ Memphis, Memphis, TN 38152 USA. [Draper, Catherine M.] Wellfit Med & Nutr Ctr, Jackson, TN USA. [Lai, Chen; Cashion, Ann K.] Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. RP Cashion, AK (reprint author), Natl Inst Nursing Res, NIH, 3 Ctr Dr,RM 5E26, Bethesda, MD 20892 USA. EM ann.cashion@nih.gov NR 23 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 0883-5691 EI 1550-5146 J9 TOP CLIN NUTR JI Top. Clin. Nutr. PD OCT-DEC PY 2015 VL 30 IS 4 BP 324 EP 332 DI 10.1097/TIN.0000000000000048 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CZ6SA UT WOS:000367229800006 ER PT J AU Wu, T Liu, J Zhang, HJ Hallett, M Zheng, Z Chan, P AF Wu, Tao Liu, Jun Zhang, Hejia Hallett, Mark Zheng, Zheng Chan, Piu TI Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode in the Striatum SO CEREBRAL CORTEX LA English DT Article DE attentional networks; controlled pattern; dopamine depletion; neural correlates; putamen ID ANTERIOR CINGULATE CORTEX; EXTERNALLY TRIGGERED MOVEMENTS; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; FRONTAL-CORTEX; BASAL GANGLIA; FUNCTIONAL CONNECTIVITY; COGNITIVE SKILL; CEREBELLAR; ACTIVATION AB We investigated neural correlates when attending to a movement that could be made automatically in healthy subjects and Parkinson's disease (PD) patients. Subjects practiced a visuomotor association task until they could perform it automatically, and then directed their attention back to the automated task. Functional MRI was obtained during the early-learning, automatic stage, and when re-attending. In controls, attention to automatic movement induced more activation in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, and rostral supplementary motor area. The motor cortex received more influence from the cortical motor association regions. In contrast, the pattern of the activity and connectivity of the striatum remained at the level of the automatic stage. In PD patients, attention enhanced activity in the DLPFC, premotor cortex, and cerebellum, but the connectivity from the putamen to the motor cortex decreased. Our findings demonstrate that, in controls, when a movement achieves the automatic stage, attention can influence the attentional networks and cortical motor association areas, but has no apparent effect on the striatum. In PD patients, attention induces a shift from the automatic mode back to the controlled pattern within the striatum. The shifting between controlled and automatic behaviors relies in part on striatal function. C1 [Wu, Tao; Zheng, Zheng; Chan, Piu] Capital Med Univ, Key Lab Neurodegenerat Disorders, Xuanwu Hosp, Dept Neurobiol,Minist Educ,Beijing Inst Geriatr, Beijing 100053, Peoples R China. [Wu, Tao; Zheng, Zheng; Chan, Piu] Beijing Inst Brain Disorders, Parkinson Dis Ctr, Beijing Key Lab Parkinsons Dis, Beijing, Peoples R China. [Liu, Jun] Nankai Univ, Dept Radiol, Affiliated Hosp, Tianjin 300071, Peoples R China. [Zhang, Hejia] Rice Univ, Dept Elect & Comp Engn, Houston, TX 77251 USA. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Key Lab Neurodegenerat Disorders, Xuanwu Hosp, Dept Neurobiol,Minist Educ,Beijing Inst Geriatr, Beijing 100053, Peoples R China. EM wutao69@gmail.com FU National Science Foundation of China [81071012, 81271429] FX National Science Foundation of China (grant numbers 81071012 and 81271429 to T.W.). NR 59 TC 8 Z9 8 U1 0 U2 8 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 OCT PY 2015 VL 25 IS 10 BP 3330 EP 3342 DI 10.1093/cercor/bhu135 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000006 PM 24925772 ER PT J AU Oliver, PL Chodroff, RA Gosal, A Edwards, B Cheung, AFP Gomez-Rodriguez, J Elliot, G Garrett, LJ Lickiss, T Szele, F Green, ED Molnar, Z Ponting, CP AF Oliver, Peter L. Chodroff, Rebecca A. Gosal, Amrit Edwards, Benjamin Cheung, Amanda F. P. Gomez-Rodriguez, Julio Elliot, Gene Garrett, Lisa J. Lickiss, Tom Szele, Francis Green, Eric D. Molnar, Zoltan Ponting, Chris P. TI Disruption of Visc-2, a Brain-Expressed Conserved Long Noncoding RNA, Does Not Elicit an Overt Anatomical or Behavioral Phenotype SO CEREBRAL CORTEX LA English DT Article DE evolutionary conservation; knockout mouse; noncoding RNA; olfactory bulb; subventricular zone ID MOUSE; TRANSCRIPTION; MICE; GENOME; MALAT1; ADULT; EVOLUTION; SEQUENCE; ELEMENTS; GENES AB Although long noncoding RNAs (lncRNAs) are proposed to play essential roles in mammalian neurodevelopment, we know little of their functions from their disruption in vivo. Combining evidence for evolutionary constraint and conserved expression data, we previously identified candidate lncRNAs that might play important and conserved roles in brain function. Here, we demonstrate that the sequence and neuronal transcription of lncRNAs transcribed from the previously uncharacterized Visc locus are conserved across diverse mammals. Consequently, one of these lncRNAs, Visc-2, was selected for targeted deletion in the mouse, and knockout animals were subjected to an extremely detailed anatomical and behavioral characterization. Despite a neurodevelopmental expression pattern of Visc-2 that is highly localized to the cortex and sites of neurogenesis, anomalies in neither cytoarchitecture nor neuroproliferation were identified in knockout mice. In addition, no abnormal motor, sensory, anxiety, or cognitive behavioral phenotypes were observed. These results are important because they contribute to a growing body of evidence that lncRNA loci contribute on average far less to brain and biological functions than protein-coding loci. A high-throughput knockout program focussing on lncRNAs, similar to that currently underway for protein-coding genes, will be required to establish the distribution of their organismal functions. C1 [Oliver, Peter L.; Edwards, Benjamin; Ponting, Chris P.] Univ Oxford, MRC Funct Genom Unit, Oxford OX1 3QX, England. [Oliver, Peter L.; Chodroff, Rebecca A.; Gosal, Amrit; Cheung, Amanda F. P.; Lickiss, Tom; Szele, Francis; Molnar, Zoltan; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. [Chodroff, Rebecca A.; Green, Eric D.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Gomez-Rodriguez, Julio; Elliot, Gene; Garrett, Lisa J.] NHGRI, Embryon Stem Cells & Transgen Mouse Core, Bethesda, MD 20892 USA. RP Ponting, CP (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Parks Rd, Oxford OX1 3PT, England. EM zoltan.molnar@dpag.ox.ac.uk; chris.ponting@dpag.ox.ac.uk OI Lickiss, Tom/0000-0002-3423-5030; Molnar, Zoltan/0000-0002-6852-6004; Ponting, Chris/0000-0003-0202-7816 FU UK Medical Research Council; Biotechnology and Biological Sciences Research Council, UK; European Research Council through DARCGENs; University of Oxford FX This work was supported by the UK Medical Research Council, Biotechnology and Biological Sciences Research Council, UK and the European Research Council through an advanced grant (DARCGENs). Funding to pay the Open Access publication charges for this article was provided by the University of Oxford. NR 50 TC 7 Z9 7 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2015 VL 25 IS 10 BP 3572 EP 3585 DI 10.1093/cercor/bhu196 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000026 PM 25209608 ER PT J AU Tomasi, D Wang, GJ Studentsova, Y Volkow, ND AF Tomasi, Dardo Wang, Gene-Jack Studentsova, Yana Volkow, Nora D. TI Dissecting Neural Responses to Temporal Prediction, Attention, and Memory: Effects of Reward Learning and Interoception on Time Perception SO CEREBRAL CORTEX LA English DT Article DE dopamine; fMRI; reward; timekeeping ID INTERNAL CLOCK; WORKING-MEMORY; DOPAMINERGIC REGULATION; DIFFERENCE MODELS; BRAIN ACTIVATION; SUBJECTIVE TIME; ACOUSTIC NOISE; VIDEO GAME; HALOPERIDOL; CIRCUITRY AB Temporal prediction (TP) is needed to anticipate future events and is essential for survival. Our sense of time is modulated by emotional and interoceptive (corporal) states that are hypothesized to rely on a dopamine (DA)-modulated "internal clock" in the basal ganglia. However, the neurobiological substrates for TP in the human brain have not been identified. We tested the hypothesis that TP involves DA striato-cortical pathways, and that accurate responses are reinforcing in themselves and activate the nucleus accumbens (NAc). Functional magnetic resonance imaging revealed the involvement of the NAc and anterior insula in the temporal precision of the responses, and of the ventral tegmental area in error processing. Moreover, NAc showed higher activation for successful than for unsuccessful trials, indicating that accurate TP per se is rewarding. Inasmuch as activation of the NAc is associated with drug-induced addictive behaviors, its activation by accurate TP could help explain why video games that rely on TP can trigger compulsive behaviors. C1 [Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Tomasi, D (reprint author), 10 Ctr Dr,Rm B2L304, Bethesda, MD 20892 USA. EM tomasidg@mail.nih.gov FU National Institute of Health's Intramural Research Program (National Institute on Alcohol Abuse and Alcoholism) [2RO1AA09481]; infrastructure of Brookhaven National Laboratory [DE-AC02-98CH10886] FX This researchwas supported by the National Institute of Health's Intramural Research Program (National Institute on Alcohol Abuse and Alcoholism; 2RO1AA09481) and was carried out using the infrastructure of Brookhaven National Laboratory under contract DE-AC02-98CH10886. NR 69 TC 1 Z9 2 U1 2 U2 14 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 OCT PY 2015 VL 25 IS 10 BP 3856 EP 3867 DI 10.1093/cercor/bhu269 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CY5NI UT WOS:000366454000046 PM 25389123 ER PT J AU Upson, K Sathyanarayana, S Scholes, D Holt, VL AF Upson, Kristen Sathyanarayana, Sheela Scholes, Delia Holt, Victoria L. TI Early-life factors and endometriosis risk SO FERTILITY AND STERILITY LA English DT Article DE Population-based case-control study; endometriosis; early-life; soy formula ID QUALITY-OF-LIFE; PITUITARY-GONADAL AXIS; IN-UTERO EXPOSURES; NEONATAL EXPOSURE; PELVIC ENDOMETRIOSIS; OVARIAN-STEROIDS; INFANT FORMULAS; GROWTH-FACTOR; MOUSE UTERUS; BLACK-WOMEN AB Objective: To study early-life factors in relation to endometriosis risk in adulthood. Design: Population-based case-control study. Setting: Integrated healthcare system. Patient(s): Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. Intervention(s): None. Main Outcome Measure(s): Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother's age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant's mother or other family member. Result(s): We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. Conclusion(s): Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood. (C)2015 by American Society for Reproductive Medicine. C1 [Upson, Kristen; Scholes, Delia; Holt, Victoria L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Upson, Kristen; Holt, Victoria L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Upson, Kristen] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Sathyanarayana, Sheela] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Sathyanarayana, Sheela] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Sathyanarayana, Sheela] Seattle Childrens Res Inst, Seattle, WA USA. [Scholes, Delia] Grp Hlth Res Inst, Seattle, WA USA. RP Upson, K (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,Rall Bldg 101,MD A3-05 NIEHS, Res Triangle Pk, NC 27709 USA. EM kristen.upson@nih.gov RI Upson, Kristen/D-4504-2017 OI Upson, Kristen/0000-0001-9598-8776 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD033792-05, T32 HD052462-05]; National Institute of Nursing Research [1F31NR013092-01]; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX Supported by award number R01HD033792-05 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; support for training (K.U.) was provided by award numbers T32 HD052462-05 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and 1F31NR013092-01 from the National Institute of Nursing Research; and supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 65 TC 7 Z9 7 U1 1 U2 5 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 OCT PY 2015 VL 104 IS 4 BP 964 EP + DI 10.1016/j.fertnstert.2015.06.040 PG 13 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZD UT WOS:000366485700027 PM 26211883 ER PT J AU Brinton, LA Moghissi, KS Scoccia, B Lamb, EJ Trabert, B Niwa, S Ruggieri, D Westhoff, CL AF Brinton, Louise A. Moghissi, Kamran S. Scoccia, Bert Lamb, Emmet J. Trabert, Britton Niwa, Shelley Ruggieri, David Westhoff, Carolyn L. TI Effects of fertility drugs on cancers other than breast and gynecologic malignancies SO FERTILITY AND STERILITY LA English DT Article DE Cancer; risk; infertility; clomiphene citrate; gonadotropins ID IN-VITRO FERTILIZATION; ORAL-CONTRACEPTIVE USE; HORMONE REPLACEMENT THERAPY; EXTENDED FOLLOW-UP; COLORECTAL-CANCER; CUTANEOUS MELANOMA; REPRODUCTIVE HISTORY; INFERTILE WOMEN; THYROID-CANCER; LUNG-CANCER AB Objective: To examine the relationship of ovulation-stimulating drugs to risk of cancers other than breast and gynecologic malignancies. Design: Retrospective cohort study, with additional follow-up since initial report. Setting: Reproductive endocrinology practices. Patient(s): Among a cohort of 12,193 women evaluated for infertility between 1965 and 1988, a total of 9,892 women (81.1% of the eligible population) were followed through 2010, via passive and active (questionnaire) approaches. Intervention(s): None. Main Outcome Measure(s): Hazard ratios (HRs) and 95% confidence intervals (CIs) for various fertility treatment parameters for select cancers. Result(s): During 30.0 median years of follow-up (285,332 person-years), 91 colorectal cancers, 84 lung cancers, 55 thyroid cancers, and 70 melanomas were diagnosed among study subjects. Clomiphene citrate (CC), used by 38.1% of patients, was not associated with colorectal or lung cancer risks, but was related significantly to melanoma (HR = 1.95; 95% CI: 1.18-3.22), and non-significantly to thyroid cancer risks (HR = 1.57; 95% CI: 0.89-2.75). The highest melanoma risks were seen among those with the lowest drug exposure levels, but thyroid cancer risk was greatest among the heavily exposed patients (HR = 1.96; 95% CI: 0.92-4.17 for those receiving >2,250 mg). Clomiphene citrate-associated risks for thyroid cancer were somewhat higher among nulligravid, compared with gravid, women, but did not differ according to distinct causes of infertility. Gonadotropins, used by only 9.7% of subjects, were not related to risk of any of the assessed cancers. Conclusion(s): Our results provide support for continued monitoring of both melanoma and thyroid cancer risk among patients receiving fertility drugs. (C)2015 by American Society for Reproductive Medicine. C1 [Brinton, Louise A.; Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Moghissi, Kamran S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Scoccia, Bert] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Lamb, Emmet J.] Stanford Univ, Stanford, CA 94305 USA. [Niwa, Shelley] Westat Corp, Rockville, MD USA. [Ruggieri, David] IMS Inc, Rockville, MD USA. [Westhoff, Carolyn L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. RP Brinton, LA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, 9609 Med Ctr Dr,MSC 9774,7E-102, Bethesda, MD 20892 USA. EM brintonl@mail.nih.gov RI Trabert, Britton/F-8051-2015; OI Brinton, Louise/0000-0003-3853-8562 FU intramural research component of the National Cancer Institute, National Institutes of Health FX Supported in part by funds from the intramural research component of the National Cancer Institute, National Institutes of Health. NR 51 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2015 VL 104 IS 4 BP 980 EP 988 DI 10.1016/j.fertnstert.2015.06.045 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZD UT WOS:000366485700029 PM 26232746 ER PT J AU Louis, GMB Chen, Z Kim, S Sapra, KJ Bae, J Kannan, K AF Louis, Germaine M. Buck Chen, Zhen Kim, Sungduk Sapra, Katherine J. Bae, Jisuk Kannan, Kurunthachalam TI Urinary concentrations of benzophenone-type ultraviolet light filters and semen quality SO FERTILITY AND STERILITY LA English DT Article DE Benzophenones; fecundity; semen; sperm; sunscreens ID TANDEM MASS-SPECTROMETRY; IN-UTERO EXPOSURE; UV FILTERS; BISPHENOL-A; SERUM COTININE; PREGNANT-WOMEN; UNITED-STATES; MEN; DERIVATIVES; PARAMETERS AB Objective: To assess benzophenone-type ultraviolet (UV) filter concentrations, chemicals used in sunscreen and personal care products, and semen endpoints. Design: Cohort. Setting: Not applicable. Patient(s): A total of 413 men provided semen and urine samples, 2005-2009. Five UV filters were quantified (ng/mL) in urine using liquid chromatography-triple quadrupole mass spectrometry: BP-1 (2,4-dihydroxybenzophenone), BP-2 (2,2',4,4'-tetrahydroxybenzophenone), BP-3 (2-hydroxy-4-methoxybenzophenone), BP-8 (2,2'-dihydroxy-4-methoxybenzophenone), and 4-OH-BP (4-hydroxybenzophenone). Using linear regression, beta-coefficients (beta) and 95% confidence intervals (CIs) for each chemical dichotomized at the 75th percentile and Box-Cox transformed semen endpoint were estimated, after adjusting for age, body mass index, cotinine, season, and site. Intervention(s): None. Main Outcome Measure(s): Thirty-five semen endpoints. Result(s): BP-2 was associated with diminished sperm concentration (beta = -0.74; 95% CI -1.41, -0.08), straight (beta = -4.57; 95% CI -8.95, -0.18) and linear movement (beta = -3.15; 95% CI -6.01, -0.30), more immature sperm (beta = 0.38; 95% CI 0.15, 0.62), and a decreased percentage of other tail abnormalities (beta = -0.16; 95% CI -0.31, -0.01). BP-8 was associated with decreased hypo-osmotic swelling (beta = -2.57; 95% CI -4.86, -0.29) and higher acrosome area (beta = 1.14; 95% CI 0.01, 2.26). No associations were observed for BP-1, BP-3, or 4OH-BP. Conclusion(s): The findings suggest that specific UV filters may be associated with some aspects of semen endpoints, but await future corroboration. (C)2015 by American Society for Reproductive Medicine. C1 [Louis, Germaine M. Buck; Sapra, Katherine J.; Bae, Jisuk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth, Rockville, MD 20852 USA. [Chen, Zhen; Kim, Sungduk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth, Rockville, MD 20852 USA. [Bae, Jisuk] Catholic Univ Daegu, Sch Med, Dept Prevent Med, Daegu, South Korea. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. EM louisg@mail.nsih.gov OI Sapra, Katherine/0000-0001-5659-6489; Bae, Jisuk/0000-0002-5809-5394; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child and Human Development (NICHD) [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, HHSN27500001] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child and Human Development (NICHD), contract nos. N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, and HHSN27500001. Semen samples were analyzed under a Memorandum of Understanding between the NICHD and the Reproductive Health Assessment Team, Biomonitoring and Health Assessments Branch, National Institute for Occupational Safety and Health. NR 49 TC 5 Z9 5 U1 7 U2 16 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 OCT PY 2015 VL 104 IS 4 BP 989 EP 996 DI 10.1016/j.fertnstert.2015.07.1129 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZD UT WOS:000366485700030 PM 26253817 ER PT J AU Berlon, NR Qi, R Sharma-Kuinkel, BK Joo, HS Park, LP George, D Thaden, JT Messina, JA Maskarinec, SA Mueller-Premru, M Athan, E Tattevin, P Pericas, JM Woods, CW Otto, M Fowler, VG AF Berlon, Nicholas R. Qi, Robert Sharma-Kuinkel, Batu K. Joo, Hwang-Soo Park, Lawrence P. George, Dennis Thaden, Joshua T. Messina, Julia A. Maskarinec, Stacey A. Mueller-Premru, Manica Athan, Eugene Tattevin, Pierre Pericas, Juan M. Woods, Christopher W. Otto, Michael Fowler, Vance G., Jr. TI Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins SO JOURNAL OF INFECTION LA English DT Article DE Phenol soluble modulin; MRSA; Skin and soft infection; Pneumonia; Endocarditis ID RESISTANT STAPHYLOCOCCUS-AUREUS; COAGULASE-NEGATIVE STAPHYLOCOCCI; GENE REGULATOR AGR; UNITED-STATES; VIRULENCE DETERMINANTS; COMPLICATED SKIN; PCR ASSAY; METHICILLIN; ENDOCARDITIS; VANCOMYCIN AB Background: Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. Methods: 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal-Wallis tests as appropriate. Results: Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMa1-4, PSMb1, and d-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis. Conclusions: Increased in vitro production of PSMs is associated with an SSTI clinical source. This significant association persisted after exclusion of USA300 genotype isolates from analysis, suggesting that PSMs play a particularly important role in the pathogenesis of SSTI as compared to other infection types. (C) 2015 Published by Elsevier Ltd on behalf of The British Infection Association. C1 [Berlon, Nicholas R.; Qi, Robert; Sharma-Kuinkel, Batu K.; Park, Lawrence P.; George, Dennis; Thaden, Joshua T.; Messina, Julia A.; Maskarinec, Stacey A.; Woods, Christopher W.; Fowler, Vance G., Jr.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Joo, Hwang-Soo; Otto, Michael] NIH, Bethesda, MD USA. [Mueller-Premru, Manica] Univ Ljubljana, Ljubljana, Slovenia. [Athan, Eugene] Deakin Univ, Barwon Hlth, Geelong, Vic 3217, Australia. [Tattevin, Pierre] Pontchaillou Univ, Pontchaillou, France. [Pericas, Juan M.] Univ Barcelona, Hosp Clin IDIBAPS, E-08007 Barcelona, Spain. RP Fowler, VG (reprint author), Duke Univ, Med Ctr, Div Infect Dis, Dept Med, Box 102359, Durham, NC 27710 USA. EM fowle003@mc.duke.edu OI Otto, Michael/0000-0002-2222-4115; Qi, Robert/0000-0001-6445-7331; JOO, HWANG-SOO/0000-0003-4668-3225 FU Infectious Disease Society of America's Medical Scholars Program; National Institute of Health [R01-AI068804, K24-AI093969]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Infectious Disease Society of America's Medical Scholars Program [to NRB], grants provided by the National Institute of Health [R01-AI068804 and K24-AI093969 to VGF], and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases [to MO]. NR 44 TC 5 Z9 5 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD OCT PY 2015 VL 71 IS 4 BP 447 EP 457 DI 10.1016/j.jinf.2015.06.005 PG 11 WC Infectious Diseases SC Infectious Diseases GA CZ1XT UT WOS:000366899900005 PM 26079275 ER PT J AU Ning, L Xu, Z Furuya, N Nonaka, R Yamada, Y Arikawa-Hirasawa, E AF Ning, Liang Xu, Zhuo Furuya, Norihiko Nonaka, Risa Yamada, Yoshihiko Arikawa-Hirasawa, Eri TI Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle SO MATRIX BIOLOGY LA English DT Article DE Perlecan; Muscle atrophy; Autophagy; Mechanical stress; Soleus muscle ID SKELETAL-MUSCLE; OXIDATIVE STRESS; CROSS-TALK; IN-VIVO; MICE; DISEASE; TARGET; PROLIFERATION; MECHANISMS; MEMBRANES AB The autophagy lysosome system is essential for muscle protein synthesis and degradation equilibrium, and its dysfunction has been linked to various muscle disorders. It has been reported that a diverse collection of extracellular matrix constituents, including decorin, collagen VI, laminin alpha 2, endorepellin, and endostatin, can modulate autophagic signaling pathways. However, the association between autophagy and perlecan in muscle homeostasis remains unclear. The mechanical unloading of perlecan-deficient soleus muscles resulted in significantly decreased wet weights and cross-section fiber area compared with those of control mice. We found that perlecan deficiency in slow-twitch soleus muscles enhanced autophagic activity. This was accompanied by a decrease in autophagic substrates, such as p62, and an increase in LC3II levels. Furthermore, perlecan deficiency caused a reduction in the phosphorylation levels of p70S6k and Akt and increased the phosphorylation of AMPK alpha. Our findings suggested that perlecan inhibits the autophagic process through the activation of the mTORC1 pathway. This autophagic response may be a novel target for enhancing the efficacy of skeletal muscle atrophy treatment. (C) 2015 Published by Elsevier B.V. C1 [Ning, Liang; Xu, Zhuo; Nonaka, Risa; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo 1138421, Japan. [Furuya, Norihiko; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Dept Neurol, Tokyo 1138421, Japan. [Furuya, Norihiko] Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Bunkyo Ku, Tokyo 1138421, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20814 USA. RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Fac Med, Res Inst Dis Old Age, Bunkyo Ku, Bldg 10,Room 606,2-1-1 Hongo, Tokyo 1138421, Japan. EM ehirasaw@juntendo.ac.jp FU NIDCR [DE000185-27]; Japan Agency for Medical Research and Development (AMED) [15ek0109017s0202]; Intramural Research Grant (26-8) for Neurological and Psychiatric Disorders of NCNP [26-8]; MEXT [S1101009 2011-2015] FX We wish to thank Andrew Cho and Ashok B. Kulkarni for their help in creating the mutant mice. This work was supported by grants from the Intramural Research Program of the NIDCR (DE000185-27 to YY), grants from the Japan Agency for Medical Research and Development (AMED, 15ek0109017s0202 to EAH), an Intramural Research Grant (26-8) for Neurological and Psychiatric Disorders of NCNP (EAH), and the MEXT-supported Program for the Strategic Research Foundation at Private Universities (S1101009 2011-2015). NR 42 TC 8 Z9 8 U1 0 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 OCT PY 2015 VL 48 BP 26 EP 35 DI 10.1016/j.matbio.2015.08.002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CY7VI UT WOS:000366617000003 PM 26319110 ER PT J AU Kirkali, Z Rasooly, R Star, RA Rodgers, GP AF Kirkali, Ziya Rasooly, Rebekah Star, Robert A. Rodgers, Griffin P. TI Urinary Stone Disease: Progress, Status, and Needs SO UROLOGY LA English DT Editorial Material ID KIDNEY-STONES; UNITED-STATES; NEPHROLITHIASIS; UROLITHIASIS; PREVALENCE; MANAGEMENT AB Urinary stone disease (USD) is an important healthcare problem in the US affecting both adults and children, and costs $10 billion to the nation. Prevalence of USD has nearly doubled during the last 15 years in parallel to the obesity and type 2 diabetes epidemic. Despite the advances in the management of an acute episode, one of three stone formers experience recurrence. A better understanding of stone formation is necessary to develop secondary prevention strategies. There are many unanswered research questions that require a multidisciplinary approach. National Institute of Diabetes and Digestive and Kidney Diseases recently held a workshop on USD, and is committed to continue conducting and supporting research in this field. Published by Elsevier Inc. C1 [Kirkali, Ziya; Rasooly, Rebekah; Star, Robert A.; Rodgers, Griffin P.] NIDDK, Bethesda, MD 20892 USA. RP Kirkali, Z (reprint author), 6707 Democracy Blvd Room 627,MSC 5458, Bethesda, MD 20892 USA. EM ziya.kirkali@nih.gov OI Rasooly, Rebekah/0000-0002-6357-5528 FU Intramural NIH HHS [Z99 DK999999] NR 13 TC 10 Z9 12 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD OCT PY 2015 VL 86 IS 4 BP 651 EP 653 DI 10.1016/j.urology.2015.07.006 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CY5RG UT WOS:000366464300004 PM 26190090 ER PT J AU Maynard, S Hejl, AM Dinh, TST Keijzers, G Hansen, AM Desler, C Moreno-Villanueva, M Burkle, A Rasmussen, LJ Waldemar, G Bohr, VA AF Maynard, Scott Hejl, Anne-Mette Dinh, Thuan-Son T. Keijzers, Guido Hansen, Ase M. Desler, Claus Moreno-Villanueva, Maria Buerkle, Alexander Rasmussen, Lene J. Waldemar, Gunhild Bohr, Vilhelm A. TI Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients SO AGING-US LA English DT Article DE Alzheimer's disease; APE1; bioenergetics; dNTP pools; DNA repair; mitochondria; peripheral blood mononuclear cells; reactive oxygen species ID OXIDATIVE DNA-DAMAGE; BASE EXCISION-REPAIR; MILD COGNITIVE IMPAIRMENT; OXYGEN SPECIES PRODUCTION; STRESS-RESPONSE; LYMPHOCYTES; BRAIN; NEURONS; NEURODEGENERATION; MAINTENANCE AB AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery. METHODS: PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency). RESULTS: In the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD. C1 [Maynard, Scott; Dinh, Thuan-Son T.; Keijzers, Guido; Desler, Claus; Rasmussen, Lene J.] Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark. [Hejl, Anne-Mette; Waldemar, Gunhild] Univ Copenhagen, Rigshosp, Danish Dementia Res Ctr, Dept Neurol, DK-2100 Copenhagen, Denmark. [Hansen, Ase M.] Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen, Denmark. [Hansen, Ase M.] Natl Res Ctr Working Environm, DK-2100 Copenhagen, Denmark. [Moreno-Villanueva, Maria; Buerkle, Alexander] Univ Konstanz, Mol Toxicol Grp, D-78457 Constance, Germany. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Maynard, S (reprint author), Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark. EM scottm@cancer.dk OI Hansen, Ase Marie/0000-0002-4075-3918 FU Nordea-fonden FX This work was supported by grants from Nordea-fonden. NR 68 TC 3 Z9 3 U1 1 U2 10 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 OCT PY 2015 VL 7 IS 10 BP 793 EP + PG 23 WC Cell Biology SC Cell Biology GA CY0MS UT WOS:000366100800014 PM 26539816 ER PT J AU Guttmacher, AE Spong, CY AF Guttmacher, Alan E. Spong, Catherine Y. TI The human placenta project: it's time for real time SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID ORIGINS C1 [Guttmacher, Alan E.; Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov NR 8 TC 2 Z9 2 U1 0 U2 2 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 OCT PY 2015 VL 213 IS 4 SU S BP S3 EP S5 DI 10.1016/j.ajog.2015.08.037 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX9VW UT WOS:000366054800002 PM 26428502 ER PT J AU Kim, CJ Romero, R Chaemsaithong, P Kim, JS AF Kim, Chong Jai Romero, Roberto Chaemsaithong, Piya Kim, Jung-Sun TI Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE allograft; C4d; CD8; chemokine; chronic chorioamnionitis; chronic deciduitis; complement; CXCL10; fetal death; fetal growth restriction; HLA; maternal floor infarction; plasma cells; prematurity; rejection; T cell; tolerance; VUE ID MATERNAL ANTIFETAL REJECTION; REGULATORY T-CELLS; VERSUS-HOST-DISEASE; MAJOR HISTOCOMPATIBILITY COMPLEX; INTRAUTERINE GROWTH RESTRICTION; LATE PRETERM BIRTH; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; SOLID-ORGAN TRANSPLANTATION; PRETRANSPLANT SERUM CXCL10; RENAL-ALLOGRAFT REJECTION AB Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from infections (viral, bacterial, parasitic) or be of immune origin (maternal anti-fetal rejection). The 3 major lesions are villitis (when the inflammatory process affects the villous tree), chronic chorioamnionitis (which affects the chorioamniotic membranes), and chronic deciduitis (which involves the decidua basalis). Maternal cellular infiltration is a common feature of the lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory lesion that is characterized by the infiltration of maternal T cells (CD8+ cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the villi is driven by the production of T-cell chemokines in the affected villi. Activation of macrophages in the villi has been implicated in the destruction of the villous architecture. VUE has been reported in association with preterm and term fetal growth restriction, preeclampsia, fetal death, and preterm labor. Infants whose placentas have VUE are at risk for death and abnormal neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the most common lesion in late spontaneous preterm birth and is characterized by the infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These cytotoxic T cells can induce trophoblast apoptosis and damage the fetal membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis consists of the presence of lymphocytes or plasma cells in the basal plate of the placenta. This lesion is more common in pregnancies that result from egg donation and has been reported in a subset of patients with premature labor. Chronic placental inflammatory lesions can be due to maternal anti-fetal rejection, a process associated with the development of a novel form of fetal systemic inflammatory response. The syndrome is characterized by an elevation of the fetal plasma T-cell chemokine. The evidence that maternal anti-fetal rejection underlies the pathogenesis of many chronic inflammatory lesions of the placenta is reviewed. This article includes figures and histologic examples of all chronic inflammatory lesions of the placenta. C1 [Kim, Chong Jai] Univ Ulsan, Dept Pathol, Coll Med, Asan Med Ctr, Seoul, South Korea. [Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Kim, Jung-Sun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Kim, Jung-Sun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Chaemsaithong, Piya] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kim, Jung-Sun] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med, Seoul, South Korea. RP Romero, R (reprint author), Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HSN275201300006C] FX Supported, in part, by the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract No. HSN275201300006C. NR 229 TC 15 Z9 15 U1 2 U2 13 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 OCT PY 2015 VL 213 IS 4 SU S BP S53 EP S69 DI 10.1016/j.ajog.2015.08.041 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX9VW UT WOS:000366054800009 PM 26428503 ER PT J AU Kim, CJ Romero, R Chaemsaithong, P Chaiyasit, N Yoon, BH Kim, YM AF Kim, Chong Jai Romero, Roberto Chaemsaithong, Piya Chaiyasit, Noppadol Yoon, Bo Hyun Kim, Yeon Mee TI Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE chorionic vasculitis; CXCL6; fetal inflammatory response syndrome; granulocyte chemotactic protein; interleukin (IL)-8; microbial invasion of the amniotic cavity; placental pathology; pregnancy; prematurity; preterm; staging; sterile inflammation ID PRETERM PREMATURE RUPTURE; TUMOR-NECROSIS-FACTOR; FETAL INFLAMMATORY RESPONSE; AMNIOTIC-FLUID INTERLEUKIN-6; POLYMERASE-CHAIN-REACTION; CERVICAL-MUCUS PLUG; BLOOD-CELL COUNT; WHITE-MATTER LESIONS; MMP-8 BEDSIDE TEST; INTRAAMNIOTIC LIPOPOLYSACCHARIDE EXPOSURE AB Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of pacentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short-and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. C1 [Kim, Chong Jai] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. [Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA. [Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Chaemsaithong, Piya; Chaiyasit, Noppadol] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea. [Kim, Yeon Mee] Inje Univ, Coll Med, Dept Pathol, Haeundae Paik Hosp, Busan, South Korea. RP Romero, R (reprint author), Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. EM romeror@mail.nih.gov FU Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Department of Health and Human Services (NICHD/NIH); Federal funds from NICHD, NIH [HSN275201300006C] FX Supported, in part, by the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH); and, in part, with Federal funds from NICHD, NIH under Contract no. HSN275201300006C. NR 384 TC 32 Z9 35 U1 1 U2 9 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 OCT PY 2015 VL 213 IS 4 SU S BP S29 EP S52 DI 10.1016/j.ajog.2015.08.040 PG 24 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX9VW UT WOS:000366054800008 PM 26428501 ER PT J AU Romero, R AF Romero, Roberto TI Images of the human placenta SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID INTERVILLOUS SPACE; CIRCULATION; PREGNANCY C1 [Romero, Roberto] Wayne State Univ, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet,Sch Med, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Detroit, MI 48202 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet,Sch Med, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Detroit, MI 48202 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2015 VL 213 IS 4 SU S BP S1 EP S2 DI 10.1016/j.ajog.2015.08.039 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX9VW UT WOS:000366054800001 PM 26428487 ER PT J AU Di Maggio, R Hsieh, MM Fitzhugh, CD Zhao, X Calvaruso, G Rigano, P Renda, D Siragusa, S Tisdale, JF Maggio, A AF Di Maggio, R. Hsieh, M. M. Fitzhugh, C. D. Zhao, X. Calvaruso, G. Rigano, P. Renda, D. Siragusa, S. Tisdale, J. F. Maggio, A. TI CHRONIC ADMINISTRATION OF HYDROXYUREA AND OUTCOMES IN PATIENTS WITH SICKLE CELL DISEASE AT A SINGLE REFERRAL INSTITUTION SO HAEMATOLOGICA LA English DT Meeting Abstract CT 45th Congress of the Italian-Society-of-Hematology CY OCT 04-07, 2015 CL Florence, ITALY SP Italian Soc Hematol, Novartis Oncol, Celgene, Takeda Oncol, Bristol Myers Squibb, Janssen, Amgen Oncol, Roche, Gilead, GlaxoSmithKline, Ariad, Alexion C1 AOR Villa Sofia V Cervello, UOC Ematol 2, Palermo, Italy. NIDDK, MCHB, NHLBI, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Off Clin, Bethesda, MD 20892 USA. Univ Palermo, UO Ematol Trapianto DIMIS AOUP P Giaccone, I-90133 Palermo, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 SU 3 MA C20 BP 14 EP 14 PG 1 WC Hematology SC Hematology GA CX5XR UT WOS:000365776300033 ER PT J AU Navarro, A Clot, G Martinez-Trillos, A Salaverria, I Trim, N Martin-Garcia, D Fernandez, V Villamor, N Colomer, D Pinyol, M Jares, P Erber, W Wiestner, A Wyndham, HW Siebert, R Aymerich, M Lopez-Guillermo, A Matutes, E Campo, E Bea, S AF Navarro, A. Clot, G. Martinez-Trillos, A. Salaverria, I Trim, N. Martin-Garcia, D. Fernandez, V Villamor, N. Colomer, D. Pinyol, M. Jares, P. Erber, W. Wiestner, A. Wilson Wyndham, H. Siebert, R. Aymerich, M. Lopez-Guillermo, A. Matutes, E. Campo, E. Bea, S. TI GENE EXPRESSION PROFILING SIGNATURES ALLOW THE IDENTIFICATION A SUBSET OF UNCLASSIFIABLE LEUKEMIC B-CELL LYMPHOID NEOPLASMS GENE SO HAEMATOLOGICA LA Spanish DT Meeting Abstract CT 57th National Congress of the Spanish-Society-of-Hematology-and-Hemotherapy CY OCT 22-24, 2015 CL Valencia, SPAIN SP Spanish Soc Hematol & Hemotherapy, Novartis Oncol, Celgene, Takeda Oncol, Bristol Myers Squibb, Janssen, Amgen Oncol, Roche, Gilead, GlaxoSmithKline, Alexion, Ariad C1 [Navarro, A.; Clot, G.; Salaverria, I; Martin-Garcia, D.; Fernandez, V; Campo, E.; Bea, S.] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Martinez-Trillos, A.; Villamor, N.; Colomer, D.; Aymerich, M.; Lopez-Guillermo, A.; Matutes, E.; Campo, E.] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain. [Trim, N.] West Midlands Reg Genet Lab, Birmingham, W Midlands, England. [Pinyol, M.; Jares, P.] IDIBAPS, Unidad Genom, Barcelona, Spain. [Jares, P.; Bea, S.] Univ Barcelona, Barcelona, Spain. [Erber, W.] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia. [Wiestner, A.] NHLBI, Bethesda, MD 20892 USA. [Wilson Wyndham, H.] NCI, Bethesda, MD 20892 USA. [Siebert, R.] Univ Kiel, Inst Human Genet, Kiel, Germany. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 SU 4 MA CO-104 BP 66 EP 67 PG 2 WC Hematology SC Hematology GA CX5XX UT WOS:000365776900114 ER PT J AU Pellicano, MV Cutrona, G Gentile, M Vigna, E Matis, S Colombo, M Massucco, C Bossio, S De Stefano, L Caruso, N Storino, F Consoli, U Vincelli, I Musolino, C Neri, A Tripodo, C Ferrarini, M Recchia, AG Morabito, F AF Pellicano, M. V. Cutrona, G. Gentile, M. Vigna, E. Matis, S. Colombo, M. Massucco, C. Bossio, S. De Stefano, L. Caruso, N. Storino, F. Consoli, U. Vincelli, I. Musolino, C. Neri, A. Tripodo, C. Ferrarini, M. Recchia, A. G. Morabito, F. TI MODULATION OF SURFACE IGM AND IGD BY AUTOLOGOUS ACTIVATED T-CELLS AND ACTIVATION OF BCR SIGNALLING IN CHRONIC LYMPHOCYTIC LEUKEMIA FOLLOWING BCR CROSS-LINKING BY ANTI-(A) AND ANTI-(A) ANTIBODIES SO HAEMATOLOGICA LA English DT Meeting Abstract CT 45th Congress of the Italian-Society-of-Hematology CY OCT 04-07, 2015 CL Florence, ITALY SP Italian Soc Hematol, Novartis Oncol, Celgene, Takeda Oncol, Bristol Myers Squibb, Janssen, Amgen Oncol, Roche, Gilead, GlaxoSmithKline, Ariad, Alexion C1 [Pellicano, M. V.; Bossio, S.; De Stefano, L.; Caruso, N.; Storino, F.; Recchia, A. G.; Morabito, F.] Azienda Sanit Prov, Unita Ric Biotecnol, Aprigliano, CS, Italy. [Cutrona, G.; Matis, S.; Colombo, M.; Morabito, F.] IRCCS AOU San Martino IST, Genoa, Italy. [Gentile, M.; Vigna, E.] Annunziata Civil Hosp Cosenza, Div Hematol, Cosenza, Italy. [Massucco, C.] Natl Canc Inst, IRCCS S Martino, Genoa, Italy. [Consoli, U.] Garibaldi Nesima Hosp Catania, Div Hematol Oncol, Catania, Italy. [Vincelli, I.] Bianchi Melacrino Morelli Civil Hosp Reggio Calab, Div Hematol, Reggio Di Calabria, Italy. [Musolino, C.] Univ Messina, Div Hematol, Messina, Italy. [Neri, A.] Univ Milan, Dept Clin & Community Sci, Milan, Italy. [Neri, A.] IRCCS Fdn Ca Granda Policlin Hosp, Milan, Italy. [Tripodo, C.] Univ Palermo, Dept Hlth Sci, Tumor Immunol Unit, Human Pathol Sect,Sch Med, Palermo, Italy. [Ferrarini, M.] IRCCS AOU San Martino IST, Div Sci, Genoa, Italy. RI Tripodo, Claudio/O-4536-2016 OI Tripodo, Claudio/0000-0002-0821-6231 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 SU 3 MA P201 BP 135 EP 135 PG 1 WC Hematology SC Hematology GA CX5XR UT WOS:000365776300334 ER PT J AU Kennedy, KV Roman, CMG Ruperez, AS Aalto, L Crowe, C Krawczyk, J Phelan, S Sheng, MTC Flavin, R Pittaluga, S Murray, M Brodie, C AF Velazquez Kennedy, K. Martinez-Geijo Roman, C. Sanz Ruperez, A. Aalto, L. Crowe, C. Krawczyk, J. Phelan, S. Chien Sheng, Tan M. Flavin, R. Pittaluga, S. Murray, M. Brodie, C. TI PRIMITIVE HEMATOPOIETIC NEOPLASM OF UNCERTAIN LINEAGE PRESENTED AS PROGRESSIVE MULTIFOCAL LYMPHADENOPATHY. CLINICAL CASE SO HAEMATOLOGICA LA Spanish DT Meeting Abstract CT 57th National Congress of the Spanish-Society-of-Hematology-and-Hemotherapy CY OCT 22-24, 2015 CL Valencia, SPAIN SP Spanish Soc Hematol & Hemotherapy, Novartis Oncol, Celgene, Takeda Oncol, Bristol Myers Squibb, Janssen, Amgen Oncol, Roche, Gilead, GlaxoSmithKline, Alexion, Ariad ID ACUTE-LEUKEMIA C1 [Velazquez Kennedy, K.; Martinez-Geijo Roman, C.; Sanz Ruperez, A.] Hosp Univ Ramon & Cajal, Serv Hematol, Barcelona, Spain. [Aalto, L.; Phelan, S.; Chien Sheng, Tan M.; Brodie, C.] Univ Hosp Galway, Pathol Dept, Galway, Ireland. [Crowe, C.; Krawczyk, J.; Murray, M.] Univ Hosp Galway, Haematol Dept, Galway, Ireland. [Flavin, R.] St James Univ Hosp, Pathol Dept, Galway, Ireland. [Pittaluga, S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 4 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 SU 4 MA PB-086 BP 267 EP 267 PG 1 WC Hematology SC Hematology GA CX5XX UT WOS:000365776900515 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, Clara J. K. Curtis, Rochelle E. Dores, Graca M. Engels, Eric A. Caporaso, Neil E. Polliack, Aaron Warren, Joan L. Young, Heather A. Levine, Paul H. Elmi, Angelo F. Fraumeni, Joseph F., Jr. Tucker, Margaret A. Morton, Lindsay M. TI Risk Factors for Melanoma Among Survivors of Non-Hodgkin Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TREATMENT-RELATED MYELODYSPLASIA; 2ND MALIGNANCIES; TRANSPLANT RECIPIENTS; UNITED-STATES; SKIN CANCERS; SOLID TUMORS; FLUDARABINE; THERAPY; CYCLOPHOSPHAMIDE AB Purpose Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Patients and Methods We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims. Results A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n = 18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n = 10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n = 36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n = 49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs). Conclusion Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma. (C) 2015 by American Society of Clinical Oncology C1 [Lam, Clara J. K.; Curtis, Rochelle E.; Dores, Graca M.; Engels, Eric A.; Caporaso, Neil E.; Warren, Joan L.; Fraumeni, Joseph F., Jr.; Tucker, Margaret A.; Morton, Lindsay M.] NCI, Rockville, MD USA. [Lam, Clara J. K.; Young, Heather A.; Levine, Paul H.; Elmi, Angelo F.] George Washington Univ, Sch Publ Hlth, Milken Inst, Washington, DC USA. [Dores, Graca M.] Oklahoma City Vet Affairs Hlth Care Syst, Oklahoma City, OK USA. [Polliack, Aaron] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RP Lam, CJK (reprint author), NCI, Radiat Epidemiol Branch, 9609 Med Ctr Dr,7E-529, Rockville, MD 20850 USA. EM kimcj2@mail.nih.gov NR 67 TC 2 Z9 2 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 OCT 1 PY 2015 VL 33 IS 28 BP 3096 EP + DI 10.1200/JCO.2014.60.2094 PG 15 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600008 PM 26240221 ER PT J AU Gounder, MM Nayak, L Sahebjam, S Muzikansky, A Sanchez, AJ Desideri, S Ye, XB Ivy, SP Nabors, LB Prados, M Grossman, S DeAngelis, LM Wen, PY AF Gounder, Mrinal M. Nayak, Lakshmi Sahebjam, Solmaz Muzikansky, Alona Sanchez, Armando J. Desideri, Serena Ye, Xiaobu Ivy, S. Percy Nabors, L. Burt Prados, Michael Grossman, Stuart DeAngelis, Lisa M. Wen, Patrick Y. TI Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS; BRAIN METASTASES; CLINICAL-TRIALS; SOLID TUMORS; ATRASENTAN; INHIBITOR; TOXICITY; CANCER; PHARMACOKINETICS AB Purpose Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. Patient and Methods Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. Results Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n = 5) and cytotoxic (n = 3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, < one to 56 cycles), and 96% were evaluable for primary end points. During cycle 1, grade >= 3 nonhematologic and grade 4 hematologic toxicities were 5% (28 of 565 adverse events) and 0.9% (five of 565 adverse events), respectively, and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (complete and partial response) was 5.5%. Median progression-free and overall survival times were 1.8 and 6 months, respectively. Conclusion Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties in this population. (C) 2015 by American Society of Clinical Oncology C1 [Gounder, Mrinal M.; Sanchez, Armando J.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Gounder, Mrinal M.; Sanchez, Armando J.; DeAngelis, Lisa M.] Weil Cornell Med Sch, New York, NY USA. [Nayak, Lakshmi; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nayak, Lakshmi; Muzikansky, Alona; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sahebjam, Solmaz] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Desideri, Serena; Ye, Xiaobu; Grossman, Stuart] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Gounder, MM (reprint author), Mem Sloan Kettering Canc Ctr, Dev Therapeut Serv, 300 E 66th St BAIC 1075, New York, NY 10065 USA. EM gounderm@mskcc.org FU Cortice Biosciences (Inst); Merck (Inst); Genentech/Roche (Inst); Erimos Pharmaceuticals (Inst); AstraZeneca; Agios; Angiochem; Exelixis; Genentech/Roche; GlaxoSmithKline; Karyopharm Therapeutics; Merck; Novartis; Sanofi; Vascular Biogenics FX Cortice Biosciences (Inst), Merck (Inst); Genentech/Roche (Inst); Erimos Pharmaceuticals (Inst); AstraZeneca, Agios, Angiochem, Exelixis, Genentech/Roche, GlaxoSmithKline, Karyopharm Therapeutics, Merck, Novartis, Sanofi, Vascular Biogenics NR 40 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2015 VL 33 IS 28 BP 3186 EP + DI 10.1200/JCO.2015.61.1525 PG 9 WC Oncology SC Oncology GA CX9IJ UT WOS:000366018600019 PM 26282642 ER PT J AU Kim, HN Han, L Iyer, S de Cabo, R Zhao, HB O'Brien, CA Manolagas, SC Almeida, M AF Kim, Ha-Neui Han, Li Iyer, Srividhya de Cabo, Rafael Zhao, Haibo O'Brien, Charles A. Manolagas, Stavros C. Almeida, Maria TI Sirtuin1 Suppresses Osteoclastogenesis by Deacetylating FoxOs SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTION FACTORS; LIFE-SPAN; BONE-RESORPTION; MUSCLE ATROPHY; SIRT1; ACTIVATION; MICE; ACETYLATION; RESVERATROL; PROTEIN AB Activation of Sirtuin1 (Sirt1), an nicotinamide adenine dinucleotide oxidized-dependent deacetylase, by natural or synthetic compounds like resveratrol, SRT2104, or SRT3025 attenuates the loss of bone mass caused by ovariectomy, aging, or unloading in mice. Conversely, Sirt1 deletion in osteoclast progenitors increases osteoclast number and bone resorption. Sirt1 deacetylates forkhead box protein (Fox) O1, FoxO3, and FoxO4, and thereby modulates their activity. FoxOs restrain osteoclastogenesis and bone resorption. Here, we tested the hypothesis that the antiresorptive effects of Sirt1 are mediated by FoxOs. We report that Sirt1 activation by SRT2104 and SRT3025 inhibited murine osteoclast progenitor proliferation and reduced osteoclastogenesis. The effect of Sirt1 stimulators on osteoclastogenesis was abrogated in cells lacking FoxO1, FoxO3, and FoxO4. FoxO1 acetylation was increased by knocking down Sirt1 or addition of receptor activator of nuclear factor kappa-B ligand, the critical cytokine for osteoclast differentiation. Furthermore, acetylation inhibited, whereas deacetylation promoted, FoxO-mediated transcription. SRT3025 increased the expression of the FoxO-target genes catalase and hemeoxygenase-1 (HO-1) in osteoclast progenitors, in a FoxO-dependent manner. HO-1 catabolizes heme and attenuates mitochondrial oxidative phosphorylation and ATP production in macrophages. HO-1 levels were strongly reduced and ATP levels increased by Receptor activator of nuclear factor kappa-B ligand. In contrast, SRT3025 and FoxOs decreased ATP production, and the effect of SRT3025 was mediated by FoxOs. These findings reveal that the antiosteoclastogenic actions of Sirt1 are mediated by FoxOs and result from impaired mitochondria activity. Along with earlier findings that the osteoblastogenic effects of Sirt1 are also mediated by FoxOs, these results establish that the dual antiosteoporotic efficacy of Sirt1 stimulators (ie, decreasing bone resorption and promoting bone formation) is mediated via FoxO deacetylation. C1 [Kim, Ha-Neui; Han, Li; Iyer, Srividhya; Zhao, Haibo; O'Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria] Univ Arkansas Med Sci, Div Endocrinol & Metab, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. [de Cabo, Rafael] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. RP Almeida, M (reprint author), Univ Arkansas Med Sci, Div Endocrinol & Metab, 4301 West Markham St 587, Little Rock, AR 72205 USA. EM schullermaria@uams.edu RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU National Institutes of Health [R01 AR56679, P01 AG13918]; Biomedical Laboratory Research and Development Service of the Veteran's Administration Office of Research and Development [I01 BX001405]; University of Arkansas for Medical Sciences Tobacco Funds and Translational Research Institute [1UL1RR029884]; Intramural Research Program of the National Institute on Aging, of the National Institutes of Health FX This work was supported by National Institutes of Health Grants R01 AR56679 (to M.A.), and P01 AG13918 (to S.C.M.); the Biomedical Laboratory Research and Development Service of the Veteran's Administration Office of Research and Development Grant I01 BX001405 (to S.C.M.); and the University of Arkansas for Medical Sciences Tobacco Funds and Translational Research Institute Grant 1UL1RR029884. R.d.C. was supported by the Intramural Research Program of the National Institute on Aging, of the National Institutes of Health. NR 53 TC 8 Z9 10 U1 1 U2 8 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 OCT PY 2015 VL 29 IS 10 BP 1498 EP 1509 DI 10.1210/me.2015-1133 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CY6HB UT WOS:000366508500010 PM 26287518 ER PT J AU Randall, TC Salicrup, LA Luciani, S Trimble, EL AF Randall, Thomas C. Salicrup, Luis A. Luciani, Silvana Trimble, Edward L. TI HPV Testing in Resource-Limited Settings: How Can We Reach the Next Level of Cervical Cancer Screening in Latin America and the Caribbean? SO ONCOLOGIST LA English DT Editorial Material ID MORTALITY; INDIA C1 [Randall, Thomas C.] Dana Farber Harvard Canc Ctr, Global Oncol Initiat, Boston, MA USA. [Salicrup, Luis A.; Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Luciani, Silvana] Pan Amer Hlth Org, Canc Prevent & Control, Washington, DC USA. RP Randall, TC (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Gates 520 B, Boston, MA 02108 USA. EM trandall@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD OCT PY 2015 VL 20 IS 10 BP 1101 EP 1104 DI 10.1634/theoncologist.2015-0201 PG 4 WC Oncology SC Oncology GA CX9QX UT WOS:000366041500001 PM 26330459 ER PT J AU Meisenberg, BR Varner, A Ellis, E Ebner, S Moxley, J Siegrist, E Weng, D AF Meisenberg, Barry R. Varner, Ashley Ellis, Erin Ebner, Stephen Moxley, John Siegrist, Erika Weng, David TI Patient Attitudes Regarding the Cost of Illness in Cancer Care SO ONCOLOGIST LA English DT Article DE Cost of illness; Attitudes; Choice behavior; Neoplasms ID FINANCIAL TOXICITY; BURDEN; EXPERIENCE; SURVIVORS; LEUKEMIA AB Background and Purpose. The cost of illness in cancer care and the subsequent distress has attracted scrutiny. Guidelines recommend enhanced discussion of costs, assuming this will reduce both stress and costs. Little is known about patient attitudes about cost considerations influencing treatment decisions. Methods. A convenience-sample survey of patients currently receiving radiation and/or intravenous chemotherapy at an outpatient cancer center was performed. Assessments included prevalence and extent of financial burden, level of financial distress, attitudes about using costs to influence treatment decisions, and frequency or desirability of cost discussions with oncologists. Results. A total of 132 participants (94%) responded. Overall, 47% reported high financial stress, 30.8% felt well informed about costs prior to treatment, and 71% rarely spoke to their oncologists about cost. More than 71% of patients did not want either society's or personal costs to influence treatment, and this result did not change based on degree of financial stress. Even when asked to assume that lower cost regimens were equally effective, only 28% would definitely want the lower cost regimen. Patients did not believe it was the oncologist's duty to perform cost discussions. Conclusion. Even insured patients have a high degree of financial distress. Most, including those with the highest levels of distress, did not speak often with oncologists about costs and were strongly adverse to having cost considerations influence choice of regimen. The findings suggest that patients are not cost sensitive with regard to treatment decisions. Oncologists will require improved tools to have meaningful cost discussion, as recommended by the American Society of Clinical Oncology. C1 [Meisenberg, Barry R.; Varner, Ashley; Weng, David] Anne Arundel Med Ctr, DeCesaris Canc Inst, Annapolis, MD 21401 USA. [Meisenberg, Barry R.; Ebner, Stephen; Moxley, John; Siegrist, Erika] Anne Arundel Hlth Syst Res Inst, Annapolis, MD USA. [Ellis, Erin] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Meisenberg, BR (reprint author), Anne Arundel Med Ctr, DeCesaris Canc Inst, 2001 Med Pkwy, Annapolis, MD 21401 USA. EM Meisenberg@AAHS.org NR 29 TC 3 Z9 3 U1 2 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD OCT PY 2015 VL 20 IS 10 BP 1199 EP 1204 DI 10.1634/theoncologist.2015-0168 PG 6 WC Oncology SC Oncology GA CX9QX UT WOS:000366041500016 PM 26330457 ER PT J AU Widmer, M Cuesta, C Khan, KS Conde-Agudelo, A Carroli, G Fusey, S Karumanchi, SA Lapaire, O Lumbiganon, P Sequeira, E Zavaleta, N Frusca, T Gulmezoglu, AM Lindheimer, MD AF Widmer, Mariana Cuesta, Cristina Khan, Khalid S. Conde-Agudelo, Agustin Carroli, Guillermo Fusey, Shalini Karumanchi, S. Ananth Lapaire, Olav Lumbiganon, Pisake Sequeira, Evan Zavaleta, Nelly Frusca, Tiziana Guelmezoglu, A. Metin Lindheimer, Marshall D. TI Accuracy of angiogenic biomarkers at <= 20 weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study SO PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH LA English DT Article DE Pre-eclampsia; Screening; Angiogenic biomarkers ID ENDOTHELIAL GROWTH-FACTOR; SOLUBLE ENDOGLIN; 1ST-TRIMESTER PREDICTION; ANTIANGIOGENIC FACTORS; TYROSINE KINASE-1; RANDOMIZED-TRIAL; WOMEN; PREGNANCY; OUTCOMES AB Objective: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. Design: Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at <= 20, 23-27 and 32-35 weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg, and proteinuria (protein/creatinine ratio >= 0.3, protein >= 1 g/l, or one dipstick measurement >= 2+) appearing after 20 weeks' gestation. Early pre-eclampsia was defined when these signs appeared <= 34 weeks' gestation. Main outcome measure: Pre-eclampsia. Results: Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at <= 20 weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at <= 34 weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability. Conclusions: Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia. (C) 2015 Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. C1 [Widmer, Mariana; Guelmezoglu, A. Metin] WHO, World Bank Special Programme Res Dev & Res Traini, Dept Reprod Hlth & Res, UNDP,UNFPA,UNICEF, CH-1201 Geneva, Switzerland. [Cuesta, Cristina] CREP, Rosario, Santa Fe, Argentina. [Khan, Khalid S.] Barts & London Med Sch, London, England. [Conde-Agudelo, Agustin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Bethesda, MA USA. [Conde-Agudelo, Agustin] NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Fusey, Shalini] Govt Med Coll & Hosp, Dept Obstet & Gynaecol, Nagpur, Maharashtra, India. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Lapaire, Olav] Univ Basel Hosp, Dept Obstet & Gynecol, CH-4031 Basel, Switzerland. [Lumbiganon, Pisake] Khon Kaen Univ, Fac Med, Dept Obstet & Gynaecol, Khon Kaen, Thailand. [Sequeira, Evan] Aga Khan Univ Hosp, Dept Obstet & Gynaecol, Nairobi, Kenya. [Zavaleta, Nelly] Inst Invest Nutr, Lima, Peru. [Frusca, Tiziana] Univ Brescia, Maternal Fetal Med Unit, Dept Obstet & Gynaecol, I-25121 Brescia, Italy. [Frusca, Tiziana] Univ Parma, Dept Obstet & Gynecol, I-43100 Parma, Italy. [Lindheimer, Marshall D.] Univ Chicago, Pritzker Sch Med, Obstet & Gynecol, Chicago, IL 60637 USA. RP Widmer, M (reprint author), WHO, World Bank Special Programme Res Dev & Res Traini, Dept Reprod Hlth & Res, UNDP,UNFPA,UNICEF, Ave Appia 20, CH-1201 Geneva, Switzerland. EM widmerm@who.int OI , Cristina/0000-0002-6127-5601 FU UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization FX UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization. NR 32 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2210-7789 J9 PREGNANCY HYPERTENS JI Pregnancy Hypertens. PD OCT PY 2015 VL 5 IS 4 BP 330 EP 338 DI 10.1016/j.preghy.2015.09.004 PG 9 WC Obstetrics & Gynecology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Cardiovascular System & Cardiology GA CY0EG UT WOS:000366078600014 PM 26597750 ER PT J AU Baselga, J Bhardwaj, N Cantley, LC DeMatteo, R DuBois, RN Foti, M Gapstur, SM Hahn, WC Helman, LJ Jensen, RA Paskett, ED Lawrence, TS Lutzker, SG Szabo, E AF Baselga, Jose Bhardwaj, Nina Cantley, Lewis C. DeMatteo, Ronald DuBois, Raymond N. Foti, Margaret Gapstur, Susan M. Hahn, William C. Helman, Lee J. Jensen, Roy A. Paskett, Electra D. Lawrence, Theodore S. Lutzker, Stuart G. Szabo, Eva TI AACR Cancer Progress Report 2015 SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-PAPILLOMAVIRUS VACCINATION; ADVANCED BREAST-CANCER; CELL LUNG-CANCER; BODY-MASS INDEX; UNITED-STATES; COLORECTAL-CANCER; ADVANCED MELANOMA; AMERICAN ASSOCIATION; PANCREATIC-CANCER; POLICY STATEMENT C1 [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Bhardwaj, Nina] Mt Sinai Med Ctr, Ctr Sci & Med, Immunotherapy, New York, NY USA. [Cantley, Lewis C.] Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, New York, NY USA. [DeMatteo, Ronald] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. [DeMatteo, Ronald] Mem Sloan Kettering Canc Ctr, Div Gen Surg Oncol, New York, NY USA. [DuBois, Raymond N.] Arizona State Univ, Biodesign Inst, Tempe, AZ USA. [Foti, Margaret] Am Assoc Canc Res, Philadelphia, PA USA. [Gapstur, Susan M.] Am Canc Soc, Epidemiol Res Program, Atlanta, GA USA. [Hahn, William C.] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Boston, MA USA. [Helman, Lee J.] NCI, Clin Res, Bethesda, MD USA. [Jensen, Roy A.] Univ Kansas, Canc Ctr, Kansas City, KS USA. [Paskett, Electra D.] Ohio State Univ, Comprehens Canc Ctr, Populat Sci Dept, Columbus, OH USA. [Lawrence, Theodore S.] Univ Michigan, Canc Ctr, Ann Arbor, MI USA. [Lawrence, Theodore S.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI USA. [Lutzker, Stuart G.] Genentech Inc, Clin Dev, BioOncol Exploratory, San Francisco, CA USA. [Szabo, Eva] NCI, Lung & Upper Aerodigest, Canc Res Grp, Potomac, MD USA. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P30 CA008748] NR 167 TC 1 Z9 1 U1 1 U2 9 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 OCT 1 PY 2015 VL 21 SU 19 BP S1 EP S128 DI 10.1158/1078-0432.CCR-15-1846 PG 128 WC Oncology SC Oncology GA CV7UE UT WOS:000364480100010 PM 26429991 ER PT J AU Malecka, A Tierens, A Ostlie, I Schmitz, R Troen, G Spetalen, S Staudt, LM Smeland, E Holte, H Delabie, J AF Malecka, Agnieszka Tierens, Anne Ostlie, Ingunn Schmitz, Roland Troen, Gunhild Spetalen, Signe Staudt, Louis M. Smeland, Erlend Holte, Harald Delabie, Jan TI Primary diffuse large B-cell lymphoma associated with clonally-related monoclonal B lymphocytosis indicates a common precursor cell SO HAEMATOLOGICA LA English DT Letter DE primary diffuse large B-cell lymphoma; monoclonal B lymphocytes; precursor cell; clonally-related ID BONE-MARROW; LEUKEMIA; IMMUNOGLOBULIN; CLONES; ORIGIN C1 [Malecka, Agnieszka; Ostlie, Ingunn; Troen, Gunhild; Spetalen, Signe] Oslo Univ Hosp, Dept Pathol, Oslo, Norway. [Tierens, Anne; Delabie, Jan] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Tierens, Anne; Delabie, Jan] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Schmitz, Roland; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Smeland, Erlend] Oslo Univ Hosp, Inst Canc Res, Oslo, Norway. [Smeland, Erlend; Holte, Harald; Delabie, Jan] Univ Oslo, Ctr Canc Biomed, N-0316 Oslo, Norway. [Holte, Harald] Oslo Univ Hosp, Canc Clin, Dept Oncol, Oslo, Norway. RP Delabie, J (reprint author), Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. EM jan.delabie@uhn.ca NR 15 TC 0 Z9 0 U1 1 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD OCT PY 2015 VL 100 IS 10 BP E415 EP E418 DI 10.3324/haematol.2015.126656 PG 4 WC Hematology SC Hematology GA CX5XM UT WOS:000365775800010 PM 26001788 ER PT J AU Dai, M Hu, P Shi, JF Ren, JS Liao, XZ Du, LB Liu, YQ Chen, ZL Wu, N Liu, Q Pinsky, P Prorok, P Fagerstrom, R Taylor, M Kramer, B He, J AF Dai, Min Hu, Ping Shi, Ju-Fang Ren, Jian-Song Liao, Xian-Zhen Du, Ling-Bin Liu, Yu-Qin Chen, Zhao-Li Wu, Ning Liu, Qian Pinsky, Paul Prorok, Philip Fagerstrom, Richard Taylor, Martina Kramer, Barnett He, Jie CA China Canc Screening Trial TI The China Cancer Screening Trial Feasibility Study SO LANCET LA English DT Meeting Abstract CT Lancet - Chinese-Academy-of-Medical-Sciences (CAMS) Health Summit CY OCT 30-31, 2015 CL Beijing, PEOPLES R CHINA SP Lancet, Chinese Acad Med Sc C1 [Dai, Min; Shi, Ju-Fang; Ren, Jian-Song] Chinese Acad Med Sci, Canc Inst & Hosp, Natl Off Canc Prevent & Control, Beijing 100730, Peoples R China. [Hu, Ping; Pinsky, Paul; Prorok, Philip; Fagerstrom, Richard; Taylor, Martina; Kramer, Barnett] Natl Canc Inst, Canc Prevent Div, Bethesda, MD USA. [Liao, Xian-Zhen] Hunan Canc Hosp, Changsha, Hunan, Peoples R China. [Du, Ling-Bin] Zhejiang Canc Hosp, Hangzhou, Zhejiang, Peoples R China. [Chen, Zhao-Li; He, Jie] Chinese Acad Med Sci, Canc Hosp, Dept Thorac Surg, Beijing 100730, Peoples R China. [Wu, Ning] Chinese Acad Med Sci, Canc Hosp, Dept Imaging Diag, Beijing 100730, Peoples R China. [Liu, Qian] Chinese Acad Med Sci, Canc Hosp, Dept Colorectal Canc Surg, Beijing 100730, Peoples R China. EM prof_hejie@163.com 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD OCT PY 2015 VL 386 SU 1 BP 35 EP 35 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CX9HR UT WOS:000366016400036 ER PT J AU Rid, A Wesley, R Pavlick, M Maynard, S Roth, K Wendler, D AF Rid, Annette Wesley, Robert Pavlick, Mark Maynard, Sharon Roth, Katalin Wendler, David TI Patients' priorities for treatment decision making during periods of incapacity: quantitative survey SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Advance care planning; Advance directive; Surrogate decision making; Incapacitated patients; Patient priorities ID OF-LIFE CARE; SERIOUSLY ILL PATIENTS; RANDOMIZED CONTROLLED-TRIAL; ADVANCE DIRECTIVES; CARDIOPULMONARY-RESUSCITATION; TREATMENT PREFERENCES; VALUES HISTORY; OLDER-ADULTS; END; DEATH AB Objective: Clinical practice aims to respect patient autonomy by basing treatment decisions for incapacitated patients on their own preferences. Yet many patients do not complete an advance directive, and those who do frequently just designate a family member to make decisions for them. This finding raises the concern that clinical practice may be based on a mistaken understanding of patient priorities. The present study aimed to collect systematic data on how patients prioritize the goals of treatment decision making. Method: We employed a self-administered, quantitative survey of patients in a tertiary care center. Results: Some 80% or more of the 1169 respondents (response rate = 59.8%) ranked six of eight listed goals for treatment decision making as important. When asked which goal was most important, 38.8% identified obtaining desired or avoiding unwanted treatments, 20.0% identified minimizing stress or financial burden on their family, and 14.6% identified having their family help to make treatment decisions. No single goal was designated as most important by 25.0% of participants. Significance of Results: Patients endorsed three primary goals with respect to decision making during periods of incapacity: being treated consistent with their own preferences; minimizing the burden on their family; and involving their family in the decision-making process. However, no single goal was prioritized by a clear majority of patients. These findings suggest that advance care planning should not be limited to documenting patients' treatment preferences. Clinicians should also discuss and document patients' priorities for how decisions are to be made. Moreover, future research should evaluate ways to modify current practice to promote all three of patients primary goals for treatment decision making. C1 [Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England. [Wesley, Robert] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Pavlick, Mark] St Elizabeth Hosp, Washington, DC USA. [Maynard, Sharon] Univ S Florida, Morsani Coll Med, Lehigh Valley Hlth Network, Div Nephrol, Allentown, PA USA. [Roth, Katalin] George Washington Univ, Dept Med, Med Fac Associates, Washington, DC USA. [Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Rid, A (reprint author), Kings Coll London, Dept Social Sci Hlth & Med, East Wing Bldg, London WC2R 2LS, England. EM annette.rid@kcl.ac.uk FU Department of Bioethics, The Clinical Center, U.S. National Institutes of Health; Swiss National Science Foundation [PA00B-117505/1, PA0033-117502/2] FX This study was funded by the Department of Bioethics, The Clinical Center, U.S. National Institutes of Health. Annette Rid received funding from the Swiss National Science Foundation (PA00B-117505/1 and PA0033-117502/2). NR 64 TC 2 Z9 2 U1 6 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD OCT PY 2015 VL 13 IS 5 BP 1165 EP 1183 DI 10.1017/S1478951514001096 PG 19 WC Health Policy & Services SC Health Care Sciences & Services GA CX4IS UT WOS:000365663900004 PM 25273677 ER PT J AU Zhang, XJ Shi, Z Lyv, JX He, XY Englert, NA Zhang, SY AF Zhang, Xiao-Jie Shi, Zhe Lyv, Jing-Xi He, Xuyan Englert, Neal A. Zhang, Shu-Yun TI Pyrene is a Novel Constitutive Androstane Receptor (CAR) Activator and Causes Hepatotoxicity by CAR SO TOXICOLOGICAL SCIENCES LA English DT Article DE hepatotoxicity; nuclear receptor CAR; pyrene ID POLYCYCLIC AROMATIC-HYDROCARBONS; NUCLEAR RECEPTOR; DRUG-METABOLISM; PARTICULATE MATTER; MOUSE-LIVER; INDUCTION; CHINA; MICE; GENES; RIVER AB Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous persistent environmental pollutants which are primarily formed from the incomplete combustion of organic materials. Many potential sources of human exposure to PAHs exist, including daily exposures from the ambient environment or occupational settings. PAHs have been found to cause harmful effects on human health. Here, we evaluated the adverse effects of pyrene, a common PAH, on the liver. The present study demonstrates that pyrene is able to activate mouse constitutive androstane receptor (CAR). CAR protein, as measured by Western blot analysis, was observed to translocate into the nucleus from the cytoplasm in mouse liver after exposure to pyrene. Utilizing CAR null mice, we identified that CAR mediates pyrene-induced hepatotoxicity. Increased relative liver weight, hepatocellular hypertrophy, and elevated serum alanine aminotransferase levels were found in wild-type but not CAR null mice after orally administered pyrene. We further show that pyrene induced the expression of mouse liver metabolism enzymes including CYP2B10, CYP3A11, GSTm1, GSTm3, and SULT1A1, and caused hepatic glutathione depletion in wild-type but not CAR null mice. Moreover, by luciferase reporter assay and quantitative real-time PCR analysis, pyrene was found to be a potential inducer of CYP2B6 expression via activation of human CAR in HepG2 cells and human primary hepatocytes. Our observations suggest that pyrene is a novel CAR activator and that CAR is essential for mediating pyrene-induced liver injury. C1 [Zhang, Xiao-Jie; Shi, Zhe; Lyv, Jing-Xi; He, Xuyan; Zhang, Shu-Yun] Wenzhou Med Univ, Sch Environm Sci & Publ Hlth, Dept Prevent Med, Wenzhou 325035, Zhejiang, Peoples R China. [Englert, Neal A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Zhang, SY (reprint author), Wenzhou Med Univ, Sch Environm Sci & Publ Hlth, Dept Prevent Med, Wenzhou 325035, Zhejiang, Peoples R China. EM shuyunzh@yahoo.com FU Wenzhou Medical University [QTJ13011] FX Wenzhou Medical University (QTJ13011 to Z.S.Y.). NR 37 TC 3 Z9 3 U1 2 U2 10 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 OCT PY 2015 VL 147 IS 2 BP 436 EP 445 DI 10.1093/toxsci/kfv142 PG 10 WC Toxicology SC Toxicology GA CX2SO UT WOS:000365547300015 PM 26160115 ER PT J AU Chen, S Hsieh, JH Huang, R Sakamuru, S Hsin, LY Xia, MH Shockley, KR Auerbach, S Kanaya, N Lu, H Svoboda, D Witt, KL Merrick, BA Teng, CT Tice, RR AF Chen, Shiuan Hsieh, Jui-Hua Huang, Ruili Sakamuru, Srilatha Hsin, Li-Yu Xia, Menghang Shockley, Keith R. Auerbach, Scott Kanaya, Noriko Lu, Hannah Svoboda, Daniel Witt, Kristine L. Merrick, B. Alex Teng, Christina T. Tice, Raymond R. TI Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library SO TOXICOLOGICAL SCIENCES LA English DT Article DE AroER tri-screen; Tox21 10K library; environmental chemicals; quantitative high throughput screening; aromatase enzyme assay ID ENDOCRINE-DISRUPTING CHEMICALS; BREAST-CANCER; ESTROGEN-RECEPTOR; IN-VITRO; IMAZALIL; DEFICIENCY; MODULATION; PESTICIDES; EXPRESSION; DISORDERS AB Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ER alpha) agonists, screening in the presence of testosterone (T) identifies AIs and/or ER alpha antagonists, and screening in the presence of 17 beta-estradiol (E2) identifies ER alpha antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. C1 [Chen, Shiuan; Hsin, Li-Yu; Kanaya, Noriko; Lu, Hannah] Beckman Res Inst City Hope, Dept Canc Biol, Duarte, CA 91010 USA. [Hsieh, Jui-Hua; Auerbach, Scott; Svoboda, Daniel; Witt, Kristine L.; Merrick, B. Alex; Teng, Christina T.; Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Huang, Ruili; Sakamuru, Srilatha; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Shockley, Keith R.] NIEHS, Biostat & Computat Biol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, S (reprint author), Beckman Res Inst City Hope, Dept Canc Biol, Duarte, CA 91010 USA. EM schen@coh.org FU Intramural Research Programs of the National Toxicology Program, NIEHS [Y2-ES-7020-01]; CBCRP grant [17UB-8701] FX Intramural Research Programs (Interagency agreement Y2-ES-7020-01) of the National Toxicology Program, NIEHS and the CBCRP grant (17UB-8701 to S.C.). NR 44 TC 5 Z9 5 U1 3 U2 11 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 OCT PY 2015 VL 147 IS 2 BP 446 EP 457 DI 10.1093/toxsci/kfv141 PG 12 WC Toxicology SC Toxicology GA CX2SO UT WOS:000365547300016 PM 26141389 ER PT J AU Tolaney, SM Tan, S Guo, H Barry, W Van Allen, E Wagle, N Brock, J Larrabee, K Paweletz, C Ivanova, E Janne, P Overmoyer, B Wright, JJ Shapiro, GI Winer, EP Krop, IE AF Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. TI Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Triple-negative breast cancer; Tivantinib; MET; ARQ 197 ID HEPATOCYTE GROWTH-FACTOR; CELL LUNG-CANCER; MET MESSENGER-RNA; HEPATOCELLULAR-CARCINOMA; CYTOTOXIC ACTIVITY; PLACEBO; TUMORS; OVEREXPRESSION; INHIBITION; EXPRESSION AB Background MET expression and activation appear to be important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that targets MET, although recent preclinical data suggests the agent may have mechanisms of action that are independent of MET signaling. We conducted a phase 2 study of tivantinib monotherapy in patients with metastatic triple-negative breast cancer. Methods Patients with metastatic triple-negative breast cancer who had received 1 to 3 prior lines of chemotherapy in the metastatic setting were enrolled into this two-stage, single arm phase 2 study. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid) during a 21-day cycle. Patients underwent restaging scans at 6 weeks, and then every 9 weeks. Tumor biomarkers that might predict response to tivantinib were explored. Results 22 patients were enrolled. The overall response rate was 5 % (95 % CI 0-25 %) and the 6-month progression-free survival (PFS) was 5 % (95 % CI 0-25 %), with one patient achieving a partial response (PR). Toxicity was minimal with only 5 grade >= 3 adverse events (one grade 3 anemia, one grade 3 fatigue, and 3 patients with grade 3/4 neutropenia). Conclusion This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy. C1 [Tolaney, Sara M.; Wagle, Nikhil; Larrabee, Katherine; Paweletz, Cloud; Ivanova, Elena; Janne, Pasi; Overmoyer, Beth; Shapiro, Geoffrey I.; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tan, Sally] Harvard Univ, Sch Med, Boston, MA USA. [Guo, Hao; Barry, William] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Van Allen, Eliezer; Wagle, Nikhil] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Brock, Jane] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Paweletz, Cloud; Ivanova, Elena; Janne, Pasi] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1257, Boston, MA 02215 USA. EM stolaney@partners.org RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 FU Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) [NCT01575522]; Susan F. Smith Executive Council Fund FX This work was supported by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) through grant number NCT01575522 as well as the Susan F. Smith Executive Council Fund. We thank Carrie Sougnez and the Broad Genomics Platform for sequencing and analysis collaborations. NR 27 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2015 VL 33 IS 5 BP 1108 EP 1114 DI 10.1007/s10637-015-0269-8 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CW4PD UT WOS:000364972700013 PM 26123926 ER PT J AU London, E Wassif, CA Horvath, A Tatsi, C Angelousi, A Karageorgiadis, AS Porter, FD Stratakis, CA AF London, Edra Wassif, Christopher A. Horvath, Anelia Tatsi, Christina Angelousi, Anna Karageorgiadis, Alexander S. Porter, Forbes D. Stratakis, Constantine A. TI Cholesterol Biosynthesis and Trafficking in Cortisol-Producing Lesions of the Adrenal Cortex SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARNEY COMPLEX; ADRENOCORTICAL TUMORS; CUSHINGS-SYNDROME; STEROIDOGENIC CELLS; PRKAR1A MUTATION; HYPERPLASIA; GENE; DISEASE; EXPRESSION; SUBUNIT AB Context: Cortisol-producing adenomas (CPAs), primary pigmented nodular adrenocortical disease (PPNAD), and primary macronodular adrenocortical hyperplasia (PMAH) cause ACTH-independent Cushing syndrome (CS). Investigation of their pathogenesis has demonstrated their integral link to the cAMP-dependent protein kinase signaling pathway. Objective: The aim of this study was to identify differences in cholesterol biosynthesis among different CS-causing adrenocortical tumors. Because of the concomitant associations of cAMP levels with cholesterol and with steroid biosynthesis, we hypothesized that benign cortisol-producing tumors would display aberration of these pathways. Design and Setting: Twenty-three patients with CPA, PPNAD, or PMAH who underwent adrenalectomy for CS were included in the study. Preoperative biochemical analyses were performed, and excised adrenal tissues were studied. Main Outcome Measures: Serum, urinary hormone levels, serum lipid profiles, and anthropometric data were obtained preoperatively. Adrenal tissues were analyzed for total protein, cholesterol, and neutral sterol content by mass spectrometry and expression of HMGCR, LDLR, ABCA1, DHCR24, and STAR genes. Results: There were differences in cholesterol content and markers of cholesterol biosynthesis and metabolism that distinguished CPAs from PMAH and PPNAD; cholesterol, lathosterol, and lathosterol/cholesterol ratio were significantly higher in CPAs. ABCA1 mRNA was lower among CPAs compared to tissues from bilateral adrenocortical hyperplasia (PMAH and PPNAD), and mRNA expression of LDL-R, DCHR24, and HMGCR tended to be higher in CPA tumor tissues. Conclusion: CPAs displayed characteristics of "cholesterol-starved" tissues when compared to PPNAD and PMAH and appeared to have increased intrinsic cholesterol production and uptake from the periphery, as well as decreased cholesterol efflux. This has implications for a potential new way of treating these tumors. C1 [London, Edra; Horvath, Anelia; Tatsi, Christina; Angelousi, Anna; Karageorgiadis, Alexander S.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Wassif, Christopher A.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP London, E (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,Clin Ctr,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM londonec@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 FU Eunice Kennedy Shriver National Institute of Child Helath and Human Development Intramural Research Program FX This research was funded by the Eunice Kennedy Shriver National Institute of Child Helath and Human Development Intramural Research Program. NR 38 TC 1 Z9 1 U1 0 U2 2 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 OCT PY 2015 VL 100 IS 10 BP 3660 EP 3667 DI 10.1210/jc.2015-2212 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600033 PM 26204136 ER PT J AU Belcher, BR Berrigan, D Papachristopoulou, A Brady, SM Bernstein, SB Brychta, RJ Hattenbach, JD Tigner, IL Courville, AB Drinkard, BE Smith, KP Rosing, DR Wolters, PL Chen, KY Yanovski, JA AF Belcher, Britni R. Berrigan, David Papachristopoulou, Alexia Brady, Sheila M. Bernstein, Shanna B. Brychta, Robert J. Hattenbach, Jacob D. Tigner, Ira L., Jr. Courville, Amber B. Drinkard, Bart E. Smith, Kevin P. Rosing, Douglas R. Wolters, Pamela L. Chen, Kong Y. Yanovski, Jack A. TI Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARDIOMETABOLIC RISK-FACTORS; PHYSICAL-ACTIVITY; GLUCOSE EFFECTIVENESS; LIFE-STYLE; TIME SPENT; EXERCISE; INSULIN; ADOLESCENTS; OVERWEIGHT; OBESITY AB Context: Limited data suggest that interrupting sedentary behaviors with activity improves metabolic parameters in adults. Objective: We tested whether interrupting sitting with short, moderate-intensity walking bouts improved glucose tolerance in children. Design: Participants underwent two experimental conditions in random order on different days: continuous sitting for 3hours or sitting interrupted by walking(3 min of moderate-intensity walking every 30 min). Insulin, C-peptide, glucose, and free fatty acids were measured every 30 minutes for 3 hours during an oral glucose tolerance test. Area under the curve (AUC) was calculated from hormone and substrate measurements. Children were given a buffet meal after each condition. Setting: The study was conducted at the National Institutes of Health Hatfield Clinical Research Center. Participants: Twenty-eight normal-weight 7-11 year olds participated. Main Outcomes: Patterns of substrate/hormone secretion and AUC, as well as energy intake, were examined by experimental condition. Results: Interrupting sitting resulted in a 32% lower insulin AUC (P < .001), 17% lower C-peptide AUC (P < .001), and 7% lower glucose AUC (P = .018) vs continuous sitting. Mixed model results indicated that insulin (P = .036) and free fatty acid concentrations (P = .009) were significantly lower in the interrupted vs the continuous sitting condition. Lunchtime buffet meal energy intake did not significantly differ between the conditions (975 +/- 387 vs 963 +/- 309 kcal; P = .85). Conclusions: Interrupting sedentary time with brief moderate-intensity walking improved short-term metabolic function in non-overweight children without increasing subsequent energy intake. These findings suggest that interrupting sedentary behavior may be a promising prevention strategy for reducing cardiometabolic risk in children. C1 [Belcher, Britni R.; Berrigan, David] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Wolters, Pamela L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Belcher, Britni R.; Papachristopoulou, Alexia; Brady, Sheila M.; Tigner, Ira L., Jr.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Bernstein, Shanna B.; Courville, Amber B.] NIH, Dept Nutr, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Drinkard, Bart E.] NIH, Dept Rehabil Med, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Smith, Kevin P.] NIH, Dept Nursing, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Brychta, Robert J.; Hattenbach, Jacob D.; Chen, Kong Y.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Rosing, Douglas R.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Belcher, BR (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Behav Res Branch, 9609 Med Ctr Dr,MSC 9762,Room 3E458, Bethesda, MD 20892 USA. EM belcherbr@mail.nih.gov; jy15i@nih.gov OI Chen, Kong/0000-0002-0306-1904 FU National Cancer Institute (NCI); National Institute of Child Health and Human Development [Z1A-HD-00641]; NCI Cancer Prevention Fellowship Program in the Division of Cancer Prevention; NCI, Division of Cancer Control and Population Sciences; NIH; NIH Office of the Director FX This study was supported by the Intramural Research Programs of the National Cancer Institute (NCI) and National Institute of Child Health and Human Development (Z1A-HD-00641; to J.A.Y.) at NIH. B.R.B. was supported by a postdoctoral training award from the NCI Cancer Prevention Fellowship Program in the Division of Cancer Prevention. D.B. was supported by the NCI, Division of Cancer Control and Population Sciences. S.M.B., R.J.B., K.P.S., D.R.R., P.L.W., A.B.C., S.B.B., and K.Y.C. are federal employees supported by the Intramural Research Program of the NIH. I.L.T. was supported by the NIH Office of the Director. The funding agencies played no role in the decision to submit the manuscript. NR 41 TC 2 Z9 3 U1 3 U2 11 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 OCT PY 2015 VL 100 IS 10 BP 3735 EP 3743 DI 10.1210/jc.2015-2803 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600042 PM 26312582 ER PT J AU Mather, KJ Kim, C Christophi, CA Aroda, VR Knowler, WC Edelstein, SE Florez, JC Labrie, F Kahn, SE Goldberg, RB Barrett-Connor, E AF Mather, K. J. Kim, C. Christophi, C. A. Aroda, V. R. Knowler, W. C. Edelstein, S. E. Florez, J. C. Labrie, F. Kahn, S. E. Goldberg, R. B. Barrett-Connor, E. CA Diabet Prevention Program TI Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED FASTING GLUCOSE; LIFE-STYLE INTERVENTION; POSTMENOPAUSAL WOMEN; TOTAL TESTOSTERONE; METABOLIC SYNDROME; MEN; RISK; METFORMIN; MELLITUS; HEALTH AB Context: Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. Objective: This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). Design and Setting: This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. Participants: The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Interventions: Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Main Outcomes: Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). Results: T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Conclusions: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones. C1 [Mather, K. J.] Indiana Univ, Dept Med, Indianapolis, IN 46202 USA. [Kim, C.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kim, C.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Christophi, C. A.; Edelstein, S. E.] George Washington Univ, Biostat Ctr, Rockville, MD 20850 USA. [Aroda, V. R.] Medstar Hlth Res Inst, Hyattsville, MD 20782 USA. [Knowler, W. C.] NIDDK, Phoenix, AZ 85014 USA. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Labrie, F.] Endoceutics Inc, Quebec City, PQ G1W 2J5, Canada. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98108 USA. [Goldberg, R. B.] Univ Miami, Miami, FL 33124 USA. [Barrett-Connor, E.] Univ Calif San Diego, San Diego, CA 92093 USA. RP Mather, KJ (reprint author), George Washington Univ, Care Diabet Prevent Program Coordinating Ctr, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20850 USA. EM dppmail@bsc.gwu.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health/National Institute of Diabetes, Digestive and Kidney Disorders; National Institute of Child Health and Human Development; National Institute of Aging; Office of Research in Minority Health and Health Disparities; Office of Research in Womens' Health Indian Health Service; Centers for Disease Control Clinical Genetics Research Program; National Center for Research Resources; American Diabetes Association; Bristol-Meyers Squibb; Lipha; Parke-Davis [R01 DK072041] FX This work was supported by National Institutes of Health/National Institute of Diabetes, Digestive and Kidney Disorders, National Institute of Child Health and Human Development, National Institute of Aging, Office of Research in Minority Health and Health Disparities, Office of Research in Womens' Health Indian Health Service, Centers for Disease Control Clinical Genetics Research Program, National Center for Research Resources, American Diabetes Association, Bristol-Meyers Squibb, Lipha, Parke-Davis, R01 DK072041. NR 35 TC 10 Z9 10 U1 3 U2 5 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 OCT PY 2015 VL 100 IS 10 BP 3778 EP 3786 DI 10.1210/jc.2015-2328 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600047 PM 26200237 ER PT J AU Afshari, A Ardeshirpour, Y Lodish, MB Gourgari, E Sinaii, N Keil, M Belyavskaya, E Lyssikatos, C Chowdhry, FA Chernomordik, V Anderson, AA Mazzuchi, TA Gandjbakhche, A Stratakis, CA AF Afshari, Ali Ardeshirpour, Yasaman Lodish, Maya Beth Gourgari, Evgenia Sinaii, Ninet Keil, Margaret Belyavskaya, Elena Lyssikatos, Charalampos Chowdhry, Fatima A. Chernomordik, Victor Anderson, Afrouz A. Mazzuchi, Thomas A. Gandjbakhche, Amir Stratakis, Constantine A. TI Facial Plethora: Modern Technology for Quantifying an Ancient Clinical Sign and Its Use in Cushing Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRANSSPHENOIDAL SURGERY; QUANTITATIVE ASSESSMENT; DISEASE; CHILDREN; CORTISOL; TESTS; CURE AB Context: Facial plethora is a clinical sign described since ancient times for a variety of diseases. In the 19th century, it was linked to increased blood volume or flow, but this has never been proven. Facial plethora is also one of the earliest described clinical features of Cushing's syndrome (CS). Objective: This study aimed to quantify facial plethora changes in CS as an early assessment of cure after surgery using noninvasive near-infrared multispectral imaging (MSI). Design: The longitudinal cohort study was initiated in August 2012 and completed in August 2014. Setting: Clinical research hospital, National Institutes of Health. Patients: Thirty-four of the 38 patients who received surgical treatment for CS under protocol 97CH0076 during this period were included. Intervention(s): MSI was performed on the right cheek of patients before surgery and 4.9 +/- 3.1 days afterward. Main Outcome Measure(s): Average blood volume fraction as measured by MSI and serum cortisol. Results: All but four of the 28 patients (86%) who were assessed as cured by postoperative plasma cortisol measurements of < 3 mu g/dL showed a decrease in blood volume fraction (17.7 +/- 0.03 vs 15.8 +/- 0.03%; P = .0019), whereas an increase was seen in patients with persistent CS (18.5 +/- 0.03 vs 21.4 +/- 0.04%; P = .0017). Change in blood volume fraction before and after surgery was correlated with postoperative cortisol (rs = 0.58; P = .0003). Conclusions: Clinical data obtained from 34 patients indicate that a decrease in facial plethora after surgery, as evidenced by a decrease in blood volume fraction, is correlated with CS outcome. This novel technology for the first time identified a physiological mechanism associated with an ancient clinical sign. Furthermore, as a proof of principle, MSI is a promising early marker of cure in patients with CS that complements biochemical and clinical data. C1 [Afshari, Ali; Ardeshirpour, Yasaman; Chowdhry, Fatima A.; Chernomordik, Victor; Anderson, Afrouz A.; Gandjbakhche, Amir] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Analyt & Funct Biophoton, NIH, Bethesda, MD 20892 USA. [Lodish, Maya Beth; Gourgari, Evgenia; Keil, Margaret; Belyavskaya, Elena; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Clin Res Ctr, Bethesda, MD 20892 USA. [Mazzuchi, Thomas A.] George Washington Univ, Dept Syst Engn, Washington, DC 20052 USA. RP Lodish, MB (reprint author), NIH, Bldg 10-CRC,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health; Human Development at the National Institutes of Health (NIH) FX This research was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (NIH). The NIH Clinical Center and the Graduate Partnership Program at the NIH and the Department of Engineering Management and Systems Engineering at The George Washington University are also acknowledged. NR 24 TC 3 Z9 3 U1 1 U2 4 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 OCT PY 2015 VL 100 IS 10 BP 3928 EP 3933 DI 10.1210/jc.2015-2497 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3WI UT WOS:000364922600065 PM 26301943 ER PT J AU Cole-Lewis, H Pugatch, J Sanders, A Varghese, A Posada, S Yun, C Schwarz, M Augustson, E AF Cole-Lewis, Heather Pugatch, Jillian Sanders, Amy Varghese, Arun Posada, Susana Yun, Christopher Schwarz, Mary Augustson, Erik TI Social Listening: A Content Analysis of E-Cigarette Discussions on Twitter SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE social media; Twitter; e-cigarettes; content analysis ID CESSATION; AWARENESS; BEHAVIOR; SEARCH AB Background: Electronic cigarette (e-cigarette) use has increased in the United States, leading to active debate in the public health sphere regarding e-cigarette use and regulation. To better understand trends in e-cigarette attitudes and behaviors, public health and communication professionals can turn to the dialogue taking place on popular social media platforms such as Twitter. Objective: The objective of this study was to conduct a content analysis to identify key conversation trends and patterns over time using historical Twitter data. Methods: A 5-category content analysis was conducted on a random sample of tweets chosen from all publicly available tweets sent between May 1, 2013, and April 30, 2014, that matched strategic keywords related to e-cigarettes. Relevant tweets were isolated from the random sample of approximately 10,000 tweets and classified according to sentiment, user description, genre, and theme. Descriptive analyses including univariate and bivariate associations, as well as correlation analyses were performed on all categories in order to identify patterns and trends. Results: The analysis revealed an increase in e-cigarette-related tweets from May 2013 through April 2014, with tweets generally being positive; 71% of the sample tweets were classified as having a positive sentiment. The top two user categories were everyday people (65%) and individuals who are part of the e-cigarette community movement (16%). These two user groups were responsible for a majority of informational (79%) and news tweets (75%), compared to reputable news sources and foundations or organizations, which combined provided 5% of informational tweets and 12% of news tweets. Personal opinion (28%), marketing (21%), and first person e-cigarette use or intent (20%) were the three most common genres of tweets, which tended to have a positive sentiment. Marketing was the most common theme (26%), and policy and government was the second most common theme (20%), with 86% of these tweets coming from everyday people and the e-cigarette community movement combined, compared to 5% of policy and government tweets coming from government, reputable news sources, and foundations or organizations combined. Conclusions: Everyday people and the e-cigarette community are dominant forces across several genres and themes, warranting continued monitoring to understand trends and their implications regarding public opinion, e-cigarette use, and smoking cessation. Analyzing social media trends is a meaningful way to inform public health practitioners of current sentiments regarding e-cigarettes, and this study contributes a replicable methodology. C1 [Cole-Lewis, Heather; Pugatch, Jillian; Sanders, Amy; Varghese, Arun; Posada, Susana; Yun, Christopher; Schwarz, Mary] ICF Int, Rockville, MD USA. [Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Augustson, E (reprint author), NCI, Tobacco Control Res Branch, 9609 Med Ctr Dr,MSC 9761, Bethesda, MD 20892 USA. EM augustse@mail.nih.gov OI Pugatch, Jillian/0000-0001-9103-5484; Yun, Christopher/0000-0002-6747-4628; Schwarz, Mary/0000-0003-0482-7323 FU National Cancer Institute's Tobacco Control Research Branch-National Institutes of Health, National Cancer Institute [HHSN261200900022C, D6-ICF-1] FX This work was funded by the National Cancer Institute's Tobacco Control Research Branch-National Institutes of Health, National Cancer Institute HHSN261200900022C, Subcontract Number D6-ICF-1. The authors would like to thank Shinett Boggan, Alex Feith-Tiongson, Samantha Letizia, Thomas Madden, Delsie Sequiera, Nick Ngugi, and Emily Grenen for their contribution to the study. NR 35 TC 7 Z9 7 U1 0 U2 12 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD OCT PY 2015 VL 17 IS 10 AR e243 DI 10.2196/jmir.4969 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CW7CI UT WOS:000365155100004 PM 26508089 ER PT J AU Katki, HA Cheung, LC Fetterman, B Castle, PE Sundaram, R AF Katki, Hormuzd A. Cheung, Li C. Fetterman, Barbara Castle, Philip E. Sundaram, Rajeshwari TI A joint model of persistent human papilloma virus infection and cervical cancer risk: implications for cervical cancer screening SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE Cancer screening; Human papilloma virus; Joint modelling of longitudinal and survival data; Medical guidelines; Risk modelling ID TO-EVENT DATA; INTRAEPITHELIAL NEOPLASIA; LONGITUDINAL DATA; WOMEN; HPV; POPULATION; PREDICTIONS; PRECURSORS; GUIDELINES; MANAGEMENT AB New cervical cancer screening guidelines in the USA and many European countries recommend that women are tested for human papilloma virus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer or cancer risk per year of continued HPV infection. However, both time to onset of precancer or cancer and time to HPV clearance are interval censored, and onset of precancer or cancer strongly informatively censors HPV clearance. We analyse these bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer or cancer by using shared random effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer or cancer. The model was fitted to data on 9553 HPV positive and negative women undergoing cervical cancer screening at Kaiser Permanente Northern California: data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model with those from population-average marginal models of precancer or cancer risk. In particular, after 2 years the marginal population-average precancer or cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models that can predict individual risk may have implications that are different from those of population-average risk models that are currently used for informing medical guideline development. C1 [Katki, Hormuzd A.] US Natl Canc Inst, Bethesda, MD 20892 USA. [Cheung, Li C.] Informat Management Serv Inc, Calverton, MD USA. [Fetterman, Barbara] Kaiser Permanente No Calif, Berkeley, CA USA. [Castle, Philip E.] Albert Einstein Coll Med, New York, NY USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Katki, HA (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Natl Inst Hlth, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM katkih@mail.nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002 FU 'Intramural research program' of US National Institutes of Health-National Cancer Institute-Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the 'Intramural research program' of the US National Institutes of Health-National Cancer Institute-Eunice Kennedy Shriver National Institute of Child Health and Human Development. We thank Dr Thomas S. Lorey and Dr Gene Pawlick (Regional Laboratory of the Northern California Kaiser Permanente Medical Care Program) for creating and supporting the data warehouse, and KPNC for allowing use of the data. NR 37 TC 1 Z9 1 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-1998 EI 1467-985X J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PD OCT PY 2015 VL 178 IS 4 BP 903 EP 923 DI 10.1111/rssa.12101 PG 21 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA CX0MO UT WOS:000365391100007 PM 26556961 ER PT J AU Burns, JC Kelly, MC Hoa, M Morell, RJ Kelley, MW AF Burns, Joseph C. Kelly, Michael C. Hoa, Michael Morell, Robert J. Kelley, Matthew W. TI Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear SO NATURE COMMUNICATIONS LA English DT Article ID DIFFERENTIAL EXPRESSION ANALYSIS; HAIR-CELLS; GENE-EXPRESSION; SUPPORTING CELLS; MOUSE UTRICLE; POSTNATAL-DEVELOPMENT; TRANSCRIPTION FACTOR; MAMMALIAN COCHLEA; QUALITY-CONTROL; STEM-CELLS AB In the inner ear, cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration. Each individual sensory epithelium is composed of highly heterogeneous populations of cells based on physiological and anatomical criteria. However, limited numbers of each cell type have impeded transcriptional characterization. Here we generated transcriptomes for 301 single cells from the utricular and cochlear sensory epithelia of newborn mice to circumvent this challenge. Cluster analysis indicates distinct profiles for each of the major sensory epithelial cell types, as well as less-distinct sub-populations. Asynchrony within utricles allows reconstruction of the temporal progression of cell-type-specific differentiation and suggests possible plasticity among cells at the sensory-nonsensory boundary. Comparisons of cell types from utricles and cochleae demonstrate divergence between auditory and vestibular cells, despite a common origin. These results provide significant insights into the developmental processes that form unique inner ear cell types. C1 [Burns, Joseph C.; Kelly, Michael C.; Hoa, Michael; Kelley, Matthew W.] NIDCD, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA. [Morell, Robert J.] NIDCD, Genom & Computat Biol Core, NIH, Bethesda, MD 20892 USA. RP Kelley, MW (reprint author), NIDCD, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA. EM kelleymt@nidcd.nih.gov OI Morell, Robert/0000-0003-1537-7356 FU Intramural Program at NIDCD [DC000059]; National Institute on Deafness and Other Communication Disorders intramural program [DC000039-18] FX This project was supported by funds from the Intramural Program at NIDCD to M.W.K. (DC000059), and M.H. Sequencing costs were covered from the National Institute on Deafness and Other Communication Disorders intramural program DC000039-18 to T.B. Friedman. We thank S.W. Hartley and J.C. Mullikin for discussions regarding bioinformatics analysis, C. Trapnell for discussions regarding Monocle, C.N. Dewey for discussions regarding RSEM, E.C. Driver for assistance with validation of Rasd2, P. Sekaric and J. Lynch for assistance with single-cell capture, NIDCR FACS core, and S. Saxena for assistance with sequencing. Finally, we thank the animal support personnel at both the Porter Neuroscience Shared Animal Facility and the NIDCD. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 71 TC 15 Z9 15 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8557 DI 10.1038/ncomms9557 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4AD UT WOS:000364932600004 PM 26469390 ER PT J AU Peters, MJ Joehanes, R Pilling, LC Schurmann, C Conneely, KN Powell, J Reinmaa, E Sutphin, GL Zhernakova, A Schramm, K Wilson, YA Kobes, S Tukiainen, T Ramos, YF Goring, HHH Fornage, M Liu, YM Gharib, SA Stranger, BE De Jager, PL Aviv, A Levy, D Murabito, JM Munson, PJ Huan, T Hofman, A Uitterlinden, AG Rivadeneira, F van Rooij, J Stolk, L Broer, L Verbiest, MMPJ Jhamai, M Arp, P Metspalu, A Tserel, L Milani, L Samani, NJ Peterson, P Kasela, S Codd, V Peters, A Ward-Caviness, CK Herder, C Waldenberger, M Roden, M Singmann, P Zeilinger, S Illig, T Homuth, G Grabe, HJ Voelzke, H Steil, L Kocher, T Murray, A Melzer, D Yaghootkar, H Bandinelli, S Moses, EK Kent, JW Curran, JE Johnson, MP Williams-Blangero, S Westra, HJ Mcrae, AF Smith, JA Kardia, SLR Hovatta, I Perola, M Ripatti, S Salomaa, V Henders, AK Martin, NG Smith, AK Mehta, D Binder, EB Nylocks, KM Kennedy, EM Klengel, T Ding, J Suchy-Dicey, AM Enquobahrie, DA Brody, J Rotter, JI Chen, YDI Houwing-Duistermaat, J Kloppenburg, M Slagboom, PE Helmer, Q den Hollander, W Bean, S Raj, T Bakhshi, N Wang, QP Oyston, LJ Psaty, BM Tracy, RP Montgomery, GW Turner, ST Blangero, J Meulenbelt, I Ressler, KJ Yang, J Franke, L Kettunen, J Visscher, PM Neely, GG Korstanje, R Hanson, RL Prokisch, H Ferrucci, L Esko, T Teumer, A van Meurs, JBJ Andrew, D AF Peters, Marjolein J. Joehanes, Roby Pilling, Luke C. Schurmann, Claudia Conneely, Karen N. Powell, Joseph Reinmaa, Eva Sutphin, George L. Zhernakova, Alexandra Schramm, Katharina Wilson, Yana A. Kobes, Sayuko Tukiainen, Taru Ramos, Yolande F. Goering, Harald H. H. Fornage, Myriam Liu, Yongmei Gharib, Sina A. Stranger, Barbara E. De Jager, Philip L. Aviv, Abraham Levy, Daniel Murabito, Joanne M. Munson, Peter J. Huan, Tianxiao Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando van Rooij, Jeroen Stolk, Lisette Broer, Linda Verbiest, Michael M. P. J. Jhamai, Mila Arp, Pascal Metspalu, Andres Tserel, Liina Milani, Lili Samani, Nilesh J. Peterson, Paert Kasela, Silva Codd, Veryan Peters, Annette Ward-Caviness, Cavin K. Herder, Christian Waldenberger, Melanie Roden, Michael Singmann, Paula Zeilinger, Sonja Illig, Thomas Homuth, Georg Grabe, Hans-Joergen Voelzke, Henry Steil, Leif Kocher, Thomas Murray, Anna Melzer, David Yaghootkar, Hanieh Bandinelli, Stefania Moses, Eric K. Kent, Jack W. Curran, Joanne E. Johnson, Matthew P. Williams-Blangero, Sarah Westra, Harm-Jan Mcrae, Allan F. Smith, Jennifer A. Kardia, Sharon L. R. Hovatta, Iiris Perola, Markus Ripatti, Samuli Salomaa, Veikko Henders, Anjali K. Martin, Nicholas G. Smith, Alicia K. Mehta, Divya Binder, Elisabeth B. Nylocks, K. Maria Kennedy, Elizabeth M. Klengel, Torsten Ding, Jingzhong Suchy-Dicey, Astrid M. Enquobahrie, Daniel A. Brody, Jennifer Rotter, Jerome I. Chen, Yii-Der I. Houwing-Duistermaat, Jeanine Kloppenburg, Margreet Slagboom, P. Eline Helmer, Quinta den Hollander, Wouter Bean, Shannon Raj, Towfique Bakhshi, Noman Wang, Qiao Ping Oyston, Lisa J. Psaty, Bruce M. Tracy, Russell P. Montgomery, Grant W. Turner, Stephen T. Blangero, John Meulenbelt, Ingrid Ressler, Kerry J. Yang, Jian Franke, Lude Kettunen, Johannes Visscher, Peter M. Neely, G. Gregory Korstanje, Ron Hanson, Robert L. Prokisch, Holger Ferrucci, Luigi Esko, Tonu Teumer, Alexander van Meurs, Joyce B. J. Johnson, Andrew D. CA NABEC UKBEC Consortium TI The transcriptional landscape of age in human peripheral blood SO NATURE COMMUNICATIONS LA English DT Article ID GENE-EXPRESSION CHANGES; GENOME-WIDE ASSOCIATION; DROSOPHILA-MELANOGASTER; HUMAN LONGEVITY; LIFE-SPAN; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; CELL-TYPES; METHYLATION; DISEASE AB Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts. C1 [Peters, Marjolein J.; Uitterlinden, Andre G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; van Meurs, Joyce B. J.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Joehanes, Roby; Levy, Daniel; Murabito, Joanne M.; Huan, Tianxiao; Johnson, Andrew D.] NHLBI, Framingham, MA 01702 USA. [Joehanes, Roby; Levy, Daniel; Murabito, Joanne M.; Huan, Tianxiao; Johnson, Andrew D.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Joehanes, Roby; Levy, Daniel; Huan, Tianxiao; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20817 USA. [Pilling, Luke C.; Murray, Anna; Melzer, David] Univ Exeter, Sch Med, Epidemiol & Publ Hlth, Exeter EX4 1DB, Devon, England. [Schurmann, Claudia; Homuth, Georg; Steil, Leif; Teumer, Alexander] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Dept Funct Genom, D-17493 Greifswald, Germany. [Schurmann, Claudia] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Conneely, Karen N.; Kennedy, Elizabeth M.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30301 USA. [Powell, Joseph] Univ Queensland, Queensland Brain Inst, Ctr Neurogenet & Stat Genom, Brisbane, Qld 4000, Australia. [Powell, Joseph; Henders, Anjali K.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4000, Australia. [Reinmaa, Eva; Metspalu, Andres; Milani, Lili; Perola, Markus; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-0794 Tartu, Estonia. [Sutphin, George L.; Bean, Shannon; Korstanje, Ron] Jackson Lab, Nathan Shock Ctr Excellence Basic Biol Aging, Bar Harbor, ME 04609 USA. [Zhernakova, Alexandra; Westra, Harm-Jan; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Schramm, Katharina; Prokisch, Holger] German Res Ctr Environm Hlth, Helmholz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Schramm, Katharina; Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-85540 Munich, Germany. [Wilson, Yana A.; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Neely, G. Gregory] Garvan Inst Med Res, Div Neurosci, Darlinghurst, NSW, Australia. [Wilson, Yana A.; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Neely, G. Gregory] Univ Sydney, Charles Perkins Ctr, Sydney, NSW 2006, Australia. [Wilson, Yana A.; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Neely, G. Gregory] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia. [Kobes, Sayuko; Hanson, Robert L.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85001 USA. [Tukiainen, Taru; Perola, Markus; Ripatti, Samuli; Kettunen, Johannes] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00131, Finland. [Tukiainen, Taru; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Kettunen, Johannes] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00131, Finland. [Ramos, Yolande F.; Slagboom, P. Eline; den Hollander, Wouter; Meulenbelt, Ingrid] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Goering, Harald H. H.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78201 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77001 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77001 USA. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC 27101 USA. [Gharib, Sina A.] Univ Washington, Ctr Lung Biol, Computat Med Core, Seattle, WA 98101 USA. [Stranger, Barbara E.] Univ Chicago, Inst Genom & Syst Biol, Med Genet Sect, Chicago, IL 60290 USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom,Dept Neurol, Boston, MA 02108 USA. [Aviv, Abraham] Univ Med & Dent New Jersey, Ctr Human Dev & Aging, Newark, NJ 07101 USA. [Murabito, Joanne M.] Boston Univ, Gen Internal Med Sect, Boston, MA 02108 USA. [Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20817 USA. [Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Tserel, Liina; Peterson, Paert] Univ Tartu, Inst Biomed, Mol Pathol, EE-0794 Tartu, Estonia. [Samani, Nilesh J.; Codd, Veryan] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1, Leics, England. [Samani, Nilesh J.; Codd, Veryan] Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester LE1, Leics, England. [Kasela, Silva] Univ Tartu, Estonian Genome Ctr, Inst Mol & Cell Biol, EE-0794 Tartu, Estonia. [Peters, Annette; Ward-Caviness, Cavin K.; Waldenberger, Melanie; Singmann, Paula; Zeilinger, Sonja] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany. [Peters, Annette; Waldenberger, Melanie; Singmann, Paula; Zeilinger, Sonja] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany. [Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40593 Dusseldorf, Germany. [Roden, Michael] Univ Dusseldorf, Univ Hosp Dusseldorf, Div Endocrinol & Diabetol, D-40593 Dusseldorf, Germany. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30519 Hannover, Germany. [Grabe, Hans-Joergen] Univ Med Greifswald, Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, D-17489 Greifswald, Germany. [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany. [Kocher, Thomas] Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, Unit Periodontol, D-17489 Greifswald, Germany. [Yaghootkar, Hanieh] Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, I-50123 Florence, Italy. [Moses, Eric K.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 9011, Australia. [Moses, Eric K.] Curtin Univ, Fac Hlth Sci, Perth, WA 9011, Australia. [Westra, Harm-Jan; Esko, Tonu] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02108 USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02108 USA. [Westra, Harm-Jan] Harvard Univ, Sch Med, Boston, MA 02108 USA. [Westra, Harm-Jan] Partners Ctr Personalized Genet Med, Boston, MA 02108 USA. [Mcrae, Allan F.; Yang, Jian; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4000, Australia. [Mcrae, Allan F.; Yang, Jian; Visscher, Peter M.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4000, Australia. [Smith, Jennifer A.; Kardia, Sharon L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48103 USA. [Hovatta, Iiris] Univ Helsinki, Dept Biosci, SF-00100 Helsinki, Finland. [Hovatta, Iiris] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki 00100, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge CB4, England. [Ripatti, Samuli] Univ Helsinki, Hjelt Inst, Dept Publ Hlth, SF-00100 Helsinki, Finland. [Martin, Nicholas G.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4000, Australia. [Smith, Alicia K.; Nylocks, K. Maria; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30301 USA. [Mehta, Divya; Binder, Elisabeth B.; Klengel, Torsten] Max Planck Inst Psychiat, D-80331 Munich, Germany. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27101 USA. [Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Brody, Jennifer] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Rotter, Jerome I.; Chen, Yii-Der I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90501 USA. [Houwing-Duistermaat, Jeanine; Helmer, Quinta] Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2300 RC Leiden, Netherlands. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands. [Raj, Towfique] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02138 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98195 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Colchester, VT 98195 USA. [Turner, Stephen T.] Mayo Clin, Dept Med, Div Nephrol & Hypertens, Rochester, MN 55901 USA. [Kettunen, Johannes] Univ Oulu, Fac Med, Inst Hlth Sci, Computat Med, FIN-90570 Oulu, Finland. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21218 USA. [Esko, Tonu] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02108 USA. [Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02108 USA. RP Peters, MJ (reprint author), Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. RI Slagboom, P. Eline/R-4790-2016; Johnson, Andrew/G-6520-2013; Franke, Lude/P-7036-2016; Klengel, Torsten/E-5629-2010; Hardy, John/C-2451-2009; Montgomery, Grant/B-7148-2008; Peters, Annette/A-6117-2011; Waldenberger, Melanie/B-5355-2014; Weale, Michael/F-2587-2010; Yang, Jian/A-5852-2010; McRae, Allan/J-2644-2014; Schurmann, Claudia/L-1204-2016; Peterson, Part/A-5788-2009 OI Visscher, Peter/0000-0002-2143-8760; Zonderman, Alan B/0000-0002-6523-4778; Smith, Jennifer/0000-0002-3575-5468; Hovatta, Iiris/0000-0002-5990-7892; Peters, Annette/0000-0001-6645-0985; Slagboom, P. Eline/0000-0002-2875-4723; Pilling, Luke/0000-0002-3332-8454; Murray, Anna/0000-0002-2351-2522; Klengel, Torsten/0000-0001-7045-9229; Melzer, David/0000-0002-0170-3838; Peters, Marjolein/0000-0003-3167-9063; Rivadeneira, Fernando/0000-0001-9435-9441; Stranger, Barbara/0000-0001-9021-7331; Franke, Lude/0000-0002-5159-8802; Montgomery, Grant/0000-0002-4140-8139; Waldenberger, Melanie/0000-0003-0583-5093; Weale, Michael/0000-0003-4593-1186; Yang, Jian/0000-0003-2001-2474; McRae, Allan/0000-0001-5286-5485; Schurmann, Claudia/0000-0003-4158-9192; Peterson, Part/0000-0001-6755-791X FU National Heart, Lung, and Blood Institute [R01HL105756]; European Commission [HEALTH-F2-2008-201865, HEALTH-F2-2008 35627]; Netherlands Organization for Scientific Research (NWO) Investments [175.010.2005.011, 911-03-012]; Netherlands Consortium for Healthy Aging; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]; VIDI [917103521] FX The infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. This study was funded by the European Commission (HEALTH-F2-2008-201865, GEFOS; HEALTH-F2-2008 35627, TREAT-OA), the Netherlands Organization for Scientific Research (NWO) Investments (nr. 175.010.2005.011, 911-03-012), the Netherlands Consortium for Healthy Aging, the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810 and VIDI grant 917103521. Additional acknowledgments to specific cohorts and their support are found in Supplementary Notes 1 and 2. NR 79 TC 31 Z9 31 U1 5 U2 19 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 OCT PY 2015 VL 6 AR 8570 DI 10.1038/ncomms9570 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4AD UT WOS:000364932600017 PM 26490707 ER PT J AU Vallabhapurapu, SD Noothi, SK Pullum, DA Lawrie, CH Pallapati, R Potluri, V Kuntzen, C Khan, S Plas, DR Orlowski, RZ Chesi, M Kuehl, WM Bergsagel, PL Karin, M Vallabhapurapu, S AF Vallabhapurapu, Subrahmanya D. Noothi, Sunil K. Pullum, Derek A. Lawrie, Charles H. Pallapati, Rachel Potluri, Veena Kuntzen, Christian Khan, Sohaib Plas, David R. Orlowski, Robert Z. Chesi, Marta Kuehl, W. Michael Bergsagel, P. Leif Karin, Michael Vallabhapurapu, Sivakumar TI Transcriptional repression by the HDAC4-RelB-p52 complex regulates multiple myeloma survival and growth SO NATURE COMMUNICATIONS LA English DT Article ID NF-KAPPA-B; MOLECULAR CLASSIFICATION; THERAPEUTIC IMPLICATIONS; PROTEASOME INHIBITORS; RELB DEGRADATION; GENE-EXPRESSION; CANCER; BORTEZOMIB; CELLS; MECHANISMS AB Although transcriptional activation by NF-kappa B is well appreciated, physiological importance of transcriptional repression by NF-kappa B in cancer has remained elusive. Here we show that an HDAC4-RelB-p52 complex maintains repressive chromatin around proapoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth. Disruption of RelB-HDAC4 complex by a HDAC4-mimetic polypeptide blocks MM growth. RelB-p52 also represses BMF translation by regulating miR-221 expression. While the NIK-dependent activation of RelB-p52 in MM has been reported, we show that regardless of the activation status of NIK and the oncogenic events that cause plasma cell malignancy, several genetically diverse MM cells including Bortezomib-resistant MM cells are addicted to RelB-p52 for survival. Importantly, RelB is constitutively phosphorylated in MM and ERK1 is a RelB kinase. Phospho-RelB remains largely nuclear and is essential for Bim repression. Thus, ERK1-dependent regulation of nuclear RelB is critical for MM survival and explains the NIK-independent role of RelB in MM. C1 [Vallabhapurapu, Subrahmanya D.; Noothi, Sunil K.; Pullum, Derek A.; Pallapati, Rachel; Potluri, Veena; Khan, Sohaib; Plas, David R.; Vallabhapurapu, Sivakumar] Univ Cincinnati, Coll Med, Dept Canc & Cell Biol, Vontz Ctr Mol Studies, Cincinnati, OH 45267 USA. [Lawrie, Charles H.] Biodonostia Res Inst, Dept Oncol, San Sebastian 20014, Spain. [Lawrie, Charles H.] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England. [Kuntzen, Christian] Bridgeport Hosp, Dept Med, Bridgeport, CT 06610 USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Chesi, Marta; Bergsagel, P. Leif] Mayo Clin, Dept Hematol Oncol, Scottsdale, AZ 85259 USA. [Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Karin, Michael] Univ Calif San Diego, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Karin, Michael] Univ Calif San Diego, Dept Pathol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. RP Vallabhapurapu, S (reprint author), Univ Cincinnati, Coll Med, Dept Canc & Cell Biol, Vontz Ctr Mol Studies, Cincinnati, OH 45267 USA. EM vallabsr@gmail.com FU Department of Cancer and Cell Biology, University of Cincinnati FX We thank Dr Gioacchino Natoli, Dr Gourisankar Ghosh and Dr Jinsong Zhang for kindly providing us with, pCDNA-RelB and pCDNA-p52, pBabe-RelB and pBabe-p52, pGL2-basic vectors respectively. We thank Dr Brian A Lewis for kindly providing us with the NHL cell lines. We thank Glenn Doerman for helping us with figure preparation. This work was supported by start-up funds provided to SV by Department of Cancer and Cell Biology, University of Cincinnati. NR 66 TC 12 Z9 12 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 OCT PY 2015 VL 6 AR 8428 DI 10.1038/ncomms9428 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3WW UT WOS:000364924000001 PM 26455434 ER PT J AU Wu, T Hallett, M Chan, P AF Wu, Tao Hallett, Mark Chan, Piu TI Motor automaticity in Parkinson's disease SO NEUROBIOLOGY OF DISEASE LA English DT Review DE Parkinson's disease; Automatic control; Attentional control; Bradykinesia; Basal ganglia ID PROGRESSIVE SUPRANUCLEAR PALSY; STRIDE LENGTH REGULATION; DEEP BRAIN-STIMULATION; DUAL-TASK-PERFORMANCE; BASAL GANGLIA; L-DOPA; FACIAL EXPRESSIONS; HABIT FORMATION; FUNCTIONAL MRI; EXTERNAL CUES AB Bradykinesia is the most important feature contributing to motor difficulties in Parkinson's disease (PD). However, the pathophysiology underlying bradykinesia is not fully understood. One important aspect is that PD patients have difficulty in performing learned motor skills automatically, but this problem has been generally overlooked. Here we review motor automaticity associated motor deficits in PD, such as reduced arm swing, decreased stride length, freezing of gait, micrographia and reduced facial expression. Recent neuroimaging studies have revealed some neural mechanisms underlying impaired motor automaticity in PD, including less efficient neural coding of movement, failure to shift automated motor skills to the sensorimotor striatum, instability of the automatic mode within the striatum, and use of attentional control and/or compensatory efforts to execute movements usually performed automatically in healthy people. PD patients lose previously acquired automatic skills due to their impaired sensorimotor striatum, and have difficulty in acquiring new automatic skills or restoring lost motor skills. More investigations on the pathophysiology of motor automaticity, the effect of L-dopa or surgical treatments on automaticity, and the potential role of using measures of automaticity in early diagnosis of PD would be valuable. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wu, Tao; Chan, Piu] Capital Med Univ, Beijing Inst Geriatr, Xuanwu Hosp, Dept Neurobiol,Key Lab Neurodegenerat Disorders,M, Beijing 100053, Peoples R China. [Wu, Tao; Chan, Piu] Beijing Inst Brain Disorders, Beijing Key Lab Parkinsons Dis, Parkinson Dis Ctr, Beijing, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Beijing Inst Geriatr, Xuanwu Hosp, Dept Neurobiol,Key Lab Neurodegenerat Disorders,M, Beijing 100053, Peoples R China. EM wutao69@gmail.com FU National Science Foundation of China [81071012, 81271429]; Seed Grant of International Alliance of Translational Neuroscience [PXM2014_014226_000015]; NINDS Intramural Program FX This work was supported by grants from the National Science Foundation of China (81071012 and 81271429), and Seed Grant of International Alliance of Translational Neuroscience (PXM2014_014226_000015). Dr. Hallett is supported by the NINDS Intramural Program. NR 140 TC 20 Z9 20 U1 6 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2015 VL 82 BP 226 EP 234 DI 10.1016/j.nbd.2015.06.014 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CW4RO UT WOS:000364980000021 PM 26102020 ER PT J AU Wandschneider, B Koepp, M Scott, C Micallef, C Balestrini, S Sisodiya, SM Thom, M Harper, RM Sander, JW Vos, SB Duncan, JS Lhatoo, S Diehl, B AF Wandschneider, Britta Koepp, Matthias Scott, Catherine Micallef, Caroline Balestrini, Simona Sisodiya, Sanjay M. Thom, Maria Harper, Ronald M. Sander, Josemir W. Vos, Sjoerd B. Duncan, John S. Lhatoo, Samden Diehl, Beate TI Structural imaging biomarkers of sudden unexpected death in epilepsy SO BRAIN LA English DT Article DE sudden death; voxel based morphometry; hippocampus; autonomic; sudep risk ID TEMPORAL-LOBE EPILEPSY; OBSTRUCTIVE SLEEP-APNEA; CENTRAL HYPOVENTILATION SYNDROME; AUTONOMIC NERVOUS-SYSTEM; BRAIN-STEM; CARDIOVASCULAR CONTROL; UNEXPLAINED DEATH; FETAL SHEEP; HIPPOCAMPAL; ABNORMALITIES AB Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T-1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. C1 [Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M.; Thom, Maria; Sander, Josemir W.; Vos, Sjoerd B.; Duncan, John S.; Diehl, Beate] UCL Inst Neurol, Dept Clin & Expt Epilepsy, NIHR Univ Coll London Hosp Biomed Res Ctr, London WC1N 3BG, England. [Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M.; Thom, Maria; Sander, Josemir W.; Vos, Sjoerd B.; Duncan, John S.; Diehl, Beate] Epilepsy Soc, Gerrards Cross SL9 0RJ, England. [Balestrini, Simona] Polytech Univ Marche, Dept Neurosci, Ancona, Italy. [Sisodiya, Sanjay M.; Thom, Maria; Harper, Ronald M.; Sander, Josemir W.; Lhatoo, Samden; Diehl, Beate] NINDS, Ctr SUDEP Res, Bethesda, MD 20892 USA. [Harper, Ronald M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA USA. [Sander, Josemir W.] Stichting Epilepsie Inst Nederland, Heemstede, Netherlands. [Vos, Sjoerd B.] UCL, Translat Imaging Grp, Ctr Med Image Comp, London, England. [Lhatoo, Samden] Univ Hosp Cleveland, Case Med Ctr, Neurol Inst, Epilepsy Ctr, Cleveland, OH 44106 USA. RP Diehl, B (reprint author), Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Queen Sq, London WC1N 3BG, England. EM b.diehl@ucl.ac.uk RI Sander, Josemir/C-1576-2008 OI Sander, Josemir/0000-0001-6041-9661 FU Department of Health's NIHR Biomedical Research Centres; NIH -National Institute of Neurological Disorders and Stroke [U01-NS090405-01, U01-NS090407-01]; Wellcome Trust [083148]; National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative); Marvin Weil Epilepsy Research Fund FX This work was undertaken at UCLH/UCL who receives a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. It was partially funded by the NIH -National Institute of Neurological Disorders and Stroke (U01-NS090405-01 and U01-NS090407-01. The Center for SUDEP Research) and Wellcome Trust (project grant 083148). S.B.V. is funded by the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative). J.W.S. is supported by the Marvin Weil Epilepsy Research Fund. NR 55 TC 11 Z9 11 U1 2 U2 6 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 OCT 1 PY 2015 VL 138 BP 2907 EP 2919 DI 10.1093/brain/awv233 PN 10 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW6VJ UT WOS:000365136200019 PM 26264515 ER PT J AU Hutson, SP Han, PKJ Hamilton, JG Rife, SC Al-Rahawan, MM Moser, RP Duty, SP Anand, S Alter, BP AF Hutson, Sadie P. Han, Paul K. J. Hamilton, Jada G. Rife, Sean C. Al-Rahawan, Mohamad M. Moser, Richard P. Duty, Seth P. Anand, Sheeba Alter, Blanche P. TI The use of haematopoietic stem cell transplantation in Fanconi anaemia patients: a survey of decision making among families in the US and Canada SO HEALTH EXPECTATIONS LA English DT Article DE decision making; Fanconi anaemia; genetics; psychosocial factors; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; CANCER; RISK; MEDICATION; FEELINGS; PATTERNS; BELIEFS AB Background Fanconi anaemia (FA) is a rare genetic disorder associated with bone marrow failure (BMF), congenital anomalies and cancer susceptibility. Stem cell transplantation (SCT) offers a potential cure for BMF or leukaemia, but incurs substantial risks. Little is known about factors influencing SCT decision making. Objective The study objective was to explore factors influencing patients' with FA and family members' decision making about SCT. Design Using a mixed-methods exploratory design, we surveyed US and Canadian patients with FA and family members who were offered SCT. Main variables studied Closed-ended survey items measured respondents' beliefs about the necessity, risks and concerns regarding SCT; multivariable logistic regression was used to examine the association between these factors and the decision to undergo SCT. Open-ended survey items measured respondents' perceptions of factors important to the SCT decision; qualitative analysis was used to identify emergent themes. Results The decision to undergo SCT was significantly associated with greater perceived necessity (OR = 2.81, P = 0.004) and lower concern about harms of SCT (OR = 0.31, P = 0.03). Qualitative analysis revealed a perceived lack of choice among respondents regarding the use of SCT, which was related to physician influence and respondent concerns about patients' quality of life. Conclusions Overall, study results emphasize the importance of the delicate interplay between provider recommendation of a medical procedure and patient/parental perceptions and decision making. Findings can help providers understand the need to acknowledge family members' perceptions of SCT decision making and offer a comprehensive discussion of the necessity, risks, benefits and potential outcomes. C1 [Hutson, Sadie P.] Univ Tennessee, Coll Nursing, Knoxville, TN 37996 USA. [Hutson, Sadie P.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD USA. [Han, Paul K. J.] Maine Med Ctr, Res Inst, Ctr Outcomes Res & Evaluat, Scarborough, ME USA. [Hamilton, Jada G.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH,DHHS, Rockville, MD USA. [Rife, Sean C.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Al-Rahawan, Mohamad M.] Univ Illinois, Dept Pediat, Coll Med Peoria, Peoria, IL USA. [Moser, Richard P.] NCI, Sci Res & Technol Branch, Div Canc Control & Populat Sci, NIH,DHHS, Rockville, MD USA. [Duty, Seth P.] E Tennessee State Univ, Coll Nursing, Johnson City, TN 37614 USA. [Anand, Sheeba] E Tennessee State Univ, Quillen Coll Med, Johnson City, TN 37614 USA. RP Hutson, SP (reprint author), Univ Tennessee, Coll Nursing, 1200 Volunteer Blvd,Room 161, Knoxville, TN 37996 USA. EM shutson@utk.edu OI Han, Paul/0000-0003-0165-1940 FU NIH; NCI in Rockville, MD, USA FX This research was supported in part by the Intramural Research Program of the NIH and NCI in Rockville, MD, USA (SPH, PKJH, BPA, JGH, RPM). NR 24 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD OCT PY 2015 VL 18 IS 5 BP 929 EP 941 DI 10.1111/hex.12066 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CW5OU UT WOS:000365046700026 PM 23621292 ER PT J AU Henry, SG Czarnecki, D Kahn, VC Chou, WYS Fagerlin, A Ubel, PA Rovner, DR Alexander, SC Knight, SJ Holmes-Rovner, M AF Henry, Stephen G. Czarnecki, Danielle Kahn, Valerie C. Chou, Wen-Ying Sylvia Fagerlin, Angela Ubel, Peter A. Rovner, David R. Alexander, Stewart C. Knight, Sara J. Holmes-Rovner, Margaret TI Patient-physician communication about early stage prostate cancer: analysis of overall visit structure SO HEALTH EXPECTATIONS LA English DT Article DE discourse analysis; patient-centred communication; prostate cancer; qualitative research; structure; transitions; veterans ID MEDICAL ENCOUNTERS; DECISION-MAKING; BAD-NEWS; TRANSITIONS; PARTICIPATION; DISCOURSE; SKILLS; MEN AB Background We know little about patient-physician communication during visits to discuss diagnosis and treatment of prostate cancer. Objective To examine the overall visit structure and how patients and physicians transition between communication activities during visits in which patients received new prostate cancer diagnoses. Participants Forty veterans and 18 urologists at one VA medical centre. Methods We coded 40 transcripts to identify major communication activities during visits and used empiric discourse analysis to analyse transitions between activities. Results We identified five communication activities that occurred in the following typical sequence: 'diagnosis delivery', 'risk classification', 'options talk', 'decision talk' and 'next steps'. The first two activities were typically brief and involved minimal patient participation. Options talk was typically the longest activity; physicians explicitly announced the beginning of options talk and framed it as their professional responsibility. Some patients were unsure of the purpose of visit and/or who should make treatment decisions. Conclusion Visits to deliver the diagnosis of early stage prostate cancer follow a regular sequence of communication activities. Physicians focus on discussing treatment options and devote comparatively little time and attention to discussing the new cancer diagnosis. Towards the goal of promoting patient-centred communication, physicians should consider eliciting patient reactions after diagnosis delivery and explaining the decision-making process before describing treatment options. C1 [Henry, Stephen G.] Univ Calif Davis, Div Gen Med Geriatr & Bioeth, Sacramento, CA 95817 USA. [Czarnecki, Danielle] Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. [Kahn, Valerie C.; Fagerlin, Angela] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA. [Chou, Wen-Ying Sylvia] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Fagerlin, Angela] Ann Arbor VA HSR&D Ctr Clin Management Res, Ann Arbor, MI USA. [Fagerlin, Angela] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Fagerlin, Angela] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. [Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Rovner, David R.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Alexander, Stewart C.] Duke Univ, Dept Med, Durham, NC USA. [Alexander, Stewart C.] Durham VA Med Ctr, Durham, NC USA. [Knight, Sara J.] Vet Hlth Adm, Off Res & Dev, VA Hlth Serv Res & Dev, Washington, DC USA. [Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Holmes-Rovner, Margaret] Michigan State Univ, Ctr Eth & Humanities Life Sci, E Lansing, MI 48824 USA. RP Henry, SG (reprint author), Univ Calif Davis, Div Gen Med Geriatr & Bioeth, 4150 5 St Suite 2400, Sacramento, CA 95817 USA. EM sghenry@ucdavis.edu FU Blue Cross Blue Shield of Michigan Foundation (Detroit, MI) [1722.II]; University of Michigan Robert Wood Johnson Foundation Health and Society Scholars program; IIR Merit Award from the U.S. Department of Veterans Affairs (Washington, DC) [IIR 05-283] FX This study was supported in part by grants from the Blue Cross Blue Shield of Michigan Foundation (1722.II; Detroit, MI) and the University of Michigan Robert Wood Johnson Foundation Health and Society Scholars program (Ann Arbor, MI) to Dr. Henry. The parent study was funded by an IIR Merit Award from the U.S. Department of Veterans Affairs (IIR 05-283, Washington, DC) to Dr. Fagerlin. NR 36 TC 2 Z9 2 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-6513 EI 1369-7625 J9 HEALTH EXPECT JI Health Expect. PD OCT PY 2015 VL 18 IS 5 BP 1757 EP 1768 DI 10.1111/hex.12168 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CW5OU UT WOS:000365046700093 PM 24372758 ER PT J AU Freedman, BR Sheehan, FT Lerner, AL AF Freedman, Benjamin R. Sheehan, Frances T. Lerner, Amy L. TI MRI-based analysis of patellofemoral cartilage contact, thickness, and alignment in extension, and during moderate and deep flexion SO KNEE LA English DT Article DE Patellofemoral joint; Patellofemoral biomechanics; Knee; Deep knee flexion ID PATELLAR TRACKING; KNEE FLEXION; ELEMENT-ANALYSIS; FEMORAL SHAPE; KINEMATICS; PAIN; JOINT; AREA; INDIVIDUALS; MECHANICS AB Background: Several factors are believed to contribute to patellofemoral joint function throughout knee flexion including patellofemoral (PF) kinematics, contact, and bone morphology. However, data evaluating the PF joint in this highly flexed state have been limited. Therefore, the purpose of this study was to evaluate patellofemoral contact and alignment in low (0 degrees), moderate (60 degrees), and deep (140 degrees) knee flexion, and then correlate these parameters to each other, as well as to femoral morphology. Methods: Sagittal magnetic resonance images were acquired on 14 healthy female adult knees (RSRB approved) using a 1.5 T scanner with the knee in full extension, mid-flexion, and deep flexion. The patellofemoral cartilage contact area, lateral contact displacement (LCD), cartilage thickness, and lateral patellar displacement (LPD) throughout flexion were defined. Intra- and inter-rater repeatability measures were determined. Correlations between patellofemoral contact parameters, alignment, and sulcus morphology were calculated. Results: Measurement repeatability ICCs ranged from 0.94 to 0.99. Patellofemoral cartilage contact area and thickness, LCD, and LPD were statistically different throughout all levels of flexion (p < 0.001). The cartilage contact area was correlated to LPD, cartilage thickness, sulcus angle, and epicondylar width (r = 0.47-0.72, p < 0.05). Discussion: This study provides a comprehensive analysis of the patellofemoral joint throughout its range of motion. Conclusions: This study agrees with past studies that investigated patellofemoral measures at a single flexion angle, and provides new insights into the relationship between patellofemoral contact and alignment at multiple flexion angles. Clinical Relevance: The study provides a detailed analysis of the patellofemoral joint in vivo, and demonstrates the feasibility of using standard clinical magnetic resonance imaging scanners to image the knee joint in deep flexion. (C) 2015 Elsevier B.V. All rights reserved. C1 [Freedman, Benjamin R.; Lerner, Amy L.] Univ Rochester, Dept Biomed Engn, Rochester, NY 14627 USA. [Freedman, Benjamin R.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Sheehan, Frances T.] NIH, Funct & Appl Biomech, Bethesda, MD USA. RP Freedman, BR (reprint author), Univ Penn, 424 Stemmler Hall,36th & Hamilton Walk, Philadelphia, PA 19104 USA. EM bfreed@seas.upenn.edu FU DePuy Orthopaedics; NSF GRFP; NIH FX This study was supported by DePuy Orthopaedics and the NSF GRFP. We are grateful for the technical contributions of Art Salo and Kristen Hovinga during image acquisition. Dr. Sheehan's contribution to this study was supported by the Intramural Research Program of the NIH. NR 44 TC 1 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0968-0160 EI 1873-5800 J9 KNEE JI Knee PD OCT PY 2015 VL 22 IS 5 BP 405 EP 410 DI 10.1016/j.knee.2015.06.012 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA CW5UY UT WOS:000365063300009 PM 26213361 ER PT J AU Oh, YM Park, HB Shin, JH Lee, JE Park, HY Kho, DH Lee, JS Choi, H Okuda, T Kokame, K Miyata, T Kim, IH Lee, SH Schwartz, RH Choi, K AF Oh, Yu Mi Park, Hyung Bae Shin, Jae Hun Lee, Ji Eun Park, Ha Young Kho, Dhong Hyo Lee, Jun Sung Choi, Heonsik Okuda, Tomohiko Kokame, Koichi Miyata, Toshiyuki Kim, In-Hoo Lee, Seung Hoon Schwartz, Ronald H. Choi, Kyungho TI Ndrg1 is a T-cell clonal anergy factor negatively regulated by CD28 costimulation and interleukin-2 SO NATURE COMMUNICATIONS LA English DT Article ID ADAPTIVE TOLERANCE; CYCLE PROGRESSION; MAMMALIAN TARGET; IN-VITRO; 2 EGR2; CBL-B; INDUCTION; ACTIVATION; GROWTH; GENE AB Induction of T-cell clonal anergy involves serial activation of transcription factors, including NFAT and Egr2/3. However, downstream effector mechanisms of these transcription factors are not fully understood yet. Here we identify Ndrg1 as an anergy factor induced by Egr2. Ndrg1 is upregulated by anergic signalling and maintained at high levels in resting anergic T cells. Overexpression of Ndrg1 mimics the anergic state and knockout of the gene prevents anergy induction. Interestingly, Ndrg1 is phosphorylated and degraded by CD28 signalling in a proteasome-dependent manner, explaining the costimulation dependence of anergy prevention. Similarly, IL-2 treatment of anergic T cells, under conditions that lead to the reversal of anergy, also induces Ndrg1 phosphorylation and degradation. Finally, older Ndrg1-deficient mice show T-cell hyperresponsiveness and Ndrg1-deficient T cells aggravate inducible autoimmune inflammation. Thus, Ndrg1 contributes to the maintenance of clonal anergy and inhibition of T-cell-mediated inflammation. C1 [Oh, Yu Mi; Park, Hyung Bae; Lee, Ji Eun; Park, Ha Young; Choi, Kyungho] Seoul Natl Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 110799, South Korea. [Oh, Yu Mi; Park, Hyung Bae; Lee, Ji Eun; Park, Ha Young; Choi, Kyungho] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul 110799, South Korea. [Oh, Yu Mi; Shin, Jae Hun; Lee, Ji Eun; Kho, Dhong Hyo; Lee, Jun Sung; Lee, Seung Hoon; Choi, Kyungho] Natl Canc Ctr, Specif Organs Canc Branch, Res Inst, Gyeonggi Do 410769, South Korea. [Park, Hyung Bae] Natl Canc Ctr, Hematol Malignancy Branch, Res Inst, Gyeonggi Do 410769, South Korea. [Choi, Heonsik; Schwartz, Ronald H.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. [Okuda, Tomohiko; Kokame, Koichi; Miyata, Toshiyuki] Natl Cerebral & Cardiovasc Ctr, Dept Mol Pathogenesis, Suita, Osaka 5658565, Japan. [Kim, In-Hoo] Natl Canc Ctr, Mol Imaging & Therapy Branch, Res Inst, Gyeonggi Do 410769, South Korea. RP Choi, K (reprint author), Seoul Natl Univ, Dept Biochem & Mol Biol, Coll Med, 103 Daehak Ro, Seoul 110799, South Korea. EM khchoi@snu.ac.kr FU National Cancer Center [NCC-1010090]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning, Republic of Korea [NRF-2013R1A2A2A01009444] FX We thank Chuan Chen (National Institutes of Health, Bethesda, Maryland) for assistance in maintaining and preparing the A.E7 T cell clone; Elizabeth Majane (National Institutes of Health, Bethesda, Maryland) and Dong Pyo Lim for help in breeding and maintaining the mouse lines; James Garvin and Hae Hyun Seo for technical assistance; Therese Commes for providing anti-Ndrg1 antibody; and Jonathan Powell (Johns Hopkins University School of Medicine, Baltimore, Maryland) for critical reading of the manuscript. We are especially grateful to Jun Yang (Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick, Maryland) for her support in the microarray experiments and analysis. This work was supported by grants from the National Cancer Center (NCC-1010090) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013R1A2A2A01009444), Republic of Korea. NR 51 TC 0 Z9 0 U1 3 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 OCT PY 2015 VL 6 AR 8698 DI 10.1038/ncomms9698 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4CC UT WOS:000364937800003 PM 26507712 ER PT J AU Pegu, A Asokan, M Wu, L Wang, KY Hataye, J Casazza, JP Guo, XT Shi, W Georgiev, I Zhou, TQ Chen, XJ O'Dell, S Todd, JP Kwong, PD Rao, SS Yang, ZY Koup, RA Mascola, JR Nabel, GJ AF Pegu, Amarendra Asokan, Mangaiarkarasi Wu, Lan Wang, Keyun Hataye, Jason Casazza, Joseph P. Guo, Xiaoti Shi, Wei Georgiev, Ivelin Zhou, Tongqing Chen, Xuejun O'Dell, Sijy Todd, John-Paul Kwong, Peter D. Rao, Srinivas S. Yang, Zhi-yong Koup, Richard A. Mascola, John R. Nabel, Gary J. TI Activation and lysis of human CD4 cells latently infected with HIV-1 SO NATURE COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; ANTIRETROVIRAL THERAPY; BISPECIFIC ANTIBODY; MONOCLONAL-ANTIBODIES; HIV-1-INFECTED CELLS; RATIONAL DESIGN; IN-VIVO; VIREMIA; ERADICATION AB The treatment of AIDS with combination antiretroviral therapy (cART) remains lifelong largely because the virus persists in latent reservoirs. Elimination of latently infected cells could therefore reduce treatment duration and facilitate immune reconstitution. Here we report an approach to reduce the viral reservoir by activating dormant viral gene expression and directing T lymphocytes to lyse previously latent, HIV-1-infected cells. An immunomodulatory protein was created that combines the specificity of a HIV-1 broadly neutralizing antibody with that of an antibody to the CD3 component of the T-cell receptor. CD3 engagement by the protein can stimulate T-cell activation that induces proviral gene expression in latently infected T cells. It further stimulates CD8 T-cell effector function and redirects T cells to lyse these previously latent-infected cells through recognition of newly expressed Env. This immunomodulatory protein could potentially help to eliminate latently infected cells and deplete the viral reservoir in HIV-1-infected individuals. C1 [Pegu, Amarendra; Asokan, Mangaiarkarasi; Wu, Lan; Wang, Keyun; Hataye, Jason; Casazza, Joseph P.; Guo, Xiaoti; Shi, Wei; Georgiev, Ivelin; Zhou, Tongqing; Chen, Xuejun; O'Dell, Sijy; Todd, John-Paul; Kwong, Peter D.; Rao, Srinivas S.; Yang, Zhi-yong; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@nih.gov; gary.nabel@sanofi.com RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health FX We thank D. Ambrozak, R. Nguyen and S. Perfetto for help with cell sorting, A. Cooper, D. Bolton and M. Louder for discussions and technical help, and A. Tislerics and B. Hartman for manuscript preparation. We thank Romas Geleziunas and Martha Vazquez from Gilead Sciences for generously providing antiretroviral drugs for use in in vivo experiments. This research was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health. NR 38 TC 19 Z9 19 U1 4 U2 11 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 OCT PY 2015 VL 6 AR 8447 DI 10.1038/ncomms9447 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3XF UT WOS:000364925000004 PM 26485194 ER PT J AU St Laurent, B Miller, B Burton, TA Amaratunga, C Men, S Sovannaroth, S Fay, MP Miotto, O Gwadz, RW Anderson, JM Fairhurst, RM AF St Laurent, Brandyce Miller, Becky Burton, Timothy A. Amaratunga, Chanaki Men, Sary Sovannaroth, Siv Fay, Michael P. Miotto, Olivo Gwadz, Robert W. Anderson, Jennifer M. Fairhurst, Rick M. TI Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa SO NATURE COMMUNICATIONS LA English DT Article ID WESTERN CAMBODIA; MALARIA; ANOPHELES; TRANSMISSION; IDENTIFICATION; POPULATIONS; PIPERAQUINE; THAILAND; IMMUNITY; COMPLEX AB Artemisinin-resistant Plasmodium falciparum parasites are rapidly spreading in Southeast Asia, yet nothing is known about their transmission. This knowledge gap and the possibility that these parasites will spread to Africa endanger global efforts to eliminate malaria. Here we produce gametocytes from parasite clinical isolates that displayed artemisinin resistance in patients and in vitro, and use them to infect native and non-native mosquito vectors. We show that contemporary artemisinin-resistant isolates from Cambodia develop and produce sporozoites in two Southeast Asian vectors, Anopheles dirus and Anopheles minimus, and the major African vector, Anopheles coluzzii (formerly Anopheles gambiae M). The ability of artemisinin-resistant parasites to infect such highly diverse Anopheles species, combined with their higher gametocyte prevalence in patients, may explain the rapid expansion of these parasites in Cambodia and neighbouring countries, and further compromise efforts to prevent their global spread. C1 [St Laurent, Brandyce; Miller, Becky; Burton, Timothy A.; Amaratunga, Chanaki; Gwadz, Robert W.; Anderson, Jennifer M.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Men, Sary; Sovannaroth, Siv] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh 12101, Cambodia. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD 20852 USA. [Miotto, Olivo] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand. [Miotto, Olivo] Wellcome Trust Sanger Inst, Malaria Programme, Hinxton CB10 1SA, England. [Miotto, Olivo] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford OX3 7BN, England. RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov OI Miotto, Olivo/0000-0001-8060-6771; St. Laurent, Brandyce/0000-0002-2957-5364; Fay, Michael P./0000-0002-8643-9625 FU Intramural Research Program of the NIAID, NIH; Wellcome Trust through core funding of the Wellcome Trust Sanger Institute [098051]; UK Medical Research Council [G0600718] FX This study was funded by the Intramural Research Program of the NIAID, NIH. We thank Dalin Dek, Andre Laughinghouse, Kevin Lee, Tovi Lehmann, Seila Suon, Vorleak Try and Thomas Wellems for their support for this work. The sequencing for this study was funded by the Wellcome Trust through core funding of the Wellcome Trust Sanger Institute (098051). The Centre for Genomics and Global Health is supported by the UK Medical Research Council (G0600718). NR 33 TC 14 Z9 14 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2015 VL 6 AR 8614 DI 10.1038/ncomms9614 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4AT UT WOS:000364934200016 PM 26485448 ER PT J AU Koso-Thomas, M McClure, EM AF Koso-Thomas, Marion McClure, Elizabeth M. CA Global Network Women's Children's TI The Global Network for Women's and Children's Health Research: A model of capacity-building research SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Article DE Global health; Maternal and child health; Low-middle income countries ID RANDOMIZED CONTROLLED-TRIAL; MIDDLE-INCOME COUNTRIES; PREVENT POSTPARTUM HEMORRHAGE; RESOURCE-LIMITED SETTINGS; NEWBORN-CARE; NEONATAL-MORTALITY; BIRTH ATTENDANTS; INFANTS; IMPLEMENTATION; RESUSCITATION AB In response to the global effort to accelerate progress towards the Millennium Development Goals 4 and 5, a partnership was created between the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the Bill and Melinda Gates Foundation to establish the Global Network for Women's and Children's Health Research (Global Network) in 2000. The Global Network was developed with a goal of building local maternal and child health research capacity in resource-poor settings. The objective of the network was to conduct research focused on several high-need areas, such as preventing life-threatening obstetric complications, improving birth weight and infant growth, and improving childbirth practices in order to reduce mortality. Scientists from developing countries, together with peers in the USA, lead research teams that identify and address population needs through randomized clinical trials and other research studies. Global Network projects develop and test cost-effective, sustainable interventions for pregnant women and newborns and provide guidance for national policy and for the practice of evidence-based medicine. This article reviews the results of the Global Network's research, the impact on policy and practice, and highlights the capacity-building efforts and collaborations developed since its inception. (C) 2015 Published by Elsevier Ltd. C1 [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [McClure, Elizabeth M.] RTI Int, Durham, NC USA. RP Koso-Thomas, M (reprint author), Eunice Kennedy Shriver NICHD, Perinatol & Pregnancy Branch, Rockville, MD 20847 USA. EM kosomari@email.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD040477, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01 HD058322, U01 HD058326, U01 HD040636, U01 HD043475] FX This study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 HD040477; U01 HD043464; U01 HD040657; U01 HD042372; U01 HD040607; U01 HD058322; U01 HD058326; U01 HD040636; U01 HD043475). NR 46 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1744-165X EI 1878-0946 J9 SEMIN FETAL NEONAT M JI Semin. Fetal Neonatal Med. PD OCT PY 2015 VL 20 IS 5 BP 293 EP 299 DI 10.1016/j.siny.2015.04.004 PG 7 WC Pediatrics SC Pediatrics GA CW1BZ UT WOS:000364725900003 PM 26043962 ER PT J AU Sharma, K Sharma, NK Singh, R Anand, A AF Sharma, Kaushal Sharma, Neel K. Singh, Ramandeep Anand, Akshay TI Exploring the role of VEGF in Indian Age related macular degeneration SO ANNALS OF NEUROSCIENCES LA English DT Article DE VEGF; Age related; macular degeneration; Anti-VEGF; Heart ailment ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; CHOROIDAL NEOVASCULARIZATION; TARGETING VEGF; PLASMA-LEVELS; AMD; POLYMORPHISMS; ANGIOGENESIS; EXPRESSION; RECEPTOR-3 AB Background: Age related macular degeneration (AMD) is major devastating neurodegenerative disorder characterized by progressive irreversible vision loss in the elderly persons. In spite of several genetic and environmental factors, the role of VEGF and CFH predispose the pathological phenomenon in the AMD patients. Purpose: The aim of the study was to estimate the VEGF levels in the serum of AMD patients and its correlation with co-morbidity of the participants. Methods: The study recruited the 98 AMD patients and 59 controls with proper consent of the participants as per the exclusion-inclusion criteria. The co-morbidity and socio-economic details were obtained by introducing the standard questionnaire amongst the participants. Serum levels of vascular endothelial growth factor (VEGF) was estimated by ELISA and compared with the control population of the study. The levels of VEGF in the serum of AMD patients and controls were compared with Mann-Whitney U-test. Kruskal Wallis one-way analysis of variance (ANOVA) was employed to analyze more than two variables in the study. Results: Elevated level of VEGF was found in AMD patients as compared to controls. Surprisingly, we did not find significant changes among wet AMD subtypes i.e. minimal, predominant and classic wet AMD. However, we have demonstrated the intravitreal anti-VEGF treatment (avastin) in AMD patients could reduce the systemic VEGF levels although it was not significant. Moreover, the heart ailment in the AMD patients could also influence the VEGF levels. Conclusion: Our study is consistent with previous studies describing the imperative significance of VEGF in AMD pathology. However, our study did not reveal the role of VEGF in wet AMD progression but it is well established causative agent for the same. The increased levels of VEGF in heart ailment among AMD patients are significant. C1 [Sharma, Kaushal; Anand, Akshay] Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India. [Sharma, Kaushal] Panjab Univ, Ctr Syst Biol & Bioinformat, Chandigarh 160014, India. [Sharma, Neel K.] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Singh, Ramandeep] Post Grad Inst Med Educ & Res, Dept Ophthalmol, Chandigarh, India. RP Anand, A (reprint author), Post Grad Inst Med Educ & Res, Dept Neurol, Neurosci Res Lab, Chandigarh, India. EM akshay1anand@rediffmail.com NR 39 TC 0 Z9 0 U1 0 U2 0 PU INDIAN ACAD NEUROSCIENCES PI CHANDIAGRH PA NEUROSCIENCE RESEARCH LAB- 3036, RESEARCH BLOCK B, PGIMER, SECTOR-12, CHANDIAGRH, 160012, INDIA SN 0972-7531 EI 0976-3260 J9 ANN NEUROSCI JI Ann. Neurosci. PD OCT PY 2015 VL 22 IS 4 BP 232 EP 237 DI 10.5214/ans.0972.7531.220408 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CV9FU UT WOS:000364593700008 PM 26526736 ER PT J AU Pilling, LC Joehanes, R Melzer, D Harries, LW Henley, W Dupuis, J Lin, HH Mitchell, M Hernandez, D Ying, SX Lunetta, KL Benjamin, EJ Singleton, A Levy, D Munson, P Murabito, JM Ferrucci, L AF Pilling, Luke C. Joehanes, Roby Melzer, David Harries, Lorna W. Henley, William Dupuis, Josee Lin, Honghuang Mitchell, Marcus Hernandez, Dena Ying, Sai-Xia Lunetta, Kathryn L. Benjamin, Emelia J. Singleton, Andrew Levy, Daniel Munson, Peter Murabito, Joanne M. Ferrucci, Luigi TI Gene expression markers of age-related inflammation in two human cohorts SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Aging; Inflammation; Transcriptome; Blood; Human; Epidemiology ID CORONARY-HEART-DISEASE; PLASMA-CONCENTRATION; OLDER PERSONS; INTERLEUKIN-6; DECLINE; BLOOD; IL-6; ASSOCIATION; RESOURCES; INCHIANTI AB Introduction: Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Methods: Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n = 2422, ages 40-92 yrs) and InCHIANTI study (n = 694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. Results: In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n = 194,35.6% mediated, p = 0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. Conclusions: This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. Published by Elsevier Inc. C1 [Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Epidemiol & Publ Hlth, RILD, Exeter EX2 5DW, Devon, England. [Joehanes, Roby; Dupuis, Josee; Lin, Honghuang; Ying, Sai-Xia; Lunetta, Kathryn L.; Benjamin, Emelia J.; Levy, Daniel; Munson, Peter; Murabito, Joanne M.] NHLBI, Framingham, MA USA. [Joehanes, Roby; Dupuis, Josee; Lin, Honghuang; Ying, Sai-Xia; Lunetta, Kathryn L.; Benjamin, Emelia J.; Levy, Daniel; Munson, Peter; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Joehanes, Roby; Ying, Sai-Xia; Munson, Peter] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Harries, Lorna W.; Mitchell, Marcus] Univ Exeter, Sch Med, Inst Biomed & Climcal Sci, RILD, Exeter EX2 5DW, Devon, England. [Henley, William] Univ Exeter, Sch Med, Inst Hlth Serv Res, Exeter EX1 2LU, Devon, England. [Lin, Honghuang] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med & Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), NIA, NIA ASTRA Unit, Harbor Hosp, 5th Floor,NM540,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Singleton, Andrew/C-3010-2009; OI Melzer, David/0000-0002-0170-3838; Pilling, Luke/0000-0002-3332-8454; Benjamin, Emelia/0000-0003-4076-2336; Lin, Honghuang/0000-0003-3043-3942 FU Division of Intramural Research; National Heart, Lung, and Blood Institute; National Institutes of Health, Bethesda, MD; Intramural Research Program, National Institute on Aging; Wellcome Trust Institutional Strategic Support Award [WT097835MF]; National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula; [RO1 HL 064753]; [RO1 HL076784]; [1 R01 AG028321]; [N01-HC-25195]; [RO1 AG29451] FX FHS gene expression profiling was funded through the Division of Intramural Research (Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, and National Institutes of Health, Bethesda, MD. Measurement of interleukin-6 was funded through RO1 HL 064753, RO1 HL076784, and 1 R01 AG028321. The Framingham Heart Study is supported by contract N01-HC-25195. JMM was supported by RO1 AG29451.; This study was supported in part by the Intramural Research Program, National Institute on Aging. The analysis was generously supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). WH was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in England. NR 41 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD OCT PY 2015 VL 70 BP 37 EP 45 DI 10.1016/j.exger.2015.05.012 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CV4QV UT WOS:000364252500006 PM 26087330 ER PT J AU Torrisi, S O'Connell, K Davis, A Reynolds, R Balderston, N Fudge, JL Grillon, C Ernst, M AF Torrisi, Salvatore O'Connell, Katherine Davis, Andrew Reynolds, Richard Balderston, Nicholas Fudge, Julie L. Grillon, Christian Ernst, Monique TI Resting State Connectivity of the Bed Nucleus of the Stria Terminalis at Ultra-High Field SO HUMAN BRAIN MAPPING LA English DT Article DE resting state; bed nucleus of the stria terminalis; 7 Tesla ID CORTICOTROPIN-RELEASING HORMONE; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; PERIAQUEDUCTAL GRAY; 7 T; PREFRONTAL CORTEX; EXTENDED AMYGDALA; FMRI; ANXIETY; NEUROSCIENCE AB The bed nucleus of the stria terminalis (BNST), a portion of the "extended amygdala," is implicated in the pathophysiology of anxiety and addiction disorders. Its small size and connection to other small regions prevents standard imaging techniques from easily capturing it and its connectivity with confidence. Seed-based resting state functional connectivity is an established method for mapping functional connections across the brain from a region of interest. We, therefore, mapped the BNST resting state network with high spatial resolution using 7 Tesla fMRI, demonstrating the in vivo reproduction of many human BNST connections previously described only in animal research. We identify strong BNST functional connectivity in amygdala, hippocampus and thalamic subregions, caudate, periaqueductal gray, hypothalamus, and cortical areas such as the medial PFC and precuneus. This work, which demonstrates the power of ultra-high field for mapping functional connections in the human, is an important step toward elucidating cortical and subcortical regions and subregions of the BNST network. (C) 2015 Wiley Periodicals, Inc. C1 [Torrisi, Salvatore; O'Connell, Katherine; Davis, Andrew; Balderston, Nicholas; Grillon, Christian; Ernst, Monique] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. [Reynolds, Richard] NIMH, Sci & Stat Comp Core, Bethesda, MD 20892 USA. [Fudge, Julie L.] Univ Rochester, Med Ctr, Dept Neurobiol & Anat, Rochester, NY 14642 USA. RP Torrisi, S (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA. EM sam.torrisi@nih.gov OI Balderston, Nicholas/0000-0002-8565-1544 FU National Institutes of Mental Health [MH002798 (Protocol 02-M-0321), MH63291 (RO1)] FX Contract grant sponsor: Intramural Research Program of the National Institutes of Mental Health; Contract grant numbers: MH002798 (Protocol 02-M-0321) and MH63291 (RO1). NR 75 TC 7 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2015 VL 36 IS 10 BP 4076 EP 4088 DI 10.1002/hbm.22899 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CV4EM UT WOS:000364219100027 PM 26178381 ER PT J AU Ribeiro, JMC Kazimirova, M Takac, P Andersen, JF Francischetti, IMB AF Ribeiro, Jose M. C. Kazimirova, Maria Takac, Peter Andersen, John F. Francischetti, Ivo M. B. TI An insight into the sialome of the horse fly, Tabanus bromius SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Medical entomology; Veterinary entomology; Tabanid; Hematophagy; Salivary glands; Transcriptome ID MOSQUITO ANOPHELES-ALBIMANUS; SALIVARY-GLAND EXTRACTS; PLATELET-AGGREGATION; ANTICOAGULANT ACTIVITIES; ANTIMICROBIAL PEPTIDES; SEQUENCE ALIGNMENT; STABLE FLY; PROTEIN; DIPTERA; TRANSCRIPTOME AB Blood feeding animals face their host's defenses against tissue injury and blood loss while attempting to feed. One adaptation to surmount these barriers involves the evolution of a salivary potion that disarms their host's inflammatory and anti-hemostatic processes. The composition of the peptide moiety of this potion, or sialome (from the Greek sialo = saliva), can be deducted in part by proper interpretation of the blood feeder' sialotranscriptome. In this work we disclose the sialome of the blood feeding adult female Tabanus bromius. Following assembly of over 75 million Illumina reads (101 nt long) 16,683 contigs were obtained from which 4078 coding sequences were extracted. From these, 320 were assigned as coding for putative secreted proteins. These 320 contigs mapped 85% of the reads. The antigen-5 proteins family was studied in detail, indicating three Tabanus specific clades with and without disintegrin domains, as well as with and without leukotriene binding domains. Defensins were also detailed; a clade of salivary tabanid peptides was found lacking the propeptide domain ending in the KR dipeptide signaling furin cleavage. Novel protein families were also disclosed. Viral transcripts were identified closely matching the Kotonkan virus capsid proteins. Full length Mariner transposases were also identified. A total of 3043 coding sequences and their protein products were deposited in Genbank. Hyperlinked excel spread-sheets containing the coding sequences and their annotation are available at http://exon.niaid.nih.gov/transcriptome/Tbromius/Tbromius-web.xlsx (hyperlinked excel spreadsheet, 11 MB) and http://exon.niaid.nih.gov/transcriptome/T_bromius/Tbromius-SA.zip (Standalone excel with all local links, 360 MB). These sequences provide for a platform from which further proteomic studies may be designed to identify salivary proteins from T bromius that are of pharmacological interest or used as immunological markers of host exposure. Published by Elsevier Ltd. C1 [Ribeiro, Jose M. C.; Andersen, John F.; Francischetti, Ivo M. B.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Kazimirova, Maria; Takac, Peter] Slovak Acad Sci, Inst Zool, SK-84506 Bratislava, Slovakia. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jribeiro@nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA [Z01 AI000810-17]; Operational Program of Research and Development; European Fund for Regional Development (EFRD) [ITMS 26240220030] FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA (Grant Z01 AI000810-17) and by the Operational Program of Research and Development and co-financed with the European Fund for Regional Development (EFRD). Grant: ITMS 26240220030: Research and development of new biotherapeutic methods and its application in some illnesses treatment. NR 67 TC 1 Z9 1 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 EI 1879-0240 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD OCT PY 2015 VL 65 BP 83 EP 90 DI 10.1016/j.ibmb.2015.09.002 PG 8 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA CV9PJ UT WOS:000364618800010 PM 26369729 ER PT J AU Scholz, SW Bras, J AF Scholz, Sonja W. Bras, Jose TI Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE atypical parkinsonism; multiple system atrophy; dementia with Lewy bodies; progressive supranuclear palsy; corticobasal degeneration ID MULTIPLE-SYSTEM ATROPHY; PROGRESSIVE SUPRANUCLEAR PALSY; MIMICKING CORTICOBASAL DEGENERATION; SWOLLEN ACHROMATIC NEURONS; CREUTZFELDT-JAKOB-DISEASE; NIEMANN-PICK-DISEASE; LEWY BODY DISEASE; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; FAMILIAL DEMENTIA AB Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions. C1 [Scholz, Sonja W.] NINDS, Neurodegenerat Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Scholz, Sonja W.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. [Bras, Jose] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. RP Scholz, SW (reprint author), NINDS, Neurodegenerat Dis Res Unit, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM sonja.scholz@nih.gov; j.bras@ucl.ac.uk OI Bras, Jose/0000-0001-8186-0333; Scholz, Sonja/0000-0002-6623-0429 FU Intramural Research Program of the U.S. National Institutes of Health, National Institute of Neurological Disorders and Stroke; National Institute of Neurological Disorders and Stroke [R25 NS065729]; Alzheimer's Society Research Fellowship FX Sonja W. Scholz reports that this work was supported (in part) by the Intramural Research Program of the U.S. National Institutes of Health, National Institute of Neurological Disorders and Stroke. Scholz received a R25 career development grant by the National Institute of Neurological Disorders and Stroke (grant number: R25 NS065729). Jose Bras is supported by an Alzheimer's Society Research Fellowship. NR 211 TC 3 Z9 3 U1 1 U2 4 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 OCT PY 2015 VL 16 IS 10 BP 24629 EP 24655 DI 10.3390/ijms161024629 PG 27 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA CV4JD UT WOS:000364232100081 PM 26501269 ER PT J AU Colpe, LJ Naifeh, JA Aliaga, PA Sampson, NA Heeringa, SG Stein, MB Ursano, RJ Fullerton, CS Nock, MK Schoenbaum, ML Zaslavsky, AM Kessler, RC AF Colpe, Lisa J. Naifeh, James A. Aliaga, Pablo A. Sampson, Nancy A. Heeringa, Steven G. Stein, Murray B. Ursano, Robert J. Fullerton, Carol S. Nock, Matthew K. Schoenbaum, Michael L. Zaslavsky, Alan M. Kessler, Ronald C. CA Army STARRS Collaboratos TI Mental Health Treatment Among Soldiers With Current Mental Disorders in the Army Study to Assess Risk and Resilience in Service Members (Army STARRS) SO MILITARY MEDICINE LA English DT Article ID COMORBIDITY SURVEY REPLICATION; INTERVIEW SCREENING SCALES; SELF-REPORTED USE; UNITED-STATES; ACTIVE-DUTY; ADMINISTRATIVE RECORDS; PERCEIVED NEED; SUBSTANCE USE; HELP-SEEKING; PRIMARY-CARE AB A representative sample of 5,428 nondeployed Regular Army soldiers completed a self-administered questionnaire (SAQ) and consented to linking SAQ data with administrative records as part of the Army Study to Assess Risk and Resilience in Service members. The SAQ included information about prevalence and treatment of mental disorders among respondents with current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) internalizing (anxiety, mood) and externalizing (disruptive behavior, substance) disorders. 21.3% of soldiers with any current disorder reported current treatment. Seven significant predictors of being in treatment were identified. Four of these 7 were indicators of psychopathology (bipolar disorder, panic disorder, post-traumatic stress disorder, 8+ months duration of disorder). Two were sociodemographics (history of marriage, not being non-Hispanic Black). The final predictor was history of deployment. Treatment rates varied between 4.7 and 71.5% depending on how many positive predictors the soldier had. The vast majority of soldiers had a low number of these predictors. These results document that most nondeployed soldiers with mental disorders are not in treatment and that untreated soldiers are not concentrated in a particular segment of the population that might be targeted for special outreach efforts. Analysis of modifiable barriers to treatment is needed to help strengthen outreach efforts. C1 [Colpe, Lisa J.; Schoenbaum, Michael L.] NIMH, Off Clin & Populat Epidemiol Res, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Naifeh, James A.; Aliaga, Pablo A.; Ursano, Robert J.; Fullerton, Carol S.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat & Family & Prevent Med, La Jolla, CA 92037 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA 92108 USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Colpe, LJ (reprint author), NIMH, Off Clin & Populat Epidemiol Res, Div Serv & Intervent Res, Room 7148,Mailstop 9635,6001 Execut Blvd, Bethesda, MD 20892 USA. RI Wessely, Simon/A-8713-2008 FU Department of the Army; U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health [U01MH087981] FX Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health. NR 43 TC 1 Z9 1 U1 2 U2 5 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD OCT PY 2015 VL 180 IS 10 BP 1041 EP 1051 DI 10.7205/MILMED-D-14-00686 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CV9UP UT WOS:000364632900015 PM 26444466 ER PT J AU Satishkumar, S Vuram, PK Relangi, SS Gurram, V Zhou, H Kreitman, RJ Montemayor, MMM Yang, LJ Kaliyaperumal, M Sharma, S Pottabathini, N Lakshman, MK AF Satishkumar, Sakilam Vuram, Prasanna K. Relangi, Siva Subrahmanyam Gurram, Venkateshwarlu Zhou, Hong Kreitman, Robert J. Montemayor, Michelle M. Martinez Yang, Lijia Kaliyaperumal, Muralidharan Sharma, Somesh Pottabathini, Narender Lakshman, Mahesh K. TI Cladribine Analogues via O-6-(Benzotriazolyl) Derivatives of Guanine Nucleosides SO MOLECULES LA English DT Article DE cladribine; nucleoside; guanosine; benzotriazole; (benzotriazol-1yl-oxy)-tris(dimethylamino)phosphonium hexafluorophosphate; BOP ID ACID RELATED-COMPOUNDS; SODIUM-SALT GLYCOSYLATION; TERT-BUTYL NITRITE; 2-CHLORO-2'-DEOXYADENOSINE CLADRIBINE; MICROBIOLOGICAL TRANSGLYCOSYLATION; NONAQUEOUS DIAZOTIZATION; DEOXYADENOSINE ANALOGS; SUBSTRATE-SPECIFICITY; PURINE NUCLEOSIDES; DIRECT AMINATION AB Cladribine, 2-chloro-2-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O-6-(benzotriazol-1-yl)-2-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active. C1 [Satishkumar, Sakilam; Vuram, Prasanna K.; Yang, Lijia; Lakshman, Mahesh K.] CUNY City Coll, Dept Chem, New York, NY 10031 USA. [Satishkumar, Sakilam; Vuram, Prasanna K.; Yang, Lijia; Lakshman, Mahesh K.] CUNY, New York, NY 10031 USA. [Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender] GVK Biosci Pvt Ltd, Discovery & Analyt Serv, Hyderabad 500076, Andhra Pradesh, India. [Zhou, Hong; Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Montemayor, Michelle M. Martinez] Univ Cent Caribe, Sch Med, Dept Biochem, Bayamon, PR 00960 USA. RP Lakshman, MK (reprint author), CUNY City Coll, Dept Chem, 160 Convent Ave, New York, NY 10031 USA. EM ssakilam@ccny.cuny.edu; vkumar@ccny.cuny.edu; siva.relangi@gvkbio.com; venkateshwarlu.gurram@gvkbio.com; hong.zhou@nih.gov; kreitmar@mail.nih.gov; mmmtz92@gmail.com; lyang@sci.ccny.cuny.edu; muralidharan.k@gvkbio.com; somesh.sharma@gvkbio.com; narender.pottabathini@gvkbio.com; mlakshman@ccny.cuny.edu FU National Science Foundation [CHE-1265687]; National Institutes of Health from the National Institute on General Medical Sciences [SC3GM111171]; Title V PPOHA US Department of Education [P031M105050]; National Institute on Minority Health and Health Disparities Grant [G12MD007603]; GVKBIO FX This work was supported by National Science Foundation Grant CHE-1265687 to MKL, in part by National Institutes of Health Grant SC3GM111171 to MMMM from the National Institute on General Medical Sciences, and Title V PPOHA US Department of Education P031M105050 to Universidad Central del Caribe. Infrastructural support at CCNY was provided by National Institute on Minority Health and Health Disparities Grant G12MD007603, while that at UCC was provided by G12MD007583. Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Muralidharan Kaliyaperumal, Somesh Sharma, and Narender Pottabathini gratefully acknowledge support from GVKBIO and Siva Subrahmanyam Relangi thanks Anna Venkateswara Rao (Koneru Lakshmaiah University, Guntur (Andhra Pradesh), India) for his support. NR 51 TC 1 Z9 1 U1 2 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD OCT PY 2015 VL 20 IS 10 BP 18437 EP 18463 DI 10.3390/molecules201018437 PG 27 WC Chemistry, Organic SC Chemistry GA CV4IU UT WOS:000364231200041 PM 26556315 ER PT J AU Green, ED Watson, JD Collins, FS AF Green, Eric D. Watson, James D. Collins, Francis S. TI Twenty-five years of big biology SO NATURE LA English DT Editorial Material C1 [Green, Eric D.] US Natl Inst Hlth, US Natl Human Genome Res Inst, Bethesda, MD 20892 USA. [Watson, James D.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Watson, James D.] US Natl Ctr Human Genome Res, Kansas City, KS USA. [Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD USA. [Collins, Francis S.] US Natl Human Genome Res Inst, Bethesda, MD USA. RP Green, ED (reprint author), US Natl Inst Hlth, US Natl Human Genome Res Inst, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov; collinsf@mail.nih.gov NR 8 TC 14 Z9 15 U1 5 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 1 PY 2015 VL 526 IS 7571 BP 29 EP 31 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100015 PM 26432225 ER PT J AU Altshuler, DM Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Donnelly, P Eichler, EE Flicek, P Gabriel, SB Gibbs, RA Green, ED Hurles, ME Knoppers, BM Korbel, JO Lander, ES Lee, C Lehrach, H Mardis, ER Marth, GT McVean, GA Nickerson, DA Schmidt, JP Sherry, ST Wang, J Wilson, RK Gibbs, RA Boerwinkle, E Doddapaneni, H Han, Y Korchina, V Kovar, C Lee, S Muzny, D Reid, JG Zhu, YM Wang, J Chang, YQ Feng, Q Fang, XD Guo, XS Jian, M Jiang, H Jin, X Lan, TM Li, GQ Li, JX Li, YR Liu, SM Liu, X Lu, Y Ma, XD Tang, MF Wang, B Wang, GB Wu, HL Wu, RH Xu, X Yin, Y Zhang, DD Zhang, WW Zhao, J Zhao, MR 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Keira Eberle, Michael Humphray, Sean Kahn, Scott Murray, Lisa Shaw, Richard Lameijer, Eric-Wubbo Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. Ding, Li Hall, Ira Ye, Kai Lacroute, Phil Lee, Charles Cerveira, Eliza Malhotra, Ankit Hwang, Jaeho Plewczynski, Dariusz Radew, Kamen Romanovitch, Mallory Zhang, Chengsheng Craig, David W. Homer, Nils Church, Deanna Xiao, Chunlin Sebat, Jonathan Antaki, Danny Bafna, Vineet Michaelson, Jacob Ye, Kenny Devine, Scott E. Gardner, Eugene J. Abecasis, Goncalo R. Kidd, Jeffrey M. Mills, Ryan E. Dayama, Gargi Emery, Sarah Jun, Goo Shi, Xinghua Quitadamo, Andrew Lunter, Gerton McVean, Gil A. Chen, Ken Fan, Xian Chong, Zechen Chen, Tenghui Witherspoon, David Xing, Jinchuan Eichler, Evan E. Chaisson, Mark J. Hormozdiari, Fereydoun Huddleston, John Malig, Maika Nelson, Bradley J. Sudmant, Peter H. Parrish, Nicholas F. Khurana, Ekta Hurles, Matthew E. Blackburne, Ben Lindsay, Sarah J. Ning, Zemin Walter, Klaudia Zhang, Yujun Gerstein, Mark B. 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Louzada, Sandra Massaia, Andrea McCarthy, Shane Ritchie, Graham R. Xue, Yali Yang, Fengtang Gibbs, Richard A. Kovar, Christie Kalra, Divya Hale, Walker Muzny, Donna Reid, Jeffrey G. Wang, Jun Dan, Xu Guo, Xiaosen Li, Guoqing Li, Yingrui Ye, Chen Zheng, Xiaole Altshuler, David M. Flicek, Paul Clarke, Laura Zheng-Bradley, Xiangqun Bentley, David R. Cox, Anthony Humphray, Sean Kahn, Scott Sudbrak, Ralf Albrecht, Marcus W. Lienhard, Matthias Larson, David Craig, David W. Izatt, Tyler Kurdoglu, Ahmet A. Sherry, Stephen T. Xiao, Chunlin Haussler, David Abecasis, Goncalo R. McVean, Gil A. Durbin, Richard M. Balasubramaniam, Senduran Keane, Thomas M. McCarthy, Shane Stalker, James Chakravarti, Aravinda Knoppers, Bartha M. Abecasis, Goncalo R. Barnes, Kathleen C. Beiswanger, Christine Burchard, Esteban G. Bustamante, Carlos D. Cai, Hongyu Cao, Hongzhi Durbin, Richard M. Gerry, Norman P. Gharani, Neda Gibbs, Richard A. Gignoux, Christopher R. Gravel, Simon Henn, Brenna Jones, Danielle Jorde, Lynn Kaye, Jane S. Keinan, Alon Kent, Alastair Kerasidou, Angeliki Li, Yingrui Mathias, Rasika McVean, Gil A. Moreno-Estrada, Andres Ossorio, Pilar N. Parker, Michael Resch, Alissa M. Rotimi, Charles N. Royal, Charmaine D. Sandoval, Karla Su, Yeyang Sudbrak, Ralf Tian, Zhongming Tishkoff, Sarah Toji, Lorraine H. Tyler-Smith, Chris Via, Marc Wang, Yuhong Yang, Huanming Yang, Ling Zhu, Jiayong Bodmer, Walter Bedoya, Gabriel Ruiz-Linares, Andres Cai, Zhiming Gao, Yang Chu, Jiayou Peltonen, Leena Garcia-Montero, Andres Orfao, Alberto Dutil, Julie Martinez-Cruzado, Juan C. Oleksyk, Taras K. Barnes, Kathleen C. Mathias, Rasika A. Hennis, Anselm Watson, Harold McKenzie, Colin Qadri, Firdausi LaRocque, Regina Sabeti, Pardis C. Zhu, Jiayong Deng, Xiaoyan Sabeti, Pardis C. Asogun, Danny Folarin, Onikepe Happi, Christian Omoniwa, Omonwunmi Stremlau, Matt Tariyal, Ridhi Jallow, Muminatou Joof, Fatoumatta Sisay Corrah, Tumani Rockett, Kirk Kwiatkowski, Dominic Kooner, Jaspal Tran Tinh Hien Dunstan, Sarah J. Nguyen Thuy Hang Fonnie, Richard Garry, Robert Kanneh, Lansana Moses, Lina Sabeti, Pardis C. Schieffelin, John Grant, Donald S. Gallo, Carla Poletti, Giovanni Saleheen, Danish Rasheed, Asif Brook, Lisa D. Felsenfeld, Adaml. McEwen, Jean E. Vaydylevich, Yekaterina Green, Eric D. Duncanson, Audrey Dunn, Michael Schloss, Jeffery A. Wang, Jun Yang, Huanming Auton, Adam Brooks, Lisa D. Durbin, Richard M. Garrison, Erik P. Kang, Hyun Min Korbel, Jan O. Marchini, Jonathan L. McCarthy, Shane McVean, Gil A. Abecasis, Goncalo R. CA Genomes Project Consortium TI A global reference for human genetic variation SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; MACULAR DEGENERATION; POPULATION HISTORY; BAYES FACTORS; MUTATION; DISEASE; VARIANT; SUSCEPTIBILITY; INDIVIDUALS AB The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. 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[Kerasidou, Angeliki; Parker, Michael] Univ Oxford, Ethox Ctr, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England. [Mathias, Rasika; Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Ossorio, Pilar N.] Univ Wisconsin, Morgridge Inst Res, Dept Med Hist & Bioeth, Madison, WI 53706 USA. [Ossorio, Pilar N.] Univ Wisconsin, Sch Law, Madison, WI 53706 USA. [Rotimi, Charles N.] NHGRI, US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Royal, Charmaine D.] Duke Univ, Dept African & African Amer Studies, Durham, NC 27708 USA. [Tishkoff, Sarah] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Via, Marc] Univ Barcelona, Dept Psychiat & Clin Psychobiol, Barcelona 08035, Spain. [Via, Marc] Univ Barcelona, Inst Brain Cognit & Behav IR3C, Barcelona 08035, Spain. [Bodmer, Walter] Univ Oxford, John Radcliffe Hosp, Canc & Immunogenet Lab, Oxford OX3 9DS, England. [Bedoya, Gabriel] Univ Antioquia, Inst Biol, Lab Mol Genet, Medellin, Colombia. 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[Asogun, Danny] Irrua Specialist Teaching Hosp, Edo, Edo State, Nigeria. [Folarin, Onikepe; Happi, Christian; Omoniwa, Omonwunmi] Redeemers Univ, Ede, Ogun State, Nigeria. [Happi, Christian; Omoniwa, Omonwunmi] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Jallow, Muminatou; Joof, Fatoumatta Sisay; Corrah, Tumani; Rockett, Kirk; Kwiatkowski, Dominic] MRC Unit, Banjul, Gambia. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, NHLI, Hammersmith Hosp, London SW7 2AZ, England. [Tran Tinh Hien; Dunstan, Sarah J.; Nguyen Thuy Hang] Univ Oxford, Clin Res Unit, Ctr Trop Med, Ho Chi Minh City, Vietnam. [Dunstan, Sarah J.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3000, Australia. [Fonnie, Richard; Kanneh, Lansana; Grant, Donald S.] Kenema Govt Hosp, Minist Hlth & Sanitat, Kenema, Sierra Leone. [Garry, Robert; Moses, Lina; Schieffelin, John; Grant, Donald S.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Gallo, Carla; Poletti, Giovanni] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Invest & Desarrollo, Lima, Peru. [Saleheen, Danish; Rasheed, Asif] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Brook, Lisa D.; Felsenfeld, Adaml.; McEwen, Jean E.; Vaydylevich, Yekaterina; Schloss, Jeffery A.; Brooks, Lisa D.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Duncanson, Audrey; Dunn, Michael] Wellcome Trust Res Labs, London NW1 2BE, England. [Yang, Huanming] James D Watson Inst Genome Sci, Hangzhou 310008, Zhejiang, Peoples R China. RP Auton, A (reprint author), Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. EM goncalo@umich.edu; adam.auton@gmail.com RI Alkan, Can/D-2982-2009; Schaffner, Stephen/D-1189-2011; Ye, Kai/B-3640-2012; Wang, Jun/C-8434-2016; Browning, Sharon/B-1530-2008; Lunter, Gerton/H-4939-2016; Browning, Brian/A-1178-2010; Li, Heng/D-9344-2011; Coin, Lachlan/A-9001-2014; Mu, Xinmeng/P-2562-2016; Mills, Ryan/A-1979-2011; Kahveci, Fatma/E-1621-2017; Jun, Goo/F-1941-2017; Wang, Jun/B-9503-2016; Myers, Simon/A-6792-2015; Colonna, Vincenza/H-2021-2014; OI Alkan, Can/0000-0002-5443-0706; Wang, Jun/0000-0002-8540-8931; Browning, Sharon/0000-0001-7251-9715; Browning, Brian/0000-0001-6454-6633; Li, Heng/0000-0003-4874-2874; Coin, Lachlan/0000-0002-4300-455X; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Kahveci, Fatma/0000-0003-3096-1753; Jun, Goo/0000-0003-0891-0204; Sisu, Cristina/0000-0001-9371-0797; Datta, Avik/0000-0002-1411-8638; Fitzgerald, Tomas/0000-0002-2370-8496; Vaughan, Brendan/0000-0002-2199-1267; /0000-0002-6086-3903; Garner, John/0000-0003-0853-0279; Meiers, Sascha/0000-0003-2609-0000; Thormann, Anja/0000-0001-8858-5506; Kretzschmar, Warren/0000-0002-2575-0807; Fuchsberger, Christian/0000-0002-5918-8947; Leinonen, Rasko/0000-0002-2639-7187; Hunt, Sarah/0000-0002-8350-1235; Horn, Heiko/0000-0003-4898-0557; Cooper, David N./0000-0002-8943-8484; Sebat, Jonathan/0000-0002-9087-526X; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Sudmant, Peter/0000-0002-9573-8248; Gil, Laurent/0000-0002-9475-4502; Gerstein, Mark/0000-0002-9746-3719; Lindsay, Sarah/0000-0002-0965-3070; Wang, Jun/0000-0002-2113-5874; Myers, Simon/0000-0002-2585-9626; Lunter, Gerton/0000-0002-3798-2058; Lappalainen, Tuuli/0000-0002-7746-8109; Chen, Tenghui/0000-0003-0683-8974; Chen, Jieming/0000-0003-3767-9486; Colonna, Vincenza/0000-0002-3966-0474; Cerezo Fernandez, Maria/0000-0003-3073-1130; Herrero, Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; Swaroop, Anand/0000-0002-1975-1141; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Dunham, Ian/0000-0003-2525-5598; Martin, Alicia/0000-0003-0241-3522; McCarthy, Shane/0000-0002-2715-4187; Dunstan, Sarah/0000-0001-7873-933X; Kwiatkowski, Dominic/0000-0002-5023-0176; Raeder, Benjamin/0000-0002-9494-8884; Iqbal, Zamin/0000-0001-8466-7547; Keane, Thomas/0000-0001-7532-6898; Zerbino, Daniel/0000-0001-5350-3056; Stegle, Oliver/0000-0002-8818-7193; Abyzov, Alexej/0000-0001-5405-6729; Via, Marc/0000-0002-9966-9921; Rodriguez-Flores, Juan L/0000-0002-0394-8062; Parrish, Nicholas/0000-0002-6971-8016; Ayub, Qasim/0000-0003-3291-0917; Mendez, Fernando/0000-0002-0879-3813 FU Wellcome Trust [090532/Z/09/Z, 095552/Z/11/Z, WT098051, WT095908, WT109497, WT086084/Z/08/Z, WT100956/Z/13/Z, WT097307, WT0855322/Z/08/Z, WT090770/Z/09/Z, 089276/Z.09/Z]; Medical Research Council UK [G0801823]; UK Biotechnology and Biological Sciences Research Council [BB/I02593X/1, BB/I021213/1]; British Heart Foundation; Monument Trust; European Molecular Biology Laboratory; European Research Council [617306]; Chinese 863 Program [2012AA02A201]; National Basic Research program of China 973 program [2011CB809201, 2011CB809202, 2011CB809203]; Natural Science Foundation of China [31161130357]; Shenzhen Municipal Government of China [ZYC201105170397A]; Canadian Institutes of Health Research [136855]; Canada Research Chair; Le Fonds de Recherche du Quebec-Sante (FRQS); Genome Quebec; Ontario Ministry of Research and Innovation - Ontario Institute for Cancer Research Investigator Award; Quebec Ministry of Economic Development, Innovation, and Exports [PSR-SIIRI-195]; German Federal Ministry of Education and Research (BMBF) [0315428A, 01GS08201]; Max Planck Society; BMBF-EPITREAT [0316190A]; German Research Foundation (Deutsche Forschungsgemeinschaft) [KO4037/1-1]; Beatriu de Pinos Program [2006 BP-A 10144, 2009 BP-B 00274]; Spanish National Institute for Health Research [PRB2 IPT13/0001-ISCIII-SGEFI/FEDER]; Ewha Womans University; Japan Society for the Promotion of Science [PE13075]; Louis Jeantet Foundation; Marie Curie Actions Career Integration grant [303772]; Swiss National Science Foundation [31003A_130342]; NCCR "Frontiers in Genetics"; University of Geneva; US National Institutes of Health National Center for Biotechnology Information; Harvard Medical School Eleanor and Miles Shore Fellowship; Lundbeck Foundation [R170-2014-1039]; NIJ [2014-DN-BX-K089]; Mary Beryl Patch Turnbull Scholar Program; NSF Graduate Research Fellowship [DGE-1147470]; Simons Foundation SFARI [SF51]; Sloan Foundation; [U54HG3067]; [U54HG3273]; [U01HG5211]; [U54HG3079]; [R01HG2898]; [R01HG2385]; [RC2HG5552]; [U01HG6513]; [U01HG5214]; [U01HG5715]; [U01HG5718]; [U01HG5728]; [U41HG7635]; [U41HG7497]; [R01HG4960]; [R01HG5701]; [R01HG5214]; [R01HG6855]; [R01HG7068]; [R01HG7644]; [DP2OD6514]; [DP5OD9154]; [R01CA166661]; [R01CA172652]; [P01GM99568]; [R01GM59290]; [R01GM104390]; [T32GM7790]; [R01HL87699]; [R01HL104608]; [T32HL94284]; [HHSN268201100040C]; [HHSN272201000025C] FX We thank the many people who were generous with contributing their samples to the project: the African Caribbean in Barbados; Bengali in Bangladesh; British in England and Scotland; Chinese Dai in Xishuangbanna, China; Colombians in Medellin, Colombia; Esan in Nigeria; Finnish in Finland; Gambian in Western Division - Mandinka; Gujarati Indians in Houston, Texas, USA; Han Chinese in Beijing, China; Iberian populations in Spain; Indian Telugu in the UK; Japanese in Tokyo, Japan; Kinh in Ho Chi Minh City, Vietnam; Luhya in Webuye, Kenya; Mende in Sierra Leone; people with African ancestry in the southwest USA; people with Mexican ancestry in Los Angeles, California, USA; Peruvians in Lima, Peru; Puerto Ricans in Puerto Rico; Punjabi in Lahore, Pakistan; southern Han Chinese; Sri Lankan Tamil in the UK; Toscani in Italia; Utah residents (CEPH) with northern and western European ancestry; and Yoruba in Ibadan, Nigeria. Many thanks to the people who contributed to this project: P. Maul, T. Maul, and C. Foster; Z. Chong, X. Fan, W. Zhou, and T. Chen; N. Sengamalay, S. Ott, L. Sadzewicz, J. Liu, and L. Tallon; L. Merson; O. Folarin, D. Asogun, O. Ikpwonmosa, E. Philomena, G. Akpede, S. Okhobgenin, and O. Omoniwa; the staff of the Institute of Lassa Fever Research and Control (ILFRC), Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; A. Schlattl and T. Zichner; S. Lewis, E. Appelbaum, and L. Fulton; A. Yurovsky and I. Padioleau; N. Kaelin and F. Laplace; E. Drury and H. Arbery; A. Naranjo, M. Victoria Parra, and C. Duque; S. Dokel, B. Lenz, and S. Schrinner; S. Bumpstead; and C. Fletcher-Hoppe. Funding for this work was from the Wellcome Trust Core Award 090532/Z/09/Z and Senior Investigator Award 095552/Z/11/Z (P. D.), and grants WT098051 (R.D.), WT095908 and WT109497 (P. F.), WT086084/Z/08/Z and WT100956/Z/13/Z (G. M.), WT097307 (W.K.), WT0855322/Z/08/Z (R.L.), WT090770/Z/09/Z (D.K.), the Wellcome Trust Major Overseas program in Vietnam grant 089276/Z.09/Z (S. D.), the Medical Research Council UK grant G0801823 (J. L. M.), the UK Biotechnology and Biological Sciences Research Council grants BB/I02593X/1 (G. M.) and BB/I021213/1 (A.R.L.), the British Heart Foundation (C. A. A.), the Monument Trust (J. H.), the European Molecular Biology Laboratory (P. F.), the European Research Council grant 617306 (J. L. M.), the Chinese 863 Program 2012AA02A201, the National Basic Research program of China 973 program no. 2011CB809201, 2011CB809202 and 2011CB809203, Natural Science Foundation of China 31161130357, the Shenzhen Municipal Government of China grant ZYC201105170397A (J. W.), the Canadian Institutes of Health Research Operating grant 136855 and Canada Research Chair (S. G.), Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (M.K.D.), a Le Fonds de Recherche du Quebec-Sante (FRQS) research fellowship (A. H.), Genome Quebec (P. A.), the Ontario Ministry of Research and Innovation - Ontario Institute for Cancer Research Investigator Award (P. A., J. S.), the Quebec Ministry of Economic Development, Innovation, and Exports grant PSR-SIIRI-195 (P. A.), the German Federal Ministry of Education and Research (BMBF) grants 0315428A and 01GS08201 (R.H.), the Max Planck Society (H. L., G. M., R.S.), BMBF-EPITREAT grant 0316190A (R.H., M. L.), the German Research Foundation (Deutsche Forschungsgemeinschaft) Emmy Noether Grant KO4037/1-1 (J.O.K.), the Beatriu de Pinos Program grants 2006 BP-A 10144 and 2009 BP-B 00274 (M.V.; ), the Spanish National Institute for Health Research grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER (A. O.), Ewha Womans University (C. L.), the Japan Society for the Promotion of Science Fellowship number PE13075 (N. P.), the Louis Jeantet Foundation (E. T. D.), the Marie Curie Actions Career Integration grant 303772 (C. A.), the Swiss National Science Foundation 31003A_130342 and NCCR "Frontiers in Genetics" (E. T. D.), the University of Geneva (E. T. D., T. L., G. M.), the US National Institutes of Health National Center for Biotechnology Information (S. S.) and grants U54HG3067 (E. S. L.), U54HG3273 and U01HG5211 (R.A.G.), U54HG3079 (R.K.W., E.R.M.), R01HG2898 (S. E. D.), R01HG2385 (E. E. E.), RC2HG5552 and U01HG6513 (G. T. M., G.R.A.), U01HG5214 (A. C.), U01HG5715 (C. D. B.), U01HG5718 (M. G.), U01HG5728 (Y.X.F.), U41HG7635 (R.K.W., E. E. E., P. H. S.), U41HG7497 (C. L., M. A. B., K.C., L. D., E. E. E., M. G., J.O.K., G. T. M., S. A. M., R.E.M., J. L. S., K.Y.), R01HG4960 and R01HG5701 (B. L. B.), R01HG5214 (G. A.), R01HG6855 (S. M.), R01HG7068 (R.E.M.), R01HG7644 (R.D.H.), DP2OD6514(P. S.), DP5OD9154 (J.K.), R01CA166661 (S. E. D.), R01CA172652 (K.C.), P01GM99568 (S.R.B.), R01GM59290 (L. B. J., M. A. B.), R01GM104390 (L. B. J., M.Y.Y.), T32GM7790 (C. D. B., A.R.M.), P01GM99568 (S.R.B.), R01HL87699 and R01HL104608 (K.C.B.), T32HL94284 (J.L.R.F.), and contracts HHSN268201100040C (A.M.R.) and HHSN272201000025C (P. S.), Harvard Medical School Eleanor and Miles Shore Fellowship (K.L.), Lundbeck Foundation Grant R170-2014-1039 (K.L.), NIJ Grant 2014-DN-BX-K089 (Y.E.), the Mary Beryl Patch Turnbull Scholar Program (K.C. B.), NSF Graduate Research Fellowship DGE-1147470 (G. D. P.), the Simons Foundation SFARI award SF51 (M. W.), and a Sloan Foundation Fellowship (R.D. H.). E. E. E. is an investigator of the Howard Hughes Medical Institute. NR 37 TC 229 Z9 231 U1 57 U2 156 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 1 PY 2015 VL 526 IS 7571 BP 68 EP + DI 10.1038/nature15393 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100036 ER PT J AU Sudmant, PH Rausch, T Gardner, EJ Handsaker, RE Abyzov, A Huddleston, J Zhang, Y Ye, K Jun, G Fritz, MHY Konkel, MK Malhotra, A Stutz, AM Shi, XH Casale, FP Chen, JM Hormozdiari, F Dayama, G Chen, K Malig, M Chaisson, MJP Walter, K Meiers, S Kashin, S Garrison, E Auton, A Lam, HYK Mu, XJ Alkan, C Antaki, D Bae, T Cerveira, E Chines, P Chong, ZC Clarke, L Dal, E Ding, L Emery, S Fan, X Gujral, M Kahveci, F Kidd, JM Kong, Y Lameijer, EW McCarthy, S Flicek, P Gibbs, RA Marth, G Mason, CE Menelaou, A Muzny, DM Nelson, BJ Noor, A Parrish, NF Pendleton, M Quitadamo, A Raeder, B Schadt, EE Romanovitch, M Schlattl, A Sebra, R Shabalin, AA Untergasser, A Walker, JA Wang, M Yu, FL Zhang, CS Zhang, J Zheng-Bradley, X Zhou, WD Zichner, T Sebat, J Batzer, MA McCarroll, SA Mills, RE Gerstein, MB Bashir, A Stegle, O Devine, SE Lee, C Eichler, EE Korbel, JO AF Sudmant, Peter H. Rausch, Tobias Gardner, Eugene J. Handsaker, Robert E. Abyzov, Alexej Huddleston, John Zhang, Yan Ye, Kai Jun, Goo Fritz, Markus Hsi-Yang Konkel, Miriam K. Malhotra, Ankit Stuetz, Adrian M. Shi, Xinghua Casale, Francesco Paolo Chen, Jieming Hormozdiari, Fereydoun Dayama, Gargi Chen, Ken Malig, Maika Chaisson, Mark J. P. Walter, Klaudia Meiers, Sascha Kashin, Seva Garrison, Erik Auton, Adam Lam, Hugo Y. K. Mu, Xinmeng Jasmine Alkan, Can Antaki, Danny Bae, Taejeong Cerveira, Eliza Chines, Peter Chong, Zechen Clarke, Laura Dal, Elif Ding, Li Emery, Sarah Fan, Xian Gujral, Madhusudan Kahveci, Fatma Kidd, Jeffrey M. Kong, Yu Lameijer, Eric-Wubbo McCarthy, Shane Flicek, Paul Gibbs, Richard A. Marth, Gabor Mason, Christopher E. Menelaou, Androniki Muzny, Donna M. Nelson, Bradley J. Noor, Amina Parrish, Nicholas F. Pendleton, Matthew Quitadamo, Andrew Raeder, Benjamin Schadt, Eric E. Romanovitch, Mallory Schlattl, Andreas Sebra, Robert Shabalin, Andrey A. Untergasser, Andreas Walker, Jerilyn A. Wang, Min Yu, Fuli Zhang, Chengsheng Zhang, Jing Zheng-Bradley, Xiangqun Zhou, Wanding Zichner, Thomas Sebat, Jonathan Batzer, Mark A. McCarroll, Steven A. Mills, Ryan E. Gerstein, Mark B. Bashir, Ali Stegle, Oliver Devine, Scott E. Lee, Charles Eichler, Evan E. Korbel, Jan O. CA Genomes Project Consortium TI An integrated map of structural variation in 2,504 human genomes SO NATURE LA English DT Article ID COPY NUMBER VARIATION; INDIVIDUAL HUMAN GENOME; CNVS; TRANSCRIPTOME; MECHANISMS; INSIGHTS; DATABASE; REGIONS; IMPACT AB Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association. C1 [Sudmant, Peter H.; Huddleston, John; Hormozdiari, Fereydoun; Malig, Maika; Chaisson, Mark J. P.; Nelson, Bradley J.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Rausch, Tobias; Fritz, Markus Hsi-Yang; Stuetz, Adrian M.; Meiers, Sascha; Raeder, Benjamin; Schlattl, Andreas; Untergasser, Andreas; Zichner, Thomas; Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany. [Gardner, Eugene J.; Devine, Scott E.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Handsaker, Robert E.; Kashin, Seva; McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Handsaker, Robert E.; Kashin, Seva; McCarroll, Steven A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Abyzov, Alexej; Bae, Taejeong] Mayo Clin, Ctr Individualized Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Huddleston, John; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Zhang, Yan; Chen, Jieming; Mu, Xinmeng Jasmine; Zhang, Jing; Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Zhang, Yan; Zhang, Jing; Gerstein, Mark B.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Ye, Kai; Ding, Li; Genomes Project Consortium] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA. [Ye, Kai; Ding, Li] Washington Univ, Dept Genet, St Louis, MO 63108 USA. [Jun, Goo; Kidd, Jeffrey M.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Jun, Goo; Kidd, Jeffrey M.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Jun, Goo] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA. [Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Malhotra, Ankit; Cerveira, Eliza; Romanovitch, Mallory; Zhang, Chengsheng; Lee, Charles] Jackson Lab Genom Med, Farmington, CT 06030 USA. [Shi, Xinghua; Quitadamo, Andrew] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA. [Casale, Francesco Paolo; Clarke, Laura; Flicek, Paul; Zheng-Bradley, Xiangqun; Stegle, Oliver; Korbel, Jan O.] European Mol Biol Lab, EBI, Cambridge CB10 1SD, England. [Chen, Jieming] Yale Univ, Integrated Grad Program Phys & Engn Biol, New Haven, CT 06520 USA. [Dayama, Gargi; Mills, Ryan E.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Chen, Ken; Chong, Zechen; Fan, Xian; Zhou, Wanding] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Walter, Klaudia; McCarthy, Shane] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Garrison, Erik; Marth, Gabor] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Auton, Adam; Kong, Yu] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Lam, Hugo Y. K.] Bina Technol, Roche Sequencing, Redwood City, CA 94065 USA. [Mu, Xinmeng Jasmine] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA. [Alkan, Can; Dal, Elif; Kahveci, Fatma] Bilkent Univ, Dept Comp Engn, TR-06800 Ankara, Turkey. [Antaki, Danny; Gujral, Madhusudan; Noor, Amina; Sebat, Jonathan] Univ Calif San Diego, La Jolla, CA 92093 USA. [Chines, Peter] NHGRI, NIH, Bethesda, MD 20892 USA. [Ding, Li] Washington Univ, Dept Med, St Louis, MO 63108 USA. [Ding, Li] Siteman Canc Ctr, St Louis, MO 63110 USA. [Emery, Sarah; Kidd, Jeffrey M.; Mills, Ryan E.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Lameijer, Eric-Wubbo] Leiden Univ, Med Ctr, Mol Epidemiol, NL-2300 RA Leiden, Netherlands. [Gibbs, Richard A.; Wang, Min; Yu, Fuli] Baylor Coll Med, Houston, TX 77030 USA. [Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Mason, Christopher E.] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA. [Mason, Christopher E.] Weill Cornell Med Coll, Feil Family Brain & Mind Res Inst, New York, NY 10065 USA. [Menelaou, Androniki] Univ Oxford, Oxford OX3 9DS, England. [Menelaou, Androniki] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, NL-3584 CG Utrecht, Netherlands. [Muzny, Donna M.; Pendleton, Matthew; Schadt, Eric E.; Sebra, Robert; Bashir, Ali] Icahn Sch Med Mt Sinai, New York Sch Nat Sci, Dept Genet & Genom Sci, New York, NY 10029 USA. [Parrish, Nicholas F.] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. [Shabalin, Andrey A.] Virginia Commonwealth Univ, Ctr Biomarker Res & Precis Med, Richmond, VA 23298 USA. [Untergasser, Andreas] Heidelberg Univ, Zentrum Mol Biol, D-69120 Heidelberg, Germany. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA. [Lee, Charles] Ewha Womans Univ, Dept Grad Studies Life Sci, Seoul 120750, South Korea. RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, 3720 15th Ave NE, Seattle, WA 98195 USA. EM eee@gs.washington.edu; korbel@embl.de RI Abyzov, Alexej/M-4284-2013; Alkan, Can/D-2982-2009; Ye, Kai/B-3640-2012; Zhou, Wanding/K-3709-2016; Mu, Xinmeng/P-2562-2016; Mills, Ryan/A-1979-2011; Kahveci, Fatma/E-1621-2017; Jun, Goo/F-1941-2017; OI Abyzov, Alexej/0000-0001-5405-6729; Parrish, Nicholas/0000-0002-6971-8016; Alkan, Can/0000-0002-5443-0706; Zhou, Wanding/0000-0001-9126-1932; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Kahveci, Fatma/0000-0003-3096-1753; Jun, Goo/0000-0003-0891-0204; Zichner, Thomas/0000-0001-9848-7598; Shabalin, Andrey/0000-0003-0309-6821; Stegle, Oliver/0000-0002-8818-7193; Sebat, Jonathan/0000-0002-9087-526X; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Sudmant, Peter/0000-0002-9573-8248; Gerstein, Mark/0000-0002-9746-3719; Bae, Taejeong/0000-0002-4626-3725; Meiers, Sascha/0000-0003-2609-0000; Chen, Jieming/0000-0003-3767-9486; Clarke, Laura/0000-0002-5989-6898; Flicek, Paul/0000-0002-3897-7955; McCarthy, Shane/0000-0002-2715-4187; Raeder, Benjamin/0000-0002-9494-8884 FU NIH [U41HG007497, RO1GM59290, R01HG002898, R01CA166661, P01HG007497, R01HG007068, RR19895, RR029676-01]; Wellcome Trust [WT085532/Z/08/Z, WT104947/Z/14/Z]; German Research Foundation [KO4037/1-1]; European Molecular Biology Laboratory FX We thank M. Hurles, R. Durbin and D. Reich for valuable comments during the preparation of this work, S. Scherer for providing PCR-based inversion genotyping data for the initial calibration of our inversion caller, B. Nelson and V. Benes for technical assistance, and T. Brown and N. Habermann for critical review of the manuscript. The following people are acknowledged for contributing to PacBio sequencing or analysis: E. Patel, S. Lee, H. Doddapaneni, L. Lewis, R. Ruth, Q. Meng, V. Vee, Y. Han, J. Jayaseelan, A. English, J. Korlach, M. Hunkapiller, B. Huttel and R. Reinhardt. We acknowledge the Yale University Biomedical High-Performance Computing Center and high-performance compute infrastructure made available through the EMBL and EMBL-EBI IT facilities. We thank the people generously contributing samples to the 1000 Genomes Project. Funding for this research project came from the following grants: NIH U41HG007497 (to C.L., E. E. E., J.O.K., M. A. B., M.G., S. A. M., R. E. M. and J. S.), RO1GM59290 (M. A. B.), R01HG002898 (S. E. D.) and R01CA166661 (S. E. D.), P01HG007497 (to E. E. E.), R01HG007068 (to R. E. M.), RR19895 and RR029676-01 (to M.B.G.), Wellcome Trust WT085532/Z/08/Z and WT104947/Z/14/Z (to P.F.), an Emmy Noether Grant from the German Research Foundation (KO4037/1-1, to J.O.K.) and the European Molecular Biology Laboratory. C.L. is on the scientific advisory board (SAB) of BioNano Genomics. E. E. E. is. on the scientific advisory board (SAB) of DNAnexus, Inc. and is a consultant for Kunming University of Science and Technology (KUST) as part of the 1000 China Talent Program. P.F. is on the SAB of Omicia, Inc. C.L. is an Ewha Womans University Distinguished Professor. E. E. E. is an investigator of the Howard Hughes Medical Institute. J.O.K. is a European Research Council investigator. NR 39 TC 93 Z9 94 U1 13 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 1 PY 2015 VL 526 IS 7571 BP 75 EP + DI 10.1038/nature15394 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100037 PM 26432246 ER PT J AU Zheng, HF Forgetta, V Hsu, YH Estrada, K Rosello-Diez, A Leo, PJ Dahia, CL Park-Min, KH Tobias, JH Kooperberg, C Kleinman, A Styrkarsdottir, U Liu, CT Uggla, C Evans, DS Nielson, CM Walter, K Pettersson-Kymmer, U McCarthy, S Eriksson, J Kwan, T Jhamai, M Trajanoska, K Memari, Y Min, J Huang, J Danecek, P Wilmot, B Li, R Chou, WC Mokry, LE Moayyeri, A Claussnitzer, M Cheng, CH Cheung, W Medina-Gomez, C Ge, B Chen, SH Choi, K Oei, L Fraser, J Kraaij, R Hibbs, MA Gregson, CL Paquette, D Hofman, A Wibom, C Tranah, GJ Marshall, M Gardiner, BB Cremin, K Auer, P Hsu, L Ring, S Tung, JY Thorleifsson, G Enneman, AW van Schoor, NM de Groot, LCPGM van der Velde, N Melin, B Kemp, JP Christiansen, C Sayers, A Zhou, YH Calderari, S van Rooij, J Carlson, C Peters, U Berlivet, S Dostie, J Uitterlinden, AG Williams, SR Farber, C Grinberg, D LaCroix, AZ Haessler, J Chasman, DI Giulianini, F Rose, LM Ridker, PM Eisman, JA Nguyen, TV Center, JR Nogues, X Garcia-Giralt, N Launer, LL Gudnason, V Mellstrom, D Vandenput, L Amin, N van Duijn, CM Karlsson, MK Ljunggren, O Svensson, O Hallmans, G Rousseau, F Giroux, S Bussiere, J Arp, PP Koromani, F Prince, RL Lewis, JR Langdahl, BL Hermann, AP Jensen, JEB Kaptoge, S Khaw, KT Reeve, J Formosa, MM Xuereb-Anastasi, A Akesson, K McGuigan, FE Garg, G Olmos, JM Zarrabeitia, MT Riancho, JA Ralston, SH Alonso, N Jiang, X Goltzman, D Pastinen, T Grundberg, E Gauguier, D Orwoll, ES Karasik, D Davey-Smith, G Smith, AV Siggeirsdottir, K Harris, TB Zillikens, MC van Meurs, JBJ Thorsteinsdottir, U Maurano, MT Timpson, NJ Soranzo, N Durbin, R Wilson, S Ntzani, EE Brown, MA Stefansson, K Hinds, DA Spector, T Cupples, LA Ohlsson, C Greenwood, CMT Jackson, RD Rowe, DW Loomis, CA Evans, DM Ackert-Bicknell, CL Joyner, AL Duncan, EL Kiel, DP Rivadeneira, F Richards, JB AF Zheng, Hou-Feng Forgetta, Vincenzo Hsu, Yi-Hsiang Estrada, Karol Rosello-Diez, Alberto Leo, Paul J. Dahia, Chitra L. Park-Min, Kyung Hyun Tobias, Jonathan H. Kooperberg, Charles Kleinman, Aaron Styrkarsdottir, Unnur Liu, Ching-Ti Uggla, Charlotta Evans, Daniel S. Nielson, Carrie M. Walter, Klaudia Pettersson-Kymmer, Ulrika McCarthy, Shane Eriksson, Joel Kwan, Tony Jhamai, Mila Trajanoska, Katerina Memari, Yasin Min, Josine Huang, Jie Danecek, Petr Wilmot, Beth Li, Rui Chou, Wen-Chi Mokry, Lauren E. Moayyeri, Alireza Claussnitzer, Melina Cheng, Chia-Ho Cheung, Warren Medina-Gomez, Carolina Ge, Bing Chen, Shu-Huang Choi, Kwangbom Oei, Ling Fraser, James Kraaij, Robert Hibbs, Matthew A. Gregson, Celia L. Paquette, Denis Hofman, Albert Wibom, Carl Tranah, Gregory J. Marshall, Mhairi Gardiner, Brooke B. Cremin, Katie Auer, Paul Hsu, Li Ring, Sue Tung, Joyce Y. Thorleifsson, Gudmar Enneman, Anke W. van Schoor, Natasja M. de Groot, Lisette C. P. G. M. van der Velde, Nathalie Melin, Beatrice Kemp, John P. Christiansen, Claus Sayers, Adrian Zhou, Yanhua Calderari, Sophie van Rooij, Jeroen Carlson, Chris Peters, Ulrike Berlivet, Soizik Dostie, Josee Uitterlinden, Andre G. Williams, Stephen R. Farber, Charles Grinberg, Daniel LaCroix, Andrea Z. Haessler, Jeff Chasman, Daniel I. Giulianini, Franco Rose, Lynda M. Ridker, Paul M. Eisman, John A. Nguyen, Tuan V. Center, Jacqueline R. Nogues, Xavier Garcia-Giralt, Natalia Launer, Lenore L. Gudnason, Vilmunder Mellstrom, Dan Vandenput, Liesbeth Amin, Najaf van Duijn, Cornelia M. Karlsson, Magnus K. Ljunggren, Osten Svensson, Olle Hallmans, Goran Rousseau, Francois Giroux, Sylvie Bussiere, Johanne Arp, Pascal P. Koromani, Fjorda Prince, Richard L. Lewis, Joshua R. Langdahl, Bente L. Hermann, A. Pernille Jensen, Jens-Erik B. Kaptoge, Stephen Khaw, Kay-Tee Reeve, Jonathan Formosa, Melissa M. Xuereb-Anastasi, Angela Akesson, Kristina McGuigan, Fiona E. Garg, Gaurav Olmos, Jose M. Zarrabeitia, Maria T. Riancho, Jose A. Ralston, Stuart H. Alonso, Nerea Jiang, Xi Goltzman, David Pastinen, Tomi Grundberg, Elin Gauguier, Dominique Orwoll, Eric S. Karasik, David Davey-Smith, George Smith, Albert V. Siggeirsdottir, Kristin Harris, Tamara B. Zillikens, M. Carola van Meurs, Joyce B. J. Thorsteinsdottir, Unnur Maurano, Matthew T. Timpson, Nicholas J. Soranzo, Nicole Durbin, Richard Wilson, ScottG. Ntzani, Evangelia E. Brown, Matthew A. Stefansson, Kari Hinds, David A. Spector, Tim Cupples, L. Adrienne Ohlsson, Claes Greenwood, Celia M. T. Jackson, Rebecca D. Rowe, David W. Loomis, Cynthia A. Evans, David M. Ackert-Bicknell, Cheryl L. Joyner, Alexandra L. Duncan, Emma L. Kiel, Douglas P. Rivadeneira, Fernando Richards, J. Brent CA AOGC Consortium UK10K Consortium TI Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture SO NATURE LA English DT Article ID WIDE ASSOCIATION LOCI; MINERAL DENSITY; COMPLEX TRAITS; HUMAN-DISEASES; VARIANTS; MOUSE; ENGRAILED-1; OSTEOPOROSIS; METAANALYSIS; GENE AB The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population. C1 [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Richards, J. Brent] McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada. [Zheng, Hou-Feng; Forgetta, Vincenzo; Li, Rui; Mokry, Lauren E.; Greenwood, Celia M. T.; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada. [Hsu, Yi-Hsiang; Chou, Wen-Chi; Claussnitzer, Melina; Cheng, Chia-Ho; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Hsu, Yi-Hsiang; Estrada, Karol; Chou, Wen-Chi; Claussnitzer, Melina; Chasman, Daniel I.; Ridker, Paul M.; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hsu, Yi-Hsiang; Estrada, Karol; Claussnitzer, Melina; Kiel, Douglas P.] Broad Inst MIT & Harvard, Boston, MA 02115 USA. [Estrada, Karol; Jhamai, Mila; Trajanoska, Katerina; Medina-Gomez, Carolina; Oei, Ling; Kraaij, Robert; Enneman, Anke W.; van der Velde, Nathalie; van Rooij, Jeroen; Uitterlinden, Andre G.; Arp, Pascal P.; Koromani, Fjorda; Zillikens, M. Carola; van Meurs, Joyce B. J.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Rosello-Diez, Alberto; Joyner, Alexandra L.] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA. [Leo, Paul J.; Marshall, Mhairi; Gardiner, Brooke B.; Cremin, Katie; Kemp, John P.; Brown, Matthew A.; Evans, David M.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Dahia, Chitra L.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA. [Dahia, Chitra L.] Hosp Special Surg, Tissue Engn Regenerat & Repair Program, New York, NY 10021 USA. [Park-Min, Kyung Hyun] Hosp Special Surg, Rheumatol Div, New York, NY 10021 USA. [Tobias, Jonathan H.] Univ Bristol, Sch Clin Sci, Bristol BS10 5NB, Avon, England. [Tobias, Jonathan H.; Min, Josine; Kemp, John P.; Davey-Smith, George; Timpson, Nicholas J.; Evans, David M.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [Kooperberg, Charles; Hsu, Li; Carlson, Chris; Peters, Ulrike; Haessler, Jeff] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kleinman, Aaron; Tung, Joyce Y.; Hinds, David A.] 23andMe, Res Dept, Mountain View, CA 94041 USA. [Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur] deCODE Genet, Dept Populat Genom, IS-101 Reykjavik, Iceland. [Liu, Ching-Ti; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Uggla, Charlotta; Eriksson, Joel; Mellstrom, Dan; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Evans, Daniel S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94158 USA. [Nielson, Carrie M.; Tranah, Gregory J.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Nielson, Carrie M.; Tranah, Gregory J.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA. [Walter, Klaudia; McCarthy, Shane; Memari, Yasin; Huang, Jie; Danecek, Petr; Soranzo, Nicole; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Pettersson-Kymmer, Ulrika] Umea Univ, Dept Pharmacol, S-90187 Umea, Sweden. [Pettersson-Kymmer, Ulrika] Umea Univ, Dept Clin Neurosci, S-90187 Umea, Sweden. [Pettersson-Kymmer, Ulrika; Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden. [Eriksson, Joel] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, S-41345 Gothenburg, Sweden. [Kwan, Tony; Cheung, Warren; Ge, Bing; Chen, Shu-Huang; Pastinen, Tomi; Grundberg, Elin] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Kwan, Tony; Cheung, Warren; Ge, Bing; Chen, Shu-Huang; Pastinen, Tomi; Grundberg, Elin] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. [Trajanoska, Katerina; Medina-Gomez, Carolina; Oei, Ling; Kraaij, Robert; Hofman, Albert; Uitterlinden, Andre G.; Koromani, Fjorda; van Meurs, Joyce B. J.; Rivadeneira, Fernando] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Wilmot, Beth] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97239 USA. [Wilmot, Beth] Oregon Hlth & Sci Univ, Dept Med & Clin Informat, Portland, OR 97239 USA. [Moayyeri, Alireza; Kaptoge, Stephen] UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England. [Moayyeri, Alireza; Wilson, ScottG.; Spector, Tim; Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Claussnitzer, Melina; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Cheung, Warren; Pastinen, Tomi; Grundberg, Elin; Greenwood, Celia M. T.] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada. [Medina-Gomez, Carolina; Oei, Ling; Kraaij, Robert; Hofman, Albert; van Rooij, Jeroen; Uitterlinden, Andre G.; Rivadeneira, Fernando] NCHA, NGI, NL-2300 RC Leiden, Netherlands. [Choi, Kwangbom; Hibbs, Matthew A.; Ackert-Bicknell, Cheryl L.] Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA. [Fraser, James; Paquette, Denis; Berlivet, Soizik; Dostie, Josee] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Fraser, James; Paquette, Denis; Berlivet, Soizik; Dostie, Josee] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada. [Hibbs, Matthew A.] Trinity Univ, Dept Comp Sci, San Antonio, TX 78212 USA. [Gregson, Celia L.; Sayers, Adrian] Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England. [Wibom, Carl; Melin, Beatrice] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. [Auer, Paul] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53726 USA. [Ring, Sue] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Thorleifsson, Gudmar] deCODE Genet, Dept Stat, IS-101 Reykjavik, Iceland. [van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands. [van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1007 MB Amsterdam, Netherlands. [de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 EV Wageningen, Netherlands. [van der Velde, Nathalie] Acad Med Ctr, Sect Geriatr, Dept Internal Med, NL-1105 Amsterdam, Netherlands. [Christiansen, Claus] Nord Biosci, DK-2730 Herlev, Denmark. [Calderari, Sophie; Gauguier, Dominique] INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France. [Calderari, Sophie; Gauguier, Dominique] Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France. [Williams, Stephen R.; Farber, Charles; Nogues, Xavier] Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA. [Williams, Stephen R.; Farber, Charles; Nogues, Xavier] Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA. [Grinberg, Daniel] Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain. [Grinberg, Daniel] Ctr Biomed Network Res Rare Dis CIBERER, U720, Barcelona 28029, Spain. [Grinberg, Daniel] Univ Barcelona, Inst Biomed, Dept Human Mol Genet, E-08028 Barcelona, Spain. [LaCroix, Andrea Z.] Univ Calif San Diego, Womens Hlth Ctr Excellence Family Med & Publ Hlth, San Diego, CA 92103 USA. [Chasman, Daniel I.; Giulianini, Franco; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia. [Eisman, John A.] Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW 6959, Australia. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia. [Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueline R.] NSW Univ, Sch Clin, Sydney, NSW 2010, Australia. [Nogues, Xavier; Garcia-Giralt, Natalia] Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain. [Garcia-Giralt, Natalia] Inst Hlth Carlos III, Cooperat Res Network Aging & Fragil RETICEF, Madrid 28029, Spain. [Nogues, Xavier] Univ Autonoma Barcelona, Hosp Mar, Dept Internal Med, E-08193 Barcelona, Spain. [Launer, Lenore L.] NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA. [Gudnason, Vilmunder; Smith, Albert V.; Siggeirsdottir, Kristin] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Gudnason, Vilmunder; Smith, Albert V.; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Amin, Najaf; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands. [Karlsson, Magnus K.; Akesson, Kristina] Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden. [Ljunggren, Osten] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Svensson, Olle] Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden. [Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ G1V 0A6, Canada. [Rousseau, Francois; Giroux, Sylvie; Bussiere, Johanne] CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada. [Prince, Richard L.; Lewis, Joshua R.; Wilson, ScottG.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. [Prince, Richard L.; Lewis, Joshua R.] Univ Western Australia, Dept Med, Perth, WA 6009, Australia. [Langdahl, Bente L.] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark. [Hermann, A. Pernille] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense C, Denmark. [Jensen, Jens-Erik B.] Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge CB2 2QQ, England. [Reeve, Jonathan] Univ Cambridge, Med & Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Reeve, Jonathan] Univ Oxford, Botnar Res Ctr, Inst Musculoskeletal Sci, Oxford OX3 7LD, England. [Formosa, Melissa M.; Xuereb-Anastasi, Angela] Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta. [Akesson, Kristina; McGuigan, Fiona E.; Garg, Gaurav] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden. [Olmos, Jose M.; Riancho, Jose A.] Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain. [Olmos, Jose M.; Riancho, Jose A.] Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain. [Zarrabeitia, Maria T.] Univ Cantabria, Dept Legal Med, Santander 39011, Spain. [Ralston, Stuart H.; Alonso, Nerea] Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Jiang, Xi; Rowe, David W.] Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA. [Goltzman, David] McGill Univ, Dept Med & Physiol, Montreal, PQ H4A 3J1, Canada. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Karasik, David] Bar Ilan Univ, Fac Med Galilee, IL-13010 Safed, Israel. [Harris, Tamara B.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA. [Maurano, Matthew T.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Wilson, ScottG.] Univ Western Australia, Sch Med & Pharmacol, Crawley 6009, Australia. [Ntzani, Evangelia E.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ntzani, Evangelia E.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA. [Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Greenwood, Celia M. T.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Greenwood, Celia M. T.] McGill Univ, Gerald Bronfman Ctr, Dept Oncol, Montreal, PQ H2W 1S6, Canada. [Jackson, Rebecca D.] Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Loomis, Cynthia A.] NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA. [Loomis, Cynthia A.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. [Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Diabet & Endocrinol, Brisbane, Qld 4029, Australia. RP Richards, JB (reprint author), McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada. EM brent.richards@mcgill.ca RI Smith, Albert Vernon/K-5150-2015; Gudnason, Vilmundur/K-6885-2015; Gardiner, Brooke/C-7773-2011; Fox, Laura /C-6249-2016; Oei, Ling/E-8163-2013; Reeve, Jonathan/C-7551-2012; Rosello Diez, Alberto/K-7295-2016; Davey Smith, George/A-7407-2013; OI Kemp, John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; Gregson, Celia/0000-0001-6414-0529; Timpson, Nicholas/0000-0002-7141-9189; Pettersson Kymmer, Ulrika/0000-0002-0557-9803; Forgetta, Vincenzo/0000-0002-6061-4720; van der Velde, Nathalie/0000-0002-6477-6209; Smith, Albert Vernon/0000-0003-1942-5845; Mellstrom, Dan/0000-0003-2761-3723; Farber, Charles/0000-0002-6748-4711; Soranzo, Nicole/0000-0003-1095-3852; Rivadeneira, Fernando/0000-0001-9435-9441; Karasik, David/0000-0002-8826-0530; Cheung, Warren/0000-0003-0267-7464; Vandenput, Liesbeth/0000-0002-1712-6131; McCarthy, Shane/0000-0002-2715-4187; Medina-Gomez, Carolina/0000-0001-7999-5538; Gudnason, Vilmundur/0000-0001-5696-0084; Gardiner, Brooke/0000-0003-3740-3244; Moayyeri, Alireza/0000-0002-9143-2161; Kiel, Douglas/0000-0001-8474-0310; Center, Jacqueline/0000-0002-5278-4527; Oei, Ling/0000-0003-3523-458X; Reeve, Jonathan/0000-0002-4364-2682; Rosello Diez, Alberto/0000-0002-5550-9846; Davey Smith, George/0000-0002-1407-8314; McKechanie, Andrew/0000-0003-4273-9906; Williams, Stephen/0000-0003-2108-2757 FU Arthritis Research UK [20000]; British Heart Foundation [RG/08/014/24067]; Canadian Institutes of Health Research [119462-1]; Medical Research Council [G0401527, G1000143, MC_PC_15018, MC_UU_12013/1, MC_UU_12013/3, MC_UU_12013/4, MR/L003120/1]; NCI NIH HHS [P30 CA008748, P30 CA015704, UM1 CA182913]; NIA NIH HHS [R01 AG005394, R01 AG005407, R01 AG027574, R01 AG027576, U01 AG018197, U01 AG042140, U01 AG042143]; NIAMS NIH HHS [K01 AR062655, P30 AR057235, R00 AR061430, R01 AR035582, R01 AR035583, R01 AR063702, RC2 AR058973, U01 AR045580, U01 AR045583, U01 AR045614, U01 AR045632, U01 AR045647, U01 AR045654, U01 AR066160]; Wellcome Trust [102215] NR 38 TC 39 Z9 39 U1 13 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 1 PY 2015 VL 526 IS 7571 BP 112 EP + DI 10.1038/nature14878 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100044 PM 26367794 ER PT J AU Lakdawala, SS Jayaraman, A Halpin, RA Lamirande, EW Shih, AR Stockwell, TB Lin, XD Simenauer, A Hanson, CT Vogel, L Paskel, M Minai, M Moore, I Orandle, M Das, SR Wentworth, DE Sasisekharan, R Subbarao, K AF Lakdawala, Seema S. Jayaraman, Akila Halpin, Rebecca A. Lamirande, Elaine W. Shih, Angela R. Stockwell, Timothy B. Lin, Xudong Simenauer, Ari Hanson, Christopher T. Vogel, Leatrice Paskel, Myeisha Minai, Mahnaz Moore, Ian Orandle, Marlene Das, Suman R. Wentworth, David E. Sasisekharan, Ram Subbarao, Kanta TI The soft palate is an important site of adaptation for transmissible influenza viruses SO NATURE LA English DT Article ID HUMAN RESPIRATORY-TRACT; AIRBORNE TRANSMISSION; RECEPTOR SPECIFICITY; A/H5N1 VIRUS; IN-VITRO; A VIRUS; FERRETS; H1N1; HEMAGGLUTININ; PATHOGENESIS AB Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached alpha 2,3 or alpha 2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind alpha 2,6-linked sialic acids whereas avian influenza A viruses bind alpha 2,3-linked sialic acids on complex glycans on airway epithelial cells(1,2). Historically, influenza A viruses with preferential association with alpha 2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets(3,4). Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind alpha 2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain alpha 2,6-linked sialic acids, without loss of alpha 2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain alpha 2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain alpha 2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (alpha 2,6-linked sialic acids) preference. C1 [Lakdawala, Seema S.; Lamirande, Elaine W.; Shih, Angela R.; Hanson, Christopher T.; Vogel, Leatrice; Paskel, Myeisha; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Jayaraman, Akila; Sasisekharan, Ram] MIT, Dept Biol Engn, Koch Inst Integrat Canc Res, Singapore MIT Alliance Res & Technol, Cambridge, MA 02139 USA. [Halpin, Rebecca A.; Stockwell, Timothy B.; Lin, Xudong; Simenauer, Ari; Das, Suman R.; Wentworth, David E.] J Craig Venter Inst, Rockville, MD 20850 USA. [Minai, Mahnaz; Moore, Ian; Orandle, Marlene] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sasisekharan, R (reprint author), MIT, Dept Biol Engn, Koch Inst Integrat Canc Res, Singapore MIT Alliance Res & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rams@mit.edu; ksubbarao@niaid.nih.gov OI Wentworth, David/0000-0002-5190-980X FU Intramural Research Program of NIAID, NIH; NIAID, NIH, DHHS [HHSN272200900007C]; NIAID/NIH Genomic Centers for Infectious Diseases (GCID) program [U19-AI-110819]; NIH Merit Award [R37 GM057073-13]; National Research Foundation supported Interdisciplinary Research group in Infectious Diseases of SMART (Singapore MIT alliance for Research and Technology); Skolkovo Foundation FX This research was supported in part by the Intramural Research Program of NIAID, NIH and with federal funds from NIAID, NIH, DHHS under contract number HHSN272200900007C and NIAID/NIH Genomic Centers for Infectious Diseases (GCID) program (U19-AI-110819). This manuscript was reviewed by the NIH's Intramural Research Program's Committee on Dual Use Research of Concern (DURC), who concluded that the methods and results do not meet DURC criteria. We thank the NIAID Comparative Medical Branch for technical assistance, Subbarao laboratory members for critical input, N. B. Fedorova from JCVI for technical help, X. J. Meng (Virginia Tech College of Veterinary Medicine) and P. Pineyro (Iowa State University) for pig soft palate tissues, and the Consortium for Functional Glycomics for providing glycans for the glycan array analysis. The data for this manuscript and its preparation were generated while D.E.W. was employed at JCVI. The opinions expressed in this article are the authors' own and do not reflect the views of the Centers for Disease Control, the Department of Health and Human Services, or the United States government. A. J. and R.S. are supported in part by NIH Merit Award (R37 GM057073-13), National Research Foundation supported Interdisciplinary Research group in Infectious Diseases of SMART (Singapore MIT alliance for Research and Technology) and the Skolkovo Foundation supported Infectious Diseases Center at MIT. NR 30 TC 15 Z9 15 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 1 PY 2015 VL 526 IS 7571 BP 122 EP + DI 10.1038/nature15379 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CS5CY UT WOS:000362095100046 PM 26416728 ER PT J AU Bozzano, F Marras, F Ascierto, ML Cantoni, C Cenderello, G Dentone, C Di Biagio, A Orofino, G Mantia, E Boni, S De Leo, P Picciotto, A Braido, F Antonini, F Wang, E Marincola, F Moretta, L De Maria, A AF Bozzano, Federica Marras, Francesco Ascierto, Maria Libera Cantoni, Claudia Cenderello, Giovanni Dentone, Chiara Di Biagio, Antonio Orofino, Giancarlo Mantia, Eugenio Boni, Silvia De Leo, Pasqualina Picciotto, Antonino Braido, Fulvio Antonini, Francesca Wang, Ena Marincola, Francesco Moretta, Lorenzo De Maria, Andrea TI 'Emergency exit' of bone-marrow-resident CD34(+)DNAM-1(bright)CXCR4(+) -committed lymphoid precursors during chronic infection and inflammation SO NATURE COMMUNICATIONS LA English DT Article ID NATURAL-KILLER-CELLS; PLASMACYTOID DENDRITIC CELLS; HEMATOPOIETIC STEM-CELLS; NK-CELL; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; RECEPTOR EXPRESSION; CYTOLYTIC FUNCTION; IMMUNE ACTIVATION; HIV-1 INFECTION AB During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34(+)CD226(DNAM-1)(bright)CXCR4(+) cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to alpha/beta T lymphocytes. CD34(+)CD226(bright)CXCR4(+) cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions. C1 [Bozzano, Federica; Cantoni, Claudia] Univ Genoa, Dept Expt Med, I-16132 Genoa, Italy. [Bozzano, Federica; Cantoni, Claudia; De Maria, Andrea] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy. [Marras, Francesco; Cantoni, Claudia; Antonini, Francesca; Moretta, Lorenzo] Ist Giannina Gaslini, I-16148 Genoa, Italy. [Ascierto, Maria Libera; Wang, Ena] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Ascierto, Maria Libera; Wang, Ena] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Ascierto, Maria Libera] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA. [Cenderello, Giovanni] Osped Galliera, UOC Malattie Infett, I-16128 Genoa, Italy. [Dentone, Chiara] Osped Sanremo, UOC Malattie Infett, I-18038 San Remo, Italy. [Di Biagio, Antonio; De Maria, Andrea] Ist Nazl Ric Sul Canc, IRCCS AOU San Martino IST Genova, Clin Malattie Infett, I-16132 Genoa, Italy. [Orofino, Giancarlo] SOC Malattie Infett ASO SS Antonio & Biagio & C A, I-15100 Alessandria, Italy. [Mantia, Eugenio] Osped Amedeo Savoia, UOC Malattie Infett, I-10149 Turin, Italy. [Boni, Silvia] Osped St Andrea, UOC Malattie Infett, I-19121 La Spezia, Italy. [De Leo, Pasqualina] Azienda Sanitaria Locale 2, UOC Malattie Infett, I-17100 Savona, Italy. [Picciotto, Antonino] Univ Genoa, Dept Internal Med, Allergy & Resp Unit, I-16132 Genoa, Italy. [Braido, Fulvio] Univ Genoa, Dept Internal Med, Hepatol Unit, I-16132 Genoa, Italy. [Wang, Ena; Marincola, Francesco] Sidra Med & Res Ctr, Doha, Qatar. [De Maria, Andrea] Univ Genoa, Dept Hlth Sci, DISSAL, I-16132 Genoa, Italy. RP De Maria, A (reprint author), Univ Genoa, Ctr Excellence Biomed Res, Via Pastore 1, I-16132 Genoa, Italy. EM de-maria@unige.it RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X FU Associazione Italiana Ricerca sul Cancro (AIRC): IG [10225]; 'Special Program Molecular Clinical Oncology 5 x 1000' project [9962]; Istituto Superiore di Sanita (I.S.S.), Programma Nazionale di Ricerca sull'AIDS [40H67] FX We wish to acknowledge the help of our patients and of all our colleagues in the clinic caring for them over the years (Dr Giuseppe Ferrea, P.D.L., G.O, Dr G. Mazzarello, Dr C. Viscoli, Dr G. Cassola, Dr E. Pontali, Dr M. Guerra, Dr S. Artioli, Dr F. Bisio, Dr E. Nicco, Dr L. Nicolini), whose help was fundamental to carry out this study. Special thanks to Prof. Guido Ferlazzo for discussion, and to Prof. Alessandro Moretta for suggestions and discussion. We also acknowledge the valuable help of Dr Elisabetta Tedone, Dr Elisa Montaldo and Prof. Franco Locatelli for providing surplus samples from bone marrow donors and from peripheral blood apheresis donors, of Dr Gino Tripodi for providing selected blood donor samples from cohorts characterized for CMV and EBV serology, and Dr S. Sivori for the gift of mAb anti-CCR, and Dr L. Gattorno and Dr Francesca Schena (Istituto G. Gaslini, Genoa, Italy) for collaboration and care for PAPA-syndrome patients. This work was supported by grants awarded by Associazione Italiana Ricerca sul Cancro (AIRC): IG 2010 project n. 10225 (L.M.) and 'Special Program Molecular Clinical Oncology 5 x 1000' project n. 9962 (L.M.); and Istituto Superiore di Sanita (I.S.S.), Programma Nazionale di Ricerca sull'AIDS (2009-10) project n. 40H67 (L.M.). Istituto Superiore di Sanita (I.S.S.): Programma nazionale di ricerca sull'AIDS, Accordi di collaborazione scientifica 45G.11 (A.D.M.), 40H69 (A.D.M.); Ministero della Salute RF-2010-2316197 (A.D.M.). NR 64 TC 1 Z9 1 U1 1 U2 5 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 OCT PY 2015 VL 6 AR 8109 DI 10.1038/ncomms9109 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3VC UT WOS:000364919200001 PM 26436997 ER PT J AU Kaestner, L Wang, J Hertz, L Ruppenthal, S Lipp, P Bimbaumer, L Freichel, M AF Kaestner, L. Wang, J. Hertz, L. Ruppenthal, S. Lipp, P. Bimbaumer, L. Freichel, M. TI Red cell calcium-channelopathies - novel approaches and mechanism SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Kaestner, L.; Wang, J.; Hertz, L.] Res Ctr Mol Imaging & Screening, Homburg, Germany. [Ruppenthal, S.; Lipp, P.] Inst Mol Cell Biol, Homburg, Germany. [Bimbaumer, L.] NIEHS, Res Triangle Pk, NC 27709 USA. [Freichel, M.] Heidelberg Univ, Inst Pharmacol, Heidelberg, Germany. RI Kaestner, Lars/P-6988-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA V351 BP 106 EP 106 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800249 ER PT J AU Balsiger, C Mumm, F Holler, E Herzberg, PY Hilgendorf, I Hemmati, P von Harsdorf, S Greinix, H Mitchell, SA Wolff, D Heussner, P AF Balsiger, C. Mumm, F. Holler, E. Herzberg, P. Y. Hilgendorf, I Hemmati, P. von Harsdorf, S. Greinix, H. Mitchell, S. A. Wolff, D. Heussner, P. TI Correlation between somatic comorbidities and anxiety and depression in patients after allogeneic hematopoietic stem cell transplantation SO Oncology Research and Treatment LA English DT Meeting Abstract C1 [Balsiger, C.; Mumm, F.; Heussner, P.] Univ Munich, Dept Internal Med 3, Klinikum Grasshadern, Munich, Germany. [Mumm, F.; Wolff, D.] Univ Klinikum Regensburg, Dept Internal Med 3, Regensburg, Germany. [Herzberg, P. Y.] Helmut Schmidt Univ, Univ Bundeswehr Hamburg, Dept Personal Psychol & Psychol Assessment, Hamburg, Germany. [Hilgendorf, I] Univ Klinikum Jena, Dept Internal Med 2, Jena, Germany. [Hemmati, P.] Charite, Dept Hematol & Oncol, D-13353 Berlin, Germany. [von Harsdorf, S.] Univ Ulm Klinikum, Dept Internal Med 3, Ulm, Germany. [Greinix, H.] Med Univ Graz, Dept Hematol, Graz, Austria. [Mitchell, S. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2015 VL 38 SU 5 MA P489 BP 148 EP 148 PG 1 WC Oncology SC Oncology GA CV4XC UT WOS:000364268800352 ER PT J AU Moody, TW Moreno, P Jensen, RT AF Moody, Terry W. Moreno, Paola Jensen, Robert T. TI Neuropeptides as lung cancer growth factors SO PEPTIDES LA English DT Article DE Lung cancer; Bombesin; Vasoactive intestinal peptide; Neurotensin ID GASTRIN-RELEASING-PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; CAUSES TYROSINE PHOSPHORYLATION; BOMBESIN-LIKE PEPTIDES; FOCAL ADHESION KINASE; FACTOR RECEPTOR; EGF-RECEPTOR; CELL-LINES; NEUROTENSIN RECEPTOR; CYTOSOLIC CALCIUM AB This manuscript is written in honor of the Festschrift for Abba Kastin. I met Abba at a Society for Neuroscience meeting and learned that he was Editor-in-Chief of the Journal Peptides. I submitted manuscripts to the journal on "Neuropeptides as Growth Factors in Cancer" and subsequently was named to the Editorial Advisory Board. Over the past 30 years I have published dozens of manuscripts in Peptides and reviewed hundreds of submitted manuscripts. It was always rewarding to interact with Abba, a consummate professional. When I attended meetings in New Orleans I would sometimes go out to dinner with him at the restaurant "Commanders Palace". When I chaired the Summer Neuropeptide Conference we were honored to have him receive the Fleur Strand Award one year in Israel. I think that his biggest editorial contribution has been the "Handbook of Biologically Active Peptides." I served as a Section Editor on "Cancer/Anticancer Peptides" and again found that it was a pleasure working with him. This review focuses on the mechanisms by which bombesin-like peptides, neurotensin and vasoactive intestinal peptide regulate the growth of lung cancer. Published by Elsevier Inc. C1 [Moody, Terry W.] NCI, US Dept HHS, Ctr Canc Res, Off Director, Bethesda, MD 20892 USA. [Moreno, Paola; Jensen, Robert T.] NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Off Director, CCR, 9609 Med Ctr Dr,Room 2W-130, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov FU intramural program of NCI; NIDDK of the NIH FX The authors thank the numerous colleagues, postdoctoral fellows, graduate students and technicians who participated in these studies. This research is supported by the intramural program of NCI and NIDDK of the NIH. NR 85 TC 3 Z9 3 U1 0 U2 6 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 OCT PY 2015 VL 72 BP 106 EP 111 DI 10.1016/j.peptides.2015.03.018 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA CW0SO UT WOS:000364699900017 PM 25836991 ER PT J AU Ramos-Alvarez, I Moreno, P Mantey, SA Nakamura, T Nuche-Berenguer, B Moody, TW Coy, DH Jensen, RT AF Ramos-Alvarez, Irene Moreno, Paola Mantey, Samuel A. Nakamura, Taichi Nuche-Berenguer, Bernardo Moody, Terry W. Coy, David H. Jensen, Robert T. TI Insights into bombesin receptors and ligands: Highlighting recent advances SO PEPTIDES LA English DT Article DE Bombesin; Gastrin releasing peptide; Neuromedin b; Obesity; Pruritus ID GASTRIN-RELEASING-PEPTIDE; NEUROMEDIN-B RECEPTOR; LUNG-CANCER CELLS; PROTEIN-KINASE-C; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; TOTAL PARENTERAL-NUTRITION; PANCREATIC ACINAR-CELLS; HUMAN ORPHAN RECEPTOR; RAT GASTROINTESTINAL-TRACT AB This following article is written for Prof. Abba Kastin's Festschrift, to add to the tribute to his important role in the advancement of the role of peptides in physiological, as well as pathophysiological processes. There have been many advances during the 35 years of his prominent role in the Peptide field, not only as editor of the journal Peptides, but also as a scientific investigator and editor of two volumes of the Handbook of Biological Active Peptides 1146,1471. Similar to the advances with many different peptides, during this 35 year period, there have been much progress made in the understanding of the pharmacology, cell biology and the role of (bombesin) Bn receptors and their ligands in various disease states, since the original isolation of bombesin from skin of the European frog Bombina bombina in 1970 [76]. This paper will briefly review some of these advances over the time period of Prof. Kastin 35 years in the peptide field concentrating on the advances since 2007 when many of the results from earlier studies were summarized [128,129]. It is appropriate to do this because there have been 280 articles published in Peptides during this time on bombesin-related peptides and it accounts for almost 5% of all publications. Furthermore, 22 Bn publications we have been involved in have been published in either Peptides 114,39,55,58,81,92,93,119,152,216,225,226,23 8280,302,309355,361,3621 or in Prof. Kastin's Handbook of Biological Active Peptides [137,138,331]. Published by Elsevier Inc. C1 [Ramos-Alvarez, Irene; Moreno, Paola; Mantey, Samuel A.; Nakamura, Taichi; Nuche-Berenguer, Bernardo; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Moody, Terry W.] NCI, Ctr Canc Res, Off Director, NIH, Bethesda, MD 20892 USA. [Coy, David H.] Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Lab, New Orleans, LA 70112 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK branch of the National Institutes of Health FX This work was supported in part by intramural funds from the NIDDK branch of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 398 TC 10 Z9 10 U1 5 U2 17 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 OCT PY 2015 VL 72 BP 128 EP 144 DI 10.1016/j.peptides.2015.04.026 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA CW0SO UT WOS:000364699900021 PM 25976083 ER PT J AU Li, CYC Munitic, I Mittelstadt, PR Castro, E Ashwell, JD AF Li, Caiyi C. Munitic, Ivana Mittelstadt, Paul R. Castro, Ehydel Ashwell, Jonathan D. TI Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis SO PLOS BIOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; SEPTIC SHOCK; IN-VIVO; ENDOTOXIN TOLERANCE; GAMMA-INTERFERON; IFN-GAMMA; NK CELLS; T-CELLS; RECEPTOR; MICE AB Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of DCs in sepsis, and the mechanisms and significance of DC loss, are poorly understood. Here, we report that mice with selective deletion of the glucocorticoid receptor (GR) in DCs (GR(CD11c-cre)) were highly susceptible to LPS-induced septic shock, evidenced by elevated inflammatory cytokine production, hypothermia, and mortality. Neutralizing anti-IL-12 antibodies prevented hypothermia and death, demonstrating that endogenous GC-mediated suppression of IL-12 is protective. In LPS-challenged GR(CD11c-cre) mice, CD8(+) DCs were identified as the major source of prolonged IL-12 production, which correlated with elevations of NK cell-derived IFN-gamma. In addition, the loss of GR in CD11c(+) cells rescued LPS-induced loss of CD8(+) DCs but not other DC subsets. Unlike wildtype animals, exposure of GR(CD11c-cre) mice to low-dose LPS did not induce CD8(+) DC loss or tolerance to subsequent challenge with high dose, but neutralization of IL-12 restored the ability of low-dose LPS to tolerize. Therefore, endogenous glucocorticoids blunt LPS-induced inflammation and promote tolerance by suppressing DC IL-12 production. C1 [Li, Caiyi C.; Munitic, Ivana; Mittelstadt, Paul R.; Castro, Ehydel; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Li, CYC (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov FU CCR, NCI intramural research program FX This work was funded by the CCR, NCI intramural research program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 6 Z9 6 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2015 VL 13 IS 10 AR e1002269 DI 10.1371/journal.pbio.1002269 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CV7ML UT WOS:000364457500005 PM 26440998 ER PT J AU Kee, T Sanda, P Gupta, N Stopfer, M Bazhenov, M AF Kee, Tiffany Sanda, Pavel Gupta, Nitin Stopfer, Mark Bazhenov, Maxim TI Feed-Forward versus Feedback Inhibition in a Basic Olfactory Circuit SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DROSOPHILA MUSHROOM BODY; COINCIDENCE DETECTION; ODOR REPRESENTATIONS; NEURAL ASSEMBLIES; NETWORK DYNAMICS; PIRIFORM CORTEX; PYRAMIDAL CELLS; ANTENNAL LOBE; NEURONS; MEMORY AB Inhibitory interneurons play critical roles in shaping the firing patterns of principal neurons in many brain systems. Despite difference in the anatomy or functions of neuronal circuits containing inhibition, two basic motifs repeatedly emerge: feed-forward and feedback. In the locust, it was proposed that a subset of lateral horn interneurons (LHNs), provide feed-forward inhibition onto Kenyon cells (KCs) to maintain their sparse firing-a property critical for olfactory learning and memory. But recently it was established that a single inhibitory cell, the giant GABAergic neuron (GGN), is the main and perhaps sole source of inhibition in the mushroom body, and that inhibition from this cell is mediated by a feedback (FB) loop including KCs and the GGN. To clarify basic differences in the effects of feedback vs. feed-forward inhibition in circuit dynamics we here use a model of the locust olfactory system. We found both inhibitory motifs were able to maintain sparse KCs responses and provide optimal odor discrimination. However, we further found that only FB inhibition could create a phase response consistent with data recorded in vivo. These findings describe general rules for feed-forward versus feedback inhibition and suggest GGN is potentially capable of providing the primary source of inhibition to the KCs. A better understanding of how inhibitory motifs impact post-synaptic neuronal activity could be used to reveal unknown inhibitory structures within biological networks. C1 [Kee, Tiffany; Sanda, Pavel; Bazhenov, Maxim] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Gupta, Nitin] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India. [Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA. RP Kee, T (reprint author), Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. EM Maksim.Bazhenov@ucr.edu OI Gupta, Nitin/0000-0002-8408-3848 FU National Institute of Health, National Institute of Deafness and other Communication Disorders [1 R01 DC012943] FX This work was funded by the National Institute of Health, National Institute of Deafness and other Communication Disorders, 1 R01 DC012943, http://www.nidcd.nih.gov/Pages/default.aspx to MB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 3 Z9 3 U1 2 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 OCT PY 2015 VL 11 IS 10 AR e1004531 DI 10.1371/journal.pcbi.1004531 PG 24 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CV6SD UT WOS:000364399700061 PM 26458212 ER PT J AU Shehu, A Nussinov, R AF Shehu, Amarda Nussinov, Ruth TI Computational Methods for Exploration and Analysis of Macromolecular Structure and Dynamics SO PLoS Computational Biology LA English DT Editorial Material C1 [Shehu, Amarda] George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA. [Shehu, Amarda] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA. [Shehu, Amarda] George Mason Univ, Sch Syst Biol, Fairfax, VA 22030 USA. [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, 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 Shehu, A (reprint author), George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA. EM amarda@gmu.edu; NussinoR@helix.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 6 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 OCT PY 2015 VL 11 IS 10 AR e1004585 DI 10.1371/journal.pcbi.1004585 PG 3 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CV6SD UT WOS:000364399700085 PM 26505479 ER PT J AU Wu, XW Brooks, BR AF Wu, Xiongwu Brooks, Bernard R. TI A Virtual Mixture Approach to the Study of Multistate Equilibrium: Application to Constant pH Simulation in Explicit Water SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID ISOTROPIC PERIODIC SUM; EXCHANGE MOLECULAR-DYNAMICS; DISCRETE PROTONATION STATES; GUIDED LANGEVIN DYNAMICS; FREE-ENERGY DIFFERENCES; SOLVENT; PROTEINS; TAUTOMERISM; PROGRAM; CHARMM AB Chemical and thermodynamic equilibrium of multiple states is a fundamental phenomenon in biology systems and has been the focus of many experimental and computational studies. This work presents a simulation method to directly study the equilibrium of multiple states. This method constructs a virtual mixture of multiple states (VMMS) to sample the conformational space of all chemical states simultaneously. The VMMS system consists of multiple subsystems, one for each state. The subsystem contains a solute and a solvent environment. The solute molecules in all subsystems share the same conformation but have their own solvent environments. Transition between states is implicated by the change of their molar fractions. Simulation of a VMMS system allows efficient calculation of relative free energies of all states, which in turn determine their equilibrium molar fractions. For systems with a large number of state transition sites, an implicit site approximation is introduced to minimize the cost of simulation. A direct application of the VMMS method is for constant pH simulation to study protonation equilibrium. Applying the VMMS method to a heptapeptide of 3 ionizable residues, we calculated the pKas of those residues both with all explicit states and with implicit sites and obtained consistent results. For mouse epidermal growth factor of 9 ionizable groups, our VMMS simulations with implicit sites produced pKas of all 9 ionizable groups and the results agree qualitatively with NMR measurement. This example demonstrates the VMMS method can be applied to systems of a large number of ionizable groups and the computational cost scales linearly with the number of ionizable groups. For one of the most challenging systems in constant pH calculation, SNase Delta+PHS/V66K, our VMMS simulation shows that it is the state-dependent water penetration that causes the large deviation in lysine66's pKa. C1 [Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wuxw@nhlbi.nih.gov FU Intramural Research Programs of National Heart, Lung, and Blood Institute [Z01 HL001027-30] FX This research was supported by the Intramural Research Programs of National Heart, Lung, and Blood Institute (Z01 HL001027-30). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 2 Z9 2 U1 3 U2 16 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 OCT PY 2015 VL 11 IS 10 AR e1004480 DI 10.1371/journal.pcbi.1004480 PG 29 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CV6SD UT WOS:000364399700039 PM 26506245 ER PT J AU Cloutier, JM Mahadevaiah, SK ElInati, E Nussenzweig, A Toth, A Turner, JMA AF Cloutier, Jeffrey M. Mahadevaiah, Shantha K. ElInati, Elias Nussenzweig, Andre Toth, Attila Turner, James M. A. TI Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals SO PLoS Genetics LA English DT Article ID DOUBLE-STRAND BREAKS; X-CHROMOSOME; SEX-CHROMOSOMES; Y-CHROMOSOME; MOUSE; MICE; SYNAPSIS; RECOMBINATION; INACTIVATION; CHROMATIN AB Chromosome abnormalities are common in the human population, causing germ cell loss at meiotic prophase I and infertility. The mechanisms driving this loss are unknown, but persistent meiotic DNA damage and asynapsis may be triggers. Here we investigate the contribution of these lesions to oocyte elimination in mice with chromosome abnormalities, e.g. Turner syndrome (XO) and translocations. We show that asynapsed chromosomes trigger oocyte elimination at diplonema, which is linked to the presence of phosphorylated H2AFX (gamma H2AFX). We find that DNA double-strand break (DSB) foci disappear on asynapsed chromosomes during pachynema, excluding persistent DNA damage as a likely cause, and demonstrating the existence in mammalian oocytes of a repair pathway for asynapsis-associated DNA DSBs. Importantly, deletion or point mutation of H2afx restores oocyte numbers in XO females to wild type (XX) levels. Unexpectedly, we find that asynapsed supernumerary chromosomes do not elicit prophase I loss, despite being enriched for gamma H2AFX and other checkpoint proteins. These results suggest that oocyte loss cannot be explained simply by asynapsis checkpoint models, but is related to the gene content of asynapsed chromosomes. A similar mechanistic basis for oocyte loss may operate in humans with chromosome abnormalities. C1 [Cloutier, Jeffrey M.; Mahadevaiah, Shantha K.; ElInati, Elias; Turner, James M. A.] Francis Crick Inst, Mill Hill Lab, London, England. [Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. [Toth, Attila] Tech Univ Dresden, Inst Physiol Chem, D-01062 Dresden, Germany. RP Cloutier, JM (reprint author), Francis Crick Inst, Mill Hill Lab, London, England. EM James.Turner@crick.ac.uk FU Medical Research Council [U117588498]; Deutsche Forschungsgemeinschaft [TO 421/3-1, 421/3-2, 421/ 4-1, 421/5-1]; Marshall Scholarship Program; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX The work was supported by the Medical Research Council (U117588498), the Deutsche Forschungsgemeinschaft (TO 421/3-1, 421/3-2, 421/ 4-1, and 421/5-1), the Marshall Scholarship Program and the Intramural Research Program of the NIH, the National Cancer Institute, and the Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 7 Z9 7 U1 1 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 OCT PY 2015 VL 11 IS 10 AR e1005462 DI 10.1371/journal.pgen.1005462 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600005 PM 26509888 ER PT J AU Wang, K Xu, RJ Schrandt, J Shah, P Gong, YZ Preston, C Wang, L Yi, JK Lin, CL Sun, W Spyropoulos, DD Rhee, S Li, MS Zhou, J Ge, SY Zhang, GF Snider, AJ Hannun, YA Obeid, LM Mao, CG AF Wang, Kai Xu, Ruijuan Schrandt, Jennifer Shah, Prithvi Gong, Yong Z. Preston, Chet Wang, Louis Yi, Jae Kyo Lin, Chih-Li Sun, Wei Spyropoulos, Demetri D. Rhee, Soyoung Li, Mingsong Zhou, Jie Ge, Shaoyu Zhang, Guofeng Snider, Ashley J. Hannun, Yusuf A. Obeid, Lina M. Mao, Cungui TI y Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain SO PLOS GENETICS LA English DT Article ID LONG-CHAIN CERAMIDES; ACID CERAMIDASE; SUBSTRATE-SPECIFICITY; ENDOPLASMIC-RETICULUM; NEUTRAL CERAMIDASE; MEMBRANE TOPOLOGY; MOLECULAR-CLONING; MUSCLE STRENGTH; FAMILY-MEMBERS; FARBER-DISEASE AB Dyshomeostasis of both ceramides and sphingosine-1-phosphate (S1P) in the brain has been implicated in aging-associated neurodegenerative disorders in humans. However, mechanisms that maintain the homeostasis of these bioactive sphingolipids in the brain remain unclear. Mouse alkaline ceramidase 3 (Acer3), which preferentially catalyzes the hydrolysis of C-18:1-ceramide, a major unsaturated long-chain ceramide species in the brain, is upregulated with age in the mouse brain. Acer3 knockout causes an age-dependent accumulation of various ceramides and C-18:1-monohexosylceramide and abolishes the age-related increase in the levels of sphingosine and S1P in the brain; thereby resulting in Purkinje cell degeneration in the cerebellum and deficits in motor coordination and balance. Our results indicate that Acer3 plays critically protective roles in controlling the homeostasis of various sphingolipids, including ceramides, sphingosine, S1P, and certain complex sphingolipids in the brain and protects Purkinje cells from premature degeneration. C1 [Wang, Kai; Xu, Ruijuan; Schrandt, Jennifer; Yi, Jae Kyo; Lin, Chih-Li; Snider, Ashley J.; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Wang, Kai; Xu, Ruijuan; Schrandt, Jennifer; Yi, Jae Kyo; Lin, Chih-Li; Snider, Ashley J.; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui] Stony Brook Canc Ctr, Stony Brook, NY USA. [Wang, Kai; Zhou, Jie] Southern Med Univ, Nanfang Hosp, Dept Hepatobiliary Surg, Guangzhou, Guangdong, Peoples R China. [Shah, Prithvi; Preston, Chet; Wang, Louis] SUNY Stony Brook, Sch Hlth Technol & Management, Dept Phys Therapy, Div Rehabil Sci, Stony Brook, NY 11794 USA. [Shah, Prithvi] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. [Gong, Yong Z.; Sun, Wei; Spyropoulos, Demetri D.; Rhee, Soyoung; Ge, Shaoyu] Med Univ S Carolina, Charleston, SC 29425 USA. [Li, Mingsong] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China. [Zhang, Guofeng] NIH, Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci Shared Resource, Bethesda, MD 20892 USA. [Snider, Ashley J.; Obeid, Lina M.] Northport Vet Affairs Med Ctr, Northport, NY USA. RP Wang, K (reprint author), SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. EM cungui.mao@stonybrook.edu FU National Institutes of Health [R01CA104834, R01CA163825, P20RR017677, P01 CA097132] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01CA104834 (to CM), R01CA163825 (to CM), P20RR017677 (to LMO), and P01 CA097132 (to YAH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 5 Z9 5 U1 0 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 OCT PY 2015 VL 11 IS 10 AR e1005591 DI 10.1371/journal.pgen.1005591 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600055 PM 26474409 ER PT J AU Winkler, TW Justice, AE Graff, M Barata, L Feitosa, MF Chu, S Czajkowski, J Esko, T Fall, T Kilpelainen, TO Lu, YC Magi, R Mihailov, E Pers, TH Rueger, S Teumer, A Ehret, GB Ferreira, T Heard-Costa, NL Karjalainen, J Lagou, V Mahajan, A Neinast, MD Prokopenko, I Simino, J Teslovich, TM Jansen, R Westra, HJ White, CC Absher, D Ahluwalia, TS Ahmad, S Albrecht, E Alves, AC Bragg-Gresham, JL de Craen, AJM Bis, JC Bonnefond, A Boucher, G Cadby, G Cheng, YC Chiang, CWK Delgado, G Demirkan, A Dueker, N Eklund, N Eiriksdottir, G Eriksson, J Feenstra, B Fischer, K Frau, F Galesloot, TE Geller, F Goel, A Gorski, M Grammer, TB Gustafsson, S Haitjema, S Hottenga, JJ Huffman, JE Jackson, AU Jacobs, KB Johansson, A Kaakinen, M Kleber, ME Lahti, J Leach, IM Lehne, B Liu, YF Lo, KS Lorentzon, M Luan, J Madden, PAF Mangino, M McKnight, B Medina-Gomez, C Monda, KL Montasser, ME Muller, G Muller-Nurasyid, M Nolte, IM Panoutsopoulou, K Pascoe, L Paternoster, L Rayner, NW Renstrom, F Rizzi, F Rose, LM Ryan, KA Salo, P Sanna, S Scharnagl, H Shi, JX Smith, AV Southam, L Stancakova, A Steinthorsdottir, V Strawbridge, RJ Sung, YJ Tachmazidou, I Tanaka, T Thorleifsson, G Trompet, S Pervjakova, N Tyrer, JP Vandenput, L van der Laan, SW van der Velde, N van Setten, J van Vliet-Ostaptchouk, JV Verweij, N Vlachopoulou, E Waite, LL Wang, SR Wang, ZM Wild, SH Willenborg, C Wilson, JF Wong, A Yang, J Yengo, L Yerges-Armstrong, LM Yu, L Zhang, WH Zhao, JH Andersson, EA Bakker, SJL Baldassarre, D Banasik, K Barcella, M Barlassina, C Bellis, C Benaglio, P Blangero, J Bluher, M Bonnet, F Bonnycastle, LL Boyd, HA Bruinenberg, M Buchman, AS Campbell, H Chen, YDI Chines, PS Claudi-Boehm, S Cole, J Collins, FS de Geus, EJC de Groot, LCPGM Dimitriou, M Duan, J Enroth, S Eury, E Farmaki, AE Forouhi, NG Friedrich, N Gejman, PV Gigante, B Glorioso, N Go, AS Gottesman, O Grassler, J Grallert, H Grarup, N Gu, YM Broer, L Ham, AC Hansen, T Harris, TB Hartman, CA Hassinen, M Hastie, N Hattersley, AT Heath, AC Henders, AK Hernandez, D Hillege, H Holmen, O Hovingh, KG Hui, J Husemoen, LL Hutri-Kahonen, N Hysi, PG Illig, T De Jager, PL Jalilzadeh, S Jorgensen, T Jukema, JW Juonala, M Kanoni, S Karaleftheri, M Khaw, KT Kinnunen, L Kittner, SJ Koenig, W Kolcic, I Kovacs, P Krarup, NT Kratzer, W Kruger, J Kuh, D Kumari, M Kyriakou, T Langenberg, C Lannfelt, L Lanzani, C Lotay, V Launer, LJ Leander, K Lindstrom, J Linneberg, A Liu, YP Lobbens, S Luben, R Lyssenko, V Mannisto, S Magnusson, PK McArdle, WL Menni, C Merger, S Milani, L Montgomery, GW Morris, AP Narisu, N Nelis, M Ong, KK Palotie, A Perusse, L Pichler, I Pilia, MG Pouta, A Rheinberger, M Ribel-Madsen, R Richards, M Rice, KM Rice, TK Rivolta, C Salomaa, V Sanders, AR Sarzynski, MA Scholtens, S Scott, RA Scott, WR Sebert, S Sengupta, S Sennblad, B Seufferlein, T Silveira, A Slagboom, PE Smit, JH Sparso, TH Stirrups, K Stolk, RP Stringham, HM Swertz, MA Swift, AJ Syvanen, AC Tan, ST Thorand, B Tonjes, A Tremblay, A Tsafantakis, E van der Most, PJ Volker, U Vohl, MC Vonk, JM Waldenberger, M Walker, RW Wennauer, R Widen, E Willemsen, G Wilsgaard, T Wright, AF Zillikens, MC van Dijk, SC van Schoor, NM Asselbergs, FW de Bakker, PIW Beckmann, JS Beilby, J Bennett, DA Bergman, RN Bergmann, S Boger, CA Boehm, BO Boerwinkle, E Boomsma, DI Bornstein, SR Bottinger, EP Bouchard, C Chambers, JC Chanock, SJ Chasman, DI Cucca, F Cusi, D Dedoussis, G Erdmann, J Eriksson, JG Evans, DA de Faire, U Farrall, M Ferrucci, L Ford, I Franke, L Franks, PW Froguel, P Gansevoort, RT Gieger, C Gronberg, H Gudnason, V Gyllensten, U Hall, P Hamsten, A van der Harst, P Hayward, C Heliovaara, M Hengstenberg, C Hicks, AA Hingorani, A Hofman, A Hu, F Huikuri, HV Hveem, K James, AL Jordan, JM Jula, A Kahonen, M Kajantie, E Kathiresan, S Kiemeney, LALM Kivimaki, M Knekt, PB Koistinen, HA Kooner, JS Koskinen, S Kuusisto, J Maerz, W Martin, NG Laakso, M Lakka, TA Lehtimaki, T Lettre, G Levinson, DF Lind, L Lokki, ML Mantyselka, P Melbye, M Metspalu, A Mitchell, BD Moll, FL Murray, JC Musk, AW Nieminen, MS Njolstad, I Ohlsson, C Oldehinkel, AJ Oostra, BA Palmer, LJ Pankow, JS Pasterkamp, G Pedersen, NL Pedersen, O Penninx, BW Perola, M Peters, A Polasek, O Pramstaller, PP Psaty, BM Qi, L Quertermous, T Raitakari, OT Rankinen, T Rauramaa, R Ridker, PM Rioux, JD Rivadeneira, F Rotter, JI Rudan, I den Ruijter, HM Saltevo, J Sattar, N Schunkert, H Schwarz, PEH Shuldiner, AR Sinisalo, J Snieder, H Sorensen, TIA Spector, TD Staessen, JA Stefania, B Thorsteinsdottir, U Stumvoll, M Tardif, JC Tremoli, E Tuomilehto, J Uitterlinden, AG Uusitupa, M Verbeek, ALM Vermeulen, SH Viikari, JS Vitart, V Volzke, H Vollenweider, P Waeber, G Walker, M Wallaschofski, H Wareham, NJ Watkins, H Zeggini, E Chakravarti, A Clegg, DJ Cupples, LA Gordon-Larsen, P Jaquish, CE Rao, DC Abecasis, GR Assimes, TL Barroso, I Berndt, SI Boehnke, M Deloukas, P Fox, CS Groop, LC Hunter, DJ Ingelsson, E Kaplan, RC McCarthy, MI Mohlke, KL O'Connell, JR Schlessinger, D Strachan, DP Stefansson, K van Duijn, CM Hirschhorn, JN Lindgren, CM Heid, IM North, KE Borecki, IB Kutalik, Z Loos, RJF AF Winkler, Thomas W. Justice, Anne E. Graff, Mariaelisa Barata, Llilda Feitosa, Mary F. Chu, Su Czajkowski, Jacek Esko, Tonu Fall, Tove Kilpelainen, Tuomas O. Lu, Yingchang Magi, Reedik Mihailov, Evelin Pers, Tune H. Rueeger, Sina Teumer, Alexander Ehret, Georg B. Ferreira, Teresa Heard-Costa, Nancy L. Karjalainen, Juha Lagou, Vasiliki Mahajan, Anubha Neinast, Michael D. Prokopenko, Inga Simino, Jeannette Teslovich, Tanya M. Jansen, Rick Westra, Harm-Jan White, Charles C. Absher, Devin Ahluwalia, Tarunveer S. Ahmad, Shafqat Albrecht, Eva Alves, Alexessander Couto Bragg-Gresham, Jennifer L. de Craen, Anton J. M. Bis, Joshua C. Bonnefond, Amelie Boucher, Gabrielle Cadby, Gemma Cheng, Yu-Ching Chiang, Charleston W. K. Delgado, Graciela Demirkan, Ayse Dueker, Nicole Eklund, Niina Eiriksdottir, Gudny Eriksson, Joel Feenstra, Bjarke Fischer, Krista Frau, Francesca Galesloot, Tessel E. Geller, Frank Goel, Anuj Gorski, Mathias Grammer, Tanja B. Gustafsson, Stefan Haitjema, Saskia Hottenga, Jouke-Jan Huffman, Jennifer E. Jackson, Anne U. Jacobs, Kevin B. Johansson, Asa Kaakinen, Marika Kleber, Marcus E. Lahti, Jari Leach, Irene Mateo Lehne, Benjamin Liu, Youfang Lo, Ken Sin Lorentzon, Mattias Luan, Jian'an Madden, Pamela A. F. Mangino, Massimo McKnight, Barbara Medina-Gomez, Carolina Monda, Keri L. Montasser, May E. Mueller, Gabriele Mueller-Nurasyid, Martina Nolte, Ilja M. Panoutsopoulou, Kalliope Pascoe, Laura Paternoster, Lavinia Rayner, Nigel W. Renstrom, Frida Rizzi, Federica Rose, Lynda M. Ryan, Kathy A. Salo, Perttu Sanna, Serena Scharnagl, Hubert Shi, Jianxin Smith, Albert Vernon Southam, Lorraine Stancakova, Alena Steinthorsdottir, Valgerdur Strawbridge, Rona J. Sung, Yun Ju Tachmazidou, Ioanna Tanaka, Toshiko Thorleifsson, Gudmar Trompet, Stella Pervjakova, Natalia Tyrer, Jonathan P. Vandenput, Liesbeth van der Laan, Sander W. van der Velde, Nathalie van Setten, Jessica van Vliet-Ostaptchouk, Jana V. Verweij, Niek Vlachopoulou, Efthymia Waite, Lindsay L. Wang, Sophie R. Wang, Zhaoming Wild, Sarah H. Willenborg, Christina Wilson, James F. Wong, Andrew Yang, Jian Yengo, Loic Yerges-Armstrong, Laura M. Yu, Lei Zhang, Weihua Zhao, Jing Hua Andersson, Ehm A. Bakker, Stephan J. L. Baldassarre, Damiano Banasik, Karina Barcella, Matteo Barlassina, Cristina Bellis, Claire Benaglio, Paola Blangero, John Blueher, Matthias Bonnet, Fabrice Bonnycastle, Lori L. Boyd, Heather A. Bruinenberg, Marcel Buchman, Aron S. Campbell, Harry Chen, Yii-Der Ida Chines, Peter S. Claudi-Boehm, Simone Cole, John Collins, Francis S. de Geus, Eco J. C. de Groot, Lisette C. P. G. M. Dimitriou, Maria Duan, Jubao Enroth, Stefan Eury, Elodie Farmaki, Aliki-Eleni Forouhi, Nita G. Friedrich, Nele Gejman, Pablo V. Gigante, Bruna Glorioso, Nicola Go, Alan S. Gottesman, Omri Graessler, Juergen Grallert, Harald Grarup, Niels Gu, Yu-Mei Broer, Linda Ham, Annelies C. Hansen, Torben Harris, Tamara B. Hartman, Catharina A. Hassinen, Maija Hastie, Nicholas Hattersley, Andrew T. Heath, Andrew C. Henders, Anjali K. Hernandez, Dena Hillege, Hans Holmen, Oddgeir Hovingh, Kees G. Hui, Jennie Husemoen, Lise L. Hutri-Kahonen, Nina Hysi, Pirro G. Illig, Thomas De Jager, Philip L. Jalilzadeh, Shapour Jorgensen, Torben Jukema, J. Wouter Juonala, Markus Kanoni, Stavroula Karaleftheri, Maria Khaw, Kay Tee Kinnunen, Leena Kittner, Steven J. Koenig, Wolfgang Kolcic, Ivana Kovacs, Peter Krarup, Nikolaj T. Kratzer, Wolfgang Krueger, Janine Kuh, Diana Kumari, Meena Kyriakou, Theodosios Langenberg, Claudia Lannfelt, Lars Lanzani, Chiara Lotay, Vaneet Launer, Lenore J. Leander, Karin Lindstrom, Jaana Linneberg, Allan Liu, Yan-Ping Lobbens, Stephane Luben, Robert Lyssenko, Valeriya Mannisto, Satu Magnusson, Patrik K. McArdle, Wendy L. Menni, Cristina Merger, Sigrun Milani, Lili Montgomery, Grant W. Morris, Andrew P. Narisu, Narisu Nelis, Mari Ong, Ken K. Palotie, Aarno Perusse, Louis Pichler, Irene Pilia, Maria G. Pouta, Anneli Rheinberger, Myriam Ribel-Madsen, Rasmus Richards, Marcus Rice, Kenneth M. Rice, Treva K. Rivolta, Carlo Salomaa, Veikko Sanders, Alan R. Sarzynski, Mark A. Scholtens, Salome Scott, Robert A. Scott, William R. Sebert, Sylvain Sengupta, Sebanti Sennblad, Bengt Seufferlein, Thomas Silveira, Angela Slagboom, P. Eline Smit, Jan H. Sparso, Thomas H. Stirrups, Kathleen Stolk, Ronald P. Stringham, Heather M. Swertz, Morris A. Swift, Amy J. Syvanen, Ann-Christine Tan, Sian-Tsung Thorand, Barbara Toenjes, Anke Tremblay, Angelo Tsafantakis, Emmanouil van der Most, Peter J. Voelker, Uwe Vohl, Marie-Claude Vonk, Judith M. Waldenberger, Melanie Walker, Ryan W. Wennauer, Roman Widen, Elisabeth Willemsen, Gonneke Wilsgaard, Tom Wright, Alan F. Zillikens, M. Carola van Dijk, Suzanne C. van Schoor, Natasja M. Asselbergs, Folkert W. de Bakker, Paul I. W. Beckmann, Jacques S. Beilby, John Bennett, David A. Bergman, Richard N. Bergmann, Sven Boeger, Carsten A. Boehm, Bernhard O. Boerwinkle, Eric Boomsma, Dorret I. Bornstein, Stefan R. Bottinger, Erwin P. Bouchard, Claude Chambers, John C. Chanock, Stephen J. Chasman, Daniel I. Cucca, Francesco Cusi, Daniele Dedoussis, George Erdmann, Jeanette Eriksson, Johan G. Evans, Denis A. de Faire, Ulf Farrall, Martin Ferrucci, Luigi Ford, Ian Franke, Lude Franks, Paul W. Froguel, Philippe Gansevoort, Ron T. Gieger, Christian Gronberg, Henrik Gudnason, Vilmundur Gyllensten, Ulf Hall, Per Hamsten, Anders van der Harst, Pim Hayward, Caroline Heliovaara, Markku Hengstenberg, Christian Hicks, Andrew A. Hingorani, Aroon Hofman, Albert Hu, Frank Huikuri, Heikki V. Hveem, Kristian James, Alan L. Jordan, Joanne M. Jula, Antti Kaehoenen, Mika Kajantie, Eero Kathiresan, Sekar Kiemeney, Lambertus A. L. M. Kivimaki, Mika Knekt, Paul B. Koistinen, Heikki A. Kooner, Jaspal S. Koskinen, Seppo Kuusisto, Johanna Maerz, Winfried Martin, Nicholas G. Laakso, Markku Lakka, Timo A. Lehtimaki, Terho Lettre, Guillaume Levinson, Douglas F. Lind, Lars Lokki, Marja-Liisa Mantyselka, Pekka Melbye, Mads Metspalu, Andres Mitchell, Braxton D. Moll, Frans L. Murray, Jeffrey C. Musk, Arthur W. Nieminen, Markku S. Njolstad, Inger Ohlsson, Claes Oldehinkel, Albertine J. Oostra, Ben A. Palmer, Lyle J. Pankow, James S. Pasterkamp, Gerard Pedersen, Nancy L. Pedersen, Oluf Penninx, Brenda W. Perola, Markus Peters, Annette Polasek, Ozren Pramstaller, Peter P. Psaty, Bruce M. Qi, Lu Quertermous, Thomas Raitakari, Olli T. Rankinen, Tuomo Rauramaa, Rainer Ridker, Paul M. Rioux, John D. Rivadeneira, Fernando Rotter, Jerome I. Rudan, Igor den Ruijter, Hester M. Saltevo, Juha Sattar, Naveed Schunkert, Heribert Schwarz, Peter E. H. Shuldiner, Alan R. Sinisalo, Juha Snieder, Harold Sorensen, Thorkild I. A. Spector, Tim D. Staessen, Jan A. Stefania, Bandinelli Thorsteinsdottir, Unnur Stumvoll, Michael Tardif, Jean-Claude Tremoli, Elena Tuomilehto, Jaakko Uitterlinden, Andre G. Uusitupa, Matti Verbeek, Andre L. M. Vermeulen, Sita H. Viikari, Jorma S. Vitart, Veronique Voelzke, Henry Vollenweider, Peter Waeber, Gerard Walker, Mark Wallaschofski, Henri Wareham, Nicholas J. Watkins, Hugh Zeggini, Eleftheria Chakravarti, Aravinda Clegg, Deborah J. Cupples, L. Adrienne Gordon-Larsen, Penny Jaquish, Cashell E. Rao, D. C. Abecasis, Goncalo R. Assimes, Themistocles L. Barroso, Ines Berndt, Sonja I. Boehnke, Michael Deloukas, Panos Fox, Caroline S. Groop, Leif C. Hunter, David J. Ingelsson, Erik Kaplan, Robert C. McCarthy, Mark I. Mohlke, Karen L. O'Connell, Jeffrey R. Schlessinger, David Strachan, David P. Stefansson, Kari van Duijn, Cornelia M. Hirschhorn, Joel N. Lindgren, Cecilia M. Heid, Iris M. North, Kari E. Borecki, Ingrid B. Kutalik, Zoltan Loos, Ruth J. F. CA CHARGE Consortium DIAGRAM Consortium GLGC Consortium Global-BPGen Consortium ICBP Consortium MAGIC Consortium TI The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study SO PLOS GENETICS LA English DT Article ID SELF-REPORTED HEIGHT; FAT DISTRIBUTION; MASS INDEX; LIFE-COURSE; BIOLOGICAL PATHWAYS; NATURAL MENOPAUSE; PERIPHERAL-BLOOD; WEIGHT-GAIN; COMMON SNPS; LOCI AB Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. C1 [Winkler, Thomas W.; Gorski, Mathias; Heid, Iris M.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany. [Justice, Anne E.; Graff, Mariaelisa; Monda, Keri L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Barata, Llilda; Feitosa, Mary F.; Czajkowski, Jacek; Rao, D. 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[Esko, Tonu; Magi, Reedik; Mihailov, Evelin; Fischer, Krista; Pervjakova, Natalia; Milani, Lili; Nelis, Mari; Metspalu, Andres; Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Pers, Tune H.; Wang, Sophie R.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Fall, Tove; Gustafsson, Stefan; Johansson, Asa; Enroth, Stefan; Syvanen, Ann-Christine; Gyllensten, Ulf; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, Uppsala, Sweden. [Fall, Tove; Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Dept Med Sci Mol Epidemiol, Uppsala, Sweden. [Kilpelainen, Tuomas O.; Ahluwalia, Tarunveer S.; Andersson, Ehm A.; Banasik, Karina; Grarup, Niels; Hansen, Torben; Krarup, Nikolaj T.; Ribel-Madsen, Rasmus; Sparso, Thomas H.; Pedersen, Oluf; Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, Copenhagen, Denmark. [Kilpelainen, Tuomas O.; Luan, Jian'an; Zhao, Jing Hua; Forouhi, Nita G.; Langenberg, Claudia; Ong, Ken K.; Scott, Robert A.; Wareham, Nicholas J.; Loos, Ruth J. F.] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Lu, Yingchang; Gottesman, Omri; Walker, Ryan W.; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Lu, Yingchang; Walker, Ryan W.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Magi, Reedik; Ferreira, Teresa; Lagou, Vasiliki; Mahajan, Anubha; Prokopenko, Inga; Goel, Anuj; Rayner, Nigel W.; Southam, Lorraine; Jalilzadeh, Shapour; Kyriakou, Theodosios; Morris, Andrew P.; Farrall, Martin; Watkins, Hugh; Ingelsson, Erik; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Pers, Tune H.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA. [Rueeger, Sina; Beckmann, Jacques S.; Bergmann, Sven; Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland. [Rueeger, Sina; Kutalik, Zoltan] Univ Hosp Lausanne CHUV, Inst Social & Prevent Med, Lausanne, Switzerland. [Teumer, Alexander; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Teumer, Alexander; Voelker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Ehret, Georg B.] Univ Hosp Geneva, Dept Specialties Internal Med, Geneva, Switzerland. [Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Heard-Costa, Nancy L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Heard-Costa, Nancy L.; Huffman, Jennifer E.; Cupples, L. Adrienne; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Karjalainen, Juha; Swertz, Morris A.; Franke, Lude; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Lagou, Vasiliki; Prokopenko, Inga; Rayner, Nigel W.; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Neinast, Michael D.; Clegg, Deborah J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Prokopenko, Inga] Hammersmith Hosp, London, England. [Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Simino, Jeannette; Sung, Yun Ju; Rice, Treva K.; Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Jansen, Rick; Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Jansen, Rick; Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Westra, Harm-Jan; Wang, Sophie R.; De Jager, Philip L.; Kathiresan, Sekar; Walker, Mark] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA. [Westra, Harm-Jan] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Westra, Harm-Jan] Partners Ctr Personalized Genet Med, Boston, MA USA. [White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Absher, Devin; Waite, Lindsay L.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Ahluwalia, Tarunveer S.; Lyssenko, Valeriya] Steno Diabet Ctr A S, Gentofte, Denmark. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Herlev & Gentofte Hosp, COPSAC, Copenhagen, Denmark. [Ahmad, Shafqat; Renstrom, Frida; Franks, Paul W.] Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Albrecht, Eva; Mueller-Nurasyid, Martina; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Alves, Alexessander Couto; Kaakinen, Marika] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England. [de Craen, Anton J. M.; Trompet, Stella] Leiden Univ Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Bis, Joshua C.; McKnight, Barbara; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Bonnefond, Amelie; Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Froguel, Philippe] CNRS, UMR 8199, Lille, France. [Bonnefond, Amelie; Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Froguel, Philippe] European Genom Inst Diabet, Lille, France. [Bonnefond, Amelie; Yengo, Loic; Eury, Elodie; Froguel, Philippe] Univ Lille 2, Lille, France. [Boucher, Gabrielle; Lo, Ken Sin; Lettre, Guillaume; Rioux, John D.; Tardif, Jean-Claude] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Cadby, Gemma] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley, WA, Australia. [Cheng, Yu-Ching; Cole, John; Kittner, Steven J.] VA Maryland Hlth Care Syst, Baltimore, MD USA. [Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Chiang, Charleston W. K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Delgado, Graciela; Grammer, Tanja B.; Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Mannheim, Germany. [Demirkan, Ayse; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Dueker, Nicole] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Eklund, Niina; Salo, Perttu; Mannisto, Satu; Salomaa, Veikko; Eriksson, Johan G.; Jula, Antti; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Eklund, Niina; Salo, Perttu; Pervjakova, Natalia] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Eklund, Niina; Palotie, Aarno; Widen, Elisabeth; Perola, Markus] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Eiriksdottir, Gudny; Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Eriksson, Joel; Lorentzon, Mattias; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden. [Feenstra, Bjarke; Geller, Frank; Boyd, Heather A.; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Frau, Francesca; Rizzi, Federica; Barcella, Matteo; Barlassina, Cristina; Cusi, Daniele] Univ Milan, Dept Hlth Sci, Milan, Italy. [Frau, Francesca; Rizzi, Federica] Filarete Fdn, Genom & Bioinformat Unit, Milan, Italy. [Galesloot, Tessel E.; Kiemeney, Lambertus A. L. M.; Verbeek, Andre L. M.; Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands. [Goel, Anuj; Jalilzadeh, Shapour; Kyriakou, Theodosios; Farrall, Martin; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Div Cardiovac Med, Oxford, England. [Gorski, Mathias; Rheinberger, Myriam; Boeger, Carsten A.] Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany. [Haitjema, Saskia; van der Laan, Sander W.; Pasterkamp, Gerard; den Ruijter, Hester M.] UMCU, Expt Cardiol & Lab Clin Chem, Utrecht, Netherlands. [Hottenga, Jouke-Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Huffman, Jennifer E.; Hastie, Nicholas; Wright, Alan F.; Hayward, Caroline; Vitart, Veronique] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Jacobs, Kevin B.; Wang, Zhaoming; Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Jacobs, Kevin B.; Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Johansson, Asa; Enroth, Stefan; Gyllensten, Ulf] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Kaakinen, Marika; Sebert, Sylvain] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Leach, Irene Mateo; Verweij, Niek; Hillege, Hans; Franke, Lude; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Lehne, Benjamin; Zhang, Weihua; Scott, William R.; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Liu, Youfang; Jordan, Joanne M.] Univ N Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chaper Hill, NC USA. [Madden, Pamela A. F.; Heath, Andrew C.] Washington Univ, Sch Med, St Louis, MO USA. [Mangino, Massimo; Hysi, Pirro G.; Menni, Cristina; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [McKnight, Barbara; Chanock, Stephen J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA. [McKnight, Barbara; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Medina-Gomez, Carolina; Zillikens, M. Carola; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.] NCHA, NGI, Leiden, Netherlands. [Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Medina-Gomez, Carolina; van der Velde, Nathalie; Broer, Linda; Ham, Annelies C.; Zillikens, M. Carola; van Dijk, Suzanne C.; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Montasser, May E.; Ryan, Kathy A.; Yerges-Armstrong, Laura M.; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr,Program Personalized, Baltimore, MD 21201 USA. [Mueller, Gabriele] Univ Dresden, Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany. [Mueller-Nurasyid, Martina; Waldenberger, Melanie; Hengstenberg, Christian; Peters, Annette; Schunkert, Heribert] Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany. [Nolte, Ilja M.; Scholtens, Salome; Stolk, Ronald P.; van der Most, Peter J.; Vonk, Judith M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Panoutsopoulou, Kalliope; Rayner, Nigel W.; Southam, Lorraine; Tachmazidou, Ioanna; Dimitriou, Maria; Kanoni, Stavroula; Palotie, Aarno; Stirrups, Kathleen; Zeggini, Eleftheria; Barroso, Ines; Deloukas, Panos] Wellcome Trust Sanger Inst, Human Genet, Cambridge, England. [Pascoe, Laura] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Paternoster, Lavinia] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Rose, Lynda M.; Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Sanna, Serena; Pilia, Maria G.; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Monserrato, Italy. [Scharnagl, Hubert; Maerz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Scharnagl, Hubert; Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Shi, Jianxin] NCI, Bethesda, MD 20892 USA. [Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] Amgen Inc, deCODE Genet, Reykjavik, Iceland. [Strawbridge, Rona J.; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Strawbridge, Rona J.; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands. [Pervjakova, Natalia] Univ Tartu, Inst Cell & Mol Biol, Dept Biotechnol, EE-50090 Tartu, Estonia. [Pervjakova, Natalia] Univ Helsinki, Helsinki, Finland. [Tyrer, Jonathan P.] Univ Cambridge, Dept Oncol, Cambridge, England. [van der Velde, Nathalie] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Geriatr Med Sect, NL-1105 AZ Amsterdam, Netherlands. [van Setten, Jessica; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Vlachopoulou, Efthymia; Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland. [Wang, Sophie R.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Wang, Sophie R.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Wang, Sophie R.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Wang, Sophie R.] Boston Childrens Hosp, Program Genom, Boston, MA USA. [Wild, Sarah H.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Willenborg, Christina; Erdmann, Jeanette] Hamburg Kiel Lubeck, DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Willenborg, Christina; Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany. [Wilson, James F.; Campbell, Harry; Polasek, Ozren; Rudan, Igor] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland. [Wong, Andrew; Kuh, Diana; Ong, Ken K.; Richards, Marcus] MRC Unit Lifelong Hlth & Ageing UCL, London, England. [Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Yu, Lei; Buchman, Aron S.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Zhang, Weihua; Scott, William R.; Tan, Sian-Tsung; Chambers, John C.; Kooner, Jaspal S.] Ealing Hosp NHS Trust, Southall, Middx, England. [Bakker, Stephan J. L.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands. [Baldassarre, Damiano; Tremoli, Elena] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy. [Bellis, Claire; Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Bellis, Claire] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Genom Res Ctr, Brisbane, Qld 4001, Australia. [Benaglio, Paola] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Benaglio, Paola; Rivolta, Carlo; Bergmann, Sven; Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Blueher, Matthias; Kovacs, Peter; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, D-04109 Leipzig, Germany. [Blueher, Matthias; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Bonnet, Fabrice] Univ Rennes 1, Rennes, France. [Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.; Narisu, Narisu; Swift, Amy J.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Bruinenberg, Marcel] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands. [Chen, Yii-Der Ida; Rotter, Jerome I.] Univ Calif Los Angeles, Med Ctr, Los Angeles BioMed Res Inst Harbor, Torrance, CA 90509 USA. [Claudi-Boehm, Simone; Kratzer, Wolfgang; Merger, Sigrun; Seufferlein, Thomas; Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany. [Cole, John; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [de Geus, Eco J. C.; van Schoor, Natasja M.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 AP Wageningen, Netherlands. [Dimitriou, Maria] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ HealthSyst, Evanston, IL USA. [Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Univ Chicago, Chicago, IL 60637 USA. [Farmaki, Aliki-Eleni; Dedoussis, George] Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece. [Friedrich, Nele; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Gigante, Bruna; Leander, Karin; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden. [Glorioso, Nicola] AOU Univ Sassari, Hypertens & Related Dis Ctr, Sassari, Italy. [Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Gottesman, Omri; Bottinger, Erwin P.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Graessler, Juergen] Univ Dresden, Dept Med Pathobiochem 3, Dresden, Germany. [Grallert, Harald; Illig, Thomas; Waldenberger, Melanie; Gieger, Christian; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Grallert, Harald; Thorand, Barbara; Waldenberger, Melanie; Gieger, Christian; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Grallert, Harald; Thorand, Barbara] German Ctr Diabet Res DZD, Neuherberg, Germany. [Gu, Yu-Mei; Liu, Yan-Ping; Staessen, Jan A.] Univ Leuven, KU Leuven Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, Leuven, Belgium. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Harris, Tamara B.; Launer, Lenore J.; Schlessinger, David] NIA, NIH, Bethesda, MD 20892 USA. [Hartman, Catharina A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Hassinen, Maija; Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland. [Hattersley, Andrew T.] Univ Exeter, Inst Biomed & Clin Sci, Exeter, Devon, England. [Henders, Anjali K.; Montgomery, Grant W.; Martin, Nicholas G.] QIMR Bergofer Med Res Inst, Brisbane, Qld, Australia. [Hernandez, Dena] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Holmen, Oddgeir; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway. [Hovingh, Kees G.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Hui, Jennie; Beilby, John] Pathwest Lab Med Western Australia, Nedlands, WA, Australia. [Hui, Jennie; Beilby, John] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Husemoen, Lise L.; Jorgensen, Torben; Linneberg, Allan] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Hutri-Kahonen, Nina] Univ Tampere, Sch Med, Dept Pediat, FIN-33101 Tampere, Finland. [Hutri-Kahonen, Nina] Tampere Univ Hosp, Dept Pediat, Tampere, Finland. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Illig, Thomas] Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany. [De Jager, Philip L.; Chasman, Daniel I.; Ridker, Paul M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Jorgensen, Torben; Linneberg, Allan; Melbye, Mads] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, Aalborg, Denmark. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Juonala, Markus] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland. [Juonala, Markus] Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Juonala, Markus; Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Kanoni, Stavroula; Stirrups, Kathleen; Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Karaleftheri, Maria] Echinos Med Ctr, Echinos, Greece. [Khaw, Kay Tee] Addenbrookes Hosp, Clin Gerontol Unit, Cambridge, England. [Kinnunen, Leena; Heliovaara, Markku; Koskinen, Seppo] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Krueger, Janine] Univ Med Greifswald, Dept Med A, Greifswald, Germany. [Kumari, Meena; Langenberg, Claudia; Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, London, England. [Lannfelt, Lars] Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden. [Lanzani, Chiara] Univ Vita Salute San Raffaele, Chair Nephrol, Segrate, Milan, Italy. [Lanzani, Chiara] IRCCS San Raffaele Sci Inst, Genom Renal Dis & Hypertens Unit, Segrate, Milan, Italy. [Lotay, Vaneet] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. [Lindstrom, Jaana; Kajantie, Eero; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Linneberg, Allan] Rigshosp, Dept Clin Expt Res, Glostrup, Denmark. [Luben, Robert] Strangeways Res Lab Worts Causeway, Cambridge, England. [Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Ctr Diabet, Malmo, Sweden. [Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Dept Clin Sci, Diabet & Endocrinol Unit, Malmo, Sweden. [Magnusson, Patrik K.; Gronberg, Henrik; Hall, Per; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [McArdle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England. [Palotie, Aarno] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perusse, Louis; Tremblay, Angelo] Univ Laval, Dept Kinesiol, Quebec City, PQ, Canada. [Perusse, Louis; Vohl, Marie-Claude] Univ Laval, Inst Nutr & Funct Foods, Quebec City, PQ, Canada. [Pichler, Irene; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Pichler, Irene; Hicks, Andrew A.; Pramstaller, Peter P.] Med Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany. [Pouta, Anneli] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki, Finland. [Pouta, Anneli] Oulu Univ Hosp, Med Res Ctr, Dept Obstet & Gynecol, Oulu, Finland. [Pouta, Anneli] Univ Oulu, Oulu, Finland. [Rice, Treva K.; Rao, D. C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Sarzynski, Mark A.; Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden. [Slagboom, P. Eline] Leiden Univ Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Syvanen, Ann-Christine; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Tan, Sian-Tsung; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Tsafantakis, Emmanouil] Anogia Med Ctr, Anogia, Greece. [Voelker, Uwe; Voelzke, Henry; Wallaschofski, Henri] DZHK German Ctr Cardiovasc Res, Greifswald, Germany. [Vohl, Marie-Claude] Univ Laval, Sch Nutr, Quebec City, PQ, Canada. [Wennauer, Roman] Univ Ulm, Med Ctr, Dept Clin Chem, D-89069 Ulm, Germany. [Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Clin Med, Tromso, Norway. [Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [van Schoor, Natasja M.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. [Asselbergs, Folkert W.; van der Harst, Pim] Netherlands Heart Inst, Interuniv Cardiol Inst Netherlands, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.; Hingorani, Aroon] UCL, Inst Cardiovasc Sci, London, England. [de Bakker, Paul I. W.] Univ Med Ctr, Dept Epidemiol, Utrecht, Netherlands. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Boehm, Bernhard O.] Univ London Imperial Coll Sci Technol & Med, London, England. [Boehm, Bernhard O.] Lee Kong Chian Sch Med, Singapore, Singapore. [Boehm, Bernhard O.] Nanyang Technol Univ, Singapore 639798, Singapore. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany. [Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London, England. [Cucca, Francesco] Univ Sassari, I-07100 Sassari, Italy. [Cusi, Daniele] Natl Inst Res, Inst Biomed Technol, Segrate, Italy. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Farrall, Martin] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Franks, Paul W.] Umea Univ Hosp, Dept Publ Hlth & Clin Med, Umea, Sweden. [Franks, Paul W.; Hu, Frank; Qi, Lu; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hamsten, Anders] Karolinska Inst, Dept Med, Stockholm, Sweden. [Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Hu, Frank; Qi, Lu; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Hu, Frank; Qi, Lu; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Huikuri, Heikki V.] Oulu Univ Hosp, Med Res Ctr Oulu, Oulu, Finland. [Huikuri, Heikki V.] Univ Oulu, Oulu, Finland. [James, Alan L.] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia. [Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kaehoenen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kajantie, Eero] Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, Helsinki, Finland. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Knekt, Paul B.; Koistinen, Heikki A.] Natl Inst Hlth & Welf, Helsinki, Finland. [Koistinen, Heikki A.] Univ Helsinki, Helsinki, Finland. [Koistinen, Heikki A.] Helsinki Univ Cent Hosp, Dept Med, Helsinki, Finland. [Koistinen, Heikki A.] Abdominal Ctr Endocrinol, Helsinki, Finland. [Koistinen, Heikki A.] Minerva Fdn, Helsinki, Finland. [Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Dept Physiol, Kuopio, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lettre, Guillaume; Rioux, John D.; Tardif, Jean-Claude] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA. [Mantyselka, Pekka] Univ Eastern Finland, Sch Med, Inst Publ Hlth & Clin Nutr, Primary Hlth Care Unit, Kuopio, Finland. [Mantyselka, Pekka] Kuopio Univ Hosp, Primary Hlth Care Unit, SF-70210 Kuopio, Finland. [Melbye, Mads; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Mitchell, Braxton D.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA. [Moll, Frans L.] Univ Med Ctr Utrecht, Dept Surg, Utrecht, Netherlands. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Musk, Arthur W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Nieminen, Markku S.; Sinisalo, Juha] Helsinki Univ Cent Hosp, HUCH Heart & Lung Ctr, Div Cardiol, Helsinki, Finland. [Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands. [Palmer, Lyle J.] Univ Adelaide, Sch Publ Hlth, Adelaide, SA, Australia. [Palmer, Lyle J.] Univ Adelaide, Robinson Res Inst, Adelaide, SA, Australia. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat, Grp Hlth Res Inst, Seatte, WA USA. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Saltevo, Juha] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland. [Sattar, Naveed] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Shuldiner, Alan R.] Vetrans Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA. [Sorensen, Thorkild I. A.] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Frederiksberg, Denmark. [Staessen, Jan A.] Maastricht Univ, R&D VitaK Grp, Maastricht, Netherlands. [Stefania, Bandinelli] ASF, Geriatr Unit, Florence, Italy. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] Hosp Univ La Paz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Uusitupa, Matti] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Espoo, Finland. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Vollenweider, Peter; Waeber, Gerard] Univ Hosp Lausanne CHUV, Dept Internal Med, Lausanne, Switzerland. [Vollenweider, Peter; Waeber, Gerard] Univ Lausanne, Lausanne, Switzerland. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [CHARGE Consortium] Cohorts Heart & Aging Res Genom Epidemiol Consort, Beijing, Peoples R China. [DIAGRAM Consortium] Diabet Genet Replicat & Metaanal Consortium, Dalian, Peoples R China. [GLGC Consortium] Global Lipids Genet Consortium, Beijing, Peoples R China. [Global-BPGen Consortium] Global Blood Pressure Genet Consortium, Beijing, Peoples R China. [ICBP Consortium] Int Consortium Blood Pressure, London, England. [Palotie, Aarno; MAGIC Consortium] Metaanal Glucose & Insulin Related Traits Consort, Beijing, Peoples R China. [Gordon-Larsen, Penny] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA. [Gordon-Larsen, Penny] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. [Deloukas, Panos] King Abdulaziz Univ, PACER HD, Jeddah 21413, Saudi Arabia. [Groop, Leif C.] Univ Helsinki, FIMM, Helsinki, Finland. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ingelsson, Erik] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Popualt Hlth, Bronx, NY 10467 USA. [McCarthy, Mark I.] Oxford NIHR Biomed Res Ctr, Oxford, England. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Strachan, David P.] St Georges Univ London, Populat Hlth Res Inst, London, England. [van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Winkler, TW (reprint author), Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany. EM iris.heid@klinik.uni-regensburg.de; kari_north@unc.edu; iborecki@wustl.edu; zoltan.kutalik@unil.ch; Ruth.loos@mssm.edu RI Yang, Jian/A-5852-2010; kinnunen, leena/B-7059-2012; Grarup, Niels/K-2807-2015; mangino, massimo/F-5134-2011; Schwarz, Peter/B-5127-2013; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Deloukas, Panos/B-2922-2013; Slagboom, P. Eline/R-4790-2016; Wong, Andrew/M-8899-2016; Verweij, Niek/A-4499-2017; Magnusson, Patrik/C-4458-2017; Galesloot, Tessel/P-6667-2015; Vermeulen, H.H.M./L-4716-2015; Waldenberger, Melanie/B-5355-2014; Polasek, Ozren/B-6002-2011; Staessen, Jan/A-1065-2011; Sarzynski, Mark/A-9798-2014; Thorand, Barbara/B-5349-2014; Montgomery, Grant/B-7148-2008; Peters, Annette/A-6117-2011; Colaus, PsyColaus/K-6607-2013; Grallert, Harald/B-3424-2013; Bouchard, Claude/A-7637-2009; Smith, Albert Vernon/K-5150-2015; Erdmann, Jeanette/P-7513-2014; Beckmann, Jacques S /A-9772-2008; Leander, Karin/C-7261-2017; Yengo, Loic/D-2692-2017; Palmer, Lyle/K-3196-2014; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Gudnason, Vilmundur/K-6885-2015; Rioux, John D./A-9599-2015; OI Yang, Jian/0000-0003-2001-2474; kinnunen, leena/0000-0001-8739-4812; Grarup, Niels/0000-0001-5526-1070; mangino, massimo/0000-0002-2167-7470; Schwarz, Peter/0000-0001-6317-7880; Franke, Lude/0000-0002-5159-8802; Deloukas, Panos/0000-0001-9251-070X; Slagboom, P. Eline/0000-0002-2875-4723; Wong, Andrew/0000-0003-2079-4779; Lakka, Timo/0000-0002-9199-2871; Gigante, Bruna/0000-0003-4508-7990; Enroth, Stefan/0000-0002-5056-9137; Luben, Robert/0000-0002-5088-6343; van der Laan, Sander W./0000-0001-6888-1404; Gieger, Christian/0000-0001-6986-9554; Kumari, Meena/0000-0001-9716-1035; Forouhi, Nita/0000-0002-5041-248X; Vandenput, Liesbeth/0000-0002-1712-6131; Waldenberger, Melanie/0000-0003-0583-5093; Polasek, Ozren/0000-0002-5765-1862; Staessen, Jan/0000-0002-3026-1637; Thorand, Barbara/0000-0002-8416-6440; Montgomery, Grant/0000-0002-4140-8139; Strawbridge, Rona/0000-0001-8506-3585; Menni, Cristina/0000-0001-9790-0571; TREMOLI, ELENA/0000-0002-0929-6106; Magi, Reedik/0000-0002-2964-6011; van der Velde, Nathalie/0000-0002-6477-6209; van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Smith, Albert Vernon/0000-0003-1942-5845; Paternoster, Lavinia/0000-0003-2514-0889; Erdmann, Jeanette/0000-0002-4486-6231; Mannisto, Satu/0000-0002-8668-3046; Beckmann, Jacques S /0000-0002-9741-1900; Leander, Karin/0000-0002-1404-9222; Yengo, Loic/0000-0002-4272-9305; Palmer, Lyle/0000-0002-1628-3055; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Zeggini, Eleftheria/0000-0003-4238-659X; Verweij, Niek/0000-0002-4303-7685; Gudnason, Vilmundur/0000-0001-5696-0084; Rioux, John D./0000-0001-7560-8326; Linneberg, Allan/0000-0002-0994-0184; Peters, Annette/0000-0001-6645-0985; Jorgensen, Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Medina-Gomez, Carolina/0000-0001-7999-5538; Mitchell, Braxton/0000-0003-4920-4744; Rivolta, Carlo/0000-0002-0733-9950; Johansson, Asa/0000-0002-2915-4498; Hattersley, Andrew/0000-0001-5620-473X; Lahti, Jari/0000-0002-4310-5297; de Geus, Eco/0000-0001-6022-2666; Kleber, Marcus/0000-0003-0663-7275 FU Aarne Koskelo Foundation; Aase and Ejner Danielsens Foundation; Academy of Finland [40758, 41071, 77299, 102318, 104781, 117787, 117844, 118590, 120315, 121584, 123885, 124243, 124282, 126925, 129269, 129293, 129378, 130326, 134309, 134791, 136895, 139635, 211497, 263836, 263924, 1114194, 24300796]; Agency for Health Care Policy Research [HS06516]; Agency for Science, Technology and Research of Singapore (A*STAR); Ahokas Foundation; ALF/LUA research grant in Gothenburg; ALK-Abello A/S (Horsholm, Denmark); Timber Merchant Vilhelm Bangs Foundation; MEKOS Laboratories Denmark; Althingi (the Icelandic Parliament); American Heart Association (AHA) [13POST16500011]; ANR ("Agence Nationale de la 359 Recherche"); Ark (NHMRC Enabling Facility); Arthritis Research UK [19542, 18030]; AstraZeneca; Augustinus Foundation; Australian National Health and Medical Research Council (NHMRC) [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601, 1011506]; Australian Research Council (ARC) [DP0770096, DP1093502]; Becket Foundation; bi-national BMBF/ANR funded project CARDomics [01KU0908A]; Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL) [184.021.007, CP 32]; Biocentrum Helsinki; Boehringer Ingelheim Foundation; British Heart Foundation [RG/10/12/28456, SP/04/ 002]; Canadian Institutes for Health Reseaerch [FRCN-CCT-83028]; Cancer Research UK [C490/A10124, C490/A10119]; Center for Medical Systems Biology (CMSB; NWO Genomics); Centers for Disease Control and Prevention and Association of Schools of Public Health [1734, S043, S3486]; Centre of Excellence Baden-Wurttemberg Metabolic Disorders; Chief Scientist Office of the Scottish Government; Clinical Research Facility at Guys & St Thomas NHS Foundation Trust; Contrat de Projets Etat-Region (CPER); Croatian Science Council [8875]; CVON (GENIUS); Danish Agency for Science, Technology and Innovation; Danish Centre for Health Technology Assessment, Novo Nordisk Inc.; Danish Council for Independent Research [DFF 1333-00124]; Danish Diabetes Association; Danish Heart Foundation; Danish Medical Research Council; Danish Ministry of Internal Affairs and Health; Danish National Research Foundation; Danish Pharmaceutical Association; Danish Pharmacists Fund; Danish Research Council; Deutsche Forschungsgemeinschaft; Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD); Dr. Robert Pfleger-Stiftung; Dresden University of Technology Funding Grant, Med Drive; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Economic Structure Enhancing Fund (FES); Dutch Kidney Foundation; Dutch Ministry for Health, Welfare and Sports; Dutch Ministry of Economic Affairs; Dutch Ministry of Education, Culture and Science; Egmont Foundation; Else Kraner-Fresenius Stiftung [2012_A147, P48/08//A11/08]; Emil Aaltonen Foundation; Erasmus Medical Center and Erasmus University, Rotterdam; Estonian Ministry of Science and Education [SF0180142s08]; European Commission [223004, 2004310, DGXII, FP6-EUROSPAN, FP6-EXGENESIS, FP6-LSHG-CT2006-018947, FP6-LSHG-CT-2006-01947, FP6-LSHM- CT-2004-503485, FP6-LSHM-CT-2006037593, FP6-LSHM-CT-2007-037273, FP7-201379, FP7-201668, FP7-279143, FP7-305739, FP7313010, FP7-ENGAGE-HEALTH-F4-2007-201413, FP7-EurHEALTHAgeing-277849, FP7-HEALTH-F42007-201550, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F2-2008-201865-GEFOS, HEALTH-F7305507 HOMAGE, LSHM-CT-2006-037593, QLG1CT-2001-01252, QLG1-CT-2002-00896, QLG2-CT2002-01254]; European Regional Development Fund (ERDF); Wissenschaftsoffensive TMO; European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN) [3.2.0304.11-0312]; European Research Council (ERC) [2011-StG-280559-SEPI, 2011-294713-EPLORE, 230374]; European Science Foundation (ESF) [EU/QLRT-2001-01254]; EuroSTRESS project [FP-006]; Finlands Slottery Machine Association; Finnish Centre for Pensions (ETK); Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish Funding Agency for Technology and Innovation [40058/07]; Finnish Medical Society; the Finnish Ministry of Education and Culture [627]; Finnish Ministry of Health and Social Affairs [5254]; Finnish National Public Health Institute (current National Institute for Health and Welfare); Finnish Special Governmental Subsidy for Health Sciences; Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation; Flemish League against Cancer, ITEA2 (project Care4Me); Folkhalsan Research Foundation; Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen; Foundation for Life and Health in Finland; the Foundation for Strategic Research (SSF); Stockholm County Council [560283]; G. Ph. Verhagen Foundation; Gene-diet Interactions in Obesity' project (GENDINOB); Genetic Association Information Network (GAIN); GENEVA Coordinating Center [U01 HG 004446]; GenomEUtwin [EU/QLRT2001-01254, QLG2-CT-2002-01254]; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; German Diabetes Association; German Ministry of Cultural Affairs; German Federal Ministry of Education and Research (BMBF) [03IS2061A, 03ZIK012, 01ZZ9603, 01ZZ0103, 01ZZ0403]; German National Genome Research Network (NGFN-2 and NGFN-plus); German Research Council [SFB1052]; Great Wine Estates of the Margaret River region of Western Australia; Greek General Secretary of Research and Technology research grant (PENED; Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; Health Fund of the Danish Health Insurance Societies; the Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Helsinki University Central Hospital special government funds (EVO) [TYH7215, TKK2012005, TYH2012209]; Hjartavernd (the Icelandic Heart Association); Ib Henriksen Foundation; Illinois Department of Public Health; Translational Genomics Research Institute; INTERREG IV Oberrhein Program [A28]; Interuniversity Cardiology Institute of the Netherlands (ICIN) [09.001]; Italian Ministry of Health "targeted project" [ICS110.1/RF97.71]; Italian National Centre of Research InterOmics [PB05_ SP3]; John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health; Johns Hopkins University Center for Inherited Disease Research (CIDR); Joint grant from Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; Juho Vainio Foundation; Juselius Foundation (Helsinki, Finland); International (JDRF); KfH Stiftung Praventivmedizin e. V.; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Leenaards Foundation; Leiden University Medical Center; Liv och Halsa; Local Government Pensions Institution (KEVA); Lokaal Gezondheids Overleg (LOGO) Leuven and Hageland; LudwigMaximilians- Universitat; LMUinnovativ; Lundberg Foundation; March of Dimes Birth Defects Foundation; Medical Research Council [G0601966, G0700931, G0000934, G0500539, G0600705, G1002319, G0701863PrevMetSyn/SALVE, MC_ U106179471, MC_ UU_ 12019/1]; MRC centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); MRC Centre for Obesity and Related Metabolic Diseases; MRC Human Genetics Unit; Medical Research Council of Canada; Mid-Atlantic Nutrition and Obesity Research Center [P30 DK072488]; Ministry of the Flemish Community, Brussels, Belgium [G. 0881.13, G. 0880.13]; MIUR-CNR Italian Flagship Project; Montreal Heart Institute Foundation; Munich Center of Health Sciences (MC Health); Municipal Health Care Center and Hospital in Jakobstad; Narpes Health Care Foundation; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Cancer Institute [CA047988]; National Center for Advancing Translational Sciences [UL1TR000124]; National Center for Research Resources [U54RR020278]; National Heart, Lung and Blood Institute (NHLBI) [1RL1MH083268-01, 5R01HL087679-02, HHSN268200800007C, HHSN268201200036C, HL043851, HL080467, HL087647, HL36310, HL45670, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N02HL64278, R01HL086694, R01HL087641, R01HL087652, R01HL087676, R01HL59367, R01HL103612, R01HL105756, R01HL120393, U01HL080295]; National Human Genome Research Institute (NHGRI) [U01HG004402]; National Institute of Child Health and Human Development (NICHD); National Institute of Diabetes and Digestive and Kidney Disease (NIDDKDRC) [P30 DK072488, 1R01DK8925601, DK063491, R01DK089256]; National Institute of Food and Agriculture [2007-35205-17883]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [263-MA-410953, 263-MD-821336, 263-MD-9164, AG023629, AG13196, NO1AG12109, P30AG10161, R01AG15819, R01AG17917, R01AG023629, R01AG30146]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [5-P60-AR30701, 5-P60-AR49465-03]; National Institutes of Health (NIH) [1R01DK8925601, 1RC2MH089951, 1RC2MH089995, 1Z01HG000024, 2T32 HL 00705536, 5R01DK075681, 5R01MH63706: 02, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, AG028555, AG08724, AG04563, AG10175, AG08861, DA12854, DK046200, DK091718, F32AR059469, HG002651, HHSN268200625226C, HHSN268200782096C, HL084729, MH081802, N01AG12100, N01HG65403, R01AG011101, R01AG030146, R01D0042157-01A, R01DK062370, R01DK072193, R01DK093757, R01DK075787, R01HL71981, R01MH59565, R01MH59566, R01MH59571, R01MH59586, R01MH59587, R01MH59588, R01MH60870, R01MH60879, R01MH61675, R01MH67257, R01MH81800, R01NS45012, U01066134, U01CA098233, U01DK062418, U01HG004423, U01HG004436, U01HG004438, U01HL072515-06, U01HL105198, U01HL84756, U01MH79469, U01MH79470, U01NS069208-01, UL1RR025005]; NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; NIHR Cambridge Biomedical research Centre; the Netherlands Heart Foundation [2001 D 032]; Netherlands Organisation for Scientific Research (NWO; Geestkracht program grant) [10-000-1002, 050-060-810, 100-001-004, 175.010.2003.005, 175.010.2005.011, 175.010.2007.006, 261-98-710, 40-0056-98-9032, 400-05-717, 452-04-314, 452-06-004, 480-01-006, 480-04-004, 480-05-003, 480-07-001, 481-08-013, 60-60600-97-118, 904-61-090, 904-61-193, 911-03012, 985-10-002, Addiction-31160008, GB-MW 94038- 011, SPI 56-464-14192]; Netherlands Organization for the Health Research and Development (ZonMw) [91111025]; Nordic Center of Excellence in Disease Genetics; Nordic Centre of Excellence on Systems biology in controlled dietary interventions and cohort studies, SYSDIET [070014]; Northern Netherlands Collaboration of Provinces (SNN); Novo Nordisk Foundation; Office of Research and Development, Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; Ollqvist Foundation; Paavo Nurmi Foundation; Pahlssons Foundation; Paivikki and Sakari Sohlberg Foundation; Perklen Foundation; Republic of Croatia Ministry of Science, Education and Sports research [108-1080315-0302]; Research Centre for Prevention and Health; Capital Region of Denmark; Research Foundation of Copenhagen County; Research Institute for Diseases in the Elderly [014-93-015]; Reynold's Foundation; Rotterdam Oncologic Thoracic Study Group, Erasmus Trust Fund, Foundation against Cancer; Royal Swedish Academy of Science; Russian Foundation for Basic Research [NWO-RFBR 047.017.043]; Rutgers University Cell and DNA Repository cooperative agreement [NIMH U24 MH068457-06]; Samfundet Folkhalsan; Sigrid Juselius Foundation; Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds [9M048, 9N035]; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Societe Francophone du 358 Diabste (SFD); South Tyrolean Sparkasse Foundation; Stichting Nationale Computerfaciliteiten (National Computing Facilities Foundation, NCF); Strategic Cardiovascular Programme of Karolinska Institutet; Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Diabetes Association; Swedish Diabetes Foundation [2013-024]; Swedish Foundation for Strategic Research (SSF) [ICA08-0047]; Swedish HeartLung Foundation [20120197]; Swedish Medical Research Council [K2007-66X-20270-01-3, 20121397]; Swedish Ministry for Higher Education; Swedish Research Council [8691, M-2005-1112, 2009-2298]; Swedish Society for Medical Research;; Swiss National Science Foundation [31003A-143914, 3200B0105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30148401]; SystemsX.ch [51RTP0_151019]; Tampere Tuberculosis Foundation; TEKES [40058/07, 70103/06]; The Paul Michael Donovan Charitable Foundation; Torsten and Ragnar Sderberg Foundation; Umea Medical Research Foundation; United Kingdom NIHR Cambridge Biomedical Research Centre; Universities and Research of the Autonomous Province of Bolzano, South Tyrol; University Hospital of Regensburg (ReForM A, ReForM C); University Hospital Oulu, Biocenter, University of Oulu, Finland [75617]; University Medical Center Groningen; University of Groningen; University of Maryland General Clinical Research Center [M01RR16500, AG000219]; University of Tartu (SP1GVARENG); University of Tromso, Norwegian Research Council [185764]; Vasterbottens Intervention Programme; Velux Foundation; VU University Institute for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam (NCA); Wellcome Trust [064890, 068545/Z/02, 076113/B/04/Z, 077016/Z/05/Z, 079895, 084723/Z/08/Z, 086596/Z/08/Z, 088869/B/09/Z, 089062, 090532, 098017, 098051, 098381]; Western Australian DNA Bank (NHMRC Enabling Facility); Yrjo Jahnsson Foundation [56358]; Zorg Onderzoek Nederland-Medische Wetenschappen, KWF Kankerbestrijding, Stichting Centraal Fonds Reserves van voormalig Vrijwillige Ziekenfondsverzekeringen; National Institute for Health and Welfare (THL); National Institute for Health Research (NIHR) [RP-PG-0407-10371]; National Institute of Allergy and Infectious Diseases (NIAID) FX Funding for this study was provided by the Aarne Koskelo Foundation; the Aase and Ejner Danielsens Foundation; the Academy of Finland (40758, 41071, 77299, 102318, 104781, 117787, 117844, 118590, 120315, 121584, 123885, 124243, 124282, 126925, 129269, 129293, 129378, 130326, 134309, 134791, 136895, 139635, 211497, 263836, 263924, 1114194, 24300796); the Agency for Health Care Policy Research (HS06516); the Agency for Science, Technology and Research of Singapore (A*STAR); the Ahokas Foundation; the ALF/LUA research grant in Gothenburg; the ALK-Abello A/S (Horsholm, Denmark), Timber Merchant Vilhelm Bangs Foundation, MEKOS Laboratories Denmark; the Althingi (the Icelandic Parliament); the American Heart Association (AHA; 13POST16500011); the ANR ("Agence Nationale de la 359 Recherche"); the Ark (NHMRC Enabling Facility); the Arthritis Research UK (19542, 18030); the AstraZeneca; the Augustinus Foundation; the Australian National Health and Medical Research Council (NHMRC; 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601 and 1011506); the Australian Research Council (ARC; DP0770096 and DP1093502); the Becket Foundation; the bi-national BMBF/ANR funded project CARDomics (01KU0908A); the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL; 184.021.007, CP 32); the Biocentrum Helsinki; the Boehringer Ingelheim Foundation; the British Heart Foundation (RG/10/12/28456, SP/04/ 002); the Canadian Institutes for Health Reseaerch (FRCN-CCT-83028); the Cancer Research UK (C490/A10124, C490/A10119); the Center for Medical Systems Biology (CMSB; NWO Genomics); the Centers for Disease Control and Prevention and Association of Schools of Public Health (1734, S043, S3486); the Centre of Excellence Baden-Wurttemberg Metabolic Disorders; the Chief Scientist Office of the Scottish Government; the Clinical Research Facility at Guys & St Thomas NHS Foundation Trust; the Contrat de Projets Etat-Region (CPER); the Croatian Science Council (Grant no. 8875); the CVON (GENIUS); the Danish Agency for Science, Technology and Innovation; the Danish Centre for Health Technology Assessment, Novo Nordisk Inc.; the Danish Council for Independent Research (DFF 1333-00124); the Danish Diabetes Association; Danish Heart Foundation; the Danish Medical Research Council; the Danish Ministry of Internal Affairs and Health; the Danish National Research Foundation; the Danish Pharmaceutical Association; Danish Pharmacists Fund; the Danish Research Council; the Deutsche Forschungsgemeinschaft; the Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD); the Dr.; Robert Pfleger-Stiftung; the Dresden University of Technology Funding Grant, Med Drive; the Dutch Brain Foundation; the Dutch Diabetes Research Foundation; the Dutch Economic Structure Enhancing Fund (FES); the Dutch Kidney Foundation; the Dutch Ministry for Health, Welfare and Sports; the Dutch Ministry of Economic Affairs; the Dutch Ministry of Education, Culture and Science; the Egmont Foundation; the Else Kraner-Fresenius Stiftung (2012_A147, P48/08//A11/08); the Emil Aaltonen Foundation; the Erasmus Medical Center and Erasmus University, Rotterdam; the Estonian Ministry of Science and Education (SF0180142s08); the European Commission (223004, 2004310, DGXII, FP6-EUROSPAN, FP6-EXGENESIS, FP6-LSHG-CT2006-018947, FP6-LSHG-CT-2006-01947, FP6-LSHM- CT-2004-503485, FP6-LSHM-CT-2006037593, FP6-LSHM-CT-2007-037273, FP7-201379, FP7-201668, FP7-279143, FP7-305739, FP7313010, FP7-ENGAGE-HEALTH-F4-2007-201413, FP7-EurHEALTHAgeing-277849, FP7-HEALTH-F42007-201550, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F2-2008-201865-GEFOS, HEALTH-F7305507 HOMAGE, LSHM-CT-2006-037593, QLG1CT-2001-01252, QLG1-CT-2002-00896, QLG2-CT2002-01254); the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO; the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN; 3.2.0304.11-0312); the European Research Council (ERC; 2011-StG-280559-SEPI, 2011-294713-EPLORE, 230374); the European Science Foundation (ESF; EU/QLRT-2001-01254); the EuroSTRESS project FP-006; the Finlands Slottery Machine Association; the Finnish Centre for Pensions (ETK); the Finnish Cultural Foundation; the Finnish Diabetes Association; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Foundation for Pediatric Research; the Finnish Funding Agency for Technology and Innovation (40058/07); the Finnish Medical Society; the Finnish Ministry of Education and Culture (627; 2004-2011); the Finnish Ministry of Health and Social Affairs (5254); the Finnish National Public Health Institute (current National Institute for Health and Welfare); the Finnish Special Governmental Subsidy for Health Sciences; the Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation; the Flemish League against Cancer, ITEA2 (project Care4Me); the Folkhalsan Research Foundation; the Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen; the Foundation for Life and Health in Finland; the Foundation for Strategic Research (SSF) and the Stockholm County Council (560283); the G. Ph.; Verhagen Foundation; the Gene-diet Interactions in Obesity' project (GENDINOB); the Genetic Association Information Network (GAIN); the GENEVA Coordinating Center (U01 HG 004446); the GenomEUtwin (EU/QLRT2001-01254; QLG2-CT-2002-01254); the German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H, 01 IG 07015 G); the German Diabetes Association; the German Ministry of Cultural Affairs; the German Federal Ministry of Education and Research (BMBF; 03IS2061A, 03ZIK012, 01ZZ9603, 01ZZ0103, 01ZZ0403); the German National Genome Research Network (NGFN-2 and NGFN-plus); the German Research Council (SFB1052 "Obesity mechanisms"); the Great Wine Estates of the Margaret River region of Western Australia; the Greek General Secretary of Research and Technology research grant (PENED 2003); the Gyllenberg Foundation; the Health Care Centers in Vasa, Narpes and Korsholm; the Health Fund of the Danish Health Insurance Societies; the Helmholtz Zentrum Munchen-German Research Center for Environmental Health; the Helsinki University Central Hospital special government funds (EVO #TYH7215, #TKK2012005, #TYH2012209); the Hjartavernd (the Icelandic Heart Association); the Ib Henriksen Foundation; the Illinois Department of Public Health, and the Translational Genomics Research Institute; the INTERREG IV Oberrhein Program (Project A28); the Interuniversity Cardiology Institute of the Netherlands (ICIN; 09.001); the Italian Ministry of Health "targeted project" (ICS110.1/RF97.71); the Italian National Centre of Research InterOmics PB05_ SP3; the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health; the Johns Hopkins University Center for Inherited Disease Research (CIDR); the Joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania; the Juho Vainio Foundation; the Juselius Foundation (Helsinki, Finland); the Juvenile Diabetes Research Foundation International (JDRF); the KfH Stiftung Praventivmedizin e. V.; the Knut and Alice Wallenberg Foundation; the Kuopio University Hospital; the Leenaards Foundation; the Leiden University Medical Center; the Liv och Halsa; the Local Government Pensions Institution (KEVA); the Lokaal Gezondheids Overleg (LOGO) Leuven and Hageland; the LudwigMaximilians- Universitat, as part of LMUinnovativ; the Lundberg Foundation; the March of Dimes Birth Defects Foundation; the Medical Research Council (G0601966; G0700931; G0000934; G0500539; G0600705; G1002319; G0701863; PrevMetSyn/SALVE; MC_ U106179471; MC_ UU_ 12019/1); the MRC centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); the MRC Centre for Obesity and Related Metabolic Diseases; the MRC Human Genetics Unit; the Medical Research Council of Canada; the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); the Ministry of the Flemish Community, Brussels, Belgium (G. 0881.13 and G. 0880.; 13); the MIUR-CNR Italian Flagship Project; the Montreal Heart Institute Foundation; the Munich Center of Health Sciences (MC Health); the Municipal Health Care Center and Hospital in Jakobstad; the Narpes Health Care Foundation; the National Alliance for Research on Schizophrenia and Depression (NARSAD); the National Cancer Institute (CA047988); the National Center for Advancing Translational Sciences (UL1TR000124); the National Center for Research Resources (U54RR020278); the National Heart, Lung and Blood Institute (NHLBI, 1RL1MH083268-01, 5R01HL087679-02, HHSN268200800007C, HHSN268201200036C, HL043851, HL080467, HL087647, HL36310, HL45670, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N02HL64278, R01HL086694, R01HL087641, R01HL087652, R01HL087676, R01HL59367, R01HL103612, R01HL105756, R01HL120393, U01HL080295); the National Human Genome Research Institute (NHGRI, U01HG004402); the National Institute for Health and Welfare (THL); the National Institute for Health Research (NIHR, RP-PG-0407-10371); the National Institute of Allergy and Infectious Diseases (NIAID); the National Institute of Child Health and Human Development (NICHD); the National Institute of Diabetes and Digestive and Kidney Disease (NIDDKDRC, 1R01DK8925601, DK063491, R01DK089256, P30 DK072488); the National Institute of Food and Agriculture (2007-35205-17883); the National Institute of Neurological Disorders and Stroke (NINDS); the National Institute on Aging (NIA; 263-MA-410953, 263-MD-821336, 263-MD-9164, AG023629, AG13196, NO1AG12109, P30AG10161, R01AG15819, R01AG17917, R01AG023629, R01AG30146); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5-P60-AR30701, 5-P60-AR49465-03); the National Institutes of Health (NIH; 1R01DK8925601, 1RC2MH089951, 1RC2MH089995, 1Z01HG000024, 2T32 HL 00705536, 5R01DK075681, 5R01MH63706: 02, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, AG028555, AG08724, AG04563, AG10175, AG08861, DA12854, DK046200, DK091718, F32AR059469, HG002651, HHSN268200625226C, HHSN268200782096C, HL084729, MH081802, N01AG12100, N01HG65403, R01AG011101, R01AG030146, R01D0042157-01A, R01DK062370, R01DK072193, R01DK093757, R01DK075787, R01DK075787, R01HL71981, R01MH59565, R01MH59566, R01MH59571, R01MH59586, R01MH59587, R01MH59588, R01MH60870, R01MH60879, R01MH61675, R01MH67257, R01MH81800, R01NS45012, U01066134, U01CA098233, U01DK062418, U01GM074518, U01HG004423, U01HG004436, U01HG004438, U01HL072515-06, U01HL105198, U01HL84756, U01MH79469, U01MH79470, U01NS069208-01, UL1RR025005); the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; the NIHR Cambridge Biomedical research Centre; the Netherlands Heart Foundation (2001 D 032); the Netherlands Organisation for Scientific Research (NWO; Geestkracht program grant 10-000-1002; 050-060-810; 100-001-004; 175.010.2003.005; 175.010.2005.011; 175.010.2007.; 006; 261-98-710; 40-0056-98-9032; 400-05-717; 452-04-314; 452-06-004; 480-01-006; 480-04-004; 480-05-003; 480-07-001; 481-08-013; 60-60600-97-118; 904-61-090; 904-61-193; 911-03012; 985-10-002; Addiction-31160008; GB-MW 94038- 011; SPI 56-464-14192); the Netherlands Organization for the Health Research and Development (ZonMw; 91111025); the Nordic Center of Excellence in Disease Genetics; the Nordic Centre of Excellence on Systems biology in controlled dietary interventions and cohort studies, SYSDIET (070014); the Northern Netherlands Collaboration of Provinces (SNN); the Novo Nordisk Foundation; the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; the Ollqvist Foundation; the Paavo Nurmi Foundation; the Pahlssons Foundation; the Paivikki and Sakari Sohlberg Foundation; the Perklen Foundation; the Republic of Croatia Ministry of Science, Education and Sports research (108-1080315-0302); the Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Foundation of Copenhagen County; the Research Institute for Diseases in the Elderly (014-93-015; RIDE2); the Reynold's Foundation; the Rotterdam Oncologic Thoracic Study Group, Erasmus Trust Fund, Foundation against Cancer; the Royal Swedish Academy of Science; the Russian Foundation for Basic Research (NWO-RFBR 047.017.043); the Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); the Samfundet Folkhalsan; the Sigrid Juselius Foundation; the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (9M048, 9N035); the Social Ministry of the Federal State of Mecklenburg-West Pomerania; the Societe Francophone du 358 Diabste (SFD); the South Tyrolean Sparkasse Foundation; the Stichting Nationale Computerfaciliteiten (National Computing Facilities Foundation, NCF); the Strategic Cardiovascular Programme of Karolinska Institutet and the Stockholm County Council (560183); the Susan G. Komen Breast Cancer Foundation; the Swedish Cancer Society; the Swedish Cultural Foundation in Finland; the Swedish Diabetes Association; the Swedish Diabetes Foundation (grant no. 2013-024); the Swedish Foundation for Strategic Research (SSF; ICA08-0047); the Swedish HeartLung Foundation (20120197); the Swedish Medical Research Council (K2007-66X-20270-01-3, 20121397); the Swedish Ministry for Higher Education; the Swedish Research Council (8691, M-2005-1112, 2009-2298); the Swedish Society for Medical Research; the Swiss National Science Foundation (31003A-143914, 3200B0105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30148401); SystemsX.; ch (51RTP0_151019); the Tampere Tuberculosis Foundation; the TEKES (70103/06, 40058/07); the The Paul Michael Donovan Charitable Foundation; the Torsten and Ragnar Sderberg Foundation; the Umea Medical Research Foundation; the United Kingdom NIHR Cambridge Biomedical Research Centre; the Universities and Research of the Autonomous Province of Bolzano, South Tyrol; the University Hospital of Regensburg (ReForM A, ReForM C); the University Hospital Oulu, Biocenter, University of Oulu, Finland (75617); the University Medical Center Groningen; the University of Groningen; the University of Maryland General Clinical Research Center (M01RR16500, AG000219); the University of Tartu (SP1GVARENG); the University of Tromso, Norwegian Research Council (185764); the Vasterbottens Intervention Programme; the Velux Foundation; the VU University Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the Wellcome Trust (064890, 068545/Z/02, 076113/B/04/Z, 077016/Z/05/Z, 079895, 084723/Z/08/Z, 086596/Z/ 08/Z, 088869/B/09/Z, 089062, 090532, 098017, 098051, 098381); the Western Australian DNA Bank (NHMRC Enabling Facility); the Yrjo Jahnsson Foundation (56358); and the Zorg Onderzoek Nederland-Medische Wetenschappen, KWF Kankerbestrijding, Stichting Centraal Fonds Reserves van voormalig Vrijwillige Ziekenfondsverzekeringen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. More details of acknowledgements can be found in S2 Text. NR 97 TC 21 Z9 21 U1 5 U2 32 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 OCT PY 2015 VL 11 IS 10 AR e1005378 DI 10.1371/journal.pgen.1005378 PG 42 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600002 PM 26426971 ER PT J AU Wongtrakoongate, P Riddick, G Fucharoen, S Felsenfeld, G AF Wongtrakoongate, Patompon Riddick, Gregory Fucharoen, Suthat Felsenfeld, Gary TI Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes SO PLOS GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; POLYCOMB REPRESSIVE COMPLEX-2; BIVALENT PROMOTERS; X-CHROMOSOME; CHIP-SEQ; BINDING; PLURIPOTENCY; CHROMATIN; MOUSE; EXPRESSION AB Long non-coding RNAs (lncRNAs) have been recognized as key players in transcriptional regulation. We show that the lncRNA steroid receptor RNA activator (SRA) participates in regulation through complex formation with trithorax group (TrxG) and polycomb repressive complex 2 (PRC2) complexes. Binding of the SRA-associated RNA helicase p68 preferentially stabilizes complex formation between SRA and a TrxG complex but not PRC2. In human pluripotent stem cells NTERA2, SRA binding sites that are also occupied by p68 are significantly enriched for H3K4 trimethylation. Consistent with its ability to interact with TrxG and PRC2 complexes, some SRA binding sites in human pluripotent stem cells overlap with bivalent domains. CTCF sites associated with SRA appear also to be enriched for bivalent modifications. We identify NANOG as a transcription factor directly interacting with SRA and co-localizing with it genome-wide in NTERA2. Further, we show that SRA is important for maintaining the stem cell state and for reprogramming of human fibroblasts to achieve the pluripotent state. Our results suggest a mechanism whereby the lncRNA SRA interacts with either TrxG or PRC2. These complexes may then be recruited by various DNA binding factors to deliver either activating or silencing signals, or both, to establish bivalent domains. C1 [Wongtrakoongate, Patompon; Riddick, Gregory; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Wongtrakoongate, Patompon] Mahidol Univ, Fac Sci, Dept Biochem, Bangkok 10700, Thailand. [Fucharoen, Suthat] Mahidol Univ, Inst Mol Biosci, Thalassemia Res Ctr, Nakhon Pathom, Thailand. RP Wongtrakoongate, P (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM garyf@intra.niddk.nih.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Project [DK036148-08]; Thailand Research Fund and Faculty of Science, Mahidol University [TRG5880105] FX This work was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Project DK036148-08. PW was supported by the Thailand Research Fund and Faculty of Science, Mahidol University (grant No. TRG5880105). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 7 Z9 8 U1 0 U2 3 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 OCT PY 2015 VL 11 IS 10 AR e1005615 DI 10.1371/journal.pgen.1005615 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA CV6SU UT WOS:000364401600075 PM 26496121 ER PT J AU Battisti, JM Lawyer, PG Minnick, MF AF Battisti, James M. Lawyer, Phillip G. Minnick, Michael F. TI Colonization of Lutzomyia verrucarum and Lutzomyia longipalpis Sand Flies (Diptera: Psychodidae) by Bartonella bacilliformis, the Etiologic Agent of Carrion's Disease SO PLoS Neglected Tropical Diseases LA English DT Article ID ENDOTHELIAL-CELLS; VERRUGA-PERUANA; OROYA FEVER; TRANSMISSION; VECTOR AB Bartonella bacilliformis is a pathogenic bacterium transmitted to humans presumably by bites of phlebotomine sand flies, infection with which results in a bi-phasic syndrome termed Carrion's disease. After constructing a low-passage GFP-labeled strain of B. bacilliformis, we artificially infected Lutzomyia verrucarum and L. longipalpis populations, and subsequently monitored colonization of sand flies by fluorescence microscopy. Initially, colonization of the two fly species was indistinguishable, with bacteria exhibiting a high degree of motility, yet still confined to the abdominal midgut. After 48h, B. bacilliformis transitioned from bacillus-shape to a non-motile, small coccoid form and appeared to be digested along with the blood meal in both fly species. Differences in colonization patterns became evident at 72h when B. bacilliformis was observed at relatively high density outside the peritrophic membrane in the lumen of the midgut in L. verrucarum, but colonization of L. longipalpis was limited to the blood meal within the intra-peritrophic space of the abdominal midgut, and the majority of bacteria were digested along with the blood meal by day 7. The viability of B. bacilliformis in L. longipalpis was assessed by artificially infecting, homogenizing, and plating for determination of colony-forming units in individual flies over a 13-d time course. Bacteria remained viable at relatively high density for approximately seven days, suggesting that L. longipalpis could potentially serve as a vector. The capacity of L. longipalpis to transmit viable B. bacilliformis from infected to uninfected meals was analyzed via interrupted feeds. No viable bacteria were retrieved from uninfected blood meals in these experiments. This study provides significant information toward understanding colonization of sand flies by B. bacilliformis and also demonstrates the utility of L. longipalpis as a user-friendly, live-vector model system for studying this severely neglected tropical disease. C1 [Battisti, James M.; Minnick, Michael F.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. [Lawyer, Phillip G.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Battisti, JM (reprint author), Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. EM jim.battisti@umontana.edu FU National Institutes of Health [AI095804] FX JMB and MFM are supported by National Institutes of Health Grant AI095804. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 1 Z9 1 U1 1 U2 8 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 OCT PY 2015 VL 9 IS 10 AR e0004128 DI 10.1371/journal.pntd.0004128 PG 17 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CV7NC UT WOS:000364459600034 PM 26436553 ER PT J AU Tuero, I Palma, S Cabeza, F Saleemi, S Rodriguez, S Gonzales, I Mayta, H Mahanty, S Garcia, HH Gilman, RH AF Tuero, Iskra Palma, Sandra Cabeza, Franco Saleemi, Sarah Rodriguez, Silvia Gonzales, Isidro Mayta, Holger Mahanty, Siddhartha Garcia, Hector H. Gilman, Robert H. CA Cysticercosis Working Grp Peru TI A Comparative Study of Peripheral Immune Responses to Taenia solium in Individuals with Parenchymal and Subarachnoid Neurocysticercosis SO PLoS Neglected Tropical Diseases LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SYMPTOMATIC NEUROCYSTICERCOSIS; CEREBROSPINAL-FLUID; CYSTICERCOSIS; CELLS; DIAGNOSIS; DISEASE; HETEROGENEITY; CYTOKINES; ANTIGENS AB Background The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection. Methodology Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg. Principal Findings Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-gamma/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1 beta/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-beta secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls. Conclusions/Significance T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system. C1 [Tuero, Iskra; Palma, Sandra; Mayta, Holger; Garcia, Hector H.; Gilman, Robert H.] Univ Peruana Cayetano Heredia, Lab Invest Desarrollo, Fac Ciencias & Filosofia, Lima, Peru. [Cabeza, Franco; Gilman, Robert H.] Asociac Benef PRISMA, Lima, Peru. [Saleemi, Sarah; Gilman, Robert H.] Johns Hopkins Univ, Dept Int Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Saleemi, Sarah] Johns Hopkins Sch Med, Baltimore, MD USA. [Rodriguez, Silvia; Gonzales, Isidro; Garcia, Hector H.] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima, Peru. [Mahanty, Siddhartha] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tuero, I (reprint author), NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. EM smahanty@niaid.nih.gov OI Mahanty, Siddhartha/0000-0003-1068-0524 FU Fundacion Instituto Hipolito Unanue, Lima, Peru; FI-NIH Training grant [D43 TW001140]; Welcome Trust Senior International Research Fellowship in Public Health and Tropical Medicine; National Institute of Allergy and Infectious Diseases, NIH FX This work was supported by Fundacion Instituto Hipolito Unanue, Lima, Peru. IG, SR and HM acknowledge support from FI-NIH Training grant D43 TW001140. HHG is supported by a Welcome Trust Senior International Research Fellowship in Public Health and Tropical Medicine. This research was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 3 Z9 3 U1 0 U2 4 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 OCT PY 2015 VL 9 IS 10 AR e0004143 DI 10.1371/journal.pntd.0004143 PG 15 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CV7NC UT WOS:000364459600048 PM 26506532 ER PT J AU Lu, R Herrera, BB Eshleman, HD Fu, Y Bloom, A Li, ZG Sacks, DB Goldberg, MB AF Lu, Richard Herrera, Bobby Brooke Eshleman, Heather D. Fu, Yang Bloom, Alexander Li, Zhigang Sacks, David B. Goldberg, Marcia B. TI Shigella Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation SO PLOS PATHOGENS LA English DT Article ID FLEXNERI; PATHWAY; DEATH; PROTEIN; PHOSPHORYLATION; INFLAMMASOME; INACTIVATION; PATHOGENESIS; CYTOSKELETON; EXPRESSION AB The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex. C1 [Lu, Richard; Herrera, Bobby Brooke; Eshleman, Heather D.; Fu, Yang; Bloom, Alexander; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02142 USA. [Lu, Richard; Eshleman, Heather D.; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Li, Zhigang; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02142 USA. EM marcia.goldberg@mgh.harvard.edu FU NIH [F32AI073035, R01AI081724]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease [U54AI057159]; ICCB-Longwood facility (Harvard Medical School) FX This work was supported by NIH F32AI073035 (to RL) and NIH R01AI081724 (to MBG) and by the Intramural Research Program of the NIH (to DBS). The human genome RNAi was made available through the support of the New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease (U54AI057159) and the ICCB-Longwood facility (Harvard Medical School). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 2 Z9 2 U1 1 U2 2 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 OCT PY 2015 VL 11 IS 10 AR e1005200 DI 10.1371/journal.ppat.1005200 PG 21 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CV7OE UT WOS:000364462700034 PM 26473364 ER PT J AU Roelofs, KG Jones, CJ Helman, SR Shang, XR Orr, MW Goodson, JR Galperin, MY Yildiz, FH Lee, VT AF Roelofs, Kevin G. Jones, Christopher J. Helman, Sarah R. Shang, Xiaoran Orr, Mona W. Goodson, Jonathan R. Galperin, Michael Y. Yildiz, Fitnat H. Lee, Vincent T. TI Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems SO PLOS PATHOGENS LA English DT Article ID MANNOSE-SENSITIVE HEMAGGLUTININ; PILZ DOMAIN PROTEINS; SIGNAL-TRANSDUCTION PROTEIN; GRAM-NEGATIVE BACTERIA; N-TERMINAL DOMAIN; EL-TOR BIOTYPE; PSEUDOMONAS-AERUGINOSA; BIOFILM FORMATION; XANTHOMONAS-CAMPESTRIS; ACETOBACTER-XYLINUM AB Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the Delta mshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP. C1 [Roelofs, Kevin G.; Helman, Sarah R.; Shang, Xiaoran; Orr, Mona W.; Goodson, Jonathan R.; Lee, Vincent T.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Jones, Christopher J.; Yildiz, Fitnat H.] Univ Calif Santa Cruz, Dept Microbiol & Environm Toxicol, Santa Cruz, CA 95064 USA. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Roelofs, KG (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM vtlee@umd.edu OI Lee, Vincent T./0000-0002-3593-0318 FU NIH [AI102584, R21AI096083]; NIH Intramural Research Program at the National Library of Medicine; NIH/NIAID Training Grant in Host-Pathogen Interactions [T32-AI089621] FX Support was provided to FHY (NIH grant AI102584) and VTL (NIH grant R21AI096083). MYG was supported by the NIH Intramural Research Program at the National Library of Medicine. KGR and MWO were supported in part by a NIH/NIAID Training Grant in Host-Pathogen Interactions (T32-AI089621). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 114 TC 9 Z9 9 U1 0 U2 9 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 OCT PY 2015 VL 11 IS 10 AR e1005232 DI 10.1371/journal.ppat.1005232 PG 29 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CV7OE UT WOS:000364462700054 PM 26506097 ER PT J AU Su, XZ AF Su, Xin-zhuan TI Translating Basic Research into Clinical Applications: Malaria Research at an NIH Lab SO PLoS Pathogens LA English DT Editorial Material C1 NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2015 VL 11 IS 10 AR e1005190 DI 10.1371/journal.ppat.1005190 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CV7OE UT WOS:000364462700027 PM 26447478 ER PT J AU Zarate, CA Niciu, MJ AF Zarate, Carlos A., Jr. Niciu, Mark J. TI Ketamine for depression: evidence, challenges and promise SO WORLD PSYCHIATRY LA English DT Editorial Material ID RESISTANT MAJOR DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; NMDA RECEPTOR BLOCKADE; D-ASPARTATE ANTAGONIST; DOSE KETAMINE; BIPOLAR DEPRESSION; ANTIDEPRESSANT; INFUSIONS; METABOLITES C1 [Zarate, Carlos A., Jr.; Niciu, Mark J.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RI Niciu, Mark/J-1766-2014 OI Niciu, Mark/0000-0002-5612-3021 FU Intramural Research Program at the National Institute of Mental Health; National Institutes of Health; NARSAD Independent Investigator grant; Brain & Behavior Mood Disorders Research Award FX Funding for this work was provided by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health, a NARSAD Independent Investigator grant, and a Brain & Behavior Mood Disorders Research Award to C.A. Zarate. The authors thank the 7SE research unit and staff for their support. I. Henter provided excellent editorial assistance. NR 29 TC 2 Z9 2 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2015 VL 14 IS 3 BP 348 EP 350 DI 10.1002/wps.20269 PG 3 WC Psychiatry SC Psychiatry GA CV9HA UT WOS:000364597100023 PM 26407791 ER PT J AU Sarris, J Logan, AC Akbaraly, TN Amminger, GP Balanza-Martinez, V Freeman, MP Hibbeln, J Matsuoka, Y Mischoulon, D Mizoue, T Nanri, A Nishi, D Parletta, N Ramsey, D Rucklidge, JJ Sanchez-Villegas, A Scholey, A Su, KP Jacka, FN AF Sarris, Jerome Logan, Alan C. Akbaraly, Tasnime N. Amminger, G. Paul Balanza-Martinez, Vicent Freeman, Marlene P. Hibbeln, Joseph Matsuoka, Yutaka Mischoulon, David Mizoue, Tetsuya Nanri, Akiko Nishi, Daisuke Parletta, Natalie Ramsey, Drew Rucklidge, Julia J. Sanchez-Villegas, Almudena Scholey, Andrew Su, Kuan-Pin Jacka, Felice N. TI International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry SO WORLD PSYCHIATRY LA English DT Letter ID DIETARY PATTERN; MENTAL-HEALTH; ASSOCIATION; DEPRESSION; SYMPTOMS; COHORT; AGE C1 [Sarris, Jerome] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. [Sarris, Jerome; Scholey, Andrew] Swinburne Univ Technol, Ctr Human Psychopharmacol, Hawthorn, Vic 3122, Australia. [Logan, Alan C.] CAMNR, Calabasas, CA USA. [Akbaraly, Tasnime N.] INSERM, U1198, Montpellier, France. [Akbaraly, Tasnime N.] EPHE, F-75006 Paris, France. [Akbaraly, Tasnime N.] Univ Montpellier 2, Montpellier, France. [Akbaraly, Tasnime N.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Amminger, G. Paul] Natl Ctr Excellence Youth Mental Hlth, Orygen, Parkville, Vic, Australia. [Balanza-Martinez, Vicent] Hosp La Fe, Teaching Unit Psychiat & Psychol Med, E-46009 Valencia, Spain. [Balanza-Martinez, Vicent] Univ Valencia, Sch Med, Polytech Hosp, CIBERSAM, Valencia, Spain. [Freeman, Marlene P.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat, Boston, MA 02114 USA. [Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA. [Matsuoka, Yutaka] Natl Ctr Neurol & Psychiat, Translat Med Ctr, Dept Clin Epidemiol, Tokyo, Japan. [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mizoue, Tetsuya; Nanri, Akiko] Natl Ctr Global Hlth & Med, Dept Epidemiol & Prevent, Tokyo, Japan. [Parletta, Natalie] Univ S Australia, Sch Populat Hlth, Adelaide, SA 5001, Australia. [Ramsey, Drew] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Rucklidge, Julia J.] Univ Canterbury, Dept Psychol, Christchurch 1, New Zealand. [Sanchez-Villegas, Almudena] Univ Palmas Gran Canaria, Res Inst Biomed & Hlth Sci, Las Palmas Gran Canaria, Spain. [Sanchez-Villegas, Almudena] Inst Salud Carlos III, CIBEROBN, Madrid, Spain. [Su, Kuan-Pin] China Med Univ Hosp, Dept Psychiat, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ Hosp, Mind Body Interface Lab, Taichung, Taiwan. [Su, Kuan-Pin] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan. [Jacka, Felice N.] Deakin Univ, Sch Med, IMPACT SRC, Geelong, Vic 3220, Australia. [Jacka, Felice N.] Murdoch Childrens Res Ctr, Parkville, Vic, Australia. [Jacka, Felice N.] Univ Melbourne, Royal Melbourne Hosp, Dept Psychiat, Melbourne, Vic 3050, Australia. [Jacka, Felice N.] Black Dog Inst, Randwick, NSW, Australia. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. NR 9 TC 6 Z9 6 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2015 VL 14 IS 3 BP 370 EP 371 DI 10.1002/wps.20223 PG 2 WC Psychiatry SC Psychiatry GA CV9HA UT WOS:000364597100031 PM 26407799 ER PT J AU Brown, AM Lindenberg, ML Sankineni, S Shih, JH Johnson, LM Pruthy, S Kurdziel, KA Merino, MJ Wood, BJ Pinto, PA Choyke, P Turkbey, B AF Brown, Anna M. Lindenberg, Maria L. Sankineni, Sandeep Shih, Joanna H. Johnson, Linda M. Pruthy, Suneha Kurdziel, Karen A. Merino, Maria J. Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. Turkbey, Baris TI Does focal incidental F-18-FDG PET/CT uptake in the prostate have significance? SO ABDOMINAL IMAGING LA English DT Article DE F-18-FDG PET; Prostate cancer; Multi-parametric MRI; Incidental FDG uptake ID POSITRON-EMISSION-TOMOGRAPHY; CANCER; BIOPSY AB F-18-FDG PET/CT is used to characterize many malignancies, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidental prostate F-18-FDG uptake. Thirty-one patients who underwent F-18-FDG PET/CT for reasons unrelated to prostate cancer and prostate mpMRI were eligible for this retrospective study. The mpMRI included T2-weighted (T2W), dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS) sequences. Fourteen patients were excluded (n = 8 insufficient histopathology, n = 6 radical prostatectomy before PET), and final analysis included 17 patients. A nuclear medicine physician, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUVmax) on F-18-FDG PET/CT. Sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/transrectal ultrasound fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal-Wallis and Dunn's multiple comparisons tests. The PPV of F-18-FDG PET alone in detecting prostate cancer was 0.65. Combining F-18-FDG PET as a base parameter with mpMRI (T2W, DCE, ADC, and MRS) increased the PPV to 0.82, 0.83, 0.83, and 0.94, respectively. All benign lesions had SUVmax < 6. Malignant lesions had higher SUVmax values that correlated with Gleason scores. There was a significant difference in SUVmax per prostate between the Gleason a parts per thousand yen 4 + 5 and benign categories (p = 0.03). Focal incidental prostate F-18-FDG uptake has low clinical utility alone, but regions of uptake may harbor high-grade prostate cancer, especially if SUVmax > 6. Using mpMRI to further evaluate incidental F-18-FDG uptake aids the diagnosis of prostate cancer. C1 [Brown, Anna M.; Lindenberg, Maria L.; Sankineni, Sandeep; Johnson, Linda M.; Pruthy, Suneha; Kurdziel, Karen A.; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Brown, Anna M.] Duke Univ, Sch Med, Durham, NC USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Room B3B85, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov FU NIH; Pfizer Inc.; Doris Duke Charitable Foundation; Newport Foundation; American Association for Dental Research; Howard Hughes Medical Institute; Colgate-Palmolive Company FX This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, 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 14 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD OCT PY 2015 VL 40 IS 8 BP 3222 EP 3229 DI 10.1007/s00261-015-0520-y PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CV0PD UT WOS:000363952000034 PM 26239399 ER PT J AU Ali, IU Chen, XY AF Ali, Iqbal Unnisa Chen, Xiaoyuan TI Penetrating the Blood-Brain Barrier: Promise of Novel Nanoplatforms and Delivery Vehicles SO ACS NANO LA English DT Article ID CANCER BIOMARKERS; NERVOUS-SYSTEM; NANOPARTICLES; MACROPHAGES; TRANSPORT; EXOSOMES; THERAPY; GROWTH; CELLS; SIRNA AB Multifunctional nanoplatforms combining versatile therapeutic modalities with a variety of imaging options have the potential to diagnose, monitor, and treat brain diseases. The promise of nanotechnology can only be realized by the simultaneous development of innovative brain-targeting delivery vehicles capable of penetrating the blood brain barrier without compromising its structural integrity. C1 [Ali, Iqbal Unnisa; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Ali, IU (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM alii@mail.nih.gov; shawn.chen@nih.gov RI Ali, Imran/F-7710-2010 OI Ali, Imran/0000-0001-6511-8374 FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-06] NR 27 TC 4 Z9 4 U1 2 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD OCT PY 2015 VL 9 IS 10 BP 9470 EP 9474 DI 10.1021/acsnano.5b05341 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CV0CP UT WOS:000363915300005 PM 26406936 ER PT J AU Huang, P Gao, Y Lin, J Hu, H Liao, HS Yan, XF Tang, YX Jin, A Song, JB Niu, G Zhang, GF Horkay, F Chen, XY AF Huang, Peng Gao, Yuan Lin, Jing Hu, Hao Liao, Hsien-Shun Yan, Xuefeng Tang, Yuxia Jin, Albert Song, Jibin Niu, Gang Zhang, Guofeng Horkay, Ferenc Chen, Xiaoyuan TI Tumor-Specific Formation of Enzyme-Instructed Supramolecular Self-Assemblies as Cancer Theranostics SO ACS NANO LA English DT Article DE self-assembly; nanofibers; indocyanine green; fluorescence imaging; photoacoustic imaging; photothermal therapy; theranostics ID PHOTOTHERMAL THERAPY; INDOCYANINE GREEN; SMALL MOLECULES; NANOPARTICLES; CELLS; NANOSTRUCTURES; HYDROGELS; ICG; NANOMATERIALS; NANOVESICLES AB Despite the effort of developing various nanodelivery systems, most of them suffer from undesired high uptakes by the reticuloendothelial system, such as liver and spleen. Herein we develop an endogenous phosphatase-triggered coassembly strategy to form tumor-specific indocyanine green (ICG)-doped nanofibers (5) for cancer theranostics. Based on coordinated intermolecular interactions, 5 significantly altered near-infrared absorbance of ICG, which improves the critical photoacoustic and photothermal properties. The phosphatase-instructed coassembly process, as well as its theranostic capability, was successfully conducted at different levels ranging from in vitro, living cell, tissue mimic, to in vivo. Specifically, the tumor uptake of ICG was markedly increased to 15.05 +/- 3.78%ID/g, which was 25-fold higher than that of free ICG (0.59 +/- 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh T/N ratios (>15) clearly differentiated tumors from the surrounding normal tissue. Complete tumor elimination with high therapeutic accuracy has been successfully achieved upon laser irradiation (0.8 W/cm(2), 5 min) within 24-48 h postinjection. As the first example, in vivo formation of tumor-specific ICG-doped nanofiber for PTT theranostics owns the immense potential for clinical translation of personalized nanomedicine with targeted drug delivery as well as for cancer theranostics. C1 [Huang, Peng; Lin, Jing; Hu, Hao; Yan, Xuefeng; Tang, Yuxia; Song, Jibin; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Gao, Yuan; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. [Gao, Yuan] Beijing Engn Res Ctr BioNanotechnol, Beijing 100190, Peoples R China. [Gao, Yuan] Natl Ctr NanoSci & Technol, CAS Key Lab Biol Effects Nanomaterials & Nanosafe, Beijing 100190, Peoples R China. [Lin, Jing; Liao, Hsien-Shun; Jin, Albert; Zhang, Guofeng] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Huang, Peng] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. RP Huang, P (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM peng.huang@nih.gov; gaoy@nanoctr.cn; shawn.chen@nih.gov RI Huang, Peng/R-2480-2016; OI Huang, Peng/0000-0003-3651-7813; Jin, Albert/0000-0003-3826-1081 FU National Science Foundation of China [81401465, 51573096]; NIBIB, NIH; NICHD, NIH FX This work was supported by the National Science Foundation of China (81401465, 51573096), and the Intramural Research Program (IRP) of the NIBIB and NICHD, NIH. Y.G. acknowledges the National Academies/National Research Council/NIH-NIST Postdoctoral Fellowship program. NR 40 TC 27 Z9 27 U1 32 U2 138 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD OCT PY 2015 VL 9 IS 10 BP 9517 EP 9527 DI 10.1021/acsnano.5b03874 PG 11 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CV0CP UT WOS:000363915300010 PM 26301492 ER PT J AU Nadkarni, NK Perera, S Hanlon, JT Lopez, O Newman, AB Aizenstein, H Elam, M Harris, TB Kritchevsky, S Yaffe, K Rosano, C AF Nadkarni, Neelesh K. Perera, Subashan Hanlon, Joseph T. Lopez, Oscar Newman, Anne B. Aizenstein, Howard Elam, Marshall Harris, Tamara B. Kritchevsky, Stephen Yaffe, Kristine Rosano, Caterina TI Statins and brain integrity in older adults: Secondary analysis of the Health ABC study SO ALZHEIMERS & DEMENTIA LA English DT Article DE Statins; White matter hyperintensities; Fractional anisotropy; Mean diffusivity; Cognition; Older adults ID MILD COGNITIVE IMPAIRMENT; SMALL-VESSEL DISEASE; WHITE-MATTER HYPERINTENSITIES; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ALZHEIMER-DISEASE; CARDIOVASCULAR HEALTH; CHOLESTEROL-METABOLISM; MR-IMAGES; SIMVASTATIN AB Introduction: We examined whether statins are associated with better cerebral white (WM) and gray matter (GM) indices in community-dwelling elders. Methods: In 295 older adults, we compared white matter hyperintensities (WMH) on brain magnetic resonance imaging and, total WM fractional anisotropy (FA) and GM mean diffusivity (MD) on diffusion tensor imaging, of Alzheimer's disease (AD) relevant regions in statin-exposed and statin-unexposed participants stratified by Modified Mini-Mental Status Examination (3MS) score. Results: There was no overall effect of statin exposure on cerebral structural indices. The interaction between statin exposure and 3MS was significant for total-WMH and WM FA (both P < .05) but not GM MD. In the lowest 3MS tertile (mean: 86), statin-exposed individuals had lower total-WMH and higher WM FA (P = .005 and P = .044) and FA of tracts linked to clinical AD (P-value range = .005-.04) despite statistical adjustments. These differences were not significant in the two higher 3MS tertiles. Discussion: Statins may benefit WM in older adults vulnerable to dementia. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Nadkarni, Neelesh K.; Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Newman, Anne B.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Lopez, Oscar] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Aizenstein, Howard] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Elam, Marshall] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Dept Gerontol & Geriatr, Winston Salem, NC USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Nadkarni, NK (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Pittsburgh, PA 15213 USA. EM nkn3@pitt.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA grants) [R01-AG028050, R01AG 027017, K07AG033174]; Intramural Research Program of the National Institutes of Health, National Institute on Aging (National Institute of Nursing Research grant) [R01-NR012459]; Pittsburgh Claude D. Pepper Older American's Independence Center [P30 AG024827] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grants R01-AG028050, R01AG 027017, K07AG033174, National Institute of Nursing Research grant R01-NR012459), and the Pittsburgh Claude D. Pepper Older American's Independence Center (P30 AG024827). NR 67 TC 3 Z9 3 U1 1 U2 6 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 OCT PY 2015 VL 11 IS 10 BP 1202 EP 1211 DI 10.1016/j.jalz.2014.11.003 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CV0UD UT WOS:000363968000009 PM 25592659 ER PT J AU Hyman, BT Growdon, JH Albers, MW Buckner, RL Chhatwal, J Gomez-Isla, MT Haass, C Hudry, E Jack, CR Johnson, KA Khachaturian, ZS Kim, DY Martin, JB Nitsch, RM Rosen, BR Selkoe, DJ Sperling, RA St George-Hyslop, P Tanzi, RE Yap, L Young, AB Phelps, CH McCaffrey, PG AF Hyman, Bradley T. Growdon, John H. Albers, Mark W. Buckner, Randy L. Chhatwal, Jasmeer Gomez-Isla, Maria Teresa Haass, Christian Hudry, Eloise Jack, Clifford R., Jr. Johnson, Keith A. Khachaturian, Zaven S. Kim, Doo Yeon Martin, Joseph B. Nitsch, Roger M. Rosen, Bruce R. Selkoe, Dennis J. Sperling, Reisa A. St George-Hyslop, Peter Tanzi, Rudolph E. Yap, Liang Young, Anne B. Phelps, Creighton H. McCaffrey, Patricia G. TI Massachusetts Alzheimer's Disease Research Center: Progress and challenges SO ALZHEIMERS & DEMENTIA LA English DT Article ID AMYLOID-BETA; PROTEIN; GENE C1 [Hyman, Bradley T.; Growdon, John H.; Albers, Mark W.; Chhatwal, Jasmeer; Gomez-Isla, Maria Teresa; Hudry, Eloise; Kim, Doo Yeon; Sperling, Reisa A.; Tanzi, Rudolph E.; Yap, Liang; Young, Anne B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hyman, Bradley T.; Growdon, John H.; Albers, Mark W.; Buckner, Randy L.; Chhatwal, Jasmeer; Gomez-Isla, Maria Teresa; Hudry, Eloise; Johnson, Keith A.; Kim, Doo Yeon; Rosen, Bruce R.; Selkoe, Dennis J.; Sperling, Reisa A.; Tanzi, Rudolph E.; Yap, Liang; Young, Anne B.] Harvard Univ, Sch Med, Boston, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Haass, Christian] Univ Munich, Dept Biochem, Munich, Bavaria, Germany. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Johnson, Keith A.; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.; Selkoe, Dennis J.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Khachaturian, Zaven S.] Khachaturian & Associates Inc, Potomac, MD USA. [Martin, Joseph B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Nitsch, Roger M.] Univ Zurich, Dept Psychiat, Zurich, Switzerland. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [St George-Hyslop, Peter] Univ Toronto, Dept Med, Toronto, ON, Canada. [Phelps, Creighton H.] NIA, NIH, Bethesda, MD 20892 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM bhyman@mgh.harvard.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU National Institute on Aging of the National Institutes of Health [P50 AG005134]; Biogen; Idec Lilly USA, LLC; FORUM Pharmaceuticals, Inc; Novartis; Pfizer, Inc.; Cure Alzheimer's Fund FX The Massachusetts Alzheimer's Disease Research Center (ADRC) is supported by the National Institute on Aging of the National Institutes of Health under award number P50 AG005134. The Center received support from the following companies for its 30th anniversary symposium: Biogen, Idec Lilly USA, LLC, FORUM Pharmaceuticals, Inc, Novartis, and Pfizer, Inc. The nonprofit Cure Alzheimer's Fund also provided funding support for the center's 30th anniversary celebrations. NR 17 TC 1 Z9 1 U1 1 U2 7 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 OCT PY 2015 VL 11 IS 10 BP 1241 EP 1245 DI 10.1016/j.jalz.2015.06.1887 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CV0UD UT WOS:000363968000013 PM 26297855 ER PT J AU Do, H Navarro, V Kleiner, DE Barnhart, H Stolz, A AF Do, Hannah Navarro, Vic Kleiner, David E. Barnhart, Huiman Stolz, Andrew TI Acute Hepatocellular Injury With Autoimmune Features Associated With Move Free (R) Dietary Supplement SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Do, Hannah] Univ So Calif, Los Angeles, CA USA. [Navarro, Vic] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Barnhart, Huiman] Duke Univ, Durham, NC USA. [Stolz, Andrew] Univ So Calif, Div Gastrointestinal & Liver Dis, Los Angeles, CA 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 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 753 BP S330 EP S330 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715901299 ER PT J AU Saito, YA Almazar, AE Locke, GR Bouras, E Howden, CW Lacy, BE DiBaise, J Prather, C Abraham, B El-Serag, H Moayyedi, P Herrick, LM Szarka, L Hamilton, F Tilkes, K Schleck, C Zinsmeister, AR Talley, NJ AF Saito, Yuri A. Almazar, Ann E. Locke, G. Richard, III Bouras, Ernest Howden, Colin W. Lacy, Brian E. DiBaise, John Prather, Charlene Abraham, Bincy El-Serag, Hashem Moayyedi, Paul Herrick, Linda M. Szarka, Lawrence Hamilton, Frank Tilkes, Katherine Schleck, Cathy Zinsmeister, Alan R. Talley, Nicholas J. TI Effect of Antidepressants on Sleep in Functional Dyspepsia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Saito, Yuri A.; Almazar, Ann E.; Locke, G. Richard, III; Herrick, Linda M.; Szarka, Lawrence; Tilkes, Katherine; Schleck, Cathy; Zinsmeister, Alan R.] Mayo Clin, Rochester, MN USA. [Bouras, Ernest] Mayo Clin, Jacksonville, FL 32224 USA. [Howden, Colin W.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Lacy, Brian E.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [DiBaise, John] Mayo Clin, Scottsdale, AZ USA. [Prather, Charlene] St Louis Univ, St Louis, MO 63103 USA. [Abraham, Bincy] Houston Methodist Hosp, Houston, TX USA. [El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Moayyedi, Paul] McMaster Univ, Hamilton, ON, Canada. [Hamilton, Frank] NIH, Bethesda, MD 20892 USA. [Talley, Nicholas J.] Univ Newcastle, New Lambton, Australia. 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 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 1744 BP S740 EP S741 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715903357 ER PT J AU Singh, N Takyar, VK Etzion, O Trowers, E AF Singh, Nirmal Takyar, Varun K. Etzion, Ohad Trowers, Eugene TI Proton Pump Inhibitor Use as a Risk Factor for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 80th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 16-21, 2015 CL Honolulu, HI SP Amer Coll Gastroenterol C1 [Singh, Nirmal] Banner Univ Med Ctr, Tucson, AZ USA. [Takyar, Varun K.; Etzion, Ohad] NIDDK, NIH, Bethesda, MD 20892 USA. [Trowers, Eugene] Banner Univ Med Ctr, Gastroenterol, Tucson, AZ 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 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 SU 1 MA 2263 BP S939 EP S939 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KO UT WOS:000363715904422 ER PT J AU Xie, YX Zhou, B Lin, MY Sheng, ZH AF Xie, Yuxiang Zhou, Bing Lin, Mei-Yao Sheng, Zu-Hang TI Progressive endolysosomal deficits impair autophagic clearance beginning at early asymptomatic stages in fALS mice SO AUTOPHAGY LA English DT Editorial Material DE ALS; autophagy; axonal transport; dynein; late endosome; lysosome; mitochondria; motor neurons; neurodegeneration; SOD1 AB Autophagy is an important homeostatic process that functions by eliminating defective organelles and aggregated proteins over a neuron's lifetime. One pathological hallmark in amyotrophic lateral sclerosis (ALS)-linked motor neurons (MNs) is axonal accumulation of autophagic vacuoles (AVs), thus raising a fundamental question as to whether reduced autophagic clearance due to an impaired lysosomal system contributes to autophagic stress and axonal degeneration. We recently revealed progressive lysosomal deficits in spinal MNs beginning at early asymptomatic stages in fALS-linked mice expressing the human (Hs) SOD1(G93A) protein. Such deficits impair the degradation of AVs engulfing damaged mitochondria from distal axons. These early pathological changes are attributable to mutant HsSOD1, which interferes with dynein-driven endolysosomal trafficking. Elucidation of this pathological mechanism is broadly relevant, because autophagy-lysosomal deficits are associated with several major neurodegenerative diseases. Therefore, enhancing autophagic clearance by rescuing endolysosomal trafficking may be a potential therapeutic strategy for ALS and perhaps other neurodegenerative diseases. C1 [Xie, Yuxiang; Zhou, Bing; Lin, Mei-Yao; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov NR 0 TC 5 Z9 6 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD OCT PY 2015 VL 11 IS 10 BP 1934 EP 1936 DI 10.1080/15548627.2015.1084460 PG 3 WC Cell Biology SC Cell Biology GA CU9ME UT WOS:000363867800020 PM 26290961 ER PT J AU Liu, YT Flynn, TJ Xia, MH Wiesenfeld, PL Ferguson, MS AF Liu, Yitong Flynn, Thomas J. Xia, Menghang Wiesenfeld, Paddy L. Ferguson, Martine S. TI Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE HuH-7 cells; DMSO; CYP3A4; Inhibition; Induction; Hepatotoxicity ID PRIMARY HUMAN HEPATOCYTES; DRUG-METABOLISM; LIVER-INJURY; IN-VITRO; CYTOCHROME-P450 ACTIVITY; DIMETHYL-SULFOXIDE; LINES; PREDICTION; TOXICITY; INDUCERS AB A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC (50) within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity. C1 [Liu, Yitong; Flynn, Thomas J.; Wiesenfeld, Paddy L.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, Laurel, MD 20708 USA. [Xia, Menghang] NIH, Div Pre Clin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Ferguson, Martine S.] US FDA, Ctr Food Safety & Appl Nutr, Off Analyt & Outreach, Div Publ Hlth Informat & Analyt, College Pk, MD USA. RP Liu, YT (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, Laurel, MD 20708 USA. EM yitong.liu@fda.hhs.gov OI Liu, Yitong/0000-0002-4300-4349; Flynn, Thomas/0000-0002-7248-0643 FU US Food and Drug Administration FX The authors thank Dr. Michael F. Santillo for image processing and critical review of the paper. The authors thank Ms. Shelia PughBishop for technical assistance. This research was supported by the US Food and Drug Administration. This research report is not an official US Food and Drug Administration guidance or policy statement. No official support or endorsement by the US Food and Drug Administration is intended, nor should it be inferred. NR 31 TC 1 Z9 1 U1 3 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0742-2091 EI 1573-6822 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD OCT PY 2015 VL 31 IS 4-5 BP 221 EP 230 DI 10.1007/s10565-015-9306-9 PG 10 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA CV4EU UT WOS:000364220000003 PM 26377104 ER PT J AU Taveira-DaSilva, AM Jones, AM Julien-Williams, P Shawker, T Glasgow, CG Stylianou, M Moss, J AF Taveira-DaSilva, Angelo M. Jones, Amanda M. Julien-Williams, Patricia Shawker, Thomas Glasgow, Connie G. Stylianou, Mario Moss, Joel TI Effect of Fasting on the Size of Lymphangioleiomyomas in Patients With Lymphangioleiomyomatosis SO CHEST LA English DT Article ID GROWTH FACTOR-D; TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; CHYLOUS EFFUSIONS; DIURNAL-VARIATION; CHYLOTHORAX; SERUM; SIROLIMUS; CT; MUTATIONS AB BACKGROUND: Lymphangioleiomyomas occur in 38% of patients with sporadic lymphangioleiomyomatosis (LAM) and may cause pain and increased abdominal girth, mimicking the presence of a malignancy. Lymphatic involvement in LAM is closely associated with elevated serum levels of vascular endothelium growth factor-D (VEGF-D). Because lymphangioleiomyomas undergo diurnal variation in volume, we hypothesized that daytime ingestion of food, by increasing chyle formation and lymphatic flow, is the cause of an increase in lymphangioleiomyoma volume. METHODS: Subjects had abdominopelvic sonograms and blood drawn for measurement of serum VEGF-D levels under nonfasting (day 1) and fasting (day 2) conditions. The size of the lymphangioleiomyomas was determined by a radiologist who was blinded to the subjects' status. The Wilcoxon signed rank test was used to determine whether the nonfasting tumor size was different from the fasting tumor size. RESULTS: Thirty-five women were studied (aged 45.2 +/- 8.5 years; FEV1, 82% +/- 25%; diffusing capacity of the lung for carbon monoxide, 64% +/- 25% predicted). Images suitable for volume measurements were obtained in 30 subjects. Fasting decreased the tumor size by 20.7 +/- 39.3 cm(3) (24% +/- 40%, P < .001). Fasting VEGF-D levels (10,650 +/- 900 pg/mL) were not significantly different from nonfasting values (12,100 +/- 800 pg/mL, P = .56). CONCLUSIONS: Lymphangioleiomyoma volume decreased during the fasting state. Conversely, a combination of food intake and decreased chyle flow through lymphatics partially obstructed by LAM cells may account for increases in lymphangioleiomyoma size. Imaging studies performed under fasting conditions may help in determining whether an abdominal tumor is a result of LAM or malignancy. C1 [Taveira-DaSilva, Angelo M.; Jones, Amanda M.; Julien-Williams, Patricia; Glasgow, Connie G.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Stylianou, Mario] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Shawker, Thomas] NIH, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov FU National Institutes of Health, National Heart, Lung, and Blood Institute [NHLBI 08-H-0016] FX This study was supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute [Grant NHLBI 08-H-0016] NR 38 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2015 VL 148 IS 4 BP 1027 EP 1033 DI 10.1378/chest.15-0456 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV0QN UT WOS:000363956300043 PM 26066372 ER PT J AU Rostomyan, L Daly, AF Petrossians, P Nachev, E Lila, AR Lecoq, AL Lecumberri, B Trivellin, G Salvatori, R Moraitis, AG Holdaway, I Kranenburg-van Klaveren, DJ Zatelli, MC Palacios, N Nozieres, C Zacharin, M Ebeling, T Ojaniemi, M Rozhinskaya, L Verrua, E Jaffrain-Rea, ML Filipponi, S Gusakova, D Pronin, V Bertherat, J Belaya, Z Ilovayskaya, I Sahnoun-Fathallah, M Sievers, C Stalla, GK Castermans, E Caberg, JH Sorkina, E Auriemma, RS Mittal, S Kareva, M Lysy, PA Emy, P De Menis, E Choong, CS Mantovani, G Bours, V De Herder, W Brue, T Barlier, A Neggers, SJCMM Zacharieva, S Chanson, P Shah, NS Stratakis, CA Naves, LA Beckers, A AF Rostomyan, Liliya Daly, Adrian F. Petrossians, Patrick Nachev, Emil Lila, Anurag R. Lecoq, Anne-Lise Lecumberri, Beatriz Trivellin, Giampaolo Salvatori, Roberto Moraitis, Andreas G. Holdaway, Ian Kranenburg-van Klaveren, Dianne J. Zatelli, Maria Chiara Palacios, Nuria Nozieres, Cecile Zacharin, Margaret Ebeling, Tapani Ojaniemi, Marja Rozhinskaya, Liudmila Verrua, Elisa Jaffrain-Rea, Marie-Lise Filipponi, Silvia Gusakova, Daria Pronin, Vyacheslav Bertherat, Jerome Belaya, Zhanna Ilovayskaya, Irena Sahnoun-Fathallah, Mona Sievers, Caroline Stalla, Gunter K. Castermans, Emilie Caberg, Jean-Hubert Sorkina, Ekaterina Auriemma, Renata Simona Mittal, Sachin Kareva, Maria Lysy, Philippe A. Emy, Philippe De Menis, Ernesto Choong, Catherine S. Mantovani, Giovanna Bours, Vincent De Herder, Wouter Brue, Thierry Barlier, Anne Neggers, Sebastian J. C. M. M. Zacharieva, Sabina Chanson, Philippe Shah, Nalini Samir Stratakis, Constantine A. Naves, Luciana A. Beckers, Albert TI Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients SO ENDOCRINE-RELATED CANCER LA English DT Article DE gigantism; pituitary adenoma; somatotropinoma; growth hormone; aryl hydrocarbon receptor interacting protein gene; familial isolated pituitary adenoma ( FIPA); X-linked acrogigantism (X-LAG) syndrome ID ADULT BODY-HEIGHT; THERAPEUTIC RESPONSES; SECULAR TRENDS; YOUNG-PATIENTS; AIP GENE; ADENOMAS; MUTATION; CHILDREN; STATURE; WEIGHT AB Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients ( 163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height > 2 S.D. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were >= 10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in > 50% of cases. C1 [Petrossians, Patrick; Castermans, Emilie; Caberg, Jean-Hubert; Bours, Vincent; Beckers, Albert] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, B-4000 Liege, Belgium. [Petrossians, Patrick; Castermans, Emilie; Caberg, Jean-Hubert; Bours, Vincent; Beckers, Albert] Univ Liege, Ctr Hosp Univ Liege, Dept Human Genet, B-4000 Liege, Belgium. [Nachev, Emil; Zacharieva, Sabina] Med Univ Sofia, Clin Ctr Endocrinol & Gerontol, Sofia, Bulgaria. [Lila, Anurag R.; Shah, Nalini Samir] King Edward Mem Hosp, Dept Endocrinol, Bombay, Maharashtra, India. [Lecoq, Anne-Lise; Chanson, Philippe] Hop Univ Paris Sud, AP HP, Serv Endocrinol & Malad Reprod, F-94275 Le Kremlin Bicetre, France. [Lecoq, Anne-Lise; Chanson, Philippe] Ctr Reference Malad Endocriniennes Rares Croissan, F-94275 Le Kremlin Bicetre, France. [Lecoq, Anne-Lise; Chanson, Philippe] Univ Paris Sud, UMR S1185, F-94276 Le Kremlin Bicetre, France. [Lecoq, Anne-Lise; Chanson, Philippe] INSERM, Fac Med Paris Sud, U1185, F-94276 Le Kremlin Bicetre, France. [Lecumberri, Beatriz] Hosp Univ La Paz, Serv Endocrinol & Nutr, Madrid, Spain. [Lecoq, Anne-Lise; Trivellin, Giampaolo; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet & Pediat Endocrino, Inter Inst Training Program,NIH, Bethesda, MD 20892 USA. [Salvatori, Roberto] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21205 USA. [Holdaway, Ian] Greenlane Clin Ctr, Dept Endocrinol, Auckland, New Zealand. [Kranenburg-van Klaveren, Dianne J.; De Herder, Wouter; Neggers, Sebastian J. C. M. M.] Erasmus MC, Dept Internal Med, Endocrinol Sect, Rotterdam, Netherlands. [Zatelli, Maria Chiara] Univ Ferrara, Dept Med Sci, Sect Endocrinol & Internal Med, I-44121 Ferrara, Italy. [Palacios, Nuria] Hosp Univ Puerta Hierro, Serv Endocrinol, Madrid, Spain. [Nozieres, Cecile] Ctr Hosp Lucien Hussel, Serv Endocrinol Diabetol, F-38209 Vienne, France. [Zacharin, Margaret] Univ Melbourne, Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Ebeling, Tapani; Ojaniemi, Marja] Univ Oulu, Oulu Univ Hosp, Dept Internal Med, Oulu, Finland. [Ebeling, Tapani; Ojaniemi, Marja] Univ Oulu, Oulu Univ Hosp, Dept Pediat, Oulu, Finland. [Rozhinskaya, Liudmila; Belaya, Zhanna; Kareva, Maria] Endocrinol Res Ctr, Dept Neuroendocrinol, Moscow, Russia. [Rozhinskaya, Liudmila; Belaya, Zhanna; Kareva, Maria] Endocrinol Res Ctr, Dept Bone Dis, Moscow, Russia. [Rozhinskaya, Liudmila; Belaya, Zhanna; Kareva, Maria] Endocrinol Res Ctr, Dept Endocrinol, Moscow, Russia. [Verrua, Elisa; Mantovani, Giovanna] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Unit Endocrinol & Metab Dis, Dept Clin Sci & Community Hlth, I-20122 Milan, Italy. [Jaffrain-Rea, Marie-Lise; Filipponi, Silvia] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy. [Jaffrain-Rea, Marie-Lise; Filipponi, Silvia] Neuromed IRCCS, Pozzilli, Italy. [Gusakova, Daria] NA Lopatkin Sci Res Inst Urol, Androl Dept, Moscow, Russia. [Pronin, Vyacheslav; Sorkina, Ekaterina] IM Sechenov First Moscow State Med Univ, Endocrinol Clin, Moscow, Russia. [Bertherat, Jerome] Univ Paris 05, Hop Cochin, Serv Endocrinol, Inst Cochin,INSERM U1016, F-75014 Paris, France. [Ilovayskaya, Irena] Moscow Reg Res & Clin Inst, Dept Endocrinol, Moscow, Russia. [Sahnoun-Fathallah, Mona; Brue, Thierry; Barlier, Anne] Aix Marseille Univ, CNRS, UMR7286, F-13015 Marseille, France. [Sievers, Caroline; Stalla, Gunter K.] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany. [Auriemma, Renata Simona] Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurgia, Naples, Italy. [Mittal, Sachin] TN Med Coll & BYL Nair Ch Hosp, Dept Endocrinol, Bombay, Maharashtra, India. [Mittal, Sachin] BYL Nair Charitable Hosp, Mumbai, Maharashtra, India. [Lysy, Philippe A.] Catholic Univ Louvain, Clin Univ St Luc, Dept Pediat, Pediat Endocrinol Unit, B-1200 Brussels, Belgium. [Emy, Philippe] CHR Orleans, Serv Endocrinol, Orleans, France. [De Menis, Ernesto] Endocrinol Osped Gen Montebelluna, Montebelluna, Italy. [Choong, Catherine S.] Univ Western Australia, Dept Paediat Endocrinol, Princess Margaret Hosp Children, Perth, WA 6009, Australia. [Choong, Catherine S.] Univ Western Australia, Sch Pediat & Child Hlth, Perth, WA 6009, Australia. [Brue, Thierry] APHM Concept, Dept Endocrinol, F-13385 Marseille, France. [Barlier, Anne] APHM Concept, Mol Biol Lab, F-13385 Marseille, France. [Naves, Luciana A.] Univ Brasilia, Fac Med, Dept Endocrinol, Brasilia, DF, Brazil. RP Beckers, A (reprint author), Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, Domaine Univ Sart Tilman, B-4000 Liege, Belgium. EM albert.beckers@chu.ulg.ac.be RI Jaffrain-Rea, Marie-Lise/D-1129-2009; Trivellin, Giampaolo/J-6583-2016; Daly, Adrian /E-2178-2011; OI Jaffrain-Rea, Marie-Lise/0000-0002-5916-8997; Trivellin, Giampaolo/0000-0003-2384-4153; Daly, Adrian /0000-0001-6130-2975; Rostomyan, Liliya/0000-0003-3784-2132; Brue, Thierry/0000-0001-8482-6691; Barlier, Anne/0000-0002-3740-6173 FU JABBS Foundation (UK) [1128402]; Fonds d'Investissement de Recherche Scientifique of the Centre Hospitalier Universitaire de Liege FX This study was supported by an educational grant from the JABBS Foundation (UK Charity Number: 1128402) and from the Fonds d'Investissement de Recherche Scientifique of the Centre Hospitalier Universitaire de Liege, to A Beckers. This study is based in part on confidential data provided by Eurostat, the statistical office of the European Union: European Health Interview Survey (EHIS) 1 microdata. The responsibility for all conclusions drawn from the data lies entirely with the authors. NR 34 TC 24 Z9 24 U1 3 U2 6 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 OCT PY 2015 VL 22 IS 5 BP 745 EP 757 DI 10.1530/ERC-15-0320 PG 13 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CV1MM UT WOS:000364022400011 PM 26187128 ER PT J AU Sahasrabudhe, R Estrada, A Lott, P Martin, L Echeverry, GP Velez, A Neta, G Takahasi, M Saenko, V Mitsutake, N Jaeguer, E Duque, CS Rios, A Bohorquez, M Prieto, R Criollo, A Echeverry, M Tomlinson, I Carmona, LGC AF Sahasrabudhe, Ruta Estrada, Ana Lott, Paul Martin, Lynn Polanco Echeverry, Guadalupe Velez, Alejandro Neta, Gila Takahasi, Meiko Saenko, Vladimir Mitsutake, Norisato Jaeguer, Emma Simon Duque, Carlos Rios, Alejandro Bohorquez, Mabel Prieto, Rodrigo Criollo, Angel Echeverry, Magdalena Tomlinson, Ian Carvajal Carmona, Luis G. CA JTCMS Consortium TCUKIN Consortium CORGI Consortium TI The 8q24 rs6983267G variant is associated with increased thyroid cancer risk SO ENDOCRINE-RELATED CANCER LA English DT Article DE thyroid cancer; rs6983267G; 8q24; genetic susceptibility ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; COLORECTAL-CANCER; COMMON VARIANTS; PROSTATE-CANCER; CHROMOSOME 8Q24; UNITED-STATES; GENETIC RISK; SUSCEPTIBILITY; POPULATION AB The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03x10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23x10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by similar to 13%. C1 [Sahasrabudhe, Ruta; Lott, Paul; Polanco Echeverry, Guadalupe; Carvajal Carmona, Luis G.] Univ Calif Davis, UC Davis Genome Ctr, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Estrada, Ana; Polanco Echeverry, Guadalupe; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Carvajal Carmona, Luis G.] Univ Tolima, Fac Ciencias, Grp Citogenet Filogenia & Evoluc Poblac, Ibague, Colombia. [Estrada, Ana; Polanco Echeverry, Guadalupe; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Carvajal Carmona, Luis G.] Univ Tolima, Fac Ciencias Salud, Ibague, Colombia. [Martin, Lynn; Jaeguer, Emma; Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Velez, Alejandro; Simon Duque, Carlos; Rios, Alejandro] Hosp Pablo Tobon Uribe, Medellin, Colombia. [Neta, Gila] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Takahasi, Meiko] Kyoto Univ, Ctr Promot Interdisciplinary Educ & Res, Kyoto, Japan. [Takahasi, Meiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan. [Saenko, Vladimir] Nagasaki Univ, Atom Bomb Dis Inst, Dept Mol Epidemiol, Nagasaki 852, Japan. [Mitsutake, Norisato] Nagasaki Univ, Atom Bomb Dis Inst, Dept Radiat Med Sci, Nagasaki 852, Japan. [Mitsutake, Norisato] Nagasaki Univ, Res Ctr Genom Instabil & Carcinogenesis, Nagasaki 852, Japan. [Carvajal Carmona, Luis G.] Fdn Genom & Genet Mol, Ibague, Colombia. RP Carmona, LGC (reprint author), Univ Calif Davis, UC Davis Genome Ctr, Sch Med, Dept Biochem & Mol Med, 451 Hlth Sci Dr, Davis, CA 95616 USA. EM lgcarvajal@ucdavis.edu OI Lott, Paul/0000-0002-1611-442X; Mitsutake, Norisato/0000-0002-2744-8046; Evans, Gareth/0000-0002-8482-5784 FU University of California Davis; V Foundation for Cancer Research; National Institute On Aging (UC Davis Latino Aging Research Resource Center) [P30AG043097]; National Cancer Institute (Paul Calabresi Career Development Award for Clinical Oncology K12 at UC Davis) of the National Institutes of Health [K12CA138464]; FP7 CHIBCHA Consortium; Wellcome Trust [075491/Z/04]; Cancer Research UK; European Commission; Programas Doctorales Becas COLCIENCIAS [528]; Research Office from University of Tolima [400111, 360113]; Japan Society for the Promotion of Science FX L G Carvajal Carmona receives funding from the University of California Davis, The V Foundation for Cancer Research, and The National Institute On Aging (UC Davis Latino Aging Research Resource Center, award number P30AG043097) and The National Cancer Institute (Paul Calabresi Career Development Award for Clinical Oncology K12 at UC Davis, award number K12CA138464) of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. L G Carvajal Carmona, M Echeverry and I Tomlinson receive funding from the FP7 CHIBCHA Consortium. The Wellcome Trust Centre for Human Genetics is funded by the Wellcome Trust (grant number 075491/Z/04). I Tomlinson receives funding from Cancer Research UK and the European Commission. A Criollo was supported by Programas Doctorales Becas COLCIENCIAS (Convocatoria 528 del 2011). A Estrada, M Bohorquez, R Prieto and M Echeverry receive support from the Research Office from University of Tolima (projects 400111 and 360113). N Mitsutake and V Saenko were supported in part by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. NR 44 TC 5 Z9 5 U1 2 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 OCT PY 2015 VL 22 IS 5 BP 841 EP 849 DI 10.1530/ERC-15-0081 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CV1MM UT WOS:000364022400018 PM 26290501 ER PT J AU Persico, AM Arango, C Buitelaar, JK Correll, CU Glennon, JC Hoekstra, PJ Moreno, C Vitiello, B Vorstman, J Zuddas, A AF Persico, Antonio M. Arango, Celso Buitelaar, Jan K. Correll, Christoph U. Glennon, Jeffrey C. Hoekstra, Pieter J. Moreno, Carmen Vitiello, Benedetto Vorstman, Jacob Zuddas, Alessandro CA European Child & Adolescent Clinic TI Unmet needs in paediatric psychopharmacology: Present scenario and future perspectives SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Autism spectrum disorder; Biomarkers; Intellectual disability; Off-label use; Pharmaceutical policies; Psychopharmacology ID AUTISM SPECTRUM DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIALS; FRAGILE-X-SYNDROME; SEROTONIN REUPTAKE INHIBITORS; MAJOR DEPRESSIVE DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; PLURIPOTENT STEM-CELLS; DOUBLE-BLIND EFFICACY AB Paediatric psychopharmacology holds great promise in two equally important areas of enormous biomedical and social impact, namely the treatment of behavioural abnormalities in children and adolescents, and the prevention of psychiatric disorders with adolescent- or adult-onset. Yet, in striking contrast, pharmacological treatment options presently available in child and adolescent psychiatry are dramatically limited. The most important currently unmet needs in paediatric psychopharmacology are: the frequent off-label prescription of medications to children and adolescents based exclusively on data from randomized controlled studies involving adult patients; the frequent lack of age-specific dose, long-term efficacy and tolerability/safety data; the lack of effective medications for many paediatric psychiatric disorders, most critically autism spectrum disorder; the scarcity and limitations of randomized placebo-controlled trials in paediatric psychopharmacology; the unexplored potential for the prevention of psychiatric disorders with adolescent- and adult-onset; the current lack of biomarkers to predict treatment response and severe adverse effects; the need for better preclinical data to foster the successful development of novel drug therapies; and the effective dissemination of evidence-based treatments to the general public, to better inform patients and families of the benefits and risks of pharmacological interventions during development. Priorities and strategies are proposed to overcome some of these limitations, including the European Child and Adolescent Clinical Psychopharmacology Network, as an overarching PanEuropean infrastructure aimed at reliably carrying out much needed psychopharmacological trials in children and adolescents, in order to fill the identified gaps and improve overall outcomes. (C) 2015 Elsevier B.V. and ECNP. All rights reserved. C1 [Persico, Antonio M.] Univ Campus Biomed, Child & Adolescent NeuroPsychiat Unit, Rome, Italy. [Persico, Antonio M.] Mafalda Luce Ctr Pervas Dev Disorders, Milan, Italy. [Arango, Celso; Moreno, Carmen] Univ Complutense, Child & Adolescent Psychiat Dept, Hosp Gen Univ Gregorio Maranon, Sch Med,IiSGM,CIBERSAM, E-28040 Madrid, Spain. [Buitelaar, Jan K.; Glennon, Jeffrey C.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Buitelaar, Jan K.; Glennon, Jeffrey C.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Correll, Christoph U.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY USA. [Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Vorstman, Jacob] Univ Med Ctr Utrecht, Dept Psychiat, Utrecht, Netherlands. [Zuddas, Alessandro] Univ Cagliari, Dept Biomed Sci, Child & Adolescent NeuroPsychiat Unit, Cagliari, Italy. RP Persico, AM (reprint author), Univ Campus Biomed, Child & Adolescent NeuroPsychiat Unit, Rome, Italy. EM a.persico@unicampus.it RI Glennon, Jeffrey/D-2379-2013; OI Persico, Antonio/0000-0001-8910-4479; Moreno, Carmen/0000-0003-0541-4846 FU European Community [242959, 278948, 260576, 261411, 603016, 602805, 241909, 242114, 603196, 602478]; Innovative Medicines Initiative Joint Undertaking [115300]; European Union; European Federation of Pharmaceutical Industries and Associations (EFPIA); Italian Ministry of Health (CCM program); Fondazione Gaetano e Mafalda Luce; Autism Speaks; Autism Research Institute; Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, Madrid Regional Government [S2010/BMD-2422 AGES]; Fundacion Alicia Koplowitz; Fundacion Mutua Madrilena FX The authors would like to acknowledge the other participants to the TNM meeting for helpful discussion. This work has been supported by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement numbers 242959 (PERS), 278948 (TACTICS), 260576 (ADDUCE), 261411 (STOP), 603016 (MATRICS), and 602805 (AGGRESSOTYPE), 241909 (EU-GEI), 242114 (OPTiMISE), 603196 (PSYSCAN) and 602478 (METSY), and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300 (EU-AIMS), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution. Additional support to AMP by the Italian Ministry of Health (CCM program 2012), the Fondazione Gaetano e Mafalda Luce, Autism Speaks and the Autism Research Institute; to AZ by the Sardinian Regional Secretary of Health (Pharmacovigilance Res. Project); to CA and CM by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, Madrid Regional Government (S2010/BMD-2422 AGES), European Union Structural Funds, Fundacion Alicia Koplowitz and Fundacion Mutua Madrilena. NR 152 TC 13 Z9 13 U1 1 U2 12 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 OCT PY 2015 VL 25 IS 10 BP 1513 EP 1531 DI 10.1016/j.euroneuro.2015.06.009 PG 19 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CV1PZ UT WOS:000364031800002 PM 26166453 ER PT J AU Steckler, T Brose, K Haas, M Kas, MJ Koustova, E Bespalov, A AF Steckler, Thomas Brose, Katja Haas, Magali Kas, Martien J. Koustova, Elena Bespalov, Anton CA ECNP Preclinical Data Forum Networ TI The preclinical data forum network: A new ECNP initiative to improve data quality and robustness for (preclinical) neuroscience SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Reproducibility; Robustness; Relevance; Quality assurance; Neuroscience; Pre-clinical ID REPRODUCIBILITY; KNOWLEDGE; FRAMEWORK; WASTE; RIGOR AB Current limitations impeding on data reproducibility are often poor statistical design, underpowered studies, lack of robust data, lack of methodological detail, biased reporting and lack of open data sharing, coupled with wrong research incentives. To improve data reproducibility, robustness and quality for brain disease research, a Preclinical Data Forum Network was formed under the umbrella of the European College of Neuropsychopharmacology (ECNP). The goal of this network, members of which met for the first time in October 2014, is to establish a forum to collaborate in precompetitive space, to exchange and develop best practices, and to bring together the members from academia, pharmaceutical industry, publishers, journal editors, funding organizations, public/private partnerships and non-profit advocacy organizations. To address the most pertinent issues identified by the Network, it was decided to establish a data sharing platform that allows open exchange of information in the area of preclinical neuroscience and to develop an educational scientific program. It is also planned to reach out to other organizations to align initiatives to enhance efficiency, and to initiate activities to improve the clinical relevance of preclinical data. Those Network activities should contribute to scientific rigor and lead to robust and relevant translational data. Here we provide a synopsis of the proceedings from the inaugural meeting. (C) 2015 Elsevier B.V. and ECNP. All rights reserved. C1 [Steckler, Thomas] Janssen Res & Dev, B-2340 Beerse, Belgium. [Brose, Katja] Cell Press, Cambridge, MA USA. [Haas, Magali] Orion Bionetworks Inc, Cambridge, MA USA. [Kas, Martien J.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands. [Koustova, Elena] NIDA, NIH, Bethesda, MD 20892 USA. [Bespalov, Anton] AbbVie, Dept Pharmacol, Neurosci Res, Ludwigshafen, Germany. [Bespalov, Anton] Pavlov Med Univ, Inst Pharmacol, St Petersburg, Russia. RP Steckler, T (reprint author), Janssen Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium. RI Trivedi, Kruti/E-7558-2015; Bespalov, Anton/R-6506-2016 FU ECNP FX The ECNP Preclinical Data Forum Network receives financial support from ECNP. NR 31 TC 4 Z9 4 U1 3 U2 5 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 OCT PY 2015 VL 25 IS 10 BP 1803 EP 1807 DI 10.1016/j.euroneuro.2015.05.011 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CV1PZ UT WOS:000364031800029 PM 26073278 ER PT J AU DeRavin, SS Reik, A Li, L Liu, PQ Song, A Pearl, JR Paschon, DE Peshwa, MV Theobald, N Choi, U Lee, J Koontz, S Sweeney, C Zarember, KA Lee, G Rebar, EJ Gregory, PD Urnov, FD Malech, HL AF DeRavin, S. S. Reik, A. Li, L. Liu, P. Q. Song, A. Pearl, J. R. Paschon, D. E. Peshwa, M. V. Theobald, N. Choi, U. Lee, J. Koontz, S. Sweeney, C. Zarember, K. A. Lee, G. Rebar, E. J. Gregory, P. D. Urnov, F. D. Malech, H. L. TI Efficient targeted gene addition to a safe harbor locus in long-term repopulating hematopoietic stem cells for correction of x-linked chronic granulomatous disease via genome editing SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy (ESGCT) and Finnish-Society-of-Gene-Therapy (FSGT) CY SEP 17-20, 2015 CL Helsinki, FINLAND SP European Soc Gene & Cell Therapy, Finnish Soc Gene Therapy C1 Sangamo BioSci, Richmond, CA USA. NIAID, Bethesda, MD USA. Maxcyte, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT 1 PY 2015 VL 26 IS 10 MA OR045 BP A17 EP A17 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CU9QE UT WOS:000363878700046 ER PT J AU Vogel, TP Milner, JD Cooper, MA AF Vogel, Tiphanie P. Milner, Joshua D. Cooper, Megan A. TI The Ying and Yang of STAT3 in Human Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE STAT3; Hyper-IgE syndrome; Job syndrome; monogenic autoimmunity; gain-of-function ID HYPER-IGE SYNDROME; GRANULAR LYMPHOCYTIC-LEUKEMIA; CHRONIC MUCOCUTANEOUS CANDIDIASIS; REGULATORY T-CELLS; SIGNAL TRANSDUCER; HYPERIMMUNOGLOBULINEMIA-E; RHEUMATOID-ARTHRITIS; TH17 CELLS; RECURRENT INFECTIONS; IMMUNE DYSREGULATION AB The transcription factor signal transducer and activator of transcription 3 (STAT3) is a critical regulator of multiple, diverse cellular processes. Heterozgyous, germline, loss-of-function mutations in STAT3 lead to the primary immune deficiency Hyper-IgE syndrome. Heterozygous, somatic, gain-of-function mutations in STAT3 have been reported in malignancy. Recently, germline, heterozygous mutations in STAT3 that confer a gain-of-function have been discovered and result in early-onset, multi-organ autoimmunity. This review summarizes what is known about the role of STAT3 in human disease. C1 [Vogel, Tiphanie P.; Cooper, Megan A.] Washington Univ, Sch Med, Div Rheumatol, Dept Pediat, St Louis, MO 63110 USA. [Vogel, Tiphanie P.] Washington Univ, Sch Med, Div Rheumatol, Dept Internal Med, St Louis, MO 63110 USA. [Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Cooper, Megan A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Cooper, MA (reprint author), Washington Univ, Sch Med, Div Rheumatol, Dept Pediat, St Louis, MO 63110 USA. EM cooper_m@kids.wustl.edu FU intramural research program of the National Institute of Allergy and Infectious Diseases, NIH; Children's Discovery Institute; Scleroderma Foundation; Rheumatic Diseases Core Center at Washington University [P30AR048335]; NIH [5T32AR007279]; St. Louis Children's Hospital FX The authors acknowledge the contributions of the members of the M.A.C. laboratory, particularly Ms. Nermina Saucier. This work was supported in part by the intramural research program of the National Institute of Allergy and Infectious Diseases, NIH. Work in M.A.C's laboratory was supported by The Children's Discovery Institute and St. Louis Children's Hospital, The Scleroderma Foundation, the Rheumatic Diseases Core Center at Washington University (P30AR048335), and NIH training grant 5T32AR007279 (T.P.V.). NR 103 TC 12 Z9 12 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD OCT PY 2015 VL 35 IS 7 BP 615 EP 623 DI 10.1007/s10875-015-0187-8 PG 9 WC Immunology SC Immunology GA CV0XG UT WOS:000363976500005 PM 26280891 ER PT J AU Yokoyama, S Perera, PY Terawaki, S Watanabe, N Kaminuma, O Waldmann, TA Hiroi, T Perera, LP AF Yokoyama, Seiji Perera, Pin-Yu Terawaki, Seigo Watanabe, Nobumasa Kaminuma, Osamu Waldmann, Thomas A. Hiroi, Takachika Perera, Liyanage P. TI Janus Kinase Inhibitor Tofacitinib Shows Potent Efficacy in a Mouse Model of Autoimmune Lymphoproliferative Syndrome (ALPS) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Autoimmunity; lymphoproliferation; ALPS; tofacitinib; SLE ID FAS GENE-MUTATIONS; NEGATIVE T-CELLS; RHEUMATOID-ARTHRITIS; SYNDROME EXPRESS; APOPTOSIS; DISEASE; CONTRIBUTES; ANTIGEN; HUMANS; MICE AB Purpose Autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant genetic disorder of lymphocyte homeostasis with defective Fas-mediated apoptosis. Current therapies for ALPS primarily target autoimmune manifestations with non-specific immune suppressants with variable success thus highlighting the need for better therapeutics for this disorder. Methods The spectrum of clinical manifestations of ALPS is mirrored by MRL/lpr mice that carry a loss of function mutation in the Fas gene and have proven to be a valuable model in predicting the efficacy of several therapeutics that are front-line modalities for the treatment of ALPS. We evaluated the potential efficacy of tofacitinib, an orally active, pan-JAK inhibitor currently approved for rheumatoid arthritis as a single agent modality against ALPS using MRL/lpr mice. Results We demonstrate that a 42-day course of tofacitinib therapy leads to a lasting reversal of lymphadenopathy and autoimmune manifestations in the treated MRL/lpr mice, Specifically, in treated mice the peripheral blood white blood cell counts were reversed to near normal levels with almost a 50 % reduction in the TCR alpha beta(+)CD4(-)CD8(-)T lymphocyte numbers that coincided with a parallel increase in CD8(+) T cells without a demonstrable effect on CD4(+) lymphocytes including FoxP3(+) regulatory T cells. The elevated plasma IgG and IgA levels were also drastically lowered along with a significant reduction in plasmablasts and plasmacytes in the spleen. Conclusion On the basis of these results, it is likely that tofacitinib would prove to be a potent single agent therapeutic modality capable of ameliorating both offending lymphadenopathy as well as autoimmunity in ALPS patients. C1 [Yokoyama, Seiji; Terawaki, Seigo; Watanabe, Nobumasa; Kaminuma, Osamu; Hiroi, Takachika] Tokyo Metropolitan Inst Med Sci, Dept Genome Med, Setagaya Ku, Tokyo 1568506, Japan. [Perera, Pin-Yu] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA. RP Hiroi, T (reprint author), Tokyo Metropolitan Inst Med Sci, Dept Genome Med, Setagaya Ku, 2-1-6 Kamikitazawa, Tokyo 1568506, Japan. EM hiroi-tk@igakuken.or.jp; pereral@mail.nih.gov FU intramural programs of the National Cancer Institute; MEXT in Japan from the Ministry of Education, Science, Sports, and Culture of Japan; Japan Society for the Promotion of Science FX This research was supported in part by the intramural programs of the National Cancer Institute and a Grant-in-Aid for 2009 Multidisciplinary Research Project from MEXT in Japan from the Ministry of Education, Science, Sports, and Culture of Japan (T. Hiroi). L.P. Perera gratefully acknowledges the receipt of an invitational fellowship from the Japan Society for the Promotion of Science. NR 29 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD OCT PY 2015 VL 35 IS 7 BP 661 EP 667 DI 10.1007/s10875-015-0203-z PG 7 WC Immunology SC Immunology GA CV0XG UT WOS:000363976500009 PM 26453583 ER PT J AU Parta, M Hilligoss, D Kelly, C Kwatemaa, N Theobald, N Malech, H Kang, EM AF Parta, Mark Hilligoss, Dianne Kelly, Corin Kwatemaa, Nana Theobald, Narda Malech, Harry Kang, Elizabeth M. TI Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in a Patient with Chronic Granulomatous Disease and Active Infection: A First Report SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Chronic granulomatous disease; haploidentical; hematopoietic cell transplantation; scedosporium apiospermum; post-transplant cyclophosphamide; graft versus host disease ID BONE-MARROW-TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; VERSUS-HOST-DISEASE; GRANULOCYTE TRANSFUSIONS; PULMONARY ASPERGILLOSIS; GVHD PROPHYLAXIS; T-CELLS; DEFICIENCY; CHILDREN; ALLOIMMUNIZATION AB Purpose We describe haploidentical hematopoietic cell transplantation (HCT) with high-dose post-transplant cyclophosphamide (PTCy) in a boy with x-linked chronic granulomatous disease (CGD). Methods A persistent and life-threatening fungal infection was the indication for HSCT. Non-myeloablative conditioning with PTCy (50 mg/kg days 3 and 4) was used in the absence of fully matched donors. Results Engraftment occurred on day 24. The patient experienced Grade 2 graft-versus-host disease of the skin and gastrointestinal tract and CMV infection, both of which were controlled. Chimerism was 100 % at days 30 and 6 months. Cessation of antifungal therapy was consistent with cure of the infection. Conclusions Haploidentical HCT with high-dose PTCy for CGD is feasible and succeeded even in the context of active infection. C1 [Parta, Mark] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Bethesda, MD 20892 USA. [Hilligoss, Dianne; Kelly, Corin; Kwatemaa, Nana; Theobald, Narda; Malech, Harry; Kang, Elizabeth M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Parta, M (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, 10 Ctr Dr,Rm 6-3754,MSC 1763, Bethesda, MD 20892 USA. EM mark.parta@nih.gov FU National Institutes of Health (NIH): National Cancer Institute, NIH [HHSN261200800001E]; National Institute of Allergy and Infectious Disease [1-ZAI-AI000989]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Intramural Research Program of the National Institute of Allergy and Infectious Diseases FX This project has been funded in whole or in part with federal funds from the following components of the National Institutes of Health (NIH): National Cancer Institute, NIH, under Contract No. HHSN261200800001E; National Institute of Allergy and Infectious Disease under Intramural Project #1-ZAI-AI000989. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; and [in part] by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 37 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD OCT PY 2015 VL 35 IS 7 BP 675 EP 680 DI 10.1007/s10875-015-0204-y PG 6 WC Immunology SC Immunology GA CV0XG UT WOS:000363976500011 PM 26453586 ER PT J AU Cheng, KCC Cao, SG Raveh, A MacArthur, R Dranchak, P Chlipala, G Okoneski, MT Guha, R Eastman, RT Yuan, J Schultz, PJ Su, XZ Tamayo-Castillo, G Matainaho, T Clardy, J Sherman, DH Inglese, J AF Cheng, Ken Chih-Chien Cao, Shugeng Raveh, Avi MacArthur, Ryan Dranchak, Patricia Chlipala, George Okoneski, Matthew T. Guha, Rajarshi Eastman, Richard T. Yuan, Jing Schultz, Pamela J. Su, Xin-zhuan Tamayo-Castillo, Giselle Matainaho, Teatulohi Clardy, Jon Sherman, David H. Inglese, James TI Actinoramide A Identified as a Potent Antimalarial from Titration-Based Screening of Marine Natural Product Extracts SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PLASMODIUM-FALCIPARUM; STREPTOMYCES SP; DISCOVERY; BIOSYNTHESIS; PROTEASES; TARGETS; SPP. AB Methods to identify the bioactive diversity within natural product extracts (NPEs) continue to evolve. NPEs constitute complex mixtures of chemical substances varying in structure, composition, and abundance. NPEs can therefore be challenging to evaluate efficiently with high-throughput screening approaches designed to test pure substances. Here we facilitate the rapid identification and prioritization of antimalarial NPEs using a pharmacologically driven, quantitative high-throughput-screening (qHTS) paradigm. In qHTS each NPE is tested across a concentration range from which sigmoidal response, efficacy, and apparent EC(50)s can be used to rank order NPEs for subsequent organism reculture, extraction, and fractionation. Using an NPE library derived from diverse marine microorganisms we observed potent antimalarial activity from two Streptomyces sp. extracts identified from thousands tested using qHTS. Seven compounds were isolated from two phylogenetically related Streptomyces species: Streptomyces ballenaensis collected from Costa Rica and Streptomyces bangulaensis collected from Papua New Guinea. Among them we identified actinoramides A and B, belonging to the unusually elaborated nonproteinogenic amino-acid-containing tetrapeptide series of natural products. In addition, we characterized a series of new compounds, including an artifact, 25-epi-actinoramide A, and actinoramides D, E, and F, which are closely related biosynthetic congeners of the previously reported metabolites. C1 [Cheng, Ken Chih-Chien; MacArthur, Ryan; Dranchak, Patricia; Guha, Rajarshi; Inglese, James] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Cao, Shugeng] Univ Hawaii, Daniel K Inouye Coll Pharm, Dept Pharmaceut Sci, Hilo, HI 96720 USA. [Cao, Shugeng; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Chlipala, George; Okoneski, Matthew T.; Schultz, Pamela J.; Sherman, David H.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Okoneski, Matthew T.; Sherman, David H.] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. [Okoneski, Matthew T.; Sherman, David H.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Okoneski, Matthew T.; Sherman, David H.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Eastman, Richard T.; Yuan, Jing; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Tamayo-Castillo, Giselle] Inst Nacl Biodiversidad INBio, Unidad Estrateg Bioprospecc, Santo Domingo De Heredia, Costa Rica. [Tamayo-Castillo, Giselle] Univ Costa Rica, CIPRONA Escuela Quim, San Pedro 2060, Costa Rica. [Matainaho, Teatulohi] Univ Papua New Guinea, Sch Med & Hlth Sci, Boroko, Papua N Guinea. RP Sherman, DH (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. EM davidhs@umich.edu; jinglese@mail.nih.gov OI Tamayo-Castillo, Giselle/0000-0002-4912-8895; Su, Xinzhuan/0000-0003-3246-3248 FU NIH as part of International Cooperative Biodiversity Group Initiative at Fogarty International Center [U01 TW007404]; Hans W. Vahlteich Professorship; National Center for Advancing Translational Sciences; NIH through Divisions of Intramural Research at National Institute of Allergy and Infectious Diseases FX This work was supported by NIH grant U01 TW007404 as part of the International Cooperative Biodiversity Group Initiative at the Fogarty International Center (D.H.S., G.T-C., and J.C.) and the Hans W. Vahlteich Professorship (D.H.S.) and at the NIH through the Divisions of Intramural Research at the National Institute of Allergy and Infectious Diseases (X.-z.S.) and the National Center for Advancing Translational Sciences (J.I.). The authors are grateful to PNG BioNet and the University of Papua New Guinea, Department of Environment and Conservation, for permission to collect research samples. We thank P. Shinn (NCATS) for compound management. We also thank S. Carmeli (Tel Aviv University), A. Lowell (UMICH LSI) for his help with the spectroscopic analysis, and R. L. Johnson (NCI) for early support of this work. The Costa Rican marine sediment sample was obtained under the permit R-CM-INBio-82-2009-OT. NR 30 TC 2 Z9 2 U1 3 U2 20 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 OCT PY 2015 VL 78 IS 10 BP 2411 EP 2422 DI 10.1021/acs.jnatprod.5b00489 PG 12 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA CV1EG UT WOS:000363995800014 PM 26465675 ER PT J AU Yu, D Makkar, G Strickland, DK Blanpied, TA Stumpo, DJ Blackshear, PJ Sarkar, R Monahan, TS AF Yu, Dan Makkar, George Strickland, Dudley K. Blanpied, Thomas A. Stumpo, Deborah J. Blackshear, Perry J. Sarkar, Rajabrata Monahan, Thomas S. TI Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE membrane lipids; migration; Rac1; restenosis; vascular smooth muscle ID NEOINTIMA FORMATION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PLASMA-MEMBRANE; PHOSPHORYLATION; ASSOCIATION; ACTIN; PROMOTES; DOMAINS; MICE; DIFFERENTIATION AB Background-Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo. Methods and Results-MARCKS knockdown blocked platelet-derived growth factor (PDGF)-induced translocation of cortactin to the cell cortex, impaired both lamellipodia and filopodia formation, and attenuated motility of human coronary artery smooth muscle cells (CASMCs). Activation of the small GTPases, Rac1 and Cdc42, was prevented by MARCKS knockdown. Phosphorylation of MARCKS resulted in a transient shift of MARCKS from the plasma membrane to the cytosol. MARCKS knockdown significantly decreased membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Cotransfection with an intact, unphosphorylated MARCKS, which has a high binding affinity for PIP2, restored membrane-associated PIP2 levels and was indispensable for activation of Rac1 and Cdc42 and, ultimately, VSMC migration. Overexpression of MARCKS in differentiated VSMCs increased membrane PIP2 abundance, Rac1 and Cdc42 activity, and cell motility. MARCKS protein was upregulated early in the development of intimal hyperplasia in the murine carotid ligation model. Decreased MARKCS expression, but not total knockdown, attenuated intimal hyperplasia formation. Conclusions-MARCKS upregulation increases VSMC motility by activation of Rac1 and Cdc42. These effects are mediated by MARCKS sequestering PIP2 at the plasma membrane. This study delineates a novel mechanism for MARCKS-mediated VSMC migration and supports the rational for MARCKS knockdown to prevent intimal hyperplasia. C1 [Yu, Dan; Monahan, Thomas S.] Vet Affairs Med Ctr, Dept Surg, Baltimore, MD USA. [Yu, Dan; Makkar, George; Strickland, Dudley K.; Sarkar, Rajabrata; Monahan, Thomas S.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Strickland, Dudley K.; Blanpied, Thomas A.; Sarkar, Rajabrata] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Yu, Dan; Strickland, Dudley K.; Sarkar, Rajabrata; Monahan, Thomas S.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Signal Transduct Lab, Res Triangle Pk, NC 27709 USA. RP Monahan, TS (reprint author), Baltimore Vet Affairs Med Ctr, 10 N Greene St, Baltimore, MD 21201 USA. EM tmonahan@smail.umaryland.edu OI Blanpied, Thomas/0000-0003-4957-557X FU Veterans Affairs Career Development Award [1IK2BX001553-01]; Vascular Cures Foundation; Wylie Scholarship; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX This work was funded, in part, by The Veterans Affairs Career Development Award 1IK2BX001553-01 and through the Vascular Cures Foundation E.J. Wylie Scholarship to T.S.M. This work was also supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 49 TC 3 Z9 3 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD OCT PY 2015 VL 4 IS 10 AR e002255 DI 10.1161/JAHA.115.002255 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IO UT WOS:000364153000027 PM 26450120 ER PT J AU Mao, L Wu, X Huang, ZJ Tatem, AJ AF Mao, Liang Wu, Xiao Huang, Zhuojie Tatem, Andrew J. TI Modeling monthly flows of global air travel passengers: An open-access data resource SO JOURNAL OF TRANSPORT GEOGRAPHY LA English DT Article DE Worldwide airline network (WAN); Air passenger flow; Monthly dynamics; Spatio-temporal modeling ID INFECTIOUS-DISEASES; GRAVITY MODELS; NETWORK; TRANSPORTATION; CITIES; VIRUS AB The global flow of air travel passengers varies over time and space, but analyses of these dynamics and their integration into applications in the fields of economics, epidemiology and migration, for example, have been constrained by a lack of data, given that air passenger flow data are often difficult and expensive to obtain. Here, these dynamics are modeled at a monthly scale to provide an open-access spatio-temporally resolved data source for research purposes (www.vbd-air.com/data). By refining an annual-scale model of Huang et al. (2013), we developed a set of Poisson regression models to predict monthly passenger volumes between directly connected airports during 2010. The models not only performed well in the United States with an overall accuracy of 93%, but also showed a reasonable confidence in estimating air passenger volumes in other regions of the world. Using the model outcomes, this research studied the spatio-temporal dynamics in the world airline network (WAN) that previous analyses were unable to capture. Findings on the monthly variation of WAN offer new knowledge for dynamic planning and strategy design to address global issues, such as disease pandemics and climate change. (C) 2015 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 [Mao, Liang] Univ Florida, Dept Geog, Gainesville, FL 32611 USA. [Wu, Xiao] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. [Huang, Zhuojie] Penn State Univ, GeoVISTA Ctr, University Pk, PA 16802 USA. [Huang, Zhuojie] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China. [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England. [Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden. RP Mao, L (reprint author), Univ Florida, Dept Geog, Gainesville, FL 32611 USA. OI Mao, Liang/0000-0002-7363-0308 FU National Academies National Academy of Sciences Airport Cooperative Research Program Board [ACRP A02-20] FX This research was funded by the National Academies National Academy of Sciences Airport Cooperative Research Program Board (#ACRP A02-20). NR 29 TC 3 Z9 3 U1 5 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-6923 EI 1873-1236 J9 J TRANSP GEOGR JI J. Transp. Geogr. PD OCT PY 2015 VL 48 BP 52 EP 60 DI 10.1016/j.jtrangeo.2015.08.017 PG 9 WC Economics; Geography; Transportation SC Business & Economics; Geography; Transportation GA CU8VI UT WOS:000363821800006 ER PT J AU Duan, Q Nair, G Gudino, N de Zwart, JA van Gelderen, P Murphy-Boesch, J Reich, DS Duyn, JH Merkle, H AF Duan, Qi Nair, Govind Gudino, Natalia de Zwart, Jacco A. van Gelderen, Peter Murphy-Boesch, Joe Reich, Daniel S. Duyn, Jeff H. Merkle, Hellmut TI A 7T Spine Array Based on Electric Dipole Transmitters SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE high field MRI; dipole antenna; spinal imaging; transmit array; receive array ID MAGNETIC-RESONANCE; COIL; EXCITATION; ELEMENT; ANTENNA; SHIFT AB Purpose: The goal of this study was to explore the feasibility of using an array of electric dipole antennas for RF transmission in spine MRI at high fields. Method: A two-channel transmit array based on an electric dipole design was quantitatively optimized for 7T spine imaging and integrated with a receive array combining eight loop coils. Using B-1(+) mapping, the transmit efficiency of the dipole array was compared with a design using quadrature loop pairs. The radiofrequency energy deposition for each array was measured using a home-built dielectric phantom and MR thermometry. The performance of the proposed array was qualitatively demonstrated in human studies. Results: The results indicate dramatically improved transmit efficiency for the dipole design compared with the loop excitation. A gain of up to 76% was achieved within the spinal region. Conclusion: For imaging of the spine, electric dipole-based transmitters provide an attractive alternative to the traditional loop-based design. Easy integration with existing receive array technology facilitates practical use at high fields. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. C1 [Duan, Qi; Gudino, Natalia; de Zwart, Jacco A.; van Gelderen, Peter; Murphy-Boesch, Joe; Duyn, Jeff H.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Nair, Govind; Reich, Daniel S.] NINDS, Div Neuroimmunol & Neurovirol, NIH, Bethesda, MD 20892 USA. RP Duan, Q (reprint author), 10 Ctr Dr,Room B1D728,Bldg 10, Bethesda, MD 20892 USA. EM qi.duan@nih.gov RI Duan, Qi/J-7916-2016; Reich, Daniel/E-5701-2010 OI Duan, Qi/0000-0002-2407-6611; Reich, Daniel/0000-0002-2628-4334 FU National Institute of Neurological Disorders and Stroke Intramural Research Program FX Grant sponsor: National Institute of Neurological Disorders and Stroke Intramural Research Program. NR 28 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2015 VL 74 IS 4 BP 1189 EP 1197 DI 10.1002/mrm.25817 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV4DF UT WOS:000364215200031 PM 26190585 ER PT J AU Polotow, TG Poppe, SC Vardaris, CV Ganini, D Guariroba, M Mattei, R Hatanaka, E Martins, MF Bondan, EF Barros, MP AF Polotow, Tatiana G. Poppe, Sandra C. Vardaris, Cristina V. Ganini, Douglas Guariroba, Maisa Mattei, Rita Hatanaka, Elaine Martins, Maria F. Bondan, Eduardo F. Barros, Marcelo P. TI Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass SO MARINE DRUGS LA English DT Article DE DHA; EPA; carotenoid; antioxidant; hormesis; brain; aging; Alzheimer; Parkinson; senescence ID ROTENONE-INDUCED APOPTOSIS; OXIDATIVE STRESS; PARKINSONS-DISEASE; FATTY-ACIDS; POSSIBLE INVOLVEMENT; EUPHAUSIA-SUPERBA; HEALTH-BENEFITS; SH-SY5Y CELLS; BRAIN; EXERCISE AB Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions. C1 [Polotow, Tatiana G.; Poppe, Sandra C.; Vardaris, Cristina V.; Ganini, Douglas; Guariroba, Maisa; Hatanaka, Elaine; Barros, Marcelo P.] Univ Cruzeiro Sul, Inst Phys Act & Sports Sci ICAFE, Postgrad Program Hlth Sci, BR-01506000 Sao Paulo, SP, Brazil. [Ganini, Douglas] NIEHS, Free Rad Metab Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Mattei, Rita] Fed Univ Sao Paulo UNIFESP, Dept Psychobiol, BR-04023062 Sao Paulo, SP, Brazil. [Martins, Maria F.; Bondan, Eduardo F.] Paulista Univ UNIP, Dept Environm & Expt Pathol, BR-04026002 Sao Paulo, SP, Brazil. [Martins, Maria F.; Bondan, Eduardo F.] Univ Cruzeiro Sul, Program Vet Med Biol Sci & Hlth CBS, BR-01506000 Sao Paulo, SP, Brazil. RP Barros, MP (reprint author), Univ Cruzeiro Sul, Inst Phys Act & Sports Sci ICAFE, Postgrad Program Hlth Sci, R Galvao Bueno 868,Bldg B,13th Floor, BR-01506000 Sao Paulo, SP, Brazil. EM tatianapolotow@gmail.com; scpoppe@uol.com.br; crisvardaris@gmail.com; douganini@uol.com.br; maisa_bizie@hotmail.com; matteipersoli@gmail.com; elaine.hatanaka@cruzeirodosul.edu.br; fa3mterra@terra.com.br; bondan@uol.com.br; marcelo.barros@cruzeirodosul.edu.br RI Barros, Marcelo/K-1410-2013; BONDAN, EDUARDO/D-5417-2016 OI Barros, Marcelo/0000-0003-3565-8331; BONDAN, EDUARDO/0000-0002-3887-0023 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2009/12342-8]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade em Pesquisa, Nivel 2, CNPq, Brazil) [307474/2012-7]; Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES); CYTED (Spain, EU) [112RT0445] FX The authors are indebted to the Brazilian funding agencies Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP 2009/12342-8), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Bolsa Produtividade em Pesquisa, Nivel 2, #307474/2012-7, CNPq, Brazil), and the Programa de Suporte a Pos-Graduacao de Instituicoes de Ensino Particulares (PROSUP/CAPES). The authors, Tatiana G. Polotow, Cristina V. Vardaris, and Marcelo P. Barros are members of the IBERCAROT network, funded by CYTED (ref. 112RT0445, Spain, EU). Marcelo Paes de Barros is also indebted to Ake Lignell, CEO and Marketing Director of AstaReal AB (Gustavsberg, Sweden) for donating astaxanthin-rich algal biomass for animal supplementation in our study. NR 70 TC 0 Z9 0 U1 5 U2 26 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD OCT PY 2015 VL 13 IS 10 BP 6117 EP 6137 DI 10.3390/md13106117 PG 21 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CV0YO UT WOS:000363980000006 PM 26426026 ER PT J AU Sargolzaei, S Sargolzaei, A Cabrerizo, M Chen, G Goryawala, M Pinzon-Ardila, A Gonzalez-Arias, SM Adjouadi, M AF Sargolzaei, Saman Sargolzaei, Arman Cabrerizo, Mercedes Chen, Gang Goryawala, Mohammed Pinzon-Ardila, Alberto Gonzalez-Arias, Sergio M. Adjouadi, Malek TI Estimating Intracranial Volume in Brain Research: An Evaluation of Methods SO NEUROINFORMATICS LA English DT Article DE Intracranial volume estimation; FreeSurfer (RRID:nif-0000-00304); FSL(RRID:nif-0000-00305); SPM(RRID:nif-0000-00343); MRI ID MILD COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE IMAGES; ALZHEIMERS-DISEASE; HIPPOCAMPAL SEGMENTATION; SPATIAL NORMALIZATION; HEALTHY-ADULTS; WHITE-MATTER; RELIABILITY; MRI; BIOMARKERS AB Intracranial volume (ICV) is a standard measure often used in morphometric analyses to correct for head size in brain studies. Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation across different subject groups in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and type of software most suitable for use in estimating the ICV measure. Four groups of 53 subjects are considered, including adult controls (AC, adults with Alzheimer's disease (AD), pediatric controls (PC) and group of pediatric epilepsy subjects (PE). Reference measurements were calculated for each subject by manually tracing intracranial cavity without sub-sampling. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (FreeSurfer Ver. 5.3.0, FSL Ver. 5.0, SPM8 and SPM12) were examined in their ability to automatically estimate ICV across the groups. Results on sub-sampling studies with a 95 % confidence showed that in order to keep the accuracy of the inter-leaved slice sampling protocol above 99 %, sampling period cannot exceed 20 mm for AC, 25 mm for PC, 15 mm for AD and 17 mm for the PE groups. The study assumes a priori knowledge about the population under study into the automated ICV estimation. Tuning of the parameters in FSL and the use of proper atlas in SPM showed significant reduction in the systematic bias and the error in ICV estimation via these automated tools. SPM12 with the use of pediatric template is found to be a more suitable candidate for PE group. SPM12 and FSL subjected to tuning are the more appropriate tools for the PC group. The random error is minimized for FS in AD group and SPM8 showed less systematic bias. Across the AC group, both SPM12 and FS performed well but SPM12 reported lesser amount of systematic bias. C1 [Sargolzaei, Saman; Sargolzaei, Arman; Cabrerizo, Mercedes; Goryawala, Mohammed; Adjouadi, Malek] Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33199 USA. [Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, HHS, Bethesda, MD 20892 USA. [Pinzon-Ardila, Alberto; Gonzalez-Arias, Sergio M.] Baptist Hosp Miami, Baptist Hlth Neurosci Ctr, Miami, FL USA. [Gonzalez-Arias, Sergio M.] Florida Int Univ, Herbert Wertheim Coll Med, Dept Neurosci, Miami, FL 33199 USA. [Adjouadi, Malek] Florida Int Univ, Dept Biomed Engn, Miami, FL 33199 USA. RP Adjouadi, M (reprint author), Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33199 USA. EM adjouadi@fiu.edu FU National Science Foundation [CNS-0959985, CNS-1042341, HRD-0833093, IIP-1230661] FX This work is supported by the National Science Foundation under grants CNS-0959985, CNS-1042341, HRD-0833093, and IIP-1230661. The support of the Ware Foundation is greatly appreciated. The authors would like to thank the anonymous reviewers for their comments and suggestions which significantly improved the quality of this work. NR 60 TC 4 Z9 4 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 EI 1559-0089 J9 NEUROINFORMATICS JI Neuroinformatics PD OCT PY 2015 VL 13 IS 4 BP 427 EP 441 DI 10.1007/s12021-015-9266-5 PG 15 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA CV3IZ UT WOS:000364154200004 PM 25822811 ER PT J AU Xia, DP Li, JH Sun, BH Weed, JL Kyes, RC AF Xia, Dong-Po Li, Jin-Hua Sun, Bing-Hua Weed, James L. Kyes, Randall C. TI Evaluation of Fecal Testosterone, Rank and Copulatory Behavior in Wild Male Macaca thibetana at Huangshan, China SO PAKISTAN JOURNAL OF ZOOLOGY LA English DT Article DE Macaca thibetana; fecal testosterone; copulatory behavior; social rank; non human primates ID MALE TIBETAN MACAQUES; CHIMPANZEES PAN-TROGLODYTES; MALE JAPANESE MACAQUES; SEASONAL-VARIATION; DOMINANCE RANK; CHALLENGE HYPOTHESIS; RHESUS-MONKEY; AGGRESSION; CORTISOL; BABOONS AB Although male testosterone levels are thought to be linked with the mating system, ecological and social factors complicate the big picture of the function of testosterone in wild nonhuman primates. We examined testosterone correlates with rank and copulatory behavior in male Tibetan macaques (Macaca thibetana) at Mt. Huangshan, China. A total of 426 fecal samples and approximately 453h of behavioral data were collected on five adult males from October 2005 to September 2006. Copulatory behaviors were significantly different between high and low ranking males in the mating season, but not during the non-mating season. No significant correlation between testosterone levels and a male's David's score indicated that testosterone was independent of social rank. Also, copulatory behaviors were positively correlated with fecal testosterone levels in both seasons, regardless of social rank. The present study represents a preliminary assessment of the relationship between testosterone level, rank, and copulatory behavior in a wild environment. The results enrich the picture of testosterone, rank, and copulatory relationships in non-human primates, and may also provide insight into what mechanisms link physiological factors to male reproductive success in natural circumstances. C1 [Xia, Dong-Po] Anhui Univ, Sch Life Sci, Hefei 230601, Peoples R China. [Li, Jin-Hua; Sun, Bing-Hua] Anhui Univ, Sch Resource & Environm Engn, Hefei 230601, Peoples R China. [Li, Jin-Hua] Hefei Normal Univ, Sch Life Sci, Hefei 241000, Peoples R China. [Weed, James L.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Kyes, Randall C.] Univ Washington, Ctr Global Field Study, Dept Psychol, Seattle, WA 98195 USA. [Kyes, Randall C.] Univ Washington, Ctr Global Field Study, Dept Global Hlth, Seattle, WA 98195 USA. [Kyes, Randall C.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. RP Li, JH (reprint author), Anhui Univ, Sch Resource & Environm Engn, Hefei 230601, Peoples R China. EM jhli@ahu.edu.cn FU National Natural Science Foundation of China [31401981, 31372215, 31172106]; Anhui Provincial Natural Science Foundation [1408085QC56]; Initial Foundation of Doctoral Scientific Research in Anhui University [J01001319]; Huangshan Garden Forest Bureau FX This study was supported in part by grants from the National Natural Science Foundation of China (No. 31401981, 31372215; 31172106), the Anhui Provincial Natural Science Foundation (No.1408085QC56), and the Initial Foundation of Doctoral Scientific Research in Anhui University (J01001319). We are grateful to the Huangshan Garden Forest Bureau for their permission and support of this study. We also gratefully acknowledge Mr. H. B. Cheng' s family for their logistic support. We thank Q. R. Ji in the Nuclear Medical laboratory of Anhui Medical University and C. W. Li for suggestions for hormonal analysis. We especially thank Prof. L. X. Sun and M. D. Matheson, for their comments to highly improve the initial draft. We also thank anonymous reviewers for valuable suggestions. NR 37 TC 0 Z9 0 U1 7 U2 11 PU ZOOLOGICAL SOC PAKISTAN PI LAHORE PA UNIV PUNJAB, NEW CAMPUS, C/O DEPT ZOOLOGY, LAHORE, PAKISTAN SN 0030-9923 J9 PAK J ZOOL JI Pak. J. Zool. PD OCT PY 2015 VL 47 IS 5 BP 1445 EP 1454 PG 10 WC Zoology SC Zoology GA CV1EQ UT WOS:000363996800030 ER PT J AU Chakhtoura, NA Reddy, UM AF Chakhtoura, Nahida A. Reddy, Uma M. TI Management of stillbirth delivery SO SEMINARS IN PERINATOLOGY LA English DT Review DE pregnancy; stillbirth; intrauterine fetal death; management ID FETAL-DEATH; CESAREAN DELIVERY; LABOR INDUCTION; EVACUATION; DILATION; PREGNANCY; TERMINATION; MISOPROSTOL; LAMINARIA; ABORTION AB Stillbirth is a common adverse outcome of pregnancy. Management should be individualized based on gestational age, maternal condition, prior uterine surgery, availability of skilled professionals, and maternal desires. This article discusses available data on management by gestational age and prior uterine surgery. Expectant management is a viable option for women and families who desire it and do not have any contraindications. In the second trimester, misoprostol induction and dilatation and evacuation are effective in the evacuation of the uterus. In the third trimester, induction of labor with prostaglandins, mechanical dilators, and augmentation with oxytocin is appropriate. Care should be taken with women with prior cesarean delivery; prostaglandins ideally should be avoided. Delivery by cesarean section should be performed selectively, i.e., when there is a maternal indication. Published by Elsevier Inc. C1 [Chakhtoura, Nahida A.] NICHHD, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD 20892 USA. [Chakhtoura, Nahida A.] Fed X, Rockville, MD 20852 USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Chakhtoura, NA (reprint author), NICHHD, Maternal & Pediat Infect Dis Branch, NIH, 6100 Execut Blvd,Rm 4B11, Bethesda, MD 20892 USA. EM Nahida.chakhtoura@nih.gov NR 25 TC 0 Z9 0 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 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2015 VL 39 IS 6 BP 501 EP 504 DI 10.1053/j.semperi.2015.07.016 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CV4VI UT WOS:000364264200016 PM 26341069 ER PT J AU Bekdash, A Darwish, M Timsah, Z Kassab, E Ghanem, H Najjar, V Ghosn, M Nasser, S El-Hajj, H Bazerbachi, A Liu, SH Leppla, SH Frankel, AE Abi-Habib, RJ AF Bekdash, Amira Darwish, Manal Timsah, Zahra Kassab, Elias Ghanem, Hadi Najjar, Vicky Ghosn, Marwan Nasser, Selim El-Hajj, Hiba Bazerbachi, Ali Liu, Shihui Leppla, Stephen H. Frankel, Arthur E. Abi-Habib, Ralph J. TI Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF) SO TRANSLATIONAL ONCOLOGY LA English DT Article ID MYELOID-LEUKEMIA CELLS; KINASE 1/2 ACTIVITY; MELANOMA-CELLS; RECEPTOR; INACTIVATION; ANTIGEN; CYTOTOXICITY; ENDOCYTOSIS; INVASION; THERAPY AB In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML) cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34+ bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML. C1 [Bekdash, Amira; Darwish, Manal; Kassab, Elias; Abi-Habib, Ralph J.] Lebanese Amer Univ, Sch Arts & Sci, Dept Nat Sci, Beirut 11022801, Lebanon. [Timsah, Zahra] Univ Leeds, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England. [Ghanem, Hadi] Lebanese Amer Univ, Sch Med, Dept Internal Med, Beirut 11022801, Lebanon. [Najjar, Vicky; Ghosn, Marwan; Nasser, Selim] Lebanese Amer Univ, Sch Med, Dept Pathol, Beirut 11022801, Lebanon. [El-Hajj, Hiba] Amer Univ Beirut, Sch Med, Dept Internal Med & Expt Pathol, Beirut, Lebanon. [El-Hajj, Hiba] Amer Univ Beirut, Sch Med, Dept Immunol & Microbiol, Beirut, Lebanon. [Bazerbachi, Ali] Amer Univ Beirut, Sch Med, Dept Internal Med, Beirut, Lebanon. [Bazerbachi, Ali] Amer Univ Beirut, Sch Med, Dept Anat, Beirut, Lebanon. [Bazerbachi, Ali] Amer Univ Beirut, Sch Med, Dept Cell Biol & Physiol, Beirut, Lebanon. [Liu, Shihui; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Frankel, Arthur E.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. RP Abi-Habib, RJ (reprint author), Lebanese Amer Univ, Sch Arts & Sci, Beirut 11022801, Lebanon. EM ralph.abihabib@lau.edu.lb FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, Bethesda, MD; National Council for Scientific Research, Lebanon FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, Bethesda, MD, and by the National Council for Scientific Research, Lebanon. NR 29 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1944-7124 EI 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD OCT PY 2015 VL 8 IS 5 BP 347 EP 357 DI 10.1016/j.tranon.2015.07.001 PG 11 WC Oncology SC Oncology GA CV2EV UT WOS:000364070600001 PM 26500025 ER PT J AU Fontana, RJ Hayashi, PH Barnhart, H Kleiner, DE Reddy, KR Chalasani, N Lee, WM Stolz, A Phillips, T Serrano, J Watkins, PB AF Fontana, Robert J. Hayashi, Paul H. Barnhart, Huiman Kleiner, David E. Reddy, K. Rajender Chalasani, Naga Lee, William M. Stolz, Andrew Phillips, Thomas Serrano, Jose Watkins, Paul B. CA DILIN Investigators TI Persistent Liver Biochemistry Abnormalities Are More Common in Older Patients and those With Cholestatic Drug Induced Liver Injury SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID TERM-FOLLOW-UP; PRIMARY BILIARY-CIRRHOSIS; UNITED-STATES; HEPATITIS-C; FAILURE; STEATOSIS; MORBIDITY; MORTALITY; OUTCOMES AB OBJECTIVES: The long-term outcomes of patients with drug induced liver injury (DILI) are not well described. The aim of this study was to determine the frequency and severity of persistent liver biochemistry abnormalities in DILI patients followed over 2 years. METHODS: Subjects with evidence of liver injury at 6 months after DILI onset were offered a month 12 and 24 study visit. RESULTS: Amongst the 99 patients with definite, probable, or very likely DILI and available laboratory data at 12 months after DILI onset, 74 (75%) had persistent liver injury (persisters) defined as a serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5xupper limit of normal (ULN) or an alkaline phosphatase >ULN, while 25 (25%) had resolved liver injury (resolvers). On multivariate analysis, month 12 persisters were significantly older (52.6 vs. 43.7 years, P=0.01) and more likely to have a cholestatic lab profile at DILI onset (54 vs. 20%, P<0.01) than resolvers. The month 12 persisters also had significantly poorer SF-36 physical summary scores at DILI onset and throughout follow-up compared with the resolvers (P< 0.01). Amongst the 17 subjects with a liver biopsy obtained at a median of 387 days after DILI onset, 9 had chronic cholestasis, 3 had steatohepatitis, and 3 had chronic hepatitis. CONCLUSIONS: In all, 75% of subjects with liver injury at 6 months after DILI onset have laboratory evidence of persistent liver injury during prolonged follow-up. Higher serum alkaline phosphatase levels at presentation and older patient age were independent predictors of persistent liver injury. Subjects with persistent liver injury at 12 months after DILI onset should be carefully monitored and assessed for liver disease progression. C1 [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hayashi, Paul H.; Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC USA. [Barnhart, Huiman; Phillips, Thomas] Duke Clin Res Inst, Durham, NC USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Chalasani, Naga] Indiana Univ, Dept Med, Indianapolis, IN USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Stolz, Andrew] Univ So Calif, Los Angeles, CA USA. [Serrano, Jose] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Fontana, RJ (reprint author), Univ Michigan, Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [2U01-DK065201-06, 5U01DK065193-04, 5U01-DK065238-08, 1U01-DK083023-01, 1U01-DK083027-01, 1U01-DK082992-01, 1U01-DK083020-01, 2U01-DK065176-06, 2U01-DK065184-06, 2U01-DK065211-06]; CTSA [UL1TR000083, UL1 RR024134, UL1 RR024982, UL1 RR024150, UL1 RR025761, UL1 RR024986]; NIH, National Cancer Institute FX The DILIN Network is structured as a U01 cooperative agreement with funds provided by the National Institute of Diabetes and Digestive and Kidney Diseases under grants: 2U01-DK065176-06 (Duke), 2U01-DK065201-06 (UNC), 2U01-DK065184-06 (Michigan), 2U01-DK065211-06 (Indiana), 5U01DK065193-04 (UConn), 5U01-DK065238-08 (UCSF/CPMC), 1U01-DK083023-01 (UTSW), 1U01-DK083027-01 (TJH/UPenn), 1U01-DK082992-01 (Mayo), 1U01-DK083020-01 (USC). Additional funding is provided by CTSA grants: UL1 RR025761 (Indiana), UL1TR000083 (UNC), UL1 RR024134 (UPenn), UL1 RR024986 (Michigan), UL1 RR024982 (UTSW), UL1 RR024150 (Mayo) and in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 28 TC 6 Z9 6 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2015 VL 110 IS 10 BP 1450 EP 1459 DI 10.1038/ajg.2015.283 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU7KP UT WOS:000363716200012 PM 26346867 ER PT J AU Durkin, MS Elsabbagh, M Barbaro, J Gladstone, M Happe, F Hoekstra, RA Lee, LC Rattazzi, A Stapel-Wax, J Stone, WL Tager-Flusberg, H Thurm, A Tomlinson, M Shih, A AF Durkin, Maureen S. Elsabbagh, Mayada Barbaro, Josephine Gladstone, Melissa Happe, Francesca Hoekstra, Rosa A. Lee, Li-Ching Rattazzi, Alexia Stapel-Wax, Jennifer Stone, Wendy L. Tager-Flusberg, Helen Thurm, Audrey Tomlinson, Mark Shih, Andy TI Autism screening and diagnosis in low resource settings: Challenges and opportunities to enhance research and services worldwide SO AUTISM RESEARCH LA English DT Review DE diagnosis; early detection; epidemiology; intervention AB Most research into the epidemiology, etiology, clinical manifestations, diagnosis and treatment of autism is based on studies in high income countries. Moreover, within high income countries, individuals of high socioeconomic status are disproportionately represented among participants in autism research. Corresponding disparities in access to autism screening, diagnosis, and treatment exist globally. One of the barriers perpetuating this imbalance is the high cost of proprietary tools for diagnosing autism and for delivering evidence-based therapies. Another barrier is the high cost of training of professionals and para-professionals to use the tools. Open-source and open access models provide a way to facilitate global collaboration and training. Using these models and technologies, the autism scientific community and clinicians worldwide should be able to work more effectively and efficiently than they have to date to address the global imbalance in autism knowledge and at the same time advance our understanding of autism and our ability to deliver cost-effective services to everyone in need. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc. on behalf of International Society for Autism Research C1 [Durkin, Maureen S.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Durkin, Maureen S.] Univ Wisconsin, Dept Pediat, Madison, WI 53726 USA. [Durkin, Maureen S.] Univ Wisconsin, Waisman Ctr, Madison, WI 53726 USA. [Elsabbagh, Mayada] McGill Univ, Dept Psychiat, Montreal, PQ H3A 1A1, Canada. [Barbaro, Josephine] La Trobe Univ, Olga Tennison Autism Res Ctr, Sch Psychol & Publ Hlth, Coll Sci Hlth & Engn, Melbourne, Vic 3086, Australia. [Gladstone, Melissa] Univ Liverpool, Inst Translat Med, Dept Women & Childrens Hlth, Alder Hey Childrens NHS Fdn Trust, Liverpool L69 3BX, Merseyside, England. [Happe, Francesca] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London SE1 1UL, England. [Hoekstra, Rosa A.] Open Univ, Fac Sci, Dept Life Hlth & Chem Sci, Milton Keynes MK7 6AA, Bucks, England. [Hoekstra, Rosa A.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, London SE1 1UL, England. [Lee, Li-Ching] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Rattazzi, Alexia] PANAACEA Programa Argentino Ninos Adolescentes &, RA-1640 Buenos Aires, DF, Argentina. [Stapel-Wax, Jennifer] Emory Univ, Sch Med, Dept Pediat, Div Autism & Related Disorders, Atlanta, GA USA. [Stapel-Wax, Jennifer] Childrens Healthcare Atlanta, Infant Toddler Clin Res Operat Marcus Autism Ctr, Atlanta, GA USA. [Stone, Wendy L.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Tager-Flusberg, Helen] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Thurm, Audrey] NIMH, Pediat & Dev Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Tomlinson, Mark] Univ Stellenbosch, Dept Psychol, ZA-7600 Stellenbosch, South Africa. [Shih, Andy] Autism Speaks, New York, NY USA. RP Durkin, MS (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, 789 WARF,610 Walnut St, Madison, WI 53726 USA. EM maureen.durkin@wisc.edu OI Hoekstra, Rosa/0000-0002-1333-9762; Happe, Francesca/0000-0001-9226-4000 FU Autism Speaks FX The commentary was developed as a result of a meeting convened by Autism Speaks and the International Society for Autism Research, 15-16 October 2014. The themes discussed in it were also raised in the World Health Organization Consultation on Autism Spectrum Disorders and Other Developmental Disorders: From Awareness Raising to Capacity Building, sponsored by Autism Speaks, 16-18 September 2013 (https://www.autismspeaks.org/science/science-news/autism-speaks-sponsor s-world-health-organization-conference-asd). The authors would also like to acknowledge helpful input to this commentary provided by Dr. Geraldine Dawson and an anonymous reviewer. NR 20 TC 9 Z9 9 U1 5 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 EI 1939-3806 J9 AUTISM RES JI Autism Res. PD OCT PY 2015 VL 8 IS 5 BP 473 EP 476 DI 10.1002/aur.1575 PG 4 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA CU9OT UT WOS:000363874700001 PM 26437907 ER PT J AU Carithers, LJ Moore, HM AF Carithers, Latarsha J. Moore, Helen M. TI The Genotype-Tissue Expression (GTEx) Project SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 [Carithers, Latarsha J.; Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, NIH, Bethesda, MD 20892 USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, Div Canc Treatment & Diag, Rm 3W428,MSC 9728,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov NR 4 TC 5 Z9 5 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD OCT 1 PY 2015 VL 13 IS 5 BP 307 EP 308 DI 10.1089/bio.2015.29031.hmm PG 2 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA CU9SX UT WOS:000363886600001 PM 26484569 ER PT J AU Carithers, LJ Ardlie, K Barcus, M Branton, PA Britton, A Buia, SA Compton, CC DeLuca, DS Peter-Demchok, J Gelfand, ET Guan, P Korzeniewski, GE Lockhart, NC Rabiner, CA Rao, AK Robinson, KL Roche, NV Sawyer, SJ Segre, AV Shive, CE Smith, AM Sobin, LH Undale, AH Valentino, KM Vaught, J Young, TR Moore, HM AF Carithers, Latarsha J. Ardlie, Kristin Barcus, Mary Branton, Philip A. Britton, Angela Buia, Stephen A. Compton, Carolyn C. DeLuca, David S. Peter-Demchok, Joanne Gelfand, Ellen T. Guan, Ping Korzeniewski, Greg E. Lockhart, Nicole C. Rabiner, Chana A. Rao, Abhi K. Robinson, Karna L. Roche, Nancy V. Sawyer, Sherilyn J. Segre, Ayellet V. Shive, Charles E. Smith, Anna M. Sobin, Leslie H. Undale, Anita H. Valentino, Kimberly M. Vaught, Jim Young, Taylor R. Moore, Helen M. CA GTEx Consortium TI A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID HUMAN TRANSCRIPTOME AB The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community. C1 [Carithers, Latarsha J.; Branton, Philip A.; Compton, Carolyn C.; Peter-Demchok, Joanne; Guan, Ping; Lockhart, Nicole C.; Rabiner, Chana A.; Rao, Abhi K.; Sawyer, Sherilyn J.; Vaught, Jim; Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Canc Diag Program, NIH, Bethesda, MD 20892 USA. [Ardlie, Kristin; DeLuca, David S.; Gelfand, Ellen T.; Segre, Ayellet V.; Young, Taylor R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Barcus, Mary; Britton, Angela; Buia, Stephen A.; Korzeniewski, Greg E.; Robinson, Karna L.; Roche, Nancy V.; Shive, Charles E.; Smith, Anna M.; Sobin, Leslie H.; Undale, Anita H.; Valentino, Kimberly M.] Leidos Biomed Res Inc, Clin Res Directorate, Biospecimen Res Grp, Frederick, MD USA. RP Moore, HM (reprint author), NCI, Biorepositories & Biospecimen Res Branch, Div Canc Treatment & Diag, Canc Diag Program, Rm 3W428,MSC 9728,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM moorehe@mail.nih.gov RI Guigo, Roderic/D-1303-2010; OI Guigo, Roderic/0000-0002-5738-4477; Wen, Xiaoquan/0000-0001-8990-2737 FU National Institutes of Health [HHSN261200800001E, 10XS170, 10XS171, 12ST1039, 10ST1035, HHSN268201000029C, R01 DA006227-17] FX This work was supported by the National Institutes of Health (HHSN261200800001E (Leidos Prime contract with NCI); 10XS170 (NDRI), 10XS171 (Roswell Park Cancer Institute), 10X172 (Science Care Inc.), 12ST1039 (IDOX); 10ST1035 (Van Andel Institute); HHSN268201000029C (Broad Institute); and R01 DA006227-17 (U Miami Brain Bank). NR 16 TC 14 Z9 14 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD OCT 1 PY 2015 VL 13 IS 5 BP 311 EP 319 DI 10.1089/bio.2015.0032 PG 9 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA CU9SX UT WOS:000363886600003 PM 26484571 ER PT J AU Reynolds, LM Wan, M Ding, JZ Taylor, JR Lohman, K Su, D Bennett, BD Porter, DK Gimple, R Pittman, GS Wang, XT Howard, TD Siscovick, D Psaty, BM Shea, S Burke, GL Jacobs, DR Rich, SS Hixson, JE Stein, JH Stunnenberg, H Barr, RG Kaufman, JD Post, WS Hoeschele, I Herrington, DM Bell, DA Liu, YM AF Reynolds, Lindsay M. Wan, Ma Ding, Jingzhong Taylor, Jackson R. Lohman, Kurt Su, Dan Bennett, Brian D. Porter, Devin K. Gimple, Ryan Pittman, Gary S. Wang, Xuting Howard, Timothy D. Siscovick, David Psaty, Bruce M. Shea, Steven Burke, Gregory L. Jacobs, David R. Rich, Stephen S. Hixson, James E. Stein, James H. Stunnenberg, Hendrik Barr, R. Graham Kaufman, Joel D. Post, Wendy S. Hoeschele, Ina Herrington, David M. Bell, Douglas A. Liu, Yongmei TI DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations With Cigarette Smoking and Subclinical Atherosclerosis SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atherosclerosis; DNA methylation; epidemiology; epigenomics; gene expression regulation; smoking ID CARDIOVASCULAR-DISEASE; CIRCULATING MONOCYTES; ENHANCER ACTIVITY; GENE-EXPRESSION; HUMAN GENOME; THICKNESS; INFLAMMATION; EPIGENETICS; SIGNATURE; DIOXINS AB Background Tobacco smoke contains numerous agonists of the aryl hydrocarbon receptor (AhR) pathway, and activation of the AhR pathway was shown to promote atherosclerosis in mice. Intriguingly, cigarette smoking is most strongly and robustly associated with DNA modifications to an AhR pathway gene, the AhR repressor (AHRR). We hypothesized that altered AHRR methylation in monocytes, a cell type sensitive to cigarette smoking and involved in atherogenesis, may be a part of the biological link between cigarette smoking and atherosclerosis. Methods and Results DNA methylation profiles of AHRR in monocytes (542 CpG sites150 kb of AHRR, using Illumina 450K array) were integrated with smoking habits and ultrasound-measured carotid plaque scores from 1256 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methylation of cg05575921 significantly associated (P=6.1x10(-134)) with smoking status (current versus never). Novel associations between cg05575921 methylation and carotid plaque scores (P=3.1x10(-10)) were identified, which remained significant in current and former smokers even after adjusting for self-reported smoking habits, urinary cotinine, and well-known cardiovascular disease risk factors. This association replicated in an independent cohort using hepatic DNA (n=141). Functionally, cg05575921 was located in a predicted gene expression regulatory element (enhancer) and had methylation correlated with AHRR mRNA profiles (P=1.4x10(-17)) obtained from RNA sequencing conducted on a subset (n=373) of the samples. Conclusions These findings suggest that AHRR methylation may be functionally related to AHRR expression in monocytes and represents a potential biomarker of subclinical atherosclerosis in smokers. C1 [Reynolds, Lindsay M.; Ding, Jingzhong; Taylor, Jackson R.; Lohman, Kurt; Howard, Timothy D.; Burke, Gregory L.; Herrington, David M.; Liu, Yongmei] Wake Forest Sch Med, J Paul Sticht Ctr Aging, Div Publ Hlth Sci, Dept Epidemiol & Prevent,Ctr Human Gen,Dept Inter, Winston Salem, NC 27157 USA. [Reynolds, Lindsay M.; Ding, Jingzhong; Taylor, Jackson R.; Lohman, Kurt; Howard, Timothy D.; Burke, Gregory L.; Herrington, David M.; Liu, Yongmei] Wake Forest Sch Med, J Paul Sticht Ctr Aging, Dept Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Wan, Ma; Su, Dan; Bennett, Brian D.; Porter, Devin K.; Gimple, Ryan; Pittman, Gary S.; Wang, Xuting; Bell, Douglas A.] NIEHS, Environm Genom, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Su, Dan] New York Acad Med, Res, New York, NY USA. [Psaty, Bruce M.; Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Psaty, Bruce M.; Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.; Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shea, Steven; Barr, R. Graham] Columbia Univ, Med Ctr, Dept Med, New York, NY USA. [Shea, Steven; Barr, R. Graham] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA. [Jacobs, David R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Hixson, James E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Stein, James H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Stunnenberg, Hendrik] Nijmegen Ctr Mol Life Sci, Dept Mol Biol, Nijmegen, Netherlands. [Post, Wendy S.] Johns Hopkins Univ, Dept Pathol & Cardiol, Baltimore, MD USA. [Hoeschele, Ina] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA. [Hoeschele, Ina] Virginia Tech, Dept Stat, Blacksburg, VA USA. RP Liu, YM (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM yoliu@wakehealth.edu RI Kaufman, Joel/B-5761-2008; OI Kaufman, Joel/0000-0003-4174-9037; Reynolds, Lindsay/0000-0001-6157-0144; Wang, Xuting/0000-0001-6781-8008 FU National Heart, Lung and Blood Institute [N01-HC]; National Center for Research Resources [UL1-RR-024156, UL1-RR-025005]; Intramural Research Program of the National Institute of Environmental Health Sciences [ZO1-ES100475, Z01 ES046008]; National Heart, Lung, and Blood Institute [R01HL101250]; MESA Lung contract [R01-HL077612]; U.S. Environmental Protection Agency [RD831697] FX This research was supported by contracts N01-HC-from the National Heart, Lung and Blood Institute, by grants UL1-RR-024156 and UL1-RR-025005 from the National Center for Research Resources, and support from the Intramural Research Program (projects: ZO1-ES100475 and Z01 ES046008) of the National Institute of Environmental Health Sciences. The Multi-Ethnic Study of Atherosclerosis (MESA) Epigenomics and Transcriptomics Study was funded by National Heart, Lung, and Blood Institute grant R01HL101250 to Wake Forest University Health Sciences. Urinary Cotinine measurements are available to the MESA study courtesy of MESA Lung contract R01-HL077612. The research described in this publication was funded in part by the U.S. Environmental Protection Agency through RD831697 to the University of Washington (MESA Air); it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. NR 43 TC 9 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2015 VL 8 IS 5 BP 707 EP 716 DI 10.1161/CIRCGENETICS.115.001097 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA CU2SN UT WOS:000363373800009 PM 26307030 ER PT J AU Zeller, T Haase, T Muller, C Riess, H Lau, D Zeller, S Krause, J Baumert, J Pless, O Dupuis, J Wild, PS Eleftheriadis, M Waldenberger, M Zeilinger, S Ziegler, A Peters, A Tiret, L Proust, C Marzi, C Munzel, T Strauch, K Prokisch, H Lackner, KJ Herder, C Thorand, B Benjamin, EJ Blankenberg, S Koenig, W Schnabel, RB AF Zeller, Tanja Haase, Tina Mueller, Christian Riess, Helene Lau, Denise Zeller, Simon Krause, Jasmin Baumert, Jens Pless, Ole Dupuis, Josee Wild, Philipp S. Eleftheriadis, Medea Waldenberger, Melanie Zeilinger, Sonja Ziegler, Andreas Peters, Annette Tiret, Laurence Proust, Carole Marzi, Carola Munzel, Thomas Strauch, Konstantin Prokisch, Holger Lackner, Karl J. Herder, Christian Thorand, Barbara Benjamin, Emilia J. Blankenberg, Stefan Koenig, Wolfgang Schnabel, Renate B. TI Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE gene expression; genetic variation; inflammasomes; interleukin-18; transcription factors ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; INFLAMMASOME; GENE; IDENTIFICATION; METAANALYSIS; REGULATOR; CYTOKINES; VARIANTS; PREDICT AB Background Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. Methods and Results To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4x10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. Conclusions Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation. C1 [Zeller, Tanja; Haase, Tina; Mueller, Christian; Lau, Denise; Zeller, Simon; Krause, Jasmin; Blankenberg, Stefan; Schnabel, Renate B.] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, D-20246 Hamburg, Germany. [Zeller, Tanja; Haase, Tina; Mueller, Christian; Blankenberg, Stefan; Schnabel, Renate B.] German Ctr Cardiovascular Res DZHK eV, Kiel, Germany. [Riess, Helene; Baumert, Jens; Waldenberger, Melanie; Zeilinger, Sonja; Peters, Annette; Marzi, Carola; Thorand, Barbara] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Waldenberger, Melanie; Zeilinger, Sonja; Marzi, Carola] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Strauch, Konstantin] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Prokisch, Holger] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Riess, Helene; Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Pless, Ole] Fraunhofer IME ScreeningPort, Hamburg, Germany. [Dupuis, Josee; Benjamin, Emilia J.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emilia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Benjamin, Emilia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol Sect,Prevent Med Sect,Evans Mem Med Dept, Boston, MA 02215 USA. [Wild, Philipp S.] Univ Med Ctr, Ctr Thrombosis & Hemostasis Prevent Cardiol & Pre, Dept Med 2, Mainz, Germany. [Eleftheriadis, Medea; Munzel, Thomas] Univ Med Ctr, Dept Med 2, Mainz, Germany. [Lackner, Karl J.] Univ Med Ctr, Inst Clin Chem & Lab Med, Mainz, Germany. [Wild, Philipp S.; Munzel, Thomas] German Ctr Cardiovasc Res DZHK eV, Mainz, Germany. [Ziegler, Andreas] Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. [Ziegler, Andreas] Med Univ Lubeck, Ctr Clin Trials, D-23538 Lubeck, Germany. [Tiret, Laurence; Proust, Carole] Univ Paris 06, Sorbonne Univ, Paris, France. [Tiret, Laurence; Proust, Carole] INSERM, UMR S 1166, Team Genom & Pathophysiol Cardiovasc Dis, Paris, France. [Tiret, Laurence; Proust, Carole] Inst Cardiometab & Nutr, Paris, France. [Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany. [Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Koenig, Wolfgang] Tech Univ Munich, Deutsch Herzzentrum, D-80290 Munich, Germany. [Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Herder, Christian] German Ctr Diabet Res DZD eV, Dusseldorf, Germany. [Koenig, Wolfgang] German Ctr Cardiovasc Res DZHK eV, Munich, Germany. RP Zeller, T (reprint author), Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, D-20246 Hamburg, Germany. EM t.zeller@uke.de RI Waldenberger, Melanie/B-5355-2014; Thorand, Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Pless, Ole/E-8348-2016; OI Waldenberger, Melanie/0000-0003-0583-5093; Thorand, Barbara/0000-0002-8416-6440; Pless, Ole/0000-0002-1468-316X; Benjamin, Emelia/0000-0003-4076-2336; Peters, Annette/0000-0001-6645-0985 FU German Center for Cardiovascular Research (DZHK) [81Z1710101]; Deutsche Herzstiftung [F/21/12]; government of Rhineland-Palatinate (Stiftung Rheinland-Pfalz fur Innovation) [AZ 961-386261/733]; research programs Wissen schafft Zukunft and Center for Translational Vascular Biology; Center for Thrombosis and Hemostasis of the Johannes Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical Systems; National Institutes of Health [HL076784, AG028321, HL064753]; Kalkhof-Rose Foundation for Young Researchers; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; National Institutes of Health National Center for Research Resources Shared Instrumentation grant [1S10RR163736-01A1]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF); State of Bavaria; German National Genome Research Network (NGFNPlus) [01GS0834]; German Research Foundation [DFG: TH 784/2-1]; University of Ulm; Munich Center of Health Sciences (MC-Health); Ludwig-Maximilians-Universitat, as part of LMUinnovativ; DZHK; Ministry of Science and Research of the State of North Rhine-Westphalia; German Federal Ministry of Health; BMBF; 'Stiftung Rheinland-Pfalz fur Innovation,' Ministry for Science and Education, Mainz [AZ 15202-386261/545]; Brandenburg Ministry of Economics, Germany; European Regional Development Fund FX Many funding agencies contributed to this work. This work was supported by the German Center for Cardiovascular Research (DZHK, 81Z1710101) and the Deutsche Herzstiftung (F/21/12) to Dr Zeller. Gutenberg Health Study: The Gutenberg Health Study was funded through the government of Rhineland-Palatinate (Stiftung Rheinland-Pfalz fur Innovation, contract AZ 961-386261/733), the research programs Wissen schafft Zukunft and Center for Translational Vascular Biology as well as the Center for Thrombosis and Hemostasis of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. Framingham Heart Study: This research was conducted, in part, using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The work was also supported, in part, by grants from the National Institutes of Health HL076784, AG028321, and HL064753 to Dr Benjamin, and Kalkhof-Rose Foundation for Young Researchers and Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 to Dr Schnabel. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the single nucleotide polymorphism Health Association Resource project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (contract no. N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1) and the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. MONICA/KORA: The MONICA/KORA studies were initiated and financed by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFNPlus, project number 01GS0834), the German Research Foundation (DFG: TH 784/2-1) and through additional funds from the University of Ulm. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. Interleukin-18 measurements in KORA F3 were funded by the DZHK. This work was further supported by the Ministry of Science and Research of the State of North Rhine-Westphalia and the German Federal Ministry of Health. Additionally, this study was supported, in part, by a grant from the BMBF to the German Center for Diabetes Research (DZD e.V.). AtheroGene: The AtheroGene study was supported by a grant of the 'Stiftung Rheinland-Pfalz fur Innovation,' Ministry for Science and Education (AZ 15202-386261/545), Mainz. This work was further supported by research grants from the Brandenburg Ministry of Economics, Germany, and the European Regional Development Fund. NR 33 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2015 VL 8 IS 5 BP 717 EP 726 DI 10.1161/CIRCGENETICS.115.001079 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA CU2SN UT WOS:000363373800010 PM 26362438 ER PT J AU Fedorova, OV Zernetkina, VI Shilova, VY Grigorova, YN Juhasz, O Wei, W Marshall, CA Lakatta, EG Bagrov, AY AF Fedorova, Olga V. Zernetkina, Valentina I. Shilova, Victoria Y. Grigorova, Yulia N. Juhasz, Ondrej Wei, Wen Marshall, Courtney A. Lakatta, Edward G. Bagrov, Alexei Y. TI Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE biosynthesis; CYP27A1 protein; Dahl Salt-Sensitive Rats; gene silencing; hypertension; Na-K ATPase inhibitor; natriuretic hormones; steroids ID EXPERIMENTAL UREMIC CARDIOMYOPATHY; CHRONIC-RENAL-FAILURE; CARDIOTONIC STEROIDS; ADRENAL-CORTEX; SODIUM-PUMP; MONOCLONAL-ANTIBODY; CHOLESTEROL; PREECLAMPSIA; RATS; 27-HYDROXYCHOLESTEROL AB Background The bioactive steroid, marinobufagenin, is an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells. Marinobufagenin binding to Na/K-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Steroids are derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1. The mechanism of marinobufagenin biosynthesis in mammals, however, remains unknown. Methods and Results Here, we show that post-transcriptional silencing of the CYP27A1 gene in human trophoblast and rat adrenocortical cells reduced the expression of CYP27A1 mRNA by 70%, reduced total bile acids 2-fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA. In contrast, silencing of the CYP11A1 gene did not affect marinobufagenin production in either cell culture, but suppressed production of progesterone 2-fold in human trophoblast cells and of corticosterone by 90% in rat adrenocortical cells when compared with cells transfected with nontargeting siRNA. In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold. Conclusions Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases. C1 [Fedorova, Olga V.; Zernetkina, Valentina I.; Shilova, Victoria Y.; Grigorova, Yulia N.; Juhasz, Ondrej; Wei, Wen; Marshall, Courtney A.; Lakatta, Edward G.; Bagrov, Alexei Y.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. RP Fedorova, OV (reprint author), NIA, Lab Cardiovasc Sci, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM fedorovo@mail.nih.gov; BagrovA@mail.nih.gov FU Intramural Research Program, National Institute on Aging, National Institutes of Health FX This study was supported by Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 44 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2015 VL 8 IS 5 BP 736 EP 745 DI 10.1161/CIRCGENETICS.115.001217 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA CU2SN UT WOS:000363373800012 PM 26374826 ER PT J AU Adgent, MA Rogan, WJ AF Adgent, Margaret A. Rogan, Walter J. TI Triclosan and prescription antibiotic exposures and enterolactone production in adults SO ENVIRONMENTAL RESEARCH LA English DT Article DE Triclosan; Enterolactone; NHANES; Antimicrobial; Intestinal metabolite ID HUMAN INTESTINAL BACTERIA; LOW SERUM ENTEROLACTONE; SECOISOLARICIRESINOL DIGLUCOSIDE; PHYTOESTROGEN CONCENTRATIONS; US POPULATION; MS/MS METHOD; LIGNANS; URINE; ENTERODIOL; WOMEN AB Background: The gut microbiome plays an important role in the development of disease. The composition of the microbiome is influenced by factors such as mode of delivery at birth, diet and antibiotic use, yet the influence of environmental chemical exposures is largely unknown. The antimicrobial compound triclosan, found in many personal care products and widely detected in human urine, is an environmental exposure for which systemic microbiotic effects may be of particular interest. To investigate the relationship between triclosan and gut microflora, we assessed the association between triclosan and enterolactone, an intestinal metabolite that is produced via bacterial transformation of dietary lignans (seeds, nuts) and has known susceptibility to oral antibiotics. Methods: We examined urinary triclosan and enterolactone for 2005-2008 U.S. National Health and Nutrition Examination Survey subjects, aged >= 20 years (n=3041). We also examined the association between prescription antibiotic use and enterolactone to confirm its susceptibility to changes in bacterial composition of the body. Associations between natural log-transformed enterolactone and (1) detected vs. not detected (< 2.3 ng/mL) triclosan, (2) triclosan quintiles (Q1-Q5), and (3) any vs. no antibiotics were estimated with multiple linear regression, adjusting for sex, age, race, body mass index, poverty income ratio, education, fiber intake, bowel movement frequency, cotinine and creatinine (n=2441). Results: Triclosan was detected in 80% of subjects (range: <2.3-3620 ng/mL), while enterolactone was detected in >99% of subjects (range: <0.1-122,000 ng/mL). After adjustment, enterolactone was not associated with triclosan (detect vs. non-detect: beta=0.07 (95% CI: -0.15, 0.30); Q5 (>= 104.5 ng/mL) vs. Q1 (none): beta=0.06 (95% CI: -0.21, 0.34)). In sex-stratified analyses, triclosan was associated with higher enterolactone in women (detect vs. non-detect: beta=0.31 (95% CI: -0.07, 0.70), but not men beta=-0.18 (95% CI: -0.47, 0.11). However, any antibiotic use (n=112), as compared to no antibiotic use, was associated with significantly lower enterolactone (beta=-0.78 (95%CI: -1.22, -036)), with no sex-specific effects. This association was driven by inverse associations with the following antibiotic classes: macrolide derivatives, quinolones, sulfonamides, and lincomycin derivatives. Conclusions: Antibiotics, but not triclosan, are negatively associated with urinary enterolactone. Antibiotics may reduce enterolactone by killing certain gut bacteria. At levels detected in the U.S., triclosan does not appear to be acting similarly, despite broad antimicrobial properties. Additional study of determinants of triclosan exposure and enterolactone production may be needed to better understand positive associations among women. Published by Elsevier Inc. C1 [Adgent, Margaret A.; Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Adgent, MA (reprint author), NIEHS, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM margaret.adgent@nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This research was supported [in part] by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 39 TC 3 Z9 3 U1 3 U2 16 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 OCT PY 2015 VL 142 BP 66 EP 71 DI 10.1016/j.envres.2015.06.017 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA CU5WN UT WOS:000363602800009 PM 26114916 ER PT J AU Gudzenko, N Hatch, M Bazyka, D Dyagil, I Reiss, RF Brenner, A Chumak, V Babkina, N Zablotska, LB Mabuchi, K AF Gudzenko, N. Hatch, M. Bazyka, D. Dyagil, I. Reiss, R. F. Brenner, A. Chumak, V. Babkina, N. Zablotska, L. B. Mabuchi, K. TI Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine SO ENVIRONMENTAL RESEARCH LA English DT Article DE Leukemia; Ukraine; Chornobyl cleanup workers; Petroleum; Benzene ID CHRONIC MYELOID-LEUKEMIA; ATOMIC-BOMB SURVIVORS; LOW-LEVEL BENZENE; PETROLEUM WORKERS; OCCUPATIONAL-EXPOSURE; LYMPHOMA SUBTYPES; CIGARETTE-SMOKING; ALCOHOL-DRINKING; TOBACCO SMOKING; COHORT AB Background: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. Methods: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. Results: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=228; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. Conclusions: These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products. (C) 2015 Elsevier Inc. All rights reserved. C1 [Gudzenko, N.; Bazyka, D.; Dyagil, I.; Chumak, V.; Babkina, N.] Natl Res Ctr Radiat Med, Kiev, Ukraine. [Hatch, M.; Brenner, A.; Mabuchi, K.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Reiss, R. F.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Zablotska, L. B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. RP Hatch, M (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM gudznat@gmail.com; hatchm@mail.nih.gov; Bazyka@yahoo.com; leuk@ukr.net; rfr1@columbia.edu; brennera@mail.nih.gov; Chumak.vadim@gmail.com; natalie.babkina@gmail.com; lydia.zablotska@ucsf.edu; mabuchik@mail.nih.gov RI Chumak, Vadim/N-6960-2015 OI Bazyka, Dimitry/0000-0001-9982-5990; Chumak, Vadim/0000-0001-6045-9356 FU Intramural Research Program of the U.S. National Institutes of Health (NIH), National Cancer Institute (NCI); NCI [K07CA132918, N01-CP-21178] FX This research was supported in part by the Intramural Research Program of the U.S. National Institutes of Health (NIH), National Cancer Institute (NCI). LBZ was supported by NCI Grant K07CA132918 and Contract N01-CP-21178. NR 34 TC 1 Z9 2 U1 0 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 OCT PY 2015 VL 142 BP 72 EP 76 DI 10.1016/j.envres.2015.06.019 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA CU5WN UT WOS:000363602800010 PM 26117815 ER PT J AU Bloom, MS Louis, GMB Sundaram, R Maisog, JM Steuerwald, AJ Parsons, PJ AF Bloom, Michael S. Louis, Germaine M. Buck Sundaram, Rajeshwari Maisog, Jose M. Steuerwald, Amy J. Parsons, Patrick J. TI Birth outcomes and background exposures to select elements, the Longitudinal Investigation of Fertility and the Environment (LIFE) (vol 138, pg 118, 2015) SO ENVIRONMENTAL RESEARCH LA English DT Correction C1 [Bloom, Michael S.; Steuerwald, Amy J.; Parsons, Patrick J.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Rensselaer, NY 12144 USA. [Bloom, Michael S.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA. [Louis, Germaine M. Buck; Sundaram, Rajeshwari; Maisog, Jose M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA. [Maisog, Jose M.] Glotech Inc, Rockville, MD USA. [Steuerwald, Amy J.; Parsons, Patrick J.] New York State Dept Hlth, Wadsworth Ctr, Lab Inorgan & Nucl Chem, Albany, NY USA. RP Bloom, MS (reprint author), SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Rensselaer, NY 12144 USA. OI Bloom, Michael/0000-0002-0028-5494 NR 1 TC 0 Z9 0 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 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2015 VL 142 BP 760 EP 761 DI 10.1016/j.envres.2015.06.012 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA CU5WN UT WOS:000363602800091 ER PT J AU Dzierzewski, JM Potter, GG Jones, RN Rostant, OS Ayotte, B Yang, FM Sachs, BC Feldman, BJ Steffens, DC AF Dzierzewski, Joseph M. Potter, Guy G. Jones, Richard N. Rostant, Ola S. Ayotte, Brian Yang, Frances M. Sachs, Bonnie C. Feldman, Betsy J. Steffens, David C. TI Cognitive functioning throughout the treatment history of clinical late-life depression SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE major depressive disorder; cognitive functioning; depressive symptoms; naturalistic study; longitudinal design ID OLDER-ADULTS; SYMPTOMS; DECLINE; COMMUNITY; POPULATION; CONCURRENT; CERAD; SCALE; STATE; MOOD AB Objective: Previous investigations into the relationship between late-life depressive symptoms and cognitive functioning have resulted in mixed findings concerning whether or not depressive symptoms and cognitive functioning are related. The mixed reports may be due in part to differences in clinical and nonclinical samples and to inadequate consideration of the dynamic nature (i.e., fluctuating course) of depressive symptoms and cognitive functioning in older adults. The current study examined the chronic, acute, and longitudinal relationships between depressive symptoms and cognitive functioning in older adults in an ongoing treatment study of major depressive disorder (MDD). Methods: The neurocognitive outcomes of depression in the elderly study operates in a naturalistic treatment milieu using a pharmacological treatment algorithm and regular psychiatric assessment. Four hundred and fifty-three older adults [mean age 70 years, standard deviation (SD)=7.2] meeting criteria for MDD at study enrollment received annual neuropsychological testing and depressive symptom monitoring for an average of 8.5 years (SD=4.5). Results: Hierarchical linear modeling revealed that higher age, lower education, and higher average/chronic levels of depressive symptoms were related to lower cognitive functioning. Additionally, results revealed that when an individual's depressive symptoms are higher than is typical for a specific individual, general cognitive function was worse than average. There was no evidence of lagged/longitudinal relationships between depressive symptoms and cognitive functioning in older adults in treatment for MDD. Conclusions: Cognitive functioning and depressive symptoms are concurrently associated in older adults with MDD, highlighting the potential importance for stabilizing mood symptoms as a means to manage cognitive deficits in late-life depression. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Dzierzewski, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dzierzewski, Joseph M.] Greater Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Potter, Guy G.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Jones, Richard N.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Rostant, Ola S.] Univ Michigan, Natl Inst Hlth, Intramural Res Program, Natl Inst Aging, Ann Arbor, MI 48109 USA. [Rostant, Ola S.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Ayotte, Brian] Univ Massachusetts, Dept Psychol, Dartmouth, MA USA. [Yang, Frances M.] Georgia Regents Univ, Med Coll Georgia, Dept Biostat & Epidemiol, Augusta, GA USA. [Sachs, Bonnie C.] Wake Forest Univ, Baptist Med Ctr, Dept Neurol, Winston Salem, NC 27109 USA. [Feldman, Betsy J.] Univ Washington, Sch Social Work, Partners Children, Seattle, WA 98195 USA. [Steffens, David C.] Univ Connecticut, Dept Psychiat, Farmington, CT 06107 USA. RP Dzierzewski, JM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM Joseph.Dzierzewski@va.gov RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIMH [MH54846]; UCLA Claude Pepper Center [5P30AG028748]; UCLA CTSI [UL1TR000124]; VA Advanced Geriatrics Fellowship; [R13 AG030995] FX This work was supported by a conference grant (R13 AG030995). The source study was supported by NIMH (MH54846). Joseph M. Dzierzewski was supported by UCLA Claude Pepper Center (5P30AG028748) and UCLA CTSI (UL1TR000124), and VA Advanced Geriatrics Fellowship. NR 37 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2015 VL 30 IS 10 BP 1076 EP 1084 DI 10.1002/gps.4264 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CU7OB UT WOS:000363729700010 PM 25703072 ER PT J AU Frenkel, TI Fox, NA Pine, DS Walker, OL Degnan, KA Chronis-Tuscano, A AF Frenkel, Tahl I. Fox, Nathan A. Pine, Daniel S. Walker, Olga L. Degnan, Kathryn A. Chronis-Tuscano, Andrea TI Early childhood behavioral inhibition, adult psychopathology and the buffering effects of adolescent social networks: a twenty-year prospective study SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Child temperament; adult psychopathology; anxiety; adolescence; social networks ID ANXIETY DISORDERS; TEMPERAMENT; CHILDREN; ASSOCIATION; FRIENDSHIPS; UNFAMILIAR; STABILITY; SYMPTOMS; RISK AB Background: We examined whether the temperament of behavioral inhibition is a significant marker for psychopathology in early adulthood and whether such risk is buffered by peer social networks. Methods: Participants (N = 165) were from a prospective study spanning the first two decades of life. Temperament was characterized during infancy and early childhood. Extent of involvement in peer social networks was measured during adolescence, and psychopathology was assessed in early adulthood. Latent Class Analyses generated comprehensive variables at each of three study time-points. Regressions assessed (a) the direct effect of early behavioral inhibition on adult psychopathology (b) the moderating effect of adolescent involvement in social peer networks on the link between temperamental risk and adult psychopathology. Results: Stable behavioral inhibition in early childhood was negatively associated with adult mental health (R-2 = .07, p = .005, beta = -.26), specifically increasing risk for adult anxiety disorders (R-2 = .04, p = .037, beta = .19). These temperament-pathology relations were significantly moderated by adolescent peer group social involvement and network size (Total R-2 = .13, p = .027, beta = -.22). Temperament predicted heightened risk for adult anxiety when adolescent social involvement was low (p = .002, beta = .43), but not when adolescent social involvement was high. Conclusions: Stable behavioral inhibition throughout early childhood is a risk factor for adult anxiety disorders and interacts with adolescent social involvement to moderate risk. This is the first study to demonstrate the critical role of adolescent involvement in socially active networks in moderating long-lasting temperamental risk over the course of two decades, thus informing prevention/intervention approaches. C1 [Frenkel, Tahl I.; Fox, Nathan A.; Walker, Olga L.; Degnan, Kathryn A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Chronis-Tuscano, Andrea] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Frenkel, TI (reprint author), Univ Maryland, Dept Human Dev & Quantitat Methodol, 3304 Benjamin, College Pk, MD 20742 USA. EM tfrenkel@umd.edu FU NIH [R37HD17899, MH093349]; National Institute of Mental Health FX This research was supported in part by NIH Grants R37HD17899 and MH093349 granted to NAF, and by the Intramural Research Program of the National Institute of Mental Health. The authors have declared that they have no potential or competing conflicts of interest. NR 58 TC 6 Z9 6 U1 4 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2015 VL 56 IS 10 BP 1065 EP 1073 DI 10.1111/jcpp.12390 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CU7PC UT WOS:000363732800006 PM 25652940 ER PT J AU Whelan, YM Leibenluft, E Stringaris, A Barker, ED AF Whelan, Yvonne M. Leibenluft, Ellen Stringaris, Argyris Barker, Edward D. TI Pathways from maternal depressive symptoms to adolescent depressive symptoms: the unique contribution of irritability symptoms SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Psychopathology; oppositional defiant disorder; depression; development; mother-child relationships ID OPPOSITIONAL DEFIANT DISORDER; DIFFICULTIES QUESTIONNAIRE SDQ; EARLY-ONSET PERSISTENT; CONDUCT PROBLEM YOUTH; ASTERISK-D-CHILD; MENTAL-HEALTH; POSTNATAL DEPRESSION; PSYCHOPATHOLOGY; STRENGTHS; RISK AB Background: The authors tested three possible pathways linking prenatal maternal depressive symptoms to adolescent depressive symptoms. These pathways went through childhood Irritability Symptoms, Anxiety/Depressive Symptoms or Conduct Problems. Method: Data were collected from 3,963 mother-child pairs participating in the Avon Longitudinal Study of Parents and Children. Measures include maternal depressive symptoms (pre- and postnatal); toddler temperament (2 years); childhood (7-13 years) irritability symptoms, anxiety/depressive symptoms, conduct problems, and adolescent depressive symptoms (16 years). Results: Irritability Symptoms: This pathway linked sequentially - prenatal maternal depressive symptoms, toddler temperament (high perceived intensity and low perceived adaptability), childhood irritability symptoms, and adolescent depressive symptoms. Anxiety/Depressive symptoms: This pathway linked sequentially -prenatal maternal depressive symptoms, toddler temperament (negative perceived mood), childhood anxiety/depressive symptoms, and adolescent depressive symptoms. Childhood conduct problems were not associated with adolescent depressive symptoms, above and beyond irritability symptoms and anxiety/depressive symptoms. Conclusions: Results suggest evidence for two distinct developmental pathways to adolescent depressive symptoms that involve specific early and midchildhood features. C1 [Whelan, Yvonne M.] Univ London, Dept Psychol Sci, London, England. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. [Stringaris, Argyris] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child & Adolescent Psychiat, London, England. [Barker, Edward D.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, London, England. RP Barker, ED (reprint author), Kings Coll London, Dept Psychol, Inst Psychiat Psychol & Neurosci, London SE5 8AF, England. EM barker@kcl.ac.uk FU UK Medical Research Council [74883]; Wellcome Trust [0754567]; Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [R01HD068437]; ESRC [ES/J500021/1 W85058B]; National Institute of Mental Health Division of Intramural Research Programs; Wellcome Trust; National Institute for Health Research (NIHR); Department of Health UK FX The authors are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The UK Medical Research Council (grant ref: 74883), the Wellcome Trust (grant ref: 0754567) and the University of Bristol provide core support for ALSPAC.; Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD068437 to E. D. B; Y. M. W. is supported by an ESRC studentship (ES/J500021/1 W85058B). E. L. is supported by the National Institute of Mental Health Division of Intramural Research Programs; A. S. is funded by the Wellcome Trust, the National Institute for Health Research (NIHR) and the Department of Health UK and receives royalties from Cambridge University Press for his book The Maudsley Reader in Phenomenological Psychiatry. All authors declare they have no potential or competing conflicts of interest with relation to this work. NR 58 TC 6 Z9 6 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2015 VL 56 IS 10 BP 1092 EP 1100 DI 10.1111/jcpp.12395 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CU7PC UT WOS:000363732800009 PM 25665134 ER PT J AU Mikita, N Hollocks, MJ Papadopoulos, AS Aslani, A Harrison, S Leibenluft, E Simonoff, E Stringaris, A AF Mikita, Nina Hollocks, Matthew J. Papadopoulos, Andrew S. Aslani, Alexandra Harrison, Simon Leibenluft, Ellen Simonoff, Emily Stringaris, Argyris TI Irritability in boys with autism spectrum disorders: an investigation of physiological reactivity SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Autism spectrum disorders; irritability; cortisol; heart rate; psychosocial stress test ID PSYCHOSOCIAL STRESS; SOCIAL STRESS; CORTISOL-LEVELS; DEPRESSED MOOD; CHILDREN; ANXIETY; ADOLESCENTS; BEHAVIOR; ASSOCIATIONS; OPPOSITIONALITY AB Background: Irritability in people with autism spectrum disorders (ASD) is common and impairing, yet its mechanisms remain understudied. We investigated symptom reporting and mechanisms of irritability in ASD, focusing on the relation between irritability and physiological stress responses. Methods: Forty-seven unmedicated boys with high-functioning ASD (hfASD) and 23 typically developing boys aged 10-16 years completed a psychosocial stress test. Changes in cortisol, heart rate and heart rate variability throughout the test were recorded. Self-and parent-reported measures of irritability were obtained. Irritability symptom reporting in the hfASD group was compared to two groups of boys without ASD: highly irritable boys (severe mood dysregulation, SMD; n = 40) and healthy-control boys (HC; n = 30). Results: Boys with hfASD scored significantly higher on irritability than HC boys, and they reported a pattern of irritability symptoms closely resembling that of boys with SMD. The internal consistency of irritability in hfASD was high by parent-and self-report. Although boys with hfASD showed significant stress-induced changes in cortisol and heart rate, those who rated themselves as highly irritable had lower cortisol levels throughout the test compared to those low on irritability. Participants rated as highly irritable by their parents showed blunted cortisol and heart rate responses to stress. The effects of irritability on heart rate, but not cortisol, were accounted for by trait anxiety. Conclusions: Irritability can be measured reliably in hfASD and is associated with distinct biological responses to stress. C1 [Mikita, Nina; Hollocks, Matthew J.; Aslani, Alexandra; Harrison, Simon; Simonoff, Emily; Stringaris, Argyris] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child & Adolescent Psychiat, London SE5 8AF, England. [Papadopoulos, Andrew S.] Kings Coll London, Dept Psychol Med, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. RP Mikita, N (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child & Adolescent Psychiat, Crespigny Pk,PO85, London SE5 8AF, England. EM nina.mikita@kcl.ac.uk RI Simonoff, Emily/B-7593-2011; OI Hollocks, Matthew/0000-0002-9513-6917 FU Wellcome Trust; Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre; Dementia Unit awarded to South London; Maudsley NHS Foundation Trust in partnership with King's College London; King's College Hospital NHS Foundation Trust; South London; Maudsley Charitable Funds FX A.S. gratefully acknowledges funding from the Wellcome Trust. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit awarded to South London and Maudsley NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Funding for equipment and saliva analyses was provided by a grant from the South London and Maudsley Charitable Funds. NR 53 TC 10 Z9 10 U1 4 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2015 VL 56 IS 10 BP 1118 EP 1126 DI 10.1111/jcpp.12382 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA CU7PC UT WOS:000363732800012 PM 25626926 ER PT J AU Mazor, R Tai, CH Lee, B Pastan, I AF Mazor, Ronit Tai, Chin-Hsien Lee, Byungkook Pastan, Ira TI Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T-cell epitope; MHC alleles; T-cell activation; Immunogenicity; HLA binding prediction; HLA binding algorithm ID PHASE-I TRIAL; RECOMBINANT IMMUNOTOXIN; VACCINE DEVELOPMENT; REDUCED IMMUNOGENICITY; SILICO PREDICTION; EPITOPES; RESPONSES; IDENTIFICATION; VALIDATION; MOLECULES AB The ability to identify immunogenic determinants that activate T-cells is important for the development of new vaccines, allergy therapy and protein therapeutics. In silico MHC-II binding prediction algorithms are often used for T-cell epitope identification. To understand how well those programs predict immunogenicity, we computed HLA binding to peptides spanning the sequence of PE38, a fragment of an anti-cancer immunotoxin, and compared the predicted and experimentally identified T-cell epitopes. We found that the prediction for individual donors did not correlate well with the experimental data. Furthermore, prediction of T-cell epitopes in an HLA heterogenic population revealed that the two strongest epitopes were predicted at multiple cutoffs but the third epitope was predicted negative at all cutoffs and overall 4/9 epitopes were missed at several cutoffs. We conclude that MHC class-II binding predictions are not sufficient to predict the T-cell epitopes in PE38 and should be supplemented by experimental work. Published by Elsevier B.V. C1 [Mazor, Ronit; Tai, Chin-Hsien; Lee, Byungkook; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM mazorr@mail.nih.gov; TaiC@mail.nih.gov; BKLee@mail.nih.gov; pastani@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 57 TC 7 Z9 7 U1 2 U2 10 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 OCT PY 2015 VL 425 BP 10 EP 20 DI 10.1016/j.jim.2015.06.003 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA CU8UM UT WOS:000363819600002 PM 26056938 ER PT J AU Brown, EP Normandin, E Osei-Owusu, NY Mahan, AE Chan, YN Lai, JI Vaccari, M Rao, M Franchini, G Alter, G Ackerman, ME AF Brown, Eric P. Normandin, Erica Osei-Owusu, Nana Yaw Mahan, Alison E. Chan, Ying N. Lai, Jennifer I. Vaccari, Monica Rao, Mangala Franchini, Genoveffa Alter, Galit Ackerman, Margaret E. TI Microscale purification of antigen-specific antibodies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Antigen; Antibody; Purification; Glycosylation; Effector function ID IGG-FC; HIGH-THROUGHPUT; MONOCLONAL-ANTIBODY; IMMUNOGLOBULIN-G; GLYCOSYLATION PROFILES; RHEUMATOID-ARTHRITIS; MASS-SPECTROMETRY; EBOLA-VIRUS; SERUM IGG; IN-VIVO AB Glycosylation of the Fc domain is an important driver of antibody effector function. While assessment of antibody glycoform compositions observed across total plasma IgG has identified differences associated with a variety of clinical conditions, in many cases it is the glycosylation state of only antibodies against a specific antigen or set of antigens that may be of interest, for example, in defining the potential effector function of antibodies produced during disease or after vaccination. Historically, glycoprofiling such antigen-specific antibodies in clinical samples has been challenging due to their low prevalence, the high sample requirement for most methods of glycan determination, and the lack of high-throughput purification methods. New methods of glycoprofiling with lower sample requirements and higher throughput have motivated the development of microscale and automatable methods for purification of antigen-specific antibodies from polyclonal sources such as clinical serum samples. In this work, we present a robot-compatible 96-well plate-based method for purification of antigen-specific antibodies, suitable for such population level glycosylation screening. We demonstrate the utility of this method across multiple antibody sources, using both purified plasma IgG and plasma, and across multiple different antigen types, with enrichment factors greater than 1000-fold observed. Using an on-column IdeS protease treatment, we further describe staged release of Fc and Fab domains, allowing for glycoprofiling of each domain. (C) 2015 Elsevier B.V. All rights reserved. C1 [Brown, Eric P.; Normandin, Erica; Chan, Ying N.; Lai, Jennifer I.; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Osei-Owusu, Nana Yaw] Dartmouth Coll, Mol & Cellular Biol Program, Hanover, NH 03755 USA. [Mahan, Alison E.; Alter, Galit] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Mahan, Alison E.; Alter, Galit] Harvard Univ, Cambridge, MA 02139 USA. [Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Vaccine Sect, Bethesda, MD 20814 USA. [Rao, Mangala] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. RP Ackerman, ME (reprint author), 14 Engn Dr, Hanover, NH 03755 USA. EM Margaret.e.ackerman@dartmouth.edu OI Mahan, Alison/0000-0003-4284-8467; Brown, Eric/0000-0002-8438-6136 FU Bill and Melinda Gates Foundation [OPP1032817]; NIH [1R01AI102691, 5R01AIl080289-03] FX These studies were conducted with support from the Bill and Melinda Gates Foundation OPP1032817; NIH 1R01AI102691 and 5R01AIl080289-03. The authors acknowledge E. Billings of MHRP for the design of the cyclic peptide. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: Catalog #3957, HIV-IG from NABI and NHLBL The opinions herein are those of the authors and should not be construed as official or representing the views of the U.S. Department of Defense or the Department of the Army, or the U.S. National Institutes of Health. NR 59 TC 3 Z9 3 U1 1 U2 5 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 OCT PY 2015 VL 425 BP 27 EP 36 DI 10.1016/j.jim.2015.06.005 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA CU8UM UT WOS:000363819600004 PM 26078040 ER PT J AU Liang, F Ploquin, A Hernandez, JD Fausther-Bovendo, H Lindgren, G Stanley, D Martinez, AS Brenchley, JM Koup, RA Lore, K Sullivan, NJ AF Liang, Frank Ploquin, Aurelie Hernandez, Jose DelaO Fausther-Bovendo, Hugues Lindgren, Gustaf Stanley, Daphne Salvador Martinez, Aiala Brenchley, Jason M. Koup, Richard A. Lore, Karin Sullivan, Nancy J. TI Dissociation of skeletal muscle for flow cytometric characterization of immune cells in macaques SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Skeletal muscle; Nonhuman primate; Vaccine administration; Flow cytometry ID COMPLEX CLASS-I; DENDRITIC CELLS; INFLAMMATORY MYOPATHIES; SATELLITE CELLS; VIRUS-INFECTION; MACROPHAGES; EXPRESSION; VACCINES; IMMUNOPHENOTYPE; EFFICIENT AB The majority of vaccines and several treatments are administered by intramuscular injection. The aim is to engage and activate immune cells, although they are rare in normal skeletal muscle. The phenotype and function of resident as well as infiltrating immune cells in the muscle after injection are largely unknown. While methods for obtaining and characterizing murine muscle cell suspensions have been reported, protocols for nonhuman primates (NHPs) have not been well defined. NHPs comprise important in vivo models for studies of immune cell function due to their high degree of resemblance with humans. In this study, we developed and systematically compared methods to collect vaccine-injected muscle tissue to be processed into single cell suspensions for flow cytometric characterization of immune cells. We found that muscle tissue processed by mechanical disruption alone resulted in significantly lower immune cell yields compared to enzymatic digestion using Liberase. Dendritic cell subsets, monocytes, macrophages, neutrophils, B cells, T cells and NM cells were readily detected in the muscle by the classic human markers. The methods for obtaining skeletal muscle cell suspension established here offer opportunities to increase the understanding of immune responses in the muscle, and provide a basis for defining immediate post-injection vaccine responses in primates. (C) 2015 Elsevier B.V. All rights reserved. C1 [Liang, Frank; Lindgren, Gustaf; Lore, Karin] Karolinska Inst, Dept Med Solna, Stockholm, Sweden. [Liang, Frank; Ploquin, Aurelie; Hernandez, Jose DelaO; Fausther-Bovendo, Hugues; Stanley, Daphne; Koup, Richard A.; Lore, Karin; Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Salvador Martinez, Aiala] Univ Basque Country, Sch Pharm, Lab Pharmaceut, Vitoria, Spain. [Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Lore, K (reprint author), Karolinska Inst, Dept Med Solna, Stockholm, Sweden. FU National Institute of Allergy and Infectious Diseases; Swedish Research Council (Vetenskapsradet); Swedish Governmental Agency for Innovation Systems (Vinnova) FX We would like to thank Dr. Srinivas Rao and John-Paul Todd at the Vaccine Research Center, NIH and the veterinarians, especially Dr. Michelle Browning and all animal care staff at Bioqual and NIHAC, NIH. This study was supported by the National Institute of Allergy and Infectious Diseases intramural research program (NJS and AP), as well as by the Swedish Research Council (Vetenskapsradet) and the Swedish Governmental Agency for Innovation Systems (Vinnova) (K.L. funding recipient). NR 44 TC 2 Z9 2 U1 2 U2 3 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 OCT PY 2015 VL 425 BP 69 EP 78 DI 10.1016/j.jim.2015.06.011 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA CU8UM UT WOS:000363819600010 PM 26099800 ER PT J AU Burns, KM Encinosa, WE Pearson, GD Kaltman, JR AF Burns, Kristin M. Encinosa, William E. Pearson, Gail D. Kaltman, Jonathan R. TI Electrocardiogram in Preparticipation Athletic Evaluations among Insured Youths SO JOURNAL OF PEDIATRICS LA English DT Article ID SUDDEN CARDIAC DEATH; AMERICAN-HEART-ASSOCIATION; COLLEGE-OF-CARDIOLOGY; CARDIOVASCULAR-ABNORMALITIES; SCIENTIFIC STATEMENT; PREVENTION; RECOMMENDATIONS; STRATEGIES; REDUCE; COST AB Objective To retrospectively characterize electrocardiogram (ECG) use among preparticipation history and examinations (PPEs). Study design Using the 2005 to 2010 MarketScan insurance database, we identified subjects aged 5-21 years with either a PPE with an ECG or a PPE alone, excluding those with known cardiac diagnoses. We described cardiology referrals and subspecialty testing within 180 days and cardiac diagnoses within 1 year of the PPE, and the costs of testing in each group. Results From 2005-2009, 503 304 PPEs occurred in 419 456 subjects, of which 8621 (2%) included an ECG. ECG use increased from 12-20 per 1000 PPEs from 2005-2009. Females, lower socioeconomic status, and rural settings were associated with fewer ECGs. Thirteen percent of PPEs with ECG and 0.5% of PPEs alone led to a cardiology referral. After PPEs with ECG, cardiac disease was identified in 18% (2% sports-limiting); after PPEs alone, cardiac disease was identified in 0.5% (0.03% sports-limiting). The PPE had a sensitivity of 44% and a specificity of 98.6% of identifying cardiac disease. The total reimbursement cost of PPEs plus testing was $ 80 396 464 ($ 160 per PPE). Conclusions These real-world data demonstrate that community providers selectively use the ECG as part of the PPE with a high rate of identification of cardiac disease. Mass ECG screening would need to be more efficient at identifying disease than this selective approach. C1 [Burns, Kristin M.; Pearson, Gail D.; Kaltman, Jonathan R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Encinosa, William E.] Agcy Healthcare Res & Qual, Ctr Delivery Org & Markets, Rockville, MD USA. RP Burns, KM (reprint author), NHLBI, Div Cardiovasc Sci, Heart Dev & Struct Dis Branch, NIH, 6701 Rockledge Dr,Room 8220, Bethesda, MD 20892 USA. EM kristin.burns@nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 27 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 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 BP 804 EP + DI 10.1016/j.jpeds.2015.06.011 PG 7 WC Pediatrics SC Pediatrics GA CU5BE UT WOS:000363545800007 PM 26148663 ER PT J AU Hirtz, DG Weiner, SJ Bulas, D DiPietro, M Seibert, J Rouse, DJ Mercer, BM Varner, MW Reddy, UM Iams, JD Wapner, RJ Sorokin, Y Thorp, JM Ramin, SM Malone, FD Carpenter, MW O'Sullivan, MJ Peaceman, AM Hankins, GDV Dudley, D Caritis, SN AF Hirtz, Deborah G. Weiner, Steven J. Bulas, Dorothy DiPietro, Michael Seibert, Joanna Rouse, Dwight J. Mercer, Brian M. Varner, Michael W. Reddy, Uma M. Iams, Jay D. Wapner, Ronald J. Sorokin, Yoram Thorp, John M., Jr. Ramin, Susan M. Malone, Fergal D. Carpenter, Marshall W. O'Sullivan, Mary J. Peaceman, Alan M. Hankins, Gary D. V. Dudley, Donald Caritis, Steve N. CA Eunice Kennedy Shriver Natl Inst TI Antenatal Magnesium and Cerebral Palsy in Preterm Infants SO JOURNAL OF PEDIATRICS LA English DT Article ID CRANIAL ULTRASOUND LESIONS; BIRTH-WEIGHT INFANTS; LOW GESTATIONAL-AGE; INTRAVENTRICULAR HEMORRHAGE; DEVELOPMENTAL-DISABILITY; NATIONAL COHORT; SULFATE; BORN; PREVENTION; CHILDREN AB Objective To evaluate the relationship of maternal antenatal magnesium sulfate (MgSO4) with neonatal cranial ultrasound abnormalities and cerebral palsy (CP). Study design In a randomized trial of MgSO4 or placebo in women at high risk of preterm delivery, up to 3 cranial ultrasounds were obtained in the neonatal period. Images were reviewed by at least 2 pediatric radiologists masked to treatment and other clinical conditions. Diagnoses were predefined for intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly. CP was diagnosed at 2 years of age by standardized neurologic examination. Results Intraventricular hemorrhage, periventricular leukomalacia, intracerebral echolucency or echodensity, and ventriculomegaly were all strongly associated with an increased risk of CP. MgSO4 administration did not affect the risk of cranial ultrasound abnormality observed at 35 weeks postmenstrual age or later. However, for the 82% of infants born at <32 weeks gestation, MgSO4 was associated with a reduction in risk of echolucency or echodensity. The reduction in risk for echolucency explained 21% of the effect of MgSO4 on CP (P = .04), and for echodensity explained 20% of the effect (P = .02). Conclusions MgSO4 given prior to preterm delivery was associated with decreased risk of developing echodensities and echolucencies at <32 weeks gestation. However, this effect can only partially explain the effect of MgSO4 on CP at 2 years of age. C1 [Hirtz, Deborah G.] NINDS, NIH, Bethesda, MD 20892 USA. [Weiner, Steven J.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Bulas, Dorothy] Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. [DiPietro, Michael] Univ Michigan, Sect Pediat Radiol, Ann Arbor, MI 48109 USA. [Seibert, Joanna] Arkansas Childrens Hosp, Div Radiol, Little Rock, AR 72202 USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. [Mercer, Brian M.] Univ Tennessee, Memphis, TN USA. [Varner, Michael W.] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. [Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA. [Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Thorp, John M., Jr.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Childrens Mem Hermann Hosp, Houston, TX 77030 USA. [Malone, Fergal D.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Carpenter, Marshall W.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. [O'Sullivan, Mary J.] Univ Miami, Dept Obstet & Gynecol, Miami, FL USA. [Peaceman, Alan M.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Hankins, Gary D. V.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Dudley, Donald] Univ Texas San Antonio, Dept Obstet & Gynecol, San Antonio, TX USA. [Caritis, Steve N.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. RP Hirtz, DG (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU National Institute of Neurological Disorders and Stroke (NINDS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897, M01-RR-000080] FX Supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897, and M01-RR-000080). Comments and views of the authors do not necessarily represent the views of the NICHD or NINDS. The authors declare no conflicts of interest. NR 37 TC 8 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 BP 834 EP + DI 10.1016/j.jpeds.2015.06.067 PG 9 WC Pediatrics SC Pediatrics GA CU5BE UT WOS:000363545800013 PM 26254839 ER PT J AU Leung, DH Ye, W Molleston, JP Weymann, A Ling, S Paranjape, SM Romero, R Schwarzenberg, SJ Palermo, J Alonso, EM Murray, KF Marshall, BC Sherker, AH Siegel, MJ Krishnamurthy, R Harned, R Karmazyn, B Magee, JC Narkewicz, MR AF Leung, Daniel H. Ye, Wen Molleston, Jean P. Weymann, Alexander Ling, Simon Paranjape, Shruti M. Romero, Rene Schwarzenberg, Sara Jane Palermo, Joseph Alonso, Estella M. Murray, Karen F. Marshall, Bruce C. Sherker, Averell H. Siegel, Marilyn J. Krishnamurthy, Rajesh Harned, Roger Karmazyn, Boaz Magee, John C. Narkewicz, Michael R. CA Cystic Fibrosis Liver TI Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis SO JOURNAL OF PEDIATRICS LA English DT Article ID FATTY LIVER-DISEASE; TRANSIENT ELASTOGRAPHY; POPULATION AB Objective To investigate the relationship between abdominal ultrasound findings and demographic, historical, and clinical features in children with cystic fibrosis (CF). Study design Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multicenter study of ultrasound to predict hepatic fibrosis. Consensus ultrasound patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and US or Toronto CF registries. x(2) or ANOVA were used to compare variables among ultrasound groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal ultrasound. Results Findings in 719 subjects were normal (n = 590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (P = .0004), homogeneous (P < .0001), and heterogeneous (P = .03) were older than normal. More males were heterogeneous (P = .001). More heterogeneous (15.0%, P = .009) and cirrhosis (25.0%, P = .005) had CF-related diabetes or impaired glucose tolerance vs normal (5.4%). Early infection with Pseudomonas aeruginosa (< 2 years old) was associated with a lower risk (OR 0.42, P = .0007) of abnormal. Ursodeoxycholic acid use (OR 3.69, P < .0001) and CF-related diabetes (OR 2.21, P = .019) were associated with increased risk of abnormal. Conclusions Unsuspected cirrhosis is seen in 3.3% of young patients with CF, heterogeneous in 8.9%. Abnormal ultrasound is associated with CF-related diabetes, and early P aeruginosa is associated with normal ultrasound. Prospective assessment of these risk factors may identify potential interventional targets. C1 [Leung, Daniel H.] Texas Childrens Hosp, Baylor Coll Med, Div Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Ye, Wen] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Molleston, Jean P.] Indiana Univ Sch Med, Riley Hosp Children, Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA. [Weymann, Alexander] Washington Univ, Sch Med, Dept Pediat, Div Gastroenterol Hepatol & Nutr, St Louis, MO 63110 USA. [Ling, Simon] Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada. [Ling, Simon] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Paranjape, Shruti M.] Johns Hopkins Univ, Sch Med, Div Pediat Pulmonol, Baltimore, MD USA. [Romero, Rene] Emory Univ, Sch Med, Div Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA 30322 USA. [Schwarzenberg, Sara Jane] Univ Minnesota, Masonic Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Minneapolis, MN USA. [Palermo, Joseph] Cincinnati Childrens Hosp Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA. [Alonso, Estella M.] Ann & Robert Lurie Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Chicago, IL USA. [Murray, Karen F.] Seattle Childrens Hosp, Div Gastroenterol & Hepatol, Seattle, WA USA. [Murray, Karen F.] Univ Washington, Seattle, WA 98195 USA. [Marshall, Bruce C.] Cyst Fibrosis Fdn, Toronto, ON, Canada. [Sherker, Averell H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Siegel, Marilyn J.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Krishnamurthy, Rajesh] Texas Childrens Hosp, EB Singleton Dept Diagnost Imaging, Houston, TX 77030 USA. [Harned, Roger] Univ Colorado, Sch Med, Dept Radiol, Aurora, CO USA. [Harned, Roger] Childrens Hosp Colorado, Aurora, CO USA. [Karmazyn, Boaz] Riley Hosp Children, Pediat Radiol, Indianapolis, IN USA. [Magee, John C.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Narkewicz, Michael R.] Univ Colorado SOM, Dept Pediat, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Narkewicz, Michael R.] Childrens Hosp Colorado, Aurora, CO USA. RP Leung, DH (reprint author), Texas Childrens Hosp, Baylor Coll Med, Div Pediat Gastroenterol Hepatol & Nutr, 6701 Fannin St,CCC 1010, Houston, TX 77030 USA. EM dhleung@texaschildrens.org; michael.narkewicz@childrenscolorado.org OI Ling, Simon/0000-0002-4223-4601; Towbin, Alexander/0000-0003-1729-5071 FU Cystic Fibrosis Foundation [Colorado] [NARKEW07A0]; National Institute of Diabetes and Digestive and Kidney [The University of Michigan] [DK062453, DK62456]; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH)/National Center for Advancing Translational Sciences [Colorado] [UL1 TR001082]; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences [Cincinnati] [UL1 TR000077, DK084536-07]; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences [Northwestern University] [UL1 TR000150]; Clinical & Translational Science Institute (CTSI) [Indiana University] [UL1TR001108]; Institute for Clinical & Translational Research/NCATS/NIH [Johns Hopkins] [UL1 TR 001079]; NIH/Northwestern University Clinical and Translational Sciences Institute/Institute of Translational Health Sciences [RR025014]; NIH (Clinical and Translational Science Award) [University of Washington] [TR000423] FX Jointly supported by the Cystic Fibrosis Foundation (NARKEW07A0 [Colorado]) and the National Institute of Diabetes and Digestive and Kidney (DK062453 and DK62456 [The University of Michigan]), the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS; UL1 TR001082 [Colorado]; UL1 TR000077 [Cincinnati], DK084536-07; UL1 TR000150 [Northwestern University]), Clinical & Translational Science Institute (CTSI UL1TR001108 [Indiana University]), Institute for Clinical & Translational Research/NCATS/NIH (UL1 TR 001079 [Johns Hopkins]), NIH/Northwestern University Clinical and Translational Sciences Institute/Institute of Translational Health Sciences (RR025014), and NIH (Clinical and Translational Science Award TR000423 [University of Washington]). Contents are the authors' sole responsibility and do not necessarily represent official NIH views. B.M. is a full time employee of the Cystic Fibrosis Foundation. The other authors declare no conflicts of interest. NR 28 TC 6 Z9 6 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2015 VL 167 IS 4 BP 862 EP + DI 10.1016/j.jpeds.2015.06.062 PG 9 WC Pediatrics SC Pediatrics GA CU5BE UT WOS:000363545800019 PM 26254836 ER PT J AU Naples, JG Marcum, ZA Perera, S Gray, SL Newman, AB Simonsick, EM Yaffe, K Shorr, RI Hanlon, JT AF Naples, Jennifer G. Marcum, Zachary A. Perera, Subashan Gray, Shelly L. Newman, Anne B. Simonsick, Eleanor M. Yaffe, Kristine Shorr, Ronald I. Hanlon, Joseph T. CA Hlth Aging Body Composition Study TI Concordance Between Anticholinergic Burden Scales SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cholinergic antagonists; aged; drug use ID OLDER-PEOPLE; DRUG BURDEN; BODY-COMPOSITION; ASSOCIATIONS; HEALTH; INDEX; MEDICATIONS; DECLINE; ELDERS AB ObjectivesTo evaluate concordance of five commonly used anticholinergic scales. DesignCross-sectional secondary analysis. SettingPittsburgh, Pennsylvania, and Memphis, Tennessee. ParticipantsCommunity-dwelling adults aged 70 to 79 with baseline medication data from the Health, Aging, and Body Composition Study (N = 3,055). MeasurementsAny anticholinergic use, weighted scores, and total standardized daily dosage were calculated using five anticholinergic measures (Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), Drug Burden Index anticholinergic component (DBI-ACh), and Summated Anticholinergic Medications Scale (SAMS)). Concordance was evaluated using kappa statistics and Spearman rank correlations. ResultsAny anticholinergic use in rank order was 51% for the ACB, 43% for the ADS, 29% for the DBI-ACh, 23% for the ARS, and 16% for the SAMS. Kappa statistics for all pairwise use comparisons ranged from 0.33 to 0.68. Similarly, concordance as measured using weighted kappa statistics ranged from 0.54 to 0.70 for the three scales not incorporating dosage (ADS, ARS, ACB). Spearman rank correlation between the DBI-ACh and SAMS was 0.50. ConclusionOnly low to moderate concordance was found between the five anticholinergic scales. Future research is needed to examine how these differences in measurement affect their predictive validity with respect to clinically relevant outcomes, such as cognitive impairment. C1 [Naples, Jennifer G.; Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Perera, Subashan] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 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. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Shorr, Ronald I.] Malcolm Randall Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. RP Naples, JG (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufmann Med Bldg Suite 500,3471 Fifth Ave, Pittsburgh, PA 15213 USA. EM jgn13@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, K07 AG033174, K07-AG033174, N01-AG-6-2103, N01-AG-6-2106, P30 AG024827, P30-AG024827, R01 AG037451, R01-AG037451, T32 AG021885, T32-AG021885]; NINR NIH HHS [NR012459, R01 NR012459] NR 22 TC 6 Z9 7 U1 2 U2 4 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 OCT PY 2015 VL 63 IS 10 BP 2120 EP 2124 DI 10.1111/jgs.13647 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CU8PQ UT WOS:000363805800021 PM 26480974 ER PT J AU Pim, D Broniarczyk, J Bergant, M Playford, MP Banks, L AF Pim, David Broniarczyk, Justyna Bergant, Martina Playford, Martin P. Banks, Lawrence TI A Novel PDZ Domain Interaction Mediates the Binding between Human Papillomavirus 16 L2 and Sorting Nexin 27 and Modulates Virion Trafficking SO JOURNAL OF VIROLOGY LA English DT Article ID WASH COMPLEX; INFECTION; RETROMER; SNX27; ENTRY; SNX27-RETROMER; IDENTIFICATION; ENDOSOME; REVEALS; TYPE-16 AB Previous studies have demonstrated an interaction between sorting nexin 17 and the L2 capsid proteins from a variety of papillomavirus types. This interaction is required for late endosomal trafficking of the L2 protein and entry of the L2/DNA complex into the nucleus during infection. Here we show an interaction between papillomavirus L2 proteins and the related PX-FERM family member sorting nexin 27 (SNX27), which is mediated in part by a novel interaction between the PDZ domain of SNX27 and sequences in a central portion of L2. The interaction is direct and, unlike that with SNX17, is variable in strength depending on the papillomavirus type. We show that small interfering RNA (siRNA)-mediated knockdown of SNX27 alone leads to a marginal reduction in the efficiency of viral infection but that double knockdown of both sorting nexins results in a striking reduction in infection, greater than that observed for the knockdown of either sorting nexin alone. These results suggest that the HPV L2 proteins can interact through distinct mechanisms with multiple components of the cellular cargo-sorting machinery. IMPORTANCE The trafficking of papillomaviruses to the host cell nucleus during their natural infectious life cycle is an incompletely understood process. Studies have suggested that the virus minor capsid protein L2 can interact with the endosomal recycling pathway, in part by association with sorting nexin 17, to ensure that virus DNA bound to L2 is recycled through the trans-Golgi network rather than back to the plasma membrane. In this study, we characterize the interaction between L2 and a second sorting nexin, SNX27, which is also part of the retromer complex. The study furthers our understanding of papillomavirus infection dynamics and provides potential tools for the further dissection of endosomal structure and function. C1 [Pim, David; Banks, Lawrence] ICGEB, Dept Tumour Virol, Trieste, Italy. [Broniarczyk, Justyna] Adam Mickiewicz Univ, Dept Mol Virol, Poznan, Poland. [Bergant, Martina] Univ Nova Gorica, Ctr Biomed Sci & Engn, Nova Gorica, Slovenia. [Playford, Martin P.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Pim, D (reprint author), ICGEB, Dept Tumour Virol, Trieste, Italy. EM pim@icgeb.org NR 31 TC 7 Z9 7 U1 2 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 OCT PY 2015 VL 89 IS 20 BP 10145 EP 10155 DI 10.1128/JVI.01499-15 PG 11 WC Virology SC Virology GA CU3ZG UT WOS:000363464700002 PM 26202251 ER EF